ALBERT

Beschreibung: A poorly understood feature of the tauopathies is their very different clinical presentations. The frontotemporal lobar degeneration (FTLD) spectrum is dominated by motor and emotional/psychiatric abnormalities, whereas cognitive and memory deficits are prominent in the early stages of Alzheimer’s disease (AD). We report two novel mouse models overexpressing different human tau protein constructs. One is a full-length tau carrying a double mutation [P301S/G335D; line 66 (L66)] and the second is a truncated 3-repeat tau fragment which constitutes the bulk of the PHF core in AD corresponding to residues 296–390 fused with a signal sequence targeting it to the endoplasmic reticulum membrane (line 1; L1). L66 has abundant tau pathology widely distributed throughout the brain, with particularly high counts of affected neurons in hippocampus and entorhinal cortex. The pathology is neuroanatomically static and declines with age. Behaviourally, the model is devoid of a higher cognitive phenotype but presents with sensorimotor impairments and motor learning phenotypes. L1 displays a much weaker histopathological phenotype, but shows evidence of neuroanatomical spread and amplification with age that resembles the Braak staging of AD. Behaviourally, the model has minimal motor deficits but shows severe cognitive impairments affecting particularly the rodent equivalent of episodic memory which progresses with advancing age. In both models, tau aggregation can be dissociated from abnormal phosphorylation. The two models make possible the demonstration of two distinct but nevertheless convergent pathways of tau molecular pathogenesis. L1 appears to be useful for modelling the cognitive impairment of AD, whereas L66 appears to be more useful for modelling the motor features of the FTLD spectrum. Differences in clinical presentation of AD-like and FTLD syndromes are therefore likely to be inherent to the respective underlying tauopathy, and are not dependent on presence or absence of concomitant APP pathology.

Beschreibung: Earlier findings on the nutritional benefits of diacylglycerols (DAGs) have attracted much attention on the synthesis of DAGs. In this study, we reported an improved method for the lipase-catalyzed synthesis of 1,3-diolein by the irreversible glycerolysis of vinyl oleate with glycerol. The effects of reaction system, lipase loading, molar ratio of vinyl oleate to glycerol, reaction temperature and time on 1,3-diolein content in crude reaction mixture were investigated. When the reaction was conducted in a solvent-free system at 30 °C for 8 h by reacting 2 mmol vinyl oleate with 1 mmol glycerol with 8 % (w/w, relative to total reactants) Lipozyme RM IM (Novozymes, Beijing, China) as catalyst, there were 90.5 ± 2.9 % (area/area) 1,3-diolein and (3.3 ± 0.3) % 1,2-diolein produced. After purification, 1,3-diolein was obtained at 81.4 % yield with 98.2 % purity. The lipase-catalyzed synthesis of 1,3-diolein using vinyl oleate as acyl donor by glycerolysis was also conducted using a medium with 50 mmol of glycerol and 100 mmol vinyl oleate. Compared to enzymatic esterification in a solvent, enzymatic glycerolysis for the synthesis 1,3-diolein is more effective due to the irreversible reaction, mild due to the low reaction temperature, and environmentally benign due to the use of solvent-free reaction system.

Beschreibung: Glia are abundant cells in the brain of animals ranging from flies to humans. They perform conserved functions not only in neural development and wiring, but also in brain homeostasis. Here we show that by manipulating gene expression in glia, a previously unidentified cell type appears in the Drosophila brain during metamorphosis. More specifically, this cell type appears in three contexts: (1) after the induction of either immunity, or (2) autophagy, or (3) by silencing of neurotrophic factor DmMANF in glial cells. We call these cells MANF immunoreactive Cells (MiCs). MiCs are migratory based on their shape, appearance in brain areas where no cell bodies exist and the nuclear localization of dSTAT. They are labeled with a unique set of molecular markers including the conserved neurotrophic factor DmMANF and the transcription factor Zfh1. They possess the nuclearly localized protein Relish, which is the hallmark of immune response activation. They also express the conserved engulfment receptor Draper, therefore indicating that they are potentially phagocytic. Surprisingly, they do not express any of the common glial and neuronal markers. In addition, ultrastructural studies show that MiCs are extremely rich in lysosomes. Our findings reveal critical molecular and functional components of an unusual cell type in the Drosophila brain. We suggest that MiCs resemble macrophages/hemocytes and vertebrate microglia based on their appearance in the brain upon genetically challenged conditions and the expression of molecular markers. Interestingly, macrophages/hemocytes or microglia-like cells have not been reported in the fly nervous system before.

Beschreibung: Canolol-enriched extracts obtained from the extraction of fluidized bed treated canola meal with supercritical carbon dioxide were added to high-oleic canola oil in different concentrations (200, 500 and 750 mg/kg). After 30 h of deep-fat frying, oils fortified with canolol-enriched extracts showed a two to three times better frying performance in comparison to the commonly used antioxidants (TBHQ, 200 mg/kg; rosemary extract, 40 and 200 mg/kg) and a control without antioxidants with regards to the formation of di- and polymer triacylglycerols, total polar compounds, secondary degradation products (anisidine value) and the iodine value. The canolol-enriched extracts were also able to slow down the degradation of α- and γ-tocopherol during frying resulting in significant amounts of tocopherols after 30 h of frying in comparison to the other oils. The influence of the canolol-enriched extracts indicated strongly concentration-dependent performance. With increasing concentration of the extract, the thermal stability of the fortified oil was improved. The only disadvantage of the addition of the extracts was an increase in the initial acid value, but within the frying time, only oil fortified with 750 mg canolol-enriched extract/kg reached the limit given in different countries.

Beschreibung: Fibrosis is an inherent response to chronic damage upon immense apoptosis or necrosis. Transforming growth factor-beta1 (TGF-β1) signaling plays a key role in the fibrotic response to chronic liver injury. To develop anti-fibrotic therapeutics, we synthesized a novel small-molecule inhibitor of the TGF-β type I receptor kinase (ALK5), EW-7197, and evaluated its therapeutic potential in carbon tetrachloride (CCl 4 ) mouse, bile duct ligation (BDL) rat, bleomycin (BLM) mouse, and unilateral ureteral obstruction (UUO) mouse models. Western blot, immunofluorescence, siRNA, and ChIP analysis were carried out to characterize EW-7197 as a TGF-β/Smad signaling inhibitor in LX-2, Hepa1c1c7, NRK52E, and MRC5 cells. In vivo anti-fibrotic activities of EW-7197 were examined by microarray, immunohistochemistry, western blotting, and a survival study in the animal models. EW-7197 decreased the expression of collagen, α-smooth muscle actin (α-SMA), fibronectin, 4-hydroxy-2, 3-nonenal, and integrins in the livers of CCl 4 mice and BDL rats, in the lungs of BLM mice, and in the kidneys of UUO mice. Furthermore, EW-7197 extended the lifespan of CCl 4 mice, BDL rats, and BLM mice. EW-7197 blocked the TGF-β1-stimulated production of reactive oxygen species (ROS), collagen, and α-SMA in LX-2 cells and hepatic stellate cells (HSCs) isolated from mice. Moreover, EW-7197 attenuated TGF-β- and ROS-induced HSCs activation to myofibroblasts as well as extracellular matrix accumulation. The mechanism of EW-7197 appeared to be blockade of both TGF-β1/Smad2/3 and ROS signaling to exert an anti-fibrotic activity. This study shows that EW-7197 has a strong potential as an anti-fibrosis therapeutic agent via inhibition of TGF-β-/Smad2/3 and ROS signaling.

Beschreibung: Aberrant glycosylation is a key feature of malignant transformation and reflects epigenetic and genetic anomalies among the multitude of molecules involved in glycan biosynthesis. Although glycan biosynthesis is not template bound, altered tumor glycosylation is not random, but associated with common glycosylation patterns. Evidence suggests that acquisition of distinct glycosylation patterns evolves from a ‘microevolutionary’ process conferring advantages in terms of tumor growth, tumor dissemination, and immune escape. Such glycosylation modifications also involve xeno- and hypersialylation. Xeno-autoantigens such as Neu5Gc-gangliosides provide potential targets for immunotherapy. Hypersialylation may display ‘enhanced self’ to escape immunosurveillance and involves several not mutually exclusive inhibitory pathways that all rely on protein–glycan interactions. A better understanding of tumor ‘glycan codes’ as deciphered by lectins, such as siglecs, selectins, C-type lectins and galectins, may lead to novel treatment strategies, not only in cancer, but also in autoimmune disease or transplantation.

Beschreibung: Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation.

Beschreibung: Cottonseed meal (CSM), a common agricultural by-product, was used as a nutrient source for the production of eicosapentaenoic acid (EPA) by Pythium irregulare . CSM can support good cell growth performance, as can yeast extract (YE). In terms of the maximum EPA content and EPA yield, CSM is superior to YE. Low concentrations of CSM are beneficial to lipid synthesis, and high concentrations favor the EPA content. Utilizing response surface methodology (RSM) analysis, the optimum contents of glucose and CSM in the fermentation medium were determined to be 40.2 and 16.1 g/l, respectively. After 6 days of fermentation at 25 °C and optimal conditions, the EPA yield and productivity were 245.3 and 40.9 mg/l day, respectively. Particle size of CSM was found to affect the EPA production, and a finely ground CSM (100 mesh) was determined to be best for EPA production. The variation in the fatty acid content of total fatty acid (TFA) indicates that EPA was synthesized through the n-6 route in P. irregulare and Δ12 desaturase was the key enzyme for EPA biosynthesis. Sodium carbonate was determined to be notably good at removing free gossypol attached to biomass. After fungal biomass from each flask had been harvested from Na 2 CO 3 -supplemented medium, 1 % (w/v) Na 2 CO 3 solution was used to wash the mycelia three times; free gossypol (FG) was not detected (detection limit 0.0018 %). This work provides a new approach using cottonseed meal to produce EPA through fungal fermentation.

Beschreibung: Steryl glucosides (SG) are common contaminants in biodiesel that form precipitates, which form and cause problems due to fouling during transport and storage. Therefore, their quantification is necessary to assess the quality of this fuel. The methods currently available for SG analysis require expensive instrumentation, need a previous concentration step by solid-phase extraction (SPE) or are of limited use for the quantitative assessment. We developed an enzymatic method for SG quantification in biodiesel samples based on the hydrolysis of the glucoside catalyzed by a broadly specific beta glucosidase and the subsequent determination of the glucose released by the reaction. The method is non-expensive, sensitive and was adapted to 96-well format fluorescence plate reader, making it useful for the parallel assay of multiple samples. The enzymatic assay presented here represent a valuable tool for both quality control and the development of improved biodiesel production and purification procedures.

Beschreibung: Di-hydroxylated soybean oil (DSO), a biobased polyol synthesized from epoxidized soybean oil (ESO) could be used to formulate resins for adhesives; however, current DSO synthesis requires harsh reaction conditions that significantly increase both cost and waste generation. In this paper, we investigate the kinetics of oxirane cleavage in ESO to DSO by water and elucidate the role of different process parameters in the reaction rate and optimization of reaction conditions. Our kinetic study showed that ESO oxirane cleavage was a first-order reaction and that the ESO oxirane cleavage rate was greatly influenced by tetrahydrofuran (THF)/ESO ratio, H 2 O/ESO ratio, catalyst content, and temperature. Optimized reaction parameters were THF/ESO of 0.5, H 2 O/ESO of 0.25, catalyst content of 1.5 %, and reaction time of 3 h at 25 °C. DSO with hydroxyl value of 242 mg KOH/g was obtained under these conditions. We also characterized the structure, thermal properties, adhesion performance, and viscoelasticity of UV-polymerized resins based on this DSO. The resin tape exhibited peel adhesion strength of 3.6 N/in., which is comparable to some commercial tapes measured under similar conditions.

Beschreibung:    The objective of this work was to synthesize a structured lipid (SL) enriched in stearidonic acid (SDA, C18:4 ω-3), from modified soybean oil (MSO) originally containing ~25% SDA. Low temperature crystallization (LTC) of MSO triacylglycerols (TAG) and free fatty acids (FFA) was performed. The TAG and FFA crystallization products (LTC-TAG and LTC-FFA, respectively) had SDA contents of 48.72 and 60.78%, respectively. Enzymatic acidolysis between MSO and LTC-FFA was studied utilizing Novozym 435 and Lipozyme TL IM as biocatalysts. Substrate molar ratio, incubation time, solvent, and enzyme load were explored. Equilibrium was reached at 96 and 48 h for Novozym 435 and Lipozyme TL IM-catalyzed reactions, respectively. The best conditions from these studies were also applied to the acidolysis of LTC-TAG and LTC-FFA. Utilizing Lipozyme TL IM and solvent free conditions, SLs with SDA contents of 37.61 ± 1.00% (20.86 ± 6.48% at sn -2 position) and 53.46 ± 1.85% SDA (36.37 ± 3.14% at sn -2 position) were obtained from the acidolysis reaction between MSO and LTC-FFA, and LTC-TAG and LTC-FFA, respectively. Compared to the original SDA content of MSO, this process leads to a 52 and 116% increase in SDA content, respectively. Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s11746-012-2022-1 Authors Leslie Kleiner, Department of Food Science and Technology, University of Georgia, Athens, GA 30602-2610, USA Luis Vázquez, Department of Food Science and Technology, University of Georgia, Athens, GA 30602-2610, USA Casimir C. Akoh, Department of Food Science and Technology, University of Georgia, Athens, GA 30602-2610, USA Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Increasing oleic acid, a monounsaturated fatty acid, is reported to strike the best balance between cold flow properties and oxidative stability in soybean seed oil to enhance biodiesel and produce a better burning fuel. In addition, it is important that elevated oleic acid soybeans have the agronomic traits of local cultivars and maintain oleic acid stability across environments. Research was conducted in 2007–2008 to evaluate six Roundup Ready ® soybean recombinant inbred lines exhibiting enhanced levels of oleic acid. The six elevated oleic lines averaged a 55% increase in oleic acid and a 43% decrease in linolenic acid over the two commercial cultivars (AG3906 and AG4103). Some elevated oleic acid genotypes fulfilled the linear regression definition of a stable genotype. TN03-93RR was the best genotype because of its oleic acid content (397 g kg −1 ) and desirable regression estimates for stability. Iodine value (IV), peroxide value (PV), and induction period (IP) were used to evaluate the fuel properties of the two lines with the highest oleic acid content and the two commercial cultivars. The elevated oleic acid lines had significantly better IP, PV and IV for better biodiesel properties and oxidative stability than the two commercial cultivars. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s11746-012-2026-x Authors Benjamin D. Fallen, Department of Plant Sciences, University of Tennessee, 2431 Joe Johnson Dr., Knoxville, TN 37996, USA Katy Rainey, Department of Agronomy, Purdue University, 915 W. State St., West Lafayette, IN 47907, USA Carl E. Sams, Department of Plant Sciences, University of Tennessee, 2431 Joe Johnson Dr., Knoxville, TN 37996, USA Dean A. Kopsell, Department of Plant Sciences, University of Tennessee, 2431 Joe Johnson Dr., Knoxville, TN 37996, USA Vincent R. Pantalone, Department of Plant Sciences, University of Tennessee, 2431 Joe Johnson Dr., Knoxville, TN 37996, USA Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    The aim of this study is to describe the physicochemical properties of Iranian virgin olive oil (Zard, Mari and Phishomi) cultivated in Roodbar, Gilan. There were statistically significant differences for most of the parameters ( P  〈 0.05). The acidity and peroxide value were in the limit established for classification as extra virgin olive oil. The oil of Zard had the highest amount of monounsaturated fatty acids followed by Mari and Phishomi oils. Mari oil proved to have the minimum value of polyunsaturated fatty acids, and the highest amount of phenolic compounds and oxidative stability. The oil of Phishomi had the maximum amount of chlorophylls and carotenoids and therefore it had the highest color index. There were no significant differences between the cultivars regarding the refractive index (1.469 at 20 °C for all three cultivars). According to the high content of monounsaturated fatty acids, the lowest amounts of polyunsaturated fatty acids and the highest amounts of phenolic compounds as well as the results of a Rancimat assay, it seems that the quality of the oil of Mari cultivar is better than Zard and Phishomi oils and is also more stable against oxidation. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s11746-012-2021-2 Authors Sepideh Haghighat Kharazi, Food Science and Technology Department, Faculty of Agricultural Engineering, Sari Agricultural Sciences and Natural Resources University, P.O. Box 578, Mazandaran, Iran Reza Esmaeilzadeh Kenari, Food Science and Technology Department, Faculty of Agricultural Engineering, Sari Agricultural Sciences and Natural Resources University, P.O. Box 578, Mazandaran, Iran Zeinab Raftani Amiri, Food Science and Technology Department, Faculty of Agricultural Engineering, Sari Agricultural Sciences and Natural Resources University, P.O. Box 578, Mazandaran, Iran Maryam Azizkhani, Department of Food Science and Technology, Khazar University, Mahmoudabad, Iran Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung: Erratum to: Quality Characteristics and Antioxidants of Mavrolia cv. Virgin Olive Oil Content Type Journal Article Category Erratum Pages 1-1 DOI 10.1007/s11746-011-1991-9 Authors Efstathios Anastasopoulos, Laboratory of Chemistry-Biochemistry-Physical Chemistry of Foods, Department of Science of Nutrition–Dietetics, Harokopio University, Athens, Greece Nick Kalogeropoulos, Laboratory of Chemistry-Biochemistry-Physical Chemistry of Foods, Department of Science of Nutrition–Dietetics, Harokopio University, Athens, Greece Andriana C. Kaliora, Laboratory of Chemistry-Biochemistry-Physical Chemistry of Foods, Department of Science of Nutrition–Dietetics, Harokopio University, Athens, Greece Ageliki Falirea, Laboratory of Chemistry-Biochemistry-Physical Chemistry of Foods, Department of Science of Nutrition–Dietetics, Harokopio University, Athens, Greece Vassilis N. Kamvissis, Analytical Laboratory Department, Minerva S.A. Edible Oils Enterprises, 165 Tatoiou and Odisseos Str, 14452, Metamorfosis Attica, Factory, 32009 Schimatari Viotias, Greece Nikolaos K. Andrikopoulos, Laboratory of Chemistry-Biochemistry-Physical Chemistry of Foods, Department of Science of Nutrition–Dietetics, Harokopio University, Athens, Greece Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    The aim of this study was to examine Peruvian anchovy oil fatty acid (FA) compositions, and to test the possibility of using the FA data to classify the oils according to geographical origin along the Peruvian coast. The levels of contaminants in a representative set of samples were determined to examine the general levels and investigate if such measurements could aid in future discrimination between oils. The FA results showed that the two known stocks of Peruvian anchovy displayed different levels of docosahexaenoic acid (DHA, 22:6n-3) (southern stock; 14.4 ± 0.8% versus central-northern stock; 9.9 ± 1.2%). However, principal component analysis (PCA) of the FA data indicated clusters according to three regions; North, Center and South. Using a data set of 57 anchovy samples and 21 FA as input, a probabilistic neural network (PNN) was constructed. For the validation data sets, “North” oils was predicted accurately 100% of the time, “Center” oils 100% and “South” oils 83% of the time. The levels of contaminants in the oils determined were low in all but one sample. Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s11746-012-2031-0 Authors Inger B. Standal, SINTEF Fisheries and Aquaculture, 7465 Trondheim, Norway José Rainuzzo, SINTEF Fisheries and Aquaculture, 7465 Trondheim, Norway David E. Axelson, MRi_Consulting, 8 Wilmot Street, Kingston, ON K7L 4V1, Canada Stig Valdersnes, National Institute of Nutrition and Seafood Research (NIFES), P.O. Box 2029, Nordnes, 5817 Bergen, Norway Kåre Julshamn, National Institute of Nutrition and Seafood Research (NIFES), P.O. Box 2029, Nordnes, 5817 Bergen, Norway Marit Aursand, MRi_Consulting, 8 Wilmot Street, Kingston, ON K7L 4V1, Canada Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    In this work, rapid and non-destructive methodology is proposed for screening of biodiesel/diesel blends with respect to the base oil, using near infrared spectroscopy and multivariate data analysis, since for both pure biodiesel and blends, the biodiesel/diesel are targets for tampering. Blends of diesel with cotton, sunflower and soybean oils were employed in this study. Two approaches were evaluated in the building of the classification model, using full-spectrum Soft Independent Modelling of Class Analogy (SIMCA), and Principal Component Analysis–Linear Discriminant Analysis (PCA–LDA). The other approaches were the use of variable selection employing Genetic Algorithm (GA), Successive Projection Algorithm (SPA) and Stepwise all coupled with the LDA model. The results showed which preprocessed NIR spectra and chemometrics are a viable alternative the conventional methods that involve the consumption of large volumes of reagents. Multivariate data analysis methods using selected variables showed a better performance than the methods using a full spectrum. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s11746-012-2028-8 Authors Gildo W. B. Silva, Departamento de Química, Universidade Estadual da Paraíba, Campina Grande, PB 58429-500, Brazil Adriano A. Gomes, Departamento de Química, Universidade Federal da Paraíba, João Pessoa, 58051-970 Brazil Priscila da Silva, Departamento de Química, Universidade Estadual da Paraíba, Campina Grande, PB 58429-500, Brazil Gean B. Costa, Departamento de Química, Universidade Estadual da Paraíba, Campina Grande, PB 58429-500, Brazil David Douglas Sousa Fernandes, Departamento de Química, Universidade Estadual da Paraíba, Campina Grande, PB 58429-500, Brazil Marcelo M. Fontes, Departamento de Química, Universidade Estadual da Paraíba, Campina Grande, PB 58429-500, Brazil Germano Veras, Departamento de Química, Universidade Estadual da Paraíba, Campina Grande, PB 58429-500, Brazil Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    An efficient solvent-free synthesis of a variety of highly pure 1,3- sn -diglycerides (1,3- sn -diacylglycerols) in a two-step one pot process is described. Heating glycerol carbonate (4-hydroxymethyl-1,3-dioxolan-2-one) with fatty acid anhydrides 2a–d affords 1:1 mixtures of glycerol carbonate fatty esters 3a–3d and the corresponding fatty acids. Further heating the reaction mixtures in the presence of catalytic amounts of 1,4-diazabicyclo[2.2.2]octane (DABCO) at 195–200 °C yields highly pure 1,3- sn -diglycerides 4a–4d . Content Type Journal Article Category Original Paper Pages 1-6 DOI 10.1007/s11746-012-2165-0 Authors Mojgan Kargar, Department of Chemistry, School of Sciences, Alzahra University, Vanak, Tehran, Iran Rahim Hekmatshoar, Department of Chemistry, School of Sciences, Alzahra University, Vanak, Tehran, Iran Mehdi Ghandi, School of Chemistry, College of Science, University of Tehran, Tehran, Iran AbdolJalil Mostashari, Industrial Chemical R&D Organization, Tehran, Iran Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Pistacia terebinthus L. is an indigenous plant growing wild in the southern regions of Turkey. Its fruits are used in foods, pharmaceuticals and cosmetics due to its high oil content (ca. 45 g/100 g). In the present study, it was found out that the kernel and the skin parts of the fruit differ significantly ( p  〈 0.05) both in terms of oil content and composition. Regardless of the geographical origin, the most abundant fatty acid was found to be monounsaturated oleic acid, 18:1n-9 whose content was in the range of 51.2–67.5 g/100 g. β-sitosterol is the predominant sterol in kernel and skin of the terebinthus fruits whose content was varying between 97.4 and 219.8 mg/100 g. Concerning different tocols (tocopherols and tocotrienols) detected in the kernel and skin, γ-T was the one with highest concentration (437.2 mg/kg) in kernels, while the most abundant one in skin parts was found to be α-T (348.7 mg/kg). In general the kernel of terebinthus fruits was more concentrated in PUFA, total sterol and tocopherols than skin, however, total tocotrienol content was higher in skin than kernel. On the basis of these findings it can be concluded that both kernel and skin are highly valuable in terms of bioactive compounds, whereas skin with a high amount saturated fatty acids is more suited to applications in cosmetic industry. Content Type Journal Article Category Original Paper Pages 1-6 DOI 10.1007/s11746-012-2168-x Authors Erdal Ertas, TUBITAK Marmara Research Center, Food Institute, P.O. Box 21, 41470 Gebze, Kocaeli, Turkey Somer Bekiroglu, TUBITAK Marmara Research Center, Food Institute, P.O. Box 21, 41470 Gebze, Kocaeli, Turkey Ibrahim Ozdemir, TUBITAK Marmara Research Center, Food Institute, P.O. Box 21, 41470 Gebze, Kocaeli, Turkey Ilknur Demirtas, TUBITAK Marmara Research Center, Food Institute, P.O. Box 21, 41470 Gebze, Kocaeli, Turkey Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Defects in membrane trafficking and degradation are hallmarks of most, and maybe all, neurodegenerative disorders. Such defects typically result in the accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal degradation, or autophagy. The genetic or environmental cause of a specific disease may directly affect these membrane trafficking processes. Alternatively, changes in intracellular sorting and degradation can occur as cellular responses of degenerating neurons to unrelated primary defects such as insoluble protein aggregates or other neurotoxic insults. Importantly, altered membrane trafficking may contribute to the pathogenesis or indeed protect the neuron. The observation of dramatic changes to membrane trafficking thus comes with the challenging need to distinguish pathological from protective alterations. Here, we will review our current knowledge about the protective and destructive roles of membrane trafficking in neuronal maintenance and degeneration. In particular, we will first focus on the question of what type of membrane trafficking keeps healthy neurons alive in the first place. Next, we will discuss what alterations of membrane trafficking are known to occur in Alzheimer’s disease and other tauopathies, Parkinson’s disease, polyQ diseases, peripheral neuropathies, and lysosomal storage disorders. Combining the maintenance and degeneration viewpoints may yield insight into how to distinguish when membrane trafficking functions protectively or contributes to degeneration. Content Type Journal Article Category Review Pages 1-16 DOI 10.1007/s00018-012-1201-4 Authors Dong Wang, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA Chih-Chiang Chan, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA Smita Cherry, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA P. Robin Hiesinger, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Effects of the alkyl chain length of rosmarinate alkyl esters on the oxidative stability in photosensitized oil-in-water (O/W) emulsions were determined by lipid hydroperoxides and headspace volatile analyses. Antioxidant capacities of 20 μM rosmarinate esters with alkyl chain length of 0, 4, 8, 12, 18, and 20 were tested in O/W emulsion containing stripped soybean oil, Tween 20 as an emulsifier, and riboflavin as a photosensitizer. Synergistic or antagonistic effects of 20 μM α-tocopherol in the presence of rosmarinate alkyl esters were also determined. Samples containing rosmarinate with 4 and 8 alkyl esters showed lower lipid hydroperoxides and headspace volatiles than those without rosmarinate and those with 0, 12, 18, and 20 alkyl esters, which indicates that phenolic free radical scavengers showed antioxidant capacities non-linearly in riboflavin photosensitized O/W emulsions. Antagonistic rather than synergistic effects were observed in all rosmarinate alkyl esters with α-tocopherol in current conditions although rosmarinates with 4, 8, and 12 alkyl esters showed better antioxidant capacities than those with other alkyl chain length. The results of this study clearly showed that rosmarinates need the proper length of non-polar groups to show optimum antioxidant capacities in O/W emulsions with Tween 20 as an emulsifier under riboflavin photosensitization. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s11746-012-2163-2 Authors Jae Hwan Lee, Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, Korea Atikorn Panya, Department of Food Science, University of Massachusetts, Amherst, MA 01002, USA Mickaël Laguerre, CIRAD, UMR IATE, Montpellier, 34398 France Christelle Bayrasy, CIRAD, UMR IATE, Montpellier, 34398 France Jérôme Lecomte, CIRAD, UMR IATE, Montpellier, 34398 France Pierre Villeneuve, CIRAD, UMR IATE, Montpellier, 34398 France Eric A. Decker, Department of Food Science, University of Massachusetts, Amherst, MA 01002, USA Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Castor oil can be used in industry. The molecular species of triacylglycerols containing hydroxy fatty acids (FA) in castor oil have been identified. We report here the identification of twelve diacylglycerols (DAG) containing hydroxy FA in castor oil using positive ion electrospray ionization mass spectrometry of the lithium adducts. They were RR (diricinolein, R is ricinoleate), RL, RS, R-diOH18:0, R-diOH18:1, R-diOH18:2, R-triOH18:0, R-triOH18:1, R-triOH18:2, diOH18:0-diOH18:1, diOH18:1-diOH18:1 and diOH18:1-diOH18:2. The MS 2 fragment ions, [M + Li − FA] + and [FA + Li] + , from the lithium adducts of DAG containing hydroxy FA (one or two hydroxy FA), were used for the identification. The additional fragment ions from the neutral losses of FA lithium salts [M + Li − FALi] + were used for the identification of eleven DAG containing two normal FA in a soybean oil bioconversion product. The MS 2 fragment ions from the neutral losses of FA lithium salts [M + Li − FALi] + were not detected from the DAG containing hydroxy FA. The DAG containing FA with more hydroxyl groups than the other FA on the same DAG molecule tended to have a prominent fragment ion [FA + Li] + and an undetectable fragment ion [M + Li − FA] + while the FA was the more hydroxylated FA. Also the less hydroxylated FA of a DAG tended to have a prominent fragment ion [M + Li − FA] + and an undetectable fragment ion [FA + Li] + while the FA was the less hydroxylated FA. Content Type Journal Article Category Original Paper Pages 1-6 DOI 10.1007/s11746-012-2136-5 Authors Jiann-Tsyh Lin, Agricultural Research Service, Western Regional Research Center, U.S. Department of Agriculture, 800 Buchanan Street, Albany, CA 94710, USA Grace Q. Chen, Agricultural Research Service, Western Regional Research Center, U.S. Department of Agriculture, 800 Buchanan Street, Albany, CA 94710, USA Ching T. Hou, Agricultural Research Service, National Center for Agricultural Utilization Research, U.S. Department of Agriculture, Peoria, IL 61604, USA Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Quality characteristics of extra-virgin olive oils depend on several factors. In order to study the effects of genotype and growing location on olive oil quality, olives from cv. Coratina, Nocellara, Ogliarola, and Peranzana, picked in four locations of the Apulia region (Italy), were crushed by a three-phase system to produce mono-cultivar extra virgin olive oils that were analyzed for acidity, peroxide value, spectrophotometric indices, total phenolic content, phenolic profile and antioxidant activity. The experimental data concerning peroxide value, spectrophotometric indices, phenolic content and profile and antioxidant activity showed great variability among the cultivars grown in the same location and also among the oils produced with olives of the same cultivar but grown in different locations. For each cultivar, no significant differences were found among locations in terms of acidity and ΔK whereas peroxide value, K 232 , and K 270 differ significantly among locations for both Ogliarola and Peranzana cv. Concerning the phenolic content of Ogliarola cv., no differences were highlighted between the locations whereas the phenolic contents of Peranzana significantly changed as a function of the place of growing. On the basis of these results, the statistical multivariate analysis did not allow the classification into homogeneous groups neither of the oils belonging to the same cultivar nor of those obtained from olives picked in the same location. Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s11746-012-2141-8 Authors Antonietta Baiano, Dipartimento di Scienze Agrarie, degli Alimenti e dell’Ambiente, University of Foggia, Foggia, Italy Carmela Terracone, Dipartimento di Scienze Agrarie, degli Alimenti e dell’Ambiente, University of Foggia, Foggia, Italy Ilaria Viggiani, Dipartimento di Scienze Agrarie, degli Alimenti e dell’Ambiente, University of Foggia, Foggia, Italy Matteo Alessandro Del Nobile, Dipartimento di Scienze Agrarie, degli Alimenti e dell’Ambiente, University of Foggia, Foggia, Italy Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma. Content Type Journal Article Category Research article Pages 1-14 DOI 10.1007/s00018-012-1145-8 Authors Verónica Parrillas, Chemokines Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain Laura Martínez-Muñoz, Chemokines Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain Borja L. Holgado, Chemokines Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain Amit Kumar, PI3K Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, 28049 Madrid, Spain Graciela Cascio, Chemokines Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain Pilar Lucas, Chemokines Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain José Miguel Rodríguez-Frade, Chemokines Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain Marcos Malumbres, Cell Division and Cancer Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain Ana C. Carrera, PI3K Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, 28049 Madrid, Spain Karel HM van Wely, Genetic Instability Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, 28049 Madrid, Spain Mario Mellado, Chemokines Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. While different mammalian species express different proportions of α and β myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (α:β) while failing human ventricles express no detectable α-myosin. We report here fast-kinetic analysis of recombinant human α and β myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin motor and the first of α-myosin from any species. Our findings reveal substantial isoform differences in individual kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, α-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow β isoform despite 91% sequence identity between the motor domains of α- and β-myosin. Among the features that differentiate α- from β-S1: the ATP hydrolysis step of α-S1 is ~ten-fold faster than β-S1, α-S1 exhibits ~five-fold weaker actin affinity than β-S1, and actin·α-S1 exhibits rapid ADP release, which is 〉ten-fold faster than ADP release for β-S1. Overall, the cycle times are ten-fold faster for α-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding. Content Type Journal Article Category Erratum Pages 1-17 DOI 10.1007/s00018-012-1111-5 Authors John C. Deacon, Department of Molecular, Cellular and Developmental Biology and Biofrontiers Institute, University of Colorado, MCDB, UCB 347, Boulder, CO 80309, USA Marieke J. Bloemink, School of Biosciences, University of Kent, Canterbury, CT2 7NJ UK Heresh Rezavandi, School of Biosciences, University of Kent, Canterbury, CT2 7NJ UK Michael A. Geeves, School of Biosciences, University of Kent, Canterbury, CT2 7NJ UK Leslie A. Leinwand, Department of Molecular, Cellular and Developmental Biology and Biofrontiers Institute, University of Colorado, MCDB, UCB 347, Boulder, CO 80309, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The T cell integrin receptor LFA-1 orchestrates adhesion between T cells and antigen-presenting cells (APCs), resulting in formation of a contact zone known as the immune synapse (IS) which is supported by the cytoskeleton. L-plastin is a leukocyte-specific actin bundling protein that rapidly redistributes to the immune synapse following T cell–APC engagement. We used single domain antibodies (nanobodies, derived from camelid heavy-chain only antibodies) directed against functional and structural modules of L-plastin to investigate its contribution to formation of an immune synapse between Raji cells and human peripheral blood mononuclear cells or Jurkat T cells. Nanobodies that interact either with the EF hands or the actin binding domains of L-plastin both trapped L-plastin in an inactive conformation, causing perturbation of IS formation, MTOC docking towards the plasma membrane, T cell proliferation and IL-2 secretion. Both nanobodies delayed Ser 5 phosphorylation of L-plastin which is required for enhanced bundling activity. Moreover, one nanobody delayed LFA-1 phosphorylation, reduced the association between LFA-1 and L-plastin and prevented LFA-1 enrichment at the IS. Our findings reveal subtle mechanistic details that are difficult to attain by conventional means and show that L-plastin contributes to immune synapse formation at distinct echelons. Content Type Journal Article Category Research article Pages 1-14 DOI 10.1007/s00018-012-1169-0 Authors Sarah De Clercq, Department of Medical Protein Research, VIB, 9000 Ghent, Belgium Olivier Zwaenepoel, Department of Medical Protein Research, VIB, 9000 Ghent, Belgium Evelien Martens, Department of Medical Protein Research, VIB, 9000 Ghent, Belgium Joël Vandekerckhove, Department of Medical Protein Research, VIB, 9000 Ghent, Belgium Aude Guillabert, Department of Medical Protein Research, VIB, 9000 Ghent, Belgium Jan Gettemans, Department of Medical Protein Research, VIB, 9000 Ghent, Belgium Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The yeast SUMO (small ubiquitin-like modifier) orthologue SMT3 was initially discovered in a genetic suppressors screen for the centromeric protein Mif2 (Meluh and Koshland in Mol Bio Cell 6:793–807, 1 ). Later, it turned out that the homologous mammalian proteins SUMO1 to SUMO4 are reversible protein modifiers that can form isopeptide bonds with lysine residues of respective target proteins (Mahajan et al. in Cell 88:97–107, 2 ). This was the discovery of a post-translational modification called sumoylation, which enzymatically resembles ubiquitination. However, very soon it became clear that SUMO attachments served a far more diverse role than ubiquitination. Meanwhile, numerous cellular processes are known to be subject to the impact of SUMO modification, including transcription, protein targeting, protein solubility, apoptosis or activity of various enzymes. In many instances, SUMO proteins create new protein interaction surfaces or block existing interaction domains (Geiss-Friedlander and Melchior in Nat Rev in Mol Cell Biol 8:947–956, 3 ). For the past few years, sumoylation attracted increasing attention as a versatile regulator of toxic protein properties in neurodegenerative diseases. In this review, we summarize the growing knowledge about the involvement of sumoylation in neurodegeneration, and discuss the underlying molecular principles affected by this multifaceted and intriguing post-translational modification. Content Type Journal Article Category Review Pages 1-16 DOI 10.1007/s00018-012-1158-3 Authors Petranka Krumova, Neuroscience, Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4002 Basel, Switzerland Jochen H. Weishaupt, Neurology Department, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The vast majority of mammalian testes are located outside the body cavity for proper thermoregulation. Heat has an adverse effect on mammalian spermatogenesis and eventually leads to sub- or infertility. Recent studies have provided insights into the molecular response of male germ cells to high temperatures. Here, we review the effects of heat on male germ cells and discuss the mechanisms underlying germ cell loss and impairment. We also discuss the role of translational control in male germ cells as a potential protective mechanism against heat-induced germ cell apoptosis. Content Type Journal Article Category Review Pages 1-14 DOI 10.1007/s00018-012-1165-4 Authors Byunghyuk Kim, Department of Biological Sciences, Seoul National University, Seoul, 151-747 Korea Kyosun Park, Department of Biological Sciences, Seoul National University, Seoul, 151-747 Korea Kunsoo Rhee, Department of Biological Sciences, Seoul National University, Seoul, 151-747 Korea Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    This work evaluated the use of allyl fatty acid esters derived from vegetable oil (palmitic acid, soybean and sunflower oils) as reactive coalescing agents in a waterborne latex system. Allyl fatty acid derivatives (AFAD) from vegetable oils were synthesized by two different processes. The synthesis was monitored by IR-spectroscopy and the final product characterized by FT-IR, GC–MS, 1 H and 13 C NMR. The presence of conjugated double bonds in the aliphatic chain was confirmed, which is a determinant for the proposed autoxidative latexes drying mechanism. Each of the AFAD were subsequently added to a standard acrylic emulsion, in order to study its potential as reactive coalescing agent. The minimum film-forming temperature (MFT), glass transition temperature ( T g ), drying time and rubbing resistance to solvents were evaluated. The results showed that, when added to water-borne acrylic resins, an AFAD acts as a non-volatile plasticizer capable of autoxidative crosslinking with itself. Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s11746-012-2114-y Authors Joana V. Barbosa, LEPAE, Departamento de Engenharia Química, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal Fernanda Oliveira, CIN, Corporação Industrial do Norte, S.A., Estrada Nacional 13 (km 6), Apartado 1008, 4471-909 Maia, Portugal Jorge Moniz, Resiquímica, Resinas Químicas, S.A., Rua Francisco Lyon de Castro, 28, 2725-397 Mem Martins, Lisbon, Portugal Fernão D. Magalhães, LEPAE, Departamento de Engenharia Química, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal Margarida M. S. M. Bastos, LEPAE, Departamento de Engenharia Química, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    A selection of plant oils was catalytically transferred into 1,19-nonadecanedioate by a direct transesterification, isomerization and methoxycarbonylation under mild conditions using Pd/ o -C 6 H 4 (CH 2 P t Bu 2 ) 2 . Additionally, sulfuric acid was demonstrated as being able to substitute methane sulfonic acid as co-catalyst without any significant loss of activity and selectivity. Content Type Journal Article Category Original Paper Pages 1-5 DOI 10.1007/s11746-012-2143-6 Authors Guido Walther, Leibniz Institute for Catalysis at the University of Rostock (LIKAT), Albert-Einstein-Str. 29A, 18059 Rostock, Germany Andreas Martin, Leibniz Institute for Catalysis at the University of Rostock (LIKAT), Albert-Einstein-Str. 29A, 18059 Rostock, Germany Angela Köckritz, Leibniz Institute for Catalysis at the University of Rostock (LIKAT), Albert-Einstein-Str. 29A, 18059 Rostock, Germany Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Triolein was used as a model material to investigate the effect of concentration on self metathesis of vegetable oils. The metathesis reaction using Grubbs' second generation catalyst (used at a level of 2.5 mol % of triolein) was carried out at 38 °C using dichloromethane as the solvent. The products from three reaction concentrations were investigated: neat, 10 and 20 mmol/L. The products from the reactions were separated by column chromatography and the fractions were characterized by 1 H-NMR, 13 C-NMR, MS and FTIR. Mono-cyclic and multi-cyclic triacylglycerol-based compounds and different level aliphatic triacylglycerol-like oligomers were produced, but the compositions of the products were found to be significantly controlled by the reaction concentrations. Cyclic compounds were favorably produced at lower reaction concentrations, whereas, linear oligomers were favorably produced at higher reaction concentrations. Cyclic compounds were formed mainly from adjacent fatty acid chains on the glycerol backbone. In the neat reactions, only linear oligomers were produced. The trans / cis ratios increased as concentration was increased. Content Type Journal Article Category Original Paper Pages 1-13 DOI 10.1007/s11746-012-2106-y Authors Shaojun Li, Departments of Physics and Astronomy and Chemistry, Trent Centre for Biomaterials Research, Trent University, 1600 West Bank Drive, Peterborough, ON K9J 7B8, Canada Leila Hojabri, Departments of Physics and Astronomy and Chemistry, Trent Centre for Biomaterials Research, Trent University, 1600 West Bank Drive, Peterborough, ON K9J 7B8, Canada Suresh S. Narine, Departments of Physics and Astronomy and Chemistry, Trent Centre for Biomaterials Research, Trent University, 1600 West Bank Drive, Peterborough, ON K9J 7B8, Canada Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Reelin-Disabled-1 (Dab1) signaling has a well-established role in regulating neuronal migration during brain development. Binding of Reelin to its receptors induces Dab1 tyrosine phosphorylation. Tyrosine-phosphorylated Dab1 recruits a wide range of SH2 domain-containing proteins and activates multiple signaling cascades, resulting in cytoskeleton remodeling and precise neuronal positioning. In this review, we summarize recent progress in the Reelin-Dab1 signaling field. We focus on Dab1 alternative splicing as a mechanism for modulating the Reelin signal in developing brain. We suggest that correct positioning of neurons in the developing brain is at least partly controlled by alternatively-spliced Dab1 isoforms that differ in the number and type of tyrosine phosphorylation motifs that they contain. We propose a model whereby different subsets of SH2 domain-containing proteins are activated by different Dab1 isoforms, resulting in coordinated migration of neurons. Content Type Journal Article Category Review Pages 1-11 DOI 10.1007/s00018-012-1171-6 Authors Zhihua Gao, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada Roseline Godbout, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The insulin signaling pathway regulates whole-body glucose homeostasis by transducing extracellular signals from the insulin receptor (IR) to downstream intracellular targets, thus coordinating a multitude of biological functions. Dysregulation of IR or its signal transduction is associated with insulin resistance, which may culminate in type 2 diabetes. Following initial stimulation of IR, insulin signaling diverges into different pathways, activating multiple substrates that have roles in various metabolic and cellular processes. The integration of multiple pathways arising from IR activation continues to expand as new IR substrates are identified and characterized. Accordingly, our review will focus on roles for IR substrates as they pertain to three primary areas: metabolism/glucose uptake, mitogenesis/growth, and aging/longevity. While IR functions in a seemingly pleiotropic manner in many cell types, through these three main roles in fat and skeletal muscle cells, IR multi-tasks to regulate whole-body glucose homeostasis to impact healthspan and lifespan. Content Type Journal Article Category Review Pages 1-20 DOI 10.1007/s00018-012-1176-1 Authors Latha Ramalingam, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA Eunjin Oh, Department of Pediatrics, Herman B Wells Center, Indiana University School of Medicine, Indianapolis, IN, USA Debbie C. Thurmond, Departments of Pediatrics, Biochemistry and Molecular Biology, and Cellular and Integrative Physiology, Herman B Wells Center, Indiana University School of Medicine, 635 Barnhill Drive MS 2031, Indianapolis, IN 46202, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The schizophrenia susceptibility gene, Rgs4 , is one of the most intensively studied regulators of G-protein signaling members, well known to be fundamental in regulating neurotransmission. However, little is known about its role in the developing nervous system. We have isolated zebrafish rgs4 and shown that it is transcribed in the developing nervous system. Rgs4 knockdown did not affect neuron number and patterning but resulted in locomotion defects and aberrant development of axons. This was confirmed using a selective Rgs4 inhibitor, CCG-4986. Rgs4 knockdown also attenuated the level of phosphorylated-Akt1, and injection of constitutively-activated AKT1 rescued the motility defects and axonal phenotypes in the spinal cord but not in the hindbrain and trigeminal neurons. Our in vivo analysis reveals a novel role for Rgs4 in regulating axonogenesis during embryogenesis, which is mediated by another schizophrenia-associated gene, Akt1 , in a region-specific manner. Content Type Journal Article Category Research article Pages 1-16 DOI 10.1007/s00018-012-1178-z Authors Yi-Chuan Cheng, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, 33383 Taiwan Paul J. Scotting, Children’s Brain Tumour Research Centre, Centre for Genetics and Genomics, Queen’s Medical Centre, University of Nottingham, Nottingham, NG7 2UH UK Li-Sung Hsu, Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, 40201 Taiwan Sheng-Jia Lin, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, 33383 Taiwan Hung-Yu Shih, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, 33383 Taiwan Fu-Yu Hsieh, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, 33383 Taiwan Hui-Lan Wu, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, 33383 Taiwan Chu-Li Tsao, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, 33383 Taiwan Chia-Jung Shen, Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, 33383 Taiwan Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Omega-3 fatty acids, namely docosahexaenoic acid and eicosapentaenoic acid, have been linked to several beneficial health effects (i.e. mitigation effects of hypertension, stroke, diabetes, osteoporosis, depression, schizophrenia, asthma, macular degeneration, rheumatoid arthritis, etc.). The main source of omega-3 fatty acids is fish oil; lately however, fish oil market prices have increased significantly. This has prompted a significant amount of research on the use of single-cell oils as a source of omega-3 fatty acids. Some of the microbes reported to produce edible oil that contains omega-3 fatty acids are from the genus Schizochytrium , Thraustochytrium and Ulkenia. An advantage of a single cell oil is that it usually contains a significant amount of natural antioxidants (i.e. carotenoids and tocopherols), which can protect omega-3 fatty acids from oxidation, hence making this oil less prone to oxidation than oils derived from plants and marine animals. Production yields of single cell oils and of omega-3 fatty acids vary with the microbe used, with the fermentative growing conditions, and extractive procedures employed to recover the oil. This paper presents an overview of recent advances, reported within the last 10 years, in the production of single cell oils rich in omega-3 fatty acids. Content Type Journal Article Category Review Article Pages 1-16 DOI 10.1007/s11746-012-2154-3 Authors Roberto E. Armenta, Fermentation and Metabolic Engineering Group, Ocean Nutrition Canada Limited, 101 Research Drive, Dartmouth, NS B2Y 4T6, Canada Mercia C. Valentine, Fermentation and Metabolic Engineering Group, Ocean Nutrition Canada Limited, 101 Research Drive, Dartmouth, NS B2Y 4T6, Canada Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    This study examined the use of supercritical carbon dioxide (SC-CO 2 ) in the extraction of triglycerides from de-shelled Aquilaria crassna seeds. A central composite response surface methodology was employed to evaluate the effects of pressure, temperature and solvent-to-solid ratio (SSR) on total yield (TY), concentration of triglycerides ( C TG ) and recovery of triglycerides ( R TG ). For this experimental design, pressures that ranged from 250 to 350 bar, temperatures that ranged from 313 to 333 K and SSR that ranged from 80 to 120 were investigated for the SC-CO 2 extractions of 15 g of powdered de-shelled A. crassna seeds at a CO 2 flow rate of 25 mL/min under the supercritical phase. The values of TY, C TG and R TG achieved were 36.89 %, 709.5 mg/g and 95.4 %, respectively, under the conditions of a pressure of 340 bar, a temperature of 333 K and an SSR of 115 obtained from the quadratic fitting models. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s11746-012-2147-2 Authors Chao-Rui Chen, Department of Chemical Engineering, National Chung Hsing University, No. 250, Kuokuang Road, Taichung, 40227 Taiwan, ROC Yang-Jung Cheng, Department of Chemical Engineering, National Chung Hsing University, No. 250, Kuokuang Road, Taichung, 40227 Taiwan, ROC Chwen-Jen Shieh, Biotechnology Center, National Chung Hsing University, No. 250, Kuokuang Road, Taichung, 40227 Taiwan, ROC Daina Hsiang, Department of Information Management, Taoyuan Innovation Institute of Technology, No. 414, Sec. 3, Jhongshan E. Road, Jhongli, 32091 Taoyuan, Taiwan, ROC Chieh-Ming J. Chang, Department of Chemical Engineering, National Chung Hsing University, No. 250, Kuokuang Road, Taichung, 40227 Taiwan, ROC Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Posttranslational modifications such as phosphorylation are universally acknowledged regulators of protein function. Recently we characterised a striated muscle-specific isoform of the formin FHOD3 that displays distinct subcellular targeting and protein half-life compared to its non-muscle counterpart and which is dependent on phosphorylation by CK2 (formerly casein kinase 2). We now show that the two isoforms of FHOD3 are already expressed in the vertebrate embryonic heart. Analysis of CK2 alpha knockout mice showed that phosphorylation by CK2 is also required for proper targeting of muscle FHOD3 to the myofibrils in embryonic cardiomyocytes in situ. The localisation of muscle FHOD3 in the sarcomere varies depending on the maturation state, being either broader or restricted to the Z -disc proper in the adult heart. Following myofibril disassembly, such as that in dedifferentiating adult rat cardiomyocytes in culture, the expression of non-muscle FHOD3 is up-regulated, which is reversed once the myofibrils are reassembled. The shift in expression levels of different isoforms is accompanied by an increased co-localisation with p62, which is involved in autophagy, and affects the half-life of FHOD3. Phosphorylation of three amino acids in the C-terminus of FHOD3 by ROCK1 is sufficient for activation, which results in increased actin filament synthesis in cardiomyocytes and also a broader localisation pattern of FHOD3 in the myofibrils. ROCK1 can directly phosphorylate FHOD3, and FHOD3 seems to be the downstream mediator of the exaggerated actin filament formation phenotype that is induced in cardiomyocytes upon the overexpression of constitutively active ROCK1. We conclude that the expression of the muscle FHOD3 isoform is characteristic of the healthy mature heart and that two distinct phosphorylation events are crucial to regulate the activity of this isoform in thin filament assembly and maintenance. Content Type Journal Article Category Research article Pages 1-16 DOI 10.1007/s00018-012-1154-7 Authors Thomas Iskratsch, Muscle Cell Biology Section, The Randall Division of Cell and Molecular Biophysics and The Cardiovascular Division, BHF Research Excellence Centre, King’s College London, New Hunt’s House, Guy’s Campus, London, SE1 1UL UK Susan Reijntjes, Institute of Medical Sciences, University of Aberdeen, Scotland, UK Joseph Dwyer, Muscle Cell Biology Section, The Randall Division of Cell and Molecular Biophysics and The Cardiovascular Division, BHF Research Excellence Centre, King’s College London, New Hunt’s House, Guy’s Campus, London, SE1 1UL UK Paul Toselli, Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA Irene R. Dégano, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA Isabel Dominguez, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA Elisabeth Ehler, Muscle Cell Biology Section, The Randall Division of Cell and Molecular Biophysics and The Cardiovascular Division, BHF Research Excellence Centre, King’s College London, New Hunt’s House, Guy’s Campus, London, SE1 1UL UK Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Trichomes, originating from epidermal cells, are present on nearly all terrestrial plants. They exist in diverse forms, are readily accessible, and serve as an excellent model system for analyzing the molecular mechanisms in plant cell differentiation, including cell fate choices, cell cycle control, and cell morphogenesis. In Arabidopsis , two regulatory models have been identified that function in parallel in trichome formation; the activator–inhibitor model and the activator–depletion model. Cotton fiber, a similar unicellular structure, is controlled by some functional homologues of Arabidopsis trichome-patterning genes. Multicellular trichomes, as in tobacco and tomato, may form through a distinct pathway from unicellular trichomes. Recent research has shown that cell cycle control participates in trichome formation. In this review, we summarize the molecular mechanisms involved in the formation of unicellular and multicellular trichomes, and discuss the integration of the cell cycle in its initiation and morphogenesis. Content Type Journal Article Category Review Pages 1-12 DOI 10.1007/s00018-012-1147-6 Authors Changxian Yang, The Key Laboratory of Horticultural Plant Biology, Ministry of Education, Huazhong Agricultural University, Wuhan, 430070 China Zhibiao Ye, The Key Laboratory of Horticultural Plant Biology, Ministry of Education, Huazhong Agricultural University, Wuhan, 430070 China Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Haberlea rhodopensis is a resurrection plant with remarkable tolerance to desiccation. Haberlea exposed to drought stress, desiccation, and subsequent rehydration showed no signs of damage or severe oxidative stress compared to untreated control plants. Transcriptome analysis by next-generation sequencing revealed a drought-induced reprogramming, which redirected resources from growth towards cell protection. Repression of photosynthetic and growth-related genes during water deficiency was concomitant with induction of transcription factors (members of the NAC, NF-YA, MADS box, HSF, GRAS, and WRKY families) presumably acting as master switches of the genetic reprogramming, as well as with an upregulation of genes related to sugar metabolism, signaling, and genes encoding early light-inducible (ELIP), late embryogenesis abundant (LEA), and heat shock (HSP) proteins. At the same time, genes encoding other LEA, HSP, and stress protective proteins were constitutively expressed at high levels even in unstressed controls. Genes normally involved in tolerance to salinity, chilling, and pathogens were also highly induced, suggesting a possible cross-tolerance against a number of abiotic and biotic stress factors. A notable percentage of the genes highly regulated in dehydration and subsequent rehydration were novel, with no sequence homology to genes from other plant genomes. Additionally, an extensive antioxidant gene network was identified with several gene families possessing a greater number of antioxidant genes than most other species with sequenced genomes. Two of the transcripts most abundant during all conditions encoded catalases and five more catalases were induced in water-deficient samples. Using the pharmacological inhibitor 3-aminotriazole (AT) to compromise catalase activity resulted in increased sensitivity to desiccation. Metabolome analysis by GC or LC–MS revealed accumulation of sucrose, verbascose, spermidine, and γ-aminobutyric acid during drought, as well as particular secondary metabolites accumulating during rehydration. This observation, together with the complex antioxidant system and the constitutive expression of stress protective genes suggests that both constitutive and inducible mechanisms contribute to the extreme desiccation tolerance of H. rhodopensis . Content Type Journal Article Category Research article Pages 1-21 DOI 10.1007/s00018-012-1155-6 Authors Tsanko S. Gechev, Department of Plant Physiology and Plant Molecular Biology, University of Plovdiv, 24 Tsar Assen Str., Plovdiv, 4000 Bulgaria Maria Benina, Department of Plant Physiology and Plant Molecular Biology, University of Plovdiv, 24 Tsar Assen Str., Plovdiv, 4000 Bulgaria Toshihiro Obata, Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany Takayuki Tohge, Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany Neerakkal Sujeeth, Department of Plant Physiology and Plant Molecular Biology, University of Plovdiv, 24 Tsar Assen Str., Plovdiv, 4000 Bulgaria Ivan Minkov, Department of Plant Physiology and Plant Molecular Biology, University of Plovdiv, 24 Tsar Assen Str., Plovdiv, 4000 Bulgaria Jacques Hille, Molecular Biology of Plants, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands Mohamed-Ramzi Temanni, ServiceXS B.V., Plesmanlaan 1d, 2333 BZ Leiden, The Netherlands Andrew S. Marriott, Department of Chemistry, University of York, Heslington, York YO10 5DD, UK Ed Bergström, Department of Chemistry, University of York, Heslington, York YO10 5DD, UK Jane Thomas-Oates, Department of Chemistry, University of York, Heslington, York YO10 5DD, UK Carla Antonio, Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany Bernd Mueller-Roeber, Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany Jos H. M. Schippers, Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany Alisdair R. Fernie, Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany Valentina Toneva, Department of Plant Physiology and Plant Molecular Biology, University of Plovdiv, 24 Tsar Assen Str., Plovdiv, 4000 Bulgaria Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    To assess the suitability of microalgal strains for biodiesel production the lipid content and composition, especially individual triacylglycerols (TAG) and free fatty acids (FFA) must be determined. In this study, the compositions and concentrations of TAG and FFA were analysed in four halophytic algal species, Dunaliella salina , D. tertiolecta , D. bardawil , and D. granulata . These species were selected as part of a larger screen to identify species suitable for biofuel feedstocks. An accelerated solvent extraction instrument was used for lipids and fatty acid extraction using a dichloromethane–hexane solvent system. Ultra-performance liquid chromatography coupled with mass spectrometry (MS) detection was optimized and applied to the quantitative analysis of TAG and FFA in the different algal extracts. Individual TAG were characterized structurally using direct electrospray ionization (ESI) MS and MS/MS techniques. Cationic adducts (NH 4 + ) of TAG were detected and quantified in the positive ESI MS and MS/MS modes, while the negative ESI mode was used for FFA analysis. Over 20 TAG were identified and quantified in the four Dunaliella strains. Analysis of FFA compositions demonstrated that the most abundant FFA in these four algal species were palmitic, linolenic, linoleic, and oleic acids. Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s11746-012-2138-3 Authors Vera Samburova, Division of Atmospheric Sciences, Desert Research Institute, Reno, NV 89512-1095, USA Mark S. Lemos, Department of Chemical Engineering and Materials Science, University of California, Davis, CA 95616-5294, USA Sage Hiibel, Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV 89557-0330, USA S. Kent Hoekman, Division of Atmospheric Sciences, Desert Research Institute, Reno, NV 89512-1095, USA John C. Cushman, Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV 89557-0330, USA Barbara Zielinska, Division of Atmospheric Sciences, Desert Research Institute, Reno, NV 89512-1095, USA Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    This communication entails development of a facile continuous flow lipase immobilized poly(glycidyl methacrylate- co -ethylene dimethacrylate (poly(GMA- co -EDMA)) monolith microreactor for application in lipid transformations. Candida antarctica lipase B was covalently immobilized on poly(GMA- co -EDMA) monolith prepared in a 700-μm (internal diameter) silica capillary. The specific activity of the immobilized lipase was calculated to be 30 ± 0.03 U/mg, where U refers to μg p -nitrophenol generated/min from 3.5 mM p -nitrophenyl butyrate solution. The microreactor performance was further tested for synthesis of lauryl laurate via esterification. Conversions of up to 97 % were realized at a flow rate of 10 μL/min of a mixture of 0.1 M in both lauric acid and lauryl alcohol. These microreactors could be reused at least 15 times over a 1 month time period, stored at room temperature, with minimal to no reduction in the activity of the enzyme. We have also demonstrated microreactors to be useful for facile transesterification of castor oil triglycerides with online ESI–MS analytics key in lipidomics applications. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s11746-012-2139-2 Authors Samuel M. Mugo, Department of Physical Sciences-Chemistry, Grant MacEwan University, Edmonton, AB T5J 4S2, Canada Karl Ayton, Department of Physical Sciences-Chemistry, Grant MacEwan University, Edmonton, AB T5J 4S2, Canada Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Three different analytical techniques, namely NMR spectroscopy, mass spectrometry and dynamic light scattering, were used to unravel the structure and morphology of polyglycerol polyricinoleate (PGPR). This material is used as an emulsifier in the preparation of chocolate and other confectionary products. The use of 1D and 2D NMR techniques led to the distinction of two separate entities in commercial ricinoleic acid (RA) and PGPR samples, namely the monomeric and oligomeric RA (estolides). 1 H and 13 C spectra of PGPR confirmed the presence of polyglycerol moieties of various lengths being esterified by RA and estolides and to a lesser extent by oleic and linoleic acids. 13 C-NMR DOSY experiments demonstrated the occurrence of several species in PGPR. Electrospray Ionization and tandem Mass Spectrometry succeeded in identifying the presence of over 30 glycerol/polyglycerol species containing n glycerol moieties with n  = 1–6 esterified by monomeric and oligomeric RA molecules. Dynamic light scattering contributed to the characterization of PGPR morphology. The PGPR mixture contains relatively small-sized entities (monomers, dimmers, trimmers) and larger aggregates resulted from chain association. The percentage of larger aggregates is minimal compared to small-sized species. Content Type Journal Article Category Original Paper Pages 1-13 DOI 10.1007/s11746-012-2137-4 Authors Andreas Orfanakis, Department of Chemistry, University of Crete, P.O. Box 2208, Voutes Campus, 71003 Heraklion, Crete, Greece Emmanuel Hatzakis, Department of Chemistry, University of Crete, P.O. Box 2208, Voutes Campus, 71003 Heraklion, Crete, Greece Katerina Kanaki, Department of Chemistry, University of Crete, P.O. Box 2208, Voutes Campus, 71003 Heraklion, Crete, Greece Spiros A. Pergantis, Department of Chemistry, University of Crete, P.O. Box 2208, Voutes Campus, 71003 Heraklion, Crete, Greece Apostolos Rizos, Department of Chemistry, University of Crete, P.O. Box 2208, Voutes Campus, 71003 Heraklion, Crete, Greece Photis Dais, Department of Chemistry, University of Crete, P.O. Box 2208, Voutes Campus, 71003 Heraklion, Crete, Greece Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Since being discovered and intensively studied for over a decade, Smad ubiquitylation regulatory factor-1 (Smurf1) has been linked with several important biological pathways, including the bone morphogenetic protein pathway, the non-canonical Wnt pathway, and the mitogen-activated protein kinase pathway. Multiple functions of this ubiquitin ligase have been discovered in cell growth and morphogenesis, cell migration, cell polarity, and autophagy. Smurf1 is related to physiological manifestations in terms of age-dependent deficiency in bone formation and invasion of tumor cells. Smurf1-knockout mice have a significant phenotype in the skeletal system and considerable manifestations during embryonic development and neural outgrowth. In depth studying of Smurf1 will help us to understand the etiopathological mechanisms of related disorders. Here, we will summarize historical and recent studies on Smurf1, and discuss the E3 ligase-dependent and -independent functions of Smurf1. Moreover, intracellular regulations of Smurf1 and related physiological phenotypes will be described in this review. Content Type Journal Article Category Review Pages 1-13 DOI 10.1007/s00018-012-1170-7 Authors Yu Cao, State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850 China Lingqiang Zhang, State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850 China Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Hypoxic/ischemic injury remains the most dreaded cause of neurological disability and mortality. Despite the humbling experiences due to lack of promising therapy, our understanding of the complex cascades underlying the neuronal insult has led to advances in basic science research. One of the most noteworthy has been the effect of opioid receptors, especially the delta-opioid receptor (DOR), on hypoxic/ischemic neurons. Our recent studies, and those of others worldwide, present strong evidence that sheds light on DOR-mediated neuroprotection in the brain, especially in the cortex. The mechanisms of DOR neuroprotection are broadly categorized as: (1) stabilization of the ionic homeostasis, (2) inhibition of excitatory transmitter release, (3) attenuation of disrupted neuronal transmission, (4) increase in antioxidant capacity, (5) regulation of intracellular pathways—inhibition of apoptotic signals and activation of pro-survival signaling, (6) regulation of specific gene and protein expression, and (7) up-regulation of endogenous opioid release and/or DOR expression. Depending upon the severity and duration of hypoxic/ischemic insult, the release of endogenous opioids and DOR expression are regulated in response to the stress, and DOR signaling acts at multiple levels to confer neuronal tolerance to harmful insult. The phenomenon of DOR neuroprotection offers a potential clue for a promising target that may have significant clinical implications in our quest for neurotherapeutics. Content Type Journal Article Category Review Pages 1-13 DOI 10.1007/s00018-012-1167-2 Authors Xiaozhou He, The Third Clinical College of Suzhou University, Changzhou, Jiangsu, China Harleen K. Sandhu, The Vivian L Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, 77030 TX, USA Yilin Yang, The Third Clinical College of Suzhou University, Changzhou, Jiangsu, China Fei Hua, The Third Clinical College of Suzhou University, Changzhou, Jiangsu, China Nathalee Belser, The Vivian L Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, 77030 TX, USA Dong H. Kim, The Vivian L Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, 77030 TX, USA Ying Xia, The Vivian L Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, 77030 TX, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Although essential for energy production and cell fate decisions, the mechanisms that govern protein homeostasis, or proteostasis, in mitochondria are only recently beginning to emerge. Fresh experimental evidence has uncovered a role of molecular chaperones of the heat shock protein 90 (Hsp90) family in overseeing the protein folding environment in mitochondria. Initially implicated in protection against cell death, there is now evidence that Hsp90-directed protein quality control in mitochondria connects to hosts of cellular homeostatic networks that become prominently exploited in human cancer. Content Type Journal Article Category Review Pages 1-10 DOI 10.1007/s00018-012-1177-0 Authors Dario C. Altieri, Prostate Cancer Discovery and Development Program, The Wistar Institute Cancer Center, 3601 Spruce Street, Philadelphia, PA 19104, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    In mammals, one of the two X chromosomes of female cells is inactivated for dosage compensation between the sexes. X chromosome inactivation is initiated in early embryos by the noncoding Xist RNA. Subsequent chromatin modifications on the inactive X chromosome (Xi) lead to a remarkable stability of gene repression in somatic cell lineages. In mice, reactivation of genes on the Xi accompanies the establishment of pluripotent cells of the female blastocyst and the development of primordial germ cells. Xi reactivation also occurs when pluripotency is established during the reprogramming of somatic cells to induced pluripotent stem cells. The mechanism of Xi reactivation has attracted increasing interest for studying changes in epigenetic patterns and for improving methods of cell reprogramming. Here, we review recent advances in the understanding of Xi reactivation during development and reprogramming and illustrate potential clinical applications. Content Type Journal Article Category Review Pages 1-19 DOI 10.1007/s00018-012-1174-3 Authors Tatsuya Ohhata, Wellcome Trust and MRC Stem Cell Institute, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR UK Anton Wutz, Wellcome Trust and MRC Stem Cell Institute, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR UK Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Matricellular proteins interact with the extracellular matrix (ECM) and modulate cellular processes by binding to cell surface receptors and initiating intracellular signal transduction. Their association with the ECM and the ability of some members of this protein family to regulate cell motility have opened up new avenues of research to investigate their functions in normal and diseased cells. In this review, we summarize the research on CyrA, an ECM calmodulin-binding protein in Dictyostelium . CyrA is proteolytically cleaved into smaller EGF-like (EGFL) repeat containing cleavage products during development. The first EGFL repeat of CyrA binds to the cell surface and activates a novel signalling pathway that modulates cell motility in this model organism. The similarity of CyrA to the most well-characterized matricellular proteins in mammals allows it to be designated as the first matricellular protein identified in Dictyostelium . Content Type Journal Article Category Review Pages 1-9 DOI 10.1007/s00018-012-1068-4 Authors Robert J. Huber, Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada Danton H. O’Day, Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The primary cilium protrudes from the cell surface and acts as a sensor for chemical and mechanical growth cues, with receptors for a number of growth factors (PDGFα, Hedgehog, Wnt, Notch) concentrated within the ciliary membrane. In normal tissues, the cilium assembles after cells exit mitosis and is resorbed as part of cell cycle re-entry. Although regulation of the cilium by cell cycle transitions has been appreciated for over 100 years, only recently have data emerged to indicate the cilium also exerts influence on the cell cycle. The resorption/protrusion cycle, regulated by proteins including Aurora-A, VHL, and GSK-3β, influences cell responsiveness to growth cues involving cilia-linked receptors; further, resorption liberates the ciliary basal body to differentiate into the centrosome, which performs discrete functions in S-, G2-, and M-phase. Besides these roles, the cilium provides a positional cue that regulates polarity of cell division, and thus directs cells towards fates of differentiation versus proliferation. In this review, we summarize the specific mechanisms mediating the cilia-cell cycle dialog. We then emphasize the examples of polycystic kidney disease (PKD), nephronopthisis (NPHP), and VHL-linked renal cysts as cases in which defects of ciliary function influence disease pathology, and may also condition response to treatment. Content Type Journal Article Category Review Pages 1-26 DOI 10.1007/s00018-012-1052-z Authors Junmin Pan, Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing, 100084 China Tamina Seeger-Nukpezah, Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA Erica A. Golemis, Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The gastrointestinal epithelium forms the boundary between the body and external environment. It effectively provides a selective permeable barrier that limits the permeation of luminal noxious molecules, such as pathogens, toxins, and antigens, while allowing the appropriate absorption of nutrients and water. This selective permeable barrier is achieved by intercellular tight junction (TJ) structures, which regulate paracellular permeability. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, and can act as a trigger for the development of intestinal and systemic diseases. In this context, much effort has been taken to understand the roles of extracellular factors, including cytokines, pathogens, and food factors, for the regulation of the intestinal TJ barrier. Here, I discuss the regulation of the intestinal TJ barrier together with its implications for the pathogenesis of diseases. Content Type Journal Article Category Review Pages 1-29 DOI 10.1007/s00018-012-1070-x Authors Takuya Suzuki, Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, 1-4-4, Kagamiyama, Higashi-Hiroshima, 739-8528 Japan Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Monoamine oxidases (MAOs) are flavoproteins of the outer mitochondrial membrane that catalyze the oxidative deamination of biogenic and xenobiotic amines. In mammals there are two isoforms (MAO-A and MAO-B) that can be distinguished on the basis of their substrate specificity and their sensitivity towards specific inhibitors. Both isoforms are expressed in most tissues, but their expression in the central nervous system and their ability to metabolize monoaminergic neurotransmitters have focused MAO research on the functionality of the mature brain. MAO activities have been related to neurodegenerative diseases as well as to neurological and psychiatric disorders. More recently evidence has been accumulating indicating that MAO isoforms are expressed not only in adult mammals, but also before birth, and that defective MAO expression induces developmental abnormalities in particular of the brain. This review is aimed at summarizing and critically evaluating the new findings on the developmental functions of MAO isoforms during embryogenesis. Content Type Journal Article Category Review Pages 1-32 DOI 10.1007/s00018-012-1065-7 Authors Chi Chiu Wang, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong Ellen Billett, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK Astrid Borchert, Institute of Biochemistry, University Medicine Berlin-Charité, Oudenarder Str. 16, 13347 Berlin, Germany Hartmut Kuhn, Institute of Biochemistry, University Medicine Berlin-Charité, Oudenarder Str. 16, 13347 Berlin, Germany Christoph Ufer, Institute of Biochemistry, University Medicine Berlin-Charité, Oudenarder Str. 16, 13347 Berlin, Germany Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    This study was conducted to investigate the possible formation of trans fatty acids due to gamma-irradiation of ground beef and liquid egg via a radical path. The effects of irradiation on trans fatty acids in ground beef and liquid egg were evaluated by GC analysis. The control sample of ground beef had higher concentrations of total trans fatty acids than the liquid egg. C18:1-11t was the major trans fatty acid detected in non-irradiated ground beef. The results showed that irradiation led to a significant increase of total trans fatty acid content in both of the two food items with an absorbed dose range between 6.743 and 11.472 kGy ( P  〈 0.05). The change in C18:1-9t content was the most significant compared with other trans fatty acids. Additionally, gamma-irradiation caused a higher rate of trans fatty acid formation in liquid egg compared with ground beef. However, a slight decrease in the total trans fatty acid amount was observed in ground beef with an absorbed dose at 21.113 kGy. The increase in trans fatty acid content was negligible in liquid egg under the same absorbed dose. This result may be due to the oxidation of unsaturated configurations of both cis and trans fatty acids. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s11746-012-2125-8 Authors An Li, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193 People’s Republic of China Feng Wang, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193 People’s Republic of China Bei Fan, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193 People’s Republic of China Weiming Li, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193 People’s Republic of China Qingpeng Li, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193 People’s Republic of China Hongjie Zhou, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193 People’s Republic of China Yiming Ha, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193 People’s Republic of China Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Understanding the peopling history of Europe is crucial to comprehend the origins of modern populations. Of course, the analysis of current genetic data offers several explanations about human migration patterns which occurred on this continent, but it fails to explain precisely the impact of each demographic event. In this context, direct access to the DNA of ancient specimens allows the overcoming of recent demographic phenomena, which probably highly modified the constitution of the current European gene pool. In recent years, several DNA studies have been successfully conducted from ancient human remains thanks to the improvement of molecular techniques. They have brought new fundamental information on the peopling of Europe and allowed us to refine our understanding of European prehistory. In this review, we will detail all the ancient DNA studies performed to date on ancient European DNA from the Middle Paleolithic to the beginning of the protohistoric period. Content Type Journal Article Category Review Pages 1-15 DOI 10.1007/s00018-012-1180-5 Authors Marie Lacan, Laboratoire AMIS, CNRS UMR 5288, 37 Allées Jules Guesde, 31073 Toulouse cedex 3, France Christine Keyser, Laboratoire AMIS, CNRS UMR 5288, 37 Allées Jules Guesde, 31073 Toulouse cedex 3, France Eric Crubézy, Laboratoire AMIS, CNRS UMR 5288, 37 Allées Jules Guesde, 31073 Toulouse cedex 3, France Bertrand Ludes, Laboratoire AMIS, CNRS UMR 5288, 37 Allées Jules Guesde, 31073 Toulouse cedex 3, France Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Most tumor cells exhibit a glycolytic phenotype. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Among the agents that can suppress glycolysis is citrate, a member of the Krebs cycle and an inhibitor of phosphofructokinase. Here, we show that citrate can trigger cell death in multiple cancer cell lines. The lethal effect of citrate was found to be related to the activation of apical caspases-8 and -2, rather than to the inhibition of cellular energy metabolism. Hence, increasing concentrations of citrate induced characteristic manifestations of apoptosis, such as caspase-3 activation, and poly-ADP-ribose polymerase cleavage, as well as the release of cytochrome c . Apoptosis induction did not involve the receptor-mediated pathway, since the processing of caspase-8 was not attenuated in cells deficient in Fas-associated protein with Death Domain. We propose that the activation of apical caspases by citrate could be explained by its kosmotropic properties. Caspase-8 is activated by proximity-induced dimerization, which might be facilitated by citrate through the stabilization of intermolecular interactions between the proteins. Content Type Journal Article Category Research article Pages 1-9 DOI 10.1007/s00018-012-1166-3 Authors Björn Kruspig, Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden Azadeh Nilchian, Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden Sten Orrenius, Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden Boris Zhivotovsky, Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden Vladimir Gogvadze, Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    We investigated the effects of bone morphogenetic proteins (BMPs) in determining the positional identity of neurons generated in vitro from mouse embryonic stem cells (ESCs), an aspect that has been neglected thus far. Classical embryological studies in lower vertebrates indicate that BMPs inhibit the default fate of pluripotent embryonic cells, which is both neural and anterior. Moreover, mammalian ESCs generate neurons more efficiently when cultured in a minimal medium containing BMP inhibitors. In this paper, we show that mouse ESCs produce, secrete, and respond to BMPs during in vitro neural differentiation. After neuralization in a minimal medium, differentiated ESCs show a gene expression profile consistent with a midbrain identity, as evaluated by the analysis of a number of markers of anterior–posterior and dorsoventral identity. We found that BMPs endogenously produced during neural differentiation mainly act by inhibiting the expression of a telencephalic gene profile, which was revealed by the treatment with Noggin or with other BMP inhibitors. To better characterize the effect of BMPs on positional fate, we compared the global gene expression profiles of differentiated ESCs with those of embryonic forebrain, midbrain, and hindbrain. Both Noggin and retinoic acid (RA) support neuronal differentiation of ESCs, but they show different effects on their positional identity: whereas RA supports the typical gene expression profile of hindbrain neurons, Noggin induces a profile characteristic of dorsal telencephalic neurons. Our findings show that endogenously produced BMPs affect the positional identity of the neurons that ESCs spontaneously generate when differentiating in vitro in a minimal medium. The data also support the existence of an intrinsic program of neuronal differentiation with dorsal telencephalic identity. Our method of ESC neuralization allows for fast differentiation of neural cells via the same signals found during in vivo embryonic development and for the acquisition of cortical identity by the inhibition of BMP alone. Content Type Journal Article Category Research Article Pages 1-17 DOI 10.1007/s00018-012-1182-3 Authors Michele Bertacchi, Scuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56100 Pisa, Italy Luca Pandolfini, Scuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56100 Pisa, Italy Elisa Murenu, CIBIO, Università di Trento, Trento, Italy Alessandro Viegi, Scuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56100 Pisa, Italy Simona Capsoni, Scuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56100 Pisa, Italy Alessandro Cellerino, Scuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56100 Pisa, Italy Andrea Messina, CIBIO, Università di Trento, Trento, Italy Simona Casarosa, CIBIO, Università di Trento, Trento, Italy Federico Cremisi, Scuola Normale Superiore di Pisa, Piazza dei Cavalieri 7, 56100 Pisa, Italy Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, IGF2BP3) belong to a conserved family of RNA-binding, oncofetal proteins. Several studies have shown that these proteins act in various important aspects of cell function, such as cell polarization, migration, morphology, metabolism, proliferation and differentiation. In this review, we discuss the IGF2BP family’s role in cancer biology and how this correlates with their proposed functions during embryogenesis. IGF2BPs are mainly expressed in the embryo, in contrast with comparatively lower or negotiable levels in adult tissues. IGF2BP1 and IGF2BP3 have been found to be re-expressed in several aggressive cancer types. Control of IGF2BPs’ expression is not well understood; however, let-7 microRNAs, β-catenin (CTNNB1) and MYC have been proposed to be involved in their regulation. In contrast to many other RNA-binding proteins, IGF2BPs are almost exclusively observed in the cytoplasm where they associate with target mRNAs in cytoplasmic ribonucleoprotein complexes (mRNPs). During development, IGF2BPs are required for proper nerve cell migration and morphological development, presumably involving the control of cytoskeletal remodeling and dynamics, respectively. Likewise, IGF2BPs modulate cell polarization, adhesion and migration in tumor-derived cells. Moreover, they are highly associated with cancer metastasis and the expression of oncogenic factors (KRAS, MYC and MDR1). However, a pro-metastatic role of IGF2BPs remains controversial due to the lack of ‘classical’ in vivo studies. Nonetheless, IGF2BPs could provide valuable targets in cancer treatment with many of their in vivo roles to be fully elucidated. Content Type Journal Article Category Review Pages 1-19 DOI 10.1007/s00018-012-1186-z Authors Jessica L. Bell, Section for Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University Halle, 06120 Halle, Germany Kristin Wächter, Section for Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University Halle, 06120 Halle, Germany Britta Mühleck, Section for Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University Halle, 06120 Halle, Germany Nikolaos Pazaitis, Section for Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University Halle, 06120 Halle, Germany Marcel Köhn, Section for Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University Halle, 06120 Halle, Germany Marcell Lederer, Section for Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University Halle, 06120 Halle, Germany Stefan Hüttelmaier, Section for Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University Halle, 06120 Halle, Germany Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Gram-negative bacteria can produce specific proteinaceous inhibitors to defend themselves against the lytic action of host lysozymes. So far, four different lysozyme inhibitor families have been identified. Here, we report the crystal structure of the Escherichia coli periplasmic lysozyme inhibitor of g-type lysozyme (PliG-Ec) in complex with Atlantic salmon g-type lysozyme (SalG) at a resolution of 0.95 Å, which is exceptionally high for a complex of two proteins. The structure reveals for the first time the mechanism of g-type lysozyme inhibition by the PliG family. The latter contains two specific conserved regions that are essential for its inhibitory activity. The inhibitory complex formation is based on a double ‘key-lock’ mechanism. The first key-lock element is formed by the insertion of two conserved PliG regions into the active site of the lysozyme. The second element is defined by a distinct pocket of PliG accommodating a lysozyme loop. Computational analysis indicates that this pocket represents a suitable site for small molecule binding, which opens an avenue for the development of novel antibacterial agents that suppress the inhibitory activity of PliG. Content Type Journal Article Category Research Article Pages 1-10 DOI 10.1007/s00018-012-1184-1 Authors S. Leysen, Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Herestraat 49 bus 822, 3000 Leuven, Belgium L. Vanderkelen, Laboratory of Food Microbiology, Leuven Food Science and Nutrition Research Centre (LFoRCe), Katholieke Universiteit Leuven, Kasteelpark Arenberg 22, 3001 Leuven, Belgium S. D. Weeks, Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Herestraat 49 bus 822, 3000 Leuven, Belgium C. W. Michiels, Laboratory of Food Microbiology, Leuven Food Science and Nutrition Research Centre (LFoRCe), Katholieke Universiteit Leuven, Kasteelpark Arenberg 22, 3001 Leuven, Belgium S. V. Strelkov, Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Herestraat 49 bus 822, 3000 Leuven, Belgium Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Cardiovascular disease is the foremost cause of morbidity and mortality in the Western world. Atherosclerosis followed by thrombosis (atherothrombosis) is the pathological process underlying most myocardial, cerebral, and peripheral vascular events. Atherothrombosis is a complex and heterogeneous inflammatory process that involves interactions between many cell types (including vascular smooth muscle cells, endothelial cells, macrophages, and platelets) and processes (including migration, proliferation, and activation). Despite a wealth of knowledge from many recent studies using knockout mouse and human genetic studies (GWAS and candidate approach) identifying genes and proteins directly involved in these processes, traditional cardiovascular risk factors (hyperlipidemia, hypertension, smoking, diabetes mellitus, sex, and age) remain the most useful predictor of disease. Eicosanoids (20 carbon polyunsaturated fatty acid derivatives of arachidonic acid and other essential fatty acids) are emerging as important regulators of cardiovascular disease processes. Drugs indirectly modulating these signals, including COX-1/COX-2 inhibitors, have proven to play major roles in the atherothrombotic process. However, the complexity of their roles and regulation by opposing eicosanoid signaling, have contributed to the lack of therapies directed at the eicosanoid receptors themselves. This is likely to change, as our understanding of the structure, signaling, and function of the eicosanoid receptors improves. Indeed, a major advance is emerging from the characterization of dysfunctional naturally occurring mutations of the eicosanoid receptors. In light of the proven and continuing importance of risk factors, we have elected to focus on the relationship between eicosanoids and cardiovascular risk factors. Content Type Journal Article Category Review Pages 1-20 DOI 10.1007/s00018-012-0982-9 Authors Scott Gleim, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, 300 George Street #795H, New Haven, CT 06511, USA Jeremiah Stitham, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, 300 George Street #795H, New Haven, CT 06511, USA Wai Ho Tang, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, 300 George Street #795H, New Haven, CT 06511, USA Kathleen A. Martin, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, 300 George Street #795H, New Haven, CT 06511, USA John Hwa, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, 300 George Street #795H, New Haven, CT 06511, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Age is an important risk for autoimmunity, and many autoimmune diseases preferentially occur in the second half of adulthood when immune competence has declined and thymic T cell generation has ceased. Many tolerance checkpoints have to fail for an autoimmune disease to develop, and several of those are susceptible to the immune aging process. Homeostatic T cell proliferation which is mainly responsible for T cell replenishment during adulthood can lead to the selection of T cells with increased affinity to self- or neoantigens and enhanced growth and survival properties. These cells can acquire a memory-like phenotype, in particular under lymphopenic conditions. Accumulation of end-differentiated effector T cells, either specific for self-antigen or for latent viruses, have a low activation threshold due to the expression of signaling and regulatory molecules and generate an inflammatory environment with their ability to be cytotoxic and to produce excessive amounts of cytokines and thereby inducing or amplifying autoimmune responses. Content Type Journal Article Category Multi-author review Pages 1-9 DOI 10.1007/s00018-012-0970-0 Authors Jörg J. Goronzy, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, CCSR Building Room 2215, Mail Code 5166, 269 Campus Drive West, Stanford, CA 94305-5166, USA Cornelia M. Weyand, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, CCSR Building Room 2215, Mail Code 5166, 269 Campus Drive West, Stanford, CA 94305-5166, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The human airway epithelium is a pseudostratified heterogenous layer comprised of ciliated, secretory, intermediate, and basal cells. As the stem/progenitor population of the airway epithelium, airway basal cells differentiate into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. Transcriptome analysis of airway basal cells revealed high expression of vascular endothelial growth factor A (VEGFA), a gene not typically associated with the function of this cell type. Using cultures of primary human airway basal cells, we demonstrate that basal cells express all of the three major isoforms of VEGFA (121, 165 and 189) but lack functional expression of the classical VEGFA receptors VEGFR1 and VEGFR2. The VEGFA is actively secreted by basal cells and while it appears to have no direct autocrine function on basal cell growth and proliferation, it functions in a paracrine manner to activate MAPK signaling cascades in endothelium via VEGFR2-dependent signaling pathways. Using a cytokine- and serum-free co-culture system of primary human airway basal cells and human endothelial cells revealed that basal cell-secreted VEGFA activated endothelium to express mediators that, in turn, stimulate and support basal cell proliferation and growth. These data demonstrate novel VEGFA-mediated cross-talk between airway basal cells and endothelium, the purpose of which is to modulate endothelial activation and in turn stimulate and sustain basal cell growth. Content Type Journal Article Category Research Article Pages 1-15 DOI 10.1007/s00018-012-0922-8 Authors Giacomo Curradi, Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 96, New York, NY 10065, USA Matthew S. Walters, Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 96, New York, NY 10065, USA Bi-Sen Ding, Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 96, New York, NY 10065, USA Shahin Rafii, Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 96, New York, NY 10065, USA Neil R. Hackett, Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 96, New York, NY 10065, USA Ronald G. Crystal, Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 96, New York, NY 10065, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The relatively homogenous clinical features and poor prognosis of chronic myelomonocytic leukemia (CMML) are associated with a molecular heterogeneity, with various mutations impacting several convergent pathways. Due to the restricted understanding of the mechanism involved in leukemogenesis, CMML still appears as a diagnostic and therapeutic undertaking, and poor prognosis of leukemia. Contrary to chronic myelogenous leukemia, BCR – ABL1 -positive, cytogenetic, and molecular abnormalities of CMML are not specific and not pathognomonic, confirming the different levels of heterogeneity of this disease. Various mutations can be associated with a common phenotype not distinct at the clinical level, further demonstrating that molecular probings are needed for choosing individual targeted therapies. Content Type Journal Article Category Review Pages 1-9 DOI 10.1007/s00018-012-0956-y Authors Jean-Noël Bastie, Faculté de Médecine, Inserm UMR 866, Université de Bourgogne, 7 bd Jeanne d’Arc, 21000 Dijon, France Romain Aucagne, Faculté de Médecine, Inserm UMR 866, Université de Bourgogne, 7 bd Jeanne d’Arc, 21000 Dijon, France Nathalie Droin, Inserm UMR 1009, IRCIV, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France Eric Solary, Inserm UMR 1009, IRCIV, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France Laurent Delva, Faculté de Médecine, Inserm UMR 866, Université de Bourgogne, 7 bd Jeanne d’Arc, 21000 Dijon, France Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The proteasome is a multi-catalytic protein complex whose primary function is the degradation of abnormal or foreign proteins. Upon exposure of cells to interferons (IFNs), the β1i/LMP2, β2i/MECL-1, and β5i/LMP7 subunits are induced and incorporated into newly synthesized immunoproteasomes (IP), which are thought to function solely as critical players in the optimization of the CD8 + T-cell response. However, the observation that IP are present in several non-immune tissues under normal conditions and/or following pathological events militates against the view that its role is limited to MHC class I presentation. In support of this concept, the recent use of genetic models deficient for β1i/LMP2, β2i/MECL-1, or β5i/LMP7 has uncovered unanticipated functions for IP in innate immunity and non-immune processes. Herein, we review recent data in an attempt to clarify the role of IP beyond MHC class I epitope presentation with emphasis on its involvement in the regulation of protein homeostasis, cell proliferation, and cytokine gene expression. Content Type Journal Article Category Review Pages 1-16 DOI 10.1007/s00018-012-0938-0 Authors Frédéric Ebstein, Institut für Biochemie, Charité-Universitätsmedizin Berlin Campus CVK, Oudenarderstr.16, 13347 Berlin, Germany Peter-Michael Kloetzel, Institut für Biochemie, Charité-Universitätsmedizin Berlin Campus CVK, Oudenarderstr.16, 13347 Berlin, Germany Elke Krüger, Institut für Biochemie, Charité-Universitätsmedizin Berlin Campus CVK, Oudenarderstr.16, 13347 Berlin, Germany Ulrike Seifert, Institut für Biochemie, Charité-Universitätsmedizin Berlin Campus CVK, Oudenarderstr.16, 13347 Berlin, Germany Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Metabolic engineering is the enabling science of development of efficient cell factories for the production of fuels, chemicals, pharmaceuticals, and food ingredients through microbial fermentations. The yeast Saccharomyces cerevisiae is a key cell factory already used for the production of a wide range of industrial products, and here we review ongoing work, particularly in industry, on using this organism for the production of butanol, which can be used as biofuel, and isoprenoids, which can find a wide range of applications including as pharmaceuticals and as biodiesel. We also look into how engineering of yeast can lead to improved uptake of sugars that are present in biomass hydrolyzates, and hereby allow for utilization of biomass as feedstock in the production of fuels and chemicals employing S. cerevisiae . Finally, we discuss the perspectives of how technologies from systems biology and synthetic biology can be used to advance metabolic engineering of yeast. Content Type Journal Article Category Review Pages 1-20 DOI 10.1007/s00018-012-0945-1 Authors Kuk-Ki Hong, Novo Nordisk Centre for Biosustainability, Department of Chemical and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden Jens Nielsen, Novo Nordisk Centre for Biosustainability, Department of Chemical and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Centrins are small, highly conserved members of the EF-hand superfamily of calcium-binding proteins that are found throughout eukaryotes. They play a major role in ensuring the duplication and appropriate functioning of the ciliary basal bodies in ciliated cells. They have also been localised to the centrosome, which is the major microtubule organising centre in animal somatic cells. We describe the identification, cloning and characterisation of centrins in multiple eukaryotic species. Although centrins have been implicated in centriole biogenesis, recent results have indicated that centrosome duplication can, in fact, occur in the absence of centrins. We discuss these data and the non-centrosomal functions that are emerging for the centrins. In particular, we discuss the involvement of centrins in nucleotide excision repair, a process that repairs the DNA lesions that are induced primarily by ultraviolet irradiation. We discuss how centrin may be involved in these diverse processes and contribute to nuclear and cytoplasmic events. Content Type Journal Article Category Review Pages 1-19 DOI 10.1007/s00018-012-0961-1 Authors Tiago J. Dantas, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, University Road, Galway, Ireland Owen M. Daly, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, University Road, Galway, Ireland Ciaran G. Morrison, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, University Road, Galway, Ireland Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The pathobiology of pulmonary arterial hypertension (PAH) involves a remodeling process in distal pulmonary arteries, as well as vasoconstriction and in situ thrombosis, leading to an increase in pulmonary vascular resistance, right heart failure and death. Its etiology may be idiopathic, but PAH is also frequently associated with underlying conditions such as connective tissue diseases. During the past decade, more than welcome novel therapies have been developed and are in development, including those increasingly targeting the remodeling process. These therapeutic options modestly increase the patients’ long-term survival, now approaching 60% at 5 years. However, non-invasive tools for confirming PAH diagnosis, and assessing disease severity and response to therapy, are tragically lacking and would help to select the best treatment. After exclusion of other causes of pulmonary hypertension, a final diagnosis still relies on right heart catheterization, an invasive technique which cannot be repeated as often as an optimal follow-up might require. Similarly, other techniques and biomarkers used for assessing disease severity and response to treatment generally lack specificity and have significant limitations. In this review, imaging as well as current and future circulating biomarkers for diagnosis, prognosis, and follow-up are discussed. Content Type Journal Article Category Review Pages 1-27 DOI 10.1007/s00018-012-0950-4 Authors Marjorie Barrier, Pulmonary Hypertension Research Group, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC G1V 4G5, Canada Jolyane Meloche, Pulmonary Hypertension Research Group, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC G1V 4G5, Canada Maria Helena Jacob, Pulmonary Hypertension Research Group, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC G1V 4G5, Canada Audrey Courboulin, Pulmonary Hypertension Research Group, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC G1V 4G5, Canada Steeve Provencher, Pulmonary Hypertension Research Group, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC G1V 4G5, Canada Sébastien Bonnet, Pulmonary Hypertension Research Group, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC G1V 4G5, Canada Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Cell adhesion molecule 1 (CADM1), expressed by human lung mast cells (HLMCs), mediates their adhesion to airway smooth muscle (ASM), and contributes to ASM-dependent HLMC proliferation and survival. CADM1 is expressed in alternatively spliced isoforms, but those present in HLMCs and their function are not known. We cloned three functional and one cryptic non-functional isoform with alternative splicing between exons 7/11 and 1/2, respectively, from HLMCs and human MC lines (HMC-1 and LAD2). Differentiated HLMCs and LAD2 cells expressed the functional isoform SP4 containing exons 7/8/11 (~80% of clones), as well as SP1 (exons 7/8/9/11) and a novel SP6 (exons 7/8/9/10/11). In contrast, immature HMC-1 cells expressed only functional SP4. SP4 overexpression in HMC-1 cells and HLMCs augmented homotypic adhesion to a greater extent than SP1 in various conditions. In contrast, CADM1 downregulation abolished homotypic adhesion, indicating that CADM1 is the sole receptor mediating mast cell aggregation. CADM1-mediated adhesion was enhanced by the presence of cell survival factors. SP1 overexpression in HMC-1 cells compromised survival compared to SP4 overexpression or control. CADM1 downregulation resulted in reduced viability and decreased expression of the pro-survival protein Mcl-1 L , but not Blc-2 or Bcl-X L , and increased caspase-3/7 activity in both HMC-1 cells and HLMCs. This coincided with decreased basal Kit levels in HLMCs. In summary, human MCs express multiple CADM1 isoforms which exhibit differential regulation of survival and homotypic adhesion. The most highly expressed SP4 isoform is likely to contribute to MC aggregation and longevity in mastocytosis, and augment the pathophysiology of allergic diseases. Content Type Journal Article Category Research Article Pages 1-14 DOI 10.1007/s00018-012-0948-y Authors Elena P. Moiseeva, Department of Infection, Immunity and Inflammation, Institute for Lung Health, Clinical Sciences Wing, Glenfield Hospital, University of Leicester, Leicester, LE3 9QP UK Mark L. Leyland, Department of Biochemistry, University of Leicester, Leicester, UK Peter Bradding, Department of Infection, Immunity and Inflammation, Institute for Lung Health, Clinical Sciences Wing, Glenfield Hospital, University of Leicester, Leicester, LE3 9QP UK Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    A disintegrin and metalloproteinase10 (ADAM10) has been implicated as a major sheddase responsible for the ectodomain shedding of a number of important surface molecules including the amyloid precursor protein and cadherins. Despite a well-documented role of ADAM10 in health and disease, little is known about the regulation of this protease. To address this issue we conducted a split-ubiquitin yeast two-hybrid screen to identify membrane proteins that interact with ADAM10. The yeast experiments and co-immunoprecipitation studies in mammalian cell lines revealed tetraspanin15 (TSPAN15) to specifically associate with ADAM10. Overexpression of TSPAN15 or RNAi-mediated knockdown of TSPAN15 led to significant changes in the maturation process and surface expression of ADAM10. Expression of an endoplasmic reticulum (ER) retention mutant of TSPAN15 demonstrated an interaction with ADAM10 already in the ER. Pulse-chase experiments confirmed that TSPAN15 accelerates the ER-exit of the ADAM10–TSPAN15 complex and stabilizes the active form of ADAM10 at the cell surface. Importantly, TSPAN15 also showed the ability to mediate the regulation of ADAM10 protease activity exemplified by an increased shedding of N-cadherin and the amyloid precursor protein. In conclusion, our data show that TSPAN15 is a central modulator of ADAM10-mediated ectodomain shedding. Therapeutic manipulation of its expression levels may be an additional approach to specifically regulate the activity of the amyloid precursor protein alpha-secretase ADAM10. Content Type Journal Article Category Research Article Pages 1-14 DOI 10.1007/s00018-012-0960-2 Authors Johannes Prox, Institut für Biochemie, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Michael Willenbrock, Institut für Biochemie, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Silvio Weber, Institut für Biochemie, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Tobias Lehmann, Institut für Biochemie, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Dirk Schmidt-Arras, Institut für Biochemie, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Ralf Schwanbeck, Institut für Biochemie, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Paul Saftig, Institut für Biochemie, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Michael Schwake, Institut für Biochemie, Christian-Albrechts-Universität zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Oxidative stress and low-grade inflammation are the hallmarks of the aging process and are even more enhanced in many age-related degenerative diseases. Mitochondrial dysfunction and oxidative stress can provoke and potentiate inflammatory responses, but the mechanism has remained elusive. Recent studies indicate that oxidative stress can induce the assembly of multiprotein inflammatory complexes called the inflammasomes. Nod-like receptor protein 3 (NLRP3) is the major immune sensor for cellular stress signals, e.g., reactive oxygen species, ceramides, and cathepsin B. NLRP3 activation triggers the caspase-1-mediated maturation of the precursors of IL-1β and IL-18 cytokines. During aging, the autophagic clearance of mitochondria declines and dysfunctional mitochondria provoke chronic oxidative stress, which disturbs the cellular redox balance. Moreover, increased NF-κB signaling observed during aging could potentiate the expression of NLRP3 and cytokine proforms enhancing the priming of NLRP3 inflammasomes. Recent studies have demonstrated that NLRP3 activation is associated with several age-related diseases, e.g., the metabolic syndrome. We will review here the emerging field of inflammasomes in the appearance of the proinflammatory phenotype during the aging process and in age-related diseases. Content Type Journal Article Category Review Pages 1-15 DOI 10.1007/s00018-012-0962-0 Authors Antero Salminen, Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland Johanna Ojala, Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland Kai Kaarniranta, Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland Anu Kauppinen, Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Rapid signal propagation along vertebrate axons is facilitated by their insulation with myelin, a plasma membrane specialization of glial cells. The recent application of ‘omics’ approaches to the myelinating cells of the central nervous system, oligodendrocytes, revealed their mRNA signatures, enhanced our understanding of how myelination is regulated, and established that the protein composition of myelin is much more complex than previously thought. This review provides a meta-analysis of the 〉1,200 proteins thus far identified by mass spectrometry in biochemically purified central nervous system myelin. Contaminating proteins are surprisingly infrequent according to bioinformatic prediction of subcellular localization and comparison with the transcriptional profile of oligodendrocytes. The integration of datasets also allowed the subcategorization of the myelin proteome into functional groups comprising genes that are coregulated during oligodendroglial differentiation. An unexpectedly large number of myelin-related genes cause—when mutated in humans—hereditary diseases affecting the physiology of the white matter. Systematic approaches to oligodendrocytes and myelin thus provide valuable resources for the molecular dissection of developmental myelination, glia–axonal interactions, leukodystrophies, and demyelinating diseases. Content Type Journal Article Category Review Pages 1-16 DOI 10.1007/s00018-012-0958-9 Authors Patricia de Monasterio-Schrader, Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany Olaf Jahn, Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany Stefan Tenzer, Institute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany Sven P. Wichert, Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany Julia Patzig, Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany Hauke B. Werner, Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Established views on the maintenance of immunological memory have been challenged recently by the description of memory plasma cells and memory T helper (Th) lymphocytes residing in the bone marrow (BM) in dedicated survival niches, resting in terms of proliferation and migration. While memory plasma cells are no longer reactive to antigen, memory Th lymphocytes are in a state of attentive rest, and can be reactivated fast and efficiently. Here, we discuss the signals controlling these resting states, which the memory lymphocytes receive from their microenvironment. Content Type Journal Article Category Multi-author review Pages 1-5 DOI 10.1007/s00018-012-0969-6 Authors Koji Tokoyoda, German Rheumatism Research Center Berlin, Chariteplatz 1, 10117 Berlin, Germany Andreas Radbruch, German Rheumatism Research Center Berlin, Chariteplatz 1, 10117 Berlin, Germany Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Tetraspanins regulate a variety of cellular functions. However, the general cellular mechanisms by which tetraspanins regulate these functions remain poorly understood. In this article we collected the observations that tetraspanins regulate the formation and/or development of various tubular structures of cell membrane. Because tetraspanins and their associated proteins (1) are localized at the tubular structures, such as the microvilli, adhesion zipper, foot processes, and penetration peg, and/or (2) regulate the morphogenesis of these membrane tubular structures, tetraspanins probably modulate various cellular functions through these membrane tubular structures. Some tetraspanins inhibit membrane tubule formation and/or extension, while others promote them. We predict that tetraspanins regulate the formation and/or development of various membrane tubular structures: (1) microvilli or nanovilli at the plasma membranes free of cell and matrix contacts, (2) membrane tubules at the plasma membrane of cell-matrix and cell-cell interfaces, and (3) membrane tubules at the intracellular membrane compartments. These different membrane tubular structures likely share a common morphogenetic mechanism that involves tetraspanins. Tetraspanins probably regulate the morphogenesis of membrane tubular structures by altering (1) the biophysical properties of the cell membrane such as curvature and/or (2) the membrane connections of cytoskeleton. Since membrane tubular structures are associated with cell functions such as adhesion, migration, and intercellular communication, in all of which tetraspanins are involved, the differential effects of tetraspanins on membrane tubular structures likely lead to the functional difference of tetraspanins. Content Type Journal Article Category Review Pages 1-10 DOI 10.1007/s00018-012-0954-0 Authors Xin A. Zhang, Department of Medicine, Vascular Biology and Cancer Centers, University of Tennessee Health Science Center, Cancer Research Building Room 220, 19 South Manassas Street, Memphis, TN 38163, USA Chao Huang, Department of Medicine, Vascular Biology and Cancer Centers, University of Tennessee Health Science Center, Cancer Research Building Room 220, 19 South Manassas Street, Memphis, TN 38163, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    MicroRNAs (miRNAs) are a family of small, non-coding RNAs that control gene expression at the post-transcriptional level by destabilizing and inhibiting translation of their target messenger RNAs. MiRNAs are involved in the regulation of a number of fundamental biological processes, and their dysregulation is thought to contribute to several disease processes. Emerging evidence suggests that miRNAs also play a critical role in protecting the heritable genome by contributing to the regulation of the DNA damage response. Consequently, much recent investigative effort has been directed towards an improved understanding of how miRNAs are regulated in response to DNA damage. In this review, we discuss the most recent findings regarding the regulation of miRNA expression and the functional roles of miRNAs in the DNA damage response. Content Type Journal Article Category Review Pages 1-12 DOI 10.1007/s00018-012-0959-8 Authors Cecil Han, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Guohui Wan, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Robert R. Langley, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Xinna Zhang, Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Xiongbin Lu, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Interkinetic nuclear migration (INM) is an oscillatory nuclear movement that is synchronized with the progression of the cell cycle. The efforts of several researchers, following the first report of INM in 1935, have revealed many of the molecular mechanisms of this fascinating phenomenon linking the timing of the cell cycle and nuclear positioning in tissue. Researchers are now faced with a more fundamental question: is INM important for tissue, particularly brain, development? In this review, I summarize the current understanding of the regulatory mechanisms governing INM, investigations involving several different tissues and species, and possible explanations for how nuclear movement affects cell-fate determination and tissue formation. Content Type Journal Article Category Review Pages 1-12 DOI 10.1007/s00018-012-0952-2 Authors Yoichi Kosodo, Department of Anatomy, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192 Japan Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The world of RNAs is much more complex than previously thought, and has rapidly emerged as one of the most actively researched topics in the life sciences. Recently, two findings in this field were reported and given special attention: promoter-associated RNAs (paRNAs), a novel class of RNAs with numerous potential functions; and promoter-targeted RNA-induced transcriptional gene regulation, a new regulatory mechanism to control transcription. In this review, we summarize the studies in these two areas, and outline the current understanding with respect to the potential biological functions of paRNAs, and the molecular mechanisms of promoter-targeted RNA-induced transcriptional gene silencing and activation. Additionally, we seek to integrate these two areas, as paRNAs may have potential biological links with promoter-targeted RNA-induced transcriptional gene regulation. Finally, we will discuss the significance of identifying paRNAs and the possible use of promoter-targeted RNAs in gene regulation and therapy. Content Type Journal Article Category Review Pages 1-10 DOI 10.1007/s00018-012-0953-1 Authors Bing-xue Yan, Icesnow Yanyan Bioscience Association, Beijing, 100094 China Jin-xia Ma, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Barrier properties of tight junctions are determined by the claudin protein family. Many claudins seal this barrier, but others form paracellular channels. Among these, no claudins with general and clear-cut anion selectivity have yet been described, while for claudin-10a and claudin-4, only circumstantial or small anion selectivities have been shown. A claudin with unknown function and tissue distribution is claudin-17. We characterized claudin-17 by overexpression and knock-down in two renal cell lines. Overexpression in MDCK C7 cell layers caused a threefold increase in paracellular anion permeability and switched these cells from cation- to anion-selective. Knockdown in LLC-PK 1 cells indorsed the finding of claudin-17-based anion channels. Mutagenesis revealed that claudin-17 anion selectivity critically depends on a positive charge at position 65. Claudin-17 expression was found in two organs: marginal in brain but abundant in kidney, where expression was intense in proximal tubules and gradually decreased towards distal segments. As claudin-17 is predominantly expressed in proximal nephrons, which exhibit substantial, though molecularly not defined, paracellular chloride reabsorption, we suggest that claudin-17 has a unique physiological function in this process. In conclusion, claudin-17 forms channels within tight junctions with distinct anion preference. Content Type Journal Article Category Research Article Pages 1-14 DOI 10.1007/s00018-012-0949-x Authors Susanne M. Krug, Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany Dorothee Günzel, Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany Marcel P. Conrad, Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany Rita Rosenthal, Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany Anja Fromm, Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany Salah Amasheh, Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany Jörg D. Schulzke, Division of Nutritional Medicine, Department of Gastroenterology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany Michael Fromm, Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203 Berlin, Germany Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    In wound healing and development, large epithelial sheets migrate collectively, in defined directions, and maintain tight cell–cell adhesion. This type of movement ensures an essential function of epithelia, a barrier, which is lost when cells lose connection and move in isolation. Unless wounded, epithelial sheets in cultures normally do not have overall directional migration. Cell migration is mostly studied when cells are in isolation and in the absence of mature cell–cell adhesion; the mechanisms of the migration of epithelial sheets are less well understood. We used small electric fields (EFs) as a directional cue to instigate and guide migration of epithelial sheets. Significantly, cells in monolayer migrated far more efficiently and directionally than cells in isolation or smaller cell clusters. We demonstrated for the first time the group size-dependent directional migratory response in several types of epithelial cells. Gap junctions made a minimal contribution to the directional collective migration. Breaking down calcium-dependent cell–cell adhesion significantly reduced directional sheet migration. Furthermore, E-cadherin blocking antibodies abolished migration of cell sheets. Traction force analysis revealed an important role of forces that cells in the leading rows exert on the substratum. With EF, the traction forces of the leading edge cells coordinated in directional re-orientation. Our study thus identifies a novel mechanism—E-cadherin dependence and coordinated traction forces of leading cells in collective directional migration of large epithelial sheets. Content Type Journal Article Category Research Article Pages 1-11 DOI 10.1007/s00018-012-0951-3 Authors Li Li, Department of Dermatology, School of Medicine, Institute for Regenerative Cures, University of California at Davis, Suite 1630, 2921 Stockton Blvd., Room 1617, Sacramento, CA 95817, USA Robert Hartley, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD UK Bjoern Reiss, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD UK Yaohui Sun, Department of Dermatology, School of Medicine, Institute for Regenerative Cures, University of California at Davis, Suite 1630, 2921 Stockton Blvd., Room 1617, Sacramento, CA 95817, USA Jin Pu, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD UK Dan Wu, Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB R3T 2N2, Canada Francis Lin, Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB R3T 2N2, Canada Trung Hoang, Department of Biomedical Engineering, University of California at Davis, Davis, CA 95616, USA Soichiro Yamada, Department of Biomedical Engineering, University of California at Davis, Davis, CA 95616, USA Jianxin Jiang, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042 China Min Zhao, Department of Dermatology, School of Medicine, Institute for Regenerative Cures, University of California at Davis, Suite 1630, 2921 Stockton Blvd., Room 1617, Sacramento, CA 95817, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Heart disease is one of the leading causes of death worldwide and the number of patients with the disease is likely to grow with the continual decline in health for most of the developed world. Heart transplantation is one of the only treatment options for heart failure due to an acute myocardial infarction, but limited donor supply and organ rejection limit its widespread use. Cellular cardiomyoplasty, or cellular implantation, combined with various tissue-engineering methods aims to regenerate functional heart tissue. This review highlights the numerous cell sources that have been used to regenerate the heart as well as cover the wide range of tissue-engineering strategies that have been devised to optimize the delivery of these cells. It will probably be a long time before an effective regenerative therapy can make a serious impact at the bedside. Content Type Journal Article Category Review Pages 1-22 DOI 10.1007/s00018-012-0942-4 Authors Andre Alcon, Yale University School of Medicine, Yale University, New Haven, CT, USA Esra Cagavi Bozkulak, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale Stem Cell Center, Yale School of Medicine, Yale University, 300 George Street, Suite 773A, New Haven, CT 06520, USA Yibing Qyang, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale Stem Cell Center, Yale School of Medicine, Yale University, 300 George Street, Suite 773A, New Haven, CT 06520, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Sex chromosome inactivation in male germ cells is a paradigm of epigenetic programming during sexual reproduction. Recent progress has revealed the underlying mechanisms of sex chromosome inactivation in male meiosis. The trigger of chromosome-wide silencing is activation of the DNA damage response (DDR) pathway, which is centered on the mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (γH2AX). This DDR pathway shares features with the somatic DDR pathway recognizing DNA replication stress in the S phase. Additionally, it is likely to be distinct from the DDR pathway that recognizes meiosis-specific double-strand breaks. This review article extensively discusses the underlying mechanism of sex chromosome inactivation. Content Type Journal Article Category Review Pages 1-14 DOI 10.1007/s00018-012-0941-5 Authors Yosuke Ichijima, Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Ho-Su Sin, Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Satoshi H. Namekawa, Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells, neurons, cardiomyocytes, and keratinocytes, is the precursor of various peptides that regulate the carbohydrate/lipid metabolism and the cardiovascular system. We have found that CgA, locally administered to injured mice, can accelerate keratinocyte proliferation and wound healing. This biological activity was abolished by the Asp 45 Glu mutation. CgA and its N-terminal fragments, but not the corresponding Asp 45 Glu mutants, could selectively recognize the αvβ6-integrin on keratinocytes (a cell-adhesion receptor that is up-regulated during wound healing) and regulate keratinocyte adhesion, proliferation, and migration. No binding was observed to other integrins such as αvβ3, αvβ5, αvβ8, α5β1, α1β1, α3β1, α6β4, α6β7 and α9β1. Structure–activity studies showed that the entire CgA 39–63 region is crucial for αvβ6 recognition ( K i  = 7 nM). This region contains an RGD site (residues CgA 43–45 ) followed by an amphipathic α-helix (residues CgA 47–63 ), both crucial for binding affinity and selectivity. These results suggest that the interaction of the RGD/α-helix motif of CgA with αvβ6 regulates keratinocyte physiology in wound healing. Content Type Journal Article Category Research Article Pages 1-13 DOI 10.1007/s00018-012-0955-z Authors Flavio Curnis, Division of Molecular Oncology and IIT Network Research Unit of Molecular Neuroscience, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy Anna Maria Gasparri, Division of Molecular Oncology and IIT Network Research Unit of Molecular Neuroscience, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy Renato Longhi, Istituto di Chimica del Riconoscimento Molecolare, CNR, 20131 Milan, Italy Barbara Colombo, Division of Molecular Oncology and IIT Network Research Unit of Molecular Neuroscience, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy Silvia D’Alessio, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy Fabio Pastorino, Laboratory of Oncology, Experimental Therapy Unit, G. Gaslini Children’s Hospital, 16148 Genoa, Italy Mirco Ponzoni, Laboratory of Oncology, Experimental Therapy Unit, G. Gaslini Children’s Hospital, 16148 Genoa, Italy Angelo Corti, Division of Molecular Oncology and IIT Network Research Unit of Molecular Neuroscience, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF’s ability to swiftly distribute signals across vast distances in the central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury. Content Type Journal Article Category Review Pages 1-16 DOI 10.1007/s00018-012-0957-x Authors Mauro W. Zappaterra, Department of Physical Medicine and Rehabilitation, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA 90073, USA Maria K. Lehtinen, Department of Pathology, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    In addition to its central roles in protein quality control, regulation of cell cycle, intracellular signaling, DNA damage response and transcription regulation, the ubiquitin–proteasome system (UPS) plays specific roles in the nervous system, where it contributes to precise connectivity through development, and later assures functionality by regulating a wide spectrum of neuron-specific cellular processes. Aberrations in this system have been implicated in the etiology of neurodevelopmental and neurodegenerative diseases. In this review, we provide an updated view on the UPS and highlight recent findings concerning its role in normal and diseased nervous systems. We discuss the advantages of the model organism Caenorhabditis elegans as a tool to unravel the major unsolved questions concerning this biochemical pathway and its involvement in nervous system function and dysfunction, and expose the new possibilities, using state-of-the-art techniques, to assess UPS function using this model system. Content Type Journal Article Category Review Pages 1-25 DOI 10.1007/s00018-012-0946-0 Authors Márcio S. Baptista, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal Carlos B. Duarte, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal Patrícia Maciel, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    microRNAs (miRNAs) are small, stable RNA molecules that post-transcriptionally regulate gene expression in plants and animals by base pairing to partially complementary sequences on target mRNAs to inhibit protein synthesis. More than 250 miRNAs are reportedly expressed in the retina, and miRNA gene regulation has been shown to affect retinal development, function, and disease. Here we highlight recent advances in understanding the functional roles of vertebrate retinal miRNAs. Details are emerging about the physiological impact of specific miRNAs in the developing and mature retina, and we discuss a group of emerging technologies for studying miRNAs, which can be employed to yield a deeper understanding of retinal miRNA gene regulation. Content Type Journal Article Category Review Pages 1-12 DOI 10.1007/s00018-012-0976-7 Authors Thomas R. Sundermeier, Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4965, USA Krzysztof Palczewski, Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4965, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Homeostasis in the immune system encompasses the mechanisms governing maintenance of a functional and diverse pool of lymphocytes, thus guaranteeing immunity to pathogens while remaining self-tolerant. Antigen-naïve T cells rely on survival signals through contact with self-peptide-loaded major histocompatibility complex (MHC) molecules plus interleukin (IL)-7. Conversely, antigen-experienced (memory) T cells are typically MHC-independent and they survive and undergo periodic homeostatic proliferation through contact with both IL-7 and IL-15. Also, non-conventional γδ T cells rely on a mix of IL-7 and IL-15 for their homeostasis, whereas natural killer cells are mainly dependent on contact with IL-15. Homeostasis of CD4 + T regulatory cells is different in being chiefly regulated by contact with IL-2. Notably, increased levels of these cytokines cause expansion of responsive lymphocytes, such as found in lymphopenic hosts or following cytokine injection, whereas reduced cytokine levels cause a decline in cell numbers. Content Type Journal Article Category Multi-author review Pages 1-12 DOI 10.1007/s00018-012-0968-7 Authors Onur Boyman, Allergy Unit, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland Carsten Krieg, Allergy Unit, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland Dirk Homann, Departments of Pediatrics, Immunology and Microbiology, Barbara Davis Center, University of Colorado Denver, M20-3202D, 1775 Aurora Court, Aurora, CO 80010, USA Jonathan Sprent, Immunology Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The discovery of discontiguous tRNA genes triggered studies dissecting the process of tRNA splicing. As a result, we have gained detailed mechanistic knowledge on enzymatic removal of tRNA introns catalyzed by endonuclease and ligase proteins. In addition to the elucidation of tRNA processing, these studies facilitated the discovery of additional functions of RNA ligases such as RNA repair and non-conventional mRNA splicing events. Recently, the identification of a new type of RNA ligases in bacteria, archaea, and humans closed a long-standing gap in the field of tRNA processing. This review summarizes past and recent findings in the field of tRNA splicing with a focus on RNA ligation as it preferentially occurs in archaea and humans. In addition to providing an integrated view of the types and phyletic distribution of RNA ligase proteins known to date, this survey also aims at highlighting known and potential accessory biological functions of RNA ligases. Content Type Journal Article Category Review Pages 1-14 DOI 10.1007/s00018-012-0944-2 Authors Johannes Popow, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria Alexander Schleiffer, Bioinformatics Department, Research Institute of Molecular Pathology (IMP)–IMBA, Dr. Bohrgasse 7, 1030 Vienna, Austria Javier Martinez, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The epidermis and its appendages, such as the hair follicle (HF), continually regenerate throughout postnatal mammalian life due to the activity of resident epithelial stem cells (SCs). The follicular SC niche, or the bulge, is composed of a heterogeneous population of self-renewing multipotent cells. Multiple intrinsic molecular mechanisms promote the transition of follicular SCs from quiescence to activation. In addition, numerous extrinsic cell types influence the activity and characteristics of bulge cells. Ultimately, the balance between these intrinsic and extrinsic mechanisms influences the function of bulge cells during homeostasis and tissue regeneration and likely contributes to skin tumorigenesis. Here, we review both the intrinsic and extrinsic factors that contribute to the skin SC niche. Content Type Journal Article Category Review Pages 1-10 DOI 10.1007/s00018-012-0943-3 Authors Jill Goldstein, Molecular Cell Biology, Genetics and Development Program, Yale University, 219 Prospect St., Box 208103, New Haven, CT 06520, USA Valerie Horsley, Department of Molecular, Cell and Developmental Biology, Yale University, 219 Prospect St., Box 208103, New Haven, CT 06520, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The non-coding microRNA (miRNA) is involved in the regulation of hepatitis C virus (HCV) infection and offers an alternative target for developing anti-HCV agent. In this study, we aim to identify novel cellular miRNAs that directly target the HCV genome with anti-HCV therapeutic potential. Bioinformatic analyses were performed to unveil liver-abundant miRNAs with predicted target sequences on HCV genome. Various cell-based systems confirmed that let-7b plays a negative role in HCV expression. In particular, let-7b suppressed HCV replicon activity and down-regulated HCV accumulation leading to reduced infectivity of HCVcc. Mutational analysis identified let-7b binding sites at the coding sequences of NS5B and 5′-UTR of HCV genome that were conserved among various HCV genotypes. We further demonstrated that the underlying mechanism for let-7b-mediated suppression of HCV RNA accumulation was not dependent on inhibition of HCV translation. Let-7b and IFNα-2a also elicited a synergistic inhibitory effect on HCV infection. Together, let-7b represents a novel cellular miRNA that targets the HCV genome and elicits anti-HCV activity. This study thereby sheds new insight into understanding the role of host miRNAs in HCV pathogenesis and to developing a potential anti-HCV therapeutic strategy. Content Type Journal Article Category Research Article Pages 1-13 DOI 10.1007/s00018-012-0940-6 Authors Ju-Chien Cheng, Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 404 Taiwan, ROC Yung-Ju Yeh, Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 404 Taiwan, ROC Ching-Ping Tseng, Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, ROC Sheng-Da Hsu, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 300 Taiwan, ROC Yu-Ling Chang, Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 404 Taiwan, ROC Naoya Sakamoto, Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan Hsien-Da Huang, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 300 Taiwan, ROC Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Microarray technology outgrew the detection of simple intermolecular interactions, as incubation of slides with living cells opened new vistas. Cell-based array technology permits simultaneous detection of several different cell surface molecules, allowing the complex characterization of cells with an amount of information that is hardly assessed by any other technique. Furthermore, binding of cells to printed antibodies or ligands may induce their activation, and consequently the outcome of these interactions, such as phosphorylation, gene expression, secretion of various products; differentiation, proliferation and apoptosis of the cells are also measurable on arrays. Moreover, since cells can be transfected with printed vectors, over- or under-expression of selected genes is also achievable simultaneously, creating a nice tool for assessing the function of a given gene. The enormously high-throughput cell-based microarray technology enables testing the effect of external stimuli on a scale that was earlier unthinkable. This review summarizes the possible applications of cell-based arrays. Content Type Journal Article Category Review Pages 1-9 DOI 10.1007/s00018-012-0947-z Authors Krisztián Papp, Immunology Research Group, Hungarian Academy of Sciences, MTA-ELTE, Pázmány P.s. 1/C, Budapest, 1117 Hungary Zoltán Szittner, Diagnosticum Ltd., Attila u. 126, Budapest, 1047 Hungary József Prechl, Immunology Research Group, Hungarian Academy of Sciences, MTA-ELTE, Pázmány P.s. 1/C, Budapest, 1117 Hungary Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The aim of the present study was to upgrade the bonding quality and water resistance of medium-density particleboards based on rice husks (RH) as a wood substitute and soybean protein concentrate (SPC) as the binder via chemical modification of SPC. Alkali (A), citric acid (CA) and boric acid (BA) were used to modify proteins and the carbohydrate complex in SPC. The effect of chemical treatment performed on SPC was followed by Fourier transform infrared, differential scanning calorimetry, thermo-gravimetric analysis and initial apparent viscosity measurements. Board properties were evaluated in terms of internal bond (IB) and physical properties. Results revealed that boards bonded with SPC treated with boric acid, exhibited the highest IB and the lowest water absorption and thickness swelling at 2 and 24 h, due to cross-linking reactions with exposed OH-groups in the amorphous region of cellulose of RH. Results demonstrate that boric acid-modified–SPC-bonded boards met the requirements of IB recommended by the US Standard ANSI A208.1-2009 for M1, MS, M2 and M3-grade medium-density particleboards but failed to pass the thickness swelling required. This issue of BSPC-RH boards is compensated for by the benefit of being formaldehyde-free which makes them suitable for indoor applications. Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s11746-012-2058-2 Authors E. M. Ciannamea, Instituto de Investigaciones en Ciencia y Tecnología de Materiales (INTEMA), Av. J. B. Justo 4302 (7600), Mar del Plata, Argentina J. F. Martucci, Instituto de Investigaciones en Ciencia y Tecnología de Materiales (INTEMA), Av. J. B. Justo 4302 (7600), Mar del Plata, Argentina P. M. Stefani, Instituto de Investigaciones en Ciencia y Tecnología de Materiales (INTEMA), Av. J. B. Justo 4302 (7600), Mar del Plata, Argentina R. A. Ruseckaite, Instituto de Investigaciones en Ciencia y Tecnología de Materiales (INTEMA), Av. J. B. Justo 4302 (7600), Mar del Plata, Argentina Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    A reversed-phase gradient ultrahigh pressure liquid chromatographic method with a water–acetonitrile mobile phase and UV detection has been developed to rapidly determine the concentration of the major tocopherol components in B100. The described method requires minimal sample preparation and provides short analysis times compatible with the needs of small to mid-size laboratories involved in B100 analyses. The objectives of this work were twofold. We wished to develop an analytical method both to rapidly screen B100 samples for their tocopherol content and to provide additional information on the source (from the distribution of tocopherols) and the nature of the processing of the B100 (absence of tocopherols would suggest distillation). Information on the tocopherol content of the B100 can be used to assess the inherent antioxidant content of the B100 and the extent to which additional stabilizers are required. The method determines the concentration of alpha, gamma and delta tocopherols and has a chromatographic run time of 4.5 min with minimal sample preparation. Calibration curves were linear over the range of 5–350 μg/mL and had correlation coefficients exceeding 0.999. The short term precision of the method was evaluated, and relative standard deviations were typically 2 % or less. Recovery of spiked tocopherols averaged 97 %. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s11746-012-2061-7 Authors R. E. Pauls, Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, IL 60439, USA Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Gap junction channels link cytoplasms of adjacent cells. Connexins, their constitutive proteins, are essential in cell homeostasis and are implicated in numerous physiological processes. Spermatogenesis is a sophisticated model of germ cell proliferation, differentiation, survival, and apoptosis, in which a connexin isotype, connexin 43, plays a crucial role as evidenced by genomic approaches based on gene deletion. The balance between cell proliferation/differentiation/apoptosis is a prerequisite for maintaining levels of spermatozoa essential for fertility and for limiting anarchic cell proliferation, a major risk of testis tumor. The present review highlights the emerging role of connexins in testis pathogenesis, focusing specifically on two intimately interconnected human testicular diseases (azoospermia with impaired spermatogenesis and testicular germ cell tumors), whose incidence increased during the last decades. This work proposes connexin 43 as a potential cancer diagnostic and prognostic marker, as well as a promising therapeutic target for testicular diseases. Content Type Journal Article Category Review Pages 1-14 DOI 10.1007/s00018-012-1121-3 Authors Daniel Chevallier, Department of Urology, Pasteur Hospital, Nice, France Diane Carette, UMR S775, University Paris Descartes, 45 rue des Saints Pères, Paris, 75006 France Dominique Segretain, UMR S775, University Paris Descartes, 45 rue des Saints Pères, Paris, 75006 France Jérome Gilleron, INSERM U 1065, Team 5 “Physiopathologic Control of Germ Cell Proliferation: Genomic and Non Genomic Mechanisms”, University Nice Sophia-Antipolis, C3M, 151 route Saint-Antoine de Ginestière BP 2 3194, Nice Cedex 3, 06204 France Georges Pointis, INSERM U 1065, Team 5 “Physiopathologic Control of Germ Cell Proliferation: Genomic and Non Genomic Mechanisms”, University Nice Sophia-Antipolis, C3M, 151 route Saint-Antoine de Ginestière BP 2 3194, Nice Cedex 3, 06204 France Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Sarcomas are a heterogeneous group of tumors with mesenchymal origins. Sarcomas are broadly classified into bone and soft tissue sarcomas with over 50 subtypes. Despite recent advances in sarcoma classification and treatment strategies, the prognosis of some aggressive sarcoma types remains poor due to treatment infectiveness and development of drug resistance. A better understanding of sarcoma pathobiology will significantly increase the potential for the development of therapeutics and treatment strategies. Recently, expressions of microRNAs (miRNA), a class of small non-coding RNAs, have been found to be deregulated in many sarcomas and are implicated in sarcoma pathobiology. Comprehensive understanding of gene regulatory networks mediated by miRNAs in each sarcoma type and the conservation of some shared/conserved miRNA-gene networks could be potentially investigated in the prevention, diagnosis, prognosis and as multi-modal treatment options in these cancers. In this review, we will discuss the current knowledge of miRNA–gene regulatory networks in various sarcoma types and give a perspective of the complex multilayer miRNA-mediated gene regulation in sarcomas. Content Type Journal Article Category Multi-author review Pages 1-15 DOI 10.1007/s00018-012-1127-x Authors Subbaya Subramanian, Department of Surgery, University of Minnesota, 11-212 Moos Tower (Mail Code: MMC 195), 515 Delaware St, S.E, Minneapolis, MN 55455, USA Reena V. Kartha, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung: MicroRNA regulatory networks and human disease Content Type Journal Article Category Multi-author review Pages 1-3 DOI 10.1007/s00018-012-1123-1 Authors Yin-Yuan Mo, University of Mississippi Medical Center, Cancer Institute, Jackson, MS, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The molecular features that dominate the binding mode of agonists by a broadly tuned olfactory receptor are analyzed through a joint approach combining cell biology, calcium imaging, and molecular modeling. The odorant/receptor affinities, estimated through statistics accrued during molecular dynamics simulations, are in accordance with the experimental ranking. Although in many systems receptors recognize their target through a network of oriented interactions, such as H-bonding, the binding by broadly tuned olfactory receptors is dominated by non-polar terms. We show how such a feature allows chemicals belonging to different chemical families to similarly activate the receptors through compensations of interactions within the binding site. Content Type Journal Article Category Research article Pages 1-9 DOI 10.1007/s00018-012-1116-0 Authors Landry Charlier, Institut de Chimie de Nice, UMR CNRS, Université de Nice Sophia Antipolis 7272, 06108 Nice Cedex 2, France Jérémie Topin, Institut de Chimie de Nice, UMR CNRS, Université de Nice Sophia Antipolis 7272, 06108 Nice Cedex 2, France Catherine Ronin, Laboratoire de Neuroglycobiologie, GLM, CNRS, 31 Ch. J. Aiguier, 13402 Marseille, France Soo-Kyung Kim, Materials and Process Simulation Center (MC139-74), California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA William A. Goddard III, Materials and Process Simulation Center (MC139-74), California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA Roman Efremov, Laboratory of Biomolecular Modeling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, 117997 Moscow, Russia Jérôme Golebiowski, Institut de Chimie de Nice, UMR CNRS, Université de Nice Sophia Antipolis 7272, 06108 Nice Cedex 2, France Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Cardiac hypertrophy is an adaptive enlargement of the myocardium in response to altered stress or injury. The cellular responses of cardiomyocytes and non-cardiomyocytes to various signaling pathways should be tightly and delicately regulated to maintain cardiac homeostasis and prevent pathological cardiac hypertrophy. MicroRNAs (miRNAs) are endogenous, single-stranded, short non-coding RNAs that act as regulators of gene expression by promoting the degradation or inhibiting the translation of target mRNAs. Recent studies have revealed expression signatures of miRNAs associated with pathological cardiac hypertrophy and heart failure in humans and mouse models of heart diseases. Increasing evidence indicates that dysregulation of specific miRNAs could alter the cellular responses of cardiomyocytes and non-cardiomyocytes to specific signaling upon the pathological hemodynamic overload, leading to cardiac hypertrophy and heart failure. This review summarizes the cell-autonomous functions of cardiomyocyte miRNAs regulated by different pathways and the roles of non-cardiomyocyte miRNAs in cardiac hypertrophy. The therapeutic effects of a number of miRNAs in heart diseases are also discussed. Content Type Journal Article Category Multi-author review Pages 1-10 DOI 10.1007/s00018-012-1126-y Authors Jian Wang, State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, 100071 Beijing, China Xiao Yang, State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, 100071 Beijing, China Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Pentameric ligand-gated ion channel (pLGIC) receptors exhibit desensitization, the progressive reduction in ionic flux in the prolonged presence of agonist. Despite its pathophysiological importance and the fact that it was first described over half a century ago, surprisingly little is known about the structural basis of desensitization in this receptor family. Here, we explain how desensitization is defined using functional criteria. We then review recent progress into reconciling the structural and functional basis of this phenomenon. The extracellular–transmembrane domain interface is a key locus. Activation is well known to involve conformational changes at this interface, and several lines of evidence suggest that desensitization involves a distinct conformational change here that is incompatible with activation. However, major questions remain unresolved, including the structural basis of the desensitization-induced agonist affinity increase and the mechanism of pore closure during desensitization. Content Type Journal Article Category Review Pages 1-13 DOI 10.1007/s00018-012-1133-z Authors Angelo Keramidas, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia Joseph W. Lynch, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    In this study, the stability of oil-in-water (O/W) emulsions prepared with structured lipid (SL) were evaluated in which the SL was produced through lipase-catalyzed interesterification between soybean oil and rice bran oil. After interesterification, the major TAG species in the SL were PLP (22.5 %), PLL/OOLn (21.8 %), LPL (16.1 %), and LLS/PLO (16.1 %), and the total amount of tocopherol and tocotrienol was 20.9 mg/100 g of SL. Sophorolipid was used as an emulsifier for preparing SL-based O/W emulsions, and the effect of pH (pH 5.8, 7 and 7.2) on stability was studied by analyzing the fat globule size. From the results, SL-based O/W emulsions showed similar stabilities to those prepared with Tween 20 at the neutral environment. In the oxidation study, any antioxidant addition of propyl gallate (PG), ascorbic acid 6-palmitate (AP) or quercetin hydrate (Que) distinctively prevented peroxide formation on the SL-based O/W emulsion throughout the 23 days of storage while AP was less effective to lower TBARS values than PG and Que. Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s11746-012-2133-8 Authors Cheng-Lian Xue, Department of Food Science and Technology, Chungnam National University, Daejeon, 305-764 South Korea Daniel K. Y. Solaiman, U.S. Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center, 600 East Mermaid Lane, Wyndmoor, PA 19038, USA Richard D. Ashby, U.S. Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center, 600 East Mermaid Lane, Wyndmoor, PA 19038, USA Jonathan Zerkowski, U.S. Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center, 600 East Mermaid Lane, Wyndmoor, PA 19038, USA Jeung Hee Lee, Department of Food and Nutrition, Daegu University, Jillyang, Gyeongsan, Gyeongbuk 712-714, South Korea Soon-Taek Hong, Department of Food Science and Technology, Chungnam National University, Daejeon, 305-764 South Korea Dan Yang, Department of Food Science and Technology, Chungnam National University, Daejeon, 305-764 South Korea Jung-Ah Shin, Department of Food Science and Technology, Chungnam National University, Daejeon, 305-764 South Korea Chen-Ming Ji, Department of Food Science and Technology, Chungnam National University, Daejeon, 305-764 South Korea Ki-Teak Lee, Department of Food Science and Technology, Chungnam National University, Daejeon, 305-764 South Korea Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Oleic acid (OA) is a renewable monounsaturated fatty acid obtained from high oleic sunflower oil. This work was focused on the oxidative scission of OA, which yields a mono-acid (pelargonic acid, PA) and a di-acid (azelaic acid, AA) through an emulsifying system. The conventional method for producing AA and PA consists of the ozonolysis of oleic acid, a process which presents numerous drawbacks. Therefore, we proposed to study a new alternative process using a green oxidant and a solvent-free system. OA was oxidized in a batch reactor with a biphasic organic-aqueous system consisting of hydrogen peroxide (H 2 O 2 , 30 %) as an oxidant and a peroxo–tungsten complex Q 3 {PO 4 [WO(O 2 ) 2 ] 4 } as a phase-transfer catalyst/co-oxidant. Several phase-transfer catalysts were prepared in situ from tungstophosphoric acid, H 2 O 2 and different quaternary ammonium salts (Q + , Cl – ). The catalyst [C 5 H 5 N( n -C 16 H 33 )] 3 {PO 4 [WO(O 2 ) 2 ] 4 } was found to give the best results and was chosen for the optimization of the other parameters of the process. This optimization led to a complete conversion of OA into AA and PA with high yields (〉80 %) using the system OA/H 2 O 2 /[C 5 H 5 N( n -C 16 H 33 )] 3 {PO 4 [WO(O 2 ) 2 ] 4 } (1/5/0.02 molar ratio) at 85 °C for 5 h. In addition, a new treatment was developed in order to recover the catalyst. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s11746-012-2134-7 Authors Anaïs Godard, Université de Toulouse, INPT-ENSIACET, LCA (Laboratoire de Chimie Agro-Industrielle), ENSIACET, 4 Allée Emile Monso, 31030 Toulouse, France Pascale De Caro, Université de Toulouse, INPT-ENSIACET, LCA (Laboratoire de Chimie Agro-Industrielle), ENSIACET, 4 Allée Emile Monso, 31030 Toulouse, France Sophie Thiebaud-Roux, Université de Toulouse, INPT-ENSIACET, LCA (Laboratoire de Chimie Agro-Industrielle), ENSIACET, 4 Allée Emile Monso, 31030 Toulouse, France Emeline Vedrenne, Université de Toulouse, INPT-ENSIACET, LCA (Laboratoire de Chimie Agro-Industrielle), ENSIACET, 4 Allée Emile Monso, 31030 Toulouse, France Zéphirin Mouloungui, Université de Toulouse, INPT-ENSIACET, LCA (Laboratoire de Chimie Agro-Industrielle), ENSIACET, 4 Allée Emile Monso, 31030 Toulouse, France Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    The availability of a reliable methodology for the quantification of fatty acid esters of monochloropropropanediol (MCPD) and glycidol is essential for understanding the mechanism of formation of these process contaminants and for developing effective mitigation strategies. While several analytical methods for the determination of MCPD esters have already been developed and evaluated, only very few procedures are currently available for the analysis of glycidyl esters. This work presents a new indirect method for the simultaneous quantification of fatty acid esters of 2-MCPD, 3-MCPD and glycidol. The method is based on the acid-catalyzed conversion of glycidyl esters into 3-monobromopropanediol (3-MBPD) monoesters which, owing to the structural similarity to MCPD esters, are quantified by using the procedure we previously optimized for the analysis of MCPD esters. The critical step of the method, which is the conversion of glycidyl esters, was optimized by testing different reagent concentrations and varying other condition settings. The novel method showed good repeatability (RSD 〈2.5 %) and between-day reproducibility (RSD ≤5 %). The limit of detection was 0.04 mg/kg for bound 2-MCPD and 3-MCPD and 0.06 mg/kg for bound glycidol. The trueness of the method was evaluated by the analysis of spiked samples and by interlaboratory comparison. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s11746-012-2132-9 Authors A. Ermacora, Department of Fat Technology, Unilever R&D Vlaardingen, Olivier van Noortlaan 120, 3133 AT Vlaardingen, The Netherlands K. Hrncirik, Department of Fat Technology, Unilever R&D Vlaardingen, Olivier van Noortlaan 120, 3133 AT Vlaardingen, The Netherlands Journal Journal of the American Oil Chemists' Society Online ISSN 1558-9331 Print ISSN 0003-021X

Beschreibung:    Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that together efficiently interact with and dissociate the tubulin dimer. In the study reported here we showed that TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO − present in TBCB, which is similar to the EEY/F-COO − element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE–TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated with microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation. Content Type Journal Article Category Research article Pages 1-15 DOI 10.1007/s00018-012-1114-2 Authors Gerardo Carranza, Departamento de Biología Molecular, Facultad de Medicina, IFIMAV-Universidad de Cantabria, 39011 Santander, Spain Raquel Castaño, Departamento de Biología Molecular, Facultad de Medicina, IFIMAV-Universidad de Cantabria, 39011 Santander, Spain Mónica L. Fanarraga, Departamento de Biología Molecular, Facultad de Medicina, IFIMAV-Universidad de Cantabria, 39011 Santander, Spain Juan Carlos Villegas, Departamento de Anatomía y Biología Celular, Facultad de Medicina, IFIMAV-Universidad de Cantabria, 39011 Santander, Spain João Gonçalves, Centro de Química eBioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal Helena Soares, Centro de Química eBioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal Jesus Avila, Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Cantoblanco, Madrid, Spain Marco Marenchino, Spectroscopy and NMR Unit, Structural Biology and Biocomputing Program, Spanish National Cancer Research Center (CNIO), Melchor Fdez. Almagro 3, 28029 Madrid, Spain Ramón Campos-Olivas, Spectroscopy and NMR Unit, Structural Biology and Biocomputing Program, Spanish National Cancer Research Center (CNIO), Melchor Fdez. Almagro 3, 28029 Madrid, Spain Guillermo Montoya, Macromolecular Crystallography Group, Structural Biology and Biocomputing Program, Spanish National Cancer Research Center (CNIO), Melchor Fdez. Almagro 3, 28029 Madrid, Spain Juan Carlos Zabala, Departamento de Biología Molecular, Facultad de Medicina, IFIMAV-Universidad de Cantabria, 39011 Santander, Spain Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Tumor cell migration is essential for invasion and dissemination from primary solid tumors and for the establishment of lethal secondary metastases at distant organs. In vivo and in vitro models enabled identification of different factors in the tumor microenvironment that regulate tumor progression and metastasis. However, the mechanisms by which tumor cells integrate these chemical and mechanical signals from multiple sources to navigate the complex microenvironment remain poorly understood. In this review, we discuss the factors that influence tumor cell migration with a focus on the migration of transformed carcinoma cells. We provide an overview of the experimental and computational methods that allow the investigation of tumor cell migration, and we highlight the benefits and shortcomings of the various assays. We emphasize that the chemical and mechanical stimulus paradigms are not independent and that crosstalk between them motivates the development of new assays capable of applying multiple, simultaneous stimuli and imaging the cellular migratory response in real-time. These next-generation assays will more closely mimic the in vivo microenvironment to provide new insights into tumor progression, inform techniques to control tumor cell migration, and render cancer more treatable. Content Type Journal Article Category Review Pages 1-22 DOI 10.1007/s00018-012-1115-1 Authors William J. Polacheck, Department of Mechanical Engineering, MIT, 77 Massachusetts Ave. Room NE47-315, Cambridge, MA 02139, USA Ioannis K. Zervantonakis, Department of Mechanical Engineering, MIT, 77 Massachusetts Ave. Room NE47-319, Cambridge, MA 02139, USA Roger D. Kamm, Departments of Mechanical Engineering and Biological Engineering, MIT, 77 Massachusetts Ave. Room NE47-321, Cambridge, MA 02139, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    The emerging role of microRNAs (miRNAs) in the epigenetic regulation of many cellular processes has become recognized in both basic research and translational medicine as an important way that gene expression can be fine-tuned. Breast cancer is the most frequent cancer in women, with about one million new cases diagnosed each year worldwide. Starting with the early work of miRNA profiling, more effort has now been put on functions of miRNAs in normal mammary stem cells, breast cancer initiating cells and metastatic cells, and therapy-resistant cancer cells. Future translational studies may focus on identifying miRNA signatures as cancer biomarkers and developing miRNA-based targeted therapeutics. Content Type Journal Article Category Multi-author review Pages 1-13 DOI 10.1007/s00018-012-1128-9 Authors Huiping Liu, The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X

Beschreibung:    Integrin-mediated cytoskeletal tension supports growth-factor-induced proliferation, and disruption of the actin cytoskeleton in growth factor-stimulated cells prevents the re-expression of cyclin D and cell cycle re-entry from quiescence. In contrast to cells that enter the cell cycle from G0, cycling cells continuously express cyclin D, and are subject to major cell shape changes during the cell cycle. Here, we investigated the cell cycle requirements for cytoskeletal tension and cell spreading in cycling mammalian cells that enter G1-phase from mitosis. Disruption of the actin cytoskeleton at progressive time-points in G1-phase induced cell rounding, FA disassembly, and attenuated both integrin signaling and growth factor-induced p44/p42 mitogen-activated protein kinase activation. Although cyclin D expression was reduced, the expression of cyclin A and entry into S-phase were not affected. Moreover, expression of cyclin B1, progression through G2- and M-phase, and commitment to a new cell cycle occurred normally. In contrast, cell cycle progression was strongly prevented by inhibition of MAPK activity in G1-phase, whereas cell spreading, cytoskeletal organization, and integrin signaling were not impaired. MAPK inhibition also prevented cytoskeleton-independent cell cycle progression. Thus, these results uncouple the requirements for cell spreading and cytoskeletal organization from MAPK signaling, and show that cycling mammalian cells can proliferate independently of actin stress fibers, focal adhesions, or cell spreading, as long as a threshold level of MAPK activity is sustained. Content Type Journal Article Category Research Article Pages 1-15 DOI 10.1007/s00018-012-1130-2 Authors Coert Margadant, Department of Cell Biology, Faculty of Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands Lobke Cremers, Department of Cell Biology, Faculty of Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands Arnoud Sonnenberg, Department of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands Johannes Boonstra, Department of Cell Biology, Faculty of Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands Journal Cellular and Molecular Life Sciences Online ISSN 1420-9071 Print ISSN 1420-682X