ALBERT

Beschreibung: The aim of this study was to examine racial differences in long-term survival among hemodialysis patients after coronary artery bypass grafting (CABG). To our knowledge this has not been previously addressed in the literature. Black and white hemodialysis patients undergoing first-time, isolated CABG procedures between 1992 and 2011 were compared. Survival probabilities were computed using the Kaplan-Meier product-limit method and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 207 (2%) patients were on hemodialysis at the time of CABG. White (n = 80) hemodialysis patients had significantly decreased 5-year survival compared with black (n = 127) patients (adjusted HR = 1.9, 95% CI = 1.2–2.8). Our finding provides useful outcome information for surgeons, primary care providers, and their patients.

Beschreibung: Background: Limited by data availability, most disease maps in the literature are for relatively large and subjectively-defined areal units, which are subject to problems associated with polygon maps. High resolution maps based on objective spatial units are needed to more precisely detect associations between disease and environmental factors. Method: We propose to use a Restricted and Controlled Monte Carlo (RCMC) process to disaggregate polygon-level location data to achieve mapping aggregate data at an approximated individual level. RCMC assigns a random point location to a polygon-level location, in which the randomization is restricted by the polygon and controlled by the background (e.g., population at risk). RCMC allows analytical processes designed for individual data to be applied, and generates high-resolution raster maps. Results: We applied RCMC to the town-level birth defect data for New Hampshire and generated raster maps at the resolution of 100 m. Besides the map of significance of birth defect risk represented by p-value, the output also includes a map of spatial uncertainty and a map of hot spots. Conclusions: RCMC is an effective method to disaggregate aggregate data. An RCMC-based disease mapping maximizes the use of available spatial information, and explicitly estimates the spatial uncertainty resulting from aggregation.

Beschreibung: The predominant microorganisms in samples taken from shower heads in residences in the Korean city “N” were Stenotrophomonas maltophilia, Sphingomonas paucimobilis, Acidovorax temperans, and Microbacterium lacticum. Legionella was not detected in this case. The volatile organic compounds (VOCs) vinylacetate, NN-DMA, cis-1,2-dichloroethylene, epichlorohydrin, and styrene were measured in five types of plastic pipes: PVC, PB, PP, PE, and cPVC. The rate of multiplication of the heterotrophic plate count (HPC) attached on the copper pipe in contact with hot tap water was higher than the rate for the copper pipe in contact with cold tap water. Biofilm accumulation on stainless steel pipes with added acetate (3 mg/L) was 2.56 times higher than the non-supplemented condition. Therefore, the growth of HPC in the pipe system was affected by the type and availability of nutrients and depended on variables such as heating during the hot water supply.

Beschreibung: Publication date: Available online 7 September 2013 Source: FEBS Open Bio Author(s): Veronika Temml , Susanne Kuehnl , Daniela Schuster , Stefan Schwaiger , Hermann Stuppner , Dietmar Fuchs Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro . We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geometry of the compounds. The interaction pattern analysis and force field-based minimization was performed within LigandScout 3.03, the docking simulation with MOE 2011.10 using the X-ray crystal structure of IDO. Results confirm the possibility of an intense interaction of arctigenin and trachelogenin with the binding site of the enzyme, while matairesinol had no such effect.

Beschreibung: Publication date: Available online 7 September 2013 Source: FEBS Open Bio Author(s): Mitsuru Ishikawa , Jun Shiota , Yuta Ishibashi , Tomoyuki Hakamata , Shizuku Shoji , Mamoru Fukuchi , Masaaki Tsuda , Tomoaki Shirao , Yuko Sekino , Toshihisa Ohtsuka , Jay M. Baraban , Akiko Tabuchi Megakaryoblastic leukemia 1 (MKL1) is a member of the MKL family of serum response factor (SRF) coactivators. Here we have identified three rat MKL1 transcripts: two are homologues of mouse MKL1 transcripts, full-length MKL1 (FLMKL1) and basic, SAP, and coiled-coil domains (BSAC), the third is a novel transcript, M KL1- elo ngated d erivative of y ield (MELODY). These rat MKL1 transcripts are differentially expressed in a wide variety of tissues with highest levels in testis and brain. During brain development, these transcripts display differential patterns of expression. The FLMKL1 transcript encodes two isoforms that utilize distinct translation start sites. The longer form possesses three actin-binding RPXXXEL (RPEL) motifs and the shorter form, MKL1met only has two RPEL motifs. All four rat MKL1 isoforms, FLMKL1, BSAC, MKL1met and MELODY increased SRF-mediated transcription, but not CREB-mediated transcription. Accordingly, the differential expression of MKL1 isoforms may help fine-tune gene expression during brain development.

Beschreibung: Tree species are predicted to track future climate by shifting their geographic distributions, but climate-mediated migrations are not apparent in a recent continental-scale analysis. To better understand the mechanisms of a possible migration lag, we analyzed relative recruitment patterns by comparing juvenile and adult tree abundances in climate space. One would expect relative recruitment to be higher in cold and dry climates as a result of tree migration with juveniles located further poleward than adults. Alternatively, relative recruitment could be higher in warm and wet climates as a result of higher tree population turnover with increased temperature and precipitation. Using the USDA Forest Service's Forest Inventory and Analysis data at regional scales, we jointly modeled juvenile and adult abundance distributions for 65 tree species in climate space of the eastern United States. We directly compared the optimal climate conditions for juveniles and adults, identified the climates where each species has high relative recruitment, and synthesized relative recruitment patterns across species. Results suggest that for 77% and 83% of the tree species, juveniles have higher optimal temperature and optimal precipitation, respectively, than adults. Across species, the relative recruitment pattern is dominated by relatively more abundant juveniles than adults in warm and wet climates. These different abundance-climate responses through life history are consistent with faster population turnover and inconsistent with the geographic trend of large-scale tree migration. Taken together, this juvenile-adult analysis suggests that tree species might respond to climate change by having faster turnover as dynamics respond to longer growing seasons and higher temperatures, before there is evidence of poleward migration at biogeographic scales. This article is protected by copyright. All rights reserved.

Beschreibung: Article The Broca area is located in the human prefrontal cortex and is involved in voluntary speech. Hage and Nieder now show that a monkey homologue of Broca’s area is similarly responsible for monkey volitional vocalizations. Nature Communications doi: 10.1038/ncomms3409 Authors: Steffen R. Hage, Andreas Nieder

Beschreibung: Article B lymphocytes respond to stimulation by proliferating and differentiating. Here the authors quantify and model the responses of B lymphocytes to TLR and CD40-dependent stimulation, and find that the latter induces a more complex response to signals of varying strength. Nature Communications doi: 10.1038/ncomms3406 Authors: E.D. Hawkins, M.L. Turner, C.J. Wellard, J.H.S. Zhou, M.R. Dowling, P.D. Hodgkin

Beschreibung: Erratum Nature Communications doi: 10.1038/ncomms3309 Authors: Ralph P. Schneider, Ianire Garrobo, Miguel Foronda, Jose A. Palacios, Rosa M. Marión, Ignacio Flores, Sagrario Ortega, Maria A. Blasco

Beschreibung: Article It has long been suggested, but never shown, than nanometre-sized particles precede mineral formation in magmatic systems. Here, Helmy et al. demonstrate that platinum and arsenic self-organize to nanoparticle precursors in magmatic liquids before mineral crystallization. Nature Communications doi: 10.1038/ncomms3405 Authors: Hassan M. Helmy, Chris Ballhaus, Raúl O.C. Fonseca, Richard Wirth, Thorsten Nagel, Marian Tredoux

Beschreibung: Article Messenger RNAs and their associated proteins are transported from the nucleus through highly selective nuclear pore complexes. Using ultrahigh resolution single-molecule imaging, the authors visualise the path taken by each messenger RNA as it negotiates the pore’s selectivity filter. Nature Communications doi: 10.1038/ncomms3414 Authors: Jiong Ma, Zhen Liu, Nicole Michelotti, Sethuramasundaram Pitchiaya, Ram Veerapaneni, John R. Androsavich, Nils G. Walter, Weidong Yang

Beschreibung: Article TRPA1 is a transient receptor potential channel family member and is involved in the detection of nociceptive stimuli. Zhou et al. identify an alternative splice variant of TRPA1, which increases TRPA1 plasma expression and channel function, and enhances pain-like behaviour in mice. Nature Communications doi: 10.1038/ncomms3399 Authors: Yiming Zhou, Yoshiro Suzuki, Kunitoshi Uchida, Makoto Tominaga

Beschreibung: Corrigendum Nature Communications doi: 10.1038/ncomms3358 Authors: Qilong Wang, Xiaoying Zhuang, Jingyao Mu, Zhong-Bin Deng, Hong Jiang, Lifeng Zhang, Xiaoyu Xiang, Baomei Wang, Jun Yan, Donald Miller, Huang-Ge Zhang

Beschreibung: Article Despite its importance for non-volatile memory, the origin of resistive switching in a metal insulator-metal structure is unclear. Park et al. fabricate such a structure inside a transmission electron microscope to show that switching occurs via oxygen-vacancy migration, which changes the conduction channels. Nature Communications doi: 10.1038/ncomms3382 Authors: Gyeong-Su Park, Young Bae Kim, Seong Yong Park, Xiang Shu Li, Sung Heo, Myoung-Jae Lee, Man Chang, Ji Hwan Kwon, M. Kim, U-In Chung, Regina Dittmann, Rainer Waser, Kinam Kim

Beschreibung: Publication date: Available online 11 September 2013 Source: FEBS Open Bio Author(s): Gisele Castro , Maria Fernanda C. Areias , Lais Weissmann , Paula G.F. Quaresma , Carlos K. Katashima , Mario J.A. Saad , Patricia O. Prada Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala.

Beschreibung: Bone remodeling is a natural process that enables growth and maintenance of the skeleton. It involves the deposition of mineralized matrix by osteoblasts and resorption by osteoclasts. Several cancers that metastasize to bone negatively perturb the remodeling process through a series of interactions with osteoclasts, and osteoblasts. These interactions have been described as the “vicious cycle” of cancer metastasis in bone. Due to the inaccessibility of the skeletal tissue it is difficult to study this system in vivo . In contrast, standard tissue culture lacks sufficient complexity. We have developed a specialized three-dimensional culture system that permits growth of a non-vascularized, multiple-cell-layer of mineralized osteoblastic tissue from pre-osteoblasts. In this study, the essential properties of bone remodeling were created in vitro by co-culturing the mineralized collagenous osteoblastic tissue with actively resorbing osteoclasts followed by reinfusion with proliferating pre-osteoblasts. Cell-cell and cell-matrix interactions were determined by confocal microscopy as well as by assays for cell specific cytokines and growth factors. Osteoclasts, differentiated in the presence of osteoblasts, led to degradation of the collagen-rich extracellular matrix. Further addition of metastatic breast cancer cells to the co-culture mimicked the vicious cycle; i.e. there was a further reduction in osteoblastic tissue thickness, an increase in osteoclastogenesis, chemotaxis of cancer cells to osteoclasts and formation of cancer cells into large colonies. The resulting model system permits detailed study of fundamental osteobiological and osteopathological processes in a manner that will enhance development of therapeutic interventions to skeletal diseases. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Beschreibung: Metastatic SW620 colon cancer cells are primed for death when detached and can be sensitized to anoikis by the BH3-mimetic ABT-737 Cell Death and Disease 4, e801 (September 2013). doi:10.1038/cddis.2013.328 Authors: A Maamer-Azzabi, O Ndozangue-Touriguine & J Bréard

Beschreibung: Smac mimetic and demethylating agents synergistically trigger cell death in acute myeloid leukemia cells and overcome apoptosis resistance by inducing necroptosis Cell Death and Disease 4, e802 (September 2013). doi:10.1038/cddis.2013.320 Authors: L Steinhart, K Belz & S Fulda

Beschreibung: Aberrant glycosylation by N -acetylgalactosaminyl transferases (GALNTs) is a well-described pathological alteration that is widespread in hereditary diseases, prominently including human cancers, familial tumoral calcinosis and hyperostosis-hyperphosphatemia. In this study, we integrated different computational tools to perform the in silico analysis of clinically significant mutations (nsSNPs/ single amino acid change) at both functional and structural levels, found in human GALNT3, GALNT8, GALNT12 and GALNT13 genes. From function and structure based insights, mutations encoding R162Q, T359K, C574G, G359D, R297W, Y396C & D313N substitutions were concordantly predicted highly deleterious for relevant GALNTs proteins. From intriguing findings, T359K- GALNT3 was simulated with high contribution for disease susceptibility (tumor calcinosis) as compared to its partner variant T272K [Ichikawa et al., 2006]. Similarly, the prediction of high damaging behavior, evolutionary conservation and structural destabilization for C574G were proposed as major contributing factors to regulate metabolic disorder underlying tumor calcinosis and hyperostosis-hyperphosphatemia syndrome. In case of R297W- GALNT12 , prediction of highly deleterious effect and disruption in ionic interactions were anticipated with reduction in enzymatic activity, associated with bilateral breast cancer and primary colorectal cancers. The second GALNT12 mutation (D303N)-known splice variant- was predicted with disease severity as a result of decrease in charge density and buried behavior neighboring the catalytic B domain. In the lack of adequate in silico data about systematic characterization of clinically significant mutations in GALNTs genes, current study can be used as a significant tool to interpret the role of GALNTs reaction chemistry in disease-association risks in body. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Beschreibung: Objective To investigate whether crosstalk between RUNX2 and miRNAs is involved in tooth eruption regulated by dental follicle cells(DFCs) and the possible molecular mechanism. Methods Blood samples and embedded dental follicles were collected from patients with cleidocranial dysplasia (CCD), and RUNX2 gene mutations were analyzed, then RUNX2 +/m DFCs were isolated and identified. The characteristics of RUNX2 +/m DFCs were analyzed. The differential expression of miRNAs was detected between the RUNX2 +/m DFCs and RUNX2 +/+ DFCs by microarray, and target genes were predicted by miRGen. miR-146a was chosen for further investigation, and its effects in DFCs were analyzed by transfecting its mimics and inhibitors, and expression of genes involved in tooth eruption were detected. Results A novel insertion mutation (c.309_310insTG) of RUNX2 gene was identified which had an effect on the characteristics of DFCs. Compared with the RUNX2 +/+ DFCs, there were 69 microRNAs more than 2-fold up-regulated and 54 microRNAs more than 2-fold down-regulated in the RUNX2 +/m DFCs. Among these, miR-146a decreased significantly in RUNX 2 +/m DFCs, and expression of RUNX2, CSF-1,EGFR and OPG was significantly altered when miR-146a was over-expressed or inhibited. Conclusion RUNX2 gene mutation contributes to the characteristic change of dental follicle cells, and the crosstalk between RUNX2 gene and miRNAs may be one of the key regulatory mechanisms of differentiation of dental follicle cells. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Beschreibung: Cancer stem cells (CSC) have a central role in driving tumor growth. Since metabolism is becoming an important diagnostic and therapeutic target, characterization of CSC line energetic properties is an emerging need. Embryonic and adult stem cells, compared to differentiated cells, exhibit a reduced mitochondrial activity and a stronger dependence on aerobic glycolysis. Here, we aimed to comparatively analyze bioenergetics features of the human osteosarcoma 3AB-OS CSC-like line, and the parental osteosarcoma MG63 cells, from which 3AB-OS cells have been previously selected. Our results suggest that 3AB-OS cells depend on glycolytic metabolism more strongly than MG63 cells. Indeed, growth in glucose shortage or in presence of galactose or pyruvate -mitochondrial specific substrates- leads to a significant reduction of their proliferation compared to MG63 cells. Accordingly, 3AB-OS cells show an increased expression of lactate dehydrogenase A (LDHA) and a larger accumulation of lactate in the culture medium. In line with these findings 3AB-OS cells as compared to MG63 cells present a reduced mitochondrial respiration, a stronger sensitivity to glucose depletion or glycolysis inhibition and a lessened sensitivity to oxidative phosphorylation inhibitors. Additionally, in contrast to MG63 cells, 3AB-OS display fragmented mitochondria, which become networked as they grow in glucose-rich medium, while almost entirely loose these structures growing in low glucose. Overall, our findings suggest that 3AB-OS CSCs energy metabolism is more similar to normal stem cells and to cancer cells characterized by a glycolytic anaerobic metabolism. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Beschreibung: Areca chewing is an important environmental risk factor for development of oral premalignant lesions and cancer. Epidemiological evidence indicates that areca chewing is tightly linked to oral carcinogenesis. However, the pathogenetic impacts of areca nut extract (ANE) on normal human oral keratinocytes (HOKs) are unclear and possibly involve oxidative stress via redox imbalance. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that play an important role in regulating cellular reactive oxygen species (ROS) production. Recent studies have confirmed that ANE and other areca ingredients can induce ROS. In this study, we examined the role of SIRT3 in the regulation of ANE-induced ROS in HOK cells. We examined HOK cell viability following treatment with various ANE concentrations. ANE-induced cytotoxicity increased in a dose-dependent manner and was approximately 48% at a concentration of 50 μg/ml after 24 h. SIRT3 expression and enzyme activity were up-regulated in HOK cells by ANE-induced oxidative stress. Additionally, we identified that SIRT3 controls the enzymatic activity of mitochondrial proteins, such as forkhead box O3a (Foxo3a) transcription factor and antioxidant-encoding gene superoxide dismutase 2 (SOD2), by deacetylation in HOK cells. Moreover, SIRT3-mediated deacetylation and activation of Foxo3a promotes nuclear localization in vivo . These findings suggest that SIRT3 is an endogenous negative regulator in response to ANE-induced oxidative stress and demonstrate an essential role for redox balance in HOK cells. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Beschreibung: Collagen is the most abundant structural protein in mammals and is expressed in various tissues. In recent years, sphingosine 1-phosphate receptors (S1PRs) have been proven to play an important role in the regulation of collagen expression. Our previous studies reported that S1PRs are involved in TGF-β1-induced collagen expression via up-regulating S1PR1/3 in mouse bone marrow-derived mesenchymal stem cells (BMSCs), and result in experimental mouse liver fibrogenesis. But it remains unclear whether this process happens in human bone marrow-derived mesenchymal stem cells (hMSCs). In this study, we provide evidences that S1PR1/3, but not S1PR2, negatively regulate the expression of collagen in hMSCs using cellular and molecular approaches in vitro . We find that treatment of hMSCs with TGF-β1 up-regulated collagen expression in a dose- and time-dependent manner. Meanwhile, TGF-β1 inhibited the expression of S1PR1/3, but not S1PR2, in hMSCs in a time-dependent manner. Furthermore, either selective knock-down of S1PR1 or silencing S1PR3 induced collagen α1(I) and collagen α1(III) expression in hMSCs. In contrast, inhibition of S1PR2 by siRNA had no effects on the expression of collagen. Altogether, all these findings demonstrated that collagen expression was negatively regulated by S1PR1 and S1PR3 in hMSCs. This study highlights the differences between hMSCs and mouse BMSCs, provides a new regulation mechanism for collagen expression, and points out the risk of utilizing hMSCs in clinical applications. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Beschreibung: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Debra A. Mayes , Tilat A. Rizvi , Haley Titus-Mitchell , Rachel Oberst , Georgianne M. Ciraolo , Charles V. Vorhees , Andrew P. Robinson , Stephen D. Miller , Jose A. Cancelas , Anat O. Stemmer-Rachamimov , Nancy Ratner Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1–NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor NG-nitro-L-arginine methyl ester or the antioxidant N-acetyl cysteine corrected cellular phenotypes. CNP-HRasG12V mice also displayed locomotor hyperactivity, which could be rescued by antioxidant treatment. We conclude that Nf1/Ras regulates oligodendrocyte NOS and that dysregulated NO signaling in oligodendrocytes can alter the surrounding vasculature. The data suggest that antioxidants may improve some behavioral deficits in Rasopathy patients. Graphical abstract Teaser In this study, Ratner and colleagues show that altering intracellular signaling in oligodendrocytes affects brain astrocytes and blood vessels that together make up the blood-brain barrier. Increasing oligodendrocyte Ras-GTP, mimicking neurofibromatosis type 1 and Costello syndrome, disrupted astrocyte and endothelial cell tight junctions and gap junctions and caused a leaky blood-brain barrier. Exposure to a nitric oxide synthase inhibitor or an antioxidant reversed cellular phenotypes and behavioral hyperactivity. Thus, oligodendrocytes contribute to brain homeostasis, and antioxidant therapy may be beneficial when homeostasis is disrupted.

Beschreibung: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Dalit Ben-Yosef , Francesca S. Boscolo , Hadar Amir , Mira Malcov , Ami Amit , Louise C. Laurent Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs) is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs) have shown that deletions and regions of loss of heterozygosity (LOH) tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs), we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs. Graphical abstract Teaser Human embryonic stem cells (hESCs) are potential sources of cells for transplantation therapy. However, given the association between mutations and cancer, the frequency of genetic aberrations observed in hESCs is concerning. Using unique pedigrees of hESC lines, Laurent and colleagues now find that aberrations that occur during cell-line derivation are mainly deletions and loss of heterozygosity, whereas duplications arise more commonly during long-term culture. These results highlight the need for improved methods for derivation and culture that preserve the genetic integrity of hESCs.

Beschreibung: Publication date: Available online 12 September 2013 Source: Cell Reports Author(s): Jason Karpac , Benoit Biteau , Heinrich Jasper Loss of metabolic homeostasis is a hallmark of aging and is commonly characterized by the deregulation of adaptive signaling interactions that coordinate energy metabolism with dietary changes. The mechanisms driving age-related changes in these adaptive responses remain unclear. Here, we characterize the deregulation of an adaptive metabolic response and the development of metabolic dysfunction in the aging intestine of Drosophila . We find that activation of the insulin-responsive transcription factor Foxo in intestinal enterocytes is required to inhibit the expression of evolutionarily conserved lipases as part of a metabolic response to dietary changes. This adaptive mechanism becomes chronically activated in the aging intestine, mediated by changes in Jun-N-terminal kinase (JNK) signaling. Age-related chronic JNK/Foxo activation in enterocytes is deleterious, leading to sustained repression of intestinal lipase expression and the disruption of lipid homeostasis. Changes in the regulation of Foxo-mediated adaptive responses thus contribute to the age-associated breakdown of metabolic homeostasis. Graphical abstract Teaser Aging is associated with a loss of metabolic homeostasis, which is a risk factor for various human pathologies. Using Drosophila , Karpac, Biteau, and Jasper show that the transcription factor Foxo regulates intestinal lipid homeostasis as part of an adaptive response to dietary changes and that chronic intestinal activation of Foxo with age leads to the disruption of lipid metabolism. These results demonstrate that changes in the regulation of adaptive signaling mechanisms can contribute to the age-associated breakdown of metabolic homeostasis.

Beschreibung: Article Control of active sites of heterogeneous catalysts can lead to enhanced product selectivity. Here, the authors use self-assembled alkanethiolate monolayers with varying surface densities to tune the selectivity of hydrogenation and hydrodeoxygenation of furfural on supported palladium catalysts. Nature Communications doi: 10.1038/ncomms3448 Authors: Simon H. Pang, Carolyn A. Schoenbaum, Daniel K. Schwartz, J. Will Medlin

Beschreibung: Article Knowing how moving droplets dissipate energy is important for designing superhydrophobic surfaces, but measuring such small energy losses is challenging. Timonen et al. develop a technique to do this, which monitors freely decaying and resonant oscillations of moving magnetic droplets. Nature Communications doi: 10.1038/ncomms3398 Authors: Jaakko V.I. Timonen, Mika Latikka, Olli Ikkala, Robin H.A. Ras

Beschreibung: Article Transport of DNA molecules across lipid membranes requires protein conduits such as the nuclear pore complex. Franceschini et al. engineer an artificial sequence-selective DNA transporter by attaching gating oligonucleotides to a bacterial nanopore. Nature Communications doi: 10.1038/ncomms3415 Authors: Lorenzo Franceschini, Misha Soskine, Annemie Biesemans, Giovanni Maglia

Beschreibung: Article Calculations suggest that ion transport through nanochannels is significantly modified as the diameter approaches molecular dimensions. Choi et al. introduce a single-nanotube platform to demonstrate this effect and find a maximum ion transport rate at a diameter of approximately 1.6 nm. Nature Communications doi: 10.1038/ncomms3397 Authors: Wonjoon Choi, Zachary W. Ulissi, Steven F.E. Shimizu, Darin O. Bellisario, Mark D. Ellison, Michael S. Strano

Beschreibung: Article In microscopy, the standard quantum limit represents the best achievable signal-to-noise ratio for a given light intensity. Here, the authors build an optical microscope that uses entanglement between photon pairs to overcome this barrier. Nature Communications doi: 10.1038/ncomms3426 Authors: Takafumi Ono, Ryo Okamoto, Shigeki Takeuchi

Beschreibung: Article Methane is a major constituent of planetary interiors, yet phase relations in the C–H system are poorly understood. This work documents the chemical reactivity of the C–H system over a wide range of temperatures and pressures, and sheds light on the chemical composition of Earth and icy giants. Nature Communications doi: 10.1038/ncomms3446 Authors: Sergey S. Lobanov, Pei-Nan Chen, Xiao-Jia Chen, Chang-Sheng Zha, Konstantin D. Litasov, Ho-Kwang Mao, Alexander F. Goncharov

Beschreibung: [1]  Although they are key components of the surface ocean carbon budget, physical processes inducing carbon fluxes across the mixed-layer base, i.e. subduction and obduction, have received much less attention than biological processes. Using a global model analysis of the pre-industrial ocean, physical carbon fluxes are quantified and compared to the other carbon fluxes in and out of the surface mixed-layer, i.e. air-sea CO 2 gas exchange and sedimentation of biogenic material. Model-based carbon obduction and subduction are evaluated against independent data-based estimates to the extent that was possible. We find that climatological physical fluxes of DIC are two orders of magnitude larger than the other carbon fluxes and vary over the globe at smaller spatial scale. At temperate latitudes, the subduction of DIC and to a much lesser extent (〈10%) the sinking of particles maintain CO 2 undersaturation, whereas DIC is obducted back to the surface in the tropical band (75%) and Southern Ocean (25%).At the global scale, these two large counter-balancing fluxes of DIC amount to +275.5 PgC y -1 for the supply by obduction and -264.5 PgC y -1 for the removal by subduction which is ~ 3 to 5 times larger than previous estimates. Moreover, we find that subduction of organic carbon (dissolved and particulate) represents ~ 20% of the total export of organic carbon: at the global scale, we evaluate that, of the 11 PgC y–1 of organic material lost from the surface every year, 2.1 PgC y -1 are lost through subduction of organic carbon. Our results emphasis the strong sensitivity of the oceanic carbon cycle to changes in mixed-layer depth, ocean currents and wind.

Beschreibung: Climate warming threatens to increase mass coral bleaching events, and several studies have projected the demise of tropical coral reefs this century. However, recent evidence indicates corals may be able to respond to thermal stress though adaptive processes (e.g., genetic adaptation, acclimatization, and symbiont shuffling). How these mechanisms might influence warming induced bleaching is largely unknown. This study compared how different adaptive processes could affect coral bleaching projections. We used the latest bias-corrected global sea surface temperature (SST) output from the NOAA/GFDL Earth System Model 2 (ESM2M) for the pre-industrial period though 2100 to project coral bleaching trajectories. Initial results showed that, in the absence of adaptive processes, application of a pre-industrial climatology to the NOAA Coral Reef Watch bleaching prediction method over-predicts the present day bleaching frequency. This suggests that corals may have already responded adaptively to some warming over the industrial period. We then modified the prediction method so that the bleaching threshold either permanently increased in response to thermal history (e.g., simulating directional genetic selection) or temporarily increased for 2-10 years in response to a bleaching event (e.g., simulating symbiont shuffling). A bleaching threshold that changes relative to the preceding 60 years of thermal history reduced the frequency of mass bleaching events by 20-80% compared with the ‘no adaptive response’ prediction model by 2100, depending on the emissions scenario. When both types of adaptive responses were applied, up to 14% more reef cells avoided high frequency bleaching by 2100. However, temporary increases in bleaching thresholds alone only delayed the occurrence of high frequency bleaching by ~10 years in all but the lowest emissions scenario. Future research should test the rate and limit of different adaptive responses for coral species across latitudes and ocean basins to determine if and how much corals can respond to increasing thermal stress. This article is protected by copyright. All rights reserved.

Beschreibung: Questions What are the general tree communities found in tidal freshwater swamps along four large coastal rivers in the southeastern United States (US)? How do these communities compare to other tidal freshwater swamps in the US and South America? Locations Tidal floodplains of major rivers along the Atlantic and Gulf coasts of the southeastern US: Savannah, Altamaha, Suwannee and Apalachicola Rivers. Methods An extensive survey of trees and shrubs was conducted to describe the communities from a range of tidal freshwater swamps. River basins studied include micro-tidal (Gulf coast) and meso-tidal (Atlantic coast) regimes, and study areas were located both near and distant to primary channels. A total of 128 plots (100 m 2 each) were inventoried, distributed evenly over the Savannah and Altamaha Rivers along the Atlantic coast, and the Suwannee and Apalachicola Rivers along the Gulf coast. Multivariate statistics helped discern communities and the significant indicator species in each. Results Four general communities were characterized and named according to the strongest individual indicator species in each: Water Tupelo ( Nyssa aquatica ) Community, Swamp Tupelo ( Nyssa biflora ) Community, Dwarf Palmetto ( Sabal minor ) Community and Cabbage Palm ( Sabal palmetto ) Community. Conclusions Descriptions of most tidal freshwater swamps in the southeastern US fit within the communities described in this study. Because studies that make inferences between environmental drivers (e.g. salinity, hydroperiod, hurricanes) and specific community types are best applied to the same communities (but perhaps different river systems), this work provides a framework by which tidal freshwater forested wetlands can be accurately compared based on their tree communities. We suggest that, within the broad range of our inventories, the four communities described identify the primary associations that should be tracked within most tidal freshwater swamps of the US. However, we identify some river basins in the US that do not fit this construct. Diversity of major tree communities in tidal freshwater swamps outside the US is generally much lower (with the notable exception of Amazonian hardwood tidal várzea), as are basal area values. Tidal freshwater forested wetlands are a poorly studied ecosystem that continues to be heavily impacted by global climate change, specifically via sea-level rise. We provide this four-community framework as a means to more accurately compare and predict ecosystem responses between different river systems. We describe how most published accounts fit into this framework and identify those that do not fit.

Beschreibung: Article The astronomical time scale is an essential geochronological tool, but is presently limited to the Cenozoic and Mesozoic eras. Here, Wu et al. time-calibrate Milankovitch cycles identified in strata from South China and extend this essential tool into the late Permian. Nature Communications doi: 10.1038/ncomms3452 Authors: Huaichun Wu, Shihong Zhang, Linda A. Hinnov, Ganqing Jiang, Qinglai Feng, Haiyan Li, Tianshui Yang

Beschreibung: Ecological Applications, Volume 0, Issue 0, Ahead of Print. Patterns of migratory connectivity are a vital yet poorly understood component of the ecology and evolution of migratory birds. Our ability to accurately characterize patterns of migratory connectivity is often limited by the spatial resolution of the data but recent advances in probabilistic assignment approaches have begun pairing stable isotopes with other sources of data (e.g., genetic and mark-recapture) to improve the accuracy and precision of inferences based on a single marker. Here, we combine stable isotopes and geographic variation in morphology (wing length) to probabilistically assign Wood thrush (Hylocichla mustilena) captured on the wintering grounds to breeding locations. In addition, we use known origin samples to validate our model and assess potentially important impacts of covariates of isotopic and morphological data (age, sex and breeding location). Our results show that despite relatively high levels of mixing across their breeding and non-breeding ranges, moderate levels of migratory connectivity along an east-west gradient exist. In addition, combining stable isotopes with geographic variation in wing improved the precision of breeding assignments by 10% and 37% compared to assignments based on isotopes alone or wing length alone, respectively. These results demonstrate that geographical variation in morphological traits can greatly improve estimates of migratory connectivity when combined with other intrinsic markers (e.g., stable isotopes or genetic data). The wealth of morphological data available from museum specimens across the world represents a tremendously valuable, but largely untapped, resource that is widely applicable for quantifying patterns of migratory connectivity.

Beschreibung: Ecology, Volume 0, Issue 0, Ahead of Print. The evolutionary pressures that drive long larval planktonic durations in some coastal marine organisms, while allowing direct development in others, have been vigorously debated. We introduce into the argument the asymmetric dispersal of larvae by coastal currents and find that the strength of the currents helps determine which dispersal strategies are evolutionarily stable. In a spatially and temporally uniform coastal ocean of finite extent, direct development is always evolutionarily stable. For passively drifting larvae, long planktonic durations are stable when the ratio of mean to fluctuating currents is small and the rate at which larvae increase in size in the plankton is greater than the mortality rate (both in units of per time). However, larval behavior that reduces downstream larval dispersal for a given time in plankton will be selected for, consistent with widespread observations of behaviors that reduce dispersal of marine larvae. Larvae with long planktonic durations are shown to be favored not for the additional dispersal they allow, but for the additional fecundity that larval feeding in the plankton enables. We analyze the spatial distribution of larval life histories in a large database of coastal marine benthic invertebrates and document a link between ocean circulation and the frequency of planktotrophy in the coastal ocean. The spatial variation in the frequency of species with planktotrophic larvae is largely consistent with our theory; increases in mean currents lead to a decrease in the fraction of species with planktotrophic larvae over a broad range of temperatures.

Beschreibung: The snow-masking effect of vegetation exerts strong control on albedo in northern high latitude ecosystems. Large-scale changes in the distribution and stature of vegetation in this region will thus have important feedbacks to climate. The snow-albedo feedback is controlled largely by the contrast between snow-covered and snow-free albedo (Δα), which influences predictions of future warming in coupled climate models, despite being poorly constrained at seasonal and century time scales. Here we compare satellite observations and coupled climate model representations of albedo and tree cover for the boreal and Arctic region. Our analyses reveal consistent declines in albedo with increasing tree cover, occurring south of latitudinal tree line, that are poorly represented in coupled climate models. Observed relationships between albedo and tree cover differ substantially between snow-covered and snow-free periods, and among plant functional type (PFT). Tree cover in models varies widely but surprisingly does not correlate well with model albedo. Further, our results demonstrate a relationship between tree cover and snow-albedo feedback that may be used to accurately constrain high latitude albedo feedbacks in coupled climate models under current and future vegetation distributions. This article is protected by copyright. All rights reserved.

Beschreibung: Because of global land surface warming, extreme temperature events are expected to occur more often and more intensely, affecting the growth and development of the major cereal crops in several ways, thus affecting the production component of food security. In this paper, we have identified rice and maize crop responses to temperature in different, but consistent, phenological phases and development stages. A literature review and data compilation of around 140 scientific articles have determined the key temperature thresholds and response to extreme temperature effects for rice and maize, complementing an earlier study on wheat. Lethal temperatures and cardinal temperatures, together with error estimates, have been identified for phenological phases and development stages. Following the methodology of previous work, we have collected and statistically analysed temperature thresholds of the three crops for the key physiological processes such as leaf initiation, shoot growth and root growth and for the most susceptible phenological phases such as sowing to emergence, anthesis and grain filling. Our summary shows that cardinal temperatures are conservative between studies and are seemingly well-defined in all three crops. Anthesis and ripening are the most sensitive temperature stages in rice as well as in wheat and maize. We call for further experimental studies of the effects of transgressing threshold temperatures so such responses can be included into crop impact and adaptation models. This article is protected by copyright. All rights reserved.

Beschreibung: Question Poikilohydric organisms can survive desiccation without damage and recover soon after re-wetting. In this work we explore the realized niches of epilithic, poikilohydric organisms, i.e. lichenized and lichenicolous fungi and bryophytes, grouped into 15 functional guilds based on growth form, reproductive strategy and photosynthetic traits. We hypothesize that in Mediterranean ecosystems, the distribution of these guilds is controlled by water availability and solar radiation, together with characteristics of the substrate. Location Western Sardinia (Italy). The area hosts Mediterranean Quercus ilex forests on basaltic substrata within an agroforestry landscape. Methods The presence or absence of species from each guild was recorded in 1025 small quadrats (10 × 10 cm). Four environmental variables were measured: solar radiation, microtopography (potential water run-off), substrate roughness and number of cracks. The occurrence of each guild was related to environmental variables using non-parametric multiplicative regression, and ecological niches of the guilds were derived from those models. Results The occurrence of all functional guilds varied significantly according to the selected environmental variables. In most cases, solar radiation was the most important variable; TI was included first in the model of two sorediate guilds, whereas four sexually reproducing functional guilds had surface relief as first variable. The growth forms were separated along a gradient of increasing solar radiation, whereas water run-off and surface roughness mainly discriminated reproductive strategies and photobionts. Vegetatively reproducing guilds with other photobionts than Euphyta-like pigments were confined to the border of the ecological space, defined by gradients of environmental factors, which was largely occupied by more competitive, sexually reproducing organisms. Conclusions Functional traits of epilithic poikilohydric organisms were associated with ecological adaptations to the stressful environment of Mediterranean outcrops. We showed that their response in terms of probability of occurrence is coherent with quantitative gradients of solar radiation and water availability at the micro-scale. Functional traits of epilithic poikilohydric organisms were associated to ecological adaptations to the stressing environment of Mediterranean outcrops. Their response in terms of probability of occurrence is coherent with quantitative gradients of solar radiation and water availability at the micro-scale.

Beschreibung: Article The social amoeba Dictyostelium discoideum displays a primitive form of agriculture with some clones carrying bacteria to seed out food crops. Brock et al . now demonstrate that these farmers also carry non-food bacteria that harm competing non-farmer amoeba clones, protecting the crop from exploitation. Nature Communications doi: 10.1038/ncomms3385 Authors: Debra A. Brock, Silven Read, Alona Bozhchenko, David C. Queller, Joan E. Strassmann

Beschreibung: Article A central tenet of population genetics is that the probability of fixing beneficial new alleles in a population is twice their fitness effect, but this has not been empirically proven. Chelo et al . show experimentally, using nematode worms, that extinction rates decrease when the number of beneficial alleles increases. Nature Communications doi: 10.1038/ncomms3417 Authors: Ivo M. Chelo, Judit Nédli, Isabel Gordo, Henrique Teotónio

Beschreibung: Article Sedimentation along convergent plate margins, the destructive sites of tectonic plate collision, is poorly understood. Malatesta et al. use a cutting-edge three-dimensinal subduction model to demonstrate that the trench-parallel motion of sediments has a much more important role than previously thought. Nature Communications doi: 10.1038/ncomms3456 Authors: Cristina Malatesta, Taras Gerya, Laura Crispini, Laura Federico, Giovanni Capponi

Beschreibung: Neuropeptide F (NPF), the invertebrate homolog of neuropeptide Y (NPY) in vertebrates, shares similarity of structure and function with NPY. However, a few NPYs were also found in some insect species. In this paper, two neuropeptide genes encoding a NPF and a NPY were cloned from a tobacco budworm Helicoverpa assulta cDNA library. The npf1 gene further produces two splicing variants of rnRNAs, i.e. npf1a (lacks the 120 bp segment) and npf1b (includes a 120 bp segment). These two splicing variants form two mature peptides, NPF1a and NPF1b by modification of transcripts. NPF and NPY co-exist in H. assulta.

Beschreibung: Cervical carcinoma represents the paradigm of virus-induced cancers, where virtually all cervical cancers come from previous “high-risk” HPV infection. The persistent expression of the HPV viral oncoproteins E6 and E7 is responsible for the reprogramming of fundamental cellular functions in the host cell, thus generating a noticeable, yet only partially explored, imbalance in protein molecular networks and cell signaling pathways. Eighty-eight cellular factors, identified as HPV direct or surrogate targets, were chosen and monitored in a retrospective analysis for their mRNA expression in HPV-induced cervical lesions, from dysplasia to cancer. Real-time quantitative PCR (qPCR) was performed by using formalin-fixed, paraffin embedded archival samples. Gene expression analysis identified 40 genes significantly modulated in LSIL, HSIL and squamous cervical carcinoma. Interestingly, among these, the expression level of a panel of four genes, TOP2A, CTNNB1, PFKM and GSN, was able to distinguish between normal tissues and cervical carcinomas. Immunohistochemistry was also done to assess protein expression of two genes among those up-regulated during the transition between dysplasia and carcinoma, namely E2F1 and CDC25A, and their correlation with clinical parameters. Besides the possibility of significantly enhancing the use of some of these factors in diagnostic or prognostic procedures, these data clearly outline specific pathways, and thus key biological processes, altered in cervical dysplasia and carcinoma. Deeper insight on how these molecular mechanisms work may help widen the spectrum of novel innovative approaches to these virus-induced cell pathologies. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Beschreibung: Cellular pathways are numerous and are highly integrated in function in the control of cellular systems. They collectively regulate cell division, proliferation, survival and apoptosis of cells and mutagenesis of key genes that control these pathways can initiate neoplastic transformations. Understanding these pathways is crucial to future therapeutic and preventive strategies of the disease. Ovarian cancers are of three major types; epithelial, germ-cell and stromal. However, ovarian cancers of epithelial origin, arising from the mesothelium, are the predominant form. Of the subtypes of ovarian cancer, the high-grade serous tumors are fatal, with low survival rate due to late detection and poor response to treatments. Close examination of preserved ovarian tissues and in vitro studies have provided insights into the mechanistic changes occurring in cells mediated by a few key genes. This review will focus on pathways and key genes of the pathways that are mutated or have aberrant functions in the pathology of ovarian cancer. Non-genetic mechanisms that are gaining prominence in the pathology of ovarian cancer, miRNAs and epigenetics, will also be discussed in the review. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Beschreibung: Normal pregnancy is associated with systemic vasodilation and decreased vascular contraction, partly due to increased release of endothelium-derived vasodilator substances. Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor acting via endothelin receptor type A (ET A R) and possibly type B (ET B R) in vascular smooth muscle cells (VSMCs), with additional vasodilator effects via endothelial ET B R. However, the role of ET-1 receptor subtypes in the regulation of vascular function during pregnancy is unclear. We investigated whether the decreased vascular contraction during pregnancy reflects changes in the expression/activity of ET A R and ET B R. Contraction was measured in single aortic VSMCs isolated from virgin, mid-pregnant (mid-Preg, day 12) and late-Preg (day 19) Sprague-Dawley rats, and the mRNA expression, protein amount, tissue and cellular distribution of ET A R and ET B R were examined using RT-PCR, Western blots, immunohistochemistry and immunofluorescence. Phenylephrine (Phe, 10 −5  M), KCl (51 mM) and ET-1 (10 −6  M) caused VSMC contraction that was in late-Preg 〈 mid-Preg and virgin rats. In VSMCs treated with ET B R antagonist BQ788, ET-1 caused significant contraction that was still in late-Preg 〈 mid-Preg and virgin rats. In VSMCs treated with the ET A R antagonist BQ123, ET-1 caused a small contraction; and the ET B R agonists IRL-1620 and sarafotoxin 6c (S6c) caused similar contraction that was in late-Preg 〈 mid-Preg and virgin rats. RT-PCR revealed similar ET A R, but greater ET B R mRNA expression in pregnant vs. virgin rats. Western blots revealed similar ET A R, and greater protein amount of ET B R in endothelium-intact vessels, but reduced ET B R in endothelium-denuded vessels of pregnant vs. virgin rats. Immunohistochemistry revealed prominent ET B R staining in the intima, but reduced ET A R and ET B R in the aortic media of pregnant rats. Immunofluorescence signal for ET A R and ET B R was less in VSMCs of pregnant vs. virgin rats. The pregnancy-associated decrease in ET A R- and ET B R-mediated VSMC contraction appears to involve downregulation of ET A R and ET B R expression/activity in VSM, and may play a role in the adaptive vasodilation during pregnancy. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Beschreibung: Neuroregenerative medicine is an ever-growing field in which regeneration of lost cells/tissues due to a neurodegenerative disease is the ultimate goal. With the scarcity of available replacement alternatives, stem cells provide an attractive source for regenerating neural tissue. While many stem cell sources exist, including: mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), the limited cellular potency, technical difficulties, and ethical considerations associated with these make finding alternate sources a desirable goal. Periodontal ligament stem cells (PDLSCs) derived from the neural crest were induced into neural-like cells using a combination of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Morphological changes were evident in our treated group, seen under both light microscopy and scanning electron microscopy (SEM). A statistically significant increase in the expression of neuron-specific β-tubulin III and the neural stem/progenitor cell marker nestin, along with positive immunohistochemical staining for glial fibrillary acidic protein (GFAP), demonstrated the success of our treatment in inducing both neuronal and glial phenotypes. Positive staining for synaptophysin demonstrated neural connections and electrophysiological recordings indicated that when subjected to whole cell patch clamping, our treated cells displayed inward currents conducted through voltage-gated sodium (Na + ) channels. Taken together, our results indicate the success of our treatment in inducing PDLSCs to neural-like cells. The ease of sourcing and expansion, their embryologic neural crest origin, and the lack of ethical implications in their use make PDLSCs an attractive source for use in neuroregenerative medicine. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Beschreibung: Urotensin II (UII), a vasoactive peptide modulates renal hemodynamics. However, the physiological functions of UII in glomerular cells are unclear. In particular, whether UII alters mesangial tone remains largely unknown. The present study investigates the physiological effects of UII on intracellular Ca 2+ ([Ca 2+ ] i ) and contraction in glomerular mesangial cells (GMCs). This study also tested the hypothesis that the regulator of G-protein signaling (RGS) controls UII receptor (UTR) activity in GMCs. RT-PCR, Western immunoblotting, and immunofluorescence revealed UTR expression and localization in cultured murine GMCs. Mouse UII (mUII) stimulated [Ca 2+ ] i elevation in GMCs in the absence and presence of extracellular Ca 2+ . mUII also caused a reduction in planar GMC surface area. mUII-induced [Ca 2+ ] i elevation and contraction in GMCs were attenuated by SB 657510, a UTR antagonist, araguspongin B, an inositol 1,4,5-trisphosphate receptor antagonist, thapsigargin, a sarco/endoplasmic reticulum Ca 2+ -ATPase inhibitor, and La 3+ , a store-operated Ca 2+ channel blocker, but not nimodipine, an L-type Ca 2+ channel blocker. In situ proximity ligation assay indicated molecular proximity between endogenous RGS2 and UTR in the cells. Treatment of GMCs with mUII increased plasma membrane association of RGS2 by ∼ 2-fold. mUII also increased the interaction between RGS2 and UTR in the cells. siRNA-mediated knockdown of RGS2 in murine GMCs increased mUII-induced [Ca 2+ ] i elevation and contraction by ∼ 35 and 31%, respectively. These findings indicate that mUII induces [Ca 2+ ] i elevation and contraction in murine GMCs. Data also suggest that UTR activation stimulates RGS2 recruitment to GMC plasma membrane as a negative feedback mechanism to regulate UTR signaling. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Beschreibung: Poly-N-acetyllactosamine (PLN) is a unique glycan composed of repeating units of the common disaccharide (Galβ1,4-GlcNAcβ1,3) n . The expression of PLN on glycoprotein core structures minimally requires enzyme activities for β1,4-galactosyltransferase (β4GalT) and β1,3-N-acetylglucosminyltransferase (β3GnT). Because β4GalTs are ubiquitous in most cells, PLN expression is generally ascribed to the tissue-specific transcription of 8 known β3GnT genes in mice. In the olfactory epithelium (OE), β3GnT2 regulates expression of extended PLN chains that are essential for axon guidance and neuronal survival. N-glycan branching and core composition, however, can also modulate the extent of PLN modification. Here we show for the first time that the β1,6-branching glycosyltransferase GCNT2 (formerly known as IGnT) is expressed at high levels specifically in the OE and other sensory ganglia. Postnatally, GCNT2 is maintained in mature olfactory neurons that coexpress β3GnT2 and PLN. This highly specific coexpression suggests that GCNT2 and β3GnT2 function cooperatively in PLN synthesis. In support of this, β3GnT2 and GCNT2 cotransfection in HEK293T cells results in high levels of PLN expression on the cell surface and on adenylyl cyclase 3, a major carrier of PLN glycans in the OE. These data clearly suggest that GCNT2 functions in vivo together with β3GnT2 to determine PLN levels in olfactory neurons by regulating β1,6-branches that promote PLN extension. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Beschreibung: Question In many plant species from fire-prone ecosystems germination is promoted by smoke. Mediterranean Basin (MB) flora is no exception. However, most information regarding germination response to smoke in the MB comes from a few experiments performed in laboratory conditions. This approach does not consider factors that occur in the field, such as species interactions, density-dependent processes or the fact that seeds spent time in the soil seed bank. In addition, species selection has been biased (e.g. there is a lack of information about annual species). Hence the importance of smoke relative to other fire cues is not clear, and we have a biased knowledge of post-fire community assembly in the MB. In this framework, we tested the following hypotheses: (1) smoke enhances seedling emergence and establishment from the soil seed bank of MB species, and (2) annual species are an important component of this smoke-stimulated flora. Location Mediterranean fire-prone shrublands in eastern Spain. Western Mediterranean Basin. Methods We performed a field experiment in which we applied a liquid smoke treatment and tracked seedling emergence and seedling establishment during 1 yr. Differences between smoke and control subplots with respect to seedling emergence and seedling establishment were analysed at different scales: community, growth form (annual or perennial), family and species level. Results At the community level, smoke played a clear role in seedling recruitment, increasing seedling emergence and seedling establishment. In addition, for most plots, families and species, establishment was higher in smoke subplots compared to the control. Annual species establishment was clearly stimulated by smoke but no effect was detected for perennials. Conclusions Smoke derived from wildfires has a key effect on plant recruitment and hence on community assembly in the MB vegetation. We applied liquid smoke in 21 plots and tracked seedling emergence and establishment during one year. Smoke increased seedling emergence and establishment globally and for most plots, families and species, and was most evident for annuals. Our results suggest that smoke derived from wildfires has a key effect on plant recruitment and community assembly in the Mediterranean Basin vegetation.

Beschreibung: Nature Reviews Microbiology 11, 660 (2013). doi:10.1038/nrmicro3130 Author: Ursula Hofer Mycobacterium bovis causes tuberculosis (TB) in cattle, but it can also infect wild animals and, occasionally, humans. In the United Kingdom, badgers are thought to spread M. bovis between farms, thereby hindering disease eradication. Two controversial programmes are now underway to tackle the

Beschreibung: Nature Reviews Microbiology 11, 657 (2013). doi:10.1038/nrmicro3128 In celebration of our tenth anniversary, we revisit selected topics from the first few issues of the journal and assess the progress that has been made over the past decade.

Beschreibung: Nature Reviews Microbiology 11, 661 (2013). doi:10.1038/nrmicro3116 Author: Rachel David Nature Reviews Microbiology11, 595 (2013)In the original article, the first author's name (Handa, Y.) was incorrect in the cited reference; this has now been corrected online. We apologize for any confusion caused.

Beschreibung: Nature Reviews Microbiology 11, 661 (2013). doi:10.1038/nrmicro3121 Author: Rachel David Recent work on H5N1 influenza A virus, in which strains have been genetically engineered to enable aerosol transmission between ferrets, has been criticized for potentially being dangerous. Here, Langlois et al. present an approach that could be used to improve the biosafety of such

Beschreibung: Nature Reviews Microbiology 11, 661 (2013). doi:10.1038/nrmicro3122 Author: Rachel David The highly conserved phosphatase calcineurin is required for hyphal growth and virulence in the filamentous fungus Aspergillus fumigatus. This study identifies a region (located in the linker between the catalytic domain (CnaA) and the regulatory domain (CnaB)) that has a key role in hyphal

Beschreibung: Nature Reviews Microbiology 11, 660 (2013). doi:10.1038/nrmicro3115 Author: Ursula Hofer The Bacillus subtilis protein BslA self-assembles into a water-repellent film that coats the surface of biofilms.

Beschreibung: Nature Reviews Microbiology 11, 660 (2013). doi:10.1038/nrmicro3113 Author: Rachel David In Caulobacter crescentus, DNA replication is paused during proteotoxic stress through Lon-mediated degradation of DnaA.

Beschreibung: Objective The aim of this study was to evaluate the effect of artemisinin on the proliferation and apoptosis of rat vascular smooth muscle cells (VSMCs). Method Primary rat VSMCs were treated with various doses of artemisinin. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the messenger RNA and protein expressions of proliferating cell nuclear antigen were determined by reverse-transcription polymerase chain reaction and immunohistochemistry. Apoptosis was measured using annexin V and propidium iodide double staining evaluated by flow cytometry. Protein expression of Bax, Bcl2, and cyclin-dependent kinase 4 was determined by Western blot. Results After 72 h of treatment, artemisinin significantly inhibited VSMC proliferation in a dose-dependent manner. Treatment with 1 mM artemisinin for 72 h significantly reduced the expression of proliferating cell nuclear antigen messenger RNA. On the other hand, the same treatment increased the apoptosis of VSMCs, the activation of caspase-3, the Bax protein expression, and the Bax/Bcl2 ratio. Conclusion The results suggest that artemisinin can effectively inhibit VSMC proliferation and induce VSMC apoptosis. Copyright © 2013 John Wiley & Sons, Ltd.

Beschreibung: Publication date: Available online 17 September 2013 Source: FEBS Open Bio Author(s): Rasheda Sultana , Maria A. Theodoraki , Avrom J. Caplan The UBR1 ubiquitin ligase promotes degradation of proteins via the N-end rule and by another mechanism that detects a misfolded conformation. Although UBR1 was shown recently to act on protein kinases whose misfolding was promoted by inhibition of Hsp90, it was unknown whether this ubiquitin ligase targeted other client types of the chaperone. We analyzed the role of UBR1 in the degradation of nuclear receptors that are classical clients of Hsp90. Our results showed that UBR1 deletion results in impaired degradation of the glucocorticoid receptor and the androgen receptor but not the estrogen receptor α. These findings demonstrate specificity in the actions of the UBR1 ubiquitin ligase in the degradation of Hsp90 clients in the presence of small molecule inhibitors that promote client misfolding. Graphical abstract

Beschreibung: In 2011 an unprecedented epidemic of equine encephalitis occurred in south-eastern (SE) Australia following heavy rainfall and severe flooding in the preceding 2–4 months. Less than 6% of the documented cases occurred in Queensland, prompting the question of pre-existing immunity in Queensland horses. A small-scale serological survey was conducted on horses residing in one of the severely flood-affected areas of SE-Queensland. Using a flavivirus-specific blocking-ELISA we found that 63% (39/62) of horses older than 3 years were positive for flavivirus antibodies, and of these 18% (7/38) had neutralizing antibodies to Murray Valley encephalitis virus (MVEV), Kunjin virus (WNVKUN) and/or Alfuy virus (ALFV). The remainder had serum-neutralizing antibodies to viruses in the Kokobera virus (KOKV) complex or antibodies to unknown/untested flaviviruses. Amongst eight yearlings one presented with clinical MVEV-encephalomyelitis, while another, clinically normal, had MVEV-neutralizing antibodies. The remaining six yearlings were flavivirus antibody negative. Of 19 foals born between August and November 2011 all were flavivirus antibody negative in January 2012. This suggests that horses in the area acquire over time active immunity to a range of flaviviruses. Nevertheless, the relatively infrequent seropositivity to MVEV, WNVKUN and ALFV (15%) suggests that factors other than pre-existing immunity may have contributed to the low incidence of arboviral disease in SE-Queensland horses during the 2011 epidemic.

Beschreibung: With an ever increasing population rate; a vast array of biomass wastes rich in organic and inorganic nutrients as well as pathogenic microorganisms will result from the diversified human, industrial and agricultural activities. Anaerobic digestion is applauded as one of the best ways to properly handle and manage these wastes. Animal wastes have been recognized as suitable substrates for anaerobic digestion process, a natural biological process in which complex organic materials are broken down into simpler molecules in the absence of oxygen by the concerted activities of four sets of metabolically linked microorganisms. This process occurs in an airtight chamber (biodigester) via four stages represented by hydrolytic, acidogenic, acetogenic and methanogenic microorganisms. The microbial population and structure can be identified by the combined use of culture-based, microscopic and molecular techniques. Overall, the process is affected by bio-digester design, operational factors and manure characteristics. The purpose of anaerobic digestion is the production of a renewable energy source (biogas) and an odor free nutrient-rich fertilizer. Conversely, if animal wastes are accidentally found in the environment, it can cause a drastic chain of environmental and public health complications.

Beschreibung: Scant information is available on determinants of smoking prevalence in the vulnerable population of the elderly, particularly in Europe. Therefore, we analyzed smoking patterns among older adults (≥65 years old), using data from a representative survey based on 3,071 elderly, conducted in 17 European countries in 2010, within the Pricing Policies And Control of Tobacco in Europe (PPACTE) project. Overall smoking prevalence in 17 European countries was 11.5% (15.3% in men and 8.6% in women). An inverse relation with level of education was observed among men, while no specific pattern was evident among women. Smoking prevalence was highest in eastern/central Europe for men (20.3%) and northern Europe for women (13.1%). In both sexes combined, smokers were more frequent in countries with low implementation of tobacco control activities (14.9%). Anti-tobacco campaigns and smoking cessation interventions specifically targeted to the elderly are urgently needed in Europe.

Beschreibung: [1]  A small hot spring that is informally called “Fe-waterfall spring” and is located in the Rehai geothermal area discharges hot (42 to 73 °C), near-neutral (pH =7.65) Fe-rich water. Submerged reddish precipitates are composed largely of ferrihydrite, goethite, lepidocrocite, opal-A, quartz, and anorthite, as revealed by X-ray diffraction (XRD) and Mössbauer spectroscopy. Molecular phylogenetic analysis demonstrates that the bacterial community in these precipitates is mainly composed of Cyanobacteria, Planctomycetes, β-proteobacteria, Deinococci-Thermus and Chlorobi. Scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM) examinations show that abundant sheath-like Fe oxyhydroxides, which exhibit different morphologies and sizes, are present in Fe-rich precipitates. These sheath-like structures are composed of ferrihydrite rather than more crystalline lepidocrocite or goethite. Energy dispersive X-ray spectrometer (EDS), scanning transmission electron microscopy (STEM) and nano secondary ion mass spectrometry (Nano-SIMS) reveal that they are mainly composed of Fe, Si and O, together with some trace elements. Most of the sheath-like structures are not morphologically comparable to biogenic Fe oxyhydroxides produced by known chemolithotrophic Fe oxidizers, which is consistent with the fact that no chemolithotrophic Fe oxidizers were identified by molecular analysis in the precipitates. We suggest that the sheath-like Fe oxyhydroxides are formed through passive Fe sorption and nucleation onto the cell walls of various thermophiles rather than by the direct metabolic activities of chemolithotrophic Fe oxidizers. Biogenic sheath-like Fe oxyhydroxides in Fe-waterfall spring have important implications for geochemical cycles driven by microorganisms, the origin of microfossils and the formation of banded iron formations (BIFs) in the Archean ocean.

Beschreibung: [1]  We present the concept of the Carbon Cycle Data Assimilation System and describe its evolution over the last two decades from an assimilation system around a simple diagnostic model of the terrestrial biosphere to a system for the calibration and initialization of the land component of a comprehensive earth system model. We critically review the capability of this modeling framework to integrate multiple data streams, to assess their mutual consistency and with the model, to reduce uncertainties in the simulation of the terrestrial carbon cycle, to provide, in a traceable manner, reanalysis products with documented uncertainty, and to assist the design of the observational network. We highlight some of the challenges we met and experience we gained, give recommendations for operating the system and suggest directions for future development.

Beschreibung: Article The structure of the human gut microbiota has been shown to vary between populations. Tyakht et al. analyse the gut microbiota assembly from Russian individuals living in urban and rural areas, and compare these with previously studied populations. Nature Communications doi: 10.1038/ncomms3469 Authors: Alexander V. Tyakht, Elena S. Kostryukova, Anna S. Popenko, Maxim S. Belenikin, Alexander V. Pavlenko, Andrey K. Larin, Irina Y. Karpova, Oksana V. Selezneva, Tatyana A. Semashko, Elena A. Ospanova, Vladislav V. Babenko, Igor V. Maev, Sergey V. Cheremushkin, Yuriy A. Kucheryavyy, Petr L. Shcherbakov, Vladimir B. Grinevich, Oleg I. Efimov, Evgenii I. Sas, Rustam A. Abdulkhakov, Sayar R. Abdulkhakov, Elena A. Lyalyukova, Maria A. Livzan, Valentin V. Vlassov, Renad Z. Sagdeev, Vladislav V. Tsukanov, Marina F. Osipenko, Irina V. Kozlova, Alexander V. Tkachev, Valery I. Sergienko, Dmitry G. Alexeev, Vadim M. Govorun

Beschreibung: Molecular Systems Biology 9, (2013). doi:10.1038/msb.2013.47 Authors: Anders R Kristensen, Joerg Gsponer & Leonard J Foster

Beschreibung: The Board of Parks and Recreation in Vancouver, BC approved a smoke-free bylaw in the city’s parks, beaches and recreational facilities, effective 1 September 2010. We analyzed local news coverage and portrayal of the bylaw to understand the potential influence of news media on public perception of the bylaw in order to inform the media advocacy work of public health interest groups. We compiled a data set of newspaper articles (n = 90) and conducted a quantitative content analysis to examine content related to the outdoor smoke-free policy, including article slant, topics related to smoking and tobacco control, and any equity-related concerns raised. Newspaper coverage in Vancouver was largely supportive of the outdoor smoke-free bylaw. However, concerns over rights were frequently discussed in letters to the editor. Such equity concerns were rarely discussed in news articles, showing a potential disconnect between the concerns expressed in the media by members of the public and the coverage provided by print media.

Beschreibung: [1]  Hypolithic microbial communities are productive niches in deserts worldwide, but many facets of their basic ecology remain unknown. The Namib Desert is an important site for hypolith study because it has abundant quartz rocks suitable for colonization and extends west to east across a transition from fog to rain dominated moisture sources. We show fog sustains and impacts hypolithic ecology in several ways: (1) fog effectively replaces rainfall in the western zone of the central Namib to enable high (≥95%) hypolithic abundance at landscape (1- 10 km) and larger scales; and (2) high water availability, through fog (western zone) and/or rainfall (eastern zone), results in smaller size-class rocks being colonized (mean 6.3 ± 1.2 cm) at higher proportions (e.g. 98% vs. ca . 3%) than in previously studied hyperarid deserts. We measured 0.1% of incident sunlight as the lower limit for hypolithic growth on quartz rocks in the Namib, and found uncolonized ventral rock surfaces were limited by light rather than moisture. In-situ monitoring showed that, although rainfall supplied more liquid water (36 hrs) per event than fog (mean, 4 hrs), on an equivalent annual basis, fog provided nearly twice as much liquid water as rainfall to the hypolithic zone. Hypolithic abundance reaches 100% at a mean annual precipitation (MAP) ca . 40-60 mm, but at a much lower MAP ( ca . 25 mm) when moisture from fog is available.

Beschreibung: Article Hydrogenosomes and mitosomes are mitochondria-related organelles with distinct properties. Here the authors find that the mitochondria-related organelle of the salmon parasite Spironucleus salmonicida has characteristics of both diplomonad mitosomes and of parabasalid hydrogenosomes, suggesting the presence of hydrogenosomes in the last common ancestor. Nature Communications doi: 10.1038/ncomms3493 Authors: Jon Jerlström-Hultqvist, Elin Einarsson, Feifei Xu, Karin Hjort, Bo Ek, Daniel Steinhauf, Kjell Hultenby, Jonas Bergquist, Jan O. Andersson, Staffan G. Svärd

Beschreibung: Article Tigers are an endangered species and therefore understanding their genetic architecture could aid conservation efforts. Here, the authors report the first genome sequence of the Amur tiger and, through close species comparative genomic analysis, provide insight into the genome organization, evolutionary divergence and diversity of big cats. Nature Communications doi: 10.1038/ncomms3433 Authors: Yun Sung Cho, Li Hu, Haolong Hou, Hang Lee, Jiaohui Xu, Soowhan Kwon, Sukhun Oh, Hak-Min Kim, Sungwoong Jho, Sangsoo Kim, Young-Ah Shin, Byung Chul Kim, Hyunmin Kim, Chang-uk Kim, Shu-Jin Luo, Warren E. Johnson, Klaus-Peter Koepfli, Anne Schmidt-Küntzel, Jason A. Turner, Laurie Marker, Cindy Harper, Susan M. Miller, Wilhelm Jacobs, Laura D. Bertola, Tae Hyung Kim, Sunghoon Lee, Qian Zhou, Hyun-Ju Jung, Xiao Xu, Priyvrat Gadhvi, Pengwei Xu, Yingqi Xiong, Yadan Luo, Shengkai Pan, Caiyun Gou, Xiuhui Chu, Jilin Zhang, Sanyang Liu, Jing He, Ying Chen, Linfeng Yang, Yulan Yang, Jiaju He, Sha Liu, Junyi Wang, Chul Hong Kim, Hwanjong Kwak, Jong-Soo Kim, Seungwoo Hwang, Junsu Ko, Chang-Bae Kim, Sangtae Kim, Damdin Bayarlkhagva, Woon Kee Paek, Seong-Jin Kim, Stephen J. O’Brien, Jun Wang, Jong Bhak

Beschreibung: Article The allenylation of terminal alkynes is a convenient route to allenes from simple starting materials, though previously limited to formaldehyde and aldehyde substrates. Here a method enabling the use of ketones is reported, giving easy access to trisubstituted allenes. Nature Communications doi: 10.1038/ncomms3450 Authors: Xinjun Tang, Can Zhu, Tao Cao, Jingqiang Kuang, Weilong Lin, Shengjun Ni, Jiasheng Zhang, Shengming Ma

Beschreibung: Article FGFR2 gene variation is associated with breast cancer risk but the molecular mechanism is unknown. Fletcher et al . provide a link between FGFR2 signalling and breast cancer susceptibility by demonstrating that FGFR2 signalling activates the ERa transcriptional network, which drives transcription of risk genes. Nature Communications doi: 10.1038/ncomms3464 Authors: Michael N. C. Fletcher, Mauro A. A. Castro, Xin Wang, Ines de Santiago, Martin O’Reilly, Suet-Feung Chin, Oscar M. Rueda, Carlos Caldas, Bruce A. J. Ponder, Florian Markowetz, Kerstin B. Meyer

Beschreibung: Article New catalysts for the oxygen evolution reaction in basic solution are important for energy storage applications. Here, the authors report the high activity and stability of double perovskites in this role, and their performance is attributed to the proximity of the oxygen p -band to the Fermi level. Nature Communications doi: 10.1038/ncomms3439 Authors: Alexis Grimaud, Kevin J. May, Christopher E. Carlton, Yueh-Lin Lee, Marcel Risch, Wesley T. Hong, Jigang Zhou, Yang Shao-Horn

Beschreibung: VDAC1-based peptides: novel pro-apoptotic agents and potential therapeutics for B-cell chronic lymphocytic leukemia Cell Death and Disease 4, e809 (September 2013). doi:10.1038/cddis.2013.316 Authors: T Prezma, A Shteinfer, L Admoni, Z Raviv, I Sela, I Levi & V Shoshan-Barmatz

Beschreibung: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): George E. Gentsch , Nick D.L. Owens , Stephen R. Martin , Paul Piccinelli , Tiago Faial , Matthew W.B. Trotter , Michael J. Gilchrist , James C. Smith The design of effective cell replacement therapies requires detailed knowledge of how embryonic stem cells form primary tissues, such as mesoderm or neurectoderm that later become skeletal muscle or nervous system. Members of the T-box transcription factor family are key in the formation of these primary tissues, but their underlying molecular activities are poorly understood. Here, we define in vivo genome-wide regulatory inputs of the T-box proteins Brachyury, Eomesodermin, and VegT, which together maintain neuromesodermal stem cells and determine their bipotential fates in frog embryos. These T-box proteins are all recruited to the same genomic recognition sites, from where they activate genes involved in stem cell maintenance and mesoderm formation while repressing neurogenic genes. Consequently, their loss causes embryos to form an oversized neural tube with no mesodermal derivatives. This collaboration between T-box family members thus ensures the continuous formation of correctly proportioned neural and mesodermal tissues in vertebrate embryos during axial elongation. Graphical abstract Teaser The development of effective cell replacement therapies requires detailed knowledge of how embryonic stem cells form primary tissues, such as mesoderm or neurectoderm that later become skeletal muscle or spinal cord. Gentsch, Smith, and colleagues now provide mechanistic insight into how T-box transcription factors regulate stem cells to form neural or mesodermal tissues. The authors show how this ensures the harmonious formation of spinal cord, muscle, and notochord as the vertebrate embryo elongates along its anteroposterior axis.

Beschreibung: Neuronal STAT3 activation is essential for CNTF- and inflammatory stimulation-induced CNS axon regeneration Cell Death and Disease 4, e805 (September 2013). doi:10.1038/cddis.2013.310 Authors: M Leibinger, A Andreadaki, H Diekmann & D Fischer

Beschreibung: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Ivan Zanoni , Roberto Spreafico , Caterina Bodio , Marco Di Gioia , Clara Cigni , Achille Broggi , Tatiana Gorletta , Michele Caccia , Giuseppe Chirico , Laura Sironi , Maddalena Collini , Mario P. Colombo , Natalio Garbi , Francesca Granucci Natural killer (NK) cells have antitumor, antiviral, and antibacterial functions, and efforts are being made to manipulate them in immunotherapeutic approaches. However, their activation mechanisms remain poorly defined, particularly during bacterial infections. Here, we show that upon lipopolysaccharide or E. coli exposure, dendritic cells (DCs) produce three cytokines—interleukin 2 (IL-2), IL-18, and interferon β (IFN-β)—necessary and sufficient for NK cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. This process allows the transfer of IL-15 on NK cell surface and its cis presentation. cis -presented NK cell-derived and trans -presented DC-derived IL-15 contribute equally to optimal NK cell activation. Graphical abstract Teaser NK cells depend on IL-15 provided by accessory cells for their survival under steady-state conditions. It has long been believed that a similar requirement is applied to NK cell activation as well. Zanoni, Granucci, and colleagues now show that NK cells express IL-15 and IL-15Rα when stimulated by type I interferons. NK cells cis -present self-produced IL-15, and this is as important to NK cell activation as trans presentation of IL-15 by dendritic cells.

Beschreibung: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Oren Ben-Ami , Dan Friedman , Dena Leshkowitz , Dalia Goldenberg , Kira Orlovsky , Niv Pencovich , Joseph Lotem , Amos Tanay , Yoram Groner The t(8;21) and inv(16) chromosomal aberrations generate the oncoproteins AML1-ETO (A-E) and CBFβ-SMMHC (C-S). The role of these oncoproteins in acute myeloid leukemia (AML) etiology has been well studied. Conversely, the function of native RUNX1 in promoting A-E- and C-S-mediated leukemias has remained elusive. We show that wild-type RUNX1 is required for the survival of t(8;21)-Kasumi-1 and inv(16)-ME-1 leukemic cells. RUNX1 knockdown in Kasumi-1 cells (Kasumi-1 RX1-KD ) attenuates the cell-cycle mitotic checkpoint, leading to apoptosis, whereas knockdown of A-E in Kasumi-1 RX1-KD rescues these cells. Mechanistically, a delicate RUNX1/A-E balance involving competition for common genomic sites that regulate RUNX1/A-E targets sustains the malignant cell phenotype. The broad medical significance of this leukemic cell addiction to native RUNX1 is underscored by clinical data showing that an active RUNX1 allele is usually preserved in both t(8;21) or inv(16) AML patients, whereas RUNX1 is frequently inactivated in other forms of leukemia. Thus, RUNX1 and its mitotic control targets are potential candidates for new therapeutic approaches. Graphical abstract Teaser The t(8;21) and inv(16) chimeric oncogenes are major etiological drivers of human acute myeloid leukemia. However, the function of native RUNX1 in these leukemias has remained unknown. Groner and colleagues demonstrate that expression of wild-type RUNX1 is essential for t(8;21) and inv(16) leukemogenesis. Reducing RUNX1 activity destines the leukemic cells for apoptosis. Importantly, an active RUNX1 allele is usually preserved in t(8;21) or inv(16) patients, whereas, in other leukemias, it is frequently inactivated, underscoring the significance of this leukemic cell addiction to RUNX1.

Beschreibung: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Markus Reschke , John G. Clohessy , Nina Seitzer , Daniel P. Goldstein , Susanne B. Breitkopf , Daniel B. Schmolze , Ugo Ala , John M. Asara , Andrew H. Beck , Pier Paolo Pandolfi Increasing evidence points to an important role for the ribosome in the regulation of biological processes and as a target for deregulation in disease. Here, we describe a SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry approach to probing mammalian riboproteomes. Using a panel of cell lines, as well as genetic and pharmacological perturbations, we obtained a comparative characterization of the cellular riboproteome. This analysis identified a set of riboproteome components, consisting of a diverse array of proteins with a strong enrichment for RNA-binding proteins. Importantly, this global analysis uncovers a high incidence of genetic alterations to riboproteome components in cancer, with a distinct bias toward genetic amplification. We further validated association with polyribosomes for several riboproteome components and demonstrate that enrichment at the riboproteome can depend on cell type, genetics, or cellular stimulus. Our results have important implications for the understanding of how ribosomes function and provide a platform for uncovering regulators of translation. Graphical abstract Teaser Increasing evidence points to an important role for the ribosome in regulating biological processes and as a target in disease. Now, Pandolfi and colleagues use mass spectrometry to probe the mammalian riboproteome. They show that the riboproteome displays differential composition in cancer cells and contains an array of proteins, many of which are frequently amplified in cancer. These results have important implications for the understanding of how ribosomes function and provide a platform to broaden our understanding of translational regulation.

Beschreibung: Ecology, Volume 94, Issue 9, Page 1955-1965, September 2013. Laboratory studies have demonstrated that the microscopic stages of kelps can rapidly resume development from a delayed state. Like terrestrial seeds or aquatic resting eggs, banks of delayed kelp stages may supplement population recovery after periods of stress, playing an important role for kelp populations that experience adult sporophyte absences due to seasonal or interannual disturbances. We found that removing the microscopic stages from natural rock substratum could prevent the appearance of juvenile kelp sporophytes for three months and the establishment of a diverse kelp assemblage for over four months within a southern California kelp forest. Juveniles were observed within one month in plots where microscopic stages were left intact, which may confer an advantage for the resulting sporophytes as they attain larger sizes before later recruiting neighbors. Microsatellite diversity was high (expected heterozygosity HE ≈ 0.9) for juveniles and adults within our sites. Using a microsatellite-based parentage analysis for the dominant kelp, Macrocystis pyrifera, we estimated that a portion of the new M. pyrifera sporophyte recruits had originated from their parents at least seven months after their parents had disappeared. Similar delay durations have been demonstrated in recent laboratory studies. Additionally, our results suggest that zoospore dispersal distances 〉50 m may be supported by including additional microsatellite loci in the analysis. We propose a mixed-age and, potentially, a mixed-origin bank of M. pyrifera gametophytes promotes maximal genetic diversity in recovering populations and reduces population genetic subdivision and self-fertilization rates for intact populations by promoting the survival of zoospores dispersed 〉10 m and during inhospitable environmental conditions.

Beschreibung: Ecology, Volume 94, Issue 9, Page 2109-2110, September 2013. Abstract Total body size, mass or linear measurements, and gonad mass or volumes have been recorded for the North American Pacific coast sea urchins Strongylocentrotus purpuratus, Mesocentrotus (Strongylocentrotus) franciscanus, and Lytechinus pictus by various workers at diverse sites and for varying lengths of time from 1954 to 2009. Some dissections included other body components such as the gut, body wall, and Aristotle's lantern, and some dissections included both wet and dry mass. There are numerous peer-reviewed publications that have used some of these data, but some data have appeared only in graduate theses or in the gray literature. There also are data that have never appeared outside the original data sheets. Historically, data were used to describe reproductive cycles and then to compare responses to stressors such as food limitation or pollution. Differences in temperature among sites also have been explored. More recently, dissection data have linked gonad development to ocean conditions, so called bottom-up forcing. The data set presented here is a historical record of gonad development for a common group of marine invertebrates in intertidal and nearshore environments, which can be used to test hypotheses concerning future changes associated with climate change and ocean acidification along the Pacific Coast of North America.

Beschreibung: Ecology, Volume 94, Issue 9, Page 2108-2111, September 2013. Abstract Chytridiomycosis caused by the fungal invasive pathogen Batrachochytrium dendrobatidis (Bd) was first detected in 1999 in Christchurch, New Zealand, in the Australian introduced frog species Litoria raniformis. It was detected in wild native frogs in the critically endangered Leiopelma archeyi in 2001 on the Coromandel Peninsula and has been suggested as responsible for a mass decline (88%) in that population between 1994 and 2002. We report the current distribution, host species and prevalence, where known, of Bd in New Zealand, which is essential for conservation management of New Zealand native frogs (Leiopelma spp.). The data set is structured so that it can be readily added to the Australian Bd database for further analyses. Our data included all regions in New Zealand and six offshore islands at 135 sites with 704 records from 23 contributors spanning collection dates 1930–2010. We report 54 positive sites from 132 positive individuals. We also detail negative findings, but declaring an area free from disease should consider the sensitivity of the test used and numbers of individuals tested. The data also included a comprehensive museum survey testing 152 individuals from five species (20 L. archeyi, 50 L. hochstetteri, 15 L. aurea, 40 L. ewingii, and 27 L. raniformis) from 1930–1999 using histology and Bd-specific immunohistochemistry. All museum specimens were negative, so the 1999 positive result is still the earliest record. In the L. archeyi Coromandel Ranges population, the period prevalence of Bd from 2006 to 2010 was relatively stable at 16%, but the number of animals tested remains low (up to N = 19) due to the now depleted population numbers. The period prevalence of Bd in the L. archeyi Whareorino population has remained both consistent and low (6%) between 2005 and 2010. In L. hochstetteri, L. hamiltoni, and L. pakeka all sampling for Bd has been negative. Positive Bd results have been found in all three Litoria spp., but Bd has not been found in the six offshore areas tested. Most data have been previously unpublished and represent the first confirmed reports of Bd in many regions and species in New Zealand.

Beschreibung: Will warming lead to an increased use of older soil organic carbon (SOC) by microbial communities, thereby inducing C losses from C-rich alpine soils? We studied soil microbial community composition, activity and substrate use after three and four years of soil warming (+4°C, 2007-2010) at the alpine treeline in Switzerland. The warming experiment was nested in a free air CO 2 enrichment experiment using depleted 13 CO 2 (δ 13 C = –30‰, 2001-2009). We traced this depleted 13 C label in phospholipid fatty acids (PLFA) of the organic layer (0-5 cm soil depth) and in C mineralized from root-free soils to distinguish substrate ages used by soil microorganisms: fixed before 2001 (“old”), from 2001 to 2009 (“new”) or in 2010 (“recent”). Warming induced a sustained stimulation of soil respiration (+38%) without decline in mineralizable SOC. PLFA concentrations did not reveal changes in microbial community composition due to soil warming, but soil microbial metabolic activity was stimulated (+66%). Warming decreased the amount of new and recent C in the fungal biomarker 18:2ω6,9 and the amount of new C mineralized from root-free soils, implying a shift in microbial substrate use towards a greater use of old SOC. This shift in substrate use could indicate an imbalance between C inputs and outputs, which could eventually decrease SOC storage in this alpine ecosystem. This article is protected by copyright. All rights reserved.

Beschreibung: Publication date: Available online 19 September 2013 Source: Cell Reports Author(s): Shunqiang Li , Dong Shen , Jieya Shao , Robert Crowder , Wenbin Liu , Aleix Prat , Xiaping He , Shuying Liu , Jeremy Hoog , Charles Lu , Li Ding , Obi L. Griffith , Christopher Miller , Dave Larson , Robert S. Fulton , Michelle Harrison , Tom Mooney , Joshua F. McMichael , Jingqin Luo , Yu Tao , Rodrigo Goncalves , Christopher Schlosberg , Jeffrey F. Hiken , Laila Saied , Cesar Sanchez , Therese Giuntoli , Caroline Bumb , Crystal Cooper , Robert T. Kitchens , Austin Lin , Chanpheng Phommaly , Sherri R. Davies , Jin Zhang , Megha Shyam Kavuri , Donna McEachern , Yi Yu Dong , Cynthia Ma , Timothy Pluard , Michael Naughton , Ron Bose , Rama Suresh , Reida McDowell , Loren Michel , Rebecca Aft , William Gillanders , Katherine DeSchryver , Richard K. Wilson , Shaomeng Wang , Gordon B. Mills , Ana Gonzalez-Angulo , John R. Edwards , Christopher Maher , Charles M. Perou , Elaine R. Mardis , Matthew J. Ellis To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation. Graphical abstract Teaser In this study, Ellis and colleagues compare whole-tumor genomes from drug-resistant breast cancers with paired xenografts. Genomic fidelity upon transplantation was high for structural variants but variable at the single-nucleotide level. Therefore, tumor and xenograft whole-genome comparisons critically assess genetic drift and clonal representation. Additional analysis revealed ESR1 mutations, amplification, and translocations associated with endocrine resistance in lumenal xenografts. Sequenced patient-derived xenografts are an important resource for functional genomics and capture treatment-resistance etiologies that are not observed in standard cell lines.

Beschreibung: The HDAC inhibitor, MPT0E028, enhances erlotinib-induced cell death in EGFR-TKI-resistant NSCLC cells Cell Death and Disease 4, e810 (September 2013). doi:10.1038/cddis.2013.330 Authors: M-C Chen, C-H Chen, J-C Wang, A-C Tsai, J-P Liou, S-L Pan & C-M Teng

Beschreibung: Ecology, Volume 94, Issue 9, Page 2055-2065, September 2013. A growing body of research documents the importance of plant genetic effects on arthropod community structure. However, the mechanisms underlying these effects are often unclear. Additionally, plant genetic effects have largely been quantified in common gardens, thus inflating the estimates of their importance by minimizing levels of natural variation. Using Valeriana edulis, a dioecious plant with genetically based sex determination, we conducted surveys and experiments on wild-grown individuals to document field patterns of arthropod association between the sexes and the mechanisms underlying these plant genetic effects. Three years of surveys revealed strong and consistent sex-biased arthropod association in wild-grown plants: female plants supported 4-fold, 1.5-fold, and 4-fold higher densities of aphids, aphid predators, and aphid-tending ants, respectively, compared to males. There was mixed evidence that the female bias for aphids was due to higher plant quality, while we found no difference between plant sexes in aphid preference or the top-down effects of predators and tending ants. Female bias for ants was due to both the greater attractiveness of female plants (direct effect mediated by floral nectar) and an independent, weaker effect of higher aphid abundance on females (density-mediated indirect effect). Conversely, the female bias for predators was driven solely by the greater attractiveness of female plants. We did not find interaction modification, i.e., ant–aphid and predator–aphid interactions were equivalent between plant sexes. Plant sex explained 0.24%, 2.28%, and 4.42% of the variance in aphids, predators, and ants, respectively, values comparable to but slightly weaker than those previously reported from common-garden studies. In contrast to the prediction of diminished plant genetic effects with increasing trophic level, we show how weak indirect effects on predators and parasitoids (via herbivores) can be complemented by strong direct effects via common plant traits (floral resources). In summary, we document direct and indirect effects of genetically based sex on a multi-trophic arthropod community that were expressed in wild-grown plants across multiple years.

Beschreibung: Ecology, Volume 94, Issue 9, Page 1893-1897, September 2013. The leaf economics spectrum (LES) has revolutionized the way many ecologists think about quantifying plant ecological trade-offs. In particular, the LES has connected a clear functional trade-off (long-lived leaves with slow carbon capture vs. short-lived leaves with fast carbon capture) to a handful of easily measured leaf traits. Building on this work, community ecologists are now able to quickly assess species carbon-capture strategies, which may have implications for community-level patterns such as competition or succession. However, there are a number of steps in this logic that require careful examination, and a potential danger arises when interpreting leaf-trait variation among species within communities where trait relationships are weak. Using data from 22 diverse communities, we show that relationships among three common functional traits (photosynthetic rate, leaf nitrogen concentration per mass, leaf mass per area) are weak in communities with low variation in leaf life span (LLS), especially communities dominated by herbaceous or deciduous woody species. However, globally there are few LLS data sets for communities dominated by herbaceous or deciduous species, and more data are needed to confirm this pattern. The context-dependent nature of trait relationships at the community level suggests that leaf-trait variation within communities, especially those dominated by herbaceous and deciduous woody species, should be interpreted with caution.

Beschreibung: Ecology, Volume 94, Issue 9, Page 2111-2112, September 2013. Abstract We present data from the first five years (2008–2012) of the establishment of the 25.6-ha Smithsonian Conservation Biology Institute (SCBI) Large Forest Dynamics Plot, comprising the initial woody stem census, woody seedling plot surveys, seed rain, and dendrochronological data. The plot is in mature secondary mixed deciduous forest 5 km south of Front Royal, Virginia, USA. The initial plot census enumerated 38 932 free-standing living stems and 29 991 living individuals ≥1 cm dbh comprising 62 species, 38 genera, and 26 families, along with an additional 1248 dead/missing standing stems, for a total of 40 180 stems. Dominant canopy trees include tulip poplar (Liriodendron tulipifera), hickories (Carya spp.), oaks (Quercus spp.), white ash (Fraxinus americana), and black gum (Nyssa sylvatica). Prominent understory components include spicebush (Lindera benzoin), pawpaw (Asimina triloba), American hornbeam (Carpinus caroliniana), witchhazel (Hamamelis virginiana), and eastern redbud (Cercis canadensis). Few species predominate numerically on the plot; seven species have 〉1000 individuals (71.3% of the total). Mean stand density was 1179 living individuals/ha, while mean basal area was 34.1 m2/ha. Of the total plot area, 4 ha have had white-tailed deer (Odocoileus virginianus) exclusion since 1990. Woody seedling surveys from 2010–2012 in 354 1-m2 plots measured 19 415 seedlings of 47 species, from new germinants up to 1 cm dbh. Community-wide seed rain data from 200 0.5-m2 litterfall traps yielded a total of 9197 records from 37 species. Long-term seed data collected from 1986–2011 for Quercus and Carya within the exclosure and two replicate sites are also presented, documenting considerable annual variation in mast production. Dendrochronological data from 492 tree cores suggested the major canopy trees established circa 1900, but scattered trees of several species existed earlier. Large-scale forest dynamics plots employing standardized methodology have a long, rich history in the tropics. Similar plots in the temperate zone have been largely lacking, however. The SCBI plot represents one of the first of its kind in the Smithsonian Global Earth Observatory's recently established network of such plots, complementing its well-known network of tropical forest plots and enabling comparative studies on forest ecology and climate change at the global scale.