bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mammary ductal epithelium controls cold-induced adipocyte thermogenesis
Authors: Santos Luis C. , Arneson Douglas , Alvarsson Alexandra , Krishnan Karthickeyan Chella , Centzone Alessia , Patel Sanil , Sadeh Shani , Ahn In Sook , Diamante Graciel , Cely Ingrid , Butte Atul J. , Blanpain Cédric , Stanley Sarah A. , Lusis Aldons J. , Yang Xia , Rajbhandari Prashant 
Published: November 2020

ABSTRACTSympathetic activation during cold exposure increases adipocyte thermogenesis via expression of mitochondrial protein uncoupling protein 1 (UCP1)1. The propensity of adipocytes to express UCP1 is under a critical influence of the adipose microenvironment and varies among various fat depots2–7. Here we report that cold-induced adipocyte UCP1 expression in female mouse subcutaneous white adipose tissue (scWAT) is regulated by mammary gland ductal epithelial cells in the adipose niche. Single cell RNA-sequencing (scRNA-seq) show that under cold condition glandular alveolar and hormone-sensing luminal epithelium subtypes express transcripts that encode secretory factors involved in regulating adipocyte UCP1 expression. We term mammary duct secretory factors as “mammokines”. Using whole-tissue immunofluorescence 3D visualization, we reveal previously undescribed sympathetic nerve-ductal points of contact and show that sympathetic nerve-activated mammary ducts limit adipocyte UCP1 expression via cold-induced mammokine production. Bothin vivoandex vivoablation of mammary ductal epithelium enhances cold-induced scWAT adipocyte thermogenic gene program. The mammary duct network extends throughout most scWATs in female mice, which under cold exposure show markedly less UCP1 expression, fat oxidation, energy expenditure, and subcutaneous fat mass loss compared to male mice. These results show a previously uncharacterized role of sympathetic nerve-activated glandular epithelium in adipocyte thermogenesis. Overall, our findings suggest an evolutionary role of mammary duct luminal cells in defending glandular adiposity during cold exposure, highlight mammary gland epithelium as a highly active metabolic cell type, and implicate a broader role of mammokines in mammary gland physiology and systemic metabolism.
3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme
Authors: Lázaro Melisa , Melero Roberto , Huet Charlotte , López-Alonso Jorge P. , Delgado Sandra , Dodu Alexandra , Bruch Eduardo M. , Abriata Luciano A. , Alzari Pedro M. , Valle Mikel , Lisa María-Natalia 
Published: November 2020

SummaryGlutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs180) contain long N- and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs180in bacterial physiology, the lack of structural data for these enzymes has limited the progress of functional studies. Here we show that the mycobacterial L-GDH180(mL-GDH180) adopts a quaternary structure that is radically different from that of related low molecular weight enzymes. Intersubunit contacts in mL-GDH180involve a C-terminal domain that we propose as a new fold and a flexible N-terminal segment comprising ACT-like and PAS-type domains that could act as metabolic sensors for allosteric regulation. These findings uncover unique aspects of the structure-function relationship in the subfamily of L-GDHs.
In silico analysis of single nucleotide polymorphisms (SNPs) in human C-C chemokine receptor type five (CCR5) gene
Authors: Ali Asma Ali Hassan , Ibrahim Muntaser 
Published: November 2020

AbstractIntroductionChemokines are small transmembrane proteins with immune surveillance and immune cell recruitment functions. the expression of CCR5 gene affects virus production and viral load(1). The CCR5 gene contains two introns, three exons, and two promoters, and it is necessary as a co-receptor for the entry of the macrophage-tropic HIV strains. Mutations in the coding region of CCR5 affect the protein structure, which will affect production, chemokine binding, transport, signaling and expression of the CCR5 receptor.MethodsSNPs within CCR5 gene were retrieved from ensemble database. Coding SNPs were analyzed using SNPnexus. Coding non-synonymous SNPs in CCR5 binding domains with Viral gp120 were analyzed using SIFT, PolyPhen and I-mutant tools. Project HOPE then used to modelled the 3D structure of the protein resulting from these SNPs. Non-coding SNPs that affects miRNAs in 3’ rejoin were analyzing using PolymiRTS. SNPs that affect transcription factor binding were analyzed using regulomeDB.Results(178) non-synonyms missense SNPs were found to have deleterious and damaging effect on the structure and function of the protein. In CCR5 binding domains with Viral gp120: 3 SNPs rs145061115, rs199824195 and rs201797884 were found to affect both structure and function and stability of chemokine protein. The 2 SNPs rs185691679 and rs199722070 has a role in disruption and creation of the target sites in miRNA seeds due to their high conservation score.ConclusionMutations in CCR5 gene may explain and represent the molecular basis of the resistance to HIV infection.
A domestic plant differs from its wild relative along multiple axes of within-plant trait variability and diversity
Authors: Robinson Moria L. , Schilmiller Anthony L. , Wetzel William C. 
Published: November 2020

AbstractFor 10,000 years humans have altered plant traits through domestication and ongoing crop improvement, shaping plant form and function in agroecosystems. To date, studies have focused on how these processes have shaped whole-plant or average traits; however, plants also have characteristic levels of trait variability among their repeated parts, which can be heritable and mediate critical ecological interactions. As concerns about sustainable pest management increase, there is growing interest in approaches that increase trait diversity in crop agroecosystems. Here, we examine an under-appreciated scale of trait variation – among leaves, within plants – that may have changed through the process of domestication and improvement in a key crop.We explore how levels of within-plant, among-leaf trait variability differ between cultivars and wild relatives of alfalfa (Medicago sativa), a key forage crop with an 8,000 year cultivation history. We grew individual plants from 30 wild populations and 30 cultivars, encompassing a range of domestication and improvement histories. For each plant, we quantify variability in a broad suite of physical, nutritive, and chemical leaf traits, including measures of chemical dissimilarity (beta diversity) among leaves.We find that intra-individual trait variability has changed over the course of domestication and crop improvement, with effects often larger than changes in trait means. Cultivated alfalfa had elevated variability in SLA, trichomes, and C:N; increased diversity in defensive compounds; and reduced variability in phytochemical composition. We also elucidate fundamental associations between trait means and overall investment in secondary metabolites with patterns of among-leaf variability and chemical diversity.We conclude that within-plant variability is an overlooked dimension of trait diversity in this globally critical agricultural crop. We find that trait variability is actually higher in cultivated plants compared to wild progenitors for multiple nutritive, physical, and chemical traits, highlighting a scale of variation that may mitigate loss of trait diversity at other scales in alfalfa agroecosystems and in other crops with similar domestication and improvement histories.
Decreasing pdzd8-mediated mitochondrial-ER contacts in neurons improves fitness by increasing mitophagy
Authors: Hewitt Victoria L. , Miller-Fleming Leonor , Andreazza Simonetta , Mattedi Francesca , Prudent Julien , Polleux Franck , Vagnoni Alessio , Whitworth Alexander J. 
Published: November 2020

AbstractThe complex cellular architecture of neurons combined with their longevity makes maintaining a healthy mitochondrial network particularly important and challenging. One of the many roles of mitochondrial-ER contact sites (MERCs) is to mediate mitochondrial quality control through regulating mitochondrial turn over. Pdzd8 is a newly discovered MERC protein, the organismal functions of which have not yet been explored. Here we identify and provide the first functional characterization of theDrosophila melanogasterortholog of Pdzd8. We find that reducing pdzd8-mediated MERCs in neurons slows age-associated decline in locomotor activity and increases lifespan inDrosophila. The protective effects of pdzd8 knockdown in neurons correlate with an increase in mitophagy, suggesting that increased mitochondrial turnover may support healthy aging of neurons. In contrast, increasing MERCs by expressing a constitutive, synthetic ER-mitochondria tether disrupts mitochondrial transport and synapse formation, accelerates age-related decline in locomotion and reduces lifespan. We also show that depletion of pdzd8 rescues the locomotor defects characterizing an Alzheimer’s disease (AD) fly model over-expressing Amyloidβ1–42(Aβ42) and prolongs the survival of flies fed with mitochondrial toxins. Together, our results provide the firstin vivoevidence that MERCs mediated by the tethering protein pdzd8 play a critical role in the regulation of mitochondrial quality control and neuronal homeostasis.
Taxonomic description and genome sequence ofChristensenella intestinihominissp. nov., a novel cholesterol-lowering bacterium isolated from human gut
Authors: Zou Yuanqiang , Xue Wenbin , Lin Xiaoqian , Luo Guangwen , Lv Mei , Dai Ying , Xiao Liang 
Published: November 2020

AbstractA Gram-staining-negative, non-spore-forming, short, straight rod, non-motile, obligate anaerobic bacterial strain, AF73-05CM02T, was isolated from faecal sample of thirty-years old healthy male. Colonies were approximately 0.2mm in diameter, beige and circular after 4 days of incubation on PYG agar under anaerobic conditions at 37°C. Strain AF73-05CM02Tgrew in a temperature range between 30-42°C and pH range from 6.0 to 8.5, with optimum growth at 37-42°C and pH 7.0. Base on the 16S rRNA gene sequence analysis, strain AF73-05CM02Tbelongs to the genusChristensenellaand showed the highest level of sequence similarity withChristensenella minutaYIT 12065T. The predominant fatty acids of strain AF73-05CM02Twere C10:0(7.5%), iso-C11:0(5.6%), C12:0(7.2%), C14:0(46.6%), iso-C15:0(7.4%), C16:0(9.7%) and C18:1ω 9c(6.9%). Acetic acid, formic acid, butyric acid and lactic acid were end products of glucose fermentation. The isolate was negative for catalase, indole production and hydrolysis of gelatin. Genomic relatedness analyses based on average nucleotide identity indicated strain AF73-05CM02Tsignificantly differed from other species of the genusChristensenella, showing ANI values under 82.89% with the phylogenetically closest species. The G+C content of the genomic DNA was 52.07 mol% from genome sequence, which differs from that ofChristensenella minuta. Several physiological biochemical and genotypic properties differentiated the novel bacterial strain from the related species, indicating that the isolate represent a new species of the genusChristensenellafor which the nameChristensenella intestinihominissp. nov. is proposed, with strain AF73-05CM02T(=CGMCC 1.5207T=DSM 103477T) being the type strain. The follow study approached the function of cholesterol-lowering for strains AF73-05CM02Tand DSM 22067Trevealed the two strains exhibit capacity for removing cholesterol with efficiency of 36.6% and 54.3%. Exopolysaccharide production of two strains were 234 and 271 mg/L, respectively.
Genome-wide Screen of Otosclerosis in Population Biobanks: 18 Loci and Shared Heritability with Skeletal Structure
Authors: Rämö Joel T. , Kiiskinen Tuomo , Karjalainen Juha , Krebs Kristi , Kurki Mitja , Havulinna Aki S. , Hämäläinen Eija , Häppölä Paavo , Hautakangas Heidi ,   FinnGen, Karczewski Konrad J. , Kanai Masahiro , Mägi Reedik , Palta Priit , Esko Tõnu , Metspalu Andres , Pirinen Matti , Ripatti Samuli , Milani Lili , Mäkitie Antti , Daly Mark J. , Palotie Aarno 
Published: November 2020

AbstractOtosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. It typically presents in adulthood and half of the patients have a positive family history. The pathophysiology of otosclerosis is poorly understood and treatment options are limited. A previous genome-wide association study (GWAS) identified a single association locus in an intronic region of RELN. Here, we report a meta-analysis of GWAS studies of otosclerosis in three population-based biobanks comprising 2,413 cases and 762,382 controls. We identify 15 novel risk loci (p < 5*10−8) and replicate the regions of RELN and two previously reported candidate genes (TGFB1 and MEPE). Implicated genes in many loci are essential for bone remodelling or mineralization. Otosclerosis is genetically correlated with height and fracture risk, and the association loci overlap with severe skeletal disorders. Our results highlight TGFβ1 signalling for follow-up mechanistic studies.
A single origin of animal excretory organs
Authors: Gąsiorowski Ludwik , Andrikou Carmen , Janssen Ralf , Bump Paul , Budd Graham E. , Lowe Christopher J. , Hejnol Andreas 
Published: November 2020

AbstractExcretion is an essential physiological process, carried out by all living organisms regardless of their size or complexity(1–3). Most animals, which include both protostomes (e.g. flies, flatworms) and deuterostomes (e.g. humans, sea urchins) (together Nephrozoa(4, 5)), possess specialized excretory organs. Those organs exhibit an astonishing diversity, ranging from units composed of just three distinct cells (e.g. protonephridia) to complex structures, built by millions of cells of multiple types with divergent morphology and function (e.g. vertebrate kidneys)(6, 7). Although some molecular similarities between the development of kidneys of vertebrates and the regeneration of the protonephridia of flatworms have been reported(8, 9), the molecular development of nephrozoan excretory organs has never been systematically studied in a comparative context(6). Here we show that a set of highly conserved transcription factors and structural proteins is expressed during the development of excretory organs of six species that represent major protostome lineages and non-vertebrate deuterostomes. We demonstrate that the molecular similarity witnessed in the vertebrate kidney and flatworm protonephridia(8) is also seen in the developing excretory organs of other Nephrozoa. In addition, orthologous structural proteins forming the ultrafiltration apparatus are expressed in all these organs in the filter-forming cells. Our results strongly suggest that excretory organs are homologous and are patterned by the conserved set of developmental genes. We propose that the last common nephrozoan ancestor possessed an ultrafiltration-based, ciliated excretory organ, a structure that later gave rise to the vast diversity of extant excretory organs, including the human kidney.Significance statementMost of the bilaterally symmetrical animals excrete through specialized excretory organs, such as kidneys and nephridia. However, due to the morphological diversity of these organs, it remains unknown whether those structures evolved from a common ancestral organ or appeared several times independently during evolution. In order to answer the question about the origin of excretory organs we investigated the molecular pathways and structural genes involved in the development of nephridia in 6 animal species representing major evolutionary lineages. We show that diverse excretory organs share an ancient molecular patterning and structural molecules. Our results provide strong evidence that all excretory organs originated from a single, simple organ that performed urine production by ultrafiltration in deep geological past.
Immunological memory to SARS-CoV-2 assessed for up to eight months after infection
Authors: Dan Jennifer M. , Mateus Jose , Kato Yu , Hastie Kathryn M. , Yu Esther Dawen , Faliti Caterina E. , Grifoni Alba , Ramirez Sydney I. , Haupt Sonya , Frazier April , Nakao Catherine , Rayaprolu Vamseedhar , Rawlings Stephen A. , Peters Bjoern , Krammer Florian , Simon Viviana , Saphire Erica Ollmann , Smith Davey M. , Weiskopf Daniela , Sette Alessandro , Crotty Shane 
Published: November 2020

ABSTRACTUnderstanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
Multidimensional single-cell modeling of cellular signaling
Authors: Wade James D. , Lun Xiao-Kang , Bodenmiller Bernd , Voit Eberhard O. 
Published: November 2020

AbstractCell-to-cell differences in signaling components can lead to qualitatively different responses to stimuli. Understanding this heterogeneity in signaling response is limited by the inability of time-lapse methods to measure multiple pathway components simultaneously in situ. Here, we presentDistribution-Independent Single-Cell ODE modeling(DISCO), a computational method for inference of continuous single-cell signaling dynamics from multiplexed snapshot data. We used DISCO to analyze signaling in the MAPK/ERK pathway of HEK293T cells stimulated with the growth factor EGF. Our model recapitulates known features of the ERK signaling response and enables the detection of hidden cell-to-cell variation in seemingly homogeneous samples. Further, DISCO analysis suggested that the MAPK/ERK pathway transmits signal duration rather than amplitude, and that cell-to-cell variation in MAPK/ERK signaling response depends primarily on initial cell states. Finally, we applied an extended version of DISCO to explain changes in signaling kinetics due to overexpression of a disease-relevant protein. Overall, DISCO enables a deeper understanding of how single-cell variation affects cellular responses in complex signaling systems.
Desert Dingo (Canis lupus dingo) genome provides insights into their role in the Australian ecosystem
Authors: Yadav Sonu , Dudchenko Olga , Esvaran Meera , Rosen Benjamin D. , Field Matt A. , Skvortsova Ksenia , Edwards Richard J. , Gopalakrishnan Shyam , Keilwagen Jens , Cochran Blake J. , Manandhar Bikash , Bucknall Martin , Bustamante Sonia , Rasmussen Jacob Agerbo , Melvin Richard G. , Omer Arina , Colaric Zane , Chan Eva K. F. , Minoche Andre E. , Smith Timothy P.L. , Gilbert M. Thomas P. , Bogdanovic Ozren , Zammit Robert A. , Thomas Torsten , Aiden Erez L. , Ballard J. William O. 
Published: November 2020

AbstractThe dingo is Australia’s iconic top-order predator and arrived on the continent between 5,000-8,000 years ago. To provide an unbiased insight into its evolutionary affiliations and biological interactions, we coupled long-read DNA sequencing with a multiplatform scaffolding approach to produce anab initiogenome assembly of the desert dingo (85X coverage) we call CanLup_DDS. We compared this genome to the Boxer (CanFam3.1) and German Shepherd dog (CanFam_GSD) assemblies and characterized lineage-specific and shared genetic variation ranging from single– to megabase pair–sized variants. We identified 21,483 dingo-specific and 16,595 domestic dog-specific homozygous structural variants mediating genic and putative regulatory changes. Comparisons between the dingo and domestic dog builds detected unique inversions on Chromosome 16, structural variations in genes linked with starch metabolism, and seven differentially methylated genes. To experimentally assess genomic differences 17 dingoes and 15 German Shepherd dogs were fed parallel diets for 14 days. In dingoes, lowAMY2Bcopy number and serum amylase levels are linked with high cholesterol and LDL levels. Gut microbiome analyses revealed enrichment of the familyClostridiaceae, which can utilize complex resistant starch, while scat metabolome studies identified high phenylethyl alcohol concentrations that we posit are linked with territory marking. Our study provides compelling genomic, microbiome, and metabolomic links showing the dingo has distinct physiology from domestic breed dogs with a unique role in the ecosystem.
EXPRESSED EMOTION AND SELECTED PATIENTS’ CLINICAL FACTORS AMONG CAREGIVERS OF SCHIZOPHRENIC PATIENTS VISITING JIMMA UNIVERSITY MEDICAL CENTER PSYCHIATRY OUT PATIENT UNIT, SOUTH WEST ETHIOPIA
Authors: Yimam Bethlehem , Soboka Matiwos , Getachew Yemiamrew , Alemu Bezaye , Ahmed Gutema , Tesfaye Elias 
Published: November 2020

ABSTRACTBackgroundExpressed emotion (EE) measures the emotion of the caregivers of persons with schizophrinia and is predictive of symptom levels in a range of medical and psychiatric conditions. It is worth to assess expressed emotion and associated factors among caregivers of patient with schizophrenia in Ethiopia since there is limited data on this issue in this part of the world.ObjectiveTo assess the status of expressed emotions and selecte patients’ clinical factors among care givers of patients with schizophrenia attending psychiatry oupatient unit of Jimma university medical center, South west, Ethiopia, 2019.MethodA cross-sectional study design employed involving 422 caregivers of schizophrenic patients using consecutive sampling technique. Data was collected using structured interviewer administrated questionnaires (Family Questioners) which assess the level of expressed emotion, entered into Epidata 4.4 and analyzed by Statistical package for social science (SPSS) version 25. Descripitive statistics used to summerize data, bivariate logistic regression was done to identify candidate variables for multivariable logistic regressions and the association between expressed emotion and predictor variables was identified by using multiple logistic regression model.ResultsHigh expressed emotion was observed in 43.6% of respondents. Caring for schizophrenic patients for about 6-8 years, having 3-4 episodes of the illness was significantly associated with high expressed emotion.ConclusionsThis study revealed that there is high status of care givers expressed emotion compared to other studies. It also showed that number of episode of illnesses had significant association with high caregivers expressed emotion. Health care systems, which provide interventions for patients with schizophrenia, need to design proper strategy to address caregivers need as well.