bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the mode of action of cell wall-inhibiting antibiotics using metabolic labeling of growing peptidoglycan in Streptococcus pyogenes
Authors: Sugimoto Atsushi , Maeda Asuka , Itto Kaori , Arimoto Hirokazu 
Published: April 2017

AbstractBecause of the scanty pipeline of antibiotics newly obtained from nature, chemical modification of established drugs is one of the major streams of current antibacterial research. Intuitive and easy-to-use assays are critical for identifying drug candidates with novel modes of action. In this study, we demonstrated that metabolic fluorescent staining of growing cell walls is a powerful tool for mode-of-action analyses of antibiotics using Streptococcus pyogenes. A set of major cell-wall-inhibiting antibiotics (bacitracin, d-cycloserine, flavomycin, oxacillin, ramoplanin, and vancomycin) was employed to validate the potential of the assay. The mechanistic differences of these antibiotics were successfully observed. For instance, d-cycloserine treatment induced fluorescently stained, excessive peripheral cell wall growth. This may indicate that the switch from the peripheral growth stage to the succeeding septal growth was disturbed by the treatment. We then applied this assay to analyze a series of vancomycin derivatives. The assay was sufficiently sensitive to detect the effects of single-site chemical modification of vancomycin on its modes of action. This metabolic fluorescent labeling method is easy to perform, especially because it does not require radiolabeled substrates. Thus, it is suitable for the preliminary evaluation of antibacterial mechanisms during antibacterial research.
Direct, rapid antimicrobial susceptibility test from positive blood cultures based on microscopic imaging analysis
Authors: Choi Jungil , Jeong Hyun Yong , Lee Gi Yoon , Han Sangkwon , Han Shinhun , Jin Bonghwan , Lim Taegeun , Kim Shin , Kim Dong Young , Kim Hee Chan , Kim Eui-Chong , Song Sang Hoon , Kim Taek Soo , Kwon Sunghoon 
Published: April 2017

AbstractFor the timely treatment of patients with infections in bloodstream and cerebrospinal fluid, a rapid antimicrobial susceptibility test (AST) is urgently needed. Here, we describe a direct and rapid antimicrobial susceptibility testing (dRAST) system, which can determine the antimicrobial susceptibility of bacteria from a positive blood culture bottle (PBCB) in six hours. The positive blood culture sample is directly mixed with agarose and inoculated into a micropatterned plastic microchip with lyophilized antibiotic agents. Using microscopic detection of bacterial colony formation in agarose, the total time to result from a PBCB for dRAST was only six hours for a wide range of bacterial concentrations in PBCBs. The results from the dRAST system were consistent with the results from a standard AST, broth microdilution test. In tests of clinical isolates (n = 206) composed of 16 Gram-negative species and seven Gram-positive species, the dRAST system was accurate compared to the standard broth microdilution test, with rates of 91.11% (2613/2868) categorical agreement, 6.69% (192/2868) minor error, 2.72% (50/1837) major error and 1.45% (13/896) very major error. Thus, the dRAST system can be used to rapidly identify appropriate antimicrobial agents for the treatment of blood stream infection (BSI) and antibiotic-resistant strain infections.
Mutational screening of SLC39A5, LEPREL1 and LRPAP1 in a cohort of 187 high myopia patients
Authors: Feng Chun-Yun , Huang Xiao-Qiong , Cheng Xue-Wen , Wu Rong-Han , Lu Fan , Jin Zi-Bing 
Published: April 2017

AbstractHigh myopia (HM) is a leading cause of mid-way blindness with a high heritability in East Asia. Although only a few disease genes have been reported, a small proportion of patients could be identified with genetic predispositions. In order to expand the mutation spectrum of the causative genes in Chinese adult population, we investigated three genes, SLC39A5, LEPREL1 and LRPAP1, in a cohort of 187 independent Chinese patients with high myopia. Sanger sequencing was used to find possible pathogenic mutations, which were further screened in normal controls. After a pipeline of database and predictive assessments filtering, we, thereby, identified totally seven heterozygous mutations in the three genes. Among them, three novel missense mutations, c.860C > T, p.Pro287Leu and c.956G > C, p.Arg319Thr in SLC39A5, c.1982A > G, p.Lys661Arg in LEPREL1, were identified as potentially causative mutations. Additionally, the two heterozygous mutations (c.1582G > A, p.Ala528Thr; c.1982A > G, p.Lys661Arg) in one patient in LEPREL1 gene were reported in this study. Our findings will not only augment the mutation spectrum of these three genes, but also provide insights of the contribution of these genes to adult high myopia in Chinese. However, further studies are still needed to address the pathogenicity of each of the mutations reported in this study.
Hunter-Gatherer Social Networks and Reproductive Success
Authors: Page Abigail E. , Chaudhary Nikhil , Viguier Sylvain , Dyble Mark , Thompson James , Smith Daniel , Salali Gul. D. , Mace Ruth , Migliano Andrea Bamberg 
Published: April 2017

AbstractIndividuals’ centrality in their social network (who they and their social ties are connected to) has been associated with fertility, longevity, disease and information transmission in a range of taxa. Here, we present the first exploration in humans of the relationship between reproductive success and different measures of network centrality of 39 Agta and 38 BaYaka mothers. We collected three-meter contact (‘proximity’) networks and reproductive histories to test the prediction that individual centrality is positively associated with reproductive fitness (number of living offspring). Rather than direct social ties influencing reproductive success, mothers with greater indirect centrality (i.e. centrality determined by second and third degree ties) produced significantly more living offspring. However, indirect centrality is also correlated with sickness in the Agta, suggesting a trade-off. In complex social species, the optimisation of individuals’ network position has important ramifications for fitness, potentially due to easy access to different parts of the network, facilitating cooperation and social influence in unpredictable ecologies.
Structural and biochemical insights of CypA and AIF interaction
Authors: Farina Biancamaria , Di Sorbo Gianluigi , Chambery Angela , Caporale Andrea , Leoni Guido , Russo Rosita , Mascanzoni Fabiola , Raimondo Domenico , Fattorusso Roberto , Ruvo Menotti , Doti Nunzianna 
Published: April 2017

AbstractThe Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370–394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed. We show that AIF(370-394) interacts with CypA on the same surface recognized by AIF(Δ1-121) protein and that the region is very close to the CypA catalytic pocket. Such region partially overlaps with the binding site of cyclosporin A (CsA), the strongest catalytic inhibitor of CypA. Our data point toward distinct CypA structural determinants governing the inhibitor selectivity and the differential biological effects of AIF and CsA, and provide new structural insights for designing CypA/AIF selective inhibitors with therapeutic relevance in neurodegenerative diseases.
Improved phylogenetic resolution for Y-chromosome Haplogroup O2a1c-002611
Authors: Yao Xiaotian , Tang Senwei , Bian Beilei , Wu Xiaoli , Chen Gang , Wang Chuan-Chao 
Published: April 2017

AbstractY-chromosome Haplogroup O2a1c-002611 is one of the dominant lineages of East Asians and Southeast Asians. However, its internal phylogeny remains insufficiently investigated. In this study, we genotyped 89 new highly informative single nucleotide polymorphisms (SNPs) in 305 individuals with Haplogroup O2a1c-002611 identified from 2139 Han Chinese males. Two major branches were identified, O2a1c1-F18 and O2a1c2-L133.2 and the first was further divided into two main subclades, O2a1c1a-F11 and O2a1c1b-F449, accounting for 11.13% and 2.20% of Han Chinese, respectively. In Haplogroup O2a1c1a-F11, we also determined seven sublineages with quite different frequency distributions in Han Chinese ranging from 0.187% to 3.553%, implying they might have different demographic history. The reconstructed haplogroup tree for all the major clades within Haplogroup O2a1c-002611 permits better resolution of male lineages in population studies of East Asia and Southeast Asia. The dataset generated in the present study are also valuable for forensic identification and paternity tests in China.
Synergistic effect of nitrate-doped TiO2 aerosols on the fast photochemical oxidation of formaldehyde
Authors: Shang Jing , Xu Wei Wei , Ye Chun Xiang , George Christian , Zhu Tong 
Published: April 2017

AbstractThe uptake of formaldehyde (HCHO) on mineral dust affects its budget as well as particle properties, yet the process has not yet been fully investigate. Here, TiO2 and nitrate-doped TiO2 aerosols were used as proxies for mineral dust, and the uptake of HCHO was explored in a chamber under both dark and illuminated conditions. The uptake loss of HCHO on UV-illuminated aerosols is 2–9 times faster than its gaseous photolysis in our experimental system. The uptake coefficient in the range of 0.43–1.68 × 10−7 is 1–2 orders of magnitude higher than previous reports on model mineral dust particles. The reaction rate exhibits a Langmuir-Hinshelwood-type dependence on nitrate content and relative humidity, suggesting the competitive role of nitrate salts, water vapor and HCHO on the TiO2 surface. The reaction produces carbon dioxide as the main product and gaseous formic acid as an important intermediate. The hydroxyl radical produced on illuminated TiO2 primarily drives the fast oxidation of HCHO. The nitrate radical arising from the TiO2-catalyzed photoreaction of nitrate synergistically promotes the oxidation process. This study suggests a novel oxidation route for HCHO in the atmosphere, taking into account high abundance of both mineral dust and anthropogenic TiO2 aerosols.
Risk and Prediction of Sudden Cardiac Death and Ventricular Arrhythmias for Patients with Atrial Fibrillation – A Nationwide Cohort Study
Authors: Chao Tze-Fan , Liu Chia-Jen , Tuan Ta-Chuan , Chen Su-Jung , Chen Tzeng-Ji , Lip Gregory Y. H. , Chen Shih-Ann 
Published: April 2017

AbstractSudden cardiac death (SCD) is the most devastating manifestation of ventricular arrhythmias (VAs), and is the leading cause of mortality among atrial fibrillation (AF) patients. The goal of the present study was to investigate the incidence of SCD/VAs amongst patients with and without AF. We also aimed to identify important risk factors of SCD/VAs among AF patients. Using the “National Health Insurance Research Database” in Taiwan, a total of 352,656 AF and 352,656 non-AF patients without antecedent SCD/VAs were identified. The annual risk of SCD/VAs was higher in AF than non-AF groups (0.97% versus 0.47%) with an adjusted hazard ratio (HR) of 1.64. The increased risk of SCD/VAs in AF patients was consistently observed in different age strata, various comorbidities and patients without use of class I/III anti-arrhythmic drugs or digoxin. Among AF patients, age ≥75 years, congestive heart failure, hypertension, diabetes mellitus, previous stroke/transient ischemic attack, vascular diseases, chronic kidney disease and chronic obstructive pulmonary disease were important risk factors for SCD/VAs. In conclusion, the risk of SCD/VAs amongst AF patients was 1.64-fold higher compared to non-AF patients, which was associated with the number of clinical risk factors associated with the particular AF patient.
Exome Analysis of Rare and Common Variants within the NOD Signaling Pathway
Authors: Andreoletti Gaia , Shakhnovich Valentina , Christenson Kathy , Coelho Tracy , Haggarty Rachel , Afzal Nadeem A , Batra Akshay , Petersen Britt-Sabina , Mort Matthew , Beattie R. Mark , Ennis Sarah 
Published: April 2017

AbstractPediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort (BIRC2p = 0.004,NFKB1p = 0.005,NOD2p = 0.029 andSUGT1p = 0.047). Statistical significance was replicated for BIRC2 (p = 0.041) andNOD2(p = 0.045) in an independent validation cohort. A gene based test on the combined discovery and replication cohort confirmed association forBIRC2(p = 0.030). We successfully applied burden of mutation testing that jointly assesses common and rare variants, identifying two previously implicated genes (NFKB1andNOD2) and confirmed a possible role in disease risk in a previously unreported gene (BIRC2). The identification of this novel gene provides a wider role for the inhibitor of apoptosis gene family in IBD pathogenesis.
The evolutionary history of bears is characterized by gene flow across species
Authors: Kumar Vikas , Lammers Fritjof , Bidon Tobias , Pfenninger Markus , Kolter Lydia , Nilsson Maria A. , Janke Axel 
Published: April 2017

AbstractBears are iconic mammals with a complex evolutionary history. Natural bear hybrids and studies of few nuclear genes indicate that gene flow among bears may be more common than expected and not limited to polar and brown bears. Here we present a genome analysis of the bear family with representatives of all living species. Phylogenomic analyses of 869 mega base pairs divided into 18,621 genome fragments yielded a well-resolved coalescent species tree despite signals for extensive gene flow across species. However, genome analyses using different statistical methods show that gene flow is not limited to closely related species pairs. Strong ancestral gene flow between the Asiatic black bear and the ancestor to polar, brown and American black bear explains uncertainties in reconstructing the bear phylogeny. Gene flow across the bear clade may be mediated by intermediate species such as the geographically wide-spread brown bears leading to large amounts of phylogenetic conflict. Genome-scale analyses lead to a more complete understanding of complex evolutionary processes. Evidence for extensive inter-specific gene flow, found also in other animal species, necessitates shifting the attention from speciation processes achieving genome-wide reproductive isolation to the selective processes that maintain species divergence in the face of gene flow.
Construction of a high-density linkage map and fine mapping of QTLs for growth and gonad related traits in blunt snout bream
Authors: Wan Shi-Ming , Liu Hong , Zhao Bo-Wen , Nie Chun-Hong , Wang Wei-Min , Gao Ze-Xia 
Published: April 2017

AbstractHigh-density genetic maps based on SNPs are essential for fine mapping loci controlling specific traits for fish species. Using restriction-site associated DNA tag sequencing (RAD-Seq) technology, we identified 42,784 SNPs evenly distributed across theMegalobrama amblycephalagenome. Based on 2 parents and 187 intra-specific hybridization progenies, a total of 14,648 high-confidence SNPs were assigned to 24 consensus linkage groups (LGs) of maternal and paternal map. The total length of the integrated map was 3,258.38 cM with an average distance of 0.57 cM among 5676 effective loci, thereby representing the first high-density genetic map reported forM. amblycephala. A total of eight positive quantitative trait loci (QTLs) were detected in QTL analysis. Of that, five QTL explained ≥35% of phenotypic variation for growth traits and three QTL explained ≥16% phenotypic variation for gonad related traits. A total of 176 mapped markers had significant hits in the zebrafish genome and almost all of the 24 putative-chromosomes ofM. amblycephalawere in relatively conserved synteny with chromosomes of zebrafish. Almost allM. amblycephalaand zebrafish chromosomes had a 1:1 correspondence except for putative-chromosome 4, which mapped to two chromosomes of zebrafish caused by the difference in chromosome numbers between two species.
Detection of a new pyrethroid resistance mutation (V410L) in the sodium channel of Aedes aegypti: a potential challenge for mosquito control
Authors: Haddi Khalid , Tomé Hudson V. V. , Du Yuzhe , Valbon Wilson R. , Nomura Yoshiko , Martins Gustavo F. , Dong Ke , Oliveira Eugênio E. 
Published: April 2017

AbstractThe yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is the principal vector of dengue, yellow fever, Zika and Chikungunya viruses. Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes, despite the development of pyrethroid resistance in many mosquito populations worldwide. Here, we report a Brazilian strain of A. aegypti with high levels (approximately 100–60,000 fold) of resistance to both type I and type II pyrethroids. We detected two mutations (V410L and F1534C) in the sodium channel from this resistant strain. This study is the first report of the V410L mutation in mosquitoes. Alone or in combination with the F1534C mutation, the V410L mutation drastically reduced the sensitivity of mosquito sodium channels expressed in Xenopus oocytes to both type I and type II pyrethroids. The V410L mutation presents a serious challenge for the control of A. aegypti and will compromise the use of pyrethroids for the control of A. aegypti in Brazil; therefore, early monitoring of the frequency of the V410L mutation will be a key resistance management strategy to preserve the effectiveness of pyrethroid insecticides.
Chemical and Bioactive Profiling, and Biological Activities of Coral Fungi from Northwestern Himalayas
Authors: Kumar Sharma Sapan , Gautam Nandini 
Published: April 2017

AbstractRamaria Fr. and Clavaria L. are the two major genera of coral mushrooms within families Gomphaceae and Clavariaceae, respectively. Besides having important role in forest ecology, some species of these are reported to possess high nutraceutical and bioactive potential. There is a hidden diversity of coral mushrooms in Northwestern Himalayas. Present studies describe the detailed biochemical profiling and antioxidant, and antibacterial activities of twelve coral mushroom species. Biochemical profiling of nutrients and nutraceuticals was done with standard techniques and by using HPLC, UPLC and GC. Experiments were also conducted to check the toxic metals detection. Antioxidant activities were calculated using EC50 values from mushroom extracts. Antibacterial activities were checked on six pathogenic bacterial strains through minimum inhibition concenterations. Although, differences were observed in the net values of individual species but all the species were found to be rich in protein, macro and micro minerals, carbohydrates, unsaturated fatty acids, essential amino acids, phenolics, tocopherols, anthocynadins and carotenoids. All the species showed significant antioxidant and antibacterial activities. These species are reported to free from heavy toxic metals. Present studies will open the way for their large scale commercial exploitations and use in pharmaceutical industries as antioxidant, antibacterial and nutraceutical constituents.
A comparative analysis of human and mouse islet G-protein coupled receptor expression
Authors: Amisten Stefan , Atanes Patricio , Hawkes Ross , Ruz-Maldonado Inmaculada , Liu Bo , Parandeh Fariborz , Zhao Min , Huang Guo Cai , Salehi Albert , Persaud Shanta J. 
Published: April 2017

AbstractG-protein coupled receptors (GPCRs) are essential for islet function, but most studies use rodent islets due to limited human islet availability. We have systematically compared the GPCR mRNA expression in human and mouse islets to determine to what extent mouse islets can be used as surrogates for human islets to study islet GPCR function, and we have identified species-specific expression of several GPCRs. The A3 receptor (ADORA3) was expressed only in mouse islets and the A3 agonist MRS 5698 inhibited glucose-induced insulin secretion from mouse islets, with no effect on human islets. Similarly, mRNAs encoding the galanin receptors GAL1 (GALR1), GAL2 (GALR2) and GAL3 GALR3) were abundantly expressed in mouse islets but present only at low levels in human islets, so that it reads (GALR3) and galanin inhibited insulin secretion only from mouse islets. Conversely, the sst1 receptor (SSTR1) was abundant only in human islets and its selective activation by CH 275 inhibited insulin secretion from human islets, with no effect on mouse islets. Our comprehensive human and mouse islet GPCR atlas has demonstrated that species differences do exist in islet GPCR expression and function, which are likely to impact on the translatability of mouse studies to the human context.
Current carried by the Slc26 family member prestin does not flow through the transporter pathway
Authors: Bai Jun-Ping , Moeini-Naghani Iman , Zhong Sheng , Li Fang-Yong , Bian Shumin , Sigworth Fred J. , Santos-Sacchi Joseph , Navaratnam Dhasakumar 
Published: April 2017

AbstractPrestin in the lateral membrane of outer hair cells, is responsible for electromotility (EM) and a corresponding nonlinear capacitance (NLC). Prestin’s voltage sensitivity is influenced by intracellular chloride. A regulator of intracellular chloride is a stretch-sensitive, non-selective conductance within the lateral membrane, GmetL. We determine that prestin itself possesses a stretch-sensitive, non-selective conductance that is largest in the presence of thiocyanate ions. This conductance is independent of the anion transporter mechanism. Prestin has been modeled, based on structural data from related anion transporters (SLC26Dg and UraA), to have a 7 + 7 inverted repeat structure with anion transport initiated by chloride binding at the intracellular cleft. Mutation of residues that bind intracellular chloride, and salicylate treatment which prevents chloride binding, have no effect on thiocyanate conductance. In contrast, other mutations reduce the conductance while preserving NLC. When superimposed on prestin’s structure, the location of these mutations indicates that the ion permeation pathway lies between the core and gate ring of helices, distinct from the transporter pathway. The uncoupled current is reminiscent of an omega current in voltage-gated ion channels. We suggest that prestin itself is the main regulator of intracellular chloride concentration via a route distinct from its transporter pathway.