bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices
Authors: Wescott Melanie P. , Kufareva Irina , Paes Cheryl , Goodman Jason R. , Thaker Yana , Puffer Bridget A. , Berdougo Eli , Rucker Joseph B. , Handel Tracy M. , Doranz Benjamin J. 
Published: August 2016

Significance
Our study helps answer the question of how G protein-coupled receptors bind an extracellular ligand and relay this signal through its transmembrane helices into an intracellular signaling event. This has been the central thesis that G protein-coupled receptor structural studies have sought to address through static snapshots of the crystallized proteins. Our functional approach using CXC chemokine receptor 4 as a model complements these structures by identifying the dynamic atomic pathway from chemokine engagement to G protein coupling.
Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency
Authors: Reid-Bayliss Kate S. , Arron Sarah T. , Loeb Lawrence A. , Bezrookove Vladimir , Cleaver James E. 
Published: August 2016

Significance
Cockayne syndrome (CS) and xeroderma pigmentosum (XP) are photosensitive diseases with mutations in the nucleotide excision repair (NER) pathway. XP patients have a very high incidence of UV-induced skin cancer, but CS patients have never been reported to develop cancer. Cultured cells from both diseases have similar sensitivity to UV-induced cytotoxicity. We examined UV-induced mutagenesis in cells from XP patients with mutations in the global genome repair branch of the NER pathway (XP-C cells) and CS primary cells using duplex sequencing for high sensitivity without selection. XP-C cells showed increased UV-induced mutation frequencies compared with normal cells, consistent with their increased cancer incidence. CS cells, in contrast, showed no elevated mutagenesis. Therefore the absence of cancer in CS patients results from the absence of increased mutations following UV exposure.
Stromal uptake and transmission of acid is a pathway for venting cancer cell-generated acid
Authors: Hulikova Alzbeta , Black Nicholas , Hsia Lin-Ting , Wilding Jennifer , Bodmer Walter F. , Swietach Pawel 
Published: August 2016

Significance
Metabolism energizes cancer growth, but only if its end product, acid, is removed effectively. A bottleneck for acid handling is slow diffusion across the underperfused extracellular milieu of hypoxic tumors. Here, we characterize the acid-handling mechanisms operating in stromal myofibroblasts that can improve the flow of acid through tumors. We show that myofibroblasts are high-capacity reservoirs that absorb excess extracellular acidity, via the AE2 transporter, and transmit this acid load across a syncytium fused by channels, such as connexin-43. Furthermore, the cytokine TGFβ1, which orchestrates many cancer–stromal interactions, can stimulate acid uptake and transmission in stromal cells with lower baseline activities. Because many colorectal cancer cells do not express AE2 and connexin-43, acid traffic would be routed preferentially through the stromal compartment of tumors.
The U.S. swine industry: historical milestones and the future of on-farm swine welfare assessments.
Authors: Pairis-Garcia M. D. , Johnson A. K. , Azarpajouh S. , Colpoys J. D. , Rademacher C. J. , Millman S. T. , Webb S. R. 
Published: August 2016

Abstract
Swine welfare has become an ever increasing area of public interest in the United States (USA) and has resulted in dramatic changes to legislation, policy and practices in swine production. Over the past decades, consumer engagement, animal protection campaigns and increase knowledge about swine welfare arising from education and research programmes have escalated swine welfare to a top industry priority. For both mainstream and niche pork marketing streams, science based and culturally relevant programmes have been developed to assess swine welfare, articulate standards of care and verify compliance to assure purchasers and consumers of pork about on-farm husbandry practices that impact animal welfare. This response has transitioned primarily from education of producers and/or consumers, to outcome-based animal welfare assessment programmes with independent third party verification audits. This review paper will evaluate some factors that have influenced the development of swine welfare standards in the USA and describe programmes developed to improve and evolve on-farm swine welfare for the future.
Let's all get home safely: a commentary on NICE and SCIE guidelines (NG27) transition between inpatient hospital settings and community or care home settings
Authors: Winfield Anna , Burns Eileen 
Published: August 2016

AbstractSafe and appropriate transition between inpatient settings and the community is one of the major challenges facing the modern NHS. The National Institute for Health and Care Excellence in conjunction with the Social Care Institute for Excellence published guidance on this challenging area in December 2015. This commentary provides context, summary and discussion of the key areas covered. The guidance particularly emphasises the importance of a person-centred approach in which patients are individuals and equal partners in the multidisciplinary team who should be treated with dignity and respect. Additionally, communication and information sharing is crucial both on admission and when taking a proactive approach to discharge, including the role of the discharge coordinator in liaising with community teams and arranging follow-up post-discharge. Self-care and the significance of carers are also highlighted as valuable in facilitating safe discharge and reducing readmissions. It is clear that in older people with complex needs, safe appropriate transition between hospital and community settings has a positive impact on patients and their carers. Given the financial and capacity pressures facing the NHS, strategies to reduce readmissions and prevent delays in discharge are increasingly important. These guidelines are therefore both timely and advocated to improve care for older people.
Effect of salt stress on ion concentration, proline content, antioxidant enzyme activities and gene expression in tomato cultivars
Authors: Gharsallah Charfeddine , Fakhfakh Hatem , Grubb Douglas , Gorsane Faten 
Published: August 2016

AbstractSalinity is a constraint limiting plant growth and productivity of crops throughout the world. Understanding the mechanism underlying plant response to salinity provides new insights into the improvement of salt tolerance-crops of importance. In the present study, we report on the responses of twenty cultivars of tomato. We have clustered genotypes into scale classes according to their response to increased NaCl levels. Three local tomato genotypes, representative of different saline scale classes, were selected for further investigation. During early (0 h, 6 h and 12 h) and later (7 days) stages of the response to salt treatment, ion concentrations (Na + , K +  and Ca 2+ ), proline content, enzyme activities (catalase, ascorbate peroxidase and guiacol peroxidase) were recorded. qPCR analysis of candidate genes WRKY (8, 31and 39), ERF (9, 16 and 80), LeNHX (1, 3 and 4) and HKT (class I) were performed. A high K + , Ca 2 + and proline accumulation as well as a decrease of Na +  concentration-mediated salt tolerance. Concomitant with a pattern of high-antioxidant enzyme activities, tolerant genotypes also displayed differential patterns of gene expression during the response to salt stress.
MSIdV: a versatile tool to visualize biological indices from mass spectrometry imaging data
Authors: Hayakawa Eisuke , Fujimura Yoshinori , Miura Daisuke 
Published: August 2016

Summary: Mass spectrometry imaging (MSI) visualizes the simultaneous lateral distribution of multiple compounds on sample surface. However, it is still difficult to visualize biological indices such as energy charge index from multiple compounds because of the lack of publicly available tools. Here we present MSIdV, a visualization tool for biological indices calculated from mass spectrometry imaging data, which can effectively scan a series of mass spectra and process, calculate and visualize user-defined index measures accurately with a number of signal processing features.
Availability and Implementation: MSIdV is implemented in Python 2.7 and is freely available on the web at https://sourceforge.net/projects/msidv/.
Contact: eisuke.hayakawa@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Albino Leaf 2is involved in the splicing of chloroplast group I and II introns in rice
Authors: Liu Changhong , Zhu Haitao , Xing Yi , Tan Jianjie , Chen Xionghui , Zhang Jianjun , Peng Haifeng , Xie Qingjun , Zhang Zemin 
Published: August 2016

AbstractChloroplasts play an essential role in plant growth and development through manipulating photosynthesis and the production of hormones and metabolites. Although many genes or regulators involved in chloroplast biogenesis and development have been isolated and characterized, identification of novel components is still lacking. We isolated a rice ( Oryza sativa ) mutant, termed albino leaf 2 ( al2 ), using genetic screening. Phenotypic analysis revealed that the al2 mutation caused obvious albino leaves at the early developmental stage, eventually leading to al2 seedling death. Electron microscopy investigations indicated that the chloroplast structure was disrupted in the al2 mutants at an early developmental stage and subsequently resulted in the breakdown of the entire chloroplast. Molecular cloning illustrated that AL2 encodes a chloroplast group IIA intron splicing facilitator (CRS1) in rice, which was confirmed by a genetic complementation experiment. Moreover, our results demonstrated that AL2 was constitutively expressed in various tissues, including green and non-green tissues. Interestingly, we found that the expression levels of a subset of chloroplast genes that contain group IIA and IIB introns were significantly reduced in the al2 mutant compared to that in the wild type, suggesting that AL2 is a functional CRS1 in rice. Differing from the orthologous CRS1 in maize and Arabidopsis that only regulates splicing of the chloroplast group II intron, our results demonstrated that the AL2 gene is also likely to be involved in the splicing of the chloroplast group I intron. They also showed that disruption of AL2 results in the altered expression of chloroplast-associated genes, including chlorophyll biosynthetic genes, plastid-encoded polymerases and nuclear-encoded chloroplast genes. Taken together, these findings shed new light on the function of nuclear-encoded chloroplast group I and II intron splicing factors in rice.
Manual of Neurological Signs
Authors: Morris John G. , Grattan-Smith Padraic J. 
Published: August 2016

Abstract
Neurology is the most visual of the medical specialties, and videos have an ability to illustrate physical signs in a way that cannot be matched by written descriptions. The Manual of Neurological Signs comprises over 900 videos of adults and children with neurologic disorders with sections including: Higher Functions, Movement Disorders, Eyes/Eye Movement, Head and Neck, Epilepsy, Reflexes, Gait, Cerebellar Disorders, Upper Motor Neuron Disorders, Lower Motor Neuron Disorders, Faces, Psychogenic Disorders, Skin Disorders, and Miscellaneous Signs.
Discordance Between Cobas BRAF V600 Testing and VE1 Immunohistochemistry in a Melanoma Patient With Bone Marrow Metastases
Authors: Rapisuwon Suthee , Busam Klaus J. , Parks Kellie , Chapman Paul B. , Lee Elsie , Atkins Michael B. 
Published: August 2016

Abstract:
False negative result remains an ongoing problem in direct gene sequencing of cancers. It is important to use the appropriate mutation detection method most appropriate to each circumstance and the available tissue. Here, we report a patient with melanoma of unknown primary with metastases to spleen and bone marrow, who was tested negative for Cobas BRAF V600E mutation, whose cancer progressed on antiprogrammed death 1 (PD1) receptor monoclonal antibody therapy. Subsequent VE1 immunohistochemistry was positive for BRAF V600E mutation, and the tumor responded dramatically to v-Raf murine sarcoma viral oncogene homolog B (BRAF)/Mitogen-activated protein kinase inhibitor combination therapy. This demonstrates how alternative BRAF testing methodology could produce results that can influence treatment choice and the outcome.
HIV Trafficking Between Blood and Semen During Early Untreated HIV Infection
Authors: Chaillon Antoine , Smith Davey M. , Vanpouille Christophe , Lisco Andrea , Jordan Parris , Caballero Gemma , Vargas Milenka , Gianella Sara , Mehta Sanjay R. 
Published: August 2016

Background:
Understanding the dynamics of HIV across anatomic compartments is important to design effective eradication strategies. In this study, we evaluated viral trafficking between blood and semen during primary HIV infection in 6 antiretroviral-naive men who have sex with men.

Methods:
Deep sequencing data of HIV env were generated from longitudinal blood plasma, peripheral blood mononuclear cells, and seminal plasma samples. The presence or absence of viral compartmentalization was assessed using tree-based Slatkin–Maddison and distance-based Fst methods. Phylogeographic analyses were performed using a discrete Bayesian asymmetric approach of diffusion with Markov jump count estimation to evaluate the gene flow between blood and semen during primary HIV infection. Levels of DNA from human herpesviruses and selected inflammatory cytokines were also measured on genital secretions collected at baseline to evaluate potential correlates of increased viral migration between anatomic compartments.

Results:
We detected varying degrees of compartmentalization in all 6 individuals evaluated. None of them maintained viral compartmentalization between blood and seminal plasma throughout the analyzed time points. Phylogeographic analyses revealed that the HIV population circulating in blood plasma populated the seminal compartment during the earliest stages of infection. In our limited data set, we found no association between local inflammation or herpesvirus shedding at baseline and viral trafficking between semen and blood.

Conclusions:
The early spread of virus from blood plasma to genital tract and the complex viral interplay between these compartments suggest that viral eradication efforts will require monitoring viral subpopulations in anatomic sites and viral trafficking during the course of infection.
Targeted re-sequencing reveals the genomic signatures of multiple barley domestications
Authors: Pankin Artem , Altmüller Janine , Becker Christian , von Korff Maria 
Published: August 2016

SummaryBarley (Hordeum vulgareL.) is an established model to study domestication of the Fertile Crescent cereals. Recent molecular data suggested that domesticated barley genomes consist of the ancestral blocks descending from multiple wild barley populations. However, the relationship between the mosaic ancestry patterns and the process of domestication itself remained unclear.To address this knowledge gap, we identified candidate domestication genes using selection scans based on targeted resequencing of 433 wild and domesticated barley accessions. We conducted phylogenetic, population structure, and ancestry analyses to investigate the origin of the domesticated barley haplotypes separately at the neutral and candidate domestication loci.We discovered multiple selective sweeps that occurred on all barley chromosomes during domestication in the background of several ancestral wild populations. The ancestry analyses demonstrated that, although the ancestral blocks of the domesticated barley genomes descended from all over the Fertile Crescent, the candidate domestication loci originated specifically in its eastern and western parts.These findings provided first molecular evidence in favor of multiple barley domestications in the Levantine and Zagros clusters of the origin of agriculture.
Widespread Historical Contingency in Influenza Viruses
Authors: Nshogozabahizi Jean Claude , Dench Jonathan , Aris-Brosou Stéphane 
Published: August 2016

AbstractIn systems biology and genomics, epistasis characterizes the impact that a substitution at a particular location in a genome can have on a substitution at another location. This phenomenon is often implicated in the evolution of drug resistance or to explain why particular ‘disease-causing’ mutations do not have the same outcome in all individuals. Hence, uncovering these mutations and their locations in a genome is a central question in biology. However, epistasis is notoriously difficult to uncover, especially in fast-evolving organisms. Here, we present a novel statistical approach that replies on a model developed in ecology and that we adapt to analyze genetic data in fast-evolving systems such as the influenza A virus. We validate the approach using a two-pronged strategy: extensive simulations demonstrate a low-to-moderate sensitivity with excellent specificity and precision, while analyses of experimentally-validated data recover known interactions, including in a eukaryotic system. We further evaluate the ability of our approach to detect correlated evolution during antigenic shifts or at the emergence of drug resistance. We show that in all cases, correlated evolution is prevalent in influenza A viruses, involving many pairs of sites linked together in chains, a hallmark of historical contingency. Strikingly, interacting sites are separated by large physical distances, which entails either long-range conformational changes or functional tradeoffs, for which we find support with the emergence of drug resistance. Our work paves a new way for the unbiased detection of epistasis in a wide range of organisms by performing whole-genome scans.
Microbial Signatures of Oral Dysbiosis, Periodontitis and Edentulism Revealed by Gene Meter Methodology
Authors: Hunter M. Colby , Pozhitkov Alex E. , Noble Peter A. 
Published: August 2016

ABSTRACTConceptual models suggest certain microorganisms (e.g., the red complex) are indicative of a specific disease state (e.g., periodontitis); however, recent studies have questioned the validity of these models. Here, the abundances of 500+ microbial species were determined in 16 patients with clinical signs of one of the following oral conditions: periodontitis, established caries, edentulism, and oral health. Our goal was to determine if the abundances of certain microorganisms reflect dysbiosis or a specific clinical condition that could be used as a signature for dental research. Microbial abundances were determined by the analysis of 138,718 calibrated probes using Gene Meter methodology. Each 16S rRNA gene was targeted by an average of 194 unique probes (n=25 nt). The calibration involved diluting pooled gene target samples, hybridizing each dilution to a DNA microarray, and fitting the probe intensities to adsorption models. The fit of the model to the experimental data was used to assess individual and aggregate probe behavior; good fits (R2>0.90) were retained for back-calculating microbial abundances from patient samples. The abundance of a gene was determined from the median of all calibrated individual probes or from the calibrated abundance of all aggregated probes. With the exception of genes with low abundances (< 2 arbitrary units), the abundances determined by the different calibrations were highly correlated (r ∼1.0). Seventeen genera were classified as signatures of dysbiosis because they had significantly higher abundances in patients with periodontitis and edentulism when contrasted with health. Similarly, 13 genera were classified as signatures of periodontitis, and 14 genera were classified as signatures of edentulism. The signatures could be used, individually or in combination, to assess the clinical status of a patient (e.g., evaluating treatments such as antibiotic therapies). Comparisons of the same patient samples revealed high false negatives (45%) for next-generation-sequencing results and low false positives (7%) for Gene Meter results.
Association ofAKAP6andMIR2113with cognitive performance in a population based sample of older adults
Authors: Andrews Shea J. , Das Debjani , Anstey Kaarin J. , Easteal Simon 
Published: August 2016

AbstractGenetic factors make a substantial contribution to inter-individual variability in cognitive function. A recent meta-analysis of genome-wide association studies identified two loci,AKAP6andMIR2113that are associated with general cognitive function. Here, we extend this previous research by investigating the association ofMIR2113andAKAP6with baseline and longitudinal nonlinear change across a broad spectrum of cognitive domains in community-based cohort of 1,570 older adults without dementia. Two SNPs,MIR211-rs10457441 andAKAP6-rs17522122 were genotyped in 1,570 non-demented older Australians of European ancestry, who were examined up to 4 times over 12 years. Linear mixed effects models were used to examine the association betweenAKAP6andMIR2113with cognitive performance in episodic memory, working memory, vocabulary, perceptual speed and reaction time at baseline and with linear and quadratic rates of change.AKAP6-rs17522122*T was associated with worse baseline performance in episodic memory, working memory, vocabulary and perceptual speed, but it was not associated with cognitive change in any domain.MIR2113-rs10457441*T was associated with accelerated decline in episodic memory. No other associations with baseline cognitive performance or with linear or quadratic rate or cognitive changes was observed for this SNP. These results confirm the previous finding that,AKAP6is associated with performance across multiple cognitive domains at baseline but not with cognitive decline, whileMIR2113primarily affects the rate at which memory declines over time.