bluuebunny/crossref_metadata_2025_split huggingface dataset:
Energetics, kinetics, and pathway of SNARE folding and assembly revealed by optical tweezers
Authors: Zhang Yongli 
Published: January 2017

AbstractSoluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium‐triggered fusion of neurotransmitter‐containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t‐ and v‐SNAREs) join together to assemble into a parallel four‐helix bundle, releasing the energy to overcome the energy barrier for fusion. A long‐standing hypothesis suggests that SNAREs act like a zipper to draw the two membranes into proximity and thereby force them to fuse. However, a quantitative test of this SNARE zippering hypothesis was hindered by difficulties to determine the energetics and kinetics of SNARE assembly and to identify the relevant folding intermediates. Here, we first review different approaches that have been applied to study SNARE assembly and then focus on high‐resolution optical tweezers. We summarize the folding energies, kinetics, and pathways of both wild‐type and mutant SNARE complexes derived from this new approach. These results show that synaptic SNAREs assemble in four distinct stages with different functions: slow N‐terminal domain association initiates SNARE assembly; a middle domain suspends and controls SNARE assembly; and rapid sequential zippering of the C‐terminal domain and the linker domain directly drive membrane fusion. In addition, the kinetics and pathway of the stagewise assembly are shared by other SNARE complexes. These measurements prove the SNARE zippering hypothesis and suggest new mechanisms for SNARE assembly regulated by other proteins.
Force generation by titin folding
Authors: Mártonfalvi Zsolt , Bianco Pasquale , Naftz Katalin , Ferenczy György G. , Kellermayer Miklós 
Published: January 2017

AbstractTitin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force‐dependent folding mechanisms, here we manipulated skeletal‐muscle titin molecules with high‐resolution optical tweezers. In force‐clamp mode, after quenching the force (<10 pN), extension fluctuated without resolvable discrete events. In position‐clamp experiments, the time‐dependent force trace contained rapid fluctuations and a gradual increase of average force, indicating that titin can develop force via dynamic transitions between its structural states en route to the native conformation. In 4 M urea, which destabilizes H‐bonds hence the consolidated native domain structure, the net force increase disappeared but the fluctuations persisted. Thus, whereas net force generation is caused by the ensemble folding of the elastically‐coupled domains, force fluctuations arise due to a dynamic equilibrium between unfolded and molten‐globule states. Monte–Carlo simulations incorporating a compact molten‐globule intermediate in the folding landscape recovered all features of our nanomechanics results. The ensemble molten‐globule dynamics delivers significant added contractility that may assist sarcomere mechanics, and it may reduce the dissipative energy loss associated with titin unfolding/refolding during muscle contraction/relaxation cycles.
Differential dehydration effects on globular proteins and intrinsically disordered proteins during film formation
Authors: Yoneda Juliana Sakamoto , Miles Andew J. , Araujo Ana Paula Ulian , Wallace B. A. 
Published: January 2017

AbstractGlobular proteins composed of different secondary structures and fold types were examined by synchrotron radiation circular dichroism spectroscopy to determine the effects of dehydration on their secondary structures. They exhibited only minor changes upon removal of bulk water during film formation, contrary to previously reported studies of proteins dehydrated by lyophilization (where substantial loss of helical structure and gain in sheet structure was detected). This near lack of conformational change observed for globular proteins contrasts with intrinsically disordered proteins (IDPs) dried in the same manner: the IDPs, which have almost completely unordered structures in solution, exhibited increased amounts of regular (mostly helical) secondary structures when dehydrated, suggesting formation of new intra‐protein hydrogen bonds replacing solvent‐protein hydrogen bonds, in a process which may mimic interactions that occur when IDPs bind to partner molecules. This study has thus shown that the secondary structures of globular and intrinsically disordered proteins behave very differently upon dehydration, and that films are a potentially useful format for examining dehydrated soluble proteins and assessing IDPs structures.
Molecular mechanisms underlying deoxy‐ADP.Pi activation of pre‐powerstroke myosin
Authors: Nowakowski Sarah G. , Regnier Michael , Daggett Valerie 
Published: January 2017

AbstractMyosin activation is a viable approach to treat systolic heart failure. We previously demonstrated that striated muscle myosin is a promiscuous ATPase that can use most nucleoside triphosphates as energy substrates for contraction. When 2‐deoxy ATP (dATP) is used, it acts as a myosin activator, enhancing cross‐bridge binding and cycling. In vivo, we have demonstrated that elevated dATP levels increase basal cardiac function and rescues function of infarcted rodent and pig hearts. Here we investigate the molecular mechanism underlying this physiological effect. We show with molecular dynamics simulations that the binding of dADP.Pi (dATP hydrolysis products) to myosin alters the structure and dynamics of the nucleotide binding pocket, myosin cleft conformation, and actin binding sites, which collectively yield a myosin conformation that we predict favors weak, electrostatic binding to actin. In vitro motility assays at high ionic strength were conducted to test this prediction and we found that dATP increased motility. These results highlight alterations to myosin that enhance cross‐bridge formation and reveal a potential mechanism that may underlie dATP‐induced improvements in cardiac function.
Context characterization of amino acid homorepeats using evolution, position, and order
Authors: Mier Pablo , Alanis‐Lobato Gregorio , Andrade‐Navarro Miguel A. 
Published: January 2017

ABSTRACTAmino acid repeats, or homorepeats, are low complexity protein motifs consisting of tandem repetitions of a single amino acid. Their presence and relative number vary in different proteomes, and some studies have tried to address this variation, proteome by proteome. In this work, we present a full characterization of amino acid homorepeats across evolution. We studied the presence and differential usage of each possible homorepeat in proteomes from various taxonomic groups, using clusters of very similar proteins to eliminate redundancy. The position of each amino acid repeat within proteins, and the order of co‐occurring amino acid repeats were also addressed. As a result, we present evidence about the unevenly evolution of homorepeats, as well as the functional implications of their relative position in proteins. We discuss some of these cases in their taxonomic context. Collectively, our results show evolutionary and positional signals that suggest that homorepeats have biological function, likely creating unspecific protein interactions or modulating specific interactions in a context dependent manner. In conclusion, our work supports the functional importance of homorepeats and establishes a basis for the study of other low complexity repeats. Proteins 2017; 85:709–719. © 2016 Wiley Periodicals, Inc.
Reversing the Landauer's erasure: Single‐electron Maxwell's demon operating at the limit of thermodynamic efficiency
Authors: Averin Dmitri V. , Pekola Jukka P. 
Published: January 2017

AbstractAccording to Landauer's principle, erasure of information is the only part of a computation process that unavoidably involves energy dissipation. If done reversibly, such an erasure generates the minimal heat of per erased bit of information. The goal of this work is to discuss the actual reversal of the optimal erasure which can serve as the basis for the Maxwell's demon operating with ultimate thermodynamic efficiency as dictated by the second law of thermodynamics. The demon extracts of heat from an equilibrium reservoir at temperature T per one bit of information obtained about the measured system used by the demon. We have analyzed this Maxwell's demon in the situation when it uses a general quantum system with a discrete spectrum of energy levels as its working body. In the case of the effectively two‐level system, which has been realized experimentally based on tunneling of individual electron in a single‐electron box , we also studied and minimized corrections to the ideal reversible operation of the demon. These corrections include, in particular, the non‐adiabatic terms which are described by a version of the classical fluctuation–dissipation theorem. The overall reversibility of the Maxwell's demon requires, beside the reversibility of the intrinsic working body dynamics, the reversibility of the measurement, and feedback processes. The single‐electron demon can, in principle, be made fully reversible by developing a thermodynamically reversible single‐electron charge detector for measurements of the individual charge states of the single‐electron box.
Macro‐invertebrate Community Response to Multi‐annual Hydrological Indicators
Authors: Visser A. , Beevers L. , Patidar S. 
Published: January 2017

AbstractFlow is widely considered one of the primary drivers of instream ecological response. Increasingly, hydroecological models form the basis of integrated and sustainable approaches to river management, linking flow to ecological response. In doing so, the most ecologically relevant hydrological variables should be selected. Some studies have observed a delayed macro‐invertebrate (ecological) response to these variables (i.e. a cumulative inter‐annual effect, referred to as multi‐annual) in groundwater‐fed rivers. To date, only limited research has been performed investigating this phenomenon. This paper examines the ecological response to multi‐annual flow indicators for a groundwater‐fed river. Relationships between instream ecology and flow were investigated by means of a novel methodological framework developed by integrating statistical data analysis and modelling techniques, such as principal component analysis and multistep regression approaches. Results demonstrated a strong multi‐annual multi‐seasonal effect. Inclusion of additional antecedent flows indicators appears to enhance overall model performance (in some cases, goodness of fit statistics such as the adjusted R‐squared value exceeded 0.6). These results strongly suggest that, in order to understand potential changes to instream ecology arising from changing flow regimes, multi‐annual and multi‐seasonal relationships should be considered in hydroecological modelling. © 2017 The Authors River Research and Applications Published by John Wiley & Sons Ltd.
Core‐Shell Ag@TiO2 Nanocomposites for Low‐Power Blue Laser Enhanced Copper(I) Catalyzed Ullmann Coupling
Authors: Forato Florian , Talebzadeh Somayeh , Bujoli Bruno , Queffélec Clémence , Trammell Scott A. , Knight D. Andrew 
Published: January 2017

AbstractSilver nanoparticles, stabilized by a titanium dioxide shell, have been prepared and further functionalized using a bidentate 2,2′‐bipyridine ligand end‐capped with a phosphonic acid anchoring group. Then, complexation of the 2,2′‐bipyridine donor ligand with a copper(I) salt was performed. The resulting nanocomposite, while irradiating the Ag plasmon band with a blue laser at 488 nm, was found to be active for the homocoupling Ullmann reaction of iodobenzene and increased yield of 55% vs <1% for the dark reaction was observed.
Concise Review: Induced Pluripotent Stem Cell Research in the Era of Precision Medicine
Authors: Hamazaki Takashi , El Rouby Nihal , Fredette Natalie C. , Santostefano Katherine E. , Terada Naohiro 
Published: January 2017

Abstract
Recent advances in DNA sequencing technologies are revealing how human genetic variations associate with differential health risks, disease susceptibilities, and drug responses. Such information is now expected to help evaluate individual health risks, design personalized health plans and treat patients with precision. It is still challenging, however, to understand how such genetic variations cause the phenotypic alterations in pathobiologies and treatment response. Human induced pluripotent stem cell (iPSC) technologies are emerging as a promising strategy to fill the knowledge gaps between genetic association studies and underlying molecular mechanisms. Breakthroughs in genome editing technologies and continuous improvement in iPSC differentiation techniques are particularly making this research direction more realistic and practical. Pioneering studies have shown that iPSCs derived from a variety of monogenic diseases can faithfully recapitulate disease phenotypes in vitro when differentiated into disease-relevant cell types. It has been shown possible to partially recapitulate disease phenotypes, even with late onset and polygenic diseases. More recently, iPSCs have been shown to validate effects of disease and treatment-related single nucleotide polymorphisms identified through genome wide association analysis. In this review, we will discuss how iPSC research will further contribute to human health in the coming era of precision medicine.
Stromal Cells Act as Guardians for Endothelial Progenitors by Reducing Their Immunogenicity After Co-Transplantation
Authors: Souidi Naima , Stolk Meaghan , Rudeck Juliane , Strunk Dirk , Schallmoser Katharina , Volk Hans-Dieter , Seifert Martina 
Published: January 2017

Abstract
Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal stem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo. Immunodeficient mice received subcutaneous grafts containing human ECFCs alone, or pairs of human ECFCs/MSCs from the same umbilical cord (UC) to study vasculogenesis in the presence of human leukocyte antigen (HLA)-mismatched human peripheral blood mononuclear cells (PBMCs). In vitro, cell surface marker changes due to interferon gamma (IFNγ) stimulation during ECFC/MSC coculture were determined and further effects on allostimulated T cell proliferation and cytotoxic lysis were measured. IFNγ-induced HLA-DR expression on ECFCs and MSCs, but both cell types had significantly less HLA-DR in cocultures. ECFC-induced T cell proliferation was abolished after MSC coculture as a result of HLA-DR downregulation and indolamin-2,3-dioxygenase activation. Additionally, allospecific CD8+ T cell-mediated lysis of ECFCs was reduced in cocultures. ECFC/MSC coapplication in immunodeficient mice not only promoted the generation of improved blood vessel architecture after 6 weeks, but also reduced intragraft immune cell infiltration and endothelial HLA-DR expression following PBMC reconstitution. Crosstalk between UC-derived ECFCs and MSCs after combined transplantation can lower the risk of ECFC rejection, thus enabling their coapplication for therapeutic vasculogenesis.
Functional responses can unify invasion ecology
Authors: Dick Jaimie T. A. , Alexander Mhairi E. , Ricciardi Anthony , Laverty Ciaran , Downey Paul O. , Xu Meng , Jeschke Jonathan M. , Saul Wolf-Christian , Hill Matthew P. , Wasserman Ryan , Barrios-O’Neill Daniel , Weyl Olaf L. F. , Shaw Richard H. 
Published: January 2017

AbstractWe contend that invasion ecology requires a universal, measurable trait of species and their interactions with resources that predicts key elements of invasibility and ecological impact; here, we advocate that functional responses can help achieve this across taxonomic and trophic groups, among habitats and contexts, and can hence help unify disparate research interests in invasion ecology.
Intelligence and neuroticism in relation to depression and psychological distress: Evidence from two large population cohorts
Authors: Navrady L.B. , Ritchie S.J. , Chan S.W.Y. , Kerr D.M. , Adams M.J. , Hawkins E.H. , Porteous D. , Deary I.J. , Gale C.R. , Batty G.D. , McIntosh A.M. 
Published: January 2017

AbstractBackground:Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-relationships of neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined.Methods:Associations and interactions between neuroticism and general intelligence (g) on MDD, self-reported depression, and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, n = 19,200) and UK Biobank (n = 90,529). The Eysenck Personality Scale Short Form-Revised measured neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS.Results:Neuroticism was strongly associated with increased risk for depression and higher psychological distress in both samples. Although intelligence conferred no consistent independent effects on depression, it did increase the risk for depression across samples once neuroticism was adjusted for. Results suggest that higher intelligence may ameliorate the association between neuroticism and self-reported depression although no significant interaction was found for clinical MDD. Intelligence was inversely associated with psychological distress across cohorts. A small interaction was found across samples such that lower psychological distress associates with higher intelligence and lower neuroticism, although effect sizes were small.Conclusions:From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of neuroticism on psychological distress. Intelligence does not confer protection against diagnosis of depression in those high in neuroticism.
Authoritarian leadership and employee silence in China
Authors: Duan Jinyun , Bao Chanzi , Huang Caiyun , Brinsfield Chad Thomas 
Published: January 2017

AbstractWe examine the relationship between authoritarian leadership and employee silence behaviour with 324 employees in 16 state-owned manufacturing enterprises in China. We draw from theories of motivation and person–environment fit to explain the mediating roles of psychological safety and organization-based self-esteem, and the moderating effects of power distance orientation. Regression analyses show that authoritarian leadership has a positive relationship with employee silence behaviour. Mediation analyses show that both psychological safety and organization-based self-esteem partially mediate the relationship between authoritarian leadership and employee silence. Moderation analysis revealed that the direct relationship between authoritarian leadership and employee silence behaviour is stronger for employees with high (as opposed to low) power distance orientation. Additionally, moderated-mediation analyses show that the mediating effects of both psychological safety and organization-based self-esteem are stronger for employees with low (as opposed to high) power distance orientation. Implications for theory and practice are discussed.
Vitamin A deficiency suppresses fish immune function with differences in different intestinal segments: the role of transcriptional factorNF-κBandp38 mitogen-activated protein kinasesignalling pathways
Authors: Zhang Li , Feng Lin , Jiang Wei-Dan , Liu Yang , Wu Pei , Kuang Sheng-Yao , Tang Ling , Tang Wu-Neng , Zhang Yong-An , Zhou Xiao-Qiu 
Published: January 2017

AbstractThe present study investigated the effects of dietary vitamin A on immune function in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of young grass carp (Ctenopharyngodon idella). Fish were fed graded levels of dietary vitamin A for 10 weeks, and then a challenge test using an injection ofAeromonas hydrophilawas conducted for 14 d. The results showed that, compared with the optimum vitamin A level, vitamin A deficiency significantly decreased fish growth performance, increased enteritis morbidity, decreased intestinal innate humoral immune response and aggravated intestinal inflammation. However, liver-expressed antimicrobial peptide 2A/B mRNA in the DI andIL-6,IL-17D,IL-10, transforming growth factor (TGF)-β1andTGF-β2mRNA in the PI were not affected by vitamin A levels. Meanwhile, vitamin A deficiency disturbed inflammatory cytokines in the PI, MI and DI, which might be partly linked to p38 mitogen-activated protein kinase (p38MAPK) signalling andNF-κBcanonical signalling pathway (IκB kinaseβ(IKKβ),IKKγ, inhibitor ofκBα,NF-κB p65andc-Rel) rather thanNF-κBnon-canonical signalling pathway (NF-κB p52andIKKα). However, the signalling moleculesNF-κB p65andp38MAPKdid not participate in regulating cytokines in the PI. These results suggested that vitamin A deficiency decreased fish growth and impaired intestinal immune function, and that different immune responses in the PI, MI and DI were mediated partly byNF-κBcanonical signalling andp38MAPKsignalling pathways. On the basis of percentage of weight gain, to protect fish against enteritis morbidity and acid phosphatase activity, the optimum dietary vitamin A levels were estimated to be 0·664, 0·707 and 0·722 mg /kg, respectively.