bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of Rift Valley fever virus spillover to humans during the Mayotte 2018-2019 epidemic
Authors: Métras Raphaëlle , Edmunds W John , Youssouffi Chouanibou , Dommergues Laure , Fournié Guillaume , Camacho Anton , Funk Sebastian , Cardinale Eric , Godais Gilles Le , Combo Soihibou , Filleul Laurent , Youssouf Hassani , Subiros Marion 
Published: February 2020

AbstractRift Valley fever (RVF) is an emerging, zoonotic, arboviral haemorrhagic fever threatening livestock and humans mainly in Africa. RVF is of global concern, having expanded its geographical range over the last decades. The impact of control measures on epidemic dynamics using empirical data has not been assessed. Here, we combined seroprevalence livestock and human RVF case data from the 2018-2019 epidemic in Mayotte, with a dynamic mathematical model. Using a Bayesian inference framework, we estimated viral transmission potential amongst livestock, and spillover from livestock to humans, through both direct contact and vector-mediated routes. Model simulations were used to assess the impact of vaccination on reducing the human epidemic size. Reactive vaccination immunising 20% of the livestock population reduced the number of human cases by 30%. To achieve a similar impact, delaying the vaccination by one month required using 50% more vaccine doses, and vaccinating only humans required 20 times as more as the number of doses for livestock. Finally, with 53.92% (95%CrI [44.76-61.29]) of livestock estimated to be immune at the end of the epidemic wave, viral re-emergence in the next rainy season (2019-2020) was unlikely. We present the first mathematical model for RVF fitted to real-world data to estimate virus transmission parameters, and able to inform potential control programmes. Human and animal health surveillance, and timely livestock vaccination appear to be key in reducing disease risk in humans. We furthermore demonstrate the value of a One Health quantitative approach to surveillance and control of zoonotic infectious diseases.
Adaptive Baseline Fitting for1H MR Spectroscopy Analysis
Authors: Wilson Martin 
Published: February 2020

PurposeAccurate baseline modeling is essential for reliable MRS analysis and interpretation — particularly at short echo-times, where enhanced metabolite information coincides with elevated baseline interference. The degree of baseline smoothness is a key analysis parameter for metabolite estimation, and in this study a new method is presented to estimate its optimal value.MethodsAn adaptive baseline fitting algorithm (ABfit) is described, incorporating a spline basis into a frequency-domain analysis model, with a penalty parameter to enforce baseline smoothness. A series of candidate analyses are performed over a range of smoothness penalties, as part of a four stage algorithm, and the Akaike information criterion is used to estimate the appropriate penalty. ABfit is applied to a set of simulated spectra with differing baseline features and experimentally acquired 2D MRSI — both at a field strength of 3 Tesla.ResultsSimulated analyses demonstrate metabolite errors result from two main sources: bias from an inflexible baseline (underfitting) and increased variance from an overly flexible baseline (over-fitting). In the case of an ideal flat baseline ABfit is shown to correctly estimate a highly rigid baseline, and for more realistic spectra a reasonable compromise between bias and variance is found. Analysis of experimentally acquired data demonstrates good agreement with known correlations between metabolite ratios and the contributing volumes of gray and white matter tissue.ConclusionABfit has been shown to perform accurate baseline estimation and is suitable for fully-automated routine MRS analysis.
Anode surface bioaugmentation enhances deterministic biofilm assembly in microbial fuel cells
Authors: Yanuka-Golub Keren , Dubinsky Vadim , Korenblum Elisa , Reshef Leah , Ofek-Lalzar Maya , Rishpon Judith , Gophna Uri 
Published: February 2020

AbstractMicrobial fuel cells (MFCs) are devices that can generate energy while aiding biodegradation of waste through the activity of an electroactive mixed biofilm. Metabolic cooperation is considered essential for MFCs’ efficiency, especially during early-anode colonization. Yet, the specific ecological processes that drive the assembly of an optimized anode-attached community remain unknown. Here, we show, using 16S rRNA gene amplicon and shotgun metagenomic sequencing that bioaugmentation of the anode surface with an electroactive consortium originating from a well-established anodic biofilm, dominated by differentDesulfuromonasstrains, resulted in an extremely rapid voltage generation (reaching maximal voltage within several hours). This was in sharp contrast to the highly stochastic and slower biofilm assembly that occurred when the anode-surface was not augmented. By comparing two inoculation media, wastewater and filtered wastewater, we were able to illustrate two different "source-communities" for newly arriving species that with time colonized the anode surface in a different manner and resulted in dramatically different community assembly processes. Remarkably, an efficient anode colonization process was obtained only if unfiltered wastewater was added, leading to a near-complete replacement of the bioaugmented community byGeobacter lovleyi. We propose that anode bioaugmentation reduced stochasticity by creating available niches that were quickly occupied by specific newly-arriving species that positively supported the fast establishment of a highly-functional anode biofilm.
The Nucleosome Remodeling and Deacetylase complex has an asymmetric, dynamic, and modular architecture
Authors: Low Jason KK , Silva Ana PG , Tabar Mehdi Sharifi , Torrado Mario , Webb Sarah R , Parker Benjamin L , Sana Maryam , Smits Callum , Schmidberger Jason W , Brillault Lou , Jackman Matthew J , Williams David C , Blobel Gerd A. , Hake Sandra B , Shepherd Nicholas E , Landsberg Michael J , Mackay Joel P 
Published: February 2020

ABSTRACTThe Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for development in complex animals but has been refractory to biochemical analysis. We present the first integrated analysis of the architecture of the native mammalian NuRD complex, combining quantitative mass spectrometry, covalent cross-linking, protein biochemistry and electron microscopy. NuRD is built around a 2:2:4 pseudo-symmetric deacetylase module comprising MTA, HDAC and RBBP subunits. This module interacts asymmetrically with a remodeling module comprising one copy each of MBD, GATAD2 and CHD subunits. The previously enigmatic GATAD2 controls the asymmetry of the complex and directly recruits the ATP-dependent CHD remodeler. Unexpectedly, the MTA-MBD interaction acts as a point of functional switching. The transcriptional regulator PWWP2A modulates NuRD assembly by competing directly with MBD for binding to the MTA-HDAC-RBBP subcomplex, forming a ‘moonlighting’ PWWP2A-MTA-HDAC-RBBP complex that likely directs deacetylase activity to PWWP2A target sites. Taken together, our data describe the overall architecture of the intact NuRD complex and reveal aspects of its structural dynamics and functional plasticity.
Assessing predictors for new post translational modification sites: a case study on hydroxylation
Authors: Piovesan Damiano , Hatos Andras , Minervini Giovanni , Quaglia Federica , Monzon Alexander Miguel , Tosatto Silvio C.E. 
Published: February 2020

AbstractPost-translational modification (PTM) sites have become popular for predictor development. However, with the exception of phosphorylation and a handful of other examples, PTMs suffer from a limited number of available training examples and their sparsity in protein sequences. Here, proline hydroxylation is taken as an example to compare different methods and evaluate their performance on new experimentally determined sites. As a proxy for an effective experimental design, predictors require both high specificity and sensitivity. However, the self-reported performance is often not indicative of prediction quality and detection of new sites is not guaranteed. We have benchmarked seven published hydroxylation site predictors on two newly constructed independent datasets. The self-reported performance widely overestimates the real accuracy measured on independent datasets. No predictor performs better than random on new examples, indicating the refined models are not sufficiently general to detect new sites. The number of false positives is high and precision low, in particular for non-collagen proteins whose motifs are not conserved. In short, existing predictors for hydroxylation sites do not appear to generalize to new data. Caution is advised when dealing with PTM predictors in the absence of independent evaluations, in particular for unique specific sites such as those involved in signalling.Author SummaryMachine learning methods are extensively used by biologists to design and interpret experiments. Predictors which take the only sequence as input are of particular interest due to the large amount of sequence data available and self-reported performance is often very high. In this work, we evaluated post-translational modification (PTM) predictors for hydroxylation sites and found that they perform no better than random, in strong contrast to performances reported in the original publications. PTMs are chemical amino acids alterations providing the cell with conditional mechanisms to fine tune protein function, thereby regulating complex biological processes such as signalling and cell cycle. Hydroxylation sites are a good PTM test case due to the availability of a range of predictors and an abundance of newly experimentally detected modification sites. Poor performances in our results highlight the overlooked problem of predicting PTMs when best practices are not followed and training data are likely incomplete. Experimentalists should be careful when using PTM predictors blindly and more independent assessments are needed to separate the wheat from the chaff in the field.
Genome-scale conserved molecular principles of mRNA half-life regulation
Authors: Basu Sudipto , Mallik Saurav , Hait Suman , Kundu Sudip 
Published: February 2020

AbstractPrecise control of protein and mRNA degradation is essential for cellular metabolism and homeostasis. Controlled and specific degradation of both molecular species necessitates their engagements with the respective degradation machineries; this engagement involves a disordered/unstructured segment of the substrate traversing the degradation tunnel of the machinery and accessing the catalytic sites. Here, we report that mRNAs comprising longer terminal and/or internal unstructured segments have significantly shorter half-lives; the lengths of the 5′ terminal, 3′ terminal and internal unstructured segments that affect mRNA half-life are compatible with molecular structures of the 5′ exo- 3′ exo- and endo-ribonuclease machineries. Sequestration into ribonucleoprotein complexes elongates mRNA half-life, presumably by burying ribonuclease engagement sites under oligomeric interfaces. After gene duplication, differences in terminal unstructured lengths, proportions of internal unstructured segments and oligomerization modes result in significantly altered half-lives of paralogous mRNAs. Side-by-side comparison of molecular principles underlying controlled protein and mRNA degradation unravels their remarkable mechanistic similarities, and suggests how the intrinsic structural features of the two molecular species regulate their half-lives on genome-scale and during evolution.
IRE1α regulates macrophage polarization, PD-L1 expression and tumor survival
Authors: Batista Alyssa , Rodvold Jeffrey J. , Xian Su , Searles Stephen , Lew Alyssa , Iwawaki Takao , Almanza Gonzalo , Waller T. Cameron , Lin Jonathan , Jepsen Kristen , Carter Hannah , Zanetti Maurizio 
Published: February 2020

ABSTRACTIn the tumor microenvironment local immune dysregulation is driven in part by macrophages and dendritic cells that are polarized to a mixed proinflammatory/immune suppressive phenotype. The unfolded protein response (UPR) is emerging as the possible origin of these events. Here we report that the inositol-requiring enzyme 1 (IRE1α) branch of the UPR is directly involved in the polarization of macrophagesin vitroandin vivo,including the upregulation of IL-6, IL-23, Arginase1, as well as surface expression of CD86 and PD-L1. Macrophages in which the IRE1α/Xbp1 axis is blocked pharmacologically or deleted genetically have significantly reduced polarization, and CD86 and PD-L1 expression, which was induced independent of IFNγ signaling suggesting a novel mechanism in PD-L1 regulation in macrophages. Mice with IRE1α- but not Xbp1-deficient macrophages showed greater survival than controls when implanted with B16.F10 melanoma cells. Remarkably, we found a significant association between the IRE1α gene signature andCD274gene expression in tumor-infiltrating macrophages in humans. RNASeq analysis showed that bone marrow derived macrophages with IRE1α deletion lose the integrity of the gene connectivity characteristic of regulated IRE1α-dependent decay (RIDD) and the ability to activateCD274gene expression. Thus, the IRE1α/Xbp1 axis drives the polarization of macrophages in the tumor microenvironment initiating a complex immune dysregulation leading to failure of local immune surveillance.
Common postzygotic mutational signature in multiple healthy adult tissues related to embryonic hypoxia
Authors: Hong Yaqiang , Zhang Dake , Zhou Xiangtian , Chen Aili , Abliz Amir , Bai Jian , Wang Liang , Hu Qingtao , Gong Kenan , Guan Xiaonan , Liu Mengfei , Zheng Xinchang , Lai Shujuan , Qu Hongzhu , Zhao Fuxin , Hao Shuang , Wu Zhen , Cai Hong , Hu Shaoyan , Ma Yue , Zhang Junting , Ke Yang , Wang Qianfei , Chen Wei , Zeng Changqing 
Published: February 2020

AbstractPostzygotic mutations are acquired in all of the normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenesis causing factors. The process and underlying mechanism of postzygotic mutations in normal tissues is still poorly understood. In this study, we investigated postzygotic mutation spectra in healthy individuals by optimized ultra-deep exome sequencing of time series samples from the same volunteer and samples from different individuals. In cells of blood, sperm, and muscle, we resolved three common types of mutational signature. Two of them are known to represent clock-like mutational processes, and their proportions in mutation profiles associated with polymorphisms of epigenetic regulation genes, suggesting the contribution of personal genetic backgrounds to underlying biological process. Notably, the third signature, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type were likely to occur early in embryo development even before the tissue differentiation, as indicated by their relatively high allele frequencies, sharing variants between multiple tissues, and lacking of age-related accumulation. Almost all tumors shown in public datasets did not have this signature detected except for 19.6% of clear cell renal cell carcinoma samples, which featured by activation of the hypoxia-induced signaling pathway. Moreover, in vitro activation of HIF signaling pathway successfully introduced the corresponding mutation profile of this signature in a culture-expanded human embryonic stem cell line. Therefore, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggest hypoxic conditions in the early stage of embryo development may be a crucial factor for the C>T transitions at GpCpN sites and individual genetic background also related to shaping human postzygotic mutation profiles.
Transcriptome analysis reveals the effects of transgenic expression of the Gal4 protein on normal gene expression in silkworm tissues
Authors: Chen Tao , Ma Yan , Liu Rongpeng , Tan Tingting , Huang Lihua , Xu Hanfu 
Published: February 2020

AbstractThe Gal4/upstream activating sequence(UAS) system, a well-known genetic tool, has been widely used to analyze gene function in many organisms, including the silkworm (Bombyx mori), a model lepidopteran insect. Several studies have suggested that Gal4 protein activation in tissues can negatively affect transgenic individuals; however, whether and to what extent the Gal4 protein affects normal endogenous gene expression have rarely been studied. Here, we analyzed the transcriptomes of transgenic silkworms expressing the Gal4 protein at high levels in both the wing disc (WD) and epidermis (EP) and investigated gene expression changes in both tissues. Overall, 24,593 genes were identified in the WD and EP libraries, and 2,025 and 2,488 were identified as significant differentially expressed genes(DEGs) in the WD and EP between the transgenic and control groups, respectively. These DEGs were further annotated by gene function classification and pathway assessment using public databases. In addition, 506 DEGs were shared (common) between both tissues. Of these, 97 genes were commonly upregulated, and 234 were commonly downregulated; many of them were annotated to be involved in metabolic processes such as “fat digestion and absorption”, “glycine, serine and threonine metabolism” and “glutathione metabolism” and in signal transduction pathways such as the “Rap1 signaling pathway”, “MAPK signaling pathway” and “Hippo signaling pathway”. Overall, this work enhances understanding of the effects of transgenic Gal4 protein expression on normal gene expression in silkworm tissues and suggests that researchers should pay attention to unexpected effects when using the Gal4/UAS system to study gene function.
Microhabitat and ectomycorrhizal effects on the establishment, growth and survival ofQuercus ilexL. seedlings under drought
Authors: García de Jalón Laura , Limousin Jean-Marc , Richard Franck , Gessler Arthur , Peter Martina , Hättenschwiler Stephan , Milcu Alexandru 
Published: February 2020

AbstractThe success of tree recruitment in MediterraneanQuercus ilexforests is threatened by the increasing intensity, duration and frequency of drought periods. Seedling germination and growth are modulated by complex interactions between abiotic (microhabitat conditions) and biotic factors (mycorrhiza association) that may mitigate the impacts of climate change on tree recruitment. To better understand and anticipate these effects, we conducted a germination experiment in a long-term precipitation reduction (PR) field experiment where we monitored seedling establishment and survival, micro-environmental conditions and ectomycorrhizal (ECM) colonization by different mycelia exploration types during the first year of seedling growth. We hypothesized that (i) the PR treatment decreases seedling survival relative to the control with ambient conditions, (ii) the underlying mechanisms for seedling survival are better understood with detailed information of microhabitat water and light availability irrespective of the PR treatment, (iii) the PR treatment will favour the development of ECM exploration types with drought-resistance traits such as differentiated rhizomorphs. Contrary to our first hypothesis, seedling survival was lower in control plots with overall higher soil moisture. Micro-site light and soil moisture conditions were better predictors of seedling survival and growth than the plot-level PR treatment, confirming our second hypothesis. Furthermore, in line with our third hypothesis, we found that ECM with longer extramatrical mycelia were more abundant in the PR treatment plots and were positively correlated to survival, which suggests a potential role of this ECM exploration type in seedling survival and recruitment. Although summer drought was the main cause of seedling mortality, our study indicates that drier conditions in spring can increase seedling survival, presumably through a synergistic effect of drought adapted ECM species and less favourable conditions for root pathogens.
Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats
Authors: Logan Carly N. , Bechard Allison R. , Hamor Peter U. , Wu Lizhen , Schwendt Marek , Knackstedt Lori A. 
Published: February 2020

AbstractRationaleThe beta-lactam antibiotic ceftriaxone reliably attenuates the reinstatement of cocaine-seeking. While the restoration of nucleus accumbens core (NA core) GLT-1 expression is necessary for ceftriaxone to attenuate reinstatement, AAV-mediated GLT-1 overexpression is not sufficient to attenuate reinstatement and does not prevent glutamate efflux during reinstatement.AimsHere, we test the hypothesis that ceftriaxone attenuates reinstatement through interactions with glutamate autoreceptors mGlu2 and mGlu3 in the NA core.MethodsMale and female rats self-administered cocaine for 12 days followed by 2-3 weeks of extinction training. During the last 6-10 days of extinction, rats received ceftriaxone (200 mg/kg IP) or vehicle. In experiment 1, rats were killed, and NA core tissue was biotinylated for assessment of total and surface expression of mGlu2 and mGlu3 via western blotting. In experiment 2, we tested the hypothesis that mGlu2/3 signaling is necessary for ceftriaxone to attenuate cue- and cocaine-primed reinstatement by administering bilateral intra-NA core infusion of mGlu2/3 antagonist LY341495 or vehicle immediately prior to reinstatement testing.ResultsmGlu2 expression was reduced by cocaine and restored by ceftriaxone. There were no effects of cocaine or ceftriaxone on mGlu3 expression. We observed no effects of estrus on expression of either protein. The antagonism of mGlu2/3 in the NA core during both cue- and cocaine-primed reinstatement tests prevented ceftriaxone from attenuating reinstatement.ConclusionsThese results indicate that ceftriaxone’s effects depend on mGlu2/3 function and possibly mGlu2 receptor expression. Future work will test this hypothesis by manipulating mGlu2 expression in pathways that project to the NA core.
Proteomic and phosphoproteomic analysis identifies novel liver-related signaling in retinal pigment epithelial cells during epithelial-mesenchymal transition
Authors: Mertz Joseph L. , Sripathi Srinivas , Yang Xue , Chen Lijun , Esumi Noriko , Zhang Hui , Zack Donald J. 
Published: February 2020

ABSTRACTEpithelial–mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is associated with several potentially blinding retinal diseases. Proteomic and phosphoproteomic studies were performed on human pluripotent stem cell-derived RPE (hPSC-RPE) monolayers to better understand the pathways mediating RPE EMT. EMT was induced by enzymatic dissociation or by co-treatment with transforming growth factor beta (TGFβ) and tumor necrosis factor alpha (TNFα; TGNF). The global and phosphoproteomes were analyzed at 1 hr post EMT induction to capture early events in kinase/phosphatase signaling cascades and at 12 hrs to define early changes in protein abundance. Pathway enrichment analysis revealed that TGNF and Dissociation rapidly perturbed signaling in many of the same pathways, with striking similarity in the phosphoproteome at 1 hr. Surprisingly, functions related to liver cell proliferation and hyperplasia were strongly enriched in the phosphosites altered by both treatments at 1 hr and in protein abundance changes at 12 hrs. Hepatocyte Growth Factor-cMET signaling exhibited the strongest overall enrichment in both treatments. These signaling pathways may serve as suitable targets for the development of therapeutic strategies for the inhibition of RPE EMT, and thus progression of several debilitating visual diseases.