bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pentameric quaternary structure of the intracellular domain of serotonin type 3A receptors
Authors: Pandhare Akash , Grozdanov Petar N. , Jansen Michaela 
Published: April 2016

AbstractIn spite of extensive efforts over decades an experimentally-derived structure of full-length eukaryotic pentameric ligand-gated ion channels (pLGICs) is still lacking. These pharmaceutically highly-relevant channels contain structurally well-conserved and characterized extracellular and transmembrane domains. The intracellular domain (ICD), however, has been orphaned in structural studies based on the consensus assumption of being largely disordered. In the present study, we demonstrate for the first time that the serotonin type 3A (5-HT3A) ICD assembles into stable pentamers in solution in the absence of the other two domains, thought to be the drivers for oligomerization. Additionally, the soluble 5-HT3A-ICD construct interacted with the protein RIC-3 (resistance to inhibitors of cholinesterase). The interaction provides evidence that the 5-HT3A-ICD is not only required but also sufficient for interaction with RIC-3. Our results suggest the ICD constitutes an oligomerization domain. This novel role significantly adds to its known contributions in receptor trafficking, targeting and functional fine-tuning. The innate diversity of the ICDs with sizes ranging from 50 to 280 amino acids indicates new methodologies need to be developed to determine the structures of these domains. The use of soluble ICD proteins that we report in the present study constitutes a useful approach to address this gap.
Detection of Volatile Organic Compounds by Self-assembled Monolayer Coated Sensor Array with Concentration-independent Fingerprints
Authors: Chang Ye , Tang Ning , Qu Hemi , Liu Jing , Zhang Daihua , Zhang Hao , Pang Wei , Duan Xuexin 
Published: April 2016

AbstractIn this paper, we have modeled and analyzed affinities and kinetics of volatile organic compounds (VOCs) adsorption (and desorption) on various surface chemical groups using multiple self-assembled monolayers (SAMs) functionalized film bulk acoustic resonator (FBAR) array. The high-frequency and micro-scale resonator provides improved sensitivity in the detections of VOCs at trace levels. With the study of affinities and kinetics, three concentration-independent intrinsic parameters (monolayer adsorption capacity, adsorption energy constant and desorption rate) of gas-surface interactions are obtained to contribute to a multi-parameter fingerprint library of VOC analytes. Effects of functional group’s properties on gas-surface interactions are also discussed. The proposed sensor array with concentration-independent fingerprint library shows potential as a portable electronic nose (e-nose) system for VOCs discrimination and gas-sensitive materials selections.
Observation of the Zero Doppler Effect
Authors: Ran Jia , Zhang Yewen , Chen Xiaodong , Fang Kai , Zhao Junfei , Chen Hong 
Published: April 2016

AbstractThe normal Doppler effect has well-established applications in many areas of science and technology. Recently, a few experimental demonstrations of the inverse Doppler effect have begun to appear in negative-index metamaterials. Here we report an experimental observation of the zero Doppler effect, that is, no frequency shift irrespective of the relative motion between the wave signal source and the detector in a zero-index metamaterial. This unique phenomenon, accompanied by the normal and inverse Doppler effects, is generated by reflecting a wave from a moving discontinuity in a composite right/left-handed transmission line loaded with varactors when operating in the near zero-index passband, or the right/left-handed passband. This work has revealed a complete picture of the Doppler effect in metamaterials and may lead to potential applications in electromagnetic wave related metrology.
Ultrasound-promoted two-step synthesis of 3-arylselenylindoles and 3-arylthioindoles as novel combretastatin A-4 analogues
Authors: Wen Zhiyong , Li Xiaona , Zuo Daiying , Lang Binyue , Wu Yang , Jiang Mingyang , Ma Huizhuo , Bao Kai , Wu Yingliang , Zhang Weige 
Published: April 2016

AbstractA series of 3-(3′-hydroxy-4′-methoxyphenyl)selenyl-5,6,7-trimethoxy-1H-indoles and 3-(3′-hydroxy-4′-methoxyphenyl)thio-5,6,7-trimethoxy-1H-indoles were obtained as a new class of combretastatin A-4 (CA-4) analogues via a convenient ultrasound (US)-assisted two-step process involving 3-selenenylation/sulfenylation followed by O-deallylation. With the assistance of US irradiation, both the reaction rates and yields of selenenylation, sulfenylation and O-deallylation could be significantly improved. A comparison of the reaction rates of O-deallylation and ester reduction demonstrated that O-deallylation was more sensitive to US irradiation. Finally, these products were evaluated for their antiproliferative activities, and most of them showed moderate to potent activities against three human cancer cell lines in vitro.
Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens
Authors: Gharajehdaghipour Tazarve , Roth James D. , Fafard Paul M. , Markham John H. 
Published: April 2016

AbstractTop predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ15N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra.
Molecular Inversion Probes for targeted resequencing in non-model organisms
Authors: Niedzicka M. , Fijarczyk A. , Dudek K. , Stuglik M. , Babik W. 
Published: April 2016

AbstractApplications that require resequencing of hundreds or thousands of predefined genomic regions in numerous samples are common in studies of non-model organisms. However few approaches at the scale intermediate between multiplex PCR and sequence capture methods are available. Here we explored the utility of Molecular Inversion Probes (MIPs) for the medium-scale targeted resequencing in a non-model system. Markers targeting 112 bp of exonic sequence were designed from transcriptome of Lissotriton newts. We assessed performance of 248 MIP markers in a sample of 85 individuals. Among the 234 (94.4%) successfully amplified markers 80% had median coverage within one order of magnitude, indicating relatively uniform performance; coverage uniformity across individuals was also high. In the analysis of polymorphism and segregation within family, 77% of 248 tested MIPs were confirmed as single copy Mendelian markers. Genotyping concordance assessed using replicate samples exceeded 99%. MIP markers for targeted resequencing have a number of advantages: high specificity, high multiplexing level, low sample requirement, straightforward laboratory protocol, no need for preparation of genomic libraries and no ascertainment bias. We conclude that MIP markers provide an effective solution for resequencing targets of tens or hundreds of kb in any organism and in a large number of samples.
Adh enhances Actinobacillus pleuropneumoniae pathogenicity by binding to OR5M11 and activating p38 which induces apoptosis of PAMs and IL-8 release
Authors: Wang Lei , Qin Wanhai , Zhang Jing , Bao Chuntong , Zhang Hu , Che Yanyi , Sun Changjiang , Gu Jingmin , Feng Xin , Du Chongtao , Han Wenyu , Richard Paul Langford , Lei Liancheng 
Published: April 2016

AbstractMembers of the Trimeric Autotransporter Adhesin (TAA) family play a crucial role in the adhesion of Gram-negative pathogens to host cells, but the immunopathogenesis of TAAs remains unknown. Our previous studies demonstrated that Adh from Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is required for full bacterial pathogenicity. Alveolar macrophages are the first line of defense against respiratory infections. This study compared the interactions between porcine alveolar macrophages (PAMs) and wild-type A. pleuropneumoniae (5b WT) or an Adh-deletion strain (5b ΔAdh) via gene microarray, immunoprecipitation and other technologies. We found that Adh was shown to interact with the PAMs membrane protein OR5M11, an olfactory receptor, resulting in the high-level secretion of IL-8 by activation of p38 MAPK signaling pathway. Subsequently, PAMs apoptosis via the activation of the Fax and Bax signaling pathways was observed, followed by activation of caspases 8, 9, and 3. The immunological pathogenic roles of Adh were also confirmed in both murine and piglets infectious models in vivo. These results identify a novel immunological strategy for TAAs to boost the pathogenicity of A. pleuropneumoniae. Together, these datas reveal the high versatility of the Adh protein as a virulence factor and provide novel insight into the immunological pathogenic role of TAAs.
Calcium oxalate crystals increased enolase-1 secretion from renal tubular cells that subsequently enhanced crystal and monocyte invasion through renal interstitium
Authors: Chiangjong Wararat , Thongboonkerd Visith 
Published: April 2016

AbstractCalcium oxalate monohydrate (COM) crystals cause kidney stone disease by still unclear mechanisms. The present study aimed to characterize changes in secretion of proteins from basolateral compartment of renal tubular epithelial cells after exposure to COM crystals and then correlated them with the stone pathogenesis. Polarized MDCK cells were cultivated in serum-free medium with or without 100 μg/ml COM crystals for 20 h. Secreted proteins collected from the lower chamber (basolateral compartment) were then resolved in 2-D gels and visualized by Deep Purple stain (n = 5 gels/group). Spot matching and intensity analysis revealed six protein spots with significantly altered levels in COM-treated samples. These proteins were then identified by tandem mass spectrometry (Q-TOF MS/MS), including enolase-1, phosphoglycerate mutase-1, actinin, 14-3-3 protein epsilon, alpha-tubulin 2 and ubiquitin-activating enzyme E1. The increased enolase-1 level was confirmed by Western blot analysis. Functional analysis revealed that enolase-1 dramatically induced COM crystal invasion through ECM migrating chamber in a dose-dependent manner. Moreover, enolase-1 bound onto U937 monocytic cell surface markedly enhanced cell migration through the ECM migrating chamber. In summary, our data indicated that the increased secretory enolase-1 induced by COM crystals played an important role in crystal invasion and inflammatory process in renal interstitium.
Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns
Authors: Habes M , Janowitz D , Erus G , Toledo J B , Resnick S M , Doshi J , Van der Auwera S , Wittfeld K , Hegenscheid K , Hosten N , Biffar R , Homuth G , Völzke H , Grabe H J , Hoffmann W , Davatzikos C 
Published: April 2016

AbstractWe systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20–90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer’s Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.
MAOA gene hypomethylation in panic disorder—reversibility of an epigenetic risk pattern by psychotherapy
Authors: Ziegler C , Richter J , Mahr M , Gajewska A , Schiele M A , Gehrmann A , Schmidt B , Lesch K-P , Lang T , Helbig-Lang S , Pauli P , Kircher T , Reif A , Rief W , Vossbeck-Elsebusch A N , Arolt V , Wittchen H-U , Hamm A O , Deckert J , Domschke K 
Published: April 2016

AbstractEpigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
What are male teachers’ understandings of masculinities?—an exploration of sex, gender and bodies in Irish primary schools
Authors: O'Keeffe Suzanne 
Published: April 2016

AbstractPrimary teaching has traditionally been framed by assumptions about gender. These commonly held, but seldom voiced, assumptions have a strong impact on male primary schoolteachers and on men considering teaching as a career. Focusing on the lives of five Irish male primary teachers, this article unpacks a number of the assumptions relating to men who teach children at primary level. Many of the assumptions are often shrouded in silence, which increases the difficulty in addressing them. In this context, discussions surrounding the topics of care, men working with young children and teaching as a feminine occupation, are presented. The study employs three data-collection phases using the interview as the primary method of enquiry. Overall, two major challenges were identified: informal barriers and the concept of care in education. The study’s findings show that gender relations within a feminine environment are central to understanding masculinities in primary schools. This article makes a contribution towards revealing how issues of masculinities are navigated and negotiated on a daily basis. Allied to this, it also provides a context for understanding the challenges male teachers face on a continuous basis. This article is published as part of a thematic collection on gender studies.
How to explain microemulsions formed by solvent mixtures without conventional surfactants
Authors: Zemb Thomas N. , Klossek Michael , Lopian Tobias , Marcus Julien , Schöettl Sebastian , Horinek Dominik , Prevost Sylvain F. , Touraud Didier , Diat Olivier , Marčelja Stjepan , Kunz Werner 
Published: April 2016

Significance
Beginning over 40 y ago, a curious type of microemulsions—as transparent dispersion of two immiscible liquids separated by an interfacial film—at thermodynamic equilibrium has been described as “pre-Ouzo,” “detergentless,” or surfactant-free microemulsions. The experiments in ternary systems containing one hydrotropic cosolvent were ambiguous, and therefore, there was no need to come up with a general theory. Recent evidence obtained by specific deuteration in neutron scattering established the need for the extension of self-assembly theories based on Derjaguin-Landau-Verwey-Overbeck theory (DLVO), bending, or phase transfer energy. Here, we introduce a general free energy expression for weak self-assembly, where solvation effects and entropy compete without the influence of film bending, that explains all experimental results for this class of microemulsions.
Species interactions slow warming-induced upward shifts of treelines on the Tibetan Plateau
Authors: Liang Eryuan , Wang Yafeng , Piao Shilong , Lu Xiaoming , Camarero Jesús Julio , Zhu Haifeng , Zhu Liping , Ellison Aaron M. , Ciais Philippe , Peñuelas Josep 
Published: April 2016

SignificanceClimatic warming is expected to shift alpine treelines upward because regeneration and growth of trees there are limited by low temperature. However, treeline displacement is spatially heterogeneous, despite warming climate. Using data on undisturbed spruce and fir treeline plots located on the Tibetan Plateau between 28.4 and 38.5°N, we showed that climatic warming tended to promote an upward shift of alpine treelines at local and regional scales. However, upslope migration rates were controlled largely by interspecific interactions. The species interaction mechanism both helps to explain why many treelines have not advanced in response to climatic warming and highlights that predictions of treeline shifts based solely on climate may be misleading, because interspecific interactions can temper effects of climatic change.
Mechanism for accurate, protein-assisted DNA annealing by
Deinococcus radiodurans
DdrB
Authors: Sugiman-Marangos Seiji N. , Weiss Yoni M. , Junop Murray S. 
Published: April 2016

Significance
During repair of DNA double-strand breaks, cells must accurately anneal broken strands under temperatures that would normally promote mispairing of even small stretches of ssDNA. How single-strand annealing (SSA) proteins such as Rad52 and DdrB (DNA damage response B) overcome this thermodynamic barrier and achieve accurate strand pairing has remained unclear. Our structural studies of DdrB in complex with partially annealed DNA and supporting biochemical data reveal a mechanism for accurate annealing involving DdrB-mediated proofreading of strand complementarity. DdrB promotes high-fidelity annealing by constraining specific bases from unauthorized association and only releases annealed duplex when bound strands are fully complementary. To our knowledge, this work provides the first mechanistic understanding for accurate strand pairing during SSA-dependent DNA double-strand break repair.
Potential escalation of heat-related working costs with climate and socioeconomic changes in China
Authors: Zhao Yan , Sultan Benjamin , Vautard Robert , Braconnot Pascale , Wang Huijun J. , Ducharne Agnes 
Published: April 2016

Significance
China is a country with a large population, and it is very affected by heatwaves, which have disastrous consequences on human health and occupational safety. Governmental high-temperature subsidies (HTSs) are allocated to workers during hot days but this increases the labor cost. This work is the first study, to our knowledge, to estimate the HTS cost in China from the present day to the end of the 21st century. We identified three main driving factors for HTS, namely population, employment structure, and climate. The HTS cost is bound to increase during the 21st century, despite substantial uncertainty arising from the evolution scenarios of the driving factors. The evolution of the heat-related labor cost in China may serve as an example for other countries.
Lenz-Majewski mutations in
PTDSS1
affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions
Authors: Sohn Mira , Ivanova Pavlina , Brown H. Alex , Toth Daniel J. , Varnai Peter , Kim Yeun Ju , Balla Tamas 
Published: April 2016

Significance
Phosphatidylserine (PS) is synthesized in the endoplasmic reticulum by PS synthase enzymes, but most of the PS is found in the inner leaflet of the plasma membrane. The importance of the present findings is that they uncover a critical connection between PI4P turnover and PS transport and demonstrate that uncontrolled PS synthesis as seen in Lenz-Majewski syndrome patients has deleterious consequences to cells affecting other lipids and not just PS.
Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation
Authors: Brook Matthew , Tomlinson Gareth H. , Miles Katherine , Smith Richard W. P. , Rossi Adriano G. , Hiemstra Pieter S. , van ’t Wout Emily F. A. , Dean Jonathan L. E. , Gray Nicola K. , Lu Wuyuan , Gray Mohini 
Published: April 2016

Significance
Neutrophils are the major effectors of acute inflammation responding to tissue injury or infection. The clearance of apoptotic neutrophils by inflammatory macrophages also provides a powerful proresolution signal. Apoptotic or necrotic neutrophils also release abundant amounts of the antimicrobial peptides alpha defensins. In this report, we show that the most abundant of these peptides, HNP1 (Human Neutrophil Peptide 1), profoundly inhibits protein translation. It achieves this without affecting mRNA stability or preventing mRNA polysomal association. This is, to our knowledge, the first demonstration of a peptide released from one cell, a leukocyte, entering and directly modulating the translatome of another cell. It alludes to a previously unidentified mechanism, driven by dying neutrophils, that ensures the timely resolution of macrophage-driven inflammation, without compromising antimicrobial function.