bluuebunny/crossref_metadata_2025_split huggingface dataset:
An intrinsically disordered region of RPN10 plays a key role in restricting ubiquitin chain elongation in RPN10 monoubiquitination
Authors: Puig-Sàrries Pilar , Bijlmakers Marie-José , Zuin Alice , Bichmann Anne , Pons Miquel , Crosas Bernat 
Published: July 2015

Despite being a common mechanism in eukaryotes, the process by which protein monoubiquitination is produced and regulated in vivo is not completely understood. We present here the analysis of the process of monoubiquitination of the proteasomal subunit Rpn10 (regulatory particle non-ATPase 10), involved in the recruitment of polyubiquitinated substrates. Rpn10 is monoubiquitinated in vivo by the Nedd4 (neural precursor cell expressed developmentally down-regulated 4) enzyme Rsp5 (reverses SPT-phenotype protein 5) and this modification impairs the interaction of Rpn10 with substrates, having a regulatory effect on proteasome function. Remarkably, a disordered region near the ubiquitin-interacting motif of Rpn10 plays a role in the restriction of the polyubiquitin extension activity of Rsp5. Mutations in this disordered region promote ubiquitin chain extension of Rpn10. Thus, our work sheds light on the molecular basis and the functional relevance of a type of monoubiquitination that is driven by the substrate. Moreover, we uncover a putative role for disordered regions in modulating ubiquitin–protein ligation.
CD147 promotes liver fibrosis progression via VEGF-A/VEGFR2 signalling-mediated cross-talk between hepatocytes and sinusoidal endothelial cells
Authors: Yan Zhaoyong , Qu Kai , Zhang Jing , Huang Qichao , Qu Ping , Xu Xinsen , Yuan Peng , Huang Xiaojun , Shao Yongping , Liu Chang , Zhang Hongxin , Xing Jinliang 
Published: July 2015

Although previous evidence indicates close involvement of CD147 in the pathogenesis of liver fibrosis, the underlying molecular mechanisms and its therapeutic value remain largely unknown. In the present study, we investigated the biological roles of CD147 in liver fibrosis and assessed its therapeutic value as a target molecule in the CCl4-induced liver fibrosis mouse model. We found that CD147 was highly expressed in both hepatocytes and SECs (sinusoidal endothelial cells) in fibrotic liver tissues. Additionally, it was significantly associated with the fibrosis stage. TGF-β1 (transforming growth factor β1) was found to be mainly responsible for the up-regulation of CD147. Bioinformatic and experimental data suggest a functional link between CD147 expression and VEGF-A (vascular endothelial growth factor A)/VEGR-2 (VEGF receptor 2) signalling-mediated angiogenesis in fibrotic liver tissues. Furthermore, we observed that the CD147-induced activation of the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway promotes the production of VEGF-A in hepatocytes and expression of VEGFR-2 in SECs, which was found to enhance the angiogenic capability of SECs. Finally, our data indicate that blocking of CD147 using an mAb (monoclonal antibody) attenuated liver fibrosis progression via inhibition of VEGF-A/VEGFR-2 signalling and subsequent amelioration of microvascular abnormality in the CCl4-induced mouse model. Our findings suggest a novel functional mechanism that CD147 may promote liver fibrosis progression via inducing the VEGF-A/VEGFR-2 signalling pathway-mediated cross-talk between hepatocytes and SECs. New strategies based on the intervention of CD147 can be expected for prevention of liver fibrosis.
Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration
Authors: Hulse Richard P. , Beazley-Long Nicholas , Ved Nikita , Bestall Samuel M. , Riaz Hamza , Singhal Priya , Ballmer Hofer Kurt , Harper Steve J. , Bates David O. , Donaldson Lucy F. 
Published: July 2015

Diabetic peripheral neuropathy affects up to half of diabetic patients. This neuronal damage leads to sensory disturbances, including allodynia and hyperalgesia. Many growth factors have been suggested as useful treatments for prevention of neurodegeneration, including the vascular endothelial growth factor (VEGF) family. VEGF-A is generated as two alternative splice variant families. The most widely studied isoform, VEGF-A165a is both pro-angiogenic and neuroprotective, but pro-nociceptive and increases vascular permeability in animal models. Streptozotocin (STZ)-induced diabetic rats develop both hyperglycaemia and many of the resulting diabetic complications seen in patients, including peripheral neuropathy. In the present study, we show that the anti-angiogenic VEGF-A splice variant, VEGF-A165b, is also a potential therapeutic for diabetic neuropathy. Seven weeks of VEGF-A165b treatment in diabetic rats reversed enhanced pain behaviour in multiple behavioural paradigms and was neuroprotective, reducing hyperglycaemia-induced activated caspase 3 (AC3) levels in sensory neuronal subsets, epidermal sensory nerve fibre loss and aberrant sciatic nerve morphology. Furthermore, VEGF-A165b inhibited a STZ-induced increase in Evans Blue extravasation in dorsal root ganglia (DRG), saphenous nerve and plantar skin of the hind paw. Increased transient receptor potential ankyrin 1 (TRPA1) channel activity is associated with the onset of diabetic neuropathy. VEGF-A165b also prevented hyperglycaemia-enhanced TRPA1 activity in an in vitro sensory neuronal cell line indicating a novel direct neuronal mechanism that could underlie the anti-nociceptive effect observed in vivo. These results demonstrate that in a model of Type I diabetes VEGF-A165b attenuates altered pain behaviour and prevents neuronal stress, possibly through an effect on TRPA1 activity.
Longitudinal and Transverse Right Ventricular Function in Pulmonary Hypertension: Cardiovascular Magnetic Resonance Imaging Study from the ASPIRE Registry
Authors: Swift Andrew J. , Rajaram Smitha , Capener Dave , Elliot Charlie , Condliffe Robin , Wild Jim M. , Kiely David G. 
Published: July 2015

Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment‐naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of <20 mmHg, cardiovascular magnetic resonance imaging was performed within 24 hours of right heart catheterization. In patients with PH, fractional longitudinal motion (fractional tricuspid annulus to apex distance [f‐TAAD]) was significantly greater than fractional transverse motion (fractional septum to free wall distance [f‐SFD]; P = 0.002). In patients without PH, no significant difference between f‐SFD and f‐TAAD was identified (P = 0.442). Longitudinal RV motion was singularly associated with RV ejection fraction independent of age, invasive hemodynamics, and cardiac magnetic resonance measurements (P = 0.024). In contrast, transverse RV motion was independently associated with left ventricular eccentricity (P = 0.036) in addition to RV ejection fraction (P = 0.014). In conclusion, RV motion is significantly greater in the longitudinal direction in patients with PH, whereas patients without PH have equal contributions of transverse and longitudinal motion. Longitudinal RV motion is primarily associated with global RV pump function in PH. Transverse RV motion not only reflects global pump function but is independently influenced by ventricular interaction in patients with PH.
Nocturnal Intermittent Hypoxia Is Associated With Left Ventricular
Hypertrophy in Middle-Aged Men With Hypertension and Obstructive Sleep
Apnea
Authors: Yamaguchi Tasuku , Takata Yoshifumi , Usui Yasuhiro , Asanuma Ryoko , Nishihata Yosuke , Kato Kota , Shiina Kazuki , Yamashina Akira 
Published: July 2015

Abstract

BACKGROUND
Obstructive sleep apnea (OSA) and left ventricular (LV) hypertrophy are considered to be closely associated. However, the relationship has not yet been fully demonstrated and is hence still controversial. The purpose of this study was to assess in hypertensive male patients the relationship between OSA and cardiac structure using a new index, namely, integrated area of desaturation (IAD), in addition to the apnea-hypopnea index (AHI) that is currently the most frequently used index of sleep-disordered breathing.

METHODS
In our cross-sectional study, 223 hypertensive men younger than 65 years with sleep apnea and normal cardiac function were enrolled. All subjects were evaluated by fully attended polysomnography. Cardiac structure and function were evaluated by echocardiography.

RESULTS
LV mass index significantly correlated with IAD ( r = 0.203, P &lt; 0.05), but not with AHI. Multivariate linear regression analyses showed that IAD, brain natriuretic peptide (BNP), and age are independent variables affecting the LV mass index ( β = 0.262, 0.237, and 0.173, respectively, P &lt; 0.05). IAD was the one and only determinant among the indices of sleep-disordered breathing.

CONCLUSIONS
Nocturnal intermittent hypoxia defined by IAD may be associated with LV hypertrophy in men with well-controlled hypertension and obstructive sleep apnea.
TEtranscripts: a package for including transposable elements in differential expression analysis of RNA-seq datasets
Authors: Jin Ying , Tam Oliver H. , Paniagua Eric , Hammell Molly 
Published: July 2015

Abstract
Motivation: Most RNA-seq data analysis software packages are not designed to handle the complexities involved in properly apportioning short sequencing reads to highly repetitive regions of the genome. These regions are often occupied by transposable elements (TEs), which make up between 20 and 80% of eukaryotic genomes. They can contribute a substantial portion of transcriptomic and genomic sequence reads, but are typically ignored in most analyses.
Results: Here, we present a method and software package for including both gene- and TE-associated ambiguously mapped reads in differential expression analysis. Our method shows improved recovery of TE transcripts over other published expression analysis methods, in both synthetic data and qPCR/NanoString-validated published datasets.
Availability and implementation: The source code, associated GTF files for TE annotation, and testing data are freely available at http://hammelllab.labsites.cshl.edu/software.
Contact: mhammell@cshl.edu.
Supplementary information: Supplementary data are available at Bioinformatics online.
Predicting microbial relative growth in a mixed culture from growth curve data
Authors: Ram Yoav , Dellus-Gur Eynat , Bibi Maayan , Obolski Uri , Berman Judith , Hadany Lilach 
Published: July 2015

AbstractEstimates of microbial fitness from growth curves are inaccurate. Rather, competition experiments are necessary for accurate estimation. But competition experiments require unique markers and are difficult to perform with isolates derived from a common ancestor or non-model organisms. Here we describe a new approach for predicting relative growth of microbes in a mixed culture utilizing mono- and mixed culture growth curve data. We validated this approach using growth curve and competition experiments withE. coli. Our approach provides an effective way to predict growth in a mixed culture and infer relative fitness. Furthermore, by integrating several growth phases, it provides an ecological interpretation for microbial fitness.
Assessment of cladistic data availability for living mammals
Authors: Guillerme Thomas , Cooper Natalie 
Published: July 2015

AbstractAnalyses of living and fossil taxa are crucial for understanding changes in biodiversity through time. The Total Evidence method allows living and fossil taxa to be combined in phylogenies, by using molecular data for living taxa and morphological data for both living and fossil taxa. With this method, substantial overlap of morphological data among living and fossil taxa is crucial for accurately inferring topology. However, although molecular data for living species is widely available, scientists using and generating morphological data mainly focus on fossils. Therefore, there is a gap in our knowledge of neontological morphological data even in well-studied groups such as mammals.We investigated the amount of morphological (cladistic) data available for living mammals and how this data was phylogenetically distributed across orders. 22 of 28 mammalian orders have<25% species with available morphological data; this has implications for the accurate placement of fossil taxa, although the issue is less pronounced at higher taxonomic levels. In most orders, species with available data are randomly distributed across the phylogeny, which may reduce the impact of the problem. We suggest that increased morphological data collection efforts for living taxa are needed to produce accurate Total Evidence phylogenies.
Coalescence with background and balancing selection in systems with bi- and uniparental reproduction: contrasting partial asexuality and selfing
Authors: Agrawal Aneil F. , Hartfield Matthew 
Published: July 2015

AbstractUniparental reproduction in diploids, via asexual reproduction or selfing, reduces the independence with which separate loci are transmitted across generations. This is expected to increase the extent to which a neutral marker is affected by selection elsewhere in the genome. Such effects have previously been quantified in coalescent models involving selfing. Here we examine the effects of background selection and balancing selection in diploids capable of both sexual and asexual reproduction (i.e., partial asexuality). We find that the effect of background selection on reducing coalescent time (and effective population size) can be orders of magnitude greater when rates of sex are low than when sex is common. This is because asexuality enhances the effects of background selection through both a recombination effect and a segregation effect. We show that there are several reasons that the strength of background selection differs between systems with partial asexuality and those with comparable levels of uniparental reproduction via selfing. Expectations for reductions inNevia background selection have been verified using stochastic simulations. In contrast to background selection, balancing selection increases the coalescent time for a linked neutral site. With partial asexuality, the effect of balancing selection is somewhat dependent upon the mode of selection (e.g., heterozygote advantage vs. negative frequency dependent selection) in a manner that does not apply to selfing. This is because the frequency of heterozygotes, which are required for recombination onto alternative genetic backgrounds, is more dependent on the pattern of selection with partial asexuality than with selfing.
Sulfur Isotope Effects of Dissimilatory Sulfite Reductase
Authors: Leavitt William D. , Bradley Alexander S. , Santos André A. , Pereira Inês A.C. , Johnston David T. 
Published: July 2015

AbstractThe precise interpretation of environmental sulfur isotope records requires a quantitative understanding of the biochemical controls on sulfur isotope fractionation by the principle isotope-fractionating process within the S cycle, microbial sulfate reduction (MSR). Here we provide the only direct observation of the major (34S/32S) and minor (33S/32S,36S/32S) sulfur isotope fractionations imparted by a central enzyme in the energy metabolism of sulfate reducers, dissimilatory sulfite reductase (DsrAB). Results from in vitro sulfite reduction experiments allow us to calculate the in vitro DsrAB isotope effect in34S/32S (hereafter,34εDsrAB) to be 15.3±2‰, 2σ.The accompanying minor isotope effect in33S, described as33λDsrAB, is calculated to be 0.5150±0.0012, 2σ. These observations facilitate a rigorous evaluation of the isotopic fractionation associated with the dissimilatory MSR pathway, as well as of the environmental variables that govern the overall magnitude of fractionation by natural communities of sulfate reducers. The isotope effect induced by DsrAB upon sulfite reduction is a factor of 0.3 to 0.6 times prior indirect estimates, which have ranged from 25 to 53‰ in34εDsrAB. The minor isotope fractionation observed from DsrAB is consistent with a kinetic or equilibrium effect. Our in vitro constraints on the magnitude of34εDsrABis similar to the median value of experimental observations compiled from all known published work, where34εr-p= 16.1‰ (r – pindicates reactant versus product, n = 648). This value closely matches those of MSR operating at high sulfate reduction rates in both laboratory chemostat experiments (34εSO4-H2S= 17.3±1.5‰) and in modern marine sediments (34εSO4-H2S= 17.3±3.8‰). Targeting the direct isotopic consequences of a specific enzymatic processes is a fundamental step toward a biochemical foundation for reinterpreting the biogeochemical and geobiological sulfur isotope records in modern and ancient environments.
ASTRID: Accurate Species TRees from Internode Distances
Authors: Vachaspati Pranjal , Warnow Tandy 
Published: July 2015

AbstractBackgroundIncomplete lineage sorting (ILS), modelled by the multi-species coalescent (MSC), is known to create discordance between gene trees and species trees, and lead to inaccurate species tree estimations unless appropriate methods are used to estimate the species tree. While many statistically consistent methods have been developed to estimate the species tree in the presence of ILS, only ASTRAL-2 and NJst have been shown to have good accuracy on large datasets. Yet, NJst is generally slower and less accurate than ASTRAL-2, and cannot run on some datasets.ResultsWe have redesigned NJst to enable it to run on all datasets, and we have expanded its design space so that it can be used with different distance-based tree estimation methods. The resultant method, ASTRID, is statistically consistent under the MSC model, and has accuracy that is competitive with ASTRAL-2. Furthermore, ASTRID is much faster than ASTRAL-2, completing in minutes on some datasets for which ASTRAL-2 used hours.ConclusionsASTRID is a new coalescent-based method for species tree estimation that is competitive with the best current method in terms of accuracy, while being much faster. ASTRID is available in open source form on github.
Adaptation to temporally fluctuating environments by the evolution of maternal effects
Authors: Dey Snigdhadip , Proulx Stephen R. , Teotónio Henrique 
Published: July 2015

AbstractMost organisms live in ever-challenging temporally fluctuating environments. Theory suggests that the evolution of anticipatory (or deterministic) maternal effects underlies adaptation to environments that regularly fluctuate every other generation because of selection for increased offspring performance. Evolution of maternal bet-hedging reproductive strategies that randomize offspring phenotypes is in turn expected to underlie adaptation to irregularly fluctuating environments. Although maternal effects are ubiquitous their adaptive significance is unknown since they can easily evolve as a correlated response to selection for increased maternal performance. Using the nematodeCaenorhabditis elegans, we show the experimental evolution of maternal provisioning of offspring with glycogen, in populations facing a novel anoxia hatching environment every other generation. As expected with the evolution of deterministic maternal effects, improved embryo hatching survival under anoxia evolved at the expense of fecundity and glycogen provisioning when mothers experienced anoxia early in life. Unexpectedly, populations facing an irregularly fluctuating anoxia hatching environment failed to evolve maternal bet-hedging reproductive strategies. Instead, adaptation in these populations should have occurred through the evolution of balancing trade-offs over multiple generations, since they evolved reduced fitness over successive generations in anoxia but did not go extinct during experimental evolution. Mathematical modelling confirms our conclusion that adaptation to a wide range of patterns of environmental fluctuations hinges on the existence of deterministic maternal effects, and that they are generally much more likely to contribute to adaptation than maternal bet-hedging reproductive strategies.
Phenotypic and genomic differentiation ofArabidopsis thalianaalong altitudinal gradients in the North Italian alps
Authors: Günther Torsten , Lampei Christian , Barilar Ivan , Schmid Karl J. 
Published: July 2015

AbstractAltitudinal gradients represent short-range clines of environmental parameters like temperature, radiation, seasonality and pathogen abundance, which allows to study the foot-prints of natural selection in geographically close populations. We investigated phenotypic variation for frost resistance and light response in fiveArabidopsis thalianapopulations ranging from 580 to 2,350 meters altitude at two different valleys in the North Italian Alps. All populations were resequenced as pools and we used a Bayesian method to detect correlations between allele frequencies and altitude while accounting for sampling, pooled sequencing and the expected amount of shared drift among populations. The among population variation to frost resistance was not correlated with altitude. An anthocyanin deficiency causing a high leaf mortality was present in the highest population, which may be non-adaptive and potentially deleterious phenotypic variation. The genomic analysis revealed that the two high-altitude populations are more closely related than the geographically close low-altitude populations. A correlation of genetic variation with altitude revealed an enrichment of highly differentiated SNPs located in genes that are associated with biological processes like response to stress and light. We further identified regions with long blocks of presence absence variation suggesting a sweep-like pattern across populations. Our analysis indicate a complex interplay of local adaptation and a demographic history that was influenced by glaciation cycles and/or rapid seed dispersal by animals or other forces.
Stable recombination hotspots in birds
Authors: Singhal Sonal , Leffler Ellen M. , Sannareddy Keerthi , Turner Isaac , Venn Oliver , Hooper Daniel M. , Strand Alva I. , Li Qiye , Raney Brian , Balakrishnan Christopher N. , Griffith Simon C. , McVean Gil , Przeworski Molly 
Published: July 2015

AbstractAlthough the DNA-binding protein PRDM9 plays a critical role in the specification of meiotic recombination hotspots in mice and apes, it appears to be absent from many vertebrate species, including birds. To learn about the determinants of fine-scale recombination rates and their evolution in natural populations lackingPRDM9, we inferred fine-scale recombination maps from population resequencing data for two bird species, the zebra finchTaeniopygia guttata, and the long-tailed finch,Poephila acuticauda, whose divergence is on par with that between human and chimpanzee. We find that both bird species have hotspots, and these are enriched near CpG islands and transcription start sites. In sharp contrast to what is seen in mice and apes, the hotspots are largely shared between the two species, with indirect evidence of conservation extending across bird species tens of millions of years diverged. These observations link the evolution of hotspots to their genetic architecture, suggesting that in the absence of PRDM9 binding specificity, accessibility of the genome to the cellular recombination machinery, particularly around functional genomic elements, both enables increased recombination and constrains its evolution.