bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends, Determinants, and Impact on Survival of Post-Lung Transplant Weight Changes: A Single-center Longitudinal Retrospective Study
Authors: Jomphe Valérie , Nguyen Cécile , Durette Gabrielle , Chagnon Miguel , Nasir Basil , Poirier Charles , Ferraro Pasquale , Lands Larry C. , Mailhot Geneviève 
Published: August 2019

Background.
Weight gain is commonly seen in lung transplant (LTx) recipients. Although previous studies have focused on weight changes at fixed time periods and relatively early after transplant, trends over time and long-term weight evolution have not been described in this population. The study objectives were to document weight changes up to 15 years post-LTx and assess the predictors of post-LTx weight changes and their associations with mortality.

Methods.
Retrospective cohort study of LTx recipients between January 1, 2000, and November 30, 2016 (n = 502). Absolute weight changes from transplant were calculated at fixed time periods (6 mo, 1, 2, 5, 10, and 15 y), and continuous trends over time were generated. Predictors of weight changes and their association with mortality were assessed using linear and Cox regression analysis.

Results.
LTx recipients experienced a gradual increase in weight, resulting from the combination of multiple weight trajectories. Interstitial lung disease diagnosis negatively predicted post-LTx weight changes at all time points, whereas transplant body mass index categories were significant predictors at earlier time points. Patients with a weight gain of >10% at 5 years had a better survival (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.20-0.66), whereas a 10% weight loss at earlier time points was associated with worse survival (1 y: HR, 2.04; 95% CI, 1.22-3.41 and 2 y: HR, 2.37; 95% CI, 1.22-4.58).

Conclusions.
Post-LTx weight changes display various trajectories, are predicted to some extent by individual and LTx-related factors, and have a negative or positive impact on survival depending on the time post-LTx. These results may lead to a better individualization of weight management after transplant.
Classification of idiopathic inflammatory myopathies: pathology perspectives
Authors: Tanboon Jantima , Nishino Ichizo 
Published: August 2019

Purpose of review
Idiopathic inflammatory myopathies (IIM) are rare diseases with heterogenous clinicopathological features. In recent years, new classification systems considering various combinations of clinical, serological, and pathological information have been proposed. This review summarizes recent clinicoseropathological development in major subgroups of IIM.

Recent findings
Considering clinicoseropathological features, IIM are suggestively classified into four major subgroups: dermatomyositis, immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASS), and inclusion body myositis (IBM). Many historically diagnosed polymyositis have been mainly reclassified as IBM, IMNM, and ASS. Different types of myositis-specific antibodies (MSA) suggest distinct clinicopathological subsets of IIM. Excluding IBM, at least one-third of the IIMs have no known associated MSA.

Summary
MSA are crucial for IIM classification but can be negative. Thus, IIM should be universally classified using stepwise or integrated information on clinical, serological, and pathological findings.
EZH2 inhibition results in genome-wide PRC2 redistribution
Authors: Yuan Chih-Chi , Jeon Ah Jung , Tucker-Kellogg Greg , Bryant Barbara , Trojer Patrick 
Published: August 2019

SummaryHistone methyltransferase polycomb repressive complex 2 (PRC2) plays a critical role in cell fate determination, and its catalytic subunit EZH2 is a key oncogenic driver in GCB-DLBCL. EZH2 inhibition in some GCB-DLBCL cell models leads to a global loss of H3K27me3, the derepression of a subset of silenced PRC2 target genes, and ultimately cell death. Here we show that EZH2 inhibition causes global redistribution of PRC2 components. We observe a reduction in the already-low levels of PRC2 at active genes. On the other hand, focal PRC2 accumulation and concomitant H3K27me3 retention occur at many canonical embryonic stem cell PRC2 nucleation sites. PRC2 accumulation is also enriched in plasma/memory cell genes repressed by PRC2 activity in the germinal center. We see PRC2 redistribution to, and H3K27me3 retention at, differentiation-related genes not only in cell lines that are insensitive to killing by EZH2 inhibition, but also in sensitive cell lines. Thus, PRC2 redistribution to B cell differentiation genes is not sufficient to explain the resistance to EZH2 inhibitors in some DLBCL cell lines.
MesenchymalIgf2is a major paracrine regulator of pancreatic growth and function
Authors: Hammerle Constanze M. , Sandovici Ionel , Brierley Gemma V. , Smith Nicola M. , Zimmer Warren E. , Zvetkova Ilona , Prosser Haydn M. , Sekita Yoichi , Lam Brian Y.H. , Ma Marcella , Cooper Wendy N. , Vidal-Puig Antonio , Ozanne Susan E. , Medina-Gómez Gema , Constância Miguel 
Published: August 2019

AbstractThe genetic mechanisms that determine the size of the adult pancreas are poorly understood. Here we demonstrate that many imprinted genes are highly expressed in the pancreatic mesenchyme, and explore the role ofIgf2 in-vivo. Mesenchyme-specificIgf2deletion results in acinar and beta-cell hypoplasia, postnatal whole-body growth restriction and maternal glucose intolerance during pregnancy. Surprisingly, mesenchymal mass is unaffected, suggesting that the mesenchyme is a developmental reservoir of IGF2 used for paracrine signalling. The unique actions of mesenchymal IGF2 are demonstrated by the absence of phenotypes uponIgf2deletion in the developing pancreatic epithelium. Furthermore, increased IGF2 activity specifically in the mesenchyme, throughIgf2loss-of-imprinting orIgf2rdeletion, leads to pancreatic acinar overgrowth.Ex-vivoexposure of primary acinar cells to exogenous IGF2 increases cell proliferation and amylase production through AKT signalling. We propose that mesenchymalIgf2, and perhaps other imprinted genes, are key developmental regulators of adult pancreas size and function.
A scalable culturing system for the marine annelid Platynereis dumerilii
Authors: Kuehn Emily , Stockinger Alexander W. , Girard Jerome , Raible Florian , Özpolat B. Duygu 
Published: August 2019

ABSTRACTPlatynereis dumerilii is a marine segmented worm (annelid) with externally fertilized embryos and it can be cultured for the full life cycle in the laboratory. The accessibility of embryos and larvae combined with the breadth of the established molecular and functional techniques has made P. dumerilii an attractive model for studying development, cell lineages, cell type evolution, reproduction, regeneration, the nervous system, and behavior. Traditionally, these worms have been kept in rooms dedicated for their culture. This allows for the regulation of temperature and light cycles, which is critical to synchronizing sexual maturation. However, regulating the conditions of a whole room present limitations, especially if experiments require being able to change culturing conditions. Here we present scalable and flexible culture methods that provide ability to control the environmental conditions, and have a multi-purpose culture space. We provide a closed setup shelving design with proper light conditions necessary for P. dumerilii to mature. We also implemented a standardized method of feeding P. dumerilii cultures with powdered spirulina which relieves the ambiguity associated with using frozen spinach, and helps standardize nutrition conditions across experiments and across different labs. By using these methods, we were able to raise mature P. dumerilii, capable of spawning and producing viable embryos for experimentation and replenishing culture populations. These methods will allow for the further accessibility of P. dumerilii as a model system, and they can be adapted for other aquatic organisms.
Phylogenies of extant species are consistent with an infinite array of diversification histories
Authors: Louca Stilianos , Pennell Matthew W. 
Published: August 2019

AbstractTime-calibrated molecular phylogenies of extant species ("extant timetrees") are widely used for estimating the dynamics of diversification rates (1–6) and testing for associations between these rates and environmental factors (5, 7) or species traits (8). However, there has been considerable debate surrounding the reliability of these inferences in the absence of fossil data (9–13), and to date this critical question remains unresolved. Here we mathematically clarify the precise information that can be extracted from extant timetrees under the generalized birth-death model, which underlies the majority of existing estimation methods. We prove that for a given extant timetree and a candidate diversification scenario, there exists an infinite number of alternative diversification scenarios that are equally likely to have generated a given tree. These “congruent” scenarios cannot possibly be distinguished using extant timetrees alone, even in the presence of infinite data. Importantly, congruent diversification scenarios can exhibit markedly different and yet plausible diversification dynamics, suggesting that many previous studies may have over-interpreted phylogenetic evidence. We show that sets of congruent models can be uniquely described using composite variables, which contain all available information about past dynamics of diversification (14); this suggests an alternative paradigm for learning about the past from extant timetrees.
A neural network for information seeking
Authors: White J. Kael , Bromberg-Martin Ethan S. , Heilbronner Sarah R. , Zhang Kaining , Pai Julia , Haber Suzanne N. , Monosov Ilya E. 
Published: August 2019

ABSTRACTHumans and other animals often show a strong desire to know the uncertain rewards their future has in store, even when they cannot use this information to influence the outcome. However, it is unknown how the brain predicts opportunities to gain information and motivates this information seeking behavior. Here we show that neurons in a network of interconnected subregions of primate anterior cingulate cortex and basal ganglia predict the moment of gaining information about uncertain rewards. Spontaneous increases in their information prediction signals are followed by gaze shifts toward objects associated with resolving uncertainty, and pharmacologically disrupting this network reduces the motivation to seek information. These findings demonstrate a cortico-basal ganglia mechanism responsible for motivating actions to resolve uncertainty by seeking knowledge about the future.
Telomeric chromosome ends are highly mobile and behave like free double-strand DNA breaks
Authors: Toulouze Mathias , Amitai Assaf , Shukron Ofir , Holcman David , Dubrana Karine 
Published: August 2019

AbstractChromosome organization and dynamics are critical for DNA transactions, including gene expression, replication, and DNA repair. In yeast, the chromosomes are anchored through their centromeres to the spindle pole body, and their telomeres are grouped into clusters at the nuclear periphery, constraining chromosome mobility. Here, we have used experimental and computational approaches to study the effects of chromosome-nuclear envelope (NE) attachments on the dynamics ofS. cerevisiaechromosomes. We found that although centromere proximal loci were, as predicted, more dynamically constrained than distal loci, telomeres were highly mobile, even when positioned at the nuclear periphery. Polymer modeling indicated that polymer ends are intrinsically more mobile than internal sites. We tested this model by measuring the mobility of a double strand break (DSB) end within a chromosome arm. Upon separation of the DSB ends, their mobility significantly increased. Altogether, our results reveal that telomeres behave as highly mobile polymer ends, despite interactions with the nuclear membrane.
Genetic control of tracheid properties in Norway spruce wood
Authors: Baison J , Zhou Linghua , Forsberg Nils , Mörling Tommy , Grahn Thomas , Olsson Lars , Karlsson Bo , Wu Harry X , Mellerowicz Ewa J. , Lundqvist Sven-Olof , García-Gil María Rosario 
Published: August 2019

Abstract➢ Through the use of genome-wide association (GWAS) mapping it is possible to establish the genetic basis of phenotypic trait variation. Our GWAS study presents the first such an effort in Norway spruce (Picea abies(L). Karst.) for the traits related to wood tracheid characteristics.➢ The study employed an exome capture genotyping approach that generated 178 101 high quality Single Nucleotide Polymorphisms (SNPs) from 40 018 probes within a population of 517 Norway spruce mother trees. We applied a LASSO based association mapping method using a functional multi-locus mapping approach that utilizes latent traits, with a stability selection probability method as the hypothesis testing approach to determine significant Quantitative Trait Loci (QTLs). Expression of the identified candidate genes was examined using publicly available spruce databases.➢ The analysis have provided 31 loci and 26 mostly novel candidate genes, majority of which showing specific expression in wood-forming tissues or high ubiquitous expression, potentially controlling tracheids dimensions, their cell wall thickness and microfibril angle. Among most promising candidates, the analysis identifiedPicea abies BIG GRAIN 2(PabBG2) with predicted function in auxin transport and sensitivity, andMA_373300g0010- similar to wall-associated receptor kinases (WAKs), both associated to cell wall thickness.➢ The results demonstrate feasibility of GWAS to identify novel candidate genes controlling industrially-relevant tracheid traits in Norway spruce. The presence of many traits with several significant QTLs supports the notion that the majority of these traits are polygenic in nature.
Anti-inflammatory role of curcumin in Lipopolysaccharide treated A549 cells at global proteome level and on mycobacterial infection
Authors: Singh Suchita , Arya Rakesh , Bargaje Rhishikesh R , Das Mrinal Kumar , Akram Subia , Faruquee Hossain Md. , Behera Rajendra Kumar , Nanda Ranjan Kumar , Agrawal Anurag 
Published: August 2019

AbstractA diet derived agent Curcumin (Diferuloylmethane), demonstrated its clinical application in inflammation, infection and cancer conditions. Nevertheless, its impact on the proteome of epithelial cells of non-small cell lung carcinoma (NSCLC) is yet to be explored. We employed a stable isotope labeling method for cell culture (SILAC) based relative quantitative proteomics and informatics analysis to comprehend global proteome change in A549 cells treated with curcumin and/or Lipopolysaccharide (LPS). Pretreated A549 cells were infected withMycobacterium tuberculosisH37Rv strain to monitor bacterial load. With exposure to curcumin and LPS, out of the 1492 identified proteins, 305 and 346 proteins showed deregulation respectively. The expression of BID and AIFM1 mitochondrial proteins which play critical role in apoptotic pathway were deregulated in curcumin treated cells. Higher mitochondria intensity was observed in curcumin treated A549 cells than LPS treatment. Simultaneous treatment of curcumin and LPS neutralized the effect of LPS. Curcumin and/or LPS pretreated A549 cells infected with H37Rv, showed successful bacterial internalization. LPS treated A549 cells after infection showed increased bacterial load than curcumin compared to non-treated infected cells. However, simultaneous treatment of curcumin and LPS neutralized the effect of LPS. This study generated molecular evidence to deepen our understanding of the anti-inflammatory role of curcumin and may be useful to identify molecular targets for drug discovery.
A comparison of pedigree, genetic, and genomic estimates of relatedness for informing pairing decisions in two critically endangered birds
Authors: Galla Stephanie , Moraga Roger , Brown Liz , Cleland Simone , Hoeppner Marc P. , Maloney Richard , Richardson Anne , Slater Lyndon , Santure Anna W. , Steeves Tammy 
Published: August 2019

AbstractConservation management strategies for many highly threatened species include conservation breeding to prevent extinction and enhance recovery. Pairing decisions for these conservation breeding programmes can be informed by pedigree data to minimise relatedness between individuals in an effort to avoid inbreeding, maximise diversity, and maintain evolutionary potential. However, conservation breeding programmes struggle to use this approach when pedigrees are shallow or incomplete. While genetic data (i.e., microsatellites) can be used to estimate relatedness to inform pairing decisions, emerging evidence indicates this approach lacks precision in genetically depauperate species, and more effective estimates will likely be obtained from genomic data (i.e., thousands of genome-wide single nucleotide polymorphisms, or SNPs). Here, we compare relatedness estimates using pedigree-, genetic-, and genomic-based approaches for making pairing decisions in two critically endangered birds endemic to New Zealand: kakī/black stilt (Himantopus novaezelandiae) and kākāriki karaka/orange-fronted parakeet (Cyanoramphus malherbi). Our findings indicate genetic-based estimates of relatedness are indeed the least precise when assessing known parent-offspring and full sibling relationships. Furthermore, our results show that relatedness estimates and subsequent pairing recommendations using PMx are most similar between pedigree- and genomic-based approaches. These combined results indicate that in lieu of robust pedigrees, SNPs are an effective tool for informing pairing decisions, which has exciting implications for many poorly pedigreed conservation breeding programmes worldwide.
Neuroanatomical Risk Factors for Post Traumatic Stress Disorder (PTSD) in Recent Trauma Survivors
Authors: Ben-Zion Ziv , Artzi Moran , Niry Dana , Keynan Nimrod Jackob , Zeevi Yoav , Admon Roee , Sharon Haggai , Halpern Pinchas , Liberzon Israel , Shalev Arieh Y. , Hendler Talma 
Published: August 2019

AbstractBackgroundLow hippocampal volume could serve as an early risk factor for Post-traumatic Stress Disorder (PTSD) in interaction with other brain anomalies of developmental origin. One such anomaly may well be a presence of large Cavum Septum Pellucidum (CSP), which has been loosely associated with PTSD. Here, we performed a longitudinal prospective study of recent trauma survivors. We hypothesized that at one-month after trauma exposure, the relation between hippocampal volume and PTSD symptom severity will be moderated by CSP volume, and that this early interaction will account for persistent PTSD symptoms at subsequent time-points.Methods171 adults (87 females, average age=34.22, range=18-65) admitted to a general hospital’s emergency department following a traumatic event, underwent clinical assessment and structural MRI within one-month after trauma. Follow-up clinical evaluations were conducted at six (n=97) and fourteen (n=78) months after trauma. Hippocampus and CSP volumes were measured automatically by FreeSurfer software and verified manually by a neuroradiologist.ResultsAt one-month following trauma, CSP volume significantly moderated the relation between hippocampal volume and PTSD severity (p=0.026), and this interaction further predicted symptom severity at fourteen months post-trauma (p=0.018). Specifically, individuals with smaller hippocampus and larger CSP at one-month post-trauma, showed more severe symptoms at one-and fourteen months following trauma exposure.ConclusionsOur study provides evidence for an early neuroanatomical risk factors for PTSD, which could also predict the progression of the disorder in the year following trauma exposure. Such a simple-to-acquire neuroanatomical signature for PTSD could guide early management, as well as long-term monitoring.Trial RegistrationNeurobehavioral Moderators of Post-traumatic Disease Trajectories. ClinicalTrials.gov registration:NCT03756545.https://clinicaltrials.gov/ct2/show/NCT03756545
Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors
Authors: Dembny Paul , Newman Andrew G. , Singh Manvendra , Hinz Michael , Szczepek Michal , Krüger Christina , Adalbert Robert , al-Dzaye Omar , Trimbuch Thorsten , Wallach Thomas , Kleinau Gunnar , Derkow Katja , Richard Bernhard C. , Schipke Carola , Scheidereit Claus , Golenbock Douglas , Peters Oliver , Coleman Michael , Heppner Frank L. , Scheerer Patrick , Tarabykin Victor , Ruprecht Klemens , Izsvák Zsuzsanna , Mayer Jens , Lehnardt Seija 
Published: August 2019

AbstractAlthough human endogenous retroviruses (HERVs) represent a substantial proportion of the human genome and some HERVs have been suggested to be involved in neurological disorders, little is known about their biological function and pathophysiological relevance. HERV-K(HML-2) comprises evolutionarily young proviruses transcribed in the brain. We report that RNA derived from an HERV-K(HML-2) env gene region binds to the human RNA-sensing Toll-like receptor (TLR) 8, activates human TLR8, as well as murine Tlr7, and causes neurodegeneration through TLR8 and Tlr7 in neurons and microglia. HERV-K(HML-2) RNA introduced extracellularly into the cerebrospinal fluid (CSF) of either C57BL/6 wild-type mice or APPPS1 mice, a mouse model for Alzheimer’s disease (AD), resulted in neurodegeneration. Tlr7-deficient mice were protected against neurodegenerative effects, but were re-sensitized towards HERV-K(HML-2) RNA when neurons ectopically expressed murine Tlr7 or human TLR8. Accordingly, transcriptome datasets of human brain samples from AD patients revealed a specific correlation of upregulated HERV-K(HML-2) and TLR8 RNA expression. HERV-K(HML-2) RNA was detectable more frequently in CSF from AD individuals compared to controls. Our data establish HERV-K(HML-2) RNA as an endogenous ligand for human TLR8 and murine Tlr7 and imply a functional contribution of specific human endogenous retroviral transcripts to neurodegenerative processes such as AD.
Transcriptome association studies of neuropsychiatric traits in African Americans implicatePRMT7in schizophrenia
Authors: Fiorica Peter N. , Wheeler Heather E. 
Published: August 2019

ABSTRACTIn the past fifteen years, genome-wide association studies (GWAS) have provided novel insight into the genetic architecture of various complex traits; however, this insight has been primarily focused on populations of European descent. This emphasis on European populations has led to individuals of recent African descent being grossly underrepresented in the study of genetics. With African Americans making up less than two percent of participants in neuropsychiatric GWAS, this discrepancy is magnified in diseases such as schizophrenia and bipolar disorder. In this study, we performed GWAS and the gene-based association method PrediXcan for schizophrenia (n=2,256) and bipolar disorder (n=1,019) in African American cohorts. In our PrediXcan analyses, we identifiedPRMT7(P= 5.5 × 10−6, local false sign rate = 0.12) as significantly associated with schizophrenia following an adaptive shrinkage multiple testing adjustment. This association with schizophrenia was confirmed in the much larger, predominantly European, Psychiatric Genomics Consortium. In addition to thePRMT7association with schizophrenia, we identified rs10168049 (P= 1.0 × 10−6) as a potential candidate locus for bipolar disorder with highly divergent allele frequencies across populations, highlighting the need for diversity in genetic studies.