bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topoisomerases interlink genetic network underlying autism
Authors: Vokálová Lenka , Durdiaková Jaroslava , Ostatníková Daniela 
Published: August 2015

AbstractDNA topoisomerases belong to the group of proteins that play an important role in the organizational dynamics of the human genome. Their enzymatic activity solves topological strain rising from DNA supercoiling occurring during transcription. DNA topoisomerases are especially important for transcription of genes involved in neurodevelopment. Disruption of topoisomerase activity in animal models resulted in impaired neurodevelopment and changed brain architecture. Recent research revealed that topoisomerases induced expression of the same group of genes as those associated with autism. Transcriptional inhibition of neuronal genes during critical stages of brain development may be responsible for pathology of neurodevelopmental disorders such as autism. In this review we aim to outline the role of topoisomerase in neurodevelopment and its possible linkage to neuropathology of autism.
Understanding pelagic stingray (Pteroplatytrygon violacea) by-catch by Spanish longliners in the Mediterranean Sea
Authors: Báez José C. , Crespo Guillermo Ortuño , García-Barcelona Salvador , Ortiz De Urbina José M. , Macías David 
Published: August 2015

The pelagic stingray Pteroplatytrygon violacea is known to be a frequent by-catch in longline fisheries worldwide. This study analysed the eco-geographic, technical and temporal parameters that affect pelagic stingray by-catch by the Spanish surface drifting longline fleet that operates in the Mediterranean Sea. Between 2000 and 2013, 3007 longline fishing operations were monitored. Over this period, we recorded 57 574 pelagic stingray by-catches by this fleet. Two gear types were involved in 96.05% of the pelagic stingray by-catch observed: traditional surface longliners targeting swordfish (LLHB) and surface drifting longliners targeting albacore (LLALB). We obtained two statistically significant explanatory models for the two types of gear. In both cases, two of the most important variables were fisheries being sited over the continental shelf and fishing during the summer season. The LLHB explanatory model included the following variables: number of hooks, latitude where setting started, distance between the ends of the longline, and the spring season. Regarding the LLHB, we found an association between the Capture per Unit Effort of pelagic stingray from favourable sets per year and the North Atlantic Oscillation in the previous year.
Single-neuron activity and eye movements during human REM sleep and awake vision
Authors: Andrillon Thomas , Nir Yuval , Cirelli Chiara , Tononi Giulio , Fried Itzhak 
Published: August 2015

AbstractAre rapid eye movements (REMs) in sleep associated with visual-like activity, as during wakefulness? Here we examine single-unit activities (n=2,057) and intracranial electroencephalography across the human medial temporal lobe (MTL) and neocortex during sleep and wakefulness, and during visual stimulation with fixation. During sleep and wakefulness, REM onsets are associated with distinct intracranial potentials, reminiscent of ponto-geniculate-occipital waves. Individual neurons, especially in the MTL, exhibit reduced firing rates before REMs as well as transient increases in firing rate immediately after, similar to activity patterns observed upon image presentation during fixation without eye movements. Moreover, the selectivity of individual units is correlated with their response latency, such that units activated after a small number of images or REMs exhibit delayed increases in firing rates. Finally, the phase of theta oscillations is similarly reset following REMs in sleep and wakefulness, and after controlled visual stimulation. Our results suggest that REMs during sleep rearrange discrete epochs of visual-like processing as during wakefulness.
Human GPR42 is a transcribed multisite variant that exhibits copy number polymorphism and is functional when heterologously expressed
Authors: Puhl III Henry L. , Won Yu-Jin , Lu Van B. , Ikeda Stephen R. 
Published: August 2015

AbstractFFAR3 (GPR41) is a G-protein coupled receptor for which short-chain fatty acids serve as endogenous ligands. The receptor is found on gut enteroendocrine L-cells, pancreatic β-cells and sympathetic neurons and is implicated in obesity, diabetes, allergic airway disease and altered immune function. In primates, FFAR3 is segmentally duplicated resulting in GPR42, a gene currently classified as a suspected pseudogene. In this study, we sequenced FFAR3 and GPR42 open reading frames from 56 individuals and found an unexpectedly high frequency of polymorphisms contributing to several complex haplotypes. We also identified a frequent (18.8%) structural variation that results in GPR42 copy number polymorphism. Finally, sequencing revealed that 50.6% of GPR42 haplotypes differed from FFAR3 by only a single non-synonymous substitution and that the GPR42 reference sequence matched only 4.4% of the alleles. Sequencing of cDNA from human sympathetic ganglia and colon revealed processed transcripts matching the GPR42 genotype. Expression of several GPR42 haplotypes in rat sympathetic neurons revealed diverse pharmacological phenotypes that differed in potency and efficacy. Our data suggest that GPR42 be reclassified as a functioning gene and that recognition of sequence and copy number polymorphism of the FFAR3/GPR42 complex be considered during genetic and pharmacological investigation of these receptors.
Atypical spatiotemporal signatures of working memory brain processes in autism
Authors: Urbain C M , Pang E W , Taylor M J 
Published: August 2015

AbstractWorking memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM-related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed.
Protein import into mitochondria
Authors: Mokranjac D. , Neupert W. 
Published: August 2015

Mitochondria comprise approx. 1000–3000 different proteins, almost all of which must be imported from the cytosol into the organelle. So far, six complex molecular machines, protein translocases, were identified that mediate this process. The TIM23 complex is a major translocase in the inner mitochondrial membrane. It uses two energy sources, namely membrane potential and ATP, to facilitate preprotein translocation across the inner membrane and insertion into the inner membrane. Recent research has led to the discovery of a number of new constituents of the TIM23 complex and to the unravelling of the mechanisms of preprotein translocation.
Regulation of exocytosis by protein kinase C
Authors: Morgan A. , Burgoyne R.D. , Barclay J.W. , Craig T.J. , Prescott G.R. , Ciufo L.F. , Evans G.J.O. , Graham M.E. 
Published: August 2015

PKC (protein kinase C) has been known for many years to modulate regulated exocytosis in a wide variety of cell types. In neurons and neuroendocrine cells, PKC regulates several different stages of the exocytotic process, suggesting that these multiple actions of PKC are mediated by phosphorylation of distinct protein targets. In recent years, a variety of exocytotic proteins have been identified as PKC substrates, the best characterized of which are SNAP-25 (25 kDa synaptosome-associated protein) and Munc18. In the present study, we review recent evidence suggesting that site-specific phosphorylation of SNAP-25 and Munc18 by PKC regulates distinct stages of exocytosis.
Evolutionary causes and consequences of diversified CRISPR immune profiles in natural populations
Authors: England Whitney E. , Whitaker Rachel J. 
Published: August 2015

Host–pathogen co-evolution is a significant force which shapes the ecology and evolution of all types of organisms, and such interactions are driven by resistance and immunity mechanisms of the host. Diversity of resistance and immunity can affect the co-evolutionary trajectory of both host and pathogen. The microbial CRISPR (clustered regularly interspaced short palindromic repeats)–Cas (CRISPR-associated) system is one host immunity mechanism which offers a tractable model for examining the dynamics of diversity in an immune system. In the present article, we review CRISPR variation observed in a variety of natural populations, examine the forces which can push CRISPRs towards high or low diversity, and investigate the consequences of various levels of diversity on microbial populations.
Probing DNA interactions with proteins using a single-molecule toolbox: inside the cell, in a test tube and in a computer
Authors: Wollman Adam J. M. , Miller Helen , Zhou Zhaokun , Leake Mark C. 
Published: August 2015

DNA-interacting proteins have roles in multiple processes, many operating as molecular machines which undergo dynamic meta-stable transitions to bring about their biological function. To fully understand this molecular heterogeneity, DNA and the proteins that bind to it must ideally be interrogated at a single molecule level in their native in vivo environments, in a time-resolved manner, fast enough to sample the molecular transitions across the free-energy landscape. Progress has been made over the past decade in utilizing cutting-edge tools of the physical sciences to address challenging biological questions concerning the function and modes of action of several different proteins which bind to DNA. These physiologically relevant assays are technically challenging but can be complemented by powerful and often more tractable in vitro experiments which confer advantages of the chemical environment with enhanced detection signal-to-noise of molecular signatures and transition events. In the present paper, we discuss a range of techniques we have developed to monitor DNA–protein interactions in vivo, in vitro and in silico. These include bespoke single-molecule fluorescence microscopy techniques to elucidate the architecture and dynamics of the bacterial replisome and the structural maintenance of bacterial chromosomes, as well as new computational tools to extract single-molecule molecular signatures from live cells to monitor stoichiometry, spatial localization and mobility in living cells. We also discuss recent developments from our laboratory made in vitro, complementing these in vivo studies, which combine optical and magnetic tweezers to manipulate and image single molecules of DNA, with and without bound protein, in a new super-resolution fluorescence microscope.
Elevated venous thromboembolism risk in preeclampsia: molecular mechanisms and clinical impact
Authors: Egan Karl , Kevane Barry , Áinle Fionnuala Ní 
Published: August 2015

Venous thromboembolism (VTE) remains a leading cause of maternal death and morbidity in the developed world. Strategies for prevention of VTE in pregnancy have been the subject of recent guidelines and consensus statements. These guidelines recommend thrombosis prevention in women who have risk factors associated with an elevated VTE risk. Preeclampsia is characterized by maternal hypertension and proteinuria developing after 20 weeks gestation, complicating up to 7% of pregnancies and is associated with a massive annual morbidity and mortality burden. Women with preeclampsia have been shown to be at increased risk of VTE with studies to date suggesting that this risk may be up to 5-fold greater than the risk of pregnancy-associated VTE in the general population. Despite the fact that preeclampsia is so common and potentially devastating, our understanding of its pathogenesis and potential therapeutic strategies remain poor. In addition, the mechanisms underlying the prothrombotic phenotype in preeclampsia are also poorly characterized although a number of potential mechanisms have been postulated. Derangements of platelet and endothelial activation and impairment of endogenous anti-coagulant pathways have been reported and may contribute to the observed VTE risk. Recently, evidence for the role of neutrophil extracellular traps (NETs) and cell-free DNA in the pathogenesis of VTE has emerged and some evidence exists to suggest that this may be of relevance in preeclampsia. Future studies aimed at understanding the diagnostic and potential therapeutic relevance of this procoagulant state are likely to be of enormous clinical benefit for pregnant women affected with this potentially devastating condition.
Introduction to the Special Session on Intervention and Outcomes of Children With Hearing Loss
Authors: Ching Teresa Y. C. 
Published: August 2015

Purpose
This research forum article introduces the special session on “Intervention and Outcomes of Children with Hearing Loss” presented at the HEaring Across the Lifespan (HEAL) Conference in 2014.

Method
The method involved a narrative summary of the key findings of two papers presented during the session.

Results
Early intervention was effective in improving outcomes of children with significant bilateral hearing loss. Preliminary findings on children with mild or unilateral hearing loss showed communicative development on par with their normal-hearing peers.

Conclusion
Children with bilateral hearing loss benefited from early detection and intervention.
Experimental evidence that short-range intermolecular aggregation is sufficient for efficient charge transport in conjugated polymers
Authors: Wang Suhao , Fabiano Simone , Himmelberger Scott , Puzinas Skomantas , Crispin Xavier , Salleo Alberto , Berggren Magnus 
Published: August 2015

Significance
Understanding the nature of charge transport and its limitations has guided the rational design of organic semiconductors. Research has mainly focused on increasing the crystallinity of conjugated polymers as a strategy to improve the long-range charge transport properties. Here, we demonstrate that local aggregation over very few chains is a sufficient mesoscopic structure to ensure high mobility, with charge transport mainly occurring along the polymer backbones, and that extended crystallinity is not necessary. These results provide an explanation for the high mobilities observed in seemingly disordered polymers and set molecular-design guidelines for next-generation conjugated polymers.
Production diversity and dietary diversity in smallholder farm households
Authors: Sibhatu Kibrom T. , Krishna Vijesh V. , Qaim Matin 
Published: August 2015

Significance
Given that hunger and malnutrition are still widespread problems in many developing countries, the question of how to make agriculture and food systems more nutrition-sensitive is of high relevance for research and policy. Many of the undernourished people in Africa and Asia are small-scale subsistence farmers. Diversifying production on these farms is often perceived as a promising strategy to improve dietary quality and diversity. This hypothesis is tested with data from smallholder farm households in Indonesia, Kenya, Ethiopia, and Malawi. Higher farm production diversity significantly contributes to dietary diversity in some situations, but not in all. Improving small farmers’ access to markets seems to be a more effective strategy to improve nutrition than promoting production diversity on subsistence farms.
Correlating steric hydration forces with water dynamics through surface force and diffusion NMR measurements in a lipid–DMSO–H
2
O system
Authors: Schrader Alex M. , Donaldson Stephen H. , Song Jinsuk , Cheng Chi-Yuan , Lee Dong Woog , Han Songi , Israelachvili Jacob N. 
Published: August 2015

Significance
We use the common biological additive DMSO to show quantitatively the impact that surface-bound water has on interactions between lipid bilayers, the membranes that separate the interior of cells from the surroundings. We present a number of metrics to gauge the hydration of the bilayer surfaces and show how the metrics are affected by the concentration of DMSO in the solvent. This work further connects measurements of surface forces, surface structure and dynamics, and surface water diffusion with significant and broad implications for soft matter systems.
Biologically active LIL proteins built with minimal chemical diversity
Authors: Heim Erin N. , Marston Jez L. , Federman Ross S. , Edwards Anne P. B. , Karabadzhak Alexander G. , Petti Lisa M. , Engelman Donald M. , DiMaio Daniel 
Published: August 2015

Significance
Most proteins are long polymers of amino acids with 20 or more chemically distinct side-chains, whereas transmembrane domains are short membrane-spanning protein segments with mainly hydrophobic amino acids. Here, we have defined the minimal chemical diversity sufficient for a protein to display specific biological activity by isolating artificial 26-aa-long transmembrane proteins consisting of random sequences of only two hydrophobic amino acids, leucine and isoleucine. A small fraction of proteins with this composition interact with the transmembrane domain of a growth factor receptor to specifically activate the receptor, resulting in growth transformation. These findings change our view of what can constitute an active protein and have important implications for protein evolution, protein engineering, and synthetic biology.
The effect of nitrate supplementation on muscle contraction in healthy adults
Authors: Hoon Matthew W. , Fornusek Ché , Chapman Phillip G. , Johnson Nathan A. 
Published: August 2015

AbstractThis study examined the effect of dietary supplementation with inorganic nitrate () on markers of contractile function in human knee extensors. In a double‐blinded, randomized cross‐over design, 18 (12 M) healthy participants undertook four days of supplementation with either nitrate‐rich beetroot juice (NITRATE; days 1–3: 525 mg , day 4: 1050 mg ) or nitrate‐depleted beetroot juice (PLACEBO). On the fourth day, isometric knee extension force was assessed during a series of voluntary and electrically evoked (stimulation) tests. In addition, muscular fatigue was examined in two separate continuous‐stimulation (0.8 s tetanus with a 1:1 work:rest ratio for 102.4 s) fatigue tests, one with and one without blood flow restriction. There were no differences for maximum voluntary contraction, peak twitch force, half‐relaxation time and the force–frequency relationship for stimulations up to 100 Hz between the NITRATE and PLACEBO trials. No differences between trials were observed in the non‐restricted fatigue test, however NITRATE was found to attenuate the decline in force during the restricted test, such that the force at the 80 s mark (PLACEBO: 66 ± 11 vs. NITRATE 74 ± 9% of initial force; P = .01) and 102 s mark (PLACEBO: 47 ± 8% vs. NITRATE 55 ± 8%; P < .01) were significantly higher. These results suggest that four days of supplementation elicits peripheral responses in muscle that attenuate muscular fatigue during exhaustive exercise under hypovolemic conditions. This ergogenic action is likely attributable to improved Ca2+ handling in the muscle, or enhanced perfusion during ischemia.
SuccFind: a novel succinylation sites online prediction tool via enhanced characteristic strategy
Authors: Xu Hao-Dong , Shi Shao-Ping , Wen Ping-Ping , Qiu Jian-Ding 
Published: August 2015

Abstract
Summary: Lysine succinylation orchestrates a variety of biological processes. Annotation of succinylation in proteomes is the first-crucial step to decipher physiological roles of succinylation implicated in the pathological processes. In this work, we developed a novel succinylation site online prediction tool, called SuccFind, which is constructed to predict the lysine succinylation sites based on two major categories of characteristics: sequence-derived features and evolutionary-derived information of sequence and via an enhanced feature strategy for further optimizations. The assessment results obtained from cross-validation suggest that SuccFind can provide more instructive guidance for further experimental investigation of protein succinylation.
Availability and implementation: A user-friendly server is freely available on the web at: http://bioinfo.ncu.edu.cn/SuccFind.aspx
Contact: jdqiu@ncu.edu.cn
Supplementary information: Supplementary data are available at Bioinformatics online.
Work-life balance can benefit business during financial crisis and austerity
Authors: Chatrakul Na Ayudhya Uracha , Prouska Rea , Lewis Suzan 
Published: August 2015

Purpose
– Advances the view that work-life balance (WLB) can benefit business during financial crisis and austerity.

Design/methodology/approach
– Draws evidence from studies in Britain and southeastern Europe.

Findings
– Introduces and explains the dual-agenda approach as a potential framework for human resources (HR) specialists, managers and employers.

Practical implications
– Argues that part of the main challenge for HR is to convince senior and line management of the need for flexible working arrangements. In order to do this, HR should take charge in monitoring the effectiveness of policies, including implementation and take-up rates and especially in evaluating flexible working practices that are often developed from the bottom up.

Social implications
– Describes how HR’s role in developing strategies for overcoming resistance to change among managers and others is important, and outlines such barriers to success as gendered assumptions about ideal workers who do not need time for family.

Originality/value
– Argues that while WLB initiatives can be good for business and a good way of managing recession and austerity, it is crucial not to lose sight of employee needs.
Developing diversity skills with university students
Authors: Hartog Mary , Haddock-Millar Julie , Rigby Chris , Wilson Doirean 
Published: August 2015

Purpose
– Points up the importance of developing people in organizations to enhance diversity.

Design/methodology/approach
– Draws on two presentations to a conference on diversity at Middlesex University, London.

Findings
– Highlights the role mentoring can play, first to achieve access to graduate-employment opportunities in the public sector and secondly to enable people to work together effectively and harmoniously in teams with greater respect through awareness and appreciation of difference.

Practical implications
– Describes the public-sector diversity-mentoring scheme, the primary goal was to widen the pool of applicants to graduate-employment opportunities in the sector from ethnic minorities and working-class backgrounds.

Social implications
– Explains that, while respect is a common value shared by all, in one culture it may be experienced differently from in another and for teams to work harmoniously all members need to feel respected.

Originality/value
– Shows how diversity is the key to better relationships and the flourishing of human potential.