bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of detected depression and undetected depressive symptoms with long-term mortality in a cohort of institutionalised older people
Authors: Damián J. , Pastor-Barriuso R. , Valderrama-Gama E. , de Pedro-Cuesta J. 
Published: January 2016

Background.Studies on depression and mortality in nursing homes have shown inconclusive findings, and none has studied the role of detection. We sought to measure the association of depression with long-term all-cause mortality in institutionalised older people and evaluate a potential modification in the association by its detection status.Methods.We selected a stratified cluster sample of 591 residents aged 75 years or older (mean age 84.5 years) living in residential and nursing homes of Madrid, Spain, who were free of severe cognitive impairment at the 1998–1999 baseline interview. Mortality was ascertained until age 105 years or September 2013 (median/maximum follow-up 4.8/15.2 years) through linkage to the Spanish National Death Index. Detected depression was defined at baseline as a physician's diagnosis or antidepressant use, undetected depression as significant depressive symptoms (score of 4 or higher on the ten-item version of the Geriatric Depression Scale) without documented diagnosis or treatment, and no depression as the absence of diagnosis, treatment, and symptoms. Constant and age-dependent hazard ratios for mortality comparing detected and undetected depression with no depression were estimated using Cox models, and absolute years of life gained and lost using Weibull models.Results.The baseline prevalences of detected and undetected depression were 25.9 and 18.8%, respectively. A total of 499 participants died during 3575 person-years of follow-up. In models adjusted for age, sex, type of facility, number of chronic conditions, and functional dependency, overall depression was not associated with long-term all-cause mortality (hazard ratio 0.87, 95% confidence interval (CI): 0.70–1.08). However, compared with no depression, detected depression showed lower mortality (hazard ratio 0.63, 95% CI: 0.46–0.86), while undetected depression registered higher, not statistically significant, mortality (hazard ratio 1.35, 95% CI: 0.98–1.86). The median life expectancy increased by 1.8 years (95% CI: −3.1 to 6.7 years) in residents with detected depression and decreased by 6.3 years (95% CI: 2.6–10.1 years) in those undetected. Results were more marked in women than men and they were robust to the exclusion of antidepressants from the definition of depression and also to the use of a stricter cut-off for the presence of depressive symptoms.Conclusions.The long-term mortality risk associated with depression in nursing homes depends on its detection status, with better prognosis in residents with detected depression and worse in those undetected. The absolute impact of undetected depressive symptoms in terms of life expectancy can be prominent.
Standards for Experimental Research: Encouraging a Better Understanding of Experimental Methods
Authors: Mutz Diana C. , Pemantle Robin 
Published: January 2016

AbstractIn this essay, we closely examine three aspects of the Reporting Guidelines for this journal, as described by Gerber et al. (2014,Journal of Experimental Political Science1(1): 81–98) in the inaugural issue of the Journal of Experimental Political Science. These include manipulation checks and when the reporting of response rates is appropriate. The third, most critical, issue concerns the committee's recommendations for detecting errors in randomization. This is an area where there is evidence of widespread confusion about experimental methods throughout our major journals. Given that a goal of the Journal of Experimental Political Science is promoting best practices and a better understanding of experimental methods across the discipline, we recommend changes to the Standards that will allow the journal to play a leading role in correcting these misunderstandings.
Temporal activation of XRCC1-mediated DNA repair is essential for muscle differentiation
Authors: Al-Khalaf Mohammad H , Blake Leanne E , Larsen Brian D , Bell Ryan A , Brunette Steve , Parks Robin J , Rudnicki Michael A , McKinnon Peter J , Jeffrey Dilworth F , Megeney Lynn A 
Published: January 2016

AbstractTransient DNA strand break formation has been identified as an effective means to enhance gene expression in living cells. In the muscle lineage, cell differentiation is contingent upon the induction of caspase-mediated DNA strand breaks, which act to establish the terminal gene expression program. This coordinated DNA nicking is rapidly resolved, suggesting that myoblasts may deploy DNA repair machinery to stabilize the genome and entrench the differentiated phenotype. Here, we identify the base excision repair pathway component XRCC1 as an indispensable mediator of muscle differentiation. Caspase-triggered XRCC1 repair foci form rapidly within differentiating myonuclei, and then dissipate as the maturation program proceeds. Skeletal myoblast deletion of Xrcc1 does not have an impact on cell growth, yet leads to perinatal lethality, with sustained DNA damage and impaired myofiber development. Together, these results demonstrate that XRCC1 manages a temporally responsive DNA repair process to advance the muscle differentiation program.
Novel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion
Authors: Cimino Irene , Casoni Filippo , Liu Xinhuai , Messina Andrea , Parkash Jyoti , Jamin Soazik P. , Catteau-Jonard Sophie , Collier Francis , Baroncini Marc , Dewailly Didier , Pigny Pascal , Prescott Mel , Campbell Rebecca , Herbison Allan E. , Prevot Vincent , Giacobini Paolo 
Published: January 2016

AbstractAnti-Müllerian hormone (AMH) plays crucial roles in sexual differentiation and gonadal functions. However, the possible extragonadal effects of AMH on the hypothalamic–pituitary–gonadal axis remain unexplored. Here we demonstrate that a significant subset of GnRH neurons both in mice and humans express the AMH receptor, and that AMH potently activates the GnRH neuron firing in mice. Combiningin vivoandin vitroexperiments, we show that AMH increases GnRH-dependent LH pulsatility and secretion, supporting a central action of AMH on GnRH neurons. Increased LH pulsatility is an important pathophysiological feature in many cases of polycystic ovary syndrome (PCOS), the most common cause of female infertility, in which circulating AMH levels are also often elevated. However, the origin of this dysregulation remains unknown. Our findings raise the intriguing hypothesis that AMH-dependent regulation of GnRH release could be involved in the pathophysiology of fertility and could hold therapeutic potential for treating PCOS.
Spatio-temporal propagation of cascading overload failures in spatially embedded networks
Authors: Zhao Jichang , Li Daqing , Sanhedrai Hillel , Cohen Reuven , Havlin Shlomo 
Published: January 2016

AbstractDifferent from the direct contact in epidemics spread, overload failures propagate through hidden functional dependencies. Many studies focused on the critical conditions and catastrophic consequences of cascading failures. However, to understand the network vulnerability and mitigate the cascading overload failures, the knowledge of how the failures propagate in time and space is essential but still missing. Here we study the spatio-temporal propagation behaviour of cascading overload failures analytically and numerically on spatially embedded networks. The cascading overload failures are found to spread radially from the centre of the initial failure with an approximately constant velocity. The propagation velocity decreases with increasing tolerance, and can be well predicted by our theoretical framework with one single correction for all the tolerance values. This propagation velocity is found similar in various model networks and real network structures. Our findings may help to predict the dynamics of cascading overload failures in realistic systems.
Clouds enhance Greenland ice sheet meltwater runoff
Authors: Van Tricht K. , Lhermitte S. , Lenaerts J. T. M. , Gorodetskaya I. V. , L’Ecuyer T. S. , Noël B. , van den Broeke M. R. , Turner D. D. , van Lipzig N. P. M. 
Published: January 2016

AbstractThe Greenland ice sheet has become one of the main contributors to global sea level rise, predominantly through increased meltwater runoff. The main drivers of Greenland ice sheet runoff, however, remain poorly understood. Here we show that clouds enhance meltwater runoff by about one-third relative to clear skies, using a unique combination of active satellite observations, climate model data and snow model simulations. This impact results from a cloud radiative effect of 29.5 (±5.2) W m−2. Contrary to conventional wisdom, however, the Greenland ice sheet responds to this energy through a new pathway by which clouds reduce meltwater refreezing as opposed to increasing surface melt directly, thereby accelerating bare-ice exposure and enhancing meltwater runoff. The high sensitivity of the Greenland ice sheet to both ice-only and liquid-bearing clouds highlights the need for accurate cloud representations in climate models, to better predict future contributions of the Greenland ice sheet to global sea level rise.
Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2–JNK signalling in breast cancer
Authors: Puvirajesinghe Tania M. , Bertucci François , Jain Ashish , Scerbo Pierluigi , Belotti Edwige , Audebert Stéphane , Sebbagh Michael , Lopez Marc , Brech Andreas , Finetti Pascal , Charafe-Jauffret Emmanuelle , Chaffanet Max , Castellano Rémy , Restouin Audrey , Marchetto Sylvie , Collette Yves , Gonçalvès Anthony , Macara Ian , Birnbaum Daniel , Kodjabachian Laurent , Johansen Terje , Borg Jean-Paul 
Published: January 2016

AbstractThe non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway plays a crucial role in embryonic development. Recent work has linked defects of this pathway to breast cancer aggressiveness and proposed Wnt/PCP signalling as a therapeutic target. Here we show that the archetypal Wnt/PCP protein VANGL2 is overexpressed in basal breast cancers, associated with poor prognosis and implicated in tumour growth. We identify the scaffold p62/SQSTM1 protein as a novel VANGL2-binding partner and show its key role in an evolutionarily conserved VANGL2–p62/SQSTM1–JNK pathway. This proliferative signalling cascade is upregulated in breast cancer patients with shorter survival and can be inactivated in patient-derived xenograft cells by inhibition of the JNK pathway or by disruption of the VANGL2–p62/SQSTM1 interaction. VANGL2–JNK signalling is thus a potential target for breast cancer therapy.
Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus
Authors: Park Raehee , Moon Uk Yeol , Park Jun Young , Hughes Lucinda J. , Johnson Randy L. , Cho Seo-Hee , Kim Seonhee 
Published: January 2016

AbstractTimely generation and normal maturation of ependymal cells along the aqueduct are critical for preventing physical blockage between the third and fourth ventricles and the development of fetal non-communicating hydrocephalus. Our study identifies Yap, the downstream effector of the evolutionarily conserved Hippo pathway, as a central regulator for generating developmentally controlled ependymal cells along the ventricular lining of the aqueduct. Yap function is necessary for proper proliferation of progenitors and apical attachment of ependymal precursor cells. Importantly, an injury signal initiated by lysophosphatidic acid (LPA), an upstream regulator of Yap that can cause fetal haemorrhagic hydrocephalus, deregulates Yap in the developing aqueduct. LPA exposure leads to the loss of N-cadherin concentrations at the apical endfeet, which can be partially restored by forced Yap expression and more efficiently by phosphomimetic Yap. These results reveal a novel function of Yap in retaining tissue junctions during normal development and after fetal brain injury.
A draft map of the mouse pluripotent stem cell spatial proteome
Authors: Christoforou Andy , Mulvey Claire M. , Breckels Lisa M. , Geladaki Aikaterini , Hurrell Tracey , Hayward Penelope C. , Naake Thomas , Gatto Laurent , Viner Rosa , Arias Alfonso Martinez , Lilley Kathryn S. 
Published: January 2016

AbstractKnowledge of the subcellular distribution of proteins is vital for understanding cellular mechanisms. Capturing the subcellular proteome in a single experiment has proven challenging, with studies focusing on specific compartments or assigning proteins to subcellular niches with low resolution and/or accuracy. Here we introduce hyperLOPIT, a method that couples extensive fractionation, quantitative high-resolution accurate mass spectrometry with multivariate data analysis. We apply hyperLOPIT to a pluripotent stem cell population whose subcellular proteome has not been extensively studied. We provide localization data on over 5,000 proteins with unprecedented spatial resolution to reveal the organization of organelles, sub-organellar compartments, protein complexes, functional networks and steady-state dynamics of proteins and unexpected subcellular locations. The method paves the way for characterizing the impact of post-transcriptional and post-translational modification on protein location and studies involving proteome-level locational changes on cellular perturbation. An interactive open-source resource is presented that enables exploration of these data.
The Type II Secreted Lipase/Esterase LesA is a Key Virulence Factor Required for Xylella fastidiosa Pathogenesis in Grapevines
Authors: Nascimento Rafael , Gouran Hossein , Chakraborty Sandeep , Gillespie Hyrum W. , Almeida-Souza Hebréia O. , Tu Aye , Rao Basuthkar J. , Feldstein Paul A. , Bruening George , Goulart Luiz R. , Dandekar Abhaya M. 
Published: January 2016

AbstractPierce’s disease (PD) of grapevines is caused by Xylella fastidiosa (Xf), a xylem-limited gamma-proteobacterium that is responsible for several economically important crop diseases. The occlusion of xylem elements and interference with water transport by Xf and its associated biofilm have been posited as the main cause of PD symptom development; however, Xf virulence mechanisms have not been described. Analysis of the Xf secretome revealed a putative lipase/esterase (LesA) that was abundantly secreted in bacterial culture supernatant and was characterized as a protein ortholog of the cell wall-degrading enzyme LipA of Xanthomonas strains. LesA was secreted by Xf and associated with a biofilm filamentous network. Additional proteomic analysis revealed its abundant presence in outer membrane vesicles (OMVs). Accumulation of LesA in leaf regions associated positively with PD symptoms and inversely with bacterial titer. The lipase/esterase also elicited a hypersensitive response in grapevine. Xf lesA mutants were significantly deficient for virulence when mechanically inoculated into grapevines. We propose that Xf pathogenesis is caused by LesA secretion mediated by OMV cargos and that its release and accumulation in leaf margins leads to early stages of observed PD symptoms.
Impact of the 2010 Deepwater Horizon oil spill on population size and genetic structure of horse flies in Louisiana marshes
Authors: Husseneder Claudia , Donaldson Jennifer R. , Foil Lane D. 
Published: January 2016

AbstractThe greenhead horse fly, Tabanus nigrovittatus Macquart, is frequently found in coastal marshes of the Eastern United States. The greenhead horse fly larvae are top predators in the marsh and thus vulnerable to changes in the environment and the adults potentially are attracted to polarized surfaces like oil. Therefore, horse fly populations could serve as bioindicators of marsh health and toxic effects of oil intrusion. In this study, we describe the impact of the April 2010 Deep Water Horizon oil spill in the Gulf of Mexico on tabanid population abundance and genetics as well as mating structure. Horse fly populations were sampled biweekly from oiled and unaffected locations immediately after the oil spill in June 2010 until October 2011. Horse fly abundance estimates showed severe crashes of tabanid populations in oiled areas. Microsatellite genotyping of six pristine and seven oiled populations at ten polymorphic loci detected genetic bottlenecks in six of the oiled populations in association with fewer breeding parents, reduced effective population size, lower number of family clusters and fewer migrants among populations. This is the first study assessing the impact of oil contamination at the level of a top arthropod predator of the invertebrate community in salt marshes.
Conformation-controlled binding kinetics of antibodies
Authors: Galanti Marta , Fanelli Duccio , Piazza Francesco 
Published: January 2016

AbstractAntibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.
Material properties of evolutionary diverse spider silks described by variation in a single structural parameter
Authors: Madurga Rodrigo , Plaza Gustavo R. , Blackledge Todd A. , Guinea Gustavo.V. , Elices Manuel , Pérez-Rigueiro José 
Published: January 2016

AbstractSpider major ampullate gland silks (MAS) vary greatly in material properties among species but, this variation is shown here to be confined to evolutionary shifts along a single universal performance trajectory. This reveals an underlying design principle that is maintained across large changes in both spider ecology and silk chemistry. Persistence of this design principle becomes apparent after the material properties are defined relative to the true alignment parameter, which describes the orientation and stretching of the protein chains in the silk fiber. Our results show that the mechanical behavior of all Entelegynae major ampullate silk fibers, under any conditions, are described by this single parameter that connects the sequential action of three deformation micromechanisms during stretching: stressing of protein-protein hydrogen bonds, rotation of the β-nanocrystals and growth of the ordered fraction. Conservation of these traits for over 230 million years is an indication of the optimal design of the material and gives valuable clues for the production of biomimetic counterparts based on major ampullate spider silk.
Geometrical Patterning of Super-Hydrophobic Biosensing Transistors Enables Space and Time Resolved Analysis of Biological Mixtures
Authors: Gentile Francesco , Ferrara Lorenzo , Villani Marco , Bettelli Manuele , Iannotta Salvatore , Zappettini Andrea , Cesarelli Mario , Di Fabrizio Enzo , Coppedè Nicola 
Published: January 2016

AbstractPEDOT:PSS is a conductive polymer that can be integrated into last generation Organic Electrochemical Transistor (OECT) devices for biological inspection, identification and analysis. While a variety of reports in literature demonstrated the chemical and biological sensitivity of these devices, still their ability in resolving complex mixtures remains controversial. Similar OECT devices display good time dynamics behavior but lack spatial resolution. In this work, we integrated PEDOT:PSS with patterns of super-hydrophobic pillars in which a finite number of those pillars is independently controlled for site-selective measurement of a solution. We obtained a multifunctional, hierarchical OECT device that bridges the micro- to the nano-scales for specific, combined time and space resolved analysis of the sample. Due to super-hydrophobic surface properties, the biological species in the drop are driven by convection, diffusion and the externally applied electric field: the balance/unbalance between these forces will cause the molecules to be transported differently within its volume depending on particle size thus realizing a size-selective separation. Within this framework, the separation and identification of two different molecules, namely Cetyl Trimethyl Ammonium Bromid (CTAB) and adrenaline, in a biological mixture have been demonstrated, showing that geometrical control at the micro-nano scale impart unprecedented selectivity to the devices.
Direct observation of deterministic domain wall trajectory in magnetic network structures
Authors: Sethi P. , Murapaka C. , Goolaup S. , Chen Y. J. , Leong S. H. , Lew W. S. 
Published: January 2016

AbstractControlling the domain wall (DW) trajectory in magnetic network structures is crucial for spin-based device related applications. The understanding of DW dynamics in network structures is also important for study of fundamental properties like observation of magnetic monopoles at room temperature in artificial spin ice lattice. The trajectory of DW in magnetic network structures has been shown to be chirality dependent. However, the DW chirality periodically oscillates as it propagates a distance longer than its fidelity length due to Walker breakdown phenomenon. This leads to a stochastic behavior in the DW propagation through the network structure. In this study, we show that the DW trajectory can be deterministically controlled in the magnetic network structures irrespective of its chirality by introducing a potential barrier. The DW propagation in the network structure is governed by the geometrically induced potential barrier and pinning strength against the propagation. This technique can be extended for controlling the trajectory of magnetic charge carriers in an artificial spin ice lattice.
Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response
Authors: Li Tiejun , Cheng Hao , Yuan Hong , Xu Qiming , Shu Chang , Zhang Yuefan , Xu Pengbiao , Tan Jason , Rui Yaocheng , Li Pingwei , Tan Xiangshi 
Published: January 2016

AbstractImmunotherapy is one of the key strategies for cancer treatment. The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays a pivotal role in antiviral defense. We report that the STING activator cGAMP possesses significant antitumor activity in mice by triggering the STING-dependent pathway directly. cGAMP enhances innate immune responses by inducing production of cytokines such as interferon-β, interferon-γ and stimulating dendritic cells activation, which induces the cross-priming of CD8+ T cells. The antitumor mechanism of cGAMP was verified by STING and IRF3, which were up-regulated upon cGAMP treatment. STING-deficiency dramatically reduced the antitumor effect of cGAMP. Furthermore, cGAMP improved the antitumor activity of 5-FU and clearly reduced the toxicity of 5-FU. These results demonstrated that cGAMP is a novel antitumor agent and has potential applications in cancer immunotherapy.