bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome polymorphisms track trans‐Atlantic divergence and secondary contact in Atlantic salmon
Authors: Lehnert Sarah J. , Bentzen Paul , Kess Tony , Lien Sigbjørn , Horne John B. , Clément Marie , Bradbury Ian R. 
Published: March 2019

AbstractPleistocene glaciations drove repeated range contractions and expansions shaping contemporary intraspecific diversity. Atlantic salmon (Salmo salar) in the western and eastern Atlantic diverged >600,000 years before present, with the two lineages isolated in different southern refugia during glacial maxima, driving trans‐Atlantic genomic and karyotypic divergence. Here, we investigate the genomic consequences of glacial isolation and trans‐Atlantic secondary contact using 108,870 single nucleotide polymorphisms genotyped in 80 North American and European populations. Throughout North America, we identified extensive interindividual variation and discrete linkage blocks within and between chromosomes with known trans‐Atlantic differences in rearrangements: Ssa01/Ssa23 translocation and Ssa08/Ssa29 fusion. Spatial genetic analyses suggest independence of rearrangements, with Ssa01/Ssa23 showing high European introgression (>50%) in northern populations indicative of post‐glacial trans‐Atlantic secondary contact, contrasting with low European ancestry genome‐wide (3%). Ssa08/Ssa29 showed greater intrapopulation diversity, suggesting a derived chromosome fusion polymorphism that evolved within North America. Evidence of potential selection on both genomic regions suggests that the adaptive role of rearrangements warrants further investigation in Atlantic salmon. Our study highlights how Pleistocene glaciations can influence large‐scale intraspecific variation in genomic architecture of northern species.
Deletion of Robo4 prevents high‐fat diet‐induced adipose artery and systemic metabolic dysfunction
Authors: Phuong Tam T. T. , Walker Ashley E. , Henson Grant D. , Machin Daniel R. , Li Dean Y. , Donato Anthony J. , Lesniewski Lisa A. 
Published: March 2019

AbstractObjectiveAccumulating evidence suggests the vascular endothelium plays a fundamental role in the pathophysiology of obesity by regulating the functional status of white adipose and systemic metabolism. Robo4 is expressed specifically in endothelial cells and increases vascular stability and inhibits angiogenesis. We sought to determine the role of Robo4 in modulating cardiometabolic function in response to high‐fat feeding.MethodsWe examined exercise capacity, glucose tolerance, and white adipose tissue artery gene expression, endothelium‐dependent dilation (EDD), and angiogenesis in wild type and Robo4 knockout (KO) mice fed normal chow (NC) or a high‐fat diet (HFD).ResultsWe found Robo4 deletion enhances exercise capacity in NC‐fed mice and HFD markedly increased the expression of the Robo4 ligand, Slit2, in white adipose tissue. Deletion of Robo4 increased angiogenesis in white adipose tissue and protected against HFD‐induced impairments in white adipose artery vasodilation and glucose intolerance.ConclusionsWe demonstrate a novel functional role for Robo4 in endothelial cell function and metabolic homeostasis in white adipose tissue, with Robo4 deletion protecting against endothelial and metabolic dysfunction associated with a HFD. Our findings suggest that Robo4‐dependent signaling pathways may be a novel target in anti‐obesity therapy.
A two‐component regulatory system VfmIH modulates multiple virulence traits in Dickeya zeae
Authors: Lv Mingfa , Hu Ming , Li Peng , Jiang Zide , Zhang Lian‐Hui , Zhou Jianuan 
Published: March 2019

SummaryBacterial pathogen Dickeya zeae strain EC1 produces antibiotics‐like phytotoxins called zeamines, which are major virulence determinants encoded by the zms gene cluster. In this study, we identified a zeamine‐deficient mutant with a Tn5 insertion in a gene designated as vfmI encoding a two‐component system (TCS) sensor histidine kinase (HK), which is accompanied by vfmH encoding a response regulator (RR) at the same genetic locus. Domain analysis shows this TCS is analogous to the VfmIH of D. dadantii, with typical characteristics of sensor HK and RR, respectively, and sharing the same operon. Deletion of either vfmI or vfmH resulted in decreased production of zeamines and cell wall degrading enzymes (CWDEs), and alleviated virulence on rice seeds and potato tubers. In D. dadantii 3937, VfmH was shown to bind to the promoters of vfmA and vfmE, while in D. zeae EC1, VfmH could bind to the promoters of vfmA, vfmE and vfmF. RNA‐seq analysis of strain EC1 and its vfmH mutant also showed that the TCS positively regulated a range of virulence genes, including zms, T1SS, T2SS, T3SS, T6SS, flagellar and CWDE genes.
Calcineurin responsive zinc‐finger‐1 binds to a unique promoter sequence to upregulate neuronal calcium sensor‐1, whose interaction with MID‐1 increases tolerance to calcium stress in Neurospora crassa
Authors: Gohain Dibakar , Tamuli Ranjan 
Published: March 2019

SummaryWe studied the molecular mechanism of neuronal calcium sensor‐1 (NCS‐1) signaling pathway for tolerance to Ca2+ stress in Neurospora crassa. Increasing concentration of Ca2+ increased the expression of ncs‐1; however, the calcineurin inhibitor FK506 severely reduced ncs‐1 mRNA transcript levels. Chromatin immunoprecipitation (ChIP) studies revealed that the transcription factor calcineurin responsive zinc finger‐1 (CRZ‐1) binds to the ncs‐1 promoter, and CRZ‐1 binding upregulated ncs‐1 expression under high Ca2+ concentrations. These results suggested the regulation of NCS‐1 function through calcineurin‐ CRZ‐1 signaling pathway. Furthermore, the electrophoretic mobility shift assay (EMSA) revealed that the CRZ‐1 binds specifically to an 8 bp sequence 5ʹ‐CCTTCACA‐3ʹ in the ncs‐1 promoter 216 bp upstream of the ATG start codon. We also showed that NCS‐1 binds to the Ca2+ permeable channel MID‐1 for tolerance to Ca2+ stress. Therefore, CRZ‐1 binds to a unique sequence in the ncs‐1 promoter, causing upregulation of NCS‐1 that binds to MID‐1 for tolerance to Ca2+ stress.
Comparison of genotyping methods for Cunninghamella bertholletiae
Authors: Verhasselt Hedda Luise , Radke Julia , Schmidt Dirk , Killengray David , Scharmann Ulrike , Rickerts Volker , Hansen Wiebke , Seidel Danila , Falces‐Romero Iker , Buer Jan , Rath Peter‐Michael , Steinmann Joerg 
Published: March 2019

SummaryBackgroundInvasive fungal infections caused by filamentous fungi of the order Mucorales are serious complications in immunocompromised patients and often associated with fatal outcome. As a member of this order, Cunninghamella bertholletiae is a saprophytic fungus with naturally exhibited high minimum inhibitory concentrations against common antifungal drugs and with the potential for outbreaks in clinical settings.Objectives and methodsIn a proof‐of‐principle study, we evaluated the performance of microsatellite markers for the discrimination of thirteen C. bertholletiae isolates from various sources in comparison with a repetitive sequence‐based PCR (rep‐PCR) and random amplification of polymorphic DNA (RAPD). Based on the higher discriminatory power of the microsatellite PCR with five separate primer pairs (Simpson's index of 1 vs 0 [RAPD] and 0 [rep‐PCR]), the novel method was applied to eight additional isolates, including four well‐characterised isolates from a cluster of infections in a next step.ResultsIn total, microsatellite PCR identified 21 separate genotypes. A probable epidemiological association of the cluster isolates could be demonstrated by microsatellite genotyping.ConclusionIn conclusion, our findings demonstrate the value of microsatellite PCR in genotyping Cunninghamella bertholletiae and its potential for future applications with other species of the order Mucorales.
Algae−bacteria interactions that balance the planktonic microbiome
Authors: Cirri Emilio , Pohnert Georg 
Published: March 2019

SummaryPhytoplankton communities within the photic zones of the oceans and lakes are characterised by highly complex assemblages of unicellular microalgae and associated bacteria. The interconnected evolutionary history of algae and bacteria allowed the formation of a wide spectrum of associations defined by orchestrated nutrient exchange, mutual support with growth factors, quorum sensing mediation, and episodic killing of the partners to obtain more resources. In this review, we discuss how these cross‐kingdom interactions shape plankton communities that undergo annual, seasonal switching between alternative states with balanced multispecies consortia. We illustrate how these microscopic interactions can have consequences that scale up to influence global element cycling.
Evolutionary history of the buildup and breakdown of the heterostylous syndrome in Plumbaginaceae
Authors: Costa Joana , Torices Rubén , Barrett Spencer C. H. 
Published: March 2019

SummaryThe evolutionary pathways leading to the heterostylous syndrome are not well understood, and models concerning the origins of distyly differ in the order in which reciprocal herkogamy and self‐incompatibility evolve. We investigated the evolution and breakdown of distyly in Plumbaginaceae, a family with considerable diversity of floral traits and reproductive systems.Using Bayesian Markov chain Monte Carlo analyses and stochastic character mapping, we examined the evolutionary assembly and breakdown of the heterostylous syndrome based on a well‐resolved phylogeny of 121 species of Plumbaginaceae and six outgroup taxa using five nuclear and plastid gene regions. We used the distribution of reproductive traits and reconstructed ancestral characters across phylogenies to evaluate competing models for the evolution of distyly.The most likely common ancestor of Plumbaginaceae was self‐incompatible and monomorphic for sex‐organ arrangement and pollen‐stigma characters. Character state reconstructions indicated that reciprocal herkogamy evolved at least three times and that shifts to selfing and apomixis occurred on multiple occasions.Our results provide comparative support for the early ideas of H. G. Baker on evolutionary pathways in Plumbaginaceae, and the more recent selfing avoidance model by D. & B. Charlesworth in which distyly evolves from self‐incompatible ancestors.
European Society of Pediatric Nephrology survey on current practice regarding recurrent focal segmental glomerulosclerosis after pediatric kidney transplantation
Authors: Bouts Antonia , Veltkamp Floor , Tönshoff Burkhard , Vivarelli Marina ,   Members of the Working Group “Transplantation”, “Idiopathic Nephrotic Syndrome” of the European Society of Pediatric Nephrology
Published: March 2019

AbstractIntroductionPrimary FSGS is an important cause of ESRD in children. FSGS recurrence after kidney transplantation is associated with early graft loss. No guidelines for treatment of FSGS recurrence exist. We conducted a survey to gain insight into variation of treatment between centers.MethodsA survey was sent to all members of the ESPN on behalf of the “Renal Transplantation” and “Idiopathic Nephrotic Syndrome” working groups.ResultsFifty‐nine nephrologists from 31 countries responded, reporting 807 FSGS patients, with 241 (30%) FSGS recurrences after transplantation. Recurrence varied from 0% to 100% between respondents. Native nephrectomy before or during transplantation was performed, respectively, always (37%), never (39%), or on clinical indication (17%). Half of the respondents started preventive treatment before transplantation, using PF (n = 10); R (n = 4); PF or IA, plus R (n = 9); cyclosporine (n = 2); or unknown (n = 4). Immunosuppressive therapy for patients without known mutations consisted of a combination of steroids, tacrolimus/cyclosporine, and MMF, with or without IL‐2R‐blockade in, respectively, 61% and 86% of the respondents. Sixty‐three percent applied a similar regimen to patients with known mutations. FSGS recurrence was treated with PF or IA, plus R by 66% of respondents; 54% observed no response. Complete remission in >50% of patients was reported by 41% of the respondents.DiscussionFSGS recurrence after transplantation is common, but varies greatly between centers. We found great variability in preventive and therapeutic treatment regimens. Future research should focus on predisposing factors, including biopsy findings and genetic mutations, and standardized treatment.
Structural brain differences predict early traumatic memory processing
Authors: Gvozdanovic Geraldine , Stämpfli Philipp , Seifritz Erich , Rasch Björn 
Published: March 2019

AbstractIntrusive memories are a key symptom of post‐traumatic stress disorder (PTSD). They emerge early after trauma exposure and are predictive for PTSD development. There is a high relevance in evaluating the neurobiological mechanisms of early stages of intrusive symptom development to provide a further understanding of PTSD. In the present study, we explore structural differences in healthy young female subjects preceding experimental trauma exposure and their relationship to early intrusive memory development using a traumatic film paradigm. With voxel‐based morphometry, we demonstrate that smaller insular volume was associated with an increased number of early intrusive film memories. Moreover, larger lingual gyrus/cerebellar and inferior frontal gyrus/precentral gyrus volumes were also related to an increased number of early intrusive film memories. Our results identify unique brain areas associated with early experimental trauma memory processing and highlight the necessity of evaluating early symptom stages relevant for personalized PTSD prevention and treatment.
Noninvasive fetal RHD genotyping to guide targeted anti‐D prophylaxis–an external quality assessment workshop
Authors: Clausen Frederik Banch , Barrett Angela Natalie ,   The Noninvasive Fetal RHD Genotyping EQA2017 Working Group
Published: March 2019

Background and ObjectivesFetal RHD genotyping of cell‐free fetal DNA from RhD‐negative pregnant women can be used to guide targeted antenatal and postnatal anti‐D prophylaxis for the prevention of RhD immunization. To assure the quality of clinical testing, we conducted an external quality assessment workshop with the participation of 28 laboratories.Materials and MethodsAliquots of pooled maternal plasma were sent to each laboratory. One sample was positive, and the second sample was negative for fetal RHD, verified by pre‐workshop testing using quantitative real‐time PCR (qPCR) analysis of RHD exons 4, 5, 7 and 10. Plasma samples were shipped at room temperature. A reporting scheme was supplied for data collection, including questions regarding the methodological setup, results and clinical recommendations. Different methodological approaches were used, all employing qPCR with a total of eight different combinations of RHD exon targets. The samples were tested blindly.ResultsFetal RHD genotyping was performed with no false‐negative and no false‐positive results. One inconclusive result was reported for the RHD‐positive sample, and four inconclusive results were reported for the RHD‐negative sample. All clinical conclusions were satisfactory.ConclusionThis external quality assessment workshop demonstrates that despite the different approaches taken to perform the clinical assays, fetal RHD genotyping is a reliable laboratory assay to guide targeted use of Rh prophylaxis in a clinical setting.
A tractable, simplified ex vivo human skin model of wound infection
Authors: Yoon Daniel J. , Fregoso Daniel R. , Nguyen Duc , Chen Vivien , Strbo Natasa , Fuentes Jaime J. , Tomic‐Canic Marjana , Crawford Robert , Pastar Irena , Isseroff R. Rivkah 
Published: March 2019

AbstractThe prevalence of infection in chronic wounds is well documented in the literature but not optimally studied due to the drawbacks of current methodologies. Here, we describe a tractable and simplified ex vivo human skin model of infection that addresses the critical drawbacks of high costs and limited translatability. Wounds were generated from excised abdominal skin from cosmetic procedures and cultured, inoculated with Staphylococcus aureus strain UAMS‐1, or under aseptic conditions. After three days, the infected wounds exhibited biofilm formation and significantly impaired reepithelialization compared to the control. Additionally, promigratory and proreparative genes were significantly downregulated, while proinflammatory genes were significantly upregulated, demonstrating molecular characterizations of impaired healing as in chronic wounds. This model allows for a simplified and versatile tool for the study of wound infection and subsequent development of novel therapies.
The desirable donor pig to eliminate all xenoreactive antigens
Authors: Ladowski Joseph , Martens Greg , Estrada Jose , Tector Matthew , Tector Joseph 
Published: March 2019

AbstractThe humoral barrier has been the limiting factor in moving xenotransplantation towards the clinic. Improvements in somatic cell nuclear transfer and genome editing, particularly CRISPR‐Cas9, have made it possible to create pigs with multiple glycan xenoantigen deletions for the purposes of reducing xenoreactive antibody binding to the xenografted organ. Recent studies have also considered the aetiology and existence of antibodies directed at the swine leucocyte antigen (SLA) complex, and potential genetic engineering strategies to avoid these antibodies. Evaluation of xenoreactive antibody binding is very important for the advancement of xenotransplantation, because if patients do not have any detectable xenoreactive antibody, then it is reasonable to expect that cellular rejection and not antibody‐mediated rejection (AMR) will be the next hurdle to clinical application.
Comparing Predictive Accuracy and Computational Costs for Viscoelastic Modeling of Spinal Cord Tissues
Authors: Ramo Nicole L. , Troyer Kevin L. , Puttlitz Christian M. 
Published: March 2019

Abstract
The constitutive equation used to characterize and model spinal tissues can significantly influence the conclusions from experimental and computational studies. Therefore, researchers must make critical judgments regarding the balance of computational efficiency and predictive accuracy necessary for their purposes. The objective of this study is to quantitatively compare the fitting and prediction accuracy of linear viscoelastic (LV), quasi-linear viscoelastic (QLV), and (fully) nonlinear viscoelastic (NLV) modeling of spinal-cord-pia-arachnoid-construct (SCPC), isolated cord parenchyma, and isolated pia-arachnoid-complex (PAC) mechanics in order to better inform these judgements. Experimental data collected during dynamic cyclic testing of each tissue condition were used to fit each viscoelastic formulation. These fitted models were then used to predict independent experimental data from stress-relaxation testing. Relative fitting accuracy was found not to directly reflect relative predictive accuracy, emphasizing the need for material model validation through predictions of independent data. For the SCPC and isolated cord, the NLV formulation best predicted the mechanical response to arbitrary loading conditions, but required significantly greater computational run time. The mechanical response of the PAC under arbitrary loading conditions was best predicted by the QLV formulation.
Genetics of Group A Streptococci
Authors: Cho Kyu Hong , Port Gary C. , Caparon Michael 
Published: March 2019

ABSTRACT

Streptococcus pyogenes
(group A streptococcus) is remarkable in terms of the large number of diseases it can cause in humans and for the large number of streptococcal factors that have been identified as potential virulence determinants for these diseases. A challenge is to link the function of potential virulence factors to the pathogenesis of specific diseases. An exciting advance has been the development of sophisticated genetic systems for the construction of loss-of-function, conditional, hypomorphic, and gain-of-function mutations in targeted
S. pyogenes
genes that can be used to test specific hypotheses regarding these genes in pathogenesis. This will facilitate a mechanistic understanding of how a specific gene function contributes to the pathogenesis of each streptococcal disease. Since the first
S. pyogenes
genome was completed in 2001, hundreds of complete and draft genome sequences have been deposited. We now know that the average
S. pyogenes
genome is approximately 1.85 Mb and encodes ∼1,800 genes and that the function of most of those genes in pathogenesis remains to be elucidated. However, advances in the development of a variety of genetic tools for manipulation of the
S. pyogenes
genome now provide a platform for the interrogation of gene/phenotype relationships for individual
S. pyogenes
diseases, which may lead to the development of more sophisticated and targeted therapeutic interventions. This article presents an overview of these genetic tools, including the methods of genetic modification and their applications.
What does best practice care for musculoskeletal pain look like? Eleven consistent recommendations from high-quality clinical practice guidelines: systematic review
Authors: Lin Ivan , Wiles Louise , Waller Rob , Goucke Roger , Nagree Yusuf , Gibberd Michael , Straker Leon , Maher Chris G , O’Sullivan Peter P B 
Published: March 2019

ObjectivesTo identify common recommendations for high-quality care for the most common musculoskeletal (MSK) pain sites encountered by clinicians in emergency and primary care (spinal (lumbar, thoracic and cervical), hip/knee (including osteoarthritis [OA] and shoulder) from contemporary, high-quality clinical practice guidelines (CPGs).DesignSystematic review, critical appraisal and narrative synthesis of MSK pain CPG recommendations.Eligibility criteriaIncluded MSK pain CPGs were written in English, rated as high quality, published from 2011, focused on adults and described development processes. Excluded CPGs were for: traumatic MSK pain, single modalities (eg, surgery), traditional healing/medicine, specific disease processes (eg, inflammatory arthropathies) or those that required payment.Data sourcesFour scientific databases (MEDLINE, Embase, CINAHL and Physiotherapy Evidence Database) and four guideline repositories.Results6232 records were identified, 44 CPGs were appraised and 11 were rated as high quality (low back pain: 4, OA: 4, neck: 2 and shoulder: 1). We identified 11 recommendations for MSK pain care: ensure care is patient centred, screen for red flag conditions, assess psychosocial factors, use imaging selectively, undertake a physical examination, monitor patient progress, provide education/information, address physical activity/exercise, use manual therapy only as an adjunct to other treatments, offer high-quality non-surgical care prior to surgery and try to keep patients at work.ConclusionThese 11 recommendations guide healthcare consumers, clinicians, researchers and policy makers to manage MSK pain. This should improve the quality of care of MSK pain.