bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventral arkypallidal neurons modulate accumbal firing to promote reward consumption
Authors: Vachez Yvan M. , Tooley Jessica R. , Casey Eric , Earnest Tom , Abiraman Kavitha , Silberberg Hannah , Godynyuk Elizabeth , Uddin Olivia , Marconi Lauren , Le Pichon Claire , Creed Meaghan C. 
Published: April 2020

ABSTRACTA pause in firing of nucleus accumbens shell (NAcSh) neurons is critical for reward consumption; however, the substrate driving this pause is unknown. While ventral pallidal (VP) activity encodes reward value, the specific roles of VP subpopulations in computation and expression of this value are poorly understood. Here, we establish that inhibitory input from the VP is crucial for reward-related inhibition of NAc firing. A sparse, non-canonical subpopulation of VP neurons, the so-called “ventral arkypallidal (vArky)” neurons makes inhibitory synaptic contacts throughout the NAcSh, and drives inhibition of NAcSh neurons in vivo. Moreover, endogenous calcium activity of vArky neurons predicted subsequent reward consumption behavior, while optogenetically activating this pathway increased reward consumption by amplifying hedonic value of reward. Classically, the VP is considered downstream of the NAc; however, our results challenge this view and establish that vArky neurons in the VP promote reward consumption via potent modulation of NAcSh firing.
A microbial perspective on balancing trade-offs in ecosystem functions in a constructed stormwater wetland
Authors: Bledsoe Regina B. , Bean Eban Z. , Austin Samuel S. , Peralta Ariane L. 
Published: April 2020

AbstractGreen stormwater infrastructure, such as constructed wetlands (CWs), is a type of stormwater control measure that can decrease nutrient and pollutant loads from urban stormwater runoff. Wetland soil microorganisms provide nutrient and pollutant removal benefits which can also result in ecosystem disservices such as greenhouse gas (GHG) emissions and can inadvertently exacerbate climate change. Microbial respiration by facultative anaerobes in anoxic conditions is the primary pathway for nitrogen removal (benefit). Similar anoxic conditions that support denitrifying microorganisms can also support obligate anaerobes that produce methane (CH4) via methanogenesis (disservice). We examined nitrogen removal potential, GHG production, and microbial community structure within permanently flooded and shallow land or temporarily-flooded areas of a stormwater CW to identify zones for CW design optimization. Results indicate that permanently flooded zones compared to shallow land zones are greater sources of CH4emissions (80.80 ± 118.31, 2.32 ± 9.33 mg CH4-C m-2hr-1, respectively) and emit more carbon to the atmosphere (7161.27 kg CO2, 93.20 kg CO2equivalents, respectively). However, nitrogen removal potential rates were similar across both flooded and shallow land zones (24.45 ± 20.18, 20.29 ± 15.14 ng N2O-N hr-1g-1dry soil, respectively). At this particular CW, reduction of permanently flooded zones within the wetland could decrease GHG emissions (disservice) without limiting nitrogen removal (benefit) potential of the wetland. Holistic development and design of stormwater control measures, which account for microbial activity, provides the opportunity to maximize benefits (i.e., nutrient and pollutant removal) and reduce disservices (i.e., GHG emissions) of green stormwater infrastructure.
New approaches to species delimitation and population structure of corals: two case studies using ultraconserved elements and exons
Authors: Erickson Katie L. , Pentico Alicia , Quattrini Andrea M. , McFadden Catherine S. 
Published: April 2020

AbstractAs coral populations decline worldwide in the face of ongoing environmental change, documenting their distribution, diversity and conservation status is now more imperative than ever. Accurate delimitation and identification of species is a critical first step. This task, however, is not trivial as morphological variation and slowly evolving molecular markers confound species identification. New approaches to species delimitation in corals are needed to overcome these challenges. Here, we test whether target enrichment of ultraconserved elements (UCEs) and exons can be used for delimiting species boundaries and population structure within species of corals by focusing on two octocoral genera,AlcyoniumandSinularia, as exemplary case studies. We designed an updated bait set (29,363 baits) to target-capture 3,040 UCE and exon loci, recovering a mean of 1,910 ± 168 SD per sample with a mean length of 1,055 ± 208 bp. Similar numbers of loci were recovered fromSinularia(1,946 ± 227 SD) andAlcyonium(1,863 ± 177 SD). Species-level phylogenies were highly supported for both genera. Clustering methods based on filtered SNPs delimited species and populations that are congruent with previous allozyme, DNA barcoding, reproductive and ecological data forAlcyonium, and offered further evidence of hybridization among species. ForSinularia, results were congruent with those obtained from a previous study using Restriction Site Associated DNA Sequencing. Both case studies demonstrate the utility of target-enrichment of UCEs and exons to address a wide range of evolutionary and taxonomic questions across deep to shallow time scales in corals.
Is evolution in response to extreme events good for population persistence?
Authors: Lyberger Kelsey , Osmond Matthew , Schreiber Sebastian 
Published: April 2020

AbstractClimate change is predicted to increase the severity of environmental perturbations, including storms and droughts, which act as strong selective agents. These extreme events are often of finite duration (pulse disturbances). Hence, while evolution during an extreme event may be adaptive, the resulting phenotypic changes may become maladaptive when the event ends. Using individual-based models and analytic approximations that fuse quantitative genetics and demography, we explore how heritability and phenotypic variance affect population size and extinction risk in finite populations under an extreme event of fixed duration. Since more evolution leads to greater maladaptation and slower population recovery following an extreme event, slowing population recovery, greater heritability can increase extinction risk when the extreme event is short, as in random environments with low autocorrelation. Alternatively, when an extreme event is sufficiently long, heritability often helps a population persist, as under a press perturbation. We also find that when events are severe, the buffering effect of phenotypic variance can outweigh the increased load it causes. Our results highlight the importance of the length and severity of a disturbance when assessing the role of evolution on population recovery; the rapid adaptive evolution observed during extreme events may be bad for persistence.
New Viral Biogeochemical Roles Revealed Through Metagenomic Analysis of Lake Baikal
Authors: Coutinho FH , Cabello-Yeves PJ , Gonzalez-Serrano R , Rosselli R , López-Pérez M , Zemskaya TI , Zakharenko AS , Ivanov VG , Rodriguez-Valera F 
Published: April 2020

AbstractLake Baikal is the largest body of liquid freshwater on Earth. Previous studies have described the microbial composition of this habitat but the viral communities from this ecosystem have not been characterized in detail. Here we describe the viral diversity of this habitat across depth and seasonal gradients. We discovered 19,475bona fideviral sequences, which are derived from viruses predicted to infect abundant and ecologically important taxa that reside in Lake Baikal, such as Nitrospirota, Methylophilaceae and Crenarchaeota. Diversity analysis revealed significant changes in viral community composition between epipelagic and bathypelagic zones. Analysis of the gene content of individual viral populations allowed us to describe one of the first bacteriophages that infect Nitrospirota, and their extensive repertoire of auxiliary metabolic genes that might enhance carbon fixation through the reductive TCA cycle. We also described bacteriophages of methylotrophic bacteria with the potential to enhance methanol oxidation and the S-adenosyl-L-methionine cycle. These findings unraveled new ways by which viruses influence the carbon cycle in freshwater ecosystems, namely by using auxiliary metabolic genes that act upon metabolisms of dark carbon fixation and methylotrophy. Therefore, our results shed light on the processes through which viruses can impact biogeochemical cycles of major ecological relevance.
Computational prediction of Drug-Disease association based on Graph-regularized one bit Matrix completion
Authors: Mongia Aanchal , Chouzenoux Emilie , Majumdar Angshul 
Published: April 2020

AbstractMotivationInvestigation of existing drugs is an effective alternative to discovery of new drugs for treating diseases. This task of drug re-positioning can be assisted by various kinds of computational methods to predict the best indication for a drug given the open-source biological datasets. Owing to the fact that similar drugs tend to have common pathways and disease indications, the association matrix is assumed to be of low-rank structure. Hence, the problem of drug-disease association prediction can been modelled as a low-rank matrix-completion problem.ResultsIn this work, we propose a novel matrix completion framework which makes use of the sideinformation associated with drugs/diseases for the prediction of drug-disease indications modelled as neighborhood graph: Graph regularized 1-bit matrix compeltion (GR1BMC). The algorithm is specially designed for binary data and uses parallel proximal algorithm to solve the aforesaid minimization problem taking into account all the constraints including the neighborhood graph incorporation and restricting predicted scores within the specified range. The results of the proposed algorithm have been validated on two standard drug-disease association databases (Fdataset and Cdataset) by evaluating the AUC across the 10-fold cross validation splits. The usage of the method is also evaluated through a case study where top 5 indications are predicted for novel drugs and diseases, which then are verified with the CTD database. The results of these experiments demonstrate the practical usage and superiority of the proposed approach over the benchmark methods.Contactaanchalm@iiitd.ac.in
Comparative single-cell trajectory network enrichment identifies pseudo-temporal systems biology patterns in hematopoiesis and CD8 T-cell development
Authors: Grønning Alexander G. B. , Oubounyt Mhaned , Kanev Kristiyan , Lund Jesper , Kacprowski Tim , Zehn Dietmar , Röttger Richard , Baumbach Jan 
Published: April 2020

AbstractSingle cell transcriptomics (scRNA-seq) technologies allow for investigating cellular processes on an unprecedented resolution. While software packages for scRNA-seq raw data analysis exist, no method for the extraction of systems biology signatures that drive different pseudo-time trajectories exists. Hence, pseudo-temporal molecular sub-network expression profiles remain undetermined, thus, hampering our understanding of the molecular control of cellular development on a single cell resolution. We have developed Scellnetor, the first network-constraint time-series clustering algorithm implemented as interactive webtool to identify modules of genes connected in a molecular interaction network that show differentiating temporal expression patterns. Scellnetor allows selecting two differentiation courses or two developmental trajectories for comparison on a systems biology level. Scellnetor identifies mechanisms driving hematopoiesis in mouse and mechanistically interpretable subnetworks driving dysfunctional CD8 T-cell development in chronic infections. Scellnetor is the first method to allow for single cell trajectory network enrichment for systems level hypotheses generation, thus lifting scRNA-seq data analysis to a systems biology level. It is available as an interactive online tool athttps://exbio.wzw.tum.de/scellnetor/.
Recursive Convolutional Neural Networks for Epigenomics
Authors: Symeonidi Aikaterini , Nicolaou Anguelos , Johannes Frank , Christlein Vincent 
Published: April 2020

AbstractDeep learning methods have proved to be powerful classification tools in the fields of structural and functional genomics. In this paper, we introduce a Recursive Convolutional Neural Networks (RCNN) for the analysis of epigenomic data. We focus on the task of predicting gene expression from the intensity of histone modifications. The proposed RCNN architecture can be applied to data of an arbitrary size, and has a single meta-parameter that quantifies the models capacity, thus making it flexible for experimenting. The proposed architecture outperforms state-of-the-art systems, while having several orders of magnitude fewer parameters.
Plastome phylogenomic study of Gentianeae (Gentianaceae): widespread gene tree discordance and its association with evolutionary rate heterogeneity of plastid genes
Authors: Zhang Xu , Sun Yanxia , Landis Jacob B. , Lv Zhenyu , Shen Jun , Zhang Huajie , Lin Nan , Li Lijuan , Sun Jiao , Deng Tao , Sun Hang , Wang Hengchang 
Published: April 2020

AbstractBackgroundPlastome-scale data have been prevalent in reconstructing the plant Tree of Life. However, phylogenomic studies currently based on plastomes rely primarily on maximum likelihood (ML) inference of concatenated alignments of plastid genes, and thus phylogenetic discordance produced by individual plastid genes has generally been ignored. Moreover, structural and functional characteristics of plastomes indicate that plastid genes may not evolve as a single locus and are experiencing different evolutionary forces, yet the genetic characteristics of plastid genes within a lineage remain poorly studied.ResultsWe sequenced and annotated ten plastome sequences of Gentianeae. Phylogenomic analyses yielded robust relationships among genera within Gentianeae. We detected great variation of gene tree topologies and revealed more than half of the genes, including one (atpB) of the three widely used plastid markers (rbcL, atpBandmatK) in phylogenetic inference of Gentianeae, are likely contributing to phylogenetic ambiguity of Gentianeae. Estimation of nucleotide substitution rates showed extensive rate heterogeneity among different plastid genes and among different functional groups of genes. Comparative analysis suggested that the ribosomal protein (RPL and RPS) genes and the RNA polymerase (RPO) genes have higher substitution rates and genetic variations in Gentianeae. Our study revealed that just one (matK) of the three (matK, ndhBandrbcL) widely used markers show high phylogenetic informativeness (PI) value. Due to the high PI and lowest gene-tree discordance,rpoC2is advocated as a promising plastid DNA barcode for taxonomic studies of Gentianeae. Furthermore, our analyses revealed a positive correlation of evolutionary rates with genetic variation of plastid genes, but a negative correlation with gene-tree discordance under purifying selection.ConclusionsOverall, our results demonstrate the heterogeneity of nucleotide substitution rates and genetic characteristics among plastid genes providing new insights into plastome evolution, while highlighting the necessity of considering gene-tree discordance into phylogenomic studies based on plastome-scale data.
Deregulated mito-nuclear communication alters chromatin plasticity and differentiation potential of mesenchymal stem cells upon ageing
Authors: Pouikli Andromachi , Parekh Swati , Maleszewska Monika , Baghdadi Maarouf , Tripodi Ignacio , Nikopoulou Chrysa , Folz-Donahue Kat , Hinze Yvonne , Mesaros Andrea , Giavalisco Patrick , Dowell Robin , Partridge Linda , Tessarz Peter 
Published: April 2020

ABSTRACTAgeing is accompanied by a general decline in the function of many cellular pathways, with metabolic alterations, epigenetic modifications, and stem cell exhaustion representing three important hallmarks of the ageing process. However, whether these pathways are causally or functionally related at a molecular level remains poorly understood. Here, we use bone marrow-derived mesenchymal stem cells (MSCs) isolated from young and old mice to address how age-dependent changes in metabolism and epigenetics are linked and how they impact on the ageing transcriptome and differentiation potential. Given that MSCs maintain specific age-associated properties even under prolonged culture conditions, such as the age-dependent decrease in osteogenic differentiation, they are an excellent model to investigatein vitrothe connection of ageing hallmarks on a mechanistic level. In this study, we demonstrate that upon ageing, osteogenic potential of MSCs declines as a consequence of deregulated mito-nuclear communication, mediated by decreased levels of the citrate carrier (CiC). Age-dependent down-regulation of CiC results in acetyl-CoA trapping within mitochondria, hypo-acetylation of histones and chromatin compaction. Together, these changes lead to an altered transcriptional output and are responsible for the reduced differentiation capacity into osteoblasts. Strikingly, short-term supplementation of aged cells with acetate, an exogenous source for cytosolic acetyl-CoA production, rescues not only the age-associated reduction of histone acetylation, but also the osteogenesis defect, representing a potential target forin vitroMSC rejuvenation.
Subcellular localization of the J-protein Sis1 regulates the heat shock response
Authors: Feder Zoe A. , Ali Asif , Singh Abhyudai , Krakowiak Joanna , Zheng Xu , Bindokas Vytas P. , Wolfgeher Donald , Kron Stephen J. , Pincus David 
Published: April 2020

ABSTRACTCells exposed to heat shock induce a conserved gene expression program – the heat shock response (HSR) – encoding chaperones like Hsp70 and other protein homeostasis (proteostasis) factors. Heat shock also triggers proteostasis factors to form subcellular quality control bodies, but the relationship between these spatial structures and the HSR is unclear. Here we show that localization of the J-protein Sis1 – a co-chaperone for Hsp70 – controls HSR activation in yeast. Under nonstress conditions, Sis1 is concentrated in the nucleoplasm where it promotes Hsp70 binding to the transcription factor Hsf1, repressing the HSR. Upon heat shock, Sis1 forms an interconnected network with other proteostasis factors that spans the nucleolus and the surface of the cortical ER. We propose that localization of Sis1 to this network directs Hsp70 activity away from Hsf1 in the nucleoplasm, leaving Hsf1 free to induce the HSR. In this manner, Sis1 couples HSR activation to the spatial organization of the proteostasis network.One sentence summaryLocalization of the J-protein Sis1 to a subcellular network of proteostasis factors activates the heat shock response.
Identifying therapeutic drug targets for rare and common forms of short stature
Authors: Estrada Karol , Froelich Steven , Wuster Arthur , Bauer Christopher R. , Sterling Teague , Clark Wyatt T. , Ru Yuanbin , Trinidad Marena , Nguyen Hong Phuc , Luu Amanda R. , Wendt Daniel J. , Yogalingam Gouri , Yu Guoying Karen , LeBowitz Jonathan H. , Cardon Lon R. 
Published: April 2020

AbstractWhile GWAS of common diseases has delivered thousands of novel genetic findings, prioritizing genes for translation to therapeutics has been challenging. Here, we propose an approach to resolve that issue by identifying genes that have both gain of function (GoF) and loss of function (LoF) mutations associated with opposing effects on phenotype (Bidirectional Effect Selected Targets, BEST). Bidirectionality is a desirable feature of the best targets because it implies both a causal role on the phenotype in one direction and that modulating the target activity might be safe and therapeutically beneficial in the other.We used height, a highly heritable trait and a model of complex diseases, to test our approach. Using 34,231 individuals with exome sequence data and height, we identified five genes (IGF1R, NPPC, NPR2, FGFR3, andSHOX) with evidence for bidirectional effects on stature. Rare protein-altering variants significantly increased risk for idiopathic short stature (ISS) (OR=2.75, p= 3.99×10−8). These genes are key members of the only two pathways successfully targeted for short stature: Growth Hormone/Insulin-like growth factor 1 axis and C-type Natriuretic peptide (CNP) for Achondroplasia, a monogenic form of dwarfism. We assayed a subset ofNPR2mutations and identified those with elevated (GoF) and diminished (LoF) activity and found that a polygenic score for height modulates the penetrance of pathogenic variants. We also demonstrated that adding exogenous CNP (encoded byNPPC) rescues theNPR2haploinsufficiency molecular phenotype in a CRISPR-engineered cell line, thus validating its potential therapeutic treatment for inherited forms of short stature. Finally, we found that these BEST targets increase the probability of success in clinical trials above and beyond targets with other genetic evidence. Our results show the value of looking for bidirectional effects to identify and validate drug targets.
Recovery of cryo-injured rabbit urethras by biofabricated C-shaped adipose-derived mesenchymal cell structures
Authors: Gautam Sudha Silwal , Imamura Tetsuya , Shimamura Mitsuru , Minagawa Tomonori , Nakazawa Masaki , Ogawa Teruyuki , Ishizuka Osamu 
Published: April 2020

AbstractUrethral tissue damage can cause stress urinary incontinence or urinary retention, and there are few long-term, effective treatments. For structural and functional recovery of urethral tissues, we designed and constructed C-shaped structures composed of adipose-derived mesenchymal cells (AMCs) by using a three-dimensional (3D)-bioprinter system, which could be transplanted in damaged urethras without obstructing the lumen. We determined if transplantation of the biofabricated structures could reconstruct the urethral tissues. AMCs were harvested from rabbits, cultured and labeled with PKH26 to form spheroids. The spheroids were assembled on a custom-designed C-shaped support by a 3D bioprinter. Urethras of rabbits were cryo-injured by spraying with liquid nitrogen for 20 seconds, incised and biofabricated structure was autologously transplanted. Control rabbits were treated similarly but without transplantation structure. Two and four weeks after surgery, the control urethras were partially constricted; however, the structure-transplanted urethras were patent. The AMCs within the structures differentiated into skeletal muscle, smooth muscle, nerve, or endothelial cells. Some cells contained growth factors and cytokines. Therefore, biofabricated C-shaped AMC structures have potential to be an effective treatment for urethral recovery.Summary StatementThree-dimensional bioprinter was used to biofabricate novel C-shaped structures composed of adipose-derived mesenchymal cells (AMCs) and have the potential to be an effective treatment for urethral recovery.