bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Out-of-Patagonia dispersal explains most of the worldwide genetic distribution in Saccharomyces eubayanus
Authors: Nespolo Roberto F. , Villarroel Carlos A. , Oporto Christian I. , Tapia Sebastián M. , Vega Franco , Urbina Kamila , De Chiara Matteo , Mozzachiodi Simone , Mikhalev Ekaterina , Thompson Dawn , Saenz-Agudelo Pablo , Liti Gianni , Cubillos Francisco A. 
Published: July 2019

ABSTRACTSaccharomyces eubayanus represents missing cryotolerant ancestor of lager yeast hybrid and can be found in Patagonia in association with Nothofagus forests. The limited number of isolates and associated genomes available has prevented to resolve the S. eubayanus origin and evolution. Here, we present a sampling effort at an unprecedented scale and report the isolation of 160 strains from ten sampling sites along 2,000 km distance in South America. We sequenced the genome of 82 strains and, together with other 25 available genomes, performed comprehensive phylogenetic analysis. Our results revealed the presence of three main Patagonia-B lineages together with dozens of admixed strains distributed in three mosaic clusters. The PB-1 lineage isolated from Tierra del Fuego exhibited the highest genetic diversity, lowest LD blocks and highest Fis values compared to the other lineages, suggesting a successful adaptation to cold temperatures in extreme environments and greater inbreeding rates in Tierra del Fuego. Differences between lineages and strains were found in terms of aneuploidy and pangenome content, evidencing a lateral gene transfer event in PB-2 strains from an unknown donor species. Overall, the Patagonian lineages, particularly southern populations, showed a greater global genetic diversity compared to Holarctic and Chinese lineages, supporting the scenario of a S. eubayanus colonization from Patagonia and then spread towards northern and western regions, including the Holarctic (North America and China) and New Zealand. Interestingly, fermentative capacity and maltose consumption resulted negatively correlated with latitude, indicating a better fermentative performance in norther populations. Our genome analysis together with previous reports in the sister species S. uvarum strongly suggests that the S. eubayanus ancestor could have originated in Patagonia or the Southern Hemisphere, rather than China, yet further studies are needed to resolve this conflicting scenario. Understanding S. eubayanus evolutionary history is crucial to resolve the unknown origin of the lager yeast and might open new avenues for biotechnological applications.
Genome diversity and species richness in mammals
Authors: Herrick John , Sclavi Bianca 
Published: July 2019

AbstractEvolutionary changes in karyotype have long been implicated in speciation events; however, the phylogenetic relationship between karyotype diversity and species richness in closely and distantly related mammalian lineages remains to be fully elucidated. Here we examine the association between genome diversity and species diversity across the class Mammalia. We tested five different metrics of genome diversity: clade-average genome size, standard deviation of genome size, diploid and fundamental numbers (karyotype diversity), sub-chromosomal rearrangements and percent synteny block conservation. We found a significant association between species richness (phylogenetic clade diversity) and genome diversity at both order and family level clades. Karyotype diversity provided the strongest support for a relationship between genome diversity and species diversity. Our results suggest that lineage specific variations in genome and karyotype stability can account for different levels of species diversity in mammals.
Fxr1 regulates sleep and synaptic homeostasis
Authors: Khlghatyan Jivan , Evstratova Alesya , Bozoyan Lusine , Chamberland Simon , Marakhovskaia Aleksandra , Silva Tiago Soares , Toth Katalin , Mongrain Valerie , Beaulieu Jean-Martin 
Published: July 2019

AbstractThe fragile X autosomal homolog 1 (Fxr1) has been GWAS-associated to schizophrenia and insomnia but its contributions to brain functions are unclear. Homeostatic regulation of synaptic strength is essential for the maintenance of brain functions and engages both global and cell autonomous level processes. We used Crispr/Cas9-mediated somatic knockouts, overexpression, neuronal activity recordings and translatome sequencing, to examine the contribution of Fxr1 to cell-autonomous homeostatic synaptic scaling and global-level sleep homeostasis. Our findings indicate that Fxr1 is downregulated during scaling and sleep deprivation via a Gsk3β dependent mechanism. In both conditions, downregulation of Fxr1 is essential for the homeostatic modulation of synaptic strength. Furthermore, overexpression of Fxr1 during sleep deprivation results in altered EEG signatures and reverts changes of translatome profiles. These findings indicate that Fxr1 represents a shared signaling hub linking cell autonomous homeostatic plasticity and system level sleep homeostasis with potential implications for neuropsychiatric illnesses.
An ABBA-BABA Test for Introgression Using Retroposon Insertion Data
Authors: Springer Mark S. , Gatesy John 
Published: July 2019

AbstractDNA sequence alignments provide the majority of data for inferring phylogenetic relationships with both concatenation and coalescence methods. However, DNA sequences are susceptible to extensive homoplasy, especially for deep divergences in the Tree of Life. Retroposon insertions have emerged as a powerful alternative to sequences for deciphering evolutionary relationships because these data are nearly homoplasy-free. In addition, retroposon insertions satisfy the ‘no intralocus recombination’ assumption of summary coalescence methods because they are singular events and better approximate neutrality relative to DNA sequences commonly applied in phylogenomic work. Retroposons have traditionally been analyzed with phylogenetic methods that ignore incomplete lineage sorting (ILS). Here, we analyze three retroposon data sets for mammals (Placentalia, Laurasiatheria, Balaenopteroidea) with two different ILS-aware methods. The first approach constructs a species tree from retroposon bipartitions with ASTRAL, and the second is a modification of SVD-Quartets. We also develop a χ2 Quartet-Asymmetry Test to detect hybridization using retroposon data. Both coalescence methods recovered the same topology for each of the three data sets. The ASTRAL species tree for Laurasiatheria has consecutive short branch lengths that are consistent with an anomaly zone situation. For the Balaenopteroidea data set, which includes rorquals (Balaenopteridae) and gray whale (Eschrichtiidae), both coalescence methods recovered a topology that supports the paraphyly of Balaenopteridae. Application of the χ2 Quartet-Asymmetry Test to this data set detected 16 different quartets of species for which historical hybridization may be inferred, but significant asymmetry was not detected in the placental root and Laurasiatheria analyses.
The viral SUMO-targeted Ubiquitin Ligase ICP0 is phosphorylated and activated by host kinase Chk2
Authors: Hembram Dambarudhar SS , Negi Hitendra , Biswas Poulomi , Tripathi Vasvi , Bhushan Lokesh , Shet Divya , Kumar Vikas , Das Ranabir 
Published: July 2019

AbstractWhen the Herpes Simplex virus (HSV) genome enters the nucleus for replication and transcription, phase-segregated nuclear protein bodies called PML Nuclear Bodies (PML NBs) colocalize with the genome and repress it. HSV encodes a SUMO-targeted Ubiquitin ligase ICP0 that degrades PML NBs to alleviate the repression. The molecular mechanism used by ICP0 to target PML NBs is unclear. For reasons unknown, the growth of HSV is dependent on the ATM/Chk2 pathway. Here we identify a bonafide SUMO-Interacting motif in ICP0 (SLS4) that is essential and sufficient to target SUMOylated proteins in PML NBs like PML and Sp100. Phosphorylation of SLS4 creates new salt-bridges between SUMO and SLS4, increases the SUMO/SLS4 affinity and switches ICP0 into a potent STUbL. We also report that ICP0 exploits the kinase Chk2 to phosphorylate SLS4 and enhance its STUbL activity. Our results uncover how a viral STUbL counters antiviral response by exploiting an unprecedented mechanism involving three post-translational modifications; ubiquitination, SUMOylation, and phosphorylation.
Core spliceosomal Sm proteins as constituents of cytoplasmic mRNPs in plants
Authors: Hyjek-Składanowska Malwina , Bajczyk Mateusz , Gołębiewski Marcin , Nuc Przemysław , Kołowerzo-Lubnau Agnieszka , Jarmołowski Artur , Smoliński Dariusz Jan 
Published: July 2019

ABSTRACTIn light of recent studies, many of the cytoplasmic posttranscriptional mRNA processing steps take place in highly specialized microdomains referred to as cytoplasmic bodies. These evolutionarily conserved microdomains are sites of regulation for both mRNA translation and degradation. It has been shown that in the larch microsporocyte cytoplasm, there is a significant pool of Sm proteins not related to snRNP complexes. These Sm proteins accumulate within distinct cytoplasmic bodies (S-bodies) that also contain mRNA. Sm proteins constitute an evolutionarily ancient family of small RNA-binding proteins. In eukaryotic cells, these molecules are involved in pre-mRNA splicing. The latest research indicates that in addition to this well-known function, Sm proteins could also have an impact on mRNA at subsequent stages of its life cycle. The aim of this work was to verify the hypothesis that canonical Sm proteins are part of the cytoplasmic mRNP complex and thus function in the posttranscriptional regulation of gene expression in plants.
Design principles of selective transport through biopolymer barriers
Authors: Maguire Laura , Stefferson Michael , Betterton Meredith D. , Hough Loren E. 
Published: July 2019

AbstractIn biological systems, polymeric materials block the movement of some macromolecules while allowing the selective passage of others. In some cases, binding enables selective transport, while in others the most inert particles appear to transit most rapidly. To study the general principles of filtering, we develop a model motivated by features of the nuclear pore complex (NPC) which are highly conserved and could potentially be applied to other biological systems. The NPC allows selective transport of proteins called transport factors which transiently bind to disordered, flexible proteins called FG Nups. While the NPC is tuned for transport factors and their cargo, we show that a single feature is sufficient for selective transport: the bound-state motion resulting from transient binding to flexible filaments. Interchain transfer without unbinding can further improve selectivity, especially for crosslinked chains. We generalize this observation to model nanoparticle transport through mucus and show that bound-state motion accelerates transport of transient nanoparticle application, even with clearance by mucus flow. Our model provides a framework to control binding-induced selective transport in bipolymeric materials.
pyBedGraph: a Python package for fast operations on 1-dimensional genomic signal tracks
Authors: Zhang Henry B. , Kim Minji , Chuang Jeffrey H. , Ruan Yijun 
Published: July 2019

AbstractMotivationModern genomic research relies heavily on next-generation sequencing experiments such as ChIP-seq and ChIA-PET that generate coverage files for transcription factor binding, as well as DHS and ATAC-seq that yield coverage files for chromatin accessibility. Such files are in a bedGraph text format or a bigWig binary format. Obtaining summary statistics in a given region is a fundamental task in analyzing protein binding intensity or chromatin accessibility. However, the existing Python package for operating on coverage files is not optimized for speed.ResultsWe developed pyBedGraph, a Python package to quickly obtain summary statistics for a given interval in a bedGraph file. When tested on 8 ChIP-seq and ATAC-seq datasets, pyBedGraph is on average 245 times faster than the existing program. Notably, pyBedGraph can look up the exact mean signal of 1 million regions in ~0.26 second on a conventional laptop. An approximate mean for 10,000 regions can be computed in ~0.0012 second with an error rate of less than 5 percent.AvailabilitypyBedGraph is publicly available at https://github.com/TheJacksonLaboratory/pyBedGraph under the MIT license.
A Hybrid Stochastic Model of the Budding Yeast Cell Cycle
Authors: Ahmadian Mansooreh , Tyson John J. , Peccoud Jean , Cao Yang 
Published: July 2019

AbstractThe growth and division of eukaryotic cells are regulated by complex, multi-scale networks. In this process, the mechanism controlling cell cycle progression has to be robust against inherent noise in the system. In this paper, a hybrid stochastic model is developed to study the effects of noise on the control mechanism of the budding yeast cell cycle. The modeling approach leverages, in a single multi-scale model, the advantages of two regimes: 1) the computational efficiency of a deterministic approach, and 2) the accuracy of stochastic simulations. Our results show that this hybrid stochastic model achieves high computational efficiency while generating simulation results that match very well with published experimental measurements.
Large cities and the loss of green areas exclude migrant birds: a global analysis
Authors: Leveau Lucas M. 
Published: July 2019

AbstractSeveral studies around the world have shown that the proportion of migrant species in bird communities increases toward the poles as a result of greater climatic seasonality and a considerable annual variation of resources. In this context, urban areas may impose a barrier to bird migrants given their buffered seasonality of resources and human disturbance. The aim of this study is to analyze the global pattern of migrant species proportion in urban green areas, considering the effects of climatic seasonality as well as the effects of urbanization. Data of bird communities in urban green areas were gathered through a search of scientific articles, book chapters, and thesis. Datasets that included a list of observed species, the numbers of parks surveyed and other methodological characteristics were considered for the analysis. Then, generalized linear models were used to relate the proportion of migratory species in each dataset to environmental and methodological variables that controlled for different sampling effort among studies. A total of 32 cities from four continents were analyzed. As expected, the migrant proportion increased with the annual range of temperature and precipitation and was higher in the Northern Hemisphere. However, the proportion of migrants decreased with the population size of cities but increased in those datasets with the highest maximum size of green areas surveyed. Although the global pattern of migrant proportion in urban green areas follows a similar pattern than those found in natural areas, the results obtained suggest that urbanization have a negative impact on this global pattern by reducing the proportion of migrant species in large cities. Moreover, green area loss in cities may impact negatively the proportion of migrant species.
Reverse Engineering Gene Networks Using Global-Local Shrinkage Rules
Authors: Panchal Viral , Linder Daniel 
Published: July 2019

AbstractInferring gene regulatory networks from high-throughput ‘omics’ data has proven to be a computationally demanding task of critical importance. Frequently the classical methods breakdown due to the curse of dimensionality, and popular strategies to overcome this are typically based on regularized versions of the classical methods. However, these approaches rely on loss functions that may not be robust and usually do not allow for the incorporation of prior information in a straightforward way. Fully Bayesian methods are equipped to handle both of these shortcomings quite naturally, and they offer potential for improvements in network structure learning. We propose a Bayesian hierarchical model to reconstruct gene regulatory networks from time series gene expression data, such as those common in perturbation experiments of biological systems. The proposed methodology utilizes global-local shrinkage priors for posterior selection of regulatory edges and relaxes the common normal likelihood assumption in order to allow for heavy-tailed data, which was shown in several of the cited references to severely impact network inference. We provide a sufficient condition for posterior propriety and derive an efficient MCMC via Gibbs sampling in the Appendix. We describe a novel way to detect multiple scales based on the corresponding posterior quantities. Finally, we demonstrate the performance of our approach in a simulation study and compare it with existing methods on real data from a T-cell activation study.
Conformational Dynamics of Nonenveloped Circovirus Capsid to the Host Cell Receptor
Authors: Li Jiarong , Gu Jinyan , Wang Shengnan , Lin Cui , Zhou Jianwei , Lei Jin , Zhou Jiyong 
Published: July 2019

AbstractCircovirus, comprising one capsid protein, is the smallest nonenveloped virus and induces lymphopenia. Circovirus can be used to explore the cell adhesion mechanism of nonenveloped viruses. We developed a single-molecule fluorescence resonance energy transfer (smFRET) assay to directly visualize the capsid’s conformational feature. The capsid underwent reversible dynamic transformation between three conformations. The cell surface receptor heparan sulfate (HS) altered the dynamic equilibrium of the capsid to the high-FRET state, revealing the HS binding region. Neutralizing antibodies restricted capsid transition to a low-FRET state, masking the HS binding domain. The lack of positively charged amino acids in the HS binding site reduced cell surface affinity and attenuated virus infectivity via conformational changes. These intrinsic characteristics of the capsid suggested that conformational dynamics is critical for the structural changes occurring upon cell surface receptor binding, supporting a dynamics-based mechanism of receptor binding.ImportanceViral proteins were commom working as ligand to interacte with cell surface glycosaminoglycan receptors to achieve the virus attachment, during which the conformational dynamics of the protein ligand are also vital for the binding properties. In this study, PCV2 capsid and heparin sulfate were used to study the protein conformational dynamics of nonenveloped and icosahedral circovirus capsid during triggering to cell surface receptor. we demonstrated the PCV2 capsid could acts as a dynamic machine, spontaneously adopting multiple conformations with reversible interconversion and intrinsic conformational features could be regulated by glycosaminoglycan receptors and neutralizing antibodies. These increased our understanding of the mechanism by which nonenveloped virus attach to cells.
The structure of SALSA/DMBT1 SRCR domains reveal the conserved ligand-binding mechanism of the ancient SRCR-fold
Authors: Reichhardt Martin P. , Loimaranta Vuokko , Lea Susan M. , Johnson Steven 
Published: July 2019

AbstractThe scavenger receptor cysteine-rich (SRCR) family of proteins comprise more than 20 membrane-associated and secreted molecules. Characterised by the presence of one or more copies of the ~110 amino acid SRCR domain, this class of proteins have widespread functions as anti-microbial molecules, scavenger- and signalling-receptors. Despite the high level of structural conservation of SRCR domains, no molecular basis for ligand interaction has been described. The SRCR protein SALSA, also known as dmbt1/gp340, is a key player in mucosal immunology. Based on detailed structures of the SALSA SRCR domains 1 and 8, we here reveal a novel universal ligand binding mechanism for SALSA ligands. The binding interface incorporates a dual cation binding site, which is highly conserved across the SRCR super family. Along with the well-described cation dependency on most SRCR domain-ligand interactions, our data suggest that the binding mechanism described for the SALSA SRCR domains is applicable to all SRCR domains. We thus propose to have identified in SALSA a conserved functional mechanism for ligand recognition by the SRCR class of proteins.
The structural basis for distinct binding avidity of Pertuzumab and Trastuzumab IgM towards HER2
Authors: Samsudin Firdaus , Yeo Joshua Yi , Gan Samuel Ken-En , Bond Peter J. 
Published: July 2019

SUMMARYHarnessing the therapeutic potential of immunoglobulin M (IgM) is of considerable interest in immunotherapy due to its complement-activating and cell-agglutinating abilities. Pertuzumab and Trastuzumab are monoclonal antibody drugs used in therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer but exhibit significantly different binding affinities as IgM when compared to the original IgG1 form. While the affinity of Pertuzumab IgM to the HER2 extracellular domain is about one order of magnitude higher than IgG1 in experiments, it was recently reported that Trastuzumab IgM and IgG have similar equilibrium dissociation constants to one another. We now perform an integrative multiscale simulation study in order to understand the structural basis for the differences in behavior between the two antibodies, based on complete antibody assemblies. We show that Pertuzumab IgM is able to utilize all of its V-regions to engage HER2 in a more stable mode than Trastuzumab IgM due to steric clashes between the large globular HER2 domains when bound to Trastuzumab. This is subsequently validated by confirming that Pertuzumab IgM inhibits proliferation in HER2 over-expressing live cells more effectively than its IgG1 counterpart. Given the widespread clinical use of Trastuzumab and Pertuzumab, elucidating the molecular details of antibody-antigen interaction may help guide the choice of epitopes for future design and selection of improved therapeutic antibody isotypes.
A massively parallel algorithm for finding non-existing sequences in genomes
Authors: Falda Marco 
Published: July 2019

AbstractWe discuss a method for producing a set of absent words in a reference genome with a guaranteed Hamming distance along all positions and additional information about the number of mismatches, their location and the position of the best match. We implemented it exploiting the massively parallelism of modern GPUs hardware: the code is available at https://bitbucket.org/mfalda/cuda_keeseek/.
Endoplasmic reticulum associated degradation preserves hematopoietic stem cell quiescence and self-renewal by restricting mTOR activity
Authors: Liu Lu , Inoki Ayaka , Fan Kelly , Mao Fengbiao , Shi Guojun , Jin Xi , Zhao Meiling , Ney Gina , Sun Shengyi , Dou Yali , Inoki Ken , Qi Ling , Li Qing 
Published: July 2019

SummaryMany tissue-specific stem cells require quiescence to sustain stem cell pool and maintain lifelong tissue integrity. It remains unclear whether protein quality control is required for stem cells in quiescence when RNA content, protein synthesis and metabolic activities are significantly reduced. Here, we report that endoplasmic reticulum associated degradation (ERAD) is required to preserve the function of quiescent hematopoietic stem cells (HSC). The Sel1L/Hrd1 ERAD genes are enriched in the quiescent and inactive HSCs, and conditional knockout of Sel1L in hematopoietic tissues drives HSCs to hyper-proliferation which leads to reduced self-renewal and HSC depletion. ERAD deficiency induces a non-apoptotic ER stress and activates unfolded protein response (UPR). Furthermore, Sel1L knockout leads to mTOR activation, and mTOR inhibition rescues the HSC defects in Sel1L knockout mice. Protein quality control is, therefore, tightly regulated and actively engaged in quiescent HSCs. Sel1L/Hrd1 ERAD maintains HSC quiescence and self-renewal via restricting mTOR activity.