ALBERT

Description: One of the most controversially discussed topics in current biodiversity-ecosystem function research is the transfer of results from experimental and theoretical studies to natural ecosystems. At the same time, monitoring data on biodiversity are requested as key indicators for the state of an ecosystem in most environmental evaluation frameworks. We analyse two monitoring data sets comprising information on abundance and biomass of macrozoobenthos communities in the German Wadden Sea in order to evaluate how much information monitoring data on biodiversity provide concerning ecosystem functioning and what implications this information (or the lack thereof) has for future monitoring programmes. Our results show a positive correlation between number of species of macrozoobenthos and its standing stock. Despite differences in overall biomass and individual size in different functional groups, this correlation remained consistent for different feeding guilds and therefore is likely to be independent of certain species traits. Moreover, functional turnover analyses indicate that increasing species richness is needed to maintain biomass levels over increasing periods of time. Whereas our data thus corroborate predictions from theory, we could not determine any causal relationships, because monitoring data commonly include only vague proxies for very few functional parameters, in our case standing biomass as a proxy for production. As to the use of diversity as an indicator for ecosystem functioning, we advise that management decisions are to be based on verified causal relationships and therefore strongly suggest the general incorporation of unambiguous proxies for functional parameters in the measuring campaigns of monitoring programmes.

Description: Ecological indicators for monitoring strategies are expected to combine three major characteristics: ecological significance, statistical credibility, and cost-effectiveness. Strategies based on stranding networks rank highly in cost-effectiveness, but their ecological significance and statistical credibility are disputed. Our present goal is to improve the value of stranding data as population indicator as part of monitoring strategies by constructing the spatial and temporal null hypothesis for strandings. The null hypothesis is defined as: small cetacean distribution and mortality are uniform in space and constant in time. We used a drift model to map stranding probabilities and predict stranding patterns of cetacean carcasses under H0 across the North Sea, the Channel and the Bay of Biscay, for the period 1990–2009. As the most common cetacean occurring in this area, we chose the harbour porpoise Phocoena phocoena for our modelling. The difference between these strandings expected under H0 and observed strandings is defined as the stranding anomaly. It constituted the stranding data series corrected for drift conditions. Seasonal decomposition of stranding anomaly suggested that drift conditions did not explain observed seasonal variations of porpoise strandings. Long-term stranding anomalies increased first in the southern North Sea, the Channel and Bay of Biscay coasts, and finally the eastern North Sea. The hypothesis of changes in porpoise distribution was consistent with local visual surveys, mostly SCANS surveys (1994 and 2005). This new indicator could be applied to cetacean populations across the world and more widely to marine megafauna.

Description: Phylogeographic patterns and sex-biased dispersal were studied in riverine populations of West Indian (Trichechus manatus) and Amazonian manatees (T. inunguis) in South America, using 410bp D-loop (Control Region, Mitochondrial DNA) sequences and 15 nuclear microsatellite loci. This multi-locus approach was key to disentangle complex patterns of gene flow among populations. D-loop analyses revealed population structuring among all Colombian rivers for T. manatus, while microsatellite data suggested no structure. Two main populations of T. inunguis separating the Colombian and Peruvian Amazon were supported by analysis of the D-loop and microsatellite data. Overall, we provide molecular evidence for differences in dispersal patterns between sexes, demonstrating male-biased gene flow dispersal in riverine manatees. These results are in contrast with previously reported levels of population structure shown by microsatellite data in marine manatee populations, revealing low habitat restrictions to gene flow in riverine habitats, and more significant dispersal limitations for males in marine environments. © 2012 Satizábal et al.

Description: by Johnatan Aljadeff, Ronen Segev, Michael J. Berry, Tatyana O. Sharpee Many biological systems perform computations on inputs that have very large dimensionality. Determining the relevant input combinations for a particular computation is often key to understanding its function. A common way to find the relevant input dimensions is to examine the difference in variance between the input distribution and the distribution of inputs associated with certain outputs. In systems neuroscience, the corresponding method is known as spike-triggered covariance (STC). This method has been highly successful in characterizing relevant input dimensions for neurons in a variety of sensory systems. So far, most studies used the STC method with weakly correlated Gaussian inputs. However, it is also important to use this method with inputs that have long range correlations typical of the natural sensory environment. In such cases, the stimulus covariance matrix has one (or more) outstanding eigenvalues that cannot be easily equalized because of sampling variability. Such outstanding modes interfere with analyses of statistical significance of candidate input dimensions that modulate neuronal outputs. In many cases, these modes obscure the significant dimensions. We show that the sensitivity of the STC method in the regime of strongly correlated inputs can be improved by an order of magnitude or more. This can be done by evaluating the significance of dimensions in the subspace orthogonal to the outstanding mode(s). Analyzing the responses of retinal ganglion cells probed with Gaussian noise, we find that taking into account outstanding modes is crucial for recovering relevant input dimensions for these neurons.

Description: by Lydia Nakiyingi, John Mark Bwanika, Bruce Kirenga, Damalie Nakanjako, Catherine Katabira, Gloria Lubega, Joseph Sempa, Barnabas Nyesiga, Heidi Albert, Yukari C. Manabe Introduction The existing diagnostic algorithms for sputum smear-negative tuberculosis (TB) are complicated, time-consuming, and often difficult to implement. The decision to initiate TB treatment in resource-limited countries is often largely based on clinical predictors. We sought to determine the clinical predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum smear-negative TB suspects using sputum culture as a reference standard. Setting Out-patient HIV-TB integrated urban clinic in Kampala, Uganda. Methods HIV-infected TB suspects were screened using sputum smear microscopy, and mycobacterial sputum liquid and solid cultures were performed. Smear results were made available to the clinician who made a clinical decision on empiric TB treatment initiation for sputum smear-negative patients. Clinic records were reviewed for patients whose sputum smears were negative to collect data on socio-demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB treatment initiation. Results Of 253 smear-negative TB suspects, 56% (142/253) were females, median age 38 IQR (31–44) years, with a median CD4 cell count of 291 IQR (150–482) cells/mm 3 . Of the 85 (33.6%) smear-negative patients empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture positive compared to only 18 (10.7%) of the 168 untreated patients (p

Description: by Cyril Dégletagne, Damien Roussel, Jean Louis Rouanet, Fanny Baudimont, Elodie-Marie Moureaux, Steve Harvey, Claude Duchamp, Yvon Le Maho, Mireille Raccurt The evolutionary trade-off between tissue growth and mature function restricts the post natal development of polar birds. The present study uses an original integrative approach as it includes gene expression, plus biochemical and physiological analysis to investigate how Adélie penguin chicks achieve a rapid growth despite the energetic constraints linked to the cold and the very short breeding season in Antarctica. In pectoralis muscle, the main thermogenic tissue in birds, our data show that the transition from ectothermy to endothermy on Day 15 post- hatching is associated with substantial and coordinated changes in the transcription of key genes. While the early activation of genes controlling cell growth and differentiation (avGHR, avIGF-1R, T3Rβ) is rapidly down-regulated after hatching, the global increase in the relative expression of genes involved in thermoregulation (avUCP, avANT, avLPL) and transcriptional regulation (avPGC1α, avT3Rβ) underlie the muscular acquisition of oxidative metabolism. Adélie chicks only become real endotherms at 15 days of age with the development of an oxidative muscle phenotype and the ability to shiver efficiently. The persistent muscular expression of IGF-1 throughout growth probably acts as a local mediator to adjust muscle size and its oxidative capacity to anticipate the new physiological demands of future Dives in cold water. The up-regulation of T3Rβ mRNA levels suggests that circulating T3 may play an important role in the late maturation of skeletal muscle by reinforcing, at least in part, the paracrine action of IGF-1. From day 30, the metabolic shift from mixed substrate to lipid metabolism, with the markedly increased mRNA levels of muscle avLPL, avANT and avUCP, suggests the late development of a fatty acid-enhanced muscle non-shivering thermogenesis mechanism. This molecular control is the key to this finely-tuned strategy by which the Adélie penguin chick successfully heads for the sea on schedule.

Description: by Philip Wing-Lok Ho, Zero Ho-Man Tse, Hui-Fang Liu, Song Lu, Jessica Wing-Man Ho, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho Xenoestrogens are either natural or synthetic compounds that mimic the effects of endogenous estrogen. These compounds, such as bisphenol-A (BPA), and phthalates, are commonly found in plastic wares. Exposure to these compounds poses major risk to human health because of the potential to cause endocrine disruption. There is huge demand for a wide range of chemicals to be assessed for such potential for the sake of public health. Classical in vivo assays for endocrine disruption are comprehensive but time-consuming and require sacrifice of experimental animals. Simple preliminary in vitro screening assays can reduce the time and expense involved. We previously demonstrated that catechol-O-methyltransferase (COMT) is transcriptionally regulated by estrogen via estrogen receptor (ER). Therefore, detecting corresponding changes of COMT expression in estrogen-responsive cells may be a useful method to estimate estrogenic effects of various compounds. We developed a novel cell-based ELISA to evaluate cellular response to estrogenicity by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to estrogenic compounds. In contrast to various existing methods that only detect bioactivity, this method elucidates direct physiological effect in a living cell in response to a compound. We validated our assay using three well-characterized estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP), and di-n-butyl phthalate (DBP). Cells were exposed to either these plasticizers or 17β-estradiol (E2) in estrogen-depleted medium with or without an ER-antagonist, ICI 182,780, and COMT expression assayed. Exposure to each of these plasticizers (10 -9 -10 -7 M) dose-dependently reduced COMT expression (p

Description: by Luca Laudani, Giuseppe Vannozzi, Zimi Sawacha, Ugo della Croce, Andrea Cereatti, Andrea Macaluso Maintaining adequate levels of physical activity is known to preserve health status and functional independence as individuals grow older. However, the relationship between determinants of physical activity (volume and intensity) and physiological factors underlying mobility (cardio-respiratory fitness, neuromuscular function and functional abilities) is still unclear. The aim of this study was to investigate the association between objectively quantified physical activity and a spectrum of physiological factors underlying mobility in young, middle-aged and older individuals living in a city district. Experiments were carried out on 24 young (28±2 years), 24 middle-aged (48±2 years) and 24 older (70±3 years) gender-matched volunteers. Physical activity was monitored by a wearable activity monitor to quantify volume and intensity of overall physical activity and selected habitual activities over 24 hours. Ventilatory threshold was assessed during an incremental cycling test. Torque, muscle fiber conduction velocity and agonist-antagonist coactivation were measured during maximal voluntary contraction of knee extensors and flexors. Ground reaction forces were measured during sit-to-stand and counter-movement jump. K-means cluster analysis was used to classify the participants’ physical activity levels based on parameters of volume and intensity. Two clusters of physical activity volume (i.e., high and low volume) and three clusters of physical activity intensity (i.e. high, medium and low intensity) were identified in all participants. Cardio-respiratory fitness was associated with volume of overall physical activity as well as lying, sitting, standing, walking and stair climbing. On the other hand, neuromuscular function and functional abilities showed a significant association with intensity of overall physical activity as well as postural transition, walking and stair climbing. As a practical application, the relative role played by volume and intensity of overall physical activity and selected habitual activities should be taken into account in the design of preventative training interventions to preserve mobility as individuals grow older.

Description: by Daniel Garcia de la serrana, Ian A. Johnston Heat shock proteins 90 (Hsp90) have an essential role in sarcomere formation and differentiation in skeletal muscle and also act as molecular chaperones during protein folding impacting a wide range of physiological processes. We characterised and provided a phylogenetically consistent nomenclature for the complete repertoire of six Hsp90 paralogues present in duplicated salmonid fish genomes (Hsp90α1a, Hsp90α1b, Hsp90α2a, Hsp90α2b, Hsp90ß1a and Hsp90ß1b). The expression of paralogues in fast skeletal muscle was investigated using in vivo fasting-feeding experiments and primary myogenic cultures. Fasted juvenile Atlantic salmon ( Salmo salar ) showed a transient 2 to 8-fold increase in the expression of all 4 Hsp90α paralogues within 24h of satiation feeding. H sp90α1a and hsp90α1b also showed a pronounced secondary increase in expression after 10 days, concomitant with muscle differentiation and the expression of myogenin and sarcomeric proteins ( mlc2 , myhc ). Hsp90ß1b was constitutively expressed whereas Hsp90ß1a expression was downregulated 10-fold between fasted and fed individuals. Hsp90α1a and Hsp90α1b were upregulated 10 to 15-fold concomitant with myotube formation and muscle differentiation in vitro whereas other Hsp90 paralogues showed no change in expression. In cells starved of amino acid (AA) and serum for 72h the addition of AA, but not insulin-like growth factor 1, increased phosphorylation of mTor and expression of all 4 hsp90α paralogues and associated co-chaperones including hsp30 , tbcb , pdia4 , pdia6 , stga and fk504bp1 , indicating a general activation of the protein folding response. In contrast, Hsp90ß1a expression in vitro was unresponsive to AA treatment indicating that some other as yet uncharacterised signal(s) regulate its expression in response to altered nutritional state.

Description: by Monika Marejková, Květa Bláhová, Jan Janda, Angelika Fruth, Petr Petráš Background Enterohemorrhagic Escherichia coli (EHEC) cause diarrhea-associated hemolytic uremic syndrome (D+ HUS) worldwide, but no systematic study of EHEC as the causative agents of HUS was performed in the Czech Republic. We analyzed stools of all patients with D+ HUS in the Czech Republic between 1998 and 2012 for evidence of EHEC infection. We determined virulence profiles, phenotypes, antimicrobial susceptibilities and phylogeny of the EHEC isolates. Methodology/Principal Findings Virulence loci were identified using PCR, phenotypes and antimicrobial susceptibilities were determined using standard procedures, and phylogeny was assessed using multilocus sequence typing. During the 15-year period, EHEC were isolated from stools of 39 (69.4%) of 56 patients. The strains belonged to serotypes [ fliC types] O157:H7/NM[ fliC H7 ] (50% of which were sorbitol-fermenting; SF), O26:H11/NM[ fliC H11 ], O55:NM[ fliC H7 ], O111:NM[ fliC H8 ], O145:H28[ fliC H28 ], O172:NM[ fliC H25 ], and Orough:NM[ fliC H25 ]. O26:H11/NM[ fliC H11 ] was the most common serotype associated with HUS (41% isolates). Five stx genotypes were identified, the most frequent being stx 2a (71.1% isolates). Most strains contained EHEC- hlyA encoding EHEC hemolysin, and a subset (all SF O157:NM and one O157:H7) harbored cdt-V encoding cytolethal distending toxin. espP α encoding serine protease EspPα was found in EHEC O157:H7, O26:H11/NM, and O145:H28, whereas O172:NM and Orough:NM strains contained espP γ. All isolates contained eae encoding adhesin intimin, which belonged to subtypes β (O26), γ (O55, O145, O157), γ2/θ (O111), and ε (O172, Orough). Loci encoding other adhesins ( efa1, lpfA O26 , lpfA O157OI-141 , lpfA O157OI-154 , iha ) were usually associated with particular serotypes. Phylogenetic analysis demonstrated nine sequence types (STs) which correlated with serotypes. Of these, two STs (ST660 and ST1595) were not found in HUS-associated EHEC before. Conclusions/Significance EHEC strains, including O157:H7 and non-O157:H7, are frequent causes of D+ HUS in the Czech Republic. Identification of unusual EHEC serotypes/STs causing HUS calls for establishment of an European collection of HUS-associated EHEC, enabling to study properties and evolution of these important pathogens.

Description: by Hanneke K. M. Meeren, Beatrice de Gelder, Seppo P. Ahlfors, Matti S. Hämäläinen, Nouchine Hadjikhani Evidence from functional neuroimaging indicates that visual perception of human faces and bodies is carried out by distributed networks of face and body-sensitive areas in the occipito-temporal cortex. However, the dynamics of activity in these areas, needed to understand their respective functional roles, are still largely unknown. We monitored brain activity with millisecond time resolution by recording magnetoencephalographic (MEG) responses while participants viewed photographs of faces, bodies, and control stimuli. The cortical activity underlying the evoked responses was estimated with anatomically-constrained noise-normalised minimum-norm estimate and statistically analysed with spatiotemporal cluster analysis. Our findings point to distinct spatiotemporal organization of the neural systems for face and body perception. Face-selective cortical currents were found at early latencies (120–200 ms) in a widespread occipito-temporal network including the ventral temporal cortex (VTC). In contrast, early body-related responses were confined to the lateral occipito-temporal cortex (LOTC). These were followed by strong sustained body-selective responses in the orbitofrontal cortex from 200–700 ms, and in the lateral temporal cortex and VTC after 500 ms latency. Our data suggest that the VTC region has a key role in the early processing of faces, but not of bodies. Instead, the LOTC, which includes the extra-striate body area (EBA), appears the dominant area for early body perception, whereas the VTC contributes to late and post-perceptual processing.

Description: by Volkhard Göber, Andreas Hohl, Brigitta Gahl, Florian Dick, Verena Eigenmann, Thierry P. Carrel, Hendrik T. Tevaearai Background Peak levels of troponin T (TnT) reliably predict morbidity and mortality after cardiac surgery. However, the therapeutic window to manage CABG-related in-hospital complications may close before the peak is reached. We investigated whether early TnT levels correlate as well with complications after coronary artery bypass grafting (CABG) surgery. Methods A 12 month consecutive series of patients undergoing elective isolated CABG procedures (mini-extra-corporeal circuit, Cardioplegic arrest) was analyzed. Logistic regression modeling was used to investigate whether TnT levels 6 to 8 hours after surgery were independently associated with in-hospital complications (either post-operative myocardial infarction, stroke, new-onset renal insufficiency, intensive care unit (ICU) readmission, prolonged ICU stay (〉48 hours), prolonged need for vasopressors (〉24 hours), resuscitation or death). Results A total of 290 patients, including 36 patients with complications, was analyzed. Early TnT levels (odds ratio (OR): 6.8, 95% confidence interval (CI): 2.2-21.4, P=.001), logistic EuroSCORE (OR: 1.2, 95%CI: 1.0-1.3, P=.007) and the need for vasopressors during the first 6 postoperative hours (OR: 2.7, 95%CI: 1.0-7.1, P=.05) were independently associated with the risk of complications. With consideration of vasopressor use during the first 6 postoperative hours, the sum of specificity (0.958) and sensitivity (0.417) of TnT for subsequent complications was highest at a TnT cut-off value of 0.8 ng/mL. Conclusion Early TnT levels may be useful to guide ICU management of CABG patients. They predict clinically relevant complications within a potential therapeutic window, particularly in patients requiring vasopressors during the first postoperative hours, although with only moderate sensitivity.

Description: by Valentine S. Moullé, Christelle Le Foll, Erwann Philippe, Nadim Kassis, Claude Rouch, Nicolas Marsollier, Linh-Chi Bui, Christophe Guissard, Julien Dairou, Anne Lorsignol, Luc Pénicaud, Barry E. Levin, Céline Cruciani-Guglielmacci, Christophe Magnan Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/− heparin (IL, IL H , respectively) or saline/heparin (S H ) were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1) Rats previously injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA; 2) Etomoxir (CPT1 inhibitor) or saline co-infused with IL H /S H ; and 3) Triacsin C (acylCoA synthase inhibitor) or saline co-infused with IL H /S H . IL H significantly lowered food intake during refeeding compared to S H (p

Description: by Paul A. Stevenson, Jan Rillich Population density has profound influences on the physiology and behaviour of many animal species. Social isolation is generally reported to lead to increased aggressiveness, while grouping lowers it. We evaluated the effects of varying degrees of isolation and grouping on aggression in a territorial insect, the Mediterranean field cricket, Gryllus bimaculatus . Substantiating early observations, we show that dyadic contests between weight-matched, adult male crickets taken from groups rarely escalate beyond threat displays, whereas interactions between pairs of previously isolated crickets typically escalate to physical fights lasting several seconds. No significant differences were found between 1, 2 and 6-day isolates, or between individuals grouped for a few hours or lifelong. Unexpectedly, crickets grouped in immediate proximity within individual mesh cages that precluded fighting while permitting visual, olfactory and mechanical, antennal contact, were as aggressive as free isolates. This suggests that reduced aggression of grouped animals may be an acquired result of fighting. Supporting this notion, isolated crickets initially engage in vigorous fights when first grouped, but fighting intensity and duration rapidly decline to the level of life-long grouped crickets within only 10 min. Furthermore, grouped crickets become as aggressive as life-long isolates after only 3 hours of isolation, and on the same time course required for crickets to regain their aggressiveness after social defeat. We conclude that the reduced aggressiveness of grouped crickets is a manifestation of the loser effect resulting from social subjugation, while isolation allows recovery to a state of heightened aggressiveness, which in crickets can be considered as the default condition. Given the widespread occurrence of the loser effect in the Animal Kingdom, many effects generally attributed to social isolation are likely to be a consequence of recovery from social subjugation.

Description: by Horst Kierdorf, Uwe Kierdorf, Kai Frölich, Carsten Witzel We studied the structural characteristics and periodicities of regular incremental markings in sheep enamel using fluorochrome injections for vital labeling of forming enamel and backscattered electron imaging in the scanning electron microscope. Microscopic analysis of mandibular first molars revealed the presence of incremental markings with a daily periodicity (laminations) that indicated successive positions of the forming front of interprismatic enamel. In addition to the laminations, incremental markings with a sub-daily periodicity were discernible both in interprismatic enamel and in enamel prisms. Five sub-daily increments were present between two consecutive laminations. Backscattered electron imaging revealed that each sub-daily growth increment consisted of a broader and more highly mineralized band and a narrower and less mineralized band (line). The sub-daily markings in the prisms of sheep enamel morphologically resembled the (daily) prisms cross striations seen in primate enamel. Incremental markings with a supra-daily periodicity were not observed in sheep enamel. Based on the periodicity of the incremental markings, maximum mean daily apposition rates of 17.0 µm in buccal enamel and of 13.4 µm in lingual enamel were recorded. Enamel extension rates were also high, with maximum means of 180 µm/day and 217 µm/day in upper crown areas of buccal and lingual enamel, respectively. Values in more cervical crown portions were markedly lower. Our results are in accordance with previous findings in other ungulate species. Using the incremental markings present in primate enamel as a reference could result in a misinterpretation of the incremental markings in ungulate enamel. Thus, the sub-daily growth increments in the prisms of ungulate enamel might be mistaken as prism cross striations with a daily periodicity, and the laminations misidentified as striae of Retzius with a supra-daily periodicity. This would lead to a considerable overestimation of crown formation times in ungulate teeth.

Description: by Zhu Huang, Xiao-Dong Pan, Ping-Gu Wu, Jian-Long Han, Qing Chen Environmental pollution with toxic heavy metals can lead to the possible contamination of the rice. Selected metals (As, Cd, Hg and Pb) and their accumulation in rice collected from Zhejiang, China were analyzed to evaluate the potential health risk to the local adults and children. The mean levels found in rice were as follows: As, 0.080 mg/kg; Cd, 0.037 mg/kg; Hg, 0.005 mg/kg; Pb, 0.060 mg/kg. The estimated daily intakes (EDIs) were calculated in combination of the rice consumption data. The mean intakes of As, Cd, Hg and Pb through rice were estimated to be 0.49, 0.23, 0.03 and 0.37 µg/kg bw/day for adults, and 0.34, 0.29, 0.04 and 0.47 µg/kg bw/day for children. The 97.5th percentile (P97.5) daily intakes of As, Cd, Hg and Pb were 1.02, 0.64, 0.37 and 1.26 µg/kg bw/day for adults, and 0.63, 0.83, 0.47 and 1.63 µg/kg bw/day for children. The risk assessment in mean levels showed that health risk associated with these elements through consumption of rice was absent. However, estimates in P97.5 level of Cd and Pb for children, and Hg for adults have exceeded the respective safe limits.

Description: The magnetism of graphene has remained divergent and controversial due to absence of reliable experimental results. Here we show the intrinsic magnetism of graphene edge states revealed based on unidirectional aligned graphene sheets derived from completely carbonized SiC crystals. It is found that ferromagnetism, antiferromagnetism and diamagnetism along with a probable superconductivity exist in the graphene with irregular zigzag edges. A phase diagram is constructed to show the evolution of the magnetism. The ferromagnetic ordering curie-temperature of the fundamental magnetic order unit (FMOU) is 820 ± 80 K. The antiferromagnetic ordering Neel temperature of the FMOUs belonging to different sublattices is about 54 ± 2 K. The diamagnetism is similar to that of graphite and can be well described by the Kotosonov's equation. Our experimental results provide new evidences to clarify the controversial experimental phenomena observed in graphene and contribute to a deeper insight into the nature of magnetism in graphene based system. Scientific Reports 3 doi: 10.1038/srep02599

Description: The detection, differentiation and visualization of compounds such as gases, liquids or ions are key challenges for the design of selective optical chemosensors. Optical chemical sensors employ a transduction mechanism that converts a specific analyte recognition event into an optical signal. Here we report a novel concept for fluoride ion sensing where a porous crystalline framework serves as a host for a fluorescent reporter molecule. The detection is based on the decomposition of the host scaffold which induces the release of the fluorescent dye molecule. Specifically, the hybrid composite of the metal-organic framework NH2-MIL-101(Al) and fluorescein acting as reporter shows an exceptional turn-on fluorescence in aqueous fluoride-containing solutions. Using this novel strategy, the optical detection of fluoride is extremely sensitive and highly selective in the presence of many other anions. Scientific Reports 3 doi: 10.1038/srep02562

Description: Despite the pathological importance of fibrin clot formation, little is known about the structure of these clots because X-ray and nuclear magnetic resonance (NMR) analyses are not applicable to insoluble proteins. In contrast to previously reported anti-fibrin monoclonal antibodies (mAbs), our anti-fibrin clot mAb (clone 102–10) recognises an uncovered region that is exposed only when a fibrin clot forms. The epitope of the 102–10 mAb was mapped to a hydrophobic region on the Bβ chain that interacted closely with a counterpart region on the γ chain in a soluble state. New anti-Bβ and anti-γ mAbs specific to peptides lining the discovered region appeared to bind exclusively to fibrin clots. Furthermore, the radiolabelled 102–10 mAb selectively accumulated in mouse spontaneous tumours, and immunohistochemistry using this mAb revealed greater fibrin deposition in World Health Organization (WHO) grade 4 glioma than in lower-grade gliomas. Because erosive tumours are apt to cause micro-haemorrhages, even early asymptomatic tumours detected with a radiolabelled 102-10 mAb may be aggressively malignant. Scientific Reports 3 doi: 10.1038/srep02604

Description: An electrical pumped microscopic active display with integration of plasmonic polarizer and light-emitting-diode is proposed. Thanks to the strong polarized emission through the rectangular nanoholes, well designed pixels with respect to different polarizations are engineered, which give rise to flexible and controllable active display. As results, polarization multiplexed letter encoding, single and double gray-scale images and animation movies are successfully realized. Our results demonstrate a new strategy in electro-optical integration and indicate potential applications in designing new type of microscopic electro-optical devices. Scientific Reports 3 doi: 10.1038/srep02603

Description: We compare the three most commonly used scanning probe techniques to obtain a reliable value of the work function in graphene domains of different thickness. The surface potential (SP) of graphene is directly measured in Hall bar geometry via a combination of electrical functional microscopy and spectroscopy techniques, which enables calibrated work function measurements of graphene domains in ambient conditions with values Φ1LG ~4.55 ± 0.02 eV and Φ2LG ~ 4.44 ± 0.02 eV for single- and bi-layer, respectively. We demonstrate that frequency-modulated Kelvin probe force microscopy (FM-KPFM) provides more accurate measurement of the SP than amplitude-modulated (AM)-KPFM. The discrepancy between experimental results obtained by different techniques is discussed. In addition, we use FM-KPFM for contactless measurements of the specific components of the device resistance. We show a strong non-Ohmic behavior of the electrode-graphene contact resistance and extract the graphene channel resistivity. Scientific Reports 3 doi: 10.1038/srep02597

Description: The non-canonical NF-κB pathway is crucial for the immune system. A critical event in activation of the non-canonical pathway is the attenuation of NF-κB-inducing kinase (NIK) degradation, which is promoted by continuous polyubiquitination of NIK catalyzed by the NIK ubiquitin-ligase complex composed of cellular inhibitor of apoptosis protein 1 and 2 (cIAP1/2), TNF receptor-associated factor 2 (TRAF2), and TRAF3. However, the molecular mechanism of stimulation-dependent NIK stabilization remains poorly understood. Here, we show that A20, a ubiquitin-editing enzyme, promotes efficient activation of the non-canonical pathway independent of its catalytic activity. A20 directly binds to cIAP1 through the seventh zinc finger of A20, resulting in dissociation of the TRAF2/TRAF3 interaction, thereby inactivating the ligase complex to stabilize NIK. Given that A20 negatively regulates the canonical pathway, A20 is likely involved in the molecular switch that promotes the transition from canonical to non-canonical activation for proper control of the immune system. Scientific Reports 3 doi: 10.1038/srep02568

Description: Plasmon-enhanced photocurrent generation and water oxidation from visible to near-infrared wavelengths NPG Asia Materials 5, e61 (September 2013). doi:10.1038/am.2013.42 Authors: Kosei Ueno & Hiroaki Misawa

Description: 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

Description: 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

Description: 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

Description: by Simone Picelli, Justo Lorenzo Bermejo, Jenny Chang-Claude, Michael Hoffmeister, Ceres Fernández-Rozadilla, Angel Carracedo, Antoni Castells, Sergi Castellví-Bel, Members of the EPICOLON Consortium (Gastrointestinal Oncology Group of the Spanish Gastroenterological Association): , Alessio Naccarati, Barbara Pardini, Ludmila Vodickova, Heiko Müller, Bente A. Talseth-Palmer, Geoffrey Stibbard, Paolo Peterlongo, Carmela Nici, Silvia Veneroni, Li Li, Graham Casey, Albert Tenesa, Susan M. Farrington, Ian Tomlinson, Victor Moreno, Tom van Wezel, Juul Wijnen, Malcolm Dunlop, Paolo Radice, Rodney J. Scott, Pavel Vodicka, Clara Ruiz-Ponte, Hermann Brenner, Stephan Buch, Henry Völzke, Jochen Hampe, Clemens Schafmayer, Annika Lindblom In the last four years, Genome-Wide Association Studies (GWAS) have identified sixteen low-penetrance polymorphisms on fourteen different loci associated with colorectal cancer (CRC). Due to the low risks conferred by known common variants, most of the 35% broad-sense heritability estimated by twin studies remains unexplained. Recently our group performed a case-control study for eight Single Nucleotide Polymorphisms (SNPs) in 4 CRC genes. The present investigation is a follow-up of that study. We have genotyped six SNPs that showed a positive association and carried out a meta-analysis based on eight additional studies comprising in total more than 8000 cases and 6000 controls. The estimated recessive odds ratio for one of the SNPs, rs3219489 (MUTYH Q338H), decreased from 1.52 in the original Swedish study, to 1.18 in the Swedish replication, and to 1.08 in the initial meta-analysis. Since the corresponding summary probability value was 0.06, we decided to retrieve additional information for this polymorphism. The incorporation of six further studies resulted in around 13000 cases and 13000 controls. The newly updated OR was 1.03. The results from the present large, multicenter study illustrate the possibility of decreasing effect sizes with increasing samples sizes. Phenotypic heterogeneity, differential environmental exposures, and population specific linkage disequilibrium patterns may explain the observed difference of genetic effects between Sweden and the other investigated cohorts.

Description: by Takashi Ochiai, Yuji Suehiro, Katsuhiro Nishinari, Takeo Kubo, Hideaki Takeuchi Background Coordinated movement in social animal groups via social learning facilitates foraging activity. Few studies have examined the behavioral cause-and-effect between group members that mediates this social learning. Methodology/Principal Findings We first established a behavioral paradigm for visual food learning using medaka fish and demonstrated that a single fish can learn to associate a visual cue with a food reward. Grouped medaka fish (6 fish) learn to respond to the visual cue more rapidly than a single fish, indicating that medaka fish undergo social learning. We then established a data-mining method based on Kullback-Leibler divergence (KLD) to search for candidate behaviors that induce alignment and found that high-speed movement of a focal fish tended to induce alignment of the other members locally and transiently under free-swimming conditions without presentation of a visual cue. The high-speed movement of the informed and trained fish during visual cue presentation appeared to facilitate the alignment of naïve fish in response to some visual cues, thereby mediating social learning. Compared with naïve fish, the informed fish had a higher tendency to induce alignment of other naïve fish under free-swimming conditions without visual cue presentation, suggesting the involvement of individual recognition in social learning. Conclusions/Significance Behavioral cause-and-effect studies of the high-speed movement between fish group members will contribute to our understanding of the dynamics of social behaviors. The data-mining method used in the present study is a powerful method to search for candidates factors associated with inter-individual interactions using a dataset for time-series coordinate data of individuals.

Description: by Anthony Singhal, Simona Monaco, Liam D. Kaufman, Jody C. Culham Behavioral and neuropsychological research suggests that delayed actions rely on different neural substrates than immediate actions; however, the specific brain areas implicated in the two types of actions remain unknown. We used functional magnetic resonance imaging (fMRI) to measure human brain activation during delayed grasping and reaching. Specifically, we examined activation during visual stimulation and action execution separated by a 18-s delay interval in which subjects had to remember an intended action toward the remembered object. The long delay interval enabled us to unambiguously distinguish visual, memory-related, and action responses. Most strikingly, we observed reactivation of the lateral occipital complex (LOC), a ventral-stream area implicated in visual object recognition, and early visual cortex (EVC) at the time of action. Importantly this reactivation was observed even though participants remained in complete darkness with no visual stimulation at the time of the action. Moreover, within EVC, higher activation was observed for grasping than reaching during both vision and action execution. Areas in the dorsal visual stream were activated during action execution as expected and, for some, also during vision. Several areas, including the anterior intraparietal sulcus (aIPS), dorsal premotor cortex (PMd), primary motor cortex (M1) and the supplementary motor area (SMA), showed sustained activation during the delay phase. We propose that during delayed actions, dorsal-stream areas plan and maintain coarse action goals; however, at the time of execution, motor programming requires re-recruitment of detailed visual information about the object through reactivation of (1) ventral-stream areas involved in object perception and (2) early visual areas that contain richly detailed visual representations, particularly for grasping.

Description: by Annabel Meyer, Andreas Focks, Viviane Radl, Daniel Keil, Gerhard Welzl, Ingo Schöning, Steffen Boch, Sven Marhan, Ellen Kandeler, Michael Schloter Understanding factors driving the ecology of N cycling microbial communities is of central importance for sustainable land use. In this study we report changes of abundance of denitrifiers, nitrifiers and nitrogen-fixing microorganisms (based on qPCR data for selected functional genes) in response to different land use intensity levels and the consequences for potential turnover rates. We investigated selected grassland sites being comparable with respect to soil type and climatic conditions, which have been continuously treated for many years as intensely used meadows ( IM ), intensely used mown pastures ( IP ) and extensively used pastures ( EP ), respectively. The obtained data were linked to above ground biodiversity pattern as well as water extractable fractions of nitrogen and carbon in soil. Shifts in land use intensity changed plant community composition from systems dominated by s-strategists in extensive managed grasslands to c-strategist dominated communities in intensive managed grasslands. Along the different types of land use intensity, the availability of inorganic nitrogen regulated the abundance of bacterial and archaeal ammonia oxidizers. In contrast, the amount of dissolved organic nitrogen determined the abundance of denitrifiers ( nirS and nirK ). The high abundance of nifH carrying bacteria at intensive managed sites gave evidence that the amounts of substrates as energy source outcompete the high availability of inorganic nitrogen in these sites. Overall, we revealed that abundance and function of microorganisms involved in key processes of inorganic N cycling (nitrification, denitrification and N fixation) might be independently regulated by different abiotic and biotic factors in response to land use intensity.

Description: 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

Description: 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

Description: 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

Description: 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

Description: 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

Description: by Xiaofeng Wang, Liang Zhang, Zixian Chen, Yushui Ma, Yuan Zhao, Abudouaini Rewuti, Feng Zhang, Da Fu, Yusong Han Background The association between polymorphisms on 5p12 and breast cancer (BC) has been widely evaluated since it was first identified through genome-wide association approach; however, the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two wildly studied polymorphisms (rs10941679 and rs4415084) on 5p12. Methods Databases including Pubmed, EMBASE, Web of Science, EBSCO, and Cochrane Library databases were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, addressing heterogeneity and publication bias. Results A total of 19 articles involving 100,083 cases and 163,894 controls were included. An overall random-effects per-allele OR of 1.09 (95% CI: 1.06–1.12; P =  4.5×10 −8 ) and 1.09 (95% CI: 1.05–1.12; P  = 4.2×10 −7 ) was found for the rs10941679 and rs4415084 polymorphism respectively. Significant results were found in Asians and Caucasians when stratified by ethnicity; whereas no significant associations were found among Africans/African-Americans. Similar results were also observed using dominant or recessive genetic models. In addition, we find both rs4415084 and rs10941679 conferred significantly greater risks of ER-positive breast cancer than of ER-negative tumors. Conclusions Our findings demonstrated that rs10941679-G allele and rs4415084-T allele might be risk-conferring factors for the development of breast cancer, especially in Caucasians and East-Asians.

Description: by Dongnhu T. Truong, Ashley Bonet, Amanda R. Rendall, Glenn D. Rosen, Roslyn H. Fitch Disruption of neuronal migration in humans is associated with a wide range of behavioral and cognitive outcomes including severe intellectual disability, language impairment, and social dysfunction. Furthermore, malformations of cortical development have been observed in a number of neurodevelopmental disorders (e.g. autism and dyslexia), where boys are much more commonly diagnosed than girls (estimates around 4 to 1). The use of rodent models provides an excellent means to examine how sex may modulate behavioral outcomes in the presence of comparable abnormal neuroanatomical presentations. Initially characterized by Rosen et al. 2012, the BXD29- Tlr4lps−2J /J mouse mutant exhibits a highly penetrant neuroanatomical phenotype that consists of bilateral midline subcortical nodular heterotopia with partial callosal agenesis. In the current study, we confirm our initial findings of a severe impairment in rapid auditory processing in affected male mice. We also report that BXD29- Tlr4lps−2J /J (mutant) female mice show no sparing of rapid auditory processing, and in fact show deficits similar to mutant males. Interestingly, female BXD29- Tlr4lps−2J /J mice do display superiority in Morris water maze performance as compared to wild type females, an affect not seen in mutant males. Finally, we report new evidence that BXD29- Tlr4lps−2J /J mice, in general, show evidence of hyper-social behaviors. In closing, the use of the BXD29- Tlr4lps−2J /J strain of mice – with its strong behavioral and neuroanatomical phenotype – may be highly useful in characterizing sex independent versus dependent mechanisms that interact with neural reorganization, as well as clinically relevant abnormal behavior resulting from aberrant neuronal migration.

Description: by Peng Zhao, Xue-mei Zhou, Li-yao Zhang, Wei Wang, Li-gang Ma, Li-bo Yang, Xiong-bo Peng, Peter V. Bozhkov, Meng-xiang Sun Plant zygote divides asymmetrically into an apical cell that develops into the embryo proper and a basal cell that generates the suspensor, a vital organ functioning as a conduit of nutrients and growth factors to the embryo proper. After the suspensor has fulfilled its function, it is removed by programmed cell death (PCD) at the late stages of embryogenesis. The molecular trigger of this PCD is unknown. Here we use tobacco ( Nicotiana tabacum ) embryogenesis as a model system to demonstrate that the mechanism triggering suspensor PCD is based on the antagonistic action of two proteins: a protease inhibitor, cystatin NtCYS, and its target, cathepsin H-like protease NtCP14. NtCYS is expressed in the basal cell of the proembryo, where encoded cystatin binds to and inhibits NtCP14, thereby preventing precocious onset of PCD. The anti-cell death effect of NtCYS is transcriptionally regulated and is repressed at the 32-celled embryo stage, leading to increased NtCP14 activity and initiation of PCD. Silencing of NtCYS or overexpression of NtCP14 induces precocious cell death in the basal cell lineage causing embryonic arrest and seed abortion. Conversely, overexpression of NtCYS or silencing of NtCP14 leads to profound delay of suspensor PCD. Our results demonstrate that NtCYS-mediated inhibition of NtCP14 protease acts as a bipartite molecular module to control initiation of PCD in the basal cell lineage of plant embryos.

Description: by William Henry Gilbert

Description: by Kaheina Aizel, Valérie Biou, Jorge Navaza, Lionel V. Duarte, Valérie Campanacci, Jacqueline Cherfils, Mahel Zeghouf The mechanisms whereby guanine nucleotide exchange factors (GEFs) coordinate their subcellular targeting to their activation of small GTPases remain poorly understood. Here we analyzed how membranes control the efficiency of human BRAG2, an ArfGEF involved in receptor endocytosis, Wnt signaling, and tumor invasion. The crystal structure of an Arf1–BRAG2 complex that mimics a membrane-bound intermediate revealed an atypical PH domain that is constitutively anchored to the catalytic Sec7 domain and interacts with Arf. Combined with the quantitative analysis of BRAG2 exchange activity reconstituted on membranes, we find that this PH domain potentiates nucleotide exchange by about 2,000-fold by cumulative conformational and membrane-targeting contributions. Furthermore, it restricts BRAG2 activity to negatively charged membranes without phosphoinositide specificity, using a positively charged surface peripheral to but excluding the canonical lipid-binding pocket. This suggests a model of BRAG2 regulation along the early endosomal pathway that expands the repertoire of GEF regulatory mechanisms. Notably, it departs from the auto-inhibitory and feedback loop paradigm emerging from studies of SOS and cytohesins. It also uncovers a novel mechanism of unspecific lipid-sensing by PH domains that may allow sustained binding to maturating membranes.

Description: by Shuncang Zhang, Pengda Ma, Dongfeng Yang, Wenjing Li, Zongsuo Liang, Yan Liu, Fenghua Liu Salvia miltiorrhiza Bunge is one of the most renowned traditional medicinal plants in China. Phenolic acids that are derived from the rosmarinic acid pathway, such as rosmarinic acid and salvianolic acid B, are important bioactive components in S. miltiorrhiza . Accumulations of these compounds have been reported to be induced by various elicitors, while little is known about transcription factors that function in their biosynthetic pathways. We cloned a subgroup 4 R2R3 MYB transcription factor gene ( SmMYB39 ) from S. miltiorrhiza and characterized its roles through overexpression and RNAi-mediated silencing. As the results showed, the content of 4-coumaric acid, rosmarinic acid, salvianolic acid B, salvianolic acid A and total phenolics was dramatically decreased in SmMYB39 -overexpressing S. miltiorrhiza lines while being enhanced by folds in SmMYB39 -RNAi lines. Quantitative real-time PCR and enzyme activities analyses showed that SmMYB39 negatively regulated transcripts and enzyme activities of 4-hydroxylase (C4H) and tyrosine aminotransferase (TAT). These data suggest that SmMYB39 is involved in regulation of rosmarinic acid pathway and acts as a repressor through suppressing transcripts of key enzyme genes.

Description: by Sang-Eun Yeon, Da Yoon No, Sang-Hoon Lee, Suk Woo Nam, Il-Hoan Oh, Jaehwi Lee, Hyo-Jeong Kuh Intrinsic drug resistance of pancreatic ductal adenocarcinoma (PDAC) warrants studies using models that are more clinically relevant for identifying novel resistance mechanisms as well as for drug development. Tumor spheroids (TS) mimic in vivo tumor conditions associated with multicellular resistance and represent a promising model for efficient drug screening, however, pancreatic cancer cells often fail to form spheroids using conventional methods such as liquid overlay. This study describes the induction of TS of human pancreatic cancer cells (Panc-1, Aspc-1, Capan-2) in concave polydimethylsiloxane (PDMS) microwell plates and evaluation of their usefulness as an anticancer efficacy test model. All three cell lines showed TS formation with varying degree of necrosis inside TS. Among these, Panc-1 spheroid with spherical morphology, a rather rough surface, and unique adhesion structures were successfully produced with no notable necrosis in concave microwell plates. Panc-1 TS contained growth factors or enzymes such as TGF-β1, CTGF, and MT1-MMP, and extracellular matrix proteins such as collagen type I, fibronectin, and laminin. Panc-1 cells grown as TS showed changes in stem cell populations and in expression levels of miRNAs that may play roles in chemoresistance. Visualization of drug penetration and detection of viability indicators, such as Ki-67 and MitoSOX, were optimized for TS for quantitative analysis. Water-soluble tetrazolium (MTS) and acid phosphatase (APH) assays were also successfully optimized. Overall, we demonstrated that concave PDMS microwell plates are a novel platform for preparation of TS of weakly aggregating cells and that Panc-1 spheroids may represent a novel three-dimensional model for anti-pancreatic cancer drug screening.

Description: by Duncan Howie, Hugo Garcia Rueda, Marion H. Brown, Herman Waldmann Most T cell responses to pathogens or self antigens are modulated through the action of regulatory T cells and tissue-specific inhibitory mechanisms. To this end, several receptor-ligand pairs have evolved which either augment or diminish T cell function. Here we describe the tissue ligand SECTM1A (Secreted and transmembrane1A) as an alternative murine CD7 ligand. We show that SECTM1A, like SECTM1B, binds strongly to CD7, and that SECTM1B was able to compete with SECTM1A for CD7 binding. SECTM1A is ubiquitously expressed and has two major alternative transcripts which differ in expression between tissues. Both immobilised soluble forms of SECTM1A and SECTM1B and cell surface anchored forms demonstrated opposing effects on CD4+ T cell activation. Whereas SECTM1A acted as a co-stimulator of T cells, enhancing IL-2 production and proliferation, SECTM1B proved inhibitory to TCR mediated T cell activation. Surprisingly, both functional outcomes proved to be CD7-independent, indicating the existence of alternative receptors for both ligands. We used a SECTM1A-Fc fusion protein to immunoprecipitate potential alternative ligands from detergent lysates of CD7 −/− T cells and, using mass spectrometry, identified GITR as a SECTM1A binder. SECTM1A was found to bind to activated CD4+ and CD8+ T cells as well as to CHO cells expressing cell surface GITR. Binding of SECTM1A to activated primary T cells was inhibited by either GITRL-Fc or anti GITR antibodies. Thus SECTM1A and SECTM1B represent novel reciprocal alternative ligands which may function to modulate the activation of effector and regulatory T cells. The ability of SECTM1A to activate T cells may be explained by its ability to bind to GITR.

Description: by Wei-Jun Zhou, Ren-Ying Wang, Yan Li, Dong-Rui Chen, Er-Zhen Chen, Ding-Liang Zhu, Ping-Jin Gao Objective β-blockers (BBs) with different pharmacological properties may have heterogeneous effects on sympathetic nervous activity (SNA) and central aortic pressure (CAP), which are independent cardiovascular factors for hypertension. Hence, we analyzed the effects of bisoprolol and atenolol on SNA and CAP in hypertensive patients. Methods This was a prospective, randomized, controlled study in 109 never-treated hypertensive subjects randomized to bisoprolol (5 mg) or atenolol (50 mg) for 4–8 weeks. SNA, baroreflex sensitivity (BRS) and heart rate (HR) variability (HRV) were measured using power spectral analysis using a Finometer. CAP and related parameters were determined using the SphygmoCor device (pulse wave analysis). Results Both drugs were similarly effective in reducing brachial BP. However, central systolic BP (−14±10 mm Hg vs −6±9 mm Hg; P

Description: by Catherine J. Mondloch, Nicole L. Nelson, Matthew Horner The accuracy and speed with which emotional facial expressions are identified is influenced by body postures. Two influential models predict that these congruency effects will be largest when the emotion displayed in the face is similar to that displayed in the body: the emotional seed model and the dimensional model. These models differ in whether similarity is based on physical characteristics or underlying dimensions of valence and arousal. Using a 3-alternative forced-choice task in which stimuli were presented briefly (Exp 1a) or for an unlimited time (Exp 1b) we provide evidence that congruency effects are more complex than either model predicts; the effects are asymmetrical and cannot be accounted for by similarity alone. Fearful postures are especially influential when paired with facial expressions, but not when presented in a flanker task (Exp 2). We suggest refinements to each model that may account for our results and suggest that additional studies be conducted prior to drawing strong theoretical conclusions.

Description: by Robert Savit, Maria Riolo, Rick Riolo Co-adaptation (or co-evolution), the parallel feedback process by which agents continuously adapt to the changes induced by the adaptive actions of other agents, is a ubiquitous feature of complex adaptive systems, from eco-systems to economies. We wish to understand which general features of complex systems necessarily follow from the (meta)-dynamics of co-adaptation, and which features depend on the details of particular systems. To begin this project, we present a model of co-adaptation (“The Stigmergy Game”) which is designed to be as a priori featureless as possible, in order to help isolate and understand the naked consequences of co-adaptation. In the model, heterogeneous, co-adapting agents, observe, interact with and change the state of an environment. Agents do not, ab initio , directly interact with each other. Agents adapt by choosing among a set of random “strategies,” particular to each agent. Each strategy is a complete specification of an agent's actions and payoffs. A priori , all environmental states are equally likely and all strategies have payoffs that sum to zero, so without co-adaptation agents would on average have zero “wealth”. Nevertheless, the dynamics of co-adaptation generates a structured environment in which only a subset of environmental states appear with high probability (niches) and in which agents accrue positive wealth. Furthermore, although there are no direct agent-agent interactions, there are induced non-trivial inter-agent interactions mediated by the environment. As a function of the population size and the number of possible environmental states, the system can be in one of three dynamical regions. Implications for a basic understanding of complex adaptive systems are discussed.

Description: by Sandra Laner-Plamberger, Florian Wolff, Alexandra Kaser-Eichberger, Stefan Swierczynski, Cornelia Hauser-Kronberger, Anna-Maria Frischauf, Thomas Eichberger Sustained hedgehog (Hh) signaling mediated by the GLI transcription factors is implicated in many types of cancer. Identification of Hh/GLI target genes modulating the activity of other pathways involved in tumor development promise to open new ways for better understanding of tumor development and maintenance. Here we show that SOCS1 is a direct target of Hh/GLI signaling in human keratinocytes and medulloblastoma cells. SOCS1 is a potent inhibitor of interferon gamma (IFN-y)/STAT1 signaling. IFN-у/STAT1 signaling can induce cell cycle arrest, apoptosis and anti-tumor immunity. The transcription factors GLI1 and GLI2 activate the SOCS1 promoter, which contains five putative GLI binding sites, and GLI2 binding to the promoter was shown by chromatin immunoprecipitation. Consistent with a role of GLI in SOCS1 regulation, STAT1 phosphorylation is reduced in cells with active Hh/GLI signaling and IFN-у/STAT1 target gene activation is decreased. Furthermore, IFN-у signaling is restored by shRNA mediated knock down of SOCS1. Here, we identify SOCS1 as a novel Hh/GLI target gene, indicating a negative role of Hh/GLI pathway in IFN-y/STAT1 signaling.

Description: by Xuting Xu, Yunliang Wang, Lingyan Wang, Qi Liao, Lan Chang, Leiting Xu, Yi Huang, Huadan Ye, Limin Xu, Cheng Chen, Xiaowei Shen, Fuqiang Zhang, Meng Ye, Qinwen Wang, Shiwei Duan Aims The aim of this study was to evaluate the combined contribution of 8 polymorphisms to the risk of Alzheimer's disease (AD). Methods Through a comprehensive literature search for genetic variants involved in the AD association study, we harvested a total of 6 genes (8 polymorphisms) for the current meta-analyses. These genes consisted of A2M (5bp I/D and V1000I), ABCA2 (rs908832), CHAT (1882G 〉A, 2384G 〉A), COMT (Val158Met), HTR6 (267C 〉T) and LPL (Ser447Ter). Results A total of 33 studies among 9,453 cases and 10,833 controls were retrieved for the meta-analyses of 8 genetic variants. It was showed that A2M V1000I (odd ratio (OR) = 1.26, 95% confidence interval (CI) = 1.07–1.49, P = 0.007), rs908832 allele of ABCA2 (OR = 1.55, 95% CI = 1.12–2.16, P = 0.009), 2384G 〉A of CHAT (OR = 1.22, 95% CI = 1.00–1.49, P = 0.05) and Ser447Ter of LPL in the Northern-American population (OR = 0.56, 95% CI = 0.35–0.91, P = 0.02) were significantly associated with the risk of AD. No association was found between the rest of the 5 polymorphisms and the risk of AD. Conclusion Our results showed that A2M V1000I polymorphism in German, Korean, Chinese, Spanish, Italian and Polish populations, rs90883 of ABCA2 gene in French, American, Swiss, Greek and Japanese populations, 2384G 〉A of CHAT gene in British and Korean populations and LPL Ser447Ter in the Northern-American population were associated with the risk of AD.

Description: Insects face the challenge of integrating multi-sensory information to control their flight. Here we study a ‘streamlining’ response in honeybees, whereby honeybees raise their abdomen to reduce drag. We find that this response, which was recently reported to be mediated by optic flow, is also strongly modulated by the presence of air flow simulating a head wind. The Johnston's organs in the antennae were found to play a role in the measurement of the air speed that is used to control the streamlining response. The response to a combination of visual motion and wind is complex and can be explained by a model that incorporates a non-linear combination of the two stimuli. The use of visual and mechanosensory cues increases the strength of the streamlining response when the stimuli are present concurrently. We propose this multisensory integration will make the response more robust to transient disturbances in either modality. Scientific Reports 3 doi: 10.1038/srep02614

Description: A novel 3D hexadecanuclear heteropolyoxozincate organic framework, IFMC-200, has been successfully synthesized based on a late transition metal-oxygen cluster. IFMC-200 not only represents the first example of (3,4,24)-connected framework but also contains the first 24-connected single metal cluster in a crystal structure. It exhibits superior thermal stability, good water-stability, and even insensitivity to the existence of acid and base within a certain range of pH values. Furthermore, it performs as a heterogeneous crystalline Lewis acid catalyst with good activity for the conversion of long-chain fatty acids rather than short-chain ones, and high recycling efficiency for esterification reaction of fatty acids with alcohols to produce biodiesel. Scientific Reports 3 doi: 10.1038/srep02616

Description: Hybrid materials made from all inorganic components are intriguing in many fields, because they have shown in-depth potential use for electronic and optoelectronic applications including solar cells, gas sensors, photodetectors, and field effect transistors. Hybrid materials made from SnO2 nanoparticles on SnSe nanosheets have been synthesized via a facile, lost-cost and safe solution method, and have been demonstrated as promising multifunctional materials in various prototype devices, including gas sensors, photodetectors, and field effect transistors. Scientific Reports 3 doi: 10.1038/srep02613

Description: The simplification of current vaccine administration regimes is of crucial interest in order to further sustain and expand the high impact of vaccines for public health. Most vaccines including the vaccine against hepatitis B need several doses to achieve protective immunization. In order to reduce the amount of repetitive injections, depot-based approaches represent a promising strategy. We present the application of novobiocin-sensitive biohybrid hydrogels as a depot for the pharmacologically controlled release of a vaccine against hepatitis B. Upon subcutaneous implantation of the vaccine depot into mice, we were able to release the vaccine by the oral administration of the stimulus molecule novobiocin resulting in successful immunization of the mice. This material-based vaccination regime holds high promises to replace classical vaccine injections conducted by medical personnel by the simple oral uptake of the stimulus thereby solving a major obstacle in increasing hepatitis B vaccination coverage. Scientific Reports 3 doi: 10.1038/srep02610

Description: Glyphosate usage is increasing worldwide and the application schemes of this herbicide are currently changing. Amphibians migrating through arable fields may be harmed by Glyphosate applied to field crops. We investigated the population-based temporal coincidence of four amphibian species with Glyphosate from 2006 to 2008. Depending on a) age- and species-specific main migration periods, b) crop species, c) Glyphosate application mode for crops, and d) the presumed DT50 value (12 days or 47 days) of Glyphosate, we calculated up to 100% coincidence with Glyphosate. The amphibians regularly co-occur with pre-sowing/pre-emerging Glyphosate applications to maize in spring and with stubble management prior to crop sowing in late summer and autumn. Siccation treatment in summer coincides only with early pond-leaving juveniles. We suggest in-depth investigations of both acute and long-term effects of Glyphosate applications on amphibian populations not only focussed on exposure during aquatic periods but also terrestrial life stages. Scientific Reports 3 doi: 10.1038/srep02622

Description: Polymeric composite films with a high loading of nano-size silicates can hardly meet the increasingly stringent fireproof and smoke-free requirements during burning. Thus, it is desirable to prepare pure clay films that can block air, heat, and flame. Here we report an organic-free clay film capable of both flame- and heat-shielding. The film was prepared from the self-assembly of nanometer-thick silicate platelets derived from the exfoliation of natural clays. The self-assembled film has a highly regular multilayered nanostructure over a large area and an appreciable volume of air entrapped in between. The combination of regular structure and substantial air volume contributes to the low thermal conductivity and flame blocking property of the film. It was demonstrated that the film can shield flame over hour duration and prevent temperature rising on the backside of film. This remarkable clay film has a myriad of uses including gas barrier, heat insulator, and fireproof devices. Scientific Reports 3 doi: 10.1038/srep02621

Description: State-of-the art computers need high performance transistors, which consume ultra-low power resulting in longer battery lifetime. Billions of transistors are integrated neatly using matured silicon fabrication process to maintain the performance per cost advantage. In that context, low-cost mono-crystalline bulk silicon (100) based high performance transistors are considered as the heart of today's computers. One limitation is silicon's rigidity and brittleness. Here we show a generic batch process to convert high performance silicon electronics into flexible and semi-transparent one while retaining its performance, process compatibility, integration density and cost. We demonstrate high-k/metal gate stack based p-type metal oxide semiconductor field effect transistors on 4 inch silicon fabric released from bulk silicon (100) wafers with sub-threshold swing of 80 mV dec−1 and on/off ratio of near 104 within 10% device uniformity with a minimum bending radius of 5 mm and an average transmittance of ~7% in the visible spectrum. Scientific Reports 3 doi: 10.1038/srep02609

Description: by Katerina Douka, Christopher A. Bergman, Robert E. M. Hedges, Frank P. Wesselingh, Thomas F. G. Higham The Out-of-Africa model holds that anatomically modern humans (AMH) evolved and dispersed from Africa into Asia, and later Europe. Palaeoanthropological evidence from the Near East assumes great importance, but AMH remains from the region are extremely scarce. ‘Egbert’, a now-lost AMH fossil from the key site of Ksar Akil (Lebanon) and ‘Ethelruda’, a recently re-discovered fragmentary maxilla from the same site, are two rare examples where human fossils are directly linked with early Upper Palaeolithic archaeological assemblages. Here we radiocarbon date the contexts from which Egbert and Ethelruda were recovered, as well as the levels above and below the findspots. In the absence of well-preserved organic materials, we primarily used marine shell beads, often regarded as indicative of behavioural modernity. Bayesian modelling allows for the construction of a chronostratigraphic framework for Ksar Akil, which supports several conclusions. The model-generated age estimates place Egbert between 40.8–39.2 ka cal BP (68.2% prob.) and Ethelruda between 42.4–41.7 ka cal BP (68.2% prob.). This indicates that Egbert is of an age comparable to that of the oldest directly-dated European AMH (Peştera cu Oase). Ethelruda is older, but on current estimates not older than the modern human teeth from Cavallo in Italy. The dating of the so-called “transitional” or Initial Upper Palaeolithic layers of the site may indicate that the passage from the Middle to Upper Palaeolithic at Ksar Akil, and possibly in the wider northern Levant, occurred later than previously estimated, casting some doubts on the assumed singular role of the region as a locus for human dispersals into Europe. Finally, tentative interpretations of the fossil's taxonomy, combined with the chronometric dating of Ethelruda's context, provides evidence that the transitional/IUP industries of Europe and the Levant, or at least some of them, may be the result of early modern human migration(s).

Description: by Thomas Lund, Johan Hviid Andersen, Trine Nøhr Winding, Karin Biering, Merete Labriola Background Most previous studies on reliance on social benefits have focused on health, sickness absence, work environment and socioeconomic status in adulthood. Extending the focus to include early life circumstances may improve our understanding of processes leading to educational and occupational marginalisation and exclusion. The aim of this study was to investigate if multiple negative life events in childhood determined future labour market participation, and to identify important negative life events for labour market participation in young adulthood. Methods Of a cohort of 3,681 born in 1989 in the county of Ringkjoebing, Denmark, 3,058 (83%) completed a questionnaire in 2004. They were followed in a register on social benefits for 12 months in 2010-2011. Logistic regression analyses were used to investigate associations between negative life events in childhood and future labour market participation, taking into account effects of socio-economic position, school performance, educational plans, vocational expectations and general health. Results A total of 17.1% (19.9% males, 14.4% females) received social benefits for at least 4 weeks during follow-up. Labour market participation decreased with number of negative life events, especially for females: Females who had experienced their parents’ divorce, had been abused, or had witnessed a violent event, showed decreased labour market participation, when adjusting for SES, school performance, educational plans, vocational expectations and general health at baseline. Attributable fractions ranged from 2.4% (parents’ alcohol/drug abuse) to 16.1% (parents’ divorce) for women. For men, risk estimates were lower and insignificant in the most adjusted models. Attributable fractions ranged from 1.0% (parents’ alcohol/drug abuse) to 4.9% for witnessing a violent event. Conclusions Information on childhood conditions may increase the understanding of determinants of labour market participation for young adults. Knowledge of negative life events in childhood should be taken into account when considering determinants of labour market participation and identifying high-risk groups.

Description: by Britt G. de Jong, Aart Lammers, Leonora A. A. Oberendorf, Mike G. B. Nieuwland, Huub F. J. Savelkoul, Henk K. Parmentier Specificity, antibody isotype distribution and levels of natural antibodies (NAb) may be potential informative parameters for immune mediated natural disease resistance, immune modulation, and maintenance of physiological homeostasis. A large proportion of mammalian NAb have affinity for or are directed against self-antigens; so called natural auto antibodies (N(A)Ab). In the present study we showed the presence and typed levels and isotypes (total immunoglobulins, IgG and IgM) of N(A)Ab in plasma binding the ‘auto-antigen’ complex chicken liver cell lysate (CLL) of one-year old chickens from different genotype and phenotype backgrounds by ELISA and quantitative Western blotting. Higher levels of N(A)Ab binding CLL were found in plasma from chickens genetically selected for high specific antibody responses. In all birds, extensive staining patterns of plasma antibodies binding CLL were found for all isotypes, with IgG binding the highest number of CLL antigens and also showing the highest variation in staining patterns between individuals. Patterns of IgM antibodies binding CLL appeared to be more similar in all lines. Significant differences of binding patterns of N(A)Ab (antigen fragments of CLL and staining intensity) were detected between the different chicken lines, and lines could be clustered on the basis of their auto-antibody profile. In addition, also individual differences within lines were found. The present results indicate that analysis of the levels and the N(A)Ab repertoire of poultry like in mammals could provide a new way of distinguishing differences of immune competence and immune maturation between individuals, and could provide tools to select birds for health traits, or optimize hygiene and husbandry procedures.

Description: by Pei-Yi Chu, Chih-Jen Cheng, Yi-Chang Wu, Yu-Wei Fang, Tom Chau, Shinichi Uchida, Sei Sasaki, Sung-Sen Yang, Shih-Hua Lin Stimulation of the OSR1 (Oxidative stress-responsive kinase-1)/SPAK [STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase]-NCC (Na + -Cl − cotransporter) signaling cascade plays an important role in the WNK [With-No-Lysine (K)] kinase 4 D561A knock-in mouse model of pseudohypoaldosteronism type II (PHA II) characterized by salt-sensitive hypertension and hyperkalemia. The aim of this study was to investigate the respective roles of Osr1 and Spak in the pathogenesis of PHA II in vivo . Wnk4 D561A/+ mice were crossed with kidney tubule-specific (KSP) Osr1 knockout (KSP- Osr1 −/− ) and Spak knockout ( Spak −/− ) mice. Blood pressure, plasma and urine biochemistries, and the relevant protein expression in the kidneys were examined. Wnk4 D561A/+ , KSP- Osr1 −/− , and Spak −/− mice recapitulated the phenotypes of PHA II, Bartter-like syndrome, and Gitelman syndrome, respectively. Wnk4 D561A/+ .KSP- Osr1 −/− remained phenotypically PHA II while Wnk4 D561A/+ . Spak −/− mice became normotensive and lacked the PHA II phenotype. Phosphorylated Spak and Ncc were similarly increased in both Wnk4 D561A/+ and Wnk4 D561A/+ .KSP- Osr1 −/− mice while phosphorylated Ncc normalized in Wnk4 D561A/+ . Spak −/− mice. Furthermore, Wnk4 D561A/+ .KSP- Osr1 −/− mice exhibited exaggerated salt excretion in response to thiazide diuretics while Wnk4 D561A/+ . Spak −/− mice exhibited normal responses. Wnk4D561A/+.Spak −/− . KSP-Osr1 −/− triple mutant mice had low blood pressure and diminished phosphorylated Ncc. Both SPAK and OSR1 are important in the maintenance of blood pressure but activation of SPAK-NCC plays the dominant role in PHA II. SPAK may be a therapeutic target for disorders with salt-sensitive hypertension related to WNK4 activation.

Description: by Magdalena Migocka, Anna Warzybok, Anna Papierniak, Grażyna Kłobus Studies in the last few years have shed light on the process of nitrate accumulation within plant cells, achieving molecular identification and partial characterization of the genes and proteins involved in this process. However, contrary to the plasma membrane-localized nitrate transport activities, the kinetics of active nitrate influx into the vacuole and its adaptation to external nitrate availability remain poorly understood. In this work, we have investigated the activity and regulation of the tonoplast-localized H + /NO 3 − antiport in cucumber roots in response to N starvation and NO 3 − induction. The time course of nitrate availability strongly influenced H + /NO 3 − antiport activity at the tonoplast of root cells. However, under N starvation active nitrate accumulation within the vacuole still occurred. Hence, either a constitutive H + -coupled transport system specific for nitrate operates at the tonoplast, or nitrate uses another transport protein of broader specificity to different anions to enter the vacuole via a proton-dependent process. H + /NO 3 − antiport in cucumber was significantly stimulated in NO 3 − -induced plants that were supplied with nitrate for 24 hours following 6-day-long N starvation. The cytosolic fraction isolated from the roots of NO 3 − -induced plants significantly stimulated H + /NO 3 − antiport in tonoplast membranes isolated from cucumbers growing on nitrate. The stimulatory effect of the cytosolic fraction was completely abolished by EGTA and the protein kinase inhibitor staurosporine and slightly enhanced by the phosphatase inhibitors okadaic acid and cantharidin. Hence, we conclude that stimulation of H + /NO 3 − antiport at the tonoplast of cucumber roots in response to nitrate provision may occur through the phosphorylation of a membrane antiporter involving Ca-dependent, staurosporine-sensitive protein kinase.

Description: by I-Cheng Chen, Hsuan-Yuan Lin, Ya-Chin Hsiao, Chiung-Mei Chen, Yih-Ru Wu, Hsin-Chieh Shiau, Yu-Fang Shen, Kuo-Shiu Huang, Ming-Tsan Su, Hsiu-Mei Hsieh-Li, Guey-Jen Lee-Chen Spinocerebellar ataxia type 8 (SCA8) involves the expansion of CTG/CAG repeats from the overlapping ataxin 8 opposite strand ( ATXN8OS ) and ataxin 8 ( ATXN8 ) genes located on chromosome 13q21. Although being transcribed, spliced and polyadenylated in the CTG orientation, ATXN8OS does not itself appear to be protein coding, as only small open reading frames (ORFs) were noted. In the present study we investigated the translation of a novel 102 amino acids containing-ORF in the ATXN8OS RNA. Expression of chimeric construct with an in-frame ORF-EGFP gene demonstrated that ATXN8OS RNA is translatable. Using antiserum raised against ORF, ATXN8OS ORF expression was detected in various human cells including lymphoblastoid, embryonic kidney 293, neuroblastoma IMR-32, SK-N-SH, SH-SY5Y cells and human muscle tissue. The biological role of the ATXN8OS ORF and its connection to SCA8 remains to be determined.

Description: Imaging single epidermal growth factor receptors (EGFR) in intact cells is presently limited by the available microscopy methods. Environmental scanning electron microscopy (ESEM) of whole cells in hydrated state in combination with specific labeling with gold nanoparticles was used to localize activated EGFRs in the plasma membranes of COS7 and A549 cells. The use of a scanning transmission electron microscopy (STEM) detector yielded a spatial resolution of 3 nm, sufficient to identify the locations of individual EGFR dimer subunits. The sizes and distribution of dimers and higher order clusters of EGFRs were determined. The distance between labels bound to dimers amounted to 19 nm, consistent with a molecular model. A fraction of the EGFRs was found in higher order clusters with sizes ranging from 32–56 nm. ESEM can be used for quantitative whole cell screening studies of membrane receptors, and for the study of nanoparticle-cell interactions in general. Scientific Reports 3 doi: 10.1038/srep02626

Description: Ubiquitin is involved in almost every cellular process, and it is also known to be a stress-inducible protein. Based on previous reports that many types of cancer display an elevated level of ubiquitin, we hypothesized that this increased amount of ubiquitin is essential for the growth of cancer cells and that, consequently, the downregulation of ubiquitin may be a potential anti-cancer treatment. We first found that the level of ubiquitin can be effectively downregulated via knockdown of a polyubiquitin gene, Ubb, with siRNA (Ubb-KD) and then demonstrated its anti-cancer effects in several cancer cell lines and xenograft mice. Ubb-KD resulted in the attenuation of TNFα-induced NF-κB activation, the stabilization of the tumor suppressor p53, and stress-sensitization. Taken together, downregulation of ubiquitin through Ubb-KD is a potential anti-cancer treatment by inhibiting ubiquitination at multiple sites related to oncogenic pathways and by weakening the ability of cancer cells to overcome increased stress. Scientific Reports 3 doi: 10.1038/srep02623

Description: NAD kinase (NADK) is a crucial enzyme for production of NADP+. ATP-specific NADK prefers ATP to inorganic polyphosphate [poly(P)] as a phosphoryl donor, whereas poly(P)/ATP-NADK utilizes both ATP and poly(P), and is employed in industrial mass production of NADP+. Poly(P)/ATP-NADKs are distributed throughout Gram-positive bacteria and Archaea, whereas ATP-specific NADKs are found in Gram-negative α- and γ-proteobacteria and eukaryotes. In this study, we succeeded in conferring the ability to utilize poly(P) on γ-proteobacterial ATP-specific NADKs through a single amino-acid substitution; the substituted amino-acid residue is therefore important in determining the phosphoryl-donor specificity of γ-proteobacterial NADKs. We also demonstrate that a poly(P)/ATP-NADK created through this method is suitable for the poly(P)-dependent mass production of NADP+. Moreover, based on our results, we provide insight into the evolution of bacterial NADKs, in particular, how NADKs evolved from poly(P)/ATP-NADKs into ATP-specific NADKs. Scientific Reports 3 doi: 10.1038/srep02632

Description: Mass production of high-quality graphene nanosheets (GNs) is essential for practical applications. We report that oxidation of graphite by low concentration KMnO4 at relatively high temperature (60°C) leads to edge-selectively oxidized graphite (EOG) which preserves the high crystalline graphitic structure on its basal planes while the edges are functionalized by oxygen-containing groups. Long-chain tetradecyl-ammonium salt (C14N+) could be spontaneously intercalated into EOG to form intercalated EOG-C14N+ compounds. Gentle and short-time sonication of EOG-C14N+ in toluene can full exfoliate EOG into edge-oxidized graphene nanosheets (EOGNs) with concentration of 0.67 mg/ml, monolayer population up to 90% and lateral size from 1 μm to 〉100 μm. The EOG and EOGN films show excellent electrical conductance, which is far superior to their graphene oxide (GO) counterparts. Our method provides an efficient way to produce high-quality GNs, and the resultant EOG also can be directly used for production of multifunctional materials and devices. Scientific Reports 3 doi: 10.1038/srep02636

Description: by Carel P. van Schaik, Laura Damerius, Karin Isler The ability to plan for the future beyond immediate needs would be adaptive to many animal species, but is widely thought to be uniquely human. Although studies in captivity have shown that great apes are capable of planning for future needs, it is unknown whether and how they use this ability in the wild. Flanged male Sumatran orangutans ( Pongo abelii ) emit long calls, which females use to maintain earshot associations with them. We tested whether long calls serve to communicate a male's ever-changing predominant travel direction to facilitate maintaining these associations. We found that the direction in which a flanged male emits his long calls predicts his subsequent travel direction for many hours, and that a new call indicates a change in his main travel direction. Long calls given at or near the night nest indicate travel direction better than random until late afternoon on the next day. These results show that male orangutans make their travel plans well in advance and announce them to conspecifics. We suggest that such a planning ability is likely to be adaptive for great apes, as well as in other taxa.

Description: Society's techno-social systems are becoming ever faster and more computer-orientated. However, far from simply generating faster versions of existing behaviour, we show that this speed-up can generate a new behavioural regime as humans lose the ability to intervene in real time. Analyzing millisecond-scale data for the world's largest and most powerful techno-social system, the global financial market, we uncover an abrupt transition to a new all-machine phase characterized by large numbers of subsecond extreme events. The proliferation of these subsecond events shows an intriguing correlation with the onset of the system-wide financial collapse in 2008. Our findings are consistent with an emerging ecology of competitive machines featuring ‘crowds’ of predatory algorithms, and highlight the need for a new scientific theory of subsecond financial phenomena. Scientific Reports 3 doi: 10.1038/srep02627

Description: 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

Description: 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

Description: by M. H. Eileen Tan, X. Edward Zhou, Fen-Fen Soon, Xiaodan Li, Jun Li, Eu-Leong Yong, Karsten Melcher, H. Eric Xu Photoreceptor-specific nuclear receptor (PNR, NR2E3) is a key transcriptional regulator of human photoreceptor differentiation and maintenance. Mutations in the NR2E3-encoding gene cause various retinal degenerations, including Enhanced S-cone syndrome, retinitis pigmentosa, and Goldman-Favre disease. Although physiological ligands have not been identified, it is believed that binding of small molecule agonists, receptor desumoylation, and receptor heterodimerization may switch NR2E3 from a transcriptional repressor to an activator. While these features make NR2E3 a potential therapeutic target for the treatment of retinal diseases, there has been a clear lack of structural information for the receptor. Here, we report the crystal structure of the apo NR2E3 ligand binding domain (LBD) at 2.8 Å resolution. Apo NR2E3 functions as transcriptional repressor in cells and the structure of its LBD is in a dimeric auto-repressed conformation. In this conformation, the putative ligand binding pocket is filled with bulky hydrophobic residues and the activation-function-2 (AF2) helix occupies the canonical cofactor binding site. Mutations designed to disrupt either the AF2/cofactor-binding site interface or the dimer interface compromised the transcriptional repressor activity of this receptor. Together, these results reveal several conserved structural features shared by related orphan nuclear receptors, suggest that most disease-causing mutations affect the receptor’s structural integrity, and allowed us to model a putative active conformation that can accommodate small ligands in its pocket.

Description: by Ayako Suzuki, Sachiyo Mimaki, Yuki Yamane, Akikazu Kawase, Koutatsu Matsushima, Makito Suzuki, Koichi Goto, Sumio Sugano, Hiroyasu Esumi, Yutaka Suzuki, Katsuya Tsuchihara We analyzed whole-exome sequencing data from 97 Japanese lung adenocarcinoma patients and identified several putative cancer-related genes and pathways. Particularly, we observed that cancer-related mutation patterns were significantly different between different ethnic groups. As previously reported, mutations in the EGFR gene were characteristic to Japanese, while those in the KRAS gene were more frequent in Caucasians. Furthermore, during the course of this analysis, we found that cancer-specific somatic mutations can be detected without sequencing normal tissue counterparts. 64% of the germline variants could be excluded using a total of 217 external Japanese exome datasets. We also show that a similar approach may be used for other three ethnic groups, although the discriminative power depends on the ethnic group. We demonstrate that the ATM gene and the PAPPA2 gene could be identified as cancer prognosis related genes. By bypassing the sequencing of normal tissue counterparts, this approach provides a useful means of not only reducing the time and cost of sequencing but also analyzing archive samples, for which normal tissue counterparts are not available.

Description: by Lin Huang Objective: Ischemic pre-conditioning and post-conditioning are useful manipulations to reduce the undesirable effects of ischemia-reperfusion skin flap each. But the impact of post-conditioning on the pre-conditioning skin flap is not manifested. Here we investigated the influence of ischemic post-conditioning in a preconditioned axial pattern skin flap model.Method: We used the skin flap in 40 rabbits and divided them into 5 groups randomly. At first we induced the ischemic pre-conditioning of the flap which was applied by 2 periods of 15 minutes of ischemia/15 minutes of reperfusion cycle. Next post-conditioning was performed by 6 cycles of 10 seconds of repeated ischemia/reperfusion periods at different times of just after the reperfusion,5 minutes after the reperfusion,10 minutes after the reperfusion. The animals were allocated into 5 groups: group 1 (Ischemia Group); group 2: (Pre-conditioning Group); group 3: (Pre-conditioning+ Post-conditioning Group); group 4 (Pre-conditioning+ Post-conditioning 5 minutes later Group); group5 (Pre-conditioning+ Post-conditioning 10 minutes later). The neutrophil count was assessed with histologic analysis before the dissection of the skin flap. Flap viability was assessed 1 week after the operation, and surviving flap area was recorded as a percentage of the whole flap area. LSD test was used for statistical analysis among different groups to evaluate the effects of ischemic pre-conditioning against ischemia.Result: Among the varying groups, the neutrophil count varied: Group 1 was50.12±5.91; Group 2, 30.00±2.00, and Group 3, 18.87±3; Group 4, 22.50±1.92; Group 5, 30.12±1.88.The mean± SD surviving areas of the flaps for groups 1, 2, 3, 4 and 5 were 31.76±4.59, 51.26±3.24,82.18±5.28,66.85±3.87 and 51.13±2.90 respectively. Spearman correlation analysis shows an increase relation between neutrophil count and flap survival rate in the different groups (P

Description: by Hiroyuki Nishi, Taichi Sakaguchi, Shigeru Miyagawa, Yasushi Yoshikawa, Satsuki Fukushima, Shunsuke Saito, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa Background Although microRNA (miRNA) regulates initiation and/or progression of atrial fibrillation (AF) in canine AF models, the underlying mechanism in humans remains unclear. We speculated that certain miRNAs in atrial tissue are related to AF, and evaluated the relationship of miRNA expression in human atrial tissue in cardiac surgery patients. Methods Right atrial tissues from 29 patients undergoing cardiovascular surgery were divided into 3 groups [A: chronic AF or unsuccessful maze, n=6; B: successful maze, n=10; C: sinus rhythm (SR) n=13]. miRNA expression was determined using high density microarrays and with Reverse transcriptase-polymerase chain reaction (RT-PCR). Fibrosis was examined using Masson trichrome staining. Results miRNA microarray analysis showed elevated miRNA-21, miRNA-23b, miRNA-199b, and miRNA-208b in AF as compared to SR groups. RT-PCR showed elevated miRNA-21 (1.9-fold) and miRNA-208b (4.2-fold) in AF as compared to the SR groups. miRNA-21 expression increased from Group C to A (A: 2.1-fold, B: 1.8-fold, C: 1.0-fold). Fibrosis increased from C to A (A: 43.0±12.9%, B: 21.3±6.1%, C: 11.9±3.1%). Percent fibrosis and miRNA-21 expression were correlated (r=0.508, p

Description: by Habiba I. Ali, Amjad H. Jarrar, Mohamed El Sadig, Karin B. Yeatts Background Diet therapy is the cornerstone for the management of gestational diabetes mellitus (GDM). Carbohydrate is the primary nutrient affecting postprandial blood glucose levels. Hence, knowledge of food containing carbohydrates can assist women with GDM optimize glycemic control. Despite that, there is a paucity of research on carbohydrate-related knowledge of women with GDM. The United Arab Emirates (UAE) has one of the highest prevalence of diabetes (19.2%) in the world. This study compared diet and knowledge of carbohydrate-containing foods among pregnant women with and without GDM in the UAE. Methods The sample consisted of multi-ethnic women with GDM (n = 94) and a control group of healthy pregnant women (n = 90) attending prenatal clinics in three hospitals in Al Ain, UAE. Data were collected using a questionnaire and a 24-hour recall. Knowledge of food sources of carbohydrate, dietary patterns, and nutrient intakes of the two groups were compared. Results There were no significant differences in the mean knowledge score of food sources of carbohydrate between women with GDM and that of pregnant women without GDM. Similarly, there were no significant differences in energy and nutrient intakes between the two groups with the exception of percent energy from protein. Women with GDM reported significantly lower intake of fruits and fruit juices (P = 0.012) and higher consumption of milk and yogurt (P = 0.004) compared to that of women without GDM. Twenty-two percent of women with GDM indicated they never visited a dietitian for counseling while 65% reported they visited a dietitian only once or twice during the pregnancy. Predictors of carbohydrate knowledge score were perceived knowledge of diet and GDM and parity among women with GDM and parity and educational level among those without GDM. Conclusion The results of the study highlight the urgent need to provide nutrition education for women with GDM in the UAE.