bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying and predicting Drosophila larvae crawling phenotypes
Authors: Günther Maximilian N. , Nettesheim Guilherme , Shubeita George T.
Published: June 2016

The fruit fly Drosophila melanogaster is a widely used model for cell biology, development, disease, and neuroscience. The fly’s power as a genetic model for disease and neuroscience can be augmented by a quantitative description of its behavior. Here we show that we can accurately account for the complex and unique crawling patterns exhibited by individual Drosophila larvae using a small set of four parameters obtained from the trajectories of a few crawling larvae. The values of these parameters change for larvae from different genetic mutants, as we demonstrate for fly models of Alzheimer’s disease and the Fragile X syndrome, allowing applications such as genetic or drug screens. Using the quantitative model of larval crawling developed here we use the mutant-specific parameters to robustly simulate larval crawling, which allows estimating the feasibility of laborious experimental assays and aids in their design.
Thermodynamic power of non-Markovianity
Authors: Bylicka Bogna , Tukiainen Mikko , Chruściński Dariusz , Piilo Jyrki , Maniscalco Sabrina
Published: June 2016

The natural framework to discuss thermodynamics at the quantum level is the theory of open quantum systems. Memory effects arising from strong system-environment correlations may lead to information back-flow, that is non-Markovian behaviour. The relation between non-Markovianity and quantum thermodynamics has been until now largely unexplored. Here we show by means of Landauer’s principle that memory effects control the amount of work extraction by erasure in presence of realistic environments.
Combining operando synchrotron X-ray tomographic microscopy and scanning X-ray diffraction to study lithium ion batteries
Authors: Pietsch Patrick , Hess Michael , Ludwig Wolfgang , Eller Jens , Wood Vanessa
Published: June 2016

We present an operando study of a lithium ion battery combining scanning X-ray diffraction (SXRD) and synchrotron radiation X-ray tomographic microscopy (SRXTM) simultaneously for the first time. This combination of techniques facilitates the investigation of dynamic processes in lithium ion batteries containing amorphous and/or weakly attenuating active materials. While amorphous materials pose a challenge for diffraction techniques, weakly attenuating material systems pose a challenge for attenuation-contrast tomography. Furthermore, combining SXRD and SRXTM can be used to correlate processes occurring at the atomic level in the crystal lattices of the active materials with those at the scale of electrode microstructure. To demonstrate the benefits of this approach, we investigate a silicon powder electrode in lithium metal half-cell configuration. Combining SXRD and SRXTM, we are able to (i) quantify the dissolution of the metallic lithium electrode and the expansion of the silicon electrode, (ii) better understand the formation of the Li15Si4 phase and (iii) non-invasively probe kinetic limitations within the silicon electrode. A simple model based on the 1D diffusion equation allows us to qualitatively understand the observed kinetics and demonstrates why high-capacity electrodes are more prone to inhomogeneous lithiation reactions.
Mortality among People Living with HIV and AIDS in China: Implications for Enhancing Linkage
Authors: Li Meng , Tang Weiming , Bu Kai , Mahapatra Tanmay , Zhang Xiayan , Feng Yibing , Chen Fangfang , Guo Wei , Wang Liyan , Ding Zhengwei , Qin Qianqian , Liu Shiliang , Tucker Joseph D. , Wang Lu , Wang Ning
Published: June 2016

To assess the patterns and predictors of AIDS-related mortality and identify its correlates among adult people living with HIV/AIDS (PLWHA) in China, a retrospective record-based cohort study was conducted among 18 years or older PLWHA, who had at least one follow up reported to the national database between January-1989 and June-2012. Cumulative Incidence Function was used to calculate AIDS-related mortality rate. Gray’s test was used to determine the variation in cumulative incidence across strata. The Fine and Gray model was used to measure the burden of cumulative incidence of AIDS-related mortality and strength of its association with potential correlates. Among 375,629 patients, 107,634 died during study period, of which 54,759 (50.87%) deaths were AIDS-related. Cumulative mortality rates of AIDS-related death at one, two, five, 10 and 15 years post-diagnosis were 5.7%, 8.2%, 14.3%, 22.9% and 30.9%, respectively. Among PLWHA, male gender, ethnic minority and having AIDS were associated with significantly higher mortality. Further, homosexual transmission, being on ART and increasing CD4-testing frequency were associated with lower mortality. To reduce mortality among PLWHA, efficient interventions targeting males, ethnic minority, heterosexually infected and AIDS patients should be combined with immunologic monitoring, enhancement of coverage of HIV-testing and ART.
Raman scattering and anomalous Stokes–anti-Stokes ratio in MoTe2 atomic layers
Authors: Goldstein Thomas , Chen Shao-Yu , Tong Jiayue , Xiao Di , Ramasubramaniam Ashwin , Yan Jun
Published: June 2016

Stokes and anti-Stokes Raman scattering are performed on atomic layers of hexagonal molybdenum ditelluride (MoTe2), a prototypical transition metal dichalcogenide (TMDC) semiconductor. The data reveal all six types of zone center optical phonons, along with their corresponding Davydov splittings, which have been challenging to see in other TMDCs. We discover that the anti-Stokes Raman intensity of the low energy layer-breathing mode becomes more intense than the Stokes peak under certain experimental conditions and find the effect to be tunable by excitation frequency and number of atomic layers. These observations are interpreted as a result of resonance effects arising from the C excitons in the vicinity of the Brillouin zone center in the photon-electron-phonon interaction process.
Control efficacy of complex networks
Authors: Gao Xin-Dong , Wang Wen-Xu , Lai Ying-Cheng
Published: June 2016

Controlling complex networks has become a forefront research area in network science and engineering. Recent efforts have led to theoretical frameworks of controllability to fully control a network through steering a minimum set of driver nodes. However, in realistic situations not every node is accessible or can be externally driven, raising the fundamental issue of control efficacy: if driving signals are applied to an arbitrary subset of nodes, how many other nodes can be controlled? We develop a framework to determine the control efficacy for undirected networks of arbitrary topology. Mathematically, based on non-singular transformation, we prove a theorem to determine rigorously the control efficacy of the network and to identify the nodes that can be controlled for any given driver nodes. Physically, we develop the picture of diffusion that views the control process as a signal diffused from input signals to the set of controllable nodes. The combination of mathematical theory and physical reasoning allows us not only to determine the control efficacy for model complex networks and a large number of empirical networks, but also to uncover phenomena in network control, e.g., hub nodes in general possess lower control centrality than an average node in undirected networks.
Melamine Impairs Renal and Vascular Function in Rats
Authors: Tian Xiao Yu , Wong Wing Tak , Lau Chi Wai , Wang Yi-Xiang , Cheang Wai San , Liu Jian , Lu Ye , Huang Huihui , Xia Yin , Chen Zhen Yu , Mok Chuen-Shing , Lau Chau-Ming , Huang Yu
Published: June 2016

Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products.
Homotopy-Theoretic Study & Atomic-Scale Observation of Vortex Domains in Hexagonal Manganites
Authors: Li Jun , Chiang Fu-Kuo , Chen Zhen , Ma Chao , Chu Ming-Wen , Chen Cheng-Hsuan , Tian Huanfang , Yang Huaixin , Li Jianqi
Published: June 2016

Essential structural properties of the non-trivial “string-wall-bounded” topological defects in hexagonal manganites are studied through homotopy group theory and spherical aberration-corrected scanning transmission electron microscopy. The appearance of a “string-wall-bounded” configuration in RMnO3 is shown to be strongly linked with the transformation of the degeneracy space. The defect core regions (~50 Å) mainly adopt the continuous U(1) symmetry of the high-temperature phase, which is essential for the formation and proliferation of vortices. Direct visualization of vortex strings at atomic scale provides insight into the mechanisms and macro-behavior of topological defects in crystalline materials.
Effect of ionic radii on the Curie temperature in Ba1-x-ySrxCayTiO3 compounds
Authors: Berenov A. , Le Goupil F. , Alford N.
Published: June 2016

A series of Ba1-x-ySrxCayTiO3 compounds were prepared with varying average ionic radii and cation disorder on A-site. All samples showed typical ferroelectric behavior. A simple empirical equation correlated Curie temperature, TC, with the values of ionic radii of A-site cations. This correlation was related to the distortion of TiO6 octahedra observed during neutron diffraction studies. The equation was used for the selection of compounds with predetermined values of TC. The effects of A-site ionic radii on the temperatures of phase transitions in Ba1-x-ySrxCayTiO3 were discussed.
Characterization of the microbiome of nipple aspirate fluid of breast cancer survivors
Authors: Chan Alfred A. , Bashir Mina , Rivas Magali N. , Duvall Karen , Sieling Peter A. , Pieber Thomas R. , Vaishampayan Parag A. , Love Susan M. , Lee Delphine J.
Published: June 2016

The microbiome impacts human health and disease. Until recently, human breast tissue and milk were presumed to be sterile. Here, we investigated the presence of microbes in the nipple aspirate fluid (NAF) and their potential association with breast cancer. We compared the NAF microbiome between women with a history of breast cancer (BC) and healthy control women (HC) using 16S rRNA gene amplicon sequencing. The NAF microbiome from BC and HC showed significant differences in community composition. Two Operational Taxonomic Units (OTUs) showed differences in relative abundances between NAF collected from BC and HC. In NAF collected from BC, there was relatively higher incidence of the genus Alistipes. By contrast, an unclassified genus from the Sphingomonadaceae family was relatively more abundant in NAF from HC. These findings reflect the ductal source DNA since there were no differences between areolar skin samples collected from BC and HC. Furthermore, the microbes associated with BC share an enzymatic activity, Beta-Glucuronidase, which may promote breast cancer. This is the first report of bacterial DNA in human breast ductal fluid and the differences between NAF from HC and BC. Further investigation of the ductal microbiome and its potential role in breast cancer are warranted.
High salt promotes autoimmunity by TET2-induced DNA demethylation and driving the differentiation of Tfh cells
Authors: Wu Haijing , Huang Xin , Qiu Hong , Zhao Ming , Liao Wei , Yuan Shuguang , Xie Yubing , Dai Yong , Chang Christopher , Yoshimura Akihiko , Lu Qianjin
Published: June 2016

Follicular helper T cells (Tfh) have been well documented to play a critical role in autoimmunity, such as systemic lupus erythematosus (SLE), by helping B cells. In this study, high salt (sodium chloride, NaCl), under physiological conditions, was demonstrated to increase the differentiation of Tfh. A high-salt diet markedly increased lupus features in MRL/lpr mice. The mechanism is NaCl-induced DNA demethylation via the recruitment of the hydroxytransferase Ten-Eleven Translocation 2 (TET2). Gene silencing of TET2 obviously diminished NaCl-induced Tfh cell polarization in vitro. In addition, the gene expression of sh2d1a, map3k1, spn and stat5b was enhanced after NaCl treatment, consistent with the findings in lupus CD4+T cells. However, only spn was directly regulated by TET2 and spn was not the sole target for NaCl. Our findings not only explain the epigenetic mechanisms of high-salt induced autoimmunity but also provide an attractive molecular target for intervention strategies of patients.
A Local Learning Rule for Independent Component Analysis
Authors: Isomura Takuya , Toyoizumi Taro
Published: June 2016

Humans can separately recognize independent sources when they sense their superposition. This decomposition is mathematically formulated as independent component analysis (ICA). While a few biologically plausible learning rules, so-called local learning rules, have been proposed to achieve ICA, their performance varies depending on the parameters characterizing the mixed signals. Here, we propose a new learning rule that is both easy to implement and reliable. Both mathematical and numerical analyses confirm that the proposed rule outperforms other local learning rules over a wide range of parameters. Notably, unlike other rules, the proposed rule can separate independent sources without any preprocessing, even if the number of sources is unknown. The successful performance of the proposed rule is then demonstrated using natural images and movies. We discuss the implications of this finding for our understanding of neuronal information processing and its promising applications to neuromorphic engineering.
Human Protein Subcellular Localization with Integrated Source and Multi-label Ensemble Classifier
Authors: Guo Xiaotong , Liu Fulin , Ju Ying , Wang Zhen , Wang Chunyu
Published: June 2016

Predicting protein subcellular location is necessary for understanding cell function. Several machine learning methods have been developed for computational prediction of primary protein sequences because wet experiments are costly and time consuming. However, two problems still exist in state-of-the-art methods. First, several proteins appear in different subcellular structures simultaneously, whereas current methods only predict one protein sequence in one subcellular structure. Second, most software tools are trained with obsolete data and the latest new databases are missed. We proposed a novel multi-label classification algorithm to solve the first problem and integrated several latest databases to improve prediction performance. Experiments proved the effectiveness of the proposed method. The present study would facilitate research on cellular proteomics.
Circulating miRNAs are generic and versatile therapeutic monitoring biomarkers in muscular dystrophies
Authors: Israeli David , Poupiot Jérôme , Amor Fatima , Charton Karine , Lostal William , Jeanson-Leh Laurence , Richard Isabelle
Published: June 2016

The development of medical approaches requires preclinical and clinical trials for assessment of therapeutic efficacy. Such evaluation entails the use of biomarkers, which provide information on the response to the therapeutic intervention. One newly-proposed class of biomarkers is the microRNA (miRNA) molecules. In muscular dystrophies (MD), the dysregulation of miRNAs was initially observed in muscle biopsy and later extended to plasma samples, suggesting that they may be of interest as biomarkers. First, we demonstrated that dystromiRs dysregulation occurs in MD with either preserved or disrupted expression of the dystrophin-associated glycoprotein complex, supporting the utilization of dystromiRs as generic biomarkers in MD. Then, we aimed at evaluation of the capacity of miRNAs as monitoring biomarkers for experimental therapeutic approach in MD. To this end, we took advantage of our previously characterized gene therapy approach in a mouse model for α-sarcoglycanopathy. We identified a dose-response correlation between the expression of miRNAs on both muscle tissue and blood serum and the therapeutic benefit as evaluated by a set of new and classically-used evaluation methods. This study supports the utility of profiling circulating miRNAs for the evaluation of therapeutic outcome in medical approaches for MD.
Neurobiological differences in mental rotation and instrument interpretation in airline pilots
Authors: Sladky Ronald , Stepniczka Irene , Boland Edzard , Tik Martin , Lamm Claus , Hoffmann André , Buch Jan-Philipp , Niedermeier Dominik , Field Joris , Windischberger Christian
Published: June 2016

Airline pilots and similar professions require reliable spatial cognition abilities, such as mental imagery of static and moving three-dimensional objects in space. A well-known task to investigate these skills is the Shepard and Metzler mental rotation task (SMT), which is also frequently used during pre-assessment of pilot candidates. Despite the intuitive relationship between real-life spatial cognition and SMT, several studies have challenged its predictive value. Here we report on a novel instrument interpretation task (IIT) based on a realistic attitude indicator used in modern aircrafts that was designed to bridge the gap between the abstract SMT and a cockpit environment. We investigated 18 professional airline pilots using fMRI. No significant correlation was found between SMT and IIT task accuracies. Contrasting both tasks revealed higher activation in the fusiform gyrus, angular gyrus and medial precuneus for IIT, whereas SMT elicited significantly stronger activation in pre- and supplementary motor areas, as well as lateral precuneus and superior parietal lobe. Our results show that SMT skills per se are not sufficient to predict task accuracy during (close to) real-life instrument interpretation. While there is a substantial overlap of activation across the task conditions, we found that there are important differences between instrument interpretation and non-aviation based mental rotation.
The use of platelet-rich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering
Authors: Wang Zhong-Shan , Feng Zhi-Hong , Wu Guo-Feng , Bai Shi-Zhu , Dong Yan , Chen Fa-Ming , Zhao Yi-Min
Published: June 2016

Periodontal regeneration involves the restoration of at least three unique tissues: cementum, periodontal ligament tissue (PDL) and alveolar bone tissue. Here, we first isolated human PDL stem cells (PDLSCs) and jaw bone mesenchymal stem cells (JBMSCs). These cells were then induced to form cell sheets using an ascorbic acid-rich approach, and the cell sheet properties, including morphology, thickness and gene expression profile, were compared. Platelet-rich fibrin (PRF) derived from human venous blood was then fabricated into bioabsorbable fibrin scaffolds containing various growth factors. Finally, the in vivo potential of a cell-material construct based on PDLSC sheets, PRF scaffolds and JBMSC sheets to form periodontal tissue was assessed in a nude mouse model. In this model, PDLSC sheet/PRF/JBMSC sheet composites were placed in a simulated periodontal space comprising human treated dentin matrix (TDM) and hydroxyapatite (HA)/tricalcium phosphate (TCP) frameworks. Eight weeks after implantation, the PDLSC sheets tended to develop into PDL-like tissues, while the JBMSC sheets tended to produce predominantly bone-like tissues. In addition, the PDLSC sheet/PRF/JBMSC sheet composites generated periodontal tissue-like structures containing PDL- and bone-like tissues. Further improvements in this cell transplantation design may have the potential to provide an effective approach for future periodontal tissue regeneration.
HIV-specific Th2 and Th17 responses predict HIV vaccine protection efficacy
Authors: Sauce Delphine , Gorochov Guy , Larsen Martin
Published: June 2016

Understanding the factors that delineate the efficacy of T-cell responses towards pathogens is crucial for our ability to develop potent therapies and vaccines against infectious diseases, such as HIV. Here we show that a recently developed analytical tool, the polyfunctionality index (PI), not only enables prediction of protection after vaccination against HIV, but also allows identification of the immunological pathways involved. Our data suggest that induction of a synergistic network of CD4+ T-cell subsets is implicated in HIV-protection. Accordingly, we provide evidence that vaccine-induced protection is associated with CD40L expressing Th2 cells and IL-2 secreting Th17 cells. In conclusion, we describe a novel approach that is widely applicable and readily interpretable in a biological and clinical context. This approach could greatly impact our fundamental understanding of T-cell immunity as well as the search for effective vaccines.
Protein Kinase A: A Master Kinase of Granulosa Cell Differentiation
Authors: Puri Pawan , Little-Ihrig Lynda , Chandran Uma , Law Nathan C. , Hunzicker-Dunn Mary , Zeleznik Anthony J.
Published: June 2016

Activation of protein kinase A (PKA) by follicle stimulating hormone (FSH) transduces the signal that drives differentiation of ovarian granulosa cells (GCs). An unresolved question is whether PKA is sufficient to initiate the complex program of GC responses to FSH. We compared signaling pathways and gene expression profiles of GCs stimulated with FSH or expressing PKA-CQR, a constitutively active mutant of PKA. Both FSH and PKA-CQR stimulated the phosphorylation of proteins known to be involved in GC differentiation including CREB, ß-catenin, AKT, p42/44 MAPK, GAB2, GSK-3ß, FOXO1, and YAP. In contrast, FSH stimulated the phosphorylation of p38 MAP kinase but PKA-CQR did not. Microarray analysis revealed that 85% of transcripts that were up-regulated by FSH were increased to a comparable extent by PKA-CQR and of the transcripts that were down-regulated by FSH, 76% were also down-regulated by PKA-CQR. Transcripts regulated similarly by FSH and PKA-CQR are involved in steroidogenesis and differentiation, while transcripts more robustly up-regulated by PKA-CQR are involved in ovulation. Thus, PKA, under the conditions of our experimental approach appears to function as a master upstream kinase that is sufficient to initiate the complex pattern of intracellular signaling pathway and gene expression profiles that accompany GC differentiation.
Factors Affecting the Agreement Between Emergency Psychiatrists and General Practitioners Regarding Involuntary Psychiatric Hospitalizations
Authors: Geoffroy Pierre Alexis , Duhamel Alain , Behal Hélène , Zouitina-Lietaert Nadia , Duthilleul Julie , Marquette Louise , Ducrocq François , Vaiva Guillaume , Rolland Benjamin
Published: June 2016

Important discrepancies exist between physicians in deciding when to perform involuntary hospitalization measures (IHMs). The factors underlying these differences are poorly known.

We conducted a two-year single-center retrospective study in France on patients who were referred to the emergency department (ED) with an IHM certificate written by a private-practice General Practitioner (GP). For each consultation, the official IHM motive was categorized into four groups: Suicide; Psychosis, Mania, or Melancholia (PMM); Agitation; and Other. The alcohol status of the patient was also noted. The factors underlying the ED psychiatrists’ confirmation of the use of IHMs were determined using a logistic regression model. One hundred eighty-nine cases were found (165 patients; 44.2 ± 16 years, 41.3% women). The ED psychiatrists confirmed the use of IHMs in 123 instances (65.1% agreement rate). Multivariate analyses found that IHM disagreement was significantly associated with patient alcohol status and the reason for referral. Specifically, there was an increased risk of IHM disagreement when the patient had an alcohol-positive status (OR = 15.80; 95% CI [6.45–38.67]; p < 0.0001) and when the motive for IHM was “agitation” compared with “suicide” (OR = 11.44; 95% CI[3.38–38.78]; p < 0.0001). These findings reflect significant disparities between GPs and ED psychiatrists regarding the decision to proceed to an IHM.
Rice Domestication Revealed by Reduced Shattering of Archaeological rice from the Lower Yangtze valley
Authors: Zheng Yunfei , Crawford Gary W. , Jiang Leping , Chen Xugao
Published: June 2016

Plant remains dating to between 9000 and 8400 BP from a probable ditch structure at the Huxi site include the oldest rice (Oryza sativa) spikelet bases and associated plant remains recovered in China. The remains document an early stage of rice domestication and the ecological setting in which early cultivation was taking place. The rice spikelet bases from Huxi include wild (shattering), intermediate and domesticated (non-shattering) forms. The relative frequency of intermediate and non-shattering spikelet bases indicates that selection for, at the very least, non-shattering rice was underway at Huxi. The rice also has characteristics of japonica rice (Oryza sativa subsp. japonica), helping to clarify the emergence of a significant lineage of the crop. Seeds, phytoliths and their context provide evidence of increasing anthropogenesis and cultivation during the occupation. Rice spikelet bases from Kuahuqiao (8000–7700 BP), Tianluoshan (7000–6500 BP), Majiabang (6300–6000 BP) and Liangzhu (5300–4300 BP) sites indicate that rice underwent continuing selection for reduced shattering and japonica rice characteristics, confirming a prolonged domestication process for rice.
Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival
Authors: Villa Stephanie R. , Priyadarshini Medha , Fuller Miles H. , Bhardwaj Tanya , Brodsky Michael R. , Angueira Anthony R. , Mosser Rockann E. , Carboneau Bethany A. , Tersey Sarah A. , Mancebo Helena , Gilchrist Annette , Mirmira Raghavendra G. , Gannon Maureen , Layden Brian T.
Published: June 2016

The regulation of pancreatic β cell mass is a critical factor to help maintain normoglycemia during insulin resistance. Nutrient-sensing G protein-coupled receptors (GPCR) contribute to aspects of β cell function, including regulation of β cell mass. Nutrients such as free fatty acids (FFAs) contribute to precise regulation of β cell mass by signaling through cognate GPCRs and considerable evidence suggests that circulating FFAs promote β cell expansion by direct and indirect mechanisms. Free Fatty Acid Receptor 2 (FFA2) is a β cell-expressed GPCR that is activated by short chain fatty acids, particularly acetate. Recent studies of FFA2 suggest that it may act as a regulator of β cell function. Here, we set out to explore what role FFA2 may play in regulation of β cell mass. Interestingly, Ffar2−/− mice exhibit diminished β cell mass at birth and throughout adulthood and increased β cell death at adolescent time points, suggesting a role for FFA2 in establishment and maintenance of β cell mass. Additionally, activation of FFA2 with Gαq/11-biased agonists substantially increased β cell proliferation in in vitro and ex vivo proliferation assays. Collectively, these data suggest that FFA2 may be a novel therapeutic target to stimulate β cell growth and proliferation.
Identification and Characterisation of a pH-stable GFP
Authors: Roberts Tania Michelle , Rudolf Fabian , Meyer Andreas , Pellaux Rene , Whitehead Ellis , Panke Sven , Held Martin
Published: June 2016

Green fluorescent proteins (GFPs) are invaluable tools for modern cell biology. Even though many properties of GFP have been successfully engineered, a GFP retaining brightness at low pH has not emerged. This limits the use of GFP in quantitative studies performed in fluctuating or acidic conditions. We report the engineering and characterisation of tandem dimer GFP (pH-tdGFP), a bright and stable GFP that can be efficiently excited and maintains its fluorescence properties in acidic conditions. Therefore, pH-tdGFP could act as a quantitative marker for cellular processes that occur at low pH, such as endocytosis, autophagy or starvation.
Increased Cumulative Incidence of Dermatomyositis in Ulcerative Colitis: a Nationwide Cohort Study
Authors: Tseng Chia-Chun , Chang Shun-Jen , Liao Wei-Ting , Chan Ya-Ting , Tsai Wen-Chan , Ou Tsan-Teng , Wu Cheng-Chin , Sung Wan-Yu , Hsieh Ming-Chia , Yen Jeng-Hsien
Published: June 2016

On a molecular level, two autoimmune diseases: ulcerative colitis (UC) and dermatomyositis share common genetic determinants. On a clinical level, case reports evidenced the co-occurrence of these two diseases. We therefore hypothesize that UC is potentially associated with increased cumulative incidence of dermatomyositis. The goals of this retrospective cohort study were to evaluate whether UC is associated with increased cumulative incidence of dermatomyositis independent of sex and age. For comparison, we also assessed the cumulative incidence of polymyositis in UC and control subjects. The study enrolled 3,133 UC subjects and 14,726 control subjects. The cumulative incidence of dermatomyositis was significantly higher in UC than that of control subjects (p = 0.026), but the cumulative incidence of polymyositis was comparable between UC and control subjects (p = 0.596). UC was independently associated with the increased incident dermatomyositis (hazard ratio: 6.19, 95% confidence interval = 1.77–21.59, p = 0.004) after adjusting for sex, age and concomitant rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Similar trends of increased dermatomyositis in UC were observed when patients were stratified based on sex and age. In conclusion, our findings suggest that UC is probably associated with increased cumulative incidence of dermatomyositis, independent of sex, age and concomitant autoimmune diseases.
Stability of an adaptive hybrid community
Authors: Mougi A.
Published: June 2016

Contrary to stable natural ecosystems, the classical ecological theory predicts that complex ecological communities are fragile. The adaptive switching of interaction partners was proposed as a key factor to resolve the complexity–stability problem. However, this theory is based on the food webs that comprise predator–prey interactions alone; thus, the manner in which adaptive behavior affects the dynamics of hybrid communities with multiple interaction types remains unclear. Here, using a bipartite community network model with antagonistic and mutualistic interactions, I show that adaptive partner shifts by both antagonists and mutualists are crucial to the persistence of communities. The results show that adaptive behavior destabilizes the dynamics of communities with a single interaction type; however, the hybridity of multiple interaction types within a community greatly improves the stability. Moreover, adaptive behavior does not create a positive complexity–stability relationship in communities with a single interaction type but it does in the hybrid community. The diversity of interaction types is predicted to play a crucial role in community maintenance in an adaptive world.
A Self-Limiting Electro-Ablation Technique for the Top-Down Synthesis of Large-Area Monolayer Flakes of 2D Materials
Authors: Das Saptarshi , Bera Mrinal K. , Tong Sheng , Narayanan Badri , Kamath Ganesh , Mane Anil , Paulikas Arvydas P. , Antonio Mark R. , Sankaranarayanan Subramanian K. R. S. , Roelofs Andreas K.
Published: June 2016

We report the discovery of an electrochemical process that converts two dimensional layered materials of arbitrary thicknesses into monolayers. The lateral dimensions of the monolayers obtained by the process within a few seconds time at room temperature were as large as 0.5 mm. The temporal and spatial dynamics of this physical phenomenon, studied on MoS2 flakes using ex-situ AFM imaging, Raman mapping and photoluminescence measurements trace the origin of monolayer formation to a substrate-assisted self-limiting electrochemical ablation process. Electronic structure and atomistic calculations point to the interplay between three essential factors in the process: (1) strong covalent interaction of monolayer MoS2 with the substrate; (2) electric-field induced differences in Gibbs free energy of exfoliation; (3) dispersion of MoS2 in aqueous solution of hydrogen peroxide. This process was successful in obtaining monolayers of other 2D transition metal dichalcogenides, like WS2 and MoTe2 as well.
Pro-haloacetate Nanoparticles for Efficient Cancer Therapy via Pyruvate Dehydrogenase Kinase Modulation
Authors: Misra Santosh K. , Ye Mao , Ostadhossein Fatemeh , Pan Dipanjan
Published: June 2016

Anticancer agents based on haloacetic acids are developed for inhibition of pyruvate dehydrogenase kinase (PDK), an enzyme responsible for reversing the suppression of mitochondria-dependent apoptosis. Through molecular docking studies mono- and dihaloacetates are identified as potent PDK2 binders and matched their efficiency with dichloroacetic acid. In silico screening directed their conversion to phospholipid prodrugs, which were subsequently self-assembled to pro-haloacetate nanoparticles. Following a thorough physico-chemical characterization, the functional activity of these novel agents was established in wide ranges of human cancer cell lines in vitro and in vivo in rodents. Results indicated that the newly explored PDK modulators can act as efficient agent for cancer regression. A Pyruvate dehydrogenase (PDH) assay mechanistically confirmed that these agents trigger their activity through the mitochondria-dependent apoptosis.
Negative autoregulation of BMP dependent transcription by SIN3B splicing reveals a role for RBM39
Authors: Faherty Noel , Benson Matthew , Sharma Eshita , Lee Angela , Howarth Alison , Lockstone Helen , Ebner Daniel , Bhattacharya Shoumo
Published: June 2016

BMP signalling is negatively autoregulated by several genes including SMAD6, Noggin and Gremlin and autoregulators are possible targets for enhancing BMP signalling in disorders such as fibrosis and pulmonary hypertension. To identify novel negative regulators of BMP signalling, we used siRNA screening in mouse C2C12 cells with a BMP-responsive luciferase reporter. Knockdown of several splicing factors increased BMP4-dependent transcription and target gene expression. Knockdown of RBM39 produced the greatest enhancement in BMP activity. Transcriptome-wide RNA sequencing identified a change in Sin3b exon usage after RBM39 knockdown. SIN3B targets histone deacetylases to chromatin to repress transcription. In mouse, Sin3b produces long and short isoforms, with the short isoform lacking the ability to recruit HDACs. BMP4 induced a shift in SIN3B expression to the long isoform and this change in isoform ratio was prevented by RBM39 knockdown. Knockdown of long isoform SIN3B enhanced BMP4-dependent transcription, whereas knockdown of the short isoform did not. We propose that BMP4-dependent transcription is negatively autoregulated in part by SIN3B alternative splicing and that RBM39 plays a role in this process.
Genome-wide discovery of G-quadruplex forming sequences and their functional relevance in plants
Authors: Garg Rohini , Aggarwal Jyoti , Thakkar Bijal
Published: June 2016

DNA, in addition to the canonical B-form, can acquire a variety of alternate structures, such as G-quadruplexes. These structures have been implicated in several cellular processes in animals. In this study, we identified different types of G-quadruplex forming sequences (GQSes) in 15 sequenced plants and analyzed their distribution in various genomic features, including gene body, coding, intergenic and promoter regions. G2-type GQSes were most abundant in all the plant species analyzed. A strong association of G3-type GQSes with intergenic, promoter and intronic regions was found. However, G2-type GQSes were enriched in genic, CDS, exonic and untranslated regions. Further, we identified GQSes present in the conserved genes among monocots and dicots. The genes involved in development, cell growth and size, transmembrane transporter and regulation of gene expression were found to be significantly enriched. In the promoter region, we detected strong co-occurrence of Telobox, ERF, MYB, RAV1B and E2F motifs with GQSes. Further, we validated the structure formation of several plant GQSes, demonstrated their effect on stalling in-vitro replication and revealed their interaction with plant nuclear proteins. Our data provide insights into the prevalence of GQSes in plants, establish their association with different genomic features and functional relevance.
MtrA of the sodium ion pumping methyltransferase binds cobalamin in a unique mode
Authors: Wagner Tristan , Ermler Ulrich , Shima Seigo
Published: June 2016

In the three domains of life, vitamin B12 (cobalamin) is primarily used in methyltransferase and isomerase reactions. The methyltransferase complex MtrA–H of methanogenic archaea has a key function in energy conservation by catalysing the methyl transfer from methyl-tetrahydromethanopterin to coenzyme M and its coupling with sodium-ion translocation. The cobalamin-binding subunit MtrA is not homologous to any known B12-binding proteins and is proposed as the motor of the sodium-ion pump. Here, we present crystal structures of the soluble domain of the membrane-associated MtrA from Methanocaldococcus jannaschii and the cytoplasmic MtrA homologue/cobalamin complex from Methanothermus fervidus. The MtrA fold corresponds to the Rossmann-type α/β fold, which is also found in many cobalamin-containing proteins. Surprisingly, the cobalamin-binding site of MtrA differed greatly from all the other cobalamin-binding sites. Nevertheless, the hydrogen-bond linkage at the lower axial-ligand site of cobalt was equivalently constructed to that found in other methyltransferases and mutases. A distinct polypeptide segment fixed through the hydrogen-bond linkage in the relaxed Co(III) state might be involved in propagating the energy released upon corrinoid demethylation to the sodium-translocation site by a conformational change.
Porous Tantalum Implant in Treating Osteonecrosis of the Femoral Head: Still a Viable Option?
Authors: Ma Jinhui , Sun Wei , Gao Fuqiang , Guo Wanshou , Wang Yunting , Li Zirong
Published: June 2016

The purpose of this study is to evaluate the survivorship and risk factors for radiographic progression and conversion to total hip arthroplasty (THA) after porous tantalum implant surgery in the treatment of osteonecrosis of the femoral head (ONFH). The study comprised 90 ONFH patients (104 consecutive hips) who were treated with a porous tantalum implant combined with bone grafting between June 2008 and December 2013. The patients were 19–61 years of age (mean age, 38 years). The mean follow-up was 42 months. The outcome measures included Harris hip score (HHS), radiographic outcome measures and survivorship analysis with conversion to THA as the endpoint. The mean postoperative HHS was significantly lower than the mean preoperative HHS (P < 0.001). The Cox proportional hazards model showed that age and Association Research Circulation Osseous (ARCO) stage were independent risk factors for conversion to THA, while age, China-Japan Friendship Hospital (CJFH) type and ARCO stage were independent risk factors for radiological progression. Ultimately, only 52.9% hips survived. Porous tantalum implant surgery combined with bone grafting is not a viable option for treating ONFH, especially in patients >35 years of age with preoperative ARCO stage III and CJFH type L3.
The effects of nitrogen fertilization on N2O emissions from a rubber plantation
Authors: Zhou Wen-Jun , Ji Hong-li , Zhu Jing , Zhang Yi-Ping , Sha Li-Qing , Liu Yun-Tong , Zhang Xiang , Zhao Wei , Dong Yu-xin , Bai Xiao-Long , Lin You-Xin , Zhang Jun-Hui , Zheng Xun-Hua
Published: June 2016

To gain the effects of N fertilizer applications on N2O emissions and local climate change in fertilized rubber (Hevea brasiliensis) plantations in the tropics, we measured N2O fluxes from fertilized (75 kg N ha−1 yr−1) and unfertilized rubber plantations at Xishuangbanna in southwest China over a 2-year period. The N2O emissions from the fertilized and unfertilized plots were 4.0 and 2.5 kg N ha−1 yr−1, respectively and the N2O emission factor was 1.96%. Soil moisture, soil temperature and the area weighted mean ammoniacal nitrogen (NH4+-N) content controlled the variations in N2O flux from the fertilized and unfertilized rubber plantations. NH4+-N did not influence temporal changes in N2O emissions from the trench, slope, or terrace plots, but controlled spatial variations in N2O emissions among the treatments. On a unit area basis, the 100-year carbon dioxide equivalence of the fertilized rubber plantation N2O offsets 5.8% and 31.5% of carbon sink of the rubber plantation and local tropical rainforest, respectively. When entire land area in Xishuangbanna is considered, N2O emissions from fertilized rubber plantations offset 17.1% of the tropical rainforest’s carbon sink. The results show that if tropical rainforests are converted to fertilized rubber plantations, regional N2O emissions may enhance local climate warming.
A novel visualization technique for measuring liquid diffusion coefficient based on asymmetric liquid-core cylindrical lens
Authors: Sun Licun , Pu Xiaoyun
Published: June 2016

A visualization and quantification optical method for measuring binary liquid diffusion coefficient (D) based on an asymmetric liquid-core cylindrical lens (ALCL) is introduced in this paper. Four groups of control experiments were performed to verify the influences of diffusing substance category, concentration and temperature on diffusion process and the measured D values were well consistent with data measured by Holographic interferometry and Taylor dispersion methods. The drifting of the diffusion image recorded by CCD reflects the diffusion rate visually in an easily understandable way. This optical method for measuring D values based on the ALCL is characterized by visual measurement, simplified device and easy operation, which provides a new way for measuring liquid D value visually.
Optimal pathological response indicated better long-term outcome among patients with stage IB2 to IIB cervical cancer submitted to neoadjuvant chemotherapy
Authors: Huang Kecheng , Sun Haiying , Chen Zhilan , Li Xiong , Wang ShaoShuai , Zhao Xiaolin , Tang Fangxu , Jia Yao , Hu Ting , Du Xiaofang , Wang Haoran , Lu Zhiyong , Huang Jia , Gui Juan , Wang Xiaoli , Zhou Shasha , Wang Lin , Zhang Jincheng , Guo Lili , Yang Ru , Shen Jian , Zhang Qinghua , Li Shuang , Wang Shixuan
Published: June 2016

The role of pathological response in long-term outcome is still unclear in cervical cancer patients treated with neoadjuvant chemotherapy (NACT) in China. This study aimed to investigate the effect of optimal pathologic response (OPR) on survival in the patients treated with NACT and radical hysterectomy. First, 853 patients with stage IB2-IIB cervical cancer were included in a retrospective analysis; a Cox proportional hazards model was used to investigate the relationship between pathological response and disease-free survival (DFS). In the retrospective database, 64 (7.5%) patients were found to have achieved an OPR (residual disease <3 mm stromal invasion); in the multivariate Cox model, the risk of death was much greater in the non-OPR group than in the OPR group (HR, 2.61; 95%CI, 1.06 to 6.45; P = 0.037). Next, the role of OPR was also evaluated in a prospective cohort of 603 patients with cervical cancer. In the prospective cohort, 56 (9.3%) patients were found to have achieved an OPR; the log-rank tests showed that the risk of recurrence was higher in the non-OPR patients than in the OPR group (P = 0.05). After combined analysis, OPR in cervical cancer was found to be an independent prognostic factor for DFS.
Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study
Authors: Wu San-Gang , Xie Wei-Hao , Zhang Zhao-Qiang , Sun Jia-Yuan , Li Feng-Yan , Lin Huan-Xin , Yong Bao  , He Zhen-Yu
Published: June 2016

This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5% and 3.4% in primary surgery, RT only, surgery plus RT and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5% and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC.
Extracellular vimentin is a novel axonal growth facilitator for functional recovery in spinal cord-injured mice
Authors: Shigyo Michiko , Tohda Chihiro
Published: June 2016

Vimentin, an intermediate filament protein, is an intracellular protein that is involved in various cellular processes. Several groups have recently reported that vimentin also appears in the extracellular space and shows novel protein activity. We previously reported that denosomin improved motor dysfunction in mice with a contusive spinal cord injury (SCI). At the injured area, astrocytes expressing and secreting vimentin were specifically increased and axonal growth occurred in a vimentin-dependent manner in denosomin-treated mice. However, the axonal growth that was induced by extracellular vimentin was only investigated in vitro in the previous study. Here, we sought to clarify whether increased extracellular vimentin can promote the axonal extension related to motor improvement after SCI in vivo. Extracellular vimentin treatment in SCI mice significantly ameliorated motor dysfunction. In vimentin-treated mice, 5-HT-positive axons increased significantly at the rostral and central areas of the lesion and the total axonal densities increased in the central and caudal parts of the lesioned area. This finding suggests that increased axonal density may contribute to motor improvement in vimentin-treated mice. Thus, our in vivo data indicate that extracellular vimentin may be a novel neurotrophic factor that enhances axonal growth activity and motor function recovery after SCI.