bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prion-like propagation hypothesis in Alzheimer's and Parkinson's disease
Authors: Duyckaerts Charles , Clavaguera Florence , Potier Marie-Claude 
Published: February 2019

Purpose of review
This study, taking the example of Alzheimer's and Parkinson's diseases, presents the experimental and human data that support the hypothesis that Aβ, tau, and α-synuclein may seed and propagate the pathology and consider the potential clinical consequences.

Recent findings
Aβ aggregates transmit Aβ pathology to experimental animals. Interhuman transmission of Aβ pathology has also been observed in iatrogenic Creutzfeldt–Jakob disease, or after dural graft. Tau aggregates also transmit the pathology to mice when injected in the brain and propagates along neuronal pathways. Evidence of interhuman transmission is weak. Finally α-synuclein aggregates, when injected in specific areas of the brain may recapitulate Lewy pathology of Parkinson's disease but there is currently no hint of human to human transmission.

Summary
Since the first evidence that at least Aβ pathology of Alzheimer's disease could be transmitted to the animal, data have accumulated indicating that misfolded proteins characteristic of neurodegenerative diseases may seed and propagate pathology in a prion-like manner. The term propagon has been proposed to describe those proteins that act as prions at different levels. Taking the example of Alzheimer's and Parkinson's diseases, the experimental and human data supporting the hypothesis that Aβ, tau, and α-synuclein are indeed propagons are presented with their clinical consequences.
A Case of Buspirone Demonstrating Immediate and Sustained Benefit in a Man With Lifelong Non–Rapid-Eye-Movement Parasomnias
Authors: Mallapareddi Arun , Varghese Ranji 
Published: February 2019

Background
Non–rapid-eye-movement (NREM) parasomnias are disorders of sleep ranging from confusional arousals to sleepwalking and sleep-related eating disorders. Historically, antidepressants and benzodiazepines were recommended in treatment of NREM parasomnias. In this case report, we are reporting the use of buspirone in a patient with NREM parasomnias, which produced substantial resolution of symptoms.

Case Presentation
A 38-year-old man presented with confusional arousals and somnambulism. In addition, the patient had significant anxiety with work-related stress. Given the patient's concerns of side effect profile of other medications indicated in NREM parasomnias and the patient's history of anxiety, we started the patient on buspirone. The patient had significant improvement in his symptoms immediately after starting the medication with sustained relief from symptoms.

Conclusion
Buspirone can be considered an effective alternate treatment option for NREM parasomnias when other medications are not preferred or cannot be prescribed.
Association between asymmetric dimethylarginine serum levels and left ventricular longitudinal deformation in patients with normal ejection fractions: a two-dimensional speckle-tracking echocardiography examination
Authors: Hosseinsabet Ali , Akavan-Khaleghi Niloofar , Mohseni-Badalabadi Reza 
Published: February 2019

Objectives
Nitric oxide is an endogenous substance that preserves the myocardial function in patients with heart failure. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of endogenous nitric oxide synthase. We sought to explore the association between the left ventricular (LV) function as assessed with two-dimensional echocardiography and the serum level of ADMA in nondiabetic patients without significant coronary artery disease.

Patients and methods
Eighty-seven consecutive patients with normal LV ejection fractions were included in this cross-sectional study. The ADMA serum level was measured, and the longitudinal deformation indices of the LV myocardium were evaluated using two-dimensional speckle-tracking echocardiography (2DSTE).

Results
The systolic strain, the systolic strain rate, and the early and late diastolic strain rates as evaluated with 2DSTE were not statistically significantly different between the patients with normal ADMA serum levels and those with increased ADMA serum levels. The two study groups were also not significantly different in terms of the systolic and diastolic myocardial velocities obtained with tissue Doppler.

Conclusion
Our findings showed no statistically significant correlations between the serum ADMA level and the 2DSTE-derived indices of the longitudinal deformation of the LV myocardium in our nondiabetic patients without significant coronary artery stenosis and with normal LV ejection fractions.
Recent trends over time in vascular disease in type 1 diabetes: insights from the Pittsburgh Epidemiology of Diabetes Complications study
Authors: Costacou Tina , Orchard Trevor J. 
Published: February 2019

Aim
The aim of this study was to evaluate recent trends, by diagnosis year, in the cumulative incidence of vascular type 1 diabetes complications and their risk factors up to 35 years duration.

Participants and methods
Participants from the Epidemiology of Diabetes Complications study of childhood-onset type 1 diabetes were categorized into three-calendar year onset cohorts: 1965–1969, 1970–1974, and 1975–1980. All-cause, cardiovascular and renal mortality were determined both on the complete cohort (n=440) as well as in the subset with clinical examinations (n=363). Coronary artery disease (CAD, CAD death, myocardial infarction, revascularization, angina, and ischemic ECG abnormalities); lower extremity arterial disease (abnormal ankle brachial index/amputation/intermittent claudication); distal symmetric polyneuropathy (clinical exam); cardiac autonomic neuropathy (abnormal heart rate response to deep breathing); overt nephropathy (albumin excretion rate>200 μg/min); and proliferative retinopathy (fundus photography) were assessed on the subset with clinical examinations.

Results
While all-cause, cardiovascular and renal mortality improved with a more recent diagnosis in the overall cohort, no univariate differences were observed for complications requiring examination (CAD, distal symmetric polyneuropathy, cardiac autonomic neuropathy, and overt nephropathy), although a borderline trend toward improved complication-free survival with a more recent onset was observed for proliferative retinopathy (P=0.06). Lower extremity arterial disease incidence showed an anomalous pattern, being highest in the 1975–1980 and lowest in the 1970–1974 cohort (P=0.009). Allowing for risk factors over time did not materially change these results.

Conclusion
Despite declines in all-cause, cardiovascular and renal mortality in the total cohort, no improvements were observed in either mortality or complication incidence with a more recent onset in the examined cohort.
Combining the 5.8S and ITS2 gene regions to improve classification of fungi
Authors: Heeger Felix , Wurzbacher Christian , Bourne Elizabeth C. , Mazzoni Camila J. , Monaghan Michael T. 
Published: February 2019

SummaryThe internal transcribed spacer (ITS) is used in DNA metabarcoding of fungi. One disadvantage of its high variability may be a failure to classify OTUs when no similar reference sequence exists. We tested whether the 5.8S region, often sequenced with ITS2 but discarded before analysis, could provide OUT classifications when ITS fails.We usedin silicoevaluation to compare classification success of 5.8S and ITS from the UNITE database when reference sequences of the same species, genus, or family were removed. We then developed an automated pipeline for a combined 5.8S - ITS2 analysis and applied it to mixed environmental samples containing many lineages that are underrepresented in databases.ITS was clearlysuperior for species-level classifications with a complete reference database, but 5.8S outperformed ITS at higher level classifications with an incomplete database. Our combined 5.8S-ITS2 pipeline classified 3x more fungal OTUs compared to ITS2 alone, particularly within Chytridiomycota (10x) and Rozellamycota (3x).Missing reference sequences led to the failure of ITS to classify many fungal OTUs at all, and to a significant underestimation of environmental fungal diversity. Using 5.8S to complement ITS classification will likely provide better estimates of diversity in lineages for which database coverage is poor.
Brain-enriched coding and long non-coding RNA genes are overrepresented in recurrent autism spectrum disorder CNVs
Authors: Alinejad-Rokny Hamid , Heng Julian I.T. , Forrest Alistair R.R. 
Published: February 2019

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder with substantial phenotypic and etiological heterogeneity. It is estimated that 10-20% of cases are due to copy number variations (CNVs). Here we apply a newly developed CNV association tool (SNATCNV) to reanalyse CNV data from 19,663 autistic and 6,479 control subjects from the AutDB database. We demonstrate that SNATCNV outperforms existing CNV association methods by finding smaller genomic regions that better discriminate cases and controls. By integrating data from the FANTOM5 expression atlas we show that both known ASD causal genes identified by the SFARI and MSSNG consortia and genes within the CNVs identified by SNATCNV have brain enriched expression patterns; both brain-enriched coding and long-non-coding RNA genes are over-represented. We provide full lists of these brain enriched coding and lncRNA genes as a resource to the research community. We also go on to show that each CNV region is associated with a distinct set of phenotypes, that some are sex biased and highlight one deleted region where a brain-enriched lncRNA is the only gene present. Our analyses identify 47 high confidence ASD associated CNV regions and identifies brain-enriched genes which underlie this neurodevelopmental disorder.
GNI-A1mediates trade-off between grain number and grain weight in tetraploid wheat
Authors: Golan Guy , Ayalon Idan , Perry Aviad , Zimran Gil , Ade-Ajayi Toluwanimi , Mosquna Assaf , Distelfeld Assaf , Peleg Zvi 
Published: February 2019

AbstractGrain yield is a highly polygenic trait determined by the number of grains per unit area, as well as by grain weight. In wheat, grain number and grain weight are usually negatively correlated. Yet, the genetic basis underlying trade-off between the two is mostly unknown. Here, we fine-mapped a grain weight QTL using wild emmer introgressions in a durum wheat background, and showed that grain weight is associated with theGNI-A1gene, a regulator of floret fertility. In-depth characterization of grain number and grain weight indicated that suppression of distal florets by the wild emmerGNI-A1allele increase weight of proximal grains in basal and central spikelets due to alteration in assimilate distribution. Re-sequencing ofGNI-A1in tetraploid wheat demonstrated the rich allelic repertoire of the wild emmer gene pool, including a rare allele which was present in two gene copies and contained a non-synonymous mutation in the C-terminus of the protein. Using an F2population generated from a cross between wild emmer accessions Zavitan, which carries the rare allele, and TTD140, we demonstrated that this unique polymorphism is associated with grain weight, independent of grain number. Moreover, we showed, for the first time, thatGNI-A1proteins are transcriptional activators and that selection in domesticated wheat targeted compromised activity of the protein. Our finding expand the knowledge of the genetic basis underlying trade-off between key yield components and may contribute to breeding efforts for enhanced grain yield.
HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence
Authors: Sofiadis Konstantinos , Nikolic Milos , Kargapolova Yulia , Josipovic Natasa , Zirkel Anne , Papadakis Antonis , Papadionysiou Ioanna , Loughran Gary , Keanes James , Michel Audrey , Gusmao Eduardo G. , Mizi Athanasia , Georgomanolis Theodore , Altmüller Janine , Nürnberg Peter , Beyer Andreas , Papantonis Argyris 
Published: February 2019

AbstractSpatial organization and gene expression of mammalian chromosomes are maintained and regulated in conjunction with cell cycle progression. This is however disturbed once cells enter senescence and the highly abundant HMGB1 protein is depleted from senescent cell nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we know little about the positioning of HMGB1 on chromatin or about its roles in the nucleus. To address this, we mapped HMGB1 binding genome-wide in different primary cells using a tailored protocol. We integrated ChIP-seq and Hi-C data with a graph theory approach to uncover HMGB1 demarcation of a subset of topologically-associating domains (TADs) that harbor genes required for paracrine senescence. Moreover, using sCLIP, knock-down and overexpression experiments, we now show that HMGB1 is abona fideRNA-binding protein (RBP) bound to senescence-relevant mRNAs and affecting splicing. HMGB1 also has an interactome rich in RBPs, many of which are implicated in senescence regulation. The mRNAs of many of these RBPs are directly bound by HMGB1 and concertedly regulate the availability of SASP-relevant transcripts. Our findings highlight a broader than hitherto assumed role for HMGB1. It coordinates chromatin folding and RNA homeostasis as part of a feedforward loop controlling both cell-autonomous and paracrine senescence inside and outside of cells.
Identification of a functional non-coding variant in the GABAA receptor α2 subunit of the C57BL/6J mouse reference genome: Major implications for neuroscience research
Authors: Mulligan Megan K. , Abreo Timothy , Neuner Sarah M. , Parks Cory , Watkins Christine E. , Houseal M. Trevor , Shapaker Thomas M. , Hook Michael , Tan Haiyan , Wang Xusheng , Ingels Jesse , Peng Junmin , Lu Lu , Kaczorowski Catherine C. , Bryant Camron D. , Homanics Gregg E. , Williams Robert W. 
Published: February 2019

AbstractGABA type-A (GABA-A) receptors containing the α2 subunit (Gabra2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function. Genetic variation at the GABRA2 locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse. Gabra2 expression varies as a function of genotype and is modulated by sequence variants in several brain structures and populations, including F2 crosses originating from C57BL/6J (B6J) and the BXD recombinant inbred family derived from B6J and DBA/2J. Here we demonstrate a global reduction of Gabra2 brain mRNA and protein in the B6J strain relative to other inbred strains, and identify and validate the causal mutation in B6J. The mutation is a single base pair intronic deletion located adjacent to a splice acceptor site that only occurs in the B6J reference genome. The deletion became fixed in B6J between 1976 and 1991 and is now pervasive in many engineered lines, BXD strains generated after 1991, the Collaborative Cross, and the majority of consomic lines. Repair of the deletion using CRISPR-Cas9 mediated gene editing on a B6J genetic background completely restored brain levels of Gabra2 mRNA and protein. Comparison of transcript expression in hippocampus, cortex, and striatum between B6J and repaired genotypes revealed alterations in GABA-A receptor subunit expression, especially in striatum. These results suggest that naturally occurring variation in GABRA2 levels between B6J and other substrains or inbred strains may also explain strain differences in anxiety-like or alcohol and drug response traits related to striatal function. Characterization of the B6J private mutation in the Gabra2 gene is of critical importance to molecular genetic studies in neurobiological research as this strain is widely used to generate genetically engineered mice and murine genetic populations, and is the most widely utilized strain for evaluation of anxiety-like, depression-like, pain, epilepsy, and drug response traits that may be partly modulated by Gabra2 function.
Reproducible Risk Loci and Psychiatric Comorbidities in Anxiety: Results from ~200,000 Million Veteran Program Participants
Authors: Levey Daniel F. , Gelernter Joel , Polimanti Renato , Zhou Hang , Cheng Zhongshan , Aslan Mihaela , Quaden Rachel , Concato John , Radhakrishnan Krishnan , Bryois Julien , Sullivan Patrick F. ,   Million Veteran Program, Stein Murray B. 
Published: February 2019

AbstractWe used GWAS in the Million Veteran Program sample (nearly 200,000 informative individuals) using a continuous trait for anxiety (GAD-2) to identify 5 genome-wide significant (GWS) signals for European Americans (EA) and 1 for African Americans. The strongest findings were on chromosome 3 (rs4603973, p=7.40×10−11) near the SATB1 locus, a global regulator of gene expression and on chromosome 6 (rs6557168, p=1.04×10−9) near ESR1 which encodes estrogen receptor α. A locus identified on chromosome 7 near MADIL1 (p=1.62×10−8) has been previously identified in GWAS of bipolar disorder and of schizophrenia and may represent a risk factor for psychiatric disorders broadly. SNP-based heritability was estimated to be ~6% for GAD-2. We also GWASed for self-reported anxiety disorder diagnoses (N=224,330) and identified two GWS loci, one (rs35546597, MAF=0.42, p=1.88×10−8) near the AURKB locus, and the other (rsl0534613, MAF=0.41, p=4.92×10−8) near the IQCHE and MADIL1 locus identified in the GAD-2 analysis. We demonstrate reproducibility by replicating our top findings in the summary statistics from the Anxiety NeuroGenetics Study (ANGST) and a UK Biobank neuroticism GWAS. We also replicated top findings from a large UK Biobank preprint, demonstrating stability of GWAS findings in complex traits once sufficient power is attained. Finally, we found evidence of significant genetic overlap between anxiety and major depression using polygenic risk scores, but also found that the main anxiety signals are independent of those for MDD. This work presents novel insights into the neurobiological risk underpinning anxiety and related psychiatric disorders.SignificanceAnxiety disorders are common and often disabling. They are also frequently co-morbid with other mental disorders such as major depressive disorder (MDD); these disorders may share commonalities in their underlying genetic architecture. Using one of the largest homogenously phenotyped cohorts available, the Million Veteran Program sample, we investigated common variants associated with anxiety in genome-wide association studies (GWASes), using survey results from the GAD-2 anxiety scale (as a continuous trait, n=199,611), and self-reported anxiety disorder diagnosis (as a binary trait, n=224,330). This largest GWAS to date for anxiety and related traits identified numerous novel significant associations, several of which are replicated in other datasets, and allows inference of underlying biology.
Musashiexpression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival inDrosophila
Authors: Sharma Amit , Akagi Kazutaka , Pattavina Blaine , Wilson Kenneth A , Nelson Christopher , Watson Mark , Maksoud Elie , Ortega Mauricio , Brem Rachel , Kapahi Pankaj 
Published: February 2019

AbstractExposure to genotoxic stress by environmental agents or treatments, such as radiation therapy, can diminish health span and accelerate aging. We have developed aDrosophila melanogastermodel to study the molecular effects of radiation-induced damage and repair. Utilizing a quantitative intestinal permeability assay, we performed an unbiased GWAS screen (using ∼150 strains from the DGRP reference panel) to search for natural genetic variants that regulate radiation-induced gut permeability. From this screen, we identified the RNA binding protein,Musashi (msi).Msioverexpression promoted intestinal stem cell proliferation, which increased survival after irradiation and rescued radiation-induced gut permeability. We identified that a novel role ofMsi inISC proliferation a novel role forMsiin enhancing ISC function following radiation-induced gut damage, which identifiesMsias a potential therapeutic target.
Exploring the space of human exploration
Authors: Schulz Eric , Bertram Lara , Hofer Matthias , Nelson Jonathan D. 
Published: February 2019

AbstractWhat drives people’s exploration in complex scenarios where they have to actively acquire information by making queries? How do people adapt their selection of queries to their environment? We explore these questions using Entropy Mastermind, a novel variant of the Mastermind code-breaking game, in which participants have to guess a secret code by making useful queries. Participants solved games more efficiently and more quickly if the entropy of the game environment was low; moreover, people adapted their initial queries to the scenario they were in. We also investigated whether it would be possible to predict participants’ queries within the generalized Sharma-Mittal information-theoretic framework. Although predicting individual queries is difficult, the modeling framework offered important insight on human behavior. Entropy Mastermind offers rich possibilities for modeling and behavioral research.
Selfish: Discovery of Differential Chromatin Interactions via a Self-Similarity Measure
Authors: Ardakany Abbas Roayaei , Ay Ferhat , Lonardi Stefano 
Published: February 2019

AbstractMotivationHigh-throughput conformation capture experiments such as Hi-C provide genome-wide maps of chromatin interactions, enabling life scientists to investigate the role of the three-dimensional structure of genomes in gene regulation and other essential cellular functions. A fundamental problem in the analysis of Hi-C data is how to compare two contact maps derived from Hi-C experiments. Detecting similarities and differences between contact maps is critical in evaluating the reproducibility of replicate experiments and identifying differential genomic regions with biological significance. Due to the complexity of chromatin conformations and the presence of technology-driven and sequence-specific biases, the comparative analysis of Hi-C data is analytically and computationally challenging.ResultsWe present a novel method called Selfish for the comparative analysis of Hi-C data that takes advantage of the structural self-similarity in contact maps. We define a novel self-similarity measure to design algorithms for (i) measuring reproducibility for Hi-C replicate experiments and (ii) finding differential chromatin interactions between two contact maps. Extensive experimental results on simulated and real data show that Selfish is more accurate and robust than state-of-the-art methods.Availabilityhttps://github.com/ucrbioinfo/SelfishContactaroay001@ucr.eduandstelo@cs.ucr.edu
Making ATP fast and slow: do yeasts play a mixed strategy to metabolise glucose?
Authors: Safdari Hadiseh , Sadeghi Mehdi , Kalirad Ata 
Published: February 2019

AbstractThe ability of some microorganisms to switch from respiration to fermentation in the presence of oxygen-the so-called Crabtree effect-has been a fascinating subject of study at the theoretical and experimental fronts. Game-theoretical approaches have been routinely used to examine and explain the way a microorganism, such as yeast, would switch between the two ATP-producing pathways, i.e., respiration and fermentation. Here we attempt to explain the switch between respiration and fermentation in yeast by constructing a simple metabolic switch. We then utilise an individual-based model, in which each individual is equipped with all the relevant chemical reactions, to see how cells equipped with such metabolic switch would behave in different conditions. We further investigate our proposed metabolic switch using the game-theoretical approach. Based on this model, we postulate that individuals play a mixed game of glucose metabolism in the population. This approach not only sheds some light in the varieties of metabolic regulations that can be utilised by the individual in the population in competition with others for a common resource, it would also allow a better understanding of the causes of the Warburg effect and similar phenomena observed in nature.