ALBERT

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: A proper orthogonal decomposition (POD) method is used to interpolate the flow around an airfoil for various Mach numbers and angles of attack in the transonic regime. POD uses a few numerical simulations, called snapshots, to create eigenfunctions. These eigenfunctions are combined using weighting coefficients to create a new solution for different values of the input parameters. Since POD methods are linear, their interpolation capabilities are quite limited when dealing with flow presenting nonlinearities, such as shocks. In order to improve their performance for cases involving shocks, a new method is proposed using variable fidelity. The main idea is to use POD to interpolate the difference between the CFD solution obtained on two different grids, a coarse one and a fine one. Then, for any new input parameter value, a coarse grid solution is computed using CFD and the POD interpolated difference is added to predict the fine grid solution. This allows some nonlinearities associated with the flow to be introduced. Results for various Mach numbers and angles of attack are compared to full CFD results. The variable fidelity-based POD method shows good improvement over the classical approach.

Description: The preparation of carbon nanotube/metallic particle hybrids using pressed porous stainless steel pellets as a substrate is described. The catalytic growth of carbon nanotubes was carried out by CVD on a nickel catalyst obtained by impregnation of pellets with a highly dispersive colloidal solution of nickel acetate tetrahydrate in ethanol. Granular polyethylene was used as the carbon source. Metallic particles were deposited by thermal evaporation of Pt and Ag using pellets with grown carbon nanotubes as a base. The use of such composites as fuel cell electrodes is discussed.

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: 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: 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: This work provides a distributed fault-tolerant event region detection algorithm for wireless sensor networks. The proposed algorithm can identify faulty and fault-free sensors and ignore the abnormal readings to avoid false alarm. Moreover, every event region can also be detected and identified. Simulation results show that fault detection accuracy (FDA) is greater than 92%, false alarm rate (FAR) is near 0%, and event detection accuracy (EDA) is greater than 99% under uniform distribution. FDA is greater than 92%, FAR is less than 1.2%, and EDA is greater than 88% under random distribution when sensor fault probability is less than 0.3.

Description: Pupylation, one of the most important posttranslational modifications of proteins, typically takes place when prokaryotic ubiquitin-like protein (Pup) is attached to specific lysine residues on a target protein. Identification of pupylation substrates and their corresponding sites will facilitate the understanding of the molecular mechanism of pupylation. Comparing with the labor-intensive and time-consuming experiment approaches, computational prediction of pupylation sites is much desirable for their convenience and fast speed. In this study, a new bioinformatics tool named EnsemblePup was developed that used an ensemble of support vector machine classifiers to predict pupylation sites. The highlight of EnsemblePup was to utilize the Bi-profile Bayes feature extraction as the encoding scheme. The performance of EnsemblePup was measured with a sensitivity of 79.49%, a specificity of 82.35%, an accuracy of 85.43%, and a Matthews correlation coefficient of 0.617 using the 5-fold cross validation on the training dataset. When compared with other existing methods on a benchmark dataset, the EnsemblePup provided better predictive performance, with a sensitivity of 80.00%, a specificity of 83.33%, an accuracy of 82.00%, and a Matthews correlation coefficient of 0.629. The experimental results suggested that EnsemblePup presented here might be useful to identify and annotate potential pupylation sites in proteins of interest. A web server for predicting pupylation sites was developed.

Description: We used a one-dimensional simulation program Solar Cell Capacitance Simulator in 1 Dimension (SCAPS-1D) to investigate Copper-Indium-Gallium-Diselenide- (CIGS-) based solar cells properties. Starting with a conventional ZnO-B/i-ZnO/CdS/CIGS structure, we simulated the parameters of current-voltage characteristics and showed how the absorber layer thickness, hole density, and band gap influence the short-circuit current density (), open-circuit voltage (), fill factor (FF), and efficiency of solar cell. Our simulation results showed that all electrical parameters are greatly affected by the absorber thickness (w) below 1000 nm, due to the increase of back-contact recombination and very poor absorption. Increasing hole density (p) or absorber band gap () improves and leads to high efficiency, which equals value of 16.1% when p = 1016 cm−3 and  eV. In order to reduce back-contact recombination, the effect of a very thin layer with high band gap inserted near the back contact and acting as electrons reflector, the so-called back-electron reflector (EBR), has been investigated. The performances of the solar cells are significantly improved, when ultrathin absorbers (w 〈 500 nm) are used; the corresponding gain of due to the EBR is 3 mA/cm2. Our results are in good agreement with those reported in the literature from experiments.

Description: The work presents comparisons of the flame stabilization characteristics of axisymmetric disk and 2D slender bluff-body burner configurations, operating with inlet mixture stratification, under ultralean conditions. A double cavity propane air premixer formed along three concentric disks, supplied with a radial equivalence ratio gradient the afterbody disk recirculation, where the first flame configuration is stabilized. Planar fuel injection along the center plane of the leading face of a slender square cylinder against the approach cross-flow results in a stratified flame configuration stabilized alongside the wake formation region in the second setup. Measurements of velocities, temperatures, and chemiluminescence, local extinction criteria, and large-eddy simulations are employed to examine a range of ultralean and close to extinction flame conditions. The variations of the reacting front disposition within these diverse reacting wake topologies, the effect of the successive suppression of heat release on the near flame region characteristics, and the reemergence of large-scale vortical activity on approach to lean blowoff (LBO) are investigated. The cross-correlation of the performance of these two popular flame holders that are at the opposite ends of current applications might offer helpful insights into more effective control measures for expanding the operational margin of a wider range of stabilization configurations.

Description: This review covers methods for modifying the structures of polysaccharides. The introduction of hydrophobic, acidic, basic, or other functionality into polysaccharide structures can alter the properties of materials based on these substances. The development of chemical methods to achieve this aim is an ongoing area of research that is expected to become more important as the emphasis on using renewable starting materials and sustainable processes increases in the future. The methods covered in this review include ester and ether formation using saccharide oxygen nucleophiles, including enzymatic reactions and aspects of regioselectivity; the introduction of heteroatomic nucleophiles into polysaccharide chains; the oxidation of polysaccharides, including oxidative glycol cleavage, chemical oxidation of primary alcohols to carboxylic acids, and enzymatic oxidation of primary alcohols to aldehydes; reactions of uronic-acid-based polysaccharides; nucleophilic reactions of the amines of chitosan; and the formation of unsaturated polysaccharide derivatives.

Description: The electroreduction behaviour and determination of cefoperazone using a hanging mercury drop electrode were investigated. Cyclic voltammograms of cefoperazone recorded in universal Britton-Robinson buffers pH 3–6 exhibited a single irreversible cathodic peak. The process was adsorption-controlled. Britton-Robinson buffer 0.04 M pH 4.0 was selected as a supporting electrolyte for quantitative purposes by differential pulse and square wave adsorptive cathodic stripping voltammetry. The experimental voltammetric conditions were optimized using Central Composite Face design. A reduction wave was seen in the range from −0.7 to −0.8 V. These voltammetric techniques were successfully validated as per ICH guidelines and applied for the determination of cefoperazone in its single and sulbactam containing powders for injection and statistically comparable to USP-HPLC. They were further extended to determine cefoperazone in spiked human urine with no matrix effect.

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: The problem of exponential stability for the uncertain neutral Markovian jump systems with interval time-varying delays and nonlinear perturbations is investigated in this paper. This study starts from the corresponding nominal systems with known and partially unknown transition rates, respectively. By constructing a novel augmented Lyapunov functional which contains triple-integral terms and fully utilizes the bound of the delay, the delay-range-dependent and rate-dependent exponential stability criteria are developed by the Lyapunov theory, reciprocally convex lemma, and free weighting matrices. Then, the results about nominal systems are extended to the uncertain case. Finally, numerical examples are given to demonstrate the effectiveness of the proposed methods.

Description: The local fractional Schrödinger equations in the one-dimensional Cantorian system are investigated. The approximations solutions are obtained by using the local fractional series expansion method. The obtained solutions show that the present method is an efficient and simple tool for solving the linear partial differentiable equations within the local fractional derivative.

Description: An experiment of hydrogen preparation from steam-carbon reaction catalyzed by K2CO3 was carried out at 700°C, which was driven by the solar reaction system simulated with Xenon lamp. It can be found that the rate of reaction with catalyst is 10 times more than that without catalyst. However, for the catalytic reaction, there is no obvious change for the rate of hydrogen generation with catalyst content range from 10% to 20%. Besides, the conversion efficiency of solar energy to chemical energy is more than 13.1% over that by photovoltaic-electrolysis route. An analysis to the mechanism of catalytic steam-carbon reaction with K2CO3 is given, and an explanation to the nonbalanced [H2]/[CO + 2CO2] is presented, which is a phenomenon usually observed in experiment.

Description: Concentrations of Cd, Co, Pb, and Zn in riverbed sediments from six sampling stations along the Sungai Kilim, Langkawi, Malaysia, were determined by using the Teflon Bomb Digestion. From this study, the concentrations of heavy metals in riverbed sediments were found ranging between 6.10 and 8.87 μg/g dry weight for Co, 0.03 and 0.45 μg/g dry weight for Cd, 59.8 and 74.9 μg/g dry weight for Zn, and 1.06 and 11.69 μg/g dry weight for Pb. From the observation, these areas were polluted by domestic waste, aquaculture, and tourism activities. For clarity, enrichment factor index was used to determine the level of sediment contamination in the study area. From this study, the average EF value is a bit high for Cd () followed by Zn (), Pb (), and lastly, Co (). Based on the contamination categories, Cd was categorised as moderately enriched, while the rest of the metals studied were in deficient-to-minimally enriched by the anthropogenic sources.

Description: A catalytic adsorptive cathodic stripping voltammetric method on an improved bismuth film electrode (BiFE) for the determination of trace germanium in the presence of pyrogallol has been investigated. A well-defined and sensitive stripping peak of Ge(IV)-pyrogallol complex was observed at −0.79 V (versus SCE) in a 0.1 M acetate buffer solution (pH 4.8) at a deposition potential of −0.34 V. The reduction current is catalytically enhanced by adding KBrO3. The experimental variables and potential interference were studied. Compared with the BiFE plated in the solution prepared based on HAc-NaAc without trisodium citrate, the improved BiFE electrodeposited in the solution of HAc-NaAc containing trisodium citrate displayed a better electroanalytical performance for the determination of germanium(IV). Under the optimized conditions, the detection limit of Ge(IV) was 60 ng L−1, and the relative standard deviation (RSD) was 3.73% at 5 μg L−1 level (). This method was successfully applied to determine the total germanium in several Chinese herbal remedies.

Description: Changes of antioxidant properties of -lipoic acid (LA) after UV irradiation were studied. LA is the typical drug used in diabetic neuropathy. Quenching of free radicals is an important factor of therapy by using this substance. -Lipoic acid is exposed to UV irradiation during the storage. The aim of our studies was to examine the effect of UV irradiation on the interactions of LA with free radicals. The -lipoic acid was irradiated by UVA 315–400 nm light during 10 to 110 minutes by intervals of 10 minutes. The electron paramagnetic resonance spectroscopy was used as the experimental technique. The antioxidant properties of LA were spectroscopically confirmed. The strong effect of UV irradiation on interactions of -lipoic acid with free radicals was observed. It was pointed out that interactions of LA with free radicals decrease after its exposition on UV. The interactions of LA with free radicals were higher after the sample irradiation during 10 minutes than for the samples irradiated longer (20–110 minutes). The results are important for problems connected with photomedicine; they pointed out that -lipoic acid should not be stored on UV exposition. Application of electron paramagnetic resonance spectroscopy to characterize interactions of pharmacological substance with free radicals was confirmed.

Description: Copper antimony sulfide (CAS) is a relatively new class of sustainable absorber material, utilizing cost effective and abundant elements. Band gap engineered, modified CAS thin films were synthesized using electrodeposition and elevated temperature sulfurization approach. A testing analog of copper zinc antimony sulfide (CZAS) film-electrolyte interface was created in order to evaluate photoelectrochemical performance of the thin film of absorber materials. Eu3+/Eu2+ redox couple was selected for this purpose, based on its relative band offset with copper antimony sulfide. It was observed that zinc has a significant effect on CAS film properties. An enhanced photocurrent was observed for CAS film, modified with zinc addition. A detailed investigation has been carried out by changing stoichiometry, and corresponding surface and optical characterization results have been evaluated. A summary of favorable processing parameters of the films showing enhanced photoelectrochemical response is presented.

Description: Tidal influence and local morphology on circulation and salt transport are investigated in the Caeté river estuary, a well-mixed estuary along the north coast of Brazil. Velocity, temperature, and salinity data were collected in three different locations along the estuary’s main channel, over three single, 13 h tidal cycles. The aim of this study was to investigate the relationship between tidal distortion and salinity by using classical methods of comparison of three cross-channel circulation characteristics, as well as computation of salt flux and vertical mixing. Findings indicate a flood-ebb asymmetry in currents, due to the distinct funneling morphology of the estuary, with shallow marginal areas being dominant towards the estuary head, while both stratification and shear dominate near the estuary mouth. The tidal currents enhanced vertical diffusion in the mid- and lower reaches, explaining the prevailing weakly stratified conditions, while the dominant well-mixed conditions in the upper estuary are a result of a combination of stronger flood currents and negligible vertical saline gradient. The predominant downstream salt transport supports the conclusion that there is little accumulation of salt in the Caeté river estuary. In addition, findings indicate that tidal correlation and Stokes drift are important components in the upper estuary, while tidal correlation played an important role in the middle estuary, with fluvial discharge most important in the lower estuary.

Description: The present paper investigates the reliability analysis of industrial systems by using vague lambda-tau methodology in which information related to system components is uncertain and imprecise in nature. The uncertainties in the data are handled with the help of intuitionistic fuzzy set (IFS) theory rather than fuzzy set theory. Various reliability parameters are addressed for strengthening the analysis in terms of degree of acceptance and rejection of IFS. Performance as well as sensitivity analysis of the system parameter has been investigated for accessing the impact of taking wrong combinations on its performance. Finally results are compared with the existing traditional crisp and fuzzy methodologies results. The technique has been demonstrated through a case study of bleaching unit of a paper mill.

Description: A new stability-indicating reversed-phase high-performance thin-layer chromatographic (RP-HPTLC) method for densitometric analysis of thiocolchicoside was developed and validated. The chromatograms were developed using aluminum plates pre-coated with silica gel 60 RP-18 F254S as a stationary phase and methanol : water (70 : 30 ) as a mobile phase. The compact band for thiocolchicoside was observed at value of at an absorption wavelength of 377 nm. The linear regression data for the calibration plots () was found with respect to peak area in the concentration range of 100–600 ng per band. The limit of detection (LOD) and limit of quantification (LOQ) were 9.77 ng and 29.63 ng, respectively. The drug was exposed to acidic and alkaline hydrolysis, oxidation, photo degradation, and dry heat conditions. The peaks of degradation products were well-resolved from the peak of the standard drug with significantly different values. Statistical analysis proved that the established RP-HPTLC method is reproducible, selective, and accurate for the determination of thiocolchicoside in its formulations. The method can effectively separate the drug from its degradation products, and it can be considered as stability-indicating assay.

Description: In CdS/CdTe solar cells, chemical interdiffusion at the interface gives rise to the formation of an interlayer of the ternary compound . In this work, we evaluate the effects of this interlayer in CdS/CdTe photovoltaic cells in order to improve theoretical results describing experimental - (capacitance versus voltage) characteristics. We extended our previous theoretical methodology developed on the basis of three cardinal equations (Castillo-Alvarado et al., 2010). The present results provide a better fit to experimental data obtained from CdS/CdTe solar cells grown in our laboratory by the chemical bath deposition (for CdS film) and the close-spaced vapor transport (for CdTe film) techniques.

Description: A relationship between sea surface temperature (SST) and surface nitrate concentrations has been obtained for the first time based on in situ datasets retrieved from U.S. JGOFS (1991–96) and Indian cruises (2000–2006) in the Arabian Sea, Bay of Bengal and Indian Ocean region around the southern Indian tip. The dataset includes 1537 points. A sigmoid relationship obtained with

Description: The ice floe speed variations were monitored at the research camp North Pole 35 established on the Arctic ice pack in 2008. A three-month time series of measured speed values was used for determining changes in the kinetic energy of the drifting ice floe. The constructed energy distributions were analyzed by methods of nonextensive statistical mechanics based on the Tsallis statistics for open nonequilibrium systems, such as tectonic formations and drifting sea ice. The nonextensivity means the nonadditivity of externally induced energy changes in multicomponent systems due to dynamic interrelation of components having no structural links. The Tsallis formalism gives one an opportunity to assess the correlation between ice floe motions through a specific parameter, the so-called parameter of nonextensivity. This formalistic assessment of the actual state of drifting pack allows one to forecast some important trends in sea ice behavior, because the level of correlated dynamics determines conditions for extended mechanical perturbations in ice pack. In this work, we revealed temporal fluctuations of the parameter of nonextensivity and observed its maximum value before a large-scale sea ice fragmentation (faulting) of consolidated sea ice. The correlation was not detected in fragmented sea ice where long-range interactions are weakened.

Description: Symbiotic diatom-diazotrophic cyanobacteria association (DDA) of Rhizosolenia hebetata and Rhizosolenia formosa with endosymbiotic cyanobacteria Richelia intracellularis was noticed and documented for the first time during a bloom of the cyanobacterium Trichodesmium erythraeum in the oligotrophic shelf waters along Kochi and Mangalore transects, southeastern Arabian Sea (SEAS), during spring intermonsoon (April 2012). Although the host is frequently seen, the symbiont is rarely reported in the Indian EEZ. The presence of nitrogen-fixing symbiotic association of Rhizosolenia-Richelia along with Trichodesmium erythraeum highlights the significance of DDAs on the nutrient and energy budgets of phytoplankton in the oligotrophic environments of the Arabian Sea during spring intermonsoon.

Description: Recent studies on the diazotrophic cyanobacterium Trichodesmium showed that increasing CO2 partial pressure (pCO2) enhances N2 fixation and growth. We studied the in situ and satellite-derived environmental parameters within and outside a Trichodesmium bloom in the western coastal Bay of Bengal (BoB) during the spring intermonsoon 2009. Here we show that the single most important nitrogen fixer in today’s ocean, Trichodesmium erythraeum, is strongly abundant in high (≥300 μatm) pCO2 concentrations. N : P ratios almost doubled (~10) at high pCO2 region. This could enhance the productivity of N-limited BoB and increase the biological carbon sequestration. We also report presence of an oxygen minimum zone at Thamnapatnam. Earlier studies have been carried out using lab cultures, showing the increase in growth rate of T. erythraeum under elevated pCO2 conditions, but to our knowledge, this study is the first to report that in natural environment also T. erythraeum prefers blooming in high pCO2 concentrations. The observed CO2 sensitivity of T. erythraeum could thereby provide a strong negative feedback to rising atmospheric CO2 but would also drive towards phosphorus limitation in a future high CO2 world.

Description: In a silicon wafer-based photovoltaic (PV) module, significant power is lost due to current transport through the ribbons interconnecting neighbour cells. Using halved cells in PV modules is an effective method to reduce the resistive power loss which has already been applied by some major PV manufacturers (Mitsubishi, BP Solar) in their commercial available PV modules. As a consequence, quantitative analysis of PV modules using halved cells is needed. In this paper we investigate theoretically and experimentally the difference between modules made with halved and full-size solar cells. Theoretically, we find an improvement in fill factor of 1.8% absolute and output power of 90 mW for the halved cell minimodule. Experimentally, we find an improvement in fill factor of 1.3% absolute and output power of 60 mW for the halved cell module. Also, we investigate theoretically how this effect confers to the case of large-size modules. It is found that the performance increment of halved cell PV modules is even higher for high-efficiency solar cells. After that, the resistive loss of large-size modules with different interconnection schemes is analysed. Finally, factors influencing the performance and cost of industrial halved cell PV modules are discussed.

Description: In three-phase photovoltaic (PV) system, three-phase filter inductors are important part for the output electrical power quality. The comparison analyses of three-phase discrete filter inductors and two kinds of three-phase integrated filter inductors in three-phase PV inverter are proposed. Firstly, the three-phase PV inverter operation with discrete filter inductors is analyzed, and the design of discrete filter inductors is given; then operation of the three-phase PV inverter with three-phase integrated five-limb magnetic core filter inductors is analyzed, the design of integrated filter inductors with five-limb magnetic core is given, then the operation of three-phase PV inverter with three-phase integrated three-limb magnetic core filter inductors is analyzed, and the design of integrated filter inductors with three limbs magnetic core is given. The conclusion of comparison between three-phase discrete filter inductors and two kinds of three-phase integrated filter inductors is done; it means that the three-phase discrete filter inductors can achieve better output electrical power quality with lower power density and three-phase integrated filter inductors can achieve higher power density with lower output electrical power quality. Finally, the experiment results are given to compare the volume and filter effect of three kinds of filter inductors in three-phase PV inverter.

Description: A classical issue in many applied fields is to obtain an approximating surface to a given set of data points. This problem arises in Computer-Aided Design and Manufacturing (CAD/CAM), virtual reality, medical imaging, computer graphics, computer animation, and many others. Very often, the preferred approximating surface is polynomial, usually described in parametric form. This leads to the problem of determining suitable parametric values for the data points, the so-called surface parameterization. In real-world settings, data points are generally irregularly sampled and subjected to measurement noise, leading to a very difficult nonlinear continuous optimization problem, unsolvable with standard optimization techniques. This paper solves the parameterization problem for polynomial Bézier surfaces by applying the firefly algorithm, a powerful nature-inspired metaheuristic algorithm introduced recently to address difficult optimization problems. The method has been successfully applied to some illustrative examples of open and closed surfaces, including shapes with singularities. Our results show that the method performs very well, being able to yield the best approximating surface with a high degree of accuracy.

Description: This paper proposes a partial refactorization for faster nonlinear analysis based on sparse matrix solution, which is nowadays the default solution choice in finite element analysis and can solve finite element models up to millions degrees of freedom. Among various fill-in’s reducing strategies for sparse matrix solution, the graph partition is in general the best in terms of resultant fill-ins and floating-point operations and furthermore produces a particular graph of sparse matrix that prevents local change of entries from wide spreading in factorization. Based on this feature, an explicit partial triangular refactorization with local change is efficiently constructed with limited additional storage requirement in row-sparse storage scheme. The partial refactorization of the changed stiffness matrix inherits a big percentage of the original factor and is carried out only on partial factor entries. The proposed method provides a new possibility for faster nonlinear analysis and is mainly suitable for material nonlinear problems and optimization problems. Compared to full factorization, it can significantly reduce the factorization time and can make nonlinear analysis more efficient.

Description: Prediction of RNA structure is a useful process for creating new drugs and understanding genetic diseases. In this paper, we proposed a particle swarm optimization (PSO) and ant colony optimization (ACO) based framework (PAF) for RNA secondary structure prediction. PAF consists of crucial stem searching (CSS) and global sequence building (GSB). In CSS, a modified ACO (MACO) is used to search the crucial stems, and then a set of stems are generated. In GSB, we used a modified PSO (MPSO) to construct all the stems in one sequence. We evaluated the performance of PAF on ten sequences, which have length from 122 to 1494. We also compared the performance of PAF with the results obtained from six existing well-known methods, SARNA-Predict, RnaPredict, ACRNA, PSOfold, IPSO, and mfold. The comparison results show that PAF could not only predict structures with higher accuracy rate but also find crucial stems.

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: 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: The problem of robust fault tolerant control for continuous-time fractional-order (FO) systems with interval parameters and sensor faults of has been investigated. By establishing sensor fault model and state observer, an observer-based FO output feedback controller is developed such that the closed-loop FO system is asymptotically stable, not only when all sensor components are working well, but also in the presence of sensor components failures. Finally, numerical simulation examples are given to illustrate the application of the proposed design method.

Description: The rural/remote IMPROVE network (Interagency Monitoring of Protected Visual Environments) and the Environmental Protection Agency's urban Chemical Speciation Network have measured PM2.5 organic (OC) and elemental carbon (EC) since 1989 and 2000, respectively. We aggregated OC and EC data from 2007 to 2010 at over 300 sites from both networks in order to characterize the spatial and seasonal patterns in rural and urban carbonaceous aerosols. The spatial extent of OC and EC was more regional in the eastern United States relative to more localized concentrations in the West. The highest urban impacts of OC and EC relative to background concentrations occurred in the West during fall and winter. Urban and rural carbonaceous aerosols experienced a large (although opposite) range in seasonality in the West compared to a much lower seasonal variability in the East. Long-term (1990–2010) trend analyses indicated a widespread decrease in rural TC (TC = OC + EC) across the country, with positive, though insignificant, trends in the summer and fall in the West. Short-term trends indicated that urban and rural TC concentrations have both decreased since 2000, with the strongest and more spatially homogeneous urban and rural trends in the West relative to the East.

Description: The Doppler velocity dealiasing technique based on alias-robust VAD and variational (AR-Var) analyses developed at the National Severe Storms Laboratory for radar data quality control and assimilation is further improved in its two-step procedures: the reference check in the first step and the continuity check in the second step. In the first step, the alias-robust variational analysis is modified adaptively and used in place of the alias-robust velocity-azimuth display (VAD) analysis for all scan modes (rather than solely the WSR-88D volume coverage pattern 31 with the Nyquist velocity reduced below 12 m s−1 and the TDWR Mod80 with reduced below 15 m s−1), so more raw data can pass the stringent threshold conditions used by the reference check in the first step. This improves the dealiased data coverage without false dealiasing to better satisfy the high data quality standard required by radar data assimilation. In the second step, new procedures are designed and added to the continuity check to increase the dealiased data coverage over storm-scale areas threatened by intense mesocyclones and their generated tornados. The performances of the improved dealiasing technique versus the existing techniques are exemplified by the results obtained for tornadic storms scanned by the operational KTLX radar in Oklahoma.

Description: It is widely accepted that tumorigenesis is a multistep process characterized by the sequential accumulation of genetic alterations. However, the molecular basis of genomic instability in cancer is still partially understood. The observation that hereditary cancers are often characterized by mutations in DNA repair and checkpoint genes suggests that accumulation of DNA damage is a major contributor to the oncogenic transformation. It is therefore of great interest to identify all the cellular pathways that contribute to the response to DNA damage. Recently, RNA processing has emerged as a novel pathway that may contribute to the maintenance of genome stability. In this review, we illustrate several different mechanisms through which pre-mRNA splicing and genomic stability can influence each other. We specifically focus on the role of splicing factors in the DNA damage response and describe how, in turn, activation of the DDR can influence the activity of splicing factors.

Description: The components and claddings of low-rise buildings are usually destroyed first during typhoon disasters in coastal areas. Roof accessory structures can change the flow pattern on the roof, thus effectively reducing the wind load on the roof surface and the damage to the low-rise buildings. Three types of aerodynamic mitigation plates, that is, (1) 0.3 m high full-length roof-edge plate, (2) 0.3 m high and 0.5 m + 0.5 m long roof-corner plate, and (3) discrete roof-edge plates with different spaces (which can be used as advertisement boards), are studied on the basis of the field measurement results under roof pitches of 10° and 18.4°. By comparing the results of the roof with and without constructed plates, it is implied that the three types of plates can affect the formation of conical vortexes and can significantly reduce the mean and fluctuating pressure coefficients in the windward corner. Compared with the constructed plate, the roof ridge has a larger influence on the wind loads on leeward roof.

Description: Composite silicon dioxide-titanium dioxide (SiO2-TiO2) films are deposited on a large area of 15.6 × 15.6 cm2 textured multicrystalline silicon solar cells to increase the incident light trapped within the device. For further improvement of the antireflective coatings (ARCs) quality, dimethylformamide (DMF) solution is added to the original SiO2-TiO2 solutions. DMF solution solves the cracking problem, thus effectively decreasing reflectance as well as surface recombination. The ARCs prepared by sol-gel process and plasma-enhanced chemical vapor deposition (PECVD) on multicrystalline silicon substrate are compared. The average efficiency of the devices with improved sol-gel ARCs is 16.3%, only 0.5% lower than that of devices with PECVD ARCs (16.8%). However, from equipment depreciation point of view (the expiration date of equipment is generally considered as 5 years), the running cost (USD/watt) of sol-gel technique is 80% lower than that of PECVD method for the first five years and 66% lower than that of PECVD method from the start of the sixth year. This result proves that sol-gel-deposited ARCs process has potential applications in manufacturing low-cost, large-area solar cells.

Description: We study the lattice dynamical system of a nonlinear Boussinesq equation. We first verify the Lipschitz continuity of the continuous semigroup associated with the system. Then, we provide an estimation of the tail of the difference between two solutions of the system. Finally, we obtain the existence of an exponential attractor of the system.

Description: A novel scheme for fault-tolerant control is proposed in this paper, in which model reference adaptive control method is incorporated with control allocation to cope with simultaneous actuator failures, input saturation, and model mismatch in the flight system. In order to reduce performance degradation caused by actuator failures, the proposed scheme redistributes the control signal to healthy actuators and updates the weighting matrix based on actuator effectiveness. Because of saturation errors resulting from actuator constraints and model mismatch caused by abnormal changes in the system, the original reference model may not be appropriate. Under this circumstance, an adaptive reference model which can also provide satisfactory performance is designed. Simulations of a flight control example are given to illustrate the effectiveness of the proposed scheme.

Description: A virtual channels scheduling algorithm with broad applicability based on movable boundary is proposed. According to the types of date sources, transmission time slots are divided into synchronous ones and asynchronous ones with a movable boundary between them. During the synchronous time slots, the virtual channels are scheduled with a polling algorithm; during the asynchronous time slots, the virtual channels are scheduled with an algorithm based on virtual channel urgency and frame urgency. If there are no valid frames in the corresponding VC at a certain synchronous time slot, a frame of the other synchronous VCs or asynchronous VCs will be transmitted through the physical channel. Only when there are no valid frames in all VCs would an idle frame be generated and transmitted. Experiments show that the proposed algorithm yields much lower scheduling delay and higher channel utilization ratio than those based on unmovable boundary or virtual channel urgency in many kinds of sources. Therefore, broad applicability can be achieved by the proposed algorithm.

Description: Self-localization is a basic skill for mobile robots in the dynamic environments. It is usually modeled as a state estimation problem for nonlinear system with non-Gaussian noise and needs the real-time processing. Unscented particle filter (UPF) can handle the state estimation problem for nonlinear system with non-Gaussian noise; however the computation of UPF is very high. In order to reduce the computation cost of UPF and meanwhile maintain the accuracy, we propose an adaptive unscented particle filter (AUPF) algorithm through relative entropy. AUPF can adaptively adjust the number of particles during filtering to reduce the necessary computation and hence improve the real-time capability of UPF. In AUPF, the relative entropy is used to measure the distance between the empirical distribution and the true posterior distribution. The least number of particles for the next step is then decided according to the relative entropy. In order to offset the difference between the proposal distribution, and the true distribution the least number is adjusted thereafter. The ideal performance of AUPF in real robot self-localization is demonstrated.

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.

Description: by Soumya Lipsa Rath, Sanjib Senapati Cyclin-dependent kinases (CDKs) belong to the CMGC subfamily of protein kinases and play crucial roles in eukaryotic cell division cycle. At least seven different CDKs have been reported to be implicated in the cell cycle regulation in vertebrates. These CDKs are highly homologous and contain a conserved catalytic core. This makes the design of inhibitors specific for a particular CDK difficult. There is, however, growing need for CDK5 specific inhibitors to treat various neurodegenerative diseases. Recently, cis-substituted cyclobutyl-4-aminoimidazole inhibitors have been identified as potent CDK5 inhibitors that gave up to 30-fold selectivity over CDK2. Available IC 50 values also indicate a higher potency of this class of inhibitors over commercially available drugs, such as roscovitine. To understand the molecular basis of higher potency and selectivity of these inhibitors, here, we present molecular dynamics simulation results of CDK5/p25 and CDK2/CyclinE complexed with a series of cyclobutyl-substituted imidazole inhibitors and roscovitine. The atomic details of the stereospecificity and selectivity of these inhibitors are obtained from energetics and binding characteristics to the CDK binding pocket. The study not only complements the experimental findings, but also provides a wealth of detailed information that could help the structure-based drug designing processes.

Description: by Valente Aritua, Diann Achor, Frederick G. Gmitter, Gene Albrigo, Nian Wang Huanglongbing (HLB) is the most destructive disease that affects citrus worldwide. The disease has been associated with Candidatus Liberibacter. HLB diseased citrus plants develop a multitude of symptoms including zinc and copper deficiencies, blotchy mottle, corky veins, stunting, and twig dieback. Ca . L. asiaticus infection also seriously affects the roots. Previous study focused on gene expression of leaves and fruit to Ca . L. asiaticus infection. In this study, we compared the gene expression levels of stems and roots of healthy plants with those in Ca . L. asiaticus infected plants using microarrays. Affymetrix microarray analysis showed a total of 988 genes were significantly altered in expression, of which 885 were in the stems, and 111 in the roots. Of these, 551 and 56 were up-regulated, while 334 and 55 were down-regulated in the stem and root samples of HLB diseased trees compared to healthy plants, respectively. Dramatic differences in the transcriptional responses were observed between citrus stems and roots to Ca . L. asiaticus infection, with only 8 genes affected in both the roots and stems. The affected genes are involved in diverse cellular functions, including carbohydrate metabolism, cell wall biogenesis, biotic and abiotic stress responses, signaling and transcriptional factors, transportation, cell organization, protein modification and degradation, development, hormone signaling, metal handling, and redox. Microscopy analysis showed the depletion of starch in the roots of the infected plants but not in healthy plants. Collapse and thickening of cell walls were observed in HLB affected roots, but not as severe as in the stems. This study provides insight into the host response of the stems and roots to Ca . L. asiaticus infection.

Description: by Hong Ding, Xin Sun, Wei-wei Chang, Liu Zhang, Xi-ping Xu Background The government of China promulgated new medical care reform policies in March 2009. After that, provincial-level governments launched new medical care reform which focusing on local comprehensive medical care reform (LCMR). Anhui Province is an example of an area affected by LCMR, in which the LCMR was started in October 2009 and implemented in June 2010. The objective of this study was to compare the job satisfaction (JS) of community health workers (CHWs) before and after the reform in Anhui Province. Methods A baseline survey was carried out among 813 community health workers (CHWs) of 57 community health centers (CHCs) (response rate: 94.1%) and an effect evaluation survey among 536 CHWs of 30 CHCs (response rate: 92.3%) in 2009 and 2012 respectively. A self-completion questionnaire was used to assess the JS of the CHWs (by the job satisfaction scale, JSS). Results The average scores of total JS and satisfaction with pay, contingent rewards, operating procedures and communication in the effect evaluation survey were statistically significantly higher than those of the baseline survey ( P

Description: by Gerda G. Fillenbaum, Sergio L. Blay, Carl F. Pieper, Katherine E. King, Sergio B. Andreoli, Fábio L. Gastal Objectives In high income, developed countries, health status tends to improve as income increases, but primarily through the 50 th -66 th percentile of income. It is unclear whether the same limitation holds in middle income countries, and for both general assessments of health and specific conditions. Methods Data were obtained from Brazil, a middle income country. In-person interviews with a representative sample of community residents age ≥60 (N=6963), in the southern state of Rio Grande do Sul, obtained information on demographic characteristics including household income and number of persons supported, general health status (self-rated health, functional status), depression, and seven physician-diagnosed, self-reported health conditions. Analyses used household income (adjusted for number supported and economies of scale) together with higher order income terms, and controlled for demographics and comorbidities, to ascertain nonlinearity between income and general and specific health measures. Results In fully controlled analyses income was associated with general measures of health (linearly with self-rated health, nonlinearly with functional status). For specific health measures there was a consistent linear association with depression, pulmonary disorders, renal disorders, and sensory impairment. For musculoskeletal, cardiovascular (negative association), and gastrointestinal disorders this association no longer held when comorbidities were controlled. There was no association with diabetes. Conclusion Contrary to findings in high income countries, the association of household-size-adjusted income with health was generally linear, sometimes negative, and sometimes absent when comorbidities were controlled.

Description: by Sudheer Gupta, Pallavi Kapoor, Kumardeep Chaudhary, Ankur Gautam, Rahul Kumar, Open Source Drug Discovery Consortium , Gajendra P. S. Raghava Background Over the past few decades, scientific research has been focused on developing peptide/protein-based therapies to treat various diseases. With the several advantages over small molecules, including high specificity, high penetration, ease of manufacturing, peptides have emerged as promising therapeutic molecules against many diseases. However, one of the bottlenecks in peptide/protein-based therapy is their toxicity. Therefore, in the present study, we developed in silico models for predicting toxicity of peptides and proteins. Description We obtained toxic peptides having 35 or fewer residues from various databases for developing prediction models. Non-toxic or random peptides were obtained from SwissProt and TrEMBL. It was observed that certain residues like Cys, His, Asn, and Pro are abundant as well as preferred at various positions in toxic peptides. We developed models based on machine learning technique and quantitative matrix using various properties of peptides for predicting toxicity of peptides. The performance of dipeptide-based model in terms of accuracy was 94.50% with MCC 0.88. In addition, various motifs were extracted from the toxic peptides and this information was combined with dipeptide-based model for developing a hybrid model. In order to evaluate the over-optimization of the best model based on dipeptide composition, we evaluated its performance on independent datasets and achieved accuracy around 90%. Based on above study, a web server, ToxinPred has been developed, which would be helpful in predicting (i) toxicity or non-toxicity of peptides, (ii) minimum mutations in peptides for increasing or decreasing their toxicity, and (iii) toxic regions in proteins. Conclusion ToxinPred is a unique in silico method of its kind, which will be useful in predicting toxicity of peptides/proteins. In addition, it will be useful in designing least toxic peptides and discovering toxic regions in proteins. We hope that the development of ToxinPred will provide momentum to peptide/protein-based drug discovery (http://crdd.osdd.net/raghava/toxinpred/).

Description: by Peter Walentek, Isabelle Schneider, Axel Schweickert, Martin Blum Breakage of bilateral symmetry in amphibian embryos depends on the development of a ciliated epithelium at the gastrocoel roof during early neurulation. Motile cilia at the gastrocoel roof plate (GRP) give rise to leftward flow of extracellular fluids. Flow is required for asymmetric gene expression and organ morphogenesis. Wnt signaling has previously been involved in two steps, Wnt/ß-catenin mediated induction of Foxj1 , a regulator of motile cilia, and Wnt/planar cell polarity (PCP) dependent cilia polarization to the posterior pole of cells. We have studied Wnt11b in the context of laterality determination, as this ligand was reported to activate canonical and non-canonical Wnt signaling. Wnt11b was found to be expressed in the so-called superficial mesoderm (SM), from which the GRP derives. Surprisingly, Foxj1 was only marginally affected in loss-of-function experiments, indicating that another ligand acts in this early step of laterality specification. Wnt11b was required, however, for polarization of GRP cilia and GRP morphogenesis, in line with the known function of Wnt/PCP in cilia-driven leftward flow. In addition Xnr1 and Coco expression in the lateral-most GRP cells, which sense flow and generate the first asymmetric signal, was attenuated in morphants, involving Wnt signaling in yet another process related to symmetry breakage in Xenopus .

Description: by Heng Zhao, Jiani Liu, Shinong Pan, Yingwei Sun, Qi Li, Fei Li, Li Ma, Qiyong Guo Purpose Although superoxide dismutase (SOD) and malondialdehyde (MDA) affect Delayed Onset Muscle Soreness (DOMS), their effects are unclear in rectus femoris muscles (RFM) of rats with different eccentric exercise programs and time points. The purpose of this study is to investigate the effects of the various eccentric exercise programs at different time points on the SOD mRNA expression and MDA using rat as the animal model. Methods 248 male rats were randomly divided into 4 groups: control group (CTL, n  = 8), once-only exercise group (OEG, n  = 80), continuous exercise group (CEG, n  = 80), and intermittent exercise group (IEG, n =  80). Each exercise group was divided into 10 subgroups that exercised 0.5 h, 6 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, or 168 h. Rats were sacrificed and their SOD mRNA expression, and MDA concentrations of skeletal muscle tissue were measured. Results The specimen in all eccentric exercise programs showed increased RFM SOD1 mRNA expression levels at 0.5 h ( P 〈 0.05), and decreased RFM SOD3 mRNA expression at 0.5 h ( P 〈 0.05). The continuous eccentric exercise (CE) significantly enhanced muscle SOD2 mRNA level at 0.5 h ( P 〈 0.05). After once-only eccentric exercise (OE), SOD1 , SOD2 , and SOD3 mRNA expression significantly increased at 96 h, whereas MDA concentrations decreased at 96 h. After CE, the correlation coefficients of SOD1 , SOD2 , SOD3 mRNA expression levels and MDA concentrations were −0.814, −0.763, −0.845 (all P 〈 0.05) at 12 h. Conclusion Regular eccentric exercise, especially CE could enhance SOD1 and SOD2 mRNA expression in acute stage and the SOD2 mRNA expression correlates to MDA concentration in vivo , which may improve the oxidative adaption ability of skeletal muscles.

Description: by Qian Fan, Zheng M. Huang, Matthieu Boucher, Xiying Shang, Lin Zuo, Henriette Brinks, Wayne Bond Lau, Jianke Zhang, J. Kurt Chuprun, Erhe Gao Aim As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure. Methods Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV) catheterization and cardiomyocyte death was measured by Evans blue-TTC staining, TUNEL staining, and caspase-3, -8, and -9 activities. In vitro, H9C2 cells transfected with ether scramble siRNA or FADD siRNA were stressed with chelerythrin for 30 min and cleaved caspase-3 was assessed. Results FADD expression was significantly decreased in FADD knockout mice compared to NLC. Ischemia/reperfusion (I/R) upregulated FADD expression in NLC mice, but not in FADD knockout mice at the early time. FADD deletion significantly attenuated I/R-induced cardiac dysfunction, decreased myocardial necrosis, and inhibited cardiomyocyte apoptosis. Furthermore, in 6 weeks long term permanent ischemia model, FADD deletion significantly reduced the infarct size (from 41.20±3.90% in NLC to 26.83±4.17% in FADD deletion), attenuated myocardial remodeling, improved cardiac function and improved survival. In vitro, FADD knockdown significantly reduced chelerythrin-induced the level of cleaved caspase-3. Conclusion Taken together, our results suggest FADD plays a critical role in post-ischemic heart failure. Inhibition of FADD retards heart failure progression. Our data supports the further investigation of FADD as a potential target for genetic manipulation in the treatment of heart failure.

Description: by Shuang Li, Ting Hu, Yile Chen, Hang Zhou, Xiong Li, Xiaodong Cheng, Ru Yang, Shixuan Wang, Xing Xie, Ding Ma Radiotherapy is the standard treatment for cervical cancer, but causes radiotherapy-induced complications. Recently, chemotherapy has been more extensively utilized. Here, we perform a large-scale comparison of chemotherapy and radiotherapy. From 2002 to 2008, 2,268 patients were grouped according to adjuvant radiotherapy or chemotherapy before and/or after surgery, and we compared the 5-year overall survival (OS) and disease-free survival (DFS) rates, recurrence rates, side effects, quality of life (QoL), and sexual activity. There were no significant differences between the treatment groups for the 5-year OS and DFS rates (OS: p =  0.053, DFS: p  = 0.095), although marginally improved outcomes were observed in the chemotherapy group (OS: 86.5% vs. 82.8%; DFS: 84.5% vs. 81.4%). However, patients with early-stage disease, clinical response, and younger age had increased 5-year OS and DFS rates following chemotherapy compared to radiotherapy ( p

Description: by Anne-Sophie Ay, Nazim Benzerdjerb, Henri Sevestre, Ahmed Ahidouch, Halima Ouadid-Ahidouch Orai channels have been associated with cell proliferation, survival and metastasis in several cancers. The present study investigates the expression and the role of Orai3 in cell proliferation in non-small cell lung cancer (NSCLC). We show that Orai3 is over-expressed in cancer tissues as compared to the non-tumoral ones. Furthermore, Orai3 staining is stronger in high grade tumors. Pharmacological inhibition or knockdown of Orai3 significantly reduced store operated calcium entry (SOCE), inhibited cell proliferation and arrested cells of two NSCLC cell lines in G0/G1 phase. These effects were concomitant with a down-regulation of cyclin D1, cyclin E, CDK4 and CDK2 expression. Moreover, Orai3 silencing decreased Akt phosphorylation levels. In conclusion, Orai3 constitutes a native SOCE pathway in NSCLC that controls cell proliferation and cell cycle progression likely via Akt pathway.

Description: by Katherine Scranton, Menelaos Stavrinides, Nicholas J. Mills, Perry de Valpine Life history variation is a general feature of arthropod systems, but is rarely included in models of field or laboratory data. Most studies assume that local processes occur identically across individuals, ignoring any genetic or phenotypic variation in life history traits. In this study, we tested whether field populations of Pacific spider mites ( Tetranychus pacificus ) on grapevines ( Vitis vinifera ) display significant intraspecific life history variation associated with host plant cultivar. To address this question we collected individuals from sympatric vineyard populations where either Zinfandel or Chardonnay were grown. We then conducted a “common garden experiment” of mites on bean plants ( Phaseolus lunatus ) in the laboratory. Assay populations were sampled non-destructively with digital photography to quantify development times, survival, and reproductive rates. Two classes of models were fit to the data: standard generalized linear mixed models and a time-to-event model, common in survival analysis, that allowed for interval-censored data and hierarchical random effects. We found a significant effect of cultivar on development time in both GLMM and time-to-event analyses, a slight cultivar effect on juvenile survival, and no effect on reproductive rate. There were shorter development times and a trend towards higher juvenile survival in populations from Zinfandel vineyards compared to those from Chardonnay vineyards. Lines of the same species, originating from field populations on different host plant cultivars, expressed different development times and slightly different survival rates when reared on a common host plant in a common environment.

Description: by Yi Ding, Lirong Song, Bojan Sedmak Due to the stratospheric ozone depletion, several organisms will become exposed to increased biologically active UVB (280–320 nm) radiation, not only at polar but also at temperate and tropical latitudes. Bloom forming cyanobacteria are exposed to UVB radiation on a mass scale, particularly during the surface bloom and scum formation that can persist for long periods of time. All buoyant species of cyanobacteria are at least periodically exposed to higher irradiation during their vertical migration to the surface that usually occurs several times a day. The aim of this study is to assess the influence on cyanobacteria of UVB radiation at realistic environmental intensities. The effects of two UVB intensities of 0.5 and 0.99 W/m 2 in up to 0.5 cm water depth were studied in vitro on Microcystis aeruginosa strains, two microcystin producing and one non-producing. After UVB exposure their ability to proliferate was estimated by cell counting, while cell fitness and integrity were evaluated using light microscopy, autofluorescence and immunofluorescence. Gene damage was assessed by TUNEL assay and SYBR Green staining of the nucleoide area. We conclude that UVB exposure causes damage to the genetic material, cytoskeletal elements, higher sedimentation rates and consequent cell death. In contrast to microcystin producers (PCC7806 and FACHB905), the microcystin non-producing strain PCC7005 is more susceptible to the deleterious effects of radiation, with weak recovery ability. The ecological relevance of the results is discussed using data from eleven years’ continuous UVB radiation measurements within the area of Ljubljana city (Slovenia, Central Europe). Our results suggest that increased solar radiation in temperate latitudes can have its strongest effect during cyanobacterial bloom formation in spring and early summer. UVB radiation in this period may significantly influence strain composition of cyanobacterial blooms in favor of microcystin producers.

Description: by Yimin, Masashi Kohanawa, Songji Zhao, Michitaka Ozaki, Sanae Haga, Guangxian Nan, Yuji Kuge, Nagara Tamaki Staphylococcus aureus is a common pathogen that causes a wide range of infectious diseases. The function of TLRs, specifically TLR2, during S. aureus infection is still debated. In this study, we investigated the extent to which TLR2 contributes to the host innate response against the bacterial infection using TLR2-deficient mice. Intravenous inoculation with S. aureus resulted in all TLR2-deficient mice dying within 4 d, along with a high bacterial burden in the livers. However, histological examination showed the same degree of macrophage and neutrophil accumulation in the livers of infected TLR2-deficient mice as that in infected wild-type (WT) mice. TLR2-deficient mouse macrophages also showed normal phagocytic activity, although they failed to express CD36 that appeared on the surface of WT mouse cells upon challenge with heat-killed S. aureus . These data indicate that TLR2, as well as CD36, does not directly affect S. aureus clearance and that CD36 expression on macrophages depends on the presence of TLR2. In vivo infection with S. aureus caused significantly elevated production of TNF-α and IL-6 in the livers and blood of TLR2-deficient mice compared with those in WT mice, while the hepatic and serum levels of IL-10 decreased in these mice. In contrast, lower expression of IL-6 and IL-10, but not of TNF-α, at both the gene and protein levels was found in TLR2-deficient mouse macrophages compared to that in WT mouse cells, in response to challenge with heat-killed S. aureus . These findings suggest that the S. aureus -induced pro-inflammatory cytokine response is not dependent on macrophages and that TLR2 deficiency results in decreased IL-10 release by macrophages, which contributes to dysregulated cytokine balance, impaired bacterial clearance, and mouse death. Therefore, TLR2 possesses a protective function during S. aureus infection by regulating pro- and anti-inflammatory cytokine responses.

Description: by Kepa B. Uribe, César Martín, Aitor Etxebarria, David González-Bullón, Geraxane Gómez-Bilbao, Helena Ostolaza Humans infected with Bordetella pertussis , the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin (ACT) which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b/CD18 (CR3), its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca 2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.

Description: by Haitao Jiang, Linlin Qu, Rongrong Dou, Lianfang Lu, Sishan Bian, Weiming Zhu Background Transplantation of bone marrow mesenchymal stem cells (MSCs) provides a promising therapeutic efficiency for a variety of disorders caused by ischemia or reperfusion impairment. We have previously demonstrated the efficacy of MSCs in mitigating intestinal ischemia/reperfusion (I/R) injuries in rats, but the mechanism by which MSCs engraft ameliorates I/R injuries has largely been unknown. The present study aimed at investigating probable mechanisms by which MSCs exert their function. Methods Male donor derived rat MSCs were implanted into intestine of female recipient rat by direct submucosal injection after superior mesenteric artery clamping and unclamping. The homed MSCs were detected by Y chromosome in situ hybridization probe, and the tumor necrosis factor-α (TNF-α) content in intestinal mucosa was determined by ELISA. Expression of proliferative cell nuclear antigen (PCNA) in bowel mucosa was assayed by real-time PCR and intestinal mucosa expression of phosphorylation extracellular signal-regulated kinase (pERK1/2) and nuclear factor-κB (NF-κB) were evaluated by western blot. Results Four and seven days after MSCs transplantation, the TNF-α content of bowel mucosa in MSCs group was significantly lower than that in saline group. The PCNA in bowel mucosa showed higher expression in MSCs treated group than the saline group, both at 4 and 7 days after cell transplantation. The expression of intestinal mucosal pERK1/2 in MSCs treated group was markedly higher than that in saline group, and the expression of NF-κB in MSCs treated group was noticeably decreased than that in saline group at 4 and 7 days post MSCs transplantation. Conclusion The present investigation provides novel evidence that MSCs have the potential to reduce intestinal I/R injuries probably due to their ability to accelerate cell proliferation and decrease the inflammatory response within intestinal mucosa after ischemia and reperfusion.

Description: by Katherine M. Hiller, Lisa Stoneking, Alice Min, Suzanne Michelle Rhodes The science of surveillance is rapidly evolving due to changes in public health information and preparedness as national security issues, new information technologies and health reform. As the Emergency Department has become a much more utilized venue for acute care, it has also become a more attractive data source for disease surveillance. In recent years, influenza surveillance from the Emergency Department has increased in scope and breadth and has resulted in innovative and increasingly accepted methods of surveillance for influenza and influenza-like-illness (ILI). We undertook a systematic review of published Emergency Department-based influenza and ILI syndromic surveillance systems. A PubMed search using the keywords “syndromic”, “surveillance”, “influenza” and “emergency” was performed. Manuscripts were included in the analysis if they described (1) data from an Emergency Department (2) surveillance of influenza or ILI and (3) syndromic or clinical data. Meeting abstracts were excluded. The references of included manuscripts were examined for additional studies. A total of 38 manuscripts met the inclusion criteria, describing 24 discrete syndromic surveillance systems. Emergency Department-based influenza syndromic surveillance has been described worldwide. A wide variety of clinical data was used for surveillance, including chief complaint/presentation, preliminary or discharge diagnosis, free text analysis of the entire medical record, Google flu trends, calls to teletriage and help lines, ambulance dispatch calls, case reports of H1N1 in the media, markers of ED crowding, admission and Left Without Being Seen rates. Syndromes used to capture influenza rates were nearly always related to ILI (i.e. fever +/− a respiratory or constitutional complaint), however, other syndromes used for surveillance included fever alone, “respiratory complaint” and seizure. Two very large surveillance networks, the North American DiSTRIBuTE network and the European Triple S system have collected large-scale Emergency Department-based influenza and ILI syndromic surveillance data. Syndromic surveillance for influenza and ILI from the Emergency Department is becoming more prevalent as a measure of yearly influenza outbreaks.

Description: With the water and soil conservation forests of Robinia pseudoacacia in the Malian beach of Hongqi farm, Ji County, Shanxi province, as the research object, this study estimated the potential evapotranspiration in the open space outside the forest and at the heights of 3 m, 6 m, and 10 m in the forests with the climate data during 2011-2012 and the upgraded Penman-Monteith formula; then, this study explored the microclimate characteristics inside and outside the Robinia pseudoacacia forest and thereafter revealed the vertical variation rules of potential evapotranspiration of Robinia pseudoacacia. The results indicate that the air temperature, relative humidity, wind speed, and potential evapotranspiration at different heights above the ground surface showed similar changing trends, but with some variation during different periods. In addition, the weather also had impacts on the potential evapotranspiration. In April, July, and October, the change of potential evapotranspiration of the Robinia pseudoacacia forests showed a bimodal curve in the sunny days and rainy days, while it showed a single-peak curve with quite small fluctuation in the rainy days. However, it showed a single-peak pattern even in the sunny days in January, and it showed no fluctuation in the snowy days in January.

Description: Cooperative communications that take advantage of the broadcasting nature of wireless environments can help to increase system throughput in wireless ad hoc networks. However, the promised throughput might be lost in presence of the error transmission and the interference caused by relay transmission in cooperative communication. In this paper, we introduced the relay selection schemes that can control the interference at the relay to prevent the relay that may harm other pairs. Then, we proposed the throughput-optimal scheduling that takes into account error probability in decision and maximizes throughput, that is, the amount of packets transmitted without error in network. In addition, we derive a simple and lightweight framework to implement the proposed policy in distributed manner. The simulation results show that the proposed scheduling policy outperforms the noncooperative policy and multihop relay policy.

Description: by Zhenghui Hu, Heye Zhang, Jinwei Yuan, Minhua Lu, Siping Chen, Huafeng Liu The purpose of ultrasound elastography is to identify lesions by reconstructing the hardness characteristics of tissue reconstructed from ultrasound data. Conventional quasi-static ultrasound elastography is easily applied to obtain axial strain components along the compression direction, with the results inverted to represent the distribution of tissue hardness under the assumption of constant internal stresses. However, previous works of quasi-static ultrasound elastography have found it difficult to obtain the lateral and shear strain components, due to the poor lateral resolution of conventional ultrasound probes. The physical nature of the strain field is a continuous vector field, which should be fully described by the axial, lateral, and shear strain components, and the clinical value of lateral and shear strain components of deformed tissue is gradually being recognized by both engineers and clinicians. Therefore, a biomechanical-model-constrained filtering framework is proposed here for recovering a full displacement field at a high spatial resolution from the noisy ultrasound data. In our implementation, after the biomechanical model constraint is integrated into the state-space equation, both the axial and lateral displacement components can be recovered at a high spatial resolution from the noisy displacement measurements using a robust filter, which only requires knowledge of the worst-case noise levels in the measurements. All of the strain components can then be calculated by applying a gradient operator to the recovered displacement field. Numerical experiments on synthetic data demonstrated the robustness and effectiveness of our approach, and experiments on phantom data and in-vivo clinical data also produced satisfying results.