bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive regulatory and metabolic network models for systems analysis ofClostridioides difficile
Authors: Arrieta-Ortiz Mario L. , Immanuel Selva Rupa Christinal , Turkarslan Serdar , Wu Wei Ju , Girinathan Brintha P. , Worley Jay N. , DiBenedetto Nicholas , Soutourina Olga , Peltier Johann , Dupuy Bruno , Bry Lynn , Baliga Nitin S. 
Published: September 2020

SUMMARYThoughClostridioides difficileis among the most studied anaerobes, the interplay of metabolism and regulation that underlies its ability to colonize the human gut is unknown. We have compiled public resources into three models and a portal to support comprehensive systems analysis ofC. difficile. First, by leveraging 151 transcriptomes from 11 studies we generated a regulatory model (EGRIN) that organizes 90% ofC. difficilegenes into 297 high quality conditional co-regulation modules. EGRIN predictions, validated with independent datasets, recapitulated and extended regulons of key transcription factors, implicating new genes for sporulation, carbohydrate transport and metabolism. Second, by advancing a metabolic model, we discovered that 15 amino acids, diverse carbohydrates, and 10 metabolic genes are essential forC. difficilegrowth within an intestinal environment. Finally, by integrating EGRIN with the metabolic model, we developed a PRIME model that revealed unprecedented insights into combinatorial control of essential processes forin vivocolonization ofC. difficileand its interactions with commensals. We have developed an interactive web portal (http://networks.systemsbiology.net/cdiff-portal/) to disseminate all data, algorithms, and models to support collaborative systems analyses ofC. difficile.
First genome ofLabyrinthula, an opportunistic seagrass pathogen, reveals novel insight into marine protist phylogeny, ecology and CAZyme cell-wall degradation
Authors: Tan Mun Hua , Loke Stella , Croft Laurence J. , Gleason Frank H. , Lange Lene , Pilgaard Bo , Trevathan-Tackett Stacey M. 
Published: September 2020

AbstractLabyrinthulaspp. are saprobic, marine protists that also act as opportunistic pathogens and are the causative agents of seagrass wasting disease (SWD). Despite the threat of local- and large-scale SWD outbreaks, there are currently gaps in our understanding of the drivers of SWD, particularly surroundingLabyrinthulavirulence and ecology. Given these uncertainties, we investigatedLabyrinthulafrom a novel genomic perspective by presenting the first draft genome and predicted proteome of a pathogenic isolate ofLabyrinthulaSR_Ha_C, generated from a hybrid assembly of Nanopore and Illumina sequences. Phylogenetic and cross-phyla comparisons revealed insights into the evolutionary history of Stramenopiles. Genome annotation showed evidence of glideosome-type machinery and an apicoplast protein typically found in protist pathogens and parasites. Proteins involved inLabyrinthula’s actin-myosin mode of transport, as well as carbohydrate degradation were also prevalent. Further, CAZyme functional predictions revealed a repertoire of enzymes involved in breakdown of cell-wall and carbohydrate storage compounds common to seagrasses. The relatively low number of CAZymes annotated from the genome ofLabyrinthulaSR_Ha_C compared to other Labyrinthulea species may reflect the conservative annotation parameters, a specialised substrate affinity and the scarcity of characterised protist enzymes. Inherently, there is high probability for finding both unique and novel enzymes fromLabyrinthulaspp. This study provides resources for further exploration ofLabyrinthulaecology and evolution, and will hopefully be the catalyst for new hypothesis-driven SWD research revealing more details of molecular interactions betweenLabyrinthulaspecies and its host substrate.
Inducible expression of humanC9ORF7236x G4C2hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice
Authors: Riemslagh F.W. , van der Toorn E.C. , Verhagen R.F.M , Maas A. , Bosman L.W.J. , Hukema R.K. , Willemsen R. 
Published: September 2020

AbstractThe hexanucleotide G4C2repeat expansion in the first intron of theC9ORF72gene explains the majority of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Numerous studies have indicated the toxicity of dipeptide repeats (DPRs) which are produced via repeat-associated non-AUG (RAN) translation from the repeat expansion and accumulate in the brain of C9FTD/ALS patients. Mouse models expressing the humanC9ORF72repeat and/or DPRs show variable pathological, functional and behavioral characteristics of FTD and ALS. Here, we report a new Tet-on inducible mouse model that expresses 36x pure G4C2repeats with 100bp upstream and downstream human flanking regions. Brain specific expression causes the formation of sporadic sense DPRs aggregates upon 6 months dox induction but no apparent neurodegeneration. Expression in the rest of the body evokes abundant sense DPRs in multiple organs, leading to weight loss, neuromuscular junction disruption, myopathy and a locomotor phenotype within the time frame of four weeks. We did not observe any RNA foci or pTDP-43 pathology. Accumulation of DPRs and the myopathy phenotype could be prevented when 36x G4C2repeat expression was stopped after 1 week. After 2 weeks of expression, the phenotype could not be reversed, even though DPR levels were reduced. In conclusion, expression of 36x pure G4C2repeats including 100bp human flanking regions is sufficient for RAN translation of sense DPRs and evokes a functional locomotor phenotype. Our inducible mouse model highlights the importance of early diagnosis and treatment for C9FTD/ALS patients.Summary statementOnly 36 C9ORF72 repeats are sufficient for RAN translation in a new mouse model for ALS and FTD. Reducing toxic dipeptides can prevent but not reverse the phenotype.
MetaNetX/MNXref - unified namespace for metabolites and biochemical reactions in the context of metabolic models
Authors: Moretti Sébastien , Tran Van Du T. , Mehl Florence , Ibberson Mark , Pagni Marco 
Published: September 2020

ABSTRACTMetaNetX/MNXref is a reconciliation of metabolites and biochemical reactions providing cross-links between major public biochemistry and Genome-Scale Metabolic Network (GSMN) databases. The new release brings several improvements with respect to the quality of the reconciliation, with particular attention dedicated to preserving the intrinsic properties of GSMN models. The MetaNetX website (https://www.metanetx.org/) provides access to the full database and online services. A major improvement is for mapping of user-provided GSMNs to MXNref, which now provides diagnostic messages about model content. In addition to the website and flat files, the resource can now be accessed through a SPARQL endpoint (https://rdf.metanetx.org).
An Engineered Genetic Circuit for Lactose Intolerance Alleviation Coupled with Gut Microbiota Recovery
Authors: Cheng Mingyue , Cheng Zhangyu , Yu Yiyan , Liu Wangjie , Li Ruihao , Guo Zhenyi , Qin Jiyue , Zeng Zhi , Di Lin , Mo Yufeng , Pan Chunxiu , Liang Yuanhao , Li Jinman , Tong Yigang , Yan Yunjun , Zhan Yi , Ning Kang 
Published: September 2020

AbstractBackgroundLactose malabsorption occurs in around 68% of the world populations, causing lactose intolerance (LI) symptoms such as abdominal pain, bloating and diarrhoea. To alleviate LI, previous studies mainly focused on strengthening intestinal β-galactosidase activity but neglected the inconspicuous colon pH drop caused by gut microbes’ fermentation on non-hydrolysed lactose. The colon pH drop will reduce intestinal β-galactosidase activity and influence the intestinal homeostasis.ResultsHere, we synthesized a tri-stable-switch circuit equipped with high β-galactosidase activity and pH rescue ability. This circuit can switch in functionality between expression of β-galactosidase and expression of l-lactate dehydrogenase in respond to intestinal lactose signal and intestinal pH signal. We confirmed the circuit functionality was efficient using 12-hrsin vitroculture at a range of pH levels, as well as 6-hrsin vivosimulations in mice colon. Moreover, another 21-days mice trial indicated that this circuit can recover lactose-effected gut microbiota of mice to the status (enterotypes) similar to that of mice without lactose intake.ConclusionsTaken together, the tri-stable-switch circuit can serve as a promising prototype for LI symptoms relief, especially by flexibly adapting to environmental variation, stabilizing colon pH and restoring gut microbiota.
Sequence memory in recurrent neuronal network can develop without structured input
Authors: Loidolt Matthias , Rudelt Lucas , Priesemann Viola 
Published: September 2020

AbstractHow does spontaneous activity during development prepare cortico-cortical connections for sensory input? We here analyse the development of sequence memory, an intrinsic feature of recurrent networks that supports temporal perception. We use a recurrent neural network model with homeostatic and spike-timing-dependent plasticity (STDP). This model has been shown to learn specific sequences from structured input. We show that development even under unstructured input increases unspecific sequence memory. Moreover, networks “pre-shaped” by such unstructured input subsequently learn specific sequences faster. The key structural substrate is the emergence of strong and directed synapses due to STDP and synaptic competition. These construct self-amplifying preferential paths of activity, which can quickly encode new input sequences. Our results suggest that memory traces are not printed on atabula rasa, but instead harness building blocks already present in the brain.
High-quality carnivore genomes from roadkill samples enable species delimitation in aardwolf and bat-eared fox
Authors: Allio Rémi , Tilak Marie-Ka , Scornavacca Céline , Avenant Nico L. , Corre Erwan , Nabholz Benoit , Delsuc Frédéric 
Published: September 2020

AbstractIn a context of ongoing biodiversity erosion, obtaining genomic resources from wildlife is becoming essential for conservation. The thousands of yearly mammalian roadkill could potentially provide a useful source material for genomic surveys. To illustrate the potential of this underexploited resource, we used roadkill samples to sequence reference genomes and study the genomic diversity of the bat-eared fox (Otocyon megalotis) and the aardwolf (Proteles cristata) for which subspecies have been defined based on similar disjunct distributions in Eastern and Southern Africa. By developing an optimized DNA extraction protocol, we successfully obtained long reads using the Oxford Nanopore Technologies (ONT) MinION device. For the first time in mammals, we obtained two reference genomes with high contiguity and gene completeness by combining ONT long reads with Illumina short reads using hybrid assembly. Based on re-sequencing data from few other roakill samples, the comparison of the genetic differentiation between our two pairs of subspecies to that of pairs of well-defined species across Carnivora showed that the two subspecies of aardwolf might warrant species status (P. cristataandP. septentrionalis), whereas the two subspecies of bat-eared fox might not. Moreover, using these data, we conducted demographic analyses that revealed similar trajectories between Eastern and Southern populations of both species, suggesting that their population sizes have been shaped by similar environmental fluctuations. Finally, we obtained a well resolved genome-scale phylogeny for Carnivora with evidence for incomplete lineage sorting among the three main arctoid lineages. Overall, our cost-effective strategy opens the way for large-scale population genomic studies and phylogenomics of mammalian wildlife using roadkill.
Converting Microwave Ovens into Plasma-Generating Decontamination Units for N-95 Respirators
Authors: Ruzic David N. , Oh Chamteut , Puthussery Joseph V. , Patel Dhruval , Jeckell Zach , Verma Vishal , Nguyen Thanh H. 
Published: September 2020

AbstractWe show how a common microwave oven, a coat-hanger and a coffee cup can be used to decontaminate N-95 respirators in 30 seconds. Tulane virus in the artificial saliva was reduced by >3 log andGeobacillus stearothermophilusspores were reduced by >6 log. Respirators maintained filtration and fit even after 10 cycles. Filtration and fit tests performed by the CDC confirmed there was no damage to the respirators. Spectroscopy of the plasma reveals that OH and C-containing radicals as the most prevalent active species.
Emergence and expansion of highly infectious spike:D614G mutant SARS-CoV-2 in central India
Authors: Sharma Shashi , Dash Paban Kumar , Sharma Sushil K , Srivastava Ambuj , Kumar Jyoti S , Karothia B.S. , Chelvam K T , Singh Sandip , Gupta Abhay , Yadav Ram Govind , Yadav Ruchi , Greshma TS , Kushwah Pramod , Bhushan Ravi , Nagar D.P. , Nandan Manvendra , Kumar Subodh , Thavaselvam Duraipandian , Dubey Devendra Kumar 
Published: September 2020

AbstractCOVID 19 has emerged as global pandemic with largest damage to the economy and human psyche. The genomic signature deciphered during the ongoing pandemic period is valuable to understand the virus evolutionary patterns and spread across the globe. Increased availability of genome information of circulating strain in our country will enable to generate selective details in virulent and non virulent markers to prophylaxis and therapeutic interventions. The first case of SARS CoV-2 was detected in Chambal region of Madhya Pradesh state in mid of March 2020 followed by multiple introduction events and expansion of COVID-19 cases within 3 months in this region. We analyzed around 5000 COVID -19 suspected samples referred to Defence Research and Development Establishment, Gwalior, Madhya Pradesh. A total of 136 cases were found positive over a span of three months period this includes virus introduction to region and further spread. Whole genome sequences employing Oxford nanopore technology were deciphered for 26 SARS-CoV-2 circulating in 10 different districts in Madhya Pradesh State of India. The region witnessed index cases with multiple travel history responsible for introduction of COVID-19 followed by remarkable expansion of virus. The genome wide substitutions including in important viral proteins were observed. The detailed phylogenetic analysis revealed the circulating SARS-CoV-2 clustered in multiple clades A2a, A4 and B. The cluster wise segregation was observed suggesting multiple introduction links and evolution of virus in the region. This is the first comprehensive details of whole genome sequence analysis from central India region, which will add genome wide knowledge towards diagnostic and therapeutic interventions.
Adaptive evolution in DNMT2 supports its role in the dipteran immune response
Authors: Bhattacharya Tamanash , Rice Danny W. , Hardy Richard W. , Newton Irene L.G. 
Published: September 2020

AbstractEukaryotic nucleic acid methyltransferase (MTase) proteins are essential mediators of epigenetic and epitranscriptomic regulation. DNMT2 belongs to a large, conserved family of DNA MTases found in many organisms, including holometabolous insects like fruit flies and mosquitoes, where it is the lone MTase. Interestingly, despite its nomenclature, DNMT2 is not a DNA MTase, but instead targets and methylates RNA species. A growing body of literature suggest DNMT2 mediates the host immune response against a wide range of pathogens, including RNA viruses. Evidence of adaptive evolution, in the form of positive selection, can often be found in genes that are engaged in conflict with pathogens like viruses. Here we identify and describe evidence of positive selection that has occurred at different times over the course of DNMT2 evolution within dipteran insects. We identify specific codons within each ortholog that are under positive selection, and find they are restricted to four distinct domains of the protein and likely influence substrate binding, target recognition, and adaptation of unique intermolecular interactions. Additionally, we describe the role of the Drosophila-specific host protein IPOD, in regulating the expression and/or function of fruit fly DNMT2. Finally, heterologous expression of these orthologs suggest that DNMT2’s role as an antiviral is host dependent, indicating a requirement for additional host-specific factors. Collectively, our findings highlight the adaptive evolution of DNMT2 in Dipteran insects, underscoring its role as an important, albeit non-canonical, regulator of host-pathogen interactions in mosquitoes and fruit flies.
Hymenoptera associated eukaryotic virome lacks host specificity
Authors: Deboutte Ward , Beller Leen , Yinda Claude Kwe , Shi Chenyan , Smets Lena , Vanmechelen Bert , Conceição-Neto Nadia , Dallmeier Kai , Maes Piet , de Graaf Dirk C , Matthijnssens Jelle 
Published: September 2020

AbstractRecent advancements in sequencing technologies and metagenomic studies have increased the knowledge of the virosphere associated with honey bees tremendously. In this study, viral-like particle enrichment and deep sequencing was deployed to detect viral communities in managed Belgian honey bees. A substantial number of previously undescribed divergent virus genomes was detected, including a rhabdovirus and a recombinant virus possessing a divergentLake Sinai Viruscapsid and a Hepe-like polymerase. Furthermore, screening > 5,000 public sequencing datasets for the retrieved set of viral genomes revealed an additional plethora of undetected, divergent viruses present in a wide range of Hymenoptera species. The unexpected high number of shared viral genomes within the Apidae family and across different families within the order Hymenoptera suggests that many of these viruses are highly promiscuous, that virus sharing within and between Hymenoptera families occurs frequently, and that the concept of species-specific viral taxa inside the Hymenoptera should be revisited. In particular, this estimation implies that sharing of several viral species, thought to be specific for bees, across other eukaryotic taxa is rampant. This study provides important insights on the host taxonomical breadth of some of the known “bee viruses” and might have important implications on strategies to combat viruses that are relevant to pollinators.
Rubisco adaptation is more limited by phylogenetic constraint than by catalytic trade-off
Authors: Bouvier Jacques W. , Emms David M. , Rhodes Timothy , Bolton Jai S. , Brasnett Amelia , Eddershaw Alice , Nielsen Jochem R. , Unitt Anastasia , Whitney Spencer M. , Kelly Steven 
Published: September 2020

AbstractRubisco assimilates CO2to form the sugars that fuel life on earth. Correlations between rubisco kinetic traits across species have led to the proposition that rubisco adaptation is highly constrained by catalytic trade-offs. However, these analyses did not consider the phylogenetic context of the enzymes that were analysed. Thus, it is possible that the correlations observed were an artefact of the presence of phylogenetic signal in rubisco kinetics and the phylogenetic relationship between the species that were sampled. Here, we conducted a phylogenetically-resolved analysis of rubisco kinetics and show that there is a significant phylogenetic signal in rubisco kinetic traits. We re-evaluated the extent of catalytic trade-offs accounting for this phylogenetic signal and found that all were attenuated. Following phylogenetic correction, the largest catalytic trade-offs were observed between the Michaelis constant for CO2and carboxylase turnover (∼21-37 %), and between the Michaelis constants for CO2and O2(∼9-19 %), respectively. All other catalytic trade-offs were substantially attenuated such that they were marginal (<9 %) or non-significant. This phylogenetically resolved analysis of rubisco kinetic evolution also identified kinetic changes that occur concomitant with the evolution of C4photosynthesis. Finally, we show that phylogenetic constraints (most likely caused by a slow rate of molecular evolution) have played a larger role than catalytic trade-offs in limiting the evolution of rubisco kinetics. Thus, although there is strong evidence for some catalytic trade-offs, rubisco adaptation has been more limited by phylogenetic constraint than by the combined action of all such trade-offs.
Contrasting Variable and Stable Subsurface Microbial Populations: an ecological time series analysis from the Deep Mine Microbial Observatory, South Dakota, USA
Authors: Osburn Magdalena R. , Casar Caitlin P. , Kruger Brittany , Momper Lily , Flynn Theodore M. , Amend Jan P. 
Published: September 2020

SummaryThe deep subsurface contains a vast reservoir of microbial life. While recent studies have revealed critical details about this biosphere including the sheer diversity of microbial taxa and their metabolic potential, long-term monitoring of deep subsurface microbial populations is rare, thus limiting our understanding of subsurface microbial population dynamics. Here we present a four-year time series analysis of subsurface microbial life from the Deep Mine Microbial Observatory (DeMMO), Lead, SD, USA. We find distinct and diverse populations inhabiting each of 6 sites over this ~1.5 km deep slice of terrestrial crust, corresponding to distinct geochemical habitats. Alpha diversity decreases with depth and beta diversity measures clearly differentiate samples by site over time, even during substantial perturbations. Population dynamics are driven by a subset of variable (and often relatively abundant) OTUs, but the vast majority of detected OTUs are stable through time, constituting a core microbial community. The phylogenetic affiliations of both stable and variable taxa, including putative sulfate reducers, methanogens, spore formers, and many uncultivated lineages, are similar to those found previously in subsurface environments. This work reveals the dynamic nature of the terrestrial subsurface, contributing to a more holistic understanding than can be achieved when viewing shorter timeframes.Originality-Significance StatementThis four-year record of deep mine microbial diversity and geochemistry is the first of its kind and allows for direct investigation of temporal trends in deep subsurface biogeochemistry. We identify disparate populations of variable and stable taxa, suggesting the presence of a core deep subsurface microbiome with unique niche partitioning.
ATP activation of peritubular cells drives testicular sperm transport
Authors: Fleck David , Kenzler Lina , Mundt Nadine , Strauch Martin , Uesaka Naofumi , Moosmann Robert , Bruentgens Felicitas , Missel Annika , Mayerhofer Artur , Merhof Dorit , Spehr Jennifer , Spehr Marc 
Published: September 2020

AbstractSpermatogenesis, the complex developmental process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility and reproductive fitness. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of mitotic and meiotic divisions. The basic physiological principles, however, that control both maturation and luminal transport of the still immotile spermatozoa within the seminiferous tubules remain poorly, if at all, defined. Here, we show that coordinated contractions of smooth muscle-like testicular peritubular cells provide the propulsive force for luminal sperm transport towards the rete testis and epididymis. Using a mouse model forin vivoimaging, we describe and quantify spontaneous tubular contractions and show a causal relationship between peritubular Ca2+waves and peristaltic transport. Moreover, we identify P2 receptor-dependent purinergic signaling pathways as physiological triggers of tubular contractions bothin vitroandin vivo. When challenged with extracellular ATP, transport of luminal content inside the seminiferous tubules displays stage-dependent directionality. We thus suggest that paracrine purinergic signaling coordinates peristaltic recurrent contractions of the mouse seminiferous tubules to propel immotile spermatozoa to the rete testis. Consequently, our findings could have substantial pharmaceutical implications for both infertility treatment and / or male contraception.