bluuebunny/crossref_metadata_2025_split huggingface dataset:
T2 Mapping in Prostate Cancer
Authors: Mai Julia , Abubrig Mohamed , Lehmann Thomas , Hilbert Tom , Weiland Elisabeth , Grimm Marc O. , Teichgräber Ulf , Franiel Tobias 
Published: November 2018

Objectives
The aim of the study was to determine the quantitative T2 values in prostate tissue and evaluate them for detection and grading of prostate cancer.

Materials and Methods
After approval from the local ethics committee, morphological T2-weighted (T2w) images, apparent diffusion coefficient (ADC) maps from diffusion-weighted images, quantitative T2 maps, and calculated T2w images from 75 men (median age, 66.3 years; median PSA, 8.2 ng/mL) were acquired at 3 T magnetic resonance imaging (MRI). Data were retrospectively evaluated for their distinction between prostate pathologies.
Eight hundred fifty-seven areas of normal gland (n = 378), prostate cancer (54x Gleason score 6, 98x Gleason score 7, 25x Gleason score 8), benign prostatic hyperplasia (BPH) nodes (n = 150), prostatitis (n = 119), and precancerous lesions (n = 33) were determined on calculated and morphological T2w images. Histological criterion standards were whole gland sections (16 patients), MRI-guided in-bore biopsies (32 patients), MRI/transrectal ultrasound-fusion biopsies (15 patients), and systematic 12-core transrectal ultrasound-guided biopsies (12 patients). Significance was assumed to be P < 0.05.

Results
The quantitative T2 values vary significantly between prostate cancer and normal gland tissue (area under the curve [AUC], 0.871), cancer and BPH nodes (AUC = 0.827), and Gleason score 6 and 7 or higher (AUC, 0.742). The quantitative T2 values decrease with increasing Gleason scores and correlate significantly with the ADC values (r = 0.806).
The detection accuracy of prostate cancer on calculated (AUC = 0.682) and morphological T2w images (AUC = 0.658) is not significantly different.

Conclusions
Quantitative T2 values seem to be suitable for distinguishing between prostate cancer and normal gland tissue or BPH nodes. Similar to the ADC values, they offer an indication of the aggressiveness of the prostate cancer.
Prognostic Value of Vascular Calcifications and Regional Fat Depots Derived From Conventional Chest Computed Tomography
Authors: Rodríguez-Granillo Gastón A. , Reynoso Exequiel , Capuñay Carlos , Antoniades Charalambos , Shaw Leslee J. , Carrascosa Patricia 
Published: November 2018

Purpose:
The prognostic value of vascular calcifications as well as of regional fat depots has been reported separately, in population-based studies, and using gated-computed tomography (CT) examinations. We, therefore, explored the interplay and prognostic value of vascular calcifications and adipose tissue depots assessed during conventional nongated chest CT.

Materials and Methods:
We enrolled a consecutive series of 1250 patients aged between 35 and 74 years who underwent clinically indicated chest CT scans. We measured the extent of coronary artery calcification (CAC) using the segment-involvement score (CACSIS), and aortic and valve calcification. Pericardial fat volume (PFV), hepatic fat, and abdominal subcutaneous adipose tissue were also calculated. Patients were followed-up for all-cause mortality.

Results:
A total of 577 (46%) patients had presence of CAC in the coronary tree. Over a mean follow-up of 3.7 years, 51 (4%) deaths occurred, 23 (4.1%) in male patients and 28 (4.1%) in female patients. Patients with higher PFV were older (P<0.0001), more frequently male (P<0.0001), had higher abdominal subcutaneous adipose tissue (P<0.0001), hepatic fat (P<0.0001), as well as a larger extent of CAC (P<0.0001), aortic calcium (P<0.0001), and valve calcium (P<0.0001). From a multivariable Cox regression model, age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03-1.11), P=0.001, PFV upper tertile (HR, 4.07; 95% CI, 2.09-7.92), P<0.0001, and CACSIS>5 (HR, 2.19; 95% CI, 1.14-4.23; P<0.0001) were independent predictors of all-cause death.

Conclusions:
In this relatively large patient cohort undergoing clinically indicated conventional chest CT scans, PFV and coronary calcification were high-risk markers associated with worsening survival.
Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism
Authors: Warkocki Zbigniew , Liudkovska Vladyslava , Gewartowska Olga , Mroczek Seweryn , Dziembowski Andrzej 
Published: November 2018

In eukaryotes, almost all RNA species are processed at their 3′ ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases. In recent years, several terminal nucleotidyl transferases (TENTs) including non-canonical poly(A) polymerases (ncPAPs) and terminal uridyl transferases (TUTases) have been discovered. In contrast to canonical polymerases, TENTs' functions are more diverse; some, especially TUTases, induce RNA decay while others, such as cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. The mammalian genome encodes 11 different TENTs. This review summarizes the current knowledge about the functions and mechanisms of action of these enzymes.This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.
HIV-1 subtype C with PYxE insertion has enhanced binding of Gag-p6 to host cell protein ALIX and increased replication fitness
Authors: Domselaar Robert van , Njenda Duncan T. , Rao Rohit , Sönnerborg Anders , Singh Kamalendra , Neogi Ujjwal 
Published: November 2018

AbstractHuman immunodeficiency virus type 1 subtype C (HIV-1C) has a natural deletion of a YPxL motif in its Gag-p6 late domain. This domain mediates the binding of Gag to host cell protein ALIX and subsequently facilitates viral budding. In a subset of HIV-1C infected individuals, the tetrapeptide insertion PYxE has been identified at the deleted YPxL motif site. Here, we report the consequences of PYxE insertion on the interaction with ALIX and the relevance regarding replication fitness and drug sensitivity. In our three HIV-1C cohorts, PYKE and PYQE were most prevalent among PYxE variants. Throughin silicopredictions andin vitroexperiments, we showed that HIV-1C Gag has an increased binding to ALIX when PYxE motif is present. To go more into the clinical relevance of the PYxE insertion, we obtained patient-derived gag-pol sequences from HIV-1CPYxEiviruses and inserted them in a reference HIV-1. Viral growth was increased, and the sensitivity to protease inhibitor (PI) lopinavir (LPV) and nucleoside reverse transcriptase inhibitor tenofovir alafenamide (TAF) was decreased for some of the HIV-1C PYxE variants compared to wild-type variants. Our data suggest that PYxE insertion in Gag restores the ability of Gag to bind ALIX and correlates with enhanced viral fitness in the absence or presence of LPV and TAF. The high prevalence and increased replication fitness of the HIV-1C virus with PYxE insertion could indicate the clinical importance of these viral variants.ImportanceGenomic differences within HIV-1 subtypes is associated with a varying degree of viral spread, disease progression, and clinical outcome. Viral budding is essential in the HIV-1 life cycle and mainly mediated through the interaction of Gag with host proteins. Two motifs within Gag-p6 mediate binding of host cell proteins and facilitate budding. HIV-1 subtype C (HIV-1C) has a natural deletion of one of these two motifs resulting in an inability to bind to host cell protein ALIX. Previously, we have identified a tetrapeptide (PYxE) insertion at this deleted motif site in a subset of HIV-1C patients. Here, we report the incidence of PYxE insertions in three different HIV-1C cohorts, and the insertion restores the binding of Gag to ALIX. It also increases viral growth even in the presence of antiretroviral drugs lopinavir and tenofovir alafenamide. Hence, PYxE insertion in HIV-1C might be biologically relevant for viruses and clinically significant among patients.
The Prevalence and Impact of Model Violations in Phylogenetics Analysis
Authors: Naser-Khdour Suha , Minh Bui Quang , Zhang Wenqi , Stone Eric , Lanfear Robert 
Published: November 2018

AbstractIn phylogenetic inference we commonly use models of substitution which assume that sequence evolution is stationary, reversible and homogeneous (SRH). Although the use of such models is often criticized, the extent of SRH violations and their effects on phylogenetic inference of tree topologies and edge lengths are not well understood. Here, we introduce and apply the maximal matched-pairs tests of homogeneity to assess the scale and impact of SRH model violations on 3,572 partitions from 35 published phylogenetic datasets. We show that many partitions (39.5%) reject the SRH assumptions, and that for most datasets, the topologies of trees inferred from all partitions differ significantly from those inferred using the subset of partitions that do not reject the SRH assumptions. These results suggest that the extent and effects of model violation in phylogenetics may be substantial. They highlight the importance of testing for model violations and possibly excluding partitions that violate models prior to tree reconstruction. They also suggest that further effort in developing models that do not require SRH assumptions could lead to large improvements in the accuracy of phylogenomic inference. The scripts necessary to perform the analysis are available inhttps://github.com/roblanf/SRHtests, and the new tests we describe are available as a new option in IQ-TREE (http://www.iqtree.org).
Pre-implantation genetic diagnosis for a family with Usher syndrome through targeted sequencing and haplotype analysis
Authors: Luo Haining , Chen Chao , Yang Yun , Yuan Yuan , Wang Wanyang , Wu Renhua , Zhang Yinfeng , Peng Zhiyu , Han Ying , Jiang Lu , Yao Ruqiang , An Xiaoying , Zhang Weiwei , Le Yanqun , Xiang Jiale , Yi Na , Huang Hui , Li Wei , Zhang Yunshan , Sun Jun 
Published: November 2018

AbstractObjectiveOur objective was to investigate the applicability of targeted capture massively parallel sequencing in developing personalized pre-implantation genetic diagnosis (PGD) assay.MethodsOne couple at risk of transmitting Usher Syndrome to their offspring was recruited to this study. The genomics DNA (gDNA) was extracted from the peripheral blood and underwent in vitro fertilization (IVF)-PGD. Prenatal molecular diagnosis was performed in the 20th week of gestation and the chromosomal anomaly was analyzed.ResultsCustomized capture probe targeted at USH2A gene and 350kb flanking region were designed for PGD. Eleven blastocysts were biopsied and amplified by using multiple displacement amplification (MDA) and capture sequencing. A HMM-based haplotype analysis was performed to deduce embryo’s genotype by using SNPs identified in each sample. Four embryos were diagnosed as free of father’s rare mutation, two were transferred and one achieved a successful pregnancy. The fetal genotype was confirmed by Sanger sequencing of fetal genomic DNA obtained by amniocentesis. The PGD and prenatal diagnosis results were further confirmed by the molecular diagnosis of the baby’s genomic DNA sample. The auditory test showed that the hearing was normal.ConclusionTargeted capture massively parallel sequencing (MPS) is an effective and convenient strategy to develop customized PGD assay.Key pointsGenetic counseling session was conducted with a family having Usher patient who was molecularly diagnosed, and a healthy baby was born with the help of successful PGD assay. This is of vast importance in management plans since it is the first report of PGD in Usher syndrome based on targeted capture MPS.
Statistical Mechanical Prediction of Ligand Perturbation to RNA Secondary Structure and Application to the SAM-I Riboswitch
Authors: Alaidi Osama , Aboul-ela Fareed 
Published: November 2018

ABSTRACTThe realization that non protein-coding RNA (ncRNA) is implicated in an increasing number of cellular processes, many related to human disease, makes it imperative to understand and predict RNA folding. RNA secondary structure prediction is more tractable than tertiary structure or protein structure. Yet insights into RNA structure-function relationships are complicated by coupling between RNA folding and ligand binding. Here, we introduce a simple statistical mechanical formalism to calculate perturbations to equilibrium secondary structure conformational distributions for RNA, in the presence of bound cognate ligands. For the first time, this formalism incorporates a key factor in coupling ligand binding to RNA conformation: the differential affinity of the ligand for a range of RNA-folding intermediates. We apply the approach to the SAM-I riboswitch, for which binding data is available for analogs of intermediate secondary structure conformers. Calculations of equilibrium secondary structure distributions during the transcriptional “decision window” predict subtle shifts due to the ligand, rather than an on/off switch. The results suggest how ligand perturbation can release a kinetic block to the formation of a terminator hairpin in the full-length riboswitch. Such predictions identify aspects of folding that are most affected by ligand binding, and can readily be compared with experiment.
Impact of genetic variations on the human brain: when and where?
Authors: Vervier Kevin , Brueggeman Leo , Michaelson Jacob 
Published: November 2018

AbstractGenetic studies have found candidates in most of neurological and psychiatric conditions. However, it remains challenging to assess, in which brain region, and when in the brain development, a mutation is more likely to have an impact, especially for intergenic loci. Here we present, BRAVA, a publicly available resource for estimating genetic mutations spatio-temporal context on the human brain. Different contexts were observed for schizophrenia associated loci, suggesting both neurodevelopmental and late onset components.
Introducing double bouquet cells into a modular cortical associative memory model
Authors: Chrysanthidis Nikolaos , Fiebig Florian , Lansner Anders 
Published: November 2018

AbstractWe present an electrophysiological model of double bouquet cells and integrate them into an established cortical columnar microcircuit model that has previously been used as a spiking attractor model for memory. Learning in that model relies on a Bayesian-Hebbian learning rule to condition recurrent connectivity between pyramidal cells. We here demonstrate that the inclusion of a biophysically plausible double bouquet cell model can solve earlier concerns about learning rules that simultaneously learn excitation and inhibition and might thus violate Dale’s Principle.We show that learning ability and resulting effective connectivity between functional columns of previous network models is preserved when pyramidal synapses onto double-bouquet cells are plastic under the same Hebbian-Bayesian learning rule. The proposed architecture draws on experimental evidence on double bouquet cells and effectively solves the problem of duplexed learning of inhibition and excitation by replacing recurrent inhibition between pyramidal cells in functional columns of different stimulus selectivity with a plastic disynaptic pathway. We thus show that the resulting change to the microcircuit architecture improves the model’s biological plausibility without otherwise impacting the models spiking activity, basic operation, and learning abilities.
mtDNA recombination indicative of hybridization suggests a role of the mitogenome in the adaptation of reef-building corals to extreme environments
Authors: Banguera-Hinestroza Eulalia , Sawall Yvonne , Al-Sofyani Abdulmohsin , Mardulyn Patrick , Fuertes-Aguilar Javier , Cárdenas-Henao Heiber , Cárdenas-Henao Heiber , Jimenez-Infante Francy , Voolstra Christian R. , Flot Jean-François 
Published: November 2018

AbstractmtDNA recombination following hybridization is rarely found in animals and was never until now reported in reef-building corals. Here we report unexpected topological incongruence among mitochondrial markers as evidence of mitochondrial introgression in the phylogenetic history of Stylophora species distributed along broad geographic ranges. Our analyses include specimens from the Indo-Pacific, the Indian Ocean and the full latitudinal (2000 km) and environmental gradient (21°C-33°C) of the Red Sea (N=827). The analysis of Stylophora lineages in the framework of the mitogenome phylogenies of the family Pocilloporidae, coupled with analyses of recombination, shows the first evidence of asymmetric patterns of introgressive hybridization associated to mitochondrial recombination in this genus. Hybridization likely occurred between an ancestral lineage restricted to the Red Sea/Gulf of Aden basins and migrants from the Indo-Pacific/Indian Ocean that reached the Gulf of Aden. The resulting hybrid lives in sympatry with the descendants of the parental Red Sea lineage, from which it inherited most of its mtDNA (except a highly variable recombinant region that includes the nd6, atp6, and mtORF genes) and expanded its range into the hottest region of the Arabian Gulf, where it is scarcely found. Noticeably, across the Red Sea both lineages exhibit striking differences in terms of phylogeographic patterns, clades-morphospecies association, and zooxanthellae composition. Our data suggest that the early colonization of the Red Sea by the ancestral lineage, which involved overcoming multiple habitat changes and extreme temperatures, resulted in changes in mitochondrial proteins, which led to its successful adaptation to the novel environmental conditions.
Retinoic acid and androgens interact to regulate spermatogenesis in a non-mammalian vertebrate lackingstra8
Authors: Crespo Diego , Assis Luiz H.C. , van de Kant Henk J.G. , Waard Sjors de , Safian Diego , Lemos Moline S. , Bogerd Jan , Schulz Rüdiger W. 
Published: November 2018

AbstractIn mammals, retinoic acid (RA) signaling is critical for spermatogonial differentiation and for entering meiosis, the latter depending on RA-inducedStra8gene expression. Many fish species, including zebrafish, do not contain astra8gene, but RA signaling nevertheless is important for sperm production. However, it is not known which stages of spermatogenesis respond to RA. Here, we show in zebrafish that RA promotes spermatogonial differentiation and reduces the apoptotic loss of spermatids, but is not required for meiosis. Some of the RA effects are mediated by other genes, in particularrec8a. Surprisingly, androgens can partially compensate for the loss of RA signaling, and we identify a link between the endocrine system and RA signaling: follicle-stimulating hormone (Fsh) stimulates testicular RA production. While RA signaling is relevant at the basis of the vertebrates, it also targets processes and mechanisms that are different from those known in mammals so far.
Refolding activity of bacterial Hsp90in vivoreveals ancient chaperoning function
Authors: Luengo Tania Morán , Ahlnäs Toveann , Hoekstra Anna T. , Berkers Celia R. , Mayer Matthias P. , Rüdiger Stefan G. D. 
Published: November 2018

ABSTRACTThe conserved molecular chaperones Hsp70 and Hsp90 play a key role in protein folding. Mechanistically, Hsp90 acts downstream from Hsp70 solving an Hsp70-inflicted folding block. It is unclear, though, when and to which extend the concerted action of this cascade becomes crucial in living organisms. Here we show that, in E. coli cells, Hsp90 dramatically improves protein refolding after heat stress while it is dispensable for de novo folding. We found that Hsp90 inhibition effectively reduced the refolding yields in vivo, leading to strongly reduced enzymatic activity of the paradigmatic chaperone client luciferase and broadly increased aggregation of the E. coli proteome. Additionally, the presence of Hsp90 during refolding reduces the net ATP consumption presumably by sparing the substrate binding-and-release cycles on Hsp70. This mechanism explains how the cooperation of Hsp90 with the Hsp70 chaperone system creates robust folding machinery in a sustainable manner. Together, we describe a general function for bacterial Hsp90 as a key factor of the folding cascade, which may be the ancient activity of this evolutionary conserved machine.
eIF2B activator prevents neurological defects caused by a chronic Integrated Stress Response
Authors: Wong Yao Liang , LeBon Lauren , Basso Ana M. , Kohlhaas Kathy L. , Nikkel Arthur L. , Robb Holly M. , Donnelly-Roberts Diana L. , Prakash Janani , Swensen Andrew M. , Rubinstein Nimrod D. , Krishnan Swathi , McAllister Fiona E. , Haste Nicole V. , O’Brien Jonathon J. , Frost Jennifer M. , Shi Lei , Riedmaier Stephan , Martin Kathleen , Dart Michael J. , Sidrauski Carmela 
Published: November 2018

AbstractThe Integrated Stress Response (ISR) attenuates the rate of protein synthesis while inducing expression of stress proteins in cells. Various insults activate kinases that phosphorylate the GTPase eIF2 leading to inhibition of its exchange factor eIF2B. Vanishing White Matter (VWM) is a neurological disease caused by eIF2B mutations that, like phosphorylated eIF2, reduce its activity. We show that introduction of a human VWM mutation into mice leads to persistent ISR induction in the central nervous system. ISR activation precedes myelin loss and development of motor deficits. Remarkably, long-term treatment with a novel eIF2B activator, 2BAct, prevents all measures of pathology and normalizes the transcriptome and proteome of VWM mice. 2BAct stimulates the remaining activity of mutant eIF2B complexin vivo, abrogating the maladaptive stress response. Thus, 2BAct-like molecules may provide a promising therapeutic approach for VWM and provide relief from chronic ISR induction in a variety of other disease contexts.
Factors influencing knowledge and practice on helping babies breathe among Skilled Birth Attendants in rural areas in Lake Zone in Tanzania
Authors: Mzurikwao Cecilia B , Ng’weshemi Kapalata Secilia K , Ernest Alex Ibolinga 
Published: November 2018

ABSTRACTBackgroundIt is estimated that 1 million babies die each year due to birth asphyxia. Globally, it is approximated that 10 million babies cannot do it by themselves and need assistance. Helping babies breathe is a key component in reducing neonatal mortality due to birth asphyxia.MethodsA cross-sectional design was used, A total of 330 respondents included in the study. Simple random sampling by lottery was used to select the 2 regions and health facilities. The participants were selected through convenient. Data were collected using standard semi-structured questionnaire. Chi-square and Binary logistic regression were used to analyse the data.ResultsOut of 330 participants, Those who working in hospital and were more likely to have adequate knowledge (AOR= 3.227, P< 0.001) and practice (AOR= 43.807, P<0.001) than those working in Health Centers; Enlored nurses were more likely to have adequate knowledge (AOR= 3.118,P<0.05) than AMO/MD;Those with 1 year and above of experience in labor ward were more likely to have adequate practice(AOR=15.418,P<0.001) than those with less than 1 year of experience in labor ward; those who attended once on neonatal resuscitation training were adequate knowledge (AOR=1.778,P<0.05) than those who had never attended. Those with Enough equipment of neonatal resuscitation had adequate practice (AOR=4.355, P<0.001) than with no enough equipment.ConclusionRegarding the findings of the current study, it was revealed that working facility, Professional/ qualification, and training was significant predictor of knowledge while working facility, experience, and equipment was significant predictor of practice. There is a need to find effective measures on how to reduce those factors which affect knowledge and practice on helping babies breathe.