bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human-like telomeres in Zostera marina reveal a mode of transition from the plant to the human telomeric sequences
Authors: Peska Vratislav , Mátl Martin , Mandákova Terezie , Vitales Daniel , Fajkus Petr , Fajkus Jiří , Garcia Sònia 
Published: March 2020

AbstractA previous study describing the genome of Zostera marina, the most widespread seagrass in the Northern hemisphere, revealed some genomic signatures of adaptation to the aquatic environment. Important features related to the ‘back-to-the-sea’ reverse evolutionary pathway were found, such as the loss of stomatal genes, while other functions like an algal-like cell wall composition were acquired. Beyond these, the genome structure and organization were comparable to the majority of plant genomes sequenced, except for one striking feature that went unnoticed at that time: the presence of human-like instead of the expected plant-type telomeric sequences. By using different experimental approaches including FISH, NGS and Ba131 analysis, we have confirmed its telomeric location in the chromosomes of Z. marina. We have also identified its telomerase RNA subunit (TR), confirming the presence of the human-type telomeric sequence in the template region. Remarkably, this region was found to be very variable even in clades with a highly conserved telomeric sequence across their species. Based on this observation, we propose that alternative annealing preferences in the template borders can explain the transition between the plant and human telomeric sequences. The further identification of paralogues of TR in several plant genomes brought us to the hypothesis that plants may keep an increased ability to change their telomeric sequence. We discuss the implications of this occurrence in the evolution of telomeres while introducing a mechanistic model for the transition from the plant to the human telomeric sequences.
Expression of Wilm’s Tumor Gene in Endometrium with Potential Link to Gestational Vascular Transformation
Authors: Zhang Peilin 
Published: March 2020

AbstractBackgroundWT1 is a transcription factor with versatile cellular functions in embryonic development, maintenance of adult tissue functions and regenerations. WT1 is known to be regulated by progesterone and it is abundantly expressed in endometrium, but its function is unclear.DesignWT1 expression was detected by immunohistochemical staining in endometrium of various physiological and pathological conditions.ResultWT1 was detected in endometrial stromal cells and vascular smooth muscle cells in both proliferative and secretory phases of menstrual cycles. WT1 appeared increased in vascular smooth muscle cells in spiral artery in early pregnancy and WT1 was also detected in regenerative endothelial cells and smooth muscle cells in decidual vasculopathy at term. WT1 expression was decreased in endometrial stromal cells in adenomyosis (endometriosis).ConclusionWT1 potentially links the hormonal (progesterone) effects on endometrial decidualization and may play a role in gestational vascular transformation during pregnancy and restoration after pregnancy.
Cell-based analysis ofCADvariants identifies individuals likely to benefit from uridine therapy
Authors: del Caño-Ochoa Francisco , Ng Bobby G. , Abedalthagafi Malak , Almannai Mohammed , Cohn Ronald D. , Costain Gregory , Elpeleg Orly , Houlden Henry , Karimiani Ehsan Ghayoor , Liu Pengfei , Manzini M. Chiara , Maroofian Reza , Muriello Michael , Al-Otaibi Ali , Patel Hema , Shimon Edvardson , Sutton V. Reid , Toosi Mehran Beiraghi , Wolfe Lynne A. , Rosenfeld Jill A. , Freeze Hudson H. , Ramón-Maiques Santiago 
Published: March 2020

ABSTRACTPurposePathogenic autosomal recessive variants inCAD, encoding the multienzymatic protein initiating pyrimidinede novobiosynthesis, cause a severe inborn metabolic disorder treatable with a dietary supplement of uridine. This condition is difficult to diagnose given the large size ofCADwith over 1000 missense variants and the non-specific clinical presentation. We aimed to develop a reliable and discerning assay to assess the pathogenicity ofCADvariants and to select affected individuals that might benefit from uridine therapy.MethodsUsing CRISPR/Cas9, we generated a humanCAD-knockout cell line that requires uridine supplements for survival. Transient transfection of the knockout cells with recombinantCADrestores growth in absence of uridine. This system determines missense variants that inactivate CAD and do not rescue the growth phenotype.ResultsWe identified 25 individuals with biallelic variants inCADand a phenotype consistent with a CAD deficit. We used theCAD-knockout complementation assay to test a total of 34 variants, identifying 16 as deleterious for CAD activity. Combination of these pathogenic variants confirmed 11 subjects with a CAD deficit, for whom we describe the clinical phenotype.ConclusionsWe designed a cell-based assay to test the pathogenicity ofCADvariants, identifying 11 CAD deficient individuals, who could benefit from uridine therapy.
Confound modelling in UK Biobank brain imaging
Authors: Alfaro-Almagro Fidel , McCarthy Paul , Afyouni Soroosh , Andersson Jesper L. R. , Bastiani Matteo , Miller Karla L. , Nichols Thomas E. , Smith Stephen M. 
Published: March 2020

AbstractDealing with confounds is an essential step in large cohort studies to address problems such as unexplained variance and spurious correlations. UK Biobank is a powerful resource for studying associations between imaging and nonimaging measures such as lifestyle factors and health outcomes, in part because of the large subject numbers. However, the resulting high statistical power also raises the sensitivity to confound effects, which therefore have to be carefully considered. In this work we describe a set of possible confounds (including non-linear effects and interactions) that researchers may wish to consider for their studies using such data. We include descriptions of how we can estimate the confounds, and study the extent to which each of these confounds affects the data, and the spurious correlations that may arise if they are not controlled. Finally, we discuss several issues that future studies should consider when dealing with confounds.
Development of a clostridia-based cell-free system for prototyping genetic parts and metabolic pathways
Authors: Krüger Antje , Mueller Alexander P. , Rybnicky Grant A. , Engle Nancy L. , Yang Zamin K. , Tschaplinski Tim J. , Simpson Sean D. , Köpke Michael , Jewett Michael C. 
Published: March 2020

ABSTRACTGas fermentation by autotrophic bacteria, such as clostridia, offers a sustainable path to numerous bioproducts from a range of local, highly abundant, waste and low-cost feedstocks, such as industrial flue gases or syngas generated from biomass or municipal waste. Unfortunately, designing and engineering clostridia remains laborious and slow. The ability to prototype individual genetic parts, gene expression, and biosynthetic pathway performancein vitrobefore implementing them in cells could help address these bottlenecks by speeding up design. Unfortunately, a high-yielding cell-free gene expression (CFE) system from clostridia has yet to be developed. Here, we report the development and optimization of a high-yielding (236 ± 24 µg/mL) batch CFE platform from the industrially relevant anaerobe,Clostridium autoethanogenum.A key feature of the platform is that both circular and linear DNA templates can be applied directly to the CFE reaction to program protein synthesis. We demonstrate the ability to prototype gene expression, and quantitatively map cell-free metabolism in lysates from this system. We anticipate that theC. autoethanogenumCFE platform will not only expand the protein synthesis toolkit for synthetic biology, but also serve as a platform in expediting the screening and prototyping of gene regulatory elements in non-model, industrially relevant microbes.
Treating the Network: Targeted inhibition of two specific microRNAs in the brainstem prevents the development of hypertension
Authors: Gorky Jonathan , DeCicco Danielle , Achanta Sirisha , Schwaber James , Vadigepalli Rajanikanth 
Published: March 2020

AbstractWe here test the concept that disease states may result not from a single cause but from small changes in a network that are collectively significant. We recently showed that development of hypertension (HTN) in the spontaneously hypertensive rat (SHR) model of human essential hypertension is accompanied by changes in microRNA expression levels in the brainstem tracking the development of HTN1,2. This led to the hypothesis that preventing the change in microRNA levels could prevent the development of HTN. We propose that hypertension emerges from a network that has been pushed out of a normotensive equilibrium into a compensatory, pathological state. We show that small perturbations in the gene regulatory networks in the brainstem by selectively blocking two microRNAs highlighted in our previous results, miR-135a and miR-376a, is sufficient to prevent development of hypertension in the SHR model. This effect appears driven by only modest changes in the expression of rate-limiting genes, many of which are targets of these miRNAs, suggesting that the combination of genes that are targeted in the network is responsible for the effect. The demonstration that hypertension is an emergent property of an underlying regulatory network suggests that a new treatment paradigm altogether is needed.One Sentence SummaryA brief summary of the main result of your paper, without excessive jargon.
Identification of viruses belonging to the familyPartitiviridaefrom plant transcriptomes
Authors: Jo Yeonhwa , Cho Won Kyong 
Published: March 2020

AbstractViruses in the familyPartitiviridaeconsist of non-enveloped viruses with bisegmented double-stranded RNA genomes. Viruses in this family have been identified from plants and fungi. In this study, we identified several viruses belonging to the familyPartitiviridaeusing plant transcriptomes. From 11 different plant species, we identified a total of 74 RNA segments representing 23 partitiviruses. Of 74 RNA segments, 28 RNA segments encode RNA-dependent RNA polymerases (RdRp) while 46 RNA segments encode coat proteins (CPs). According to ICTV demarcation for the familyPartitiviridae, 25 RNAs encoding RdRp and 41 RNAs encoding CP were novel RNA segments. In addition, we identified eight RNA segments (three for RdRp and five for CP) belonging to the known partitivruses. Taken together, this study provides the largest number of partitiviruses from plant transcriptomes in a single study.
Infrared assessment of human facial temperature in the presence and absence of common cosmetics
Authors: Zheng Kaikai , Dong Ruoyu , Wang Huan , Granick Steve 
Published: March 2020

ABSTRACTUsing a sensitive research-grade infrared camera, we find that common facial cosmetics and lotions mask skin temperature in assays of the human forehead. We test a family of 10 commonly-used cosmetic products and find that volatile liquids and creams lower thermal skin temperature by at least 2 C for up to 5-10 min and at least 1 C for up to 20 min, respectively. Powder and cream that contains brightening agent lower indefinitely the skin temperature sensed by infrared camera. With the qualification that these experiments were performed in a controlled laboratory setting rather than the mass crowd screening environment where infrared temperature sensing of humans sees widespread use, our tests suggest that for human subjects whose face was treated with certain cosmetics and lotions, infrared-based screening for elevated facial temperature (fever) can be unreliable.
No one-size-fits-all solution to clean GBIF
Authors: Zizka Alexander , Carvalho Fernanda Antunes , Calvente Alice , Baez-Lizarazo Mabel Rocio , Cabral Andressa , Ramos Coelho Jéssica Fernanda , Colli-Silva Matheus , Fantinati Mariana Ramos , Fernandes Moabe Ferreira , Ferreira-Araújo Thais , Lambert Moreira Fernanda Gondim , da Cunha Santos Nathália Michelly , Borges Santos Tiago Andrade , dos Santos-Costa Renata Clicia , Serrano Filipe Cabreirinha , da Silva Ana Paula Alves , Soares Arthur de Souza , de Souza Paolla Gabryelle Cavalcante , Tomaz Eduardo Calisto , Fonseca Vale Valéria , Vieira Tiago Luiz , Antonelli Alexandre 
Published: March 2020

ABSTRACTSpecies occurrence records provide the basis for many biodiversity studies. They derive from georeferenced specimens deposited in natural history collections and visual observations, such as those obtained through various mobile applications. Given the rapid increase in availability of such data, the control of quality and accuracy constitutes a particular concern. Automatic filtering is a scalable and reproducible means to identify potentially problematic records and tailor datasets from public databases such as the Global Biodiversity Information Facility (GBIF;www.gbif.org), for biodiversity analyses. However, it is unclear how much data may be lost by filtering, whether the same filters should be applied across all taxonomic groups, and what the effect of filtering is on common downstream analyses. Here, we evaluate the effect of 13 recently proposed filters on the inference of species richness patterns and automated conservation assessments for 18 Neotropical taxa, including terrestrial and marine animals, fungi, and plants downloaded from GBIF. We find that a total of 44.3% of the records are potentially problematic, with large variation across taxonomic groups (25 - 90%). A small fraction of records was identified as erroneous in the strict sense (4.2%), and a much larger proportion as unfit for most downstream analyses (41.7%). Filters of duplicated information, collection year, and basis of record, as well as coordinates in urban areas, or for terrestrial taxa in the sea or marine taxa on land, have the greatest effect. Automated filtering can help in identifying problematic records, but requires customization of which tests and thresholds should be applied to the taxonomic group and geographic area under focus. Our results stress the importance of thorough recording and exploration of the meta-data associated with species records for biodiversity research.
Mitochondrial Complex II In Intestinal Epithelial Cells Regulates T-cell Mediated Immunopathology
Authors: Fujiwara Hideaki , Mathew Anna V , Kovalenko Ilya , Pal Anupama , Lee Ho-Joon , Peltier Daniel , Kim Stephanie , Liu Chen , Oravecz-Wilson Katherine , Li Lu , Sun Yaping , Byun Jaeman , Saunders Tom , Rehemtulla Alnawaz , Lyssiotis Costas A , Pennarthur Subramanian , Reddy Pavan 
Published: March 2020

SummaryIntestinal epithelial cell (IEC) damage by T cells contributes to alloimmune, autoimmune and iatrogenic diseases such as graft-versus-host disease (GVHD), inflammatory bowel disease (IBD) and immune checkpoint blockade (ICB) mediated colitis, respectively. Despite significant advances in understanding the aberrant biology of T cells in these diseases, little is known about how the fundamental biological processes of the target IECs influence the disease severity. Here, through analyses of metabolic pathways of IECs, we identified disruption of oxidative phosphorylation without a concomitant change in glycolysis and an increase in succinate levels in several distinct in vivo models of T cell mediated gastrointestinal damage such as GVHD, IBD and ICB mediated colitis. Metabolic flux studies, complemented by imaging and protein analyses identified a critical role for IEC intrinsic succinate dehydrogenase A (SDHA), a component of mitochondrial complex II, in causing these metabolic alterations that contributed to the severity of intestinal damage. The critical mechanistic role of IEC intrinsic SDHA was confirmed by complementary chemical and genetic reduction of SDHA and with IEC specific deletion of SDHA. Further in vitro and in vivo mechanistic studies demonstrated that loss of SDHA in IECs was mediated by the perforin-granzyme from the T cells. The loss of SDHA was also validated in human clinical samples. These data identify a critical role for the alteration of the IEC specific mitochondrial complex II component SDHA in the regulation of the severity of T cell mediated intestinal diseases.
Emergent properties in microbiome networks reveal the anthropogenic disturbance of farming practices in vineyard soil fungal communities
Authors: Ortiz-Álvarez Rüdiger , Ortega-Arranz Hector , Ontiveros Vicente J. , Ravarani Charles , Acedo Alberto , Belda Ignacio 
Published: March 2020

AbstractAgro-ecosystems are human-managed natural systems, and therefore are subject to generalized ecological rules. A deeper understanding of the factors impacting on the biotic component of ecosystem stability is needed for promoting the sustainability and productivity of global agriculture. Here we propose a method to determine ecological emergent properties through the inference of network properties in local microbial communities, and to use them as biomarkers of the anthropogenic impact of different farming practices on vineyard soil ecosystem functioning. In a dataset of 350 vineyard soil samples from USA and Spain we observed that fungal communities ranged from random to small-world network arrangements with differential levels of niche specialization. Some of the network properties studied were strongly correlated, defining patterns of ecological emergent properties that are influenced by the intensification level of the crop management. Low-intervention practices (from organic to biodynamic approaches) promoted densely clustered networks, describing an equilibrium state based on mixed (generalist-collaborative) communities. Contrary, in conventionally managed vineyards, we observed highly modular (niche-specialized) low clustered communities, supported by a higher degree of selection (more co-exclusion proportion). We also found that, although geographic factors can explain the different fungal community arrangements in both countries, the relationship between network properties in local fungal communities better capture the impact of farming practices regardless of the location. Thus, we hypothesize that local network properties can be globally used to evaluate the effect of ecosystem disturbances in crops, but also in when evaluating the effect of clinical interventions or to compare microbiomes of healthy vs. disturbed conditions.
Long-term synaptic depression triggers local biogenesis of autophagic vesicles in dendrites and requires autophagic degradation
Authors: Kallergi Emmanouela , Daskalaki Akrivi-Dimitra , Ioannou Evangelia , Kolaxi Angeliki , Plataki Maria , Haberkant Per , Stein Frank , Savitski Mikhail M , Sidiropoulou Kyriaki , Dalezios Yannis , Nikoletopoulou Vassiliki 
Published: March 2020

SummaryIn neurons, biogenesis of autophagic vesicles (AVs) is spatially confined to the axon tip under baseline conditions. However, it remains unknown whether their biogenesis can be induced in other neuronal compartments following synaptic activity in order to serve local functions. Here, we show that both major types of long-term synaptic depression (LTD), a form of plasticity expressed by the shrinkage and elimination of dendritic spines, trigger the rapid and local biogenesis of AVs in post-synaptic dendrites. In return, autophagy is indispensable for LTD, as either genetic ablation ofatg5in pyramidal neurons or acute pharmacological inhibition of AV biogenesis totally prevents LTD induction. Using quantitative proteomic profiling of purified AVs, we reveal that upon LTD the autophagic cargo is significantly enriched for synaptic proteins, as well as modulators of the actin cytoskeleton and autism-implicated proteins. In line with these findings, a mild autophagy deficit is sufficient to impair behavioral flexibility, a cognitive function that requires efficient LTD. Therefore, local synthesis and assembly of the autophagic machinery in dendrites ensure the elimination of synaptic structures via degradation of their components, facilitating plasticity and associated behaviors.Graphical AbstractIn briefKallergi, Daskalaki and colleagues demonstrate that autophagy is cell autonomously required in pyramidal excitatory neurons for the induction of long-term synaptic depression (LTD). They uncover the novel and local biogenesis of autophagic vesicles (AVs) in dendrites upon LTD, by which post-synaptic components are rapidly accessible on-site for autophagic degradation. Using quantitative proteomics on purified AVs, they reveal that upon LTD the autophagic cargo is enriched in synaptic, cytoskeletal and autism-implicated proteins.HighlightsAutophagy is required cell-autonomously in pyramidal neurons for LTD.NMDAR- and mGluR-mediated LTD trigger the local biogenesis of autophagic vesicles in dendrites.Autophagic vesicles sequester primarily synaptic and cytoskeletal cargo upon LTD.Mild impairment in autophagy leads to deficits in cognitive flexibility.
Developing a Coarse-Grained Model for Bacterial Cell Walls and Evaluating Mechanical Properties and Free Energy Barriers
Authors: Vaiwala Rakesh , Sharma Pradyumn , Puranik Mrinalini , Ayappa K. Ganapathy 
Published: March 2020

AbstractThe bacterial cell envelope of Gram-negative bacteria is a complex biological barrier with multiple layers consisting of the inner membrane, periplasm of peptidoglycan and the outer membrane with lipopolysaccharides (LPS). With rising antimicrobial resistance there is increasing interest in understanding interactions of small molecules with the cell membrane to aid in the development of novel drug molecules. Hence suitable representations of the bacterial membrane are required to carry out meaningful molecular dynamics simulations. Given the complexity of the cell envelope, fully atomistic descriptions of the cell membrane with explicit solvent are computationally prohibitive, allowing limited sampling with small system sizes. However coarse-grained (CG) models such as MARTINI allow one to study phenomena at physiologically relevant length and time scales. Although MARTINI models for lipids and the LPS are available in literature, a suitable CG model of peptidoglycan is lacking. In this manuscript we develop a CG model of the peptidoglycan network within the MARTINI framework using an all-atom model developed by Gumbart et al.1. The model is parametrized to reproduce the structural properties of the glycan strands, such as the end-to-end distance, equilibrium angle between adjacent peptides along the strands and area per disaccharide. Mechanical properties such as the area compressibility and the bending modulus are accurately reproduced. While developing novel antibiotics it is important to assess barrier properties of the peptidogylcan network. We evaluate and compare the free energy of insertion for a thymol molecule using umbrella sampling on both the MARTINI and all-atom peptidoglycan models. The insertion free energy was found to be less than kBT for both the MARTINI and all-atom models. Additional restraint free simulations reveal rapid translocation of thymol across peptidogylcan. We expect that the proposed MARTINI model for peptidoglycan will be useful in understanding phenomena associated with bacterial cell walls at larger length and time scales, thereby overcoming the current limitations of all-atom models.