bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining two large clinical cohorts (AIBL and ADNI) to identify multiple lipid metabolic pathways in prevalent and incident Alzheimer’s disease
Authors: Huynh Kevin , Lim Wei Ling Florence , Giles Corey , Jayawardana Kaushala S , Salim Agus , Mellett Natalie A , Smith Alex , Olshansky Gavriel , Drew Brian G , Chatterjee Pratishtha , Martins Ian , Laws Simon M , Bush Ashley I , Rowe Christopher C , Villemagne Victor L , Ames David , Masters Colin L , Arnold Matthias , Nho Kwangsik , Saykin Andrew J , Baillie Rebecca , Han Xianlin , Kaddurah-Daouk Rima , Martins Ralph N , Meikle Peter J 
Published: May 2020

ABSTRACTChanges to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising of many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 lipid species across 32 lipid (sub)classes) allows for detailed isomeric and isobaric lipid separation. We applied the methodology to examine plasma samples from the Australian Imaging, Biomarkers and Lifestyle flagship study of aging (AIBL, n = 1112) and serum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, n = 800) studies. Cross sectional analysis using both cohorts identified concordant unique peripheral signatures associated with AD. Specific pathways include; sphingolipids, including GM3gangliosides, where their acyl composition drove the major associations, and lipids previously associated with dysfunctional lipid metabolism in cardiometabolic disease including the phosphatidylethanolamine and triglyceride classes. Infomation derived from improved isomeric seperation highlighted pathway-specific changes with ether lipids including plasmalogens implicating perixosmal dysfunction in disease pathology. Longitudinal analysis revealed similar lipid signitures in both AIBL and ADNI cohorts with future disease onset. We utilised the two independent studies to train and validate multivariate lipid models that significantly improved disease classification and prediction. Together our results provide a holistic view of the lipidome and its relationship with AD using a comprehensive lipidomics approach, providing targets for further mechanistic investigation.
Systematic Discovery of Pseudomonad Genetic Factors Involved in Sensitivity to Tailocins
Authors: Carim Sean , Azadeh Ashley L. , Kazakov Alexey E. , Price Morgan N. , Walian Peter J. , Chakraborty Romy , Deutschbauer Adam M. , Mutalik Vivek K. , Arkin Adam P. 
Published: May 2020

AbstractTailocins are bactericidal protein complexes produced by a wide variety of bacteria to compete against closely related strains. Like tailed bacteriophages, with whom they share an evolutionary and morphological relationship, tailocins bind and kill a narrow spectrum of target cells. Thanks to their high specificity, tailocins have garnered recent attention for their potential as precision antibacterial agents. Nevertheless, the field currently lacks a systematic investigation of genetic determinants of tailocin sensitivity. Here, we employed barcoded transposon-insertion mutant libraries and comparative genomics to assess genetic contributions to tailocin sensitivity in pseudomonads. Our mutant screens identified O-specific antigen (OSA) composition and display as most important in defining sensitivity to our tailocins. Additionally, the screens suggest lipopolysaccharide (LPS) thinning as a mechanism by which resistant strains can become more sensitive to tailocins. Our comparative genomics analyses show a loose relationship between OSA biosynthetic genes and tailocin sensitivity, as well as sensitivity nuances that require further investigation. Overall, our data reinforces the model that LPS molecules can act as either a receptor for, or shield against, tailocin binding and killing. This work offers insight into the specificity of tailocins and tailocin-mediated competition, informing the potential use of tailocins in microbiome manipulation and antibacterial therapy.
Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1 positive pediatric leukemia identifies drug-targetable transcription factor activities
Authors: Mehtonen Juha , Teppo Susanna , Lahnalampi Mari , Kokko Aleksi , Kaukonen Riina , Oksa Laura , Bouvy-Liivrand Maria , Malyukova Alena , Laukkanen Saara , Mäkinen Petri I. , Rounioja Samuli , Ruusuvuori Pekka , Sangfelt Olle , Lund Riikka , Lönnberg Tapio , Lohi Olli , Heinäniemi Merja 
Published: May 2020

AbstractTight regulatory loops orchestrate commitment to B-cell fate within bone marrow. Genetic lesions in this gene regulatory network underlie the emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). The initial genetic hits, including the common translocation that fuses ETV6 and RUNX1 genes, lead to arrested cell differentiation. Here, we aimed to characterize transcription factor activities along the B-lineage differentiation trajectory as a reference to characterize the aberrant cell states present in leukemic bone marrow, and to identify those transcription factors that maintain cancer-specific cell states for more precise therapeutic intervention.We compared normal B-lineage differentiation andin vivoleukemic cell states using single cell RNA-sequencing (scRNA-seq) and several complementary genomics profiles. Based on statistical tools for scRNA-seq, we benchmarked a workflow to resolve transcription factor activities and gene expression distribution changes in healthy bone marrow lymphoid cell states. We compared these to ALL bone marrow at diagnosis andin vivoduring chemotherapy, focusing on leukemias carrying the ETV6-RUNX1 fusion.We show that lymphoid cell transcription factor activities uncovered from bone marrow scRNA-seq have high correspondence with independent ATAC- and ChIP-seq data. Using this comprehensive reference for regulatory factors coordinating B-lineage differentiation, our analysis of ETV6-RUNX1-positive ALL cases revealed elevated activity of multiple ETS-transcription factors in leukemic cells states, including the leukemia genome-wide association study hit ELK3. The accompanying gene expression changes associated with natural killer cell inactivation and depletion in the leukemic immune microenvironment. Moreover, our results suggest that the abundance of G1 cell cycle state at diagnosis and lack of differentiation-associated regulatory network changes during induction chemotherapy represent features of chemoresistance. To target the leukemic regulatory program and thereby overcome treatment-resistance, we show that selective inhibitors of ETS-transcription factors could effectively reduce cell viability.Our data provide a detailed picture of the transcription factor activities that characterize both normal B-lineage differentiation and those acquired in leukemic bone marrow and provide a rational basis for new treatment strategies targeting the immune microenvironment and the active regulatory network in leukemia.
Diffusion assessment through image processing: beyond the point-source paradigm
Authors: Postnikov Eugene B. , Namykin Anton A. , Semyachkina-Glushkovskaya Oxana V. , Postnov Dmitry E. 
Published: May 2020

AbstractThe quantification of transport processes of different substances in the brain’s parenchyma is important in the context of understanding brain functioning. Most of the currently used methods for assessment of the effective diffusion coefficient rely on the point-source paradigm.We propose a method for the quantitative characterization of the diffusion process in the brain’s parenchyma using a set of images recorded in the experiment during the spreading of a fluorescent dye. Our method exploits the frame-wise comparison of experimental data with a set of images that would be observed for an ideal diffusion process within the same topology. We obtain this reference set of images using blurring the image with an appropriate kernel function, and the degree of such blurring correlates with the spreading process of a dye. We demonstrate the applicability of the proposed method using (i) the simulated surrogate data, (ii) the set of experimentally recorded fluorescent images of the isolated event of blood-brain barrier (BBB) opening, and (iii) the images of massive multi-source spreading of fluorescent dye.
Histone lysine crotonylation regulates cell-fate determination of neural stem/progenitor cells by activating bivalent promoters
Authors: Dai Shang-Kun , Liu Pei-Pei , Du Hong-Zhen , Liu Xiao , Xu Ya-Jie , Liu Cong , Wang Ying-Ying , Teng Zhao-Qian , Liu Chang-Mei 
Published: May 2020

AbstractHistone lysine crotonylation (Kcr), an evolutionarily conserved and widely expressed non-acetyl short-chain lysine acylation, plays important roles in transcriptional regulation and disease development. However, its genome-wide distribution, correlation with gene expression, and dynamic changes during developmental processes are largely unknown. In this study, we find that histone Kcr is mainly distributed in active promoters, has a ge-nome-wide positive correlation with transcriptional activity, and regulates transcription of genes participating in metabolism and proliferation. Moreover, elevated histone Kcr activates bivalent promoters to stimulate gene expression in neural stem/progenitor cells (NSPCs), through increasing chromatin openness and recruitment of RNA polymerase II (Pol II). Functionally, these activated genes remodel transcriptome and promote neuronal differentiation.Author summaryOverall, histone Kcr marks active promoters with high gene expression and modifies the local chromatin environment to allow gene activation, which influences neuronal cell fate. It may represent a unique active histone mark involved in neural developmental regulation.
Light-Sheet Fluorescence Imaging Charts the Gastrula Origin of Vascular Endothelial Cells in Early Zebrafish Embryos
Authors: Pang Meijun , Bai Linlu , Zong Weijian , Wang Xu , Bu Ye , Xiong Connie , Zheng Jiyuan , Li Jieyi , Gao Weizheng , Feng Zhiheng , Chen Liangyi , Zhang Jue , Cheng Heping , Zhu Xiaojun , Xiong Jing-Wei 
Published: May 2020

AbstractIt remains challenging to construct a complete cell lineage map of the origin of vascular endothelial cells in any vertebrate embryo. Here, we report the application ofin totolight-sheet fluorescence imaging of embryos to tracing the origin of vascular endothelial cells (ECs) at single-cell resolution in zebrafish. We first adapted a previously-reported method to mount embryos and light-sheet imaging, created analignment,fusion, andextraction all-in-one software (AFEIO) for processing big data, and performed quantitative analysis of cell lineage relationships using commercially-available Imaris software. Our data revealed that vascular ECs originated from broad regions of the gastrula along the dorsal-ventral and anterior-posterior axes, of which the dorsal-anterior cells contributed to cerebral ECs, the dorsal-lateral cells to anterior trunk ECs, and the ventral-lateral cells to posterior trunk and tail ECs. Therefore, this work, to our knowledge, charts the first comprehensive map of the gastrula origin of vascular ECs in zebrafish, and has potential applications for studying the origin of any embryonic organs in zebrafish and other model organisms.
Dopamine neurons of the VTA encode active conspecific interaction and promote social learning through social reward prediction error
Authors: Prévost-Solié Clément , Girard Benoit , Righetti Beatrice , Tapparel Malika , Bellone Camilla 
Published: May 2020

AbstractSocial interactions motivate behavior in many species, facilitating learning, foraging and cooperative behavior. However, how the brain encodes the reinforcing properties of social interactions remains elusive. Here using in vivo recording in freely moving mice, we show that Dopamine (DA) neurons of the Ventral Tegmental Area (VTA) increase their activity during active interactions with unfamiliar conspecific. Using a social instrumental task, we then show that VTA DA neuron activity signals social reward prediction error and drives social reinforcement learning. Thereby, our findings propose that VTA DA neurons are a neural substrate for a social learning signal driving motivated behavior.One Sentence SummaryDA neurons are a substrate for social reward learning through the Social Reward Prediction Error.
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Authors: Israelow Benjamin , Song Eric , Mao Tianyang , Lu Peiwen , Meir Amit , Liu Feimei , Madel Alfajaro Mia , Wei Jin , Dong Huiping , Homer Robert J , Ring Aaron , Wilen Craig B , Iwasaki Akiko 
Published: May 2020

AbstractSevere Acute Respiratory Syndrome-Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.1–3Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy studies.4Laboratory mice have been the stalwart of these types of studies; however, they do not support infection by SARS-CoV-2 due to the inability of its spike (S) protein to engage the mouse ortholog of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis,5these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno associated virus (AAV)-mediated expression of hACE2. These mice support viral replication and antibody production and exhibit pathologic findings found in COVID-19 patients as well as non-human primate models. Moreover, we show that type I interferons are unable to control SARS-CoV2 replication and drive pathologic responses. Thus, the hACE2-AAV mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds. This represents a much-needed platform for rapidly testing prophylactic and therapeutic strategies to combat COVID-19.
Digit ratio (2D:4D) and Congenital Adrenal Hyperplasia (CAH): Systematic Literature Review and Meta-Analysis
Authors: Richards Gareth , Browne Wendy V. , Aydin Ezra , Constantinescu Mihaela , Nave Gideon , Kim Mimi S. , Watson Steven J. 
Published: May 2020

AbstractThe ratio of length between the second and fourth fingers (2D:4D) is commonly used as an indicator of prenatal sex hormone exposure. Several approaches have been used to try to validate the measure, including examining 2D:4D in people with congenital adrenal hyperplasia (CAH), a suite of conditions characterised by elevated adrenal androgen production secondary to defective steroidogenesis. We present here a systematic review that examines the relationship between these two variables. Twelve articles relating to nine CAH cohorts were identified, and 2D:4D comparisons have been made between cases and controls in eight of these cohorts. Altogether, at least one 2D:4D variable has been compared between n=251 females with CAH and n=358 unaffected females, and between n=108 males with CAH and n=204 unaffected males. A previous meta-analysis (Hönekopp & Watson, 2010) reported lower right hand (R2D:4D) and left hand (L2D:4D) digit ratios in patients with CAH relative to sex-matched controls. Our meta-analysis showed the same direction of results; however, the effects were only statistically significant for R2D:4D in males and L2D:4D in females (R2D:4D: females,p= 0.072,g= 0.591; males,p= 0.019,g= 0.513; L2D:4D: females,p= 0.020,g= 0.245; males,p= 0.334,g= 0.218), and the average effect size had reduced by 46.70%. We also found no evidence to suggest the right-left difference in 2D:4D (D[R-L]) is associated with prenatal sex hormone exposure.
A refined set of rRNA-targeted oligonucleotide probes for in situ detection and quantification of ammonia-oxidizing bacteria
Authors: Lukumbuzya Michael , Kristensen Jannie Munk , Kitzinger Katharina , Pommerening-Röser Andreas , Nielsen Per Halkjær , Wagner Michael , Daims Holger , Pjevac Petra 
Published: May 2020

AbstractAmmonia-oxidizing bacteria (AOB) of the betaproteobacterial genera Nitrosomonas and Nitrosospira are key nitrifying microorganisms in many natural and engineered ecosystems. Since many AOB remain uncultured, fluorescence in situ hybridization (FISH) with rRNA-targeted oligonucleotide probes has been one of the most widely used approaches to study the community composition, abundance, and other features of AOB directly in environmental samples. However, the established and widely used AOB-specific 16S rRNA-targeted FISH probes were designed up to two decades ago, based on much smaller rRNA gene sequence datasets than available today. Several of these probes cover their target AOB lineages incompletely and suffer from a weak target specificity, which causes cross-hybridization of probes that should detect different AOB lineages. Here, a set of new highly specific 16S rRNA-targeted oligonucleotide probes was developed and experimentally evaluated that complements the existing probes and enables the specific detection and differentiation of the known, major phylogenetic clusters of betaproteobacterial AOB. The new probes were successfully applied to visualize and quantify AOB in activated sludge and biofilm samples from seven pilot- and full-scale wastewater treatment systems. Based on its improved target group coverage and specificity, the refined probe set will facilitate future in situ analyses of AOB.
Genomic structural and transcriptional variation of Oryctes rhinoceros nudivirus (OrNV) in Coconut Rhinoceros Beetle
Authors: Etebari Kayvan , Parry Rhys , Beltran Marie Joy B. , Furlong Michael J. 
Published: May 2020

AbstractOryctes rhinoceros nudivirus (OrNV) is a large circular double-stranded DNA virus which has been used as a biological control agent to suppress Coconut Rhinoceros Beetle (Oryctes rhinoceros) in Southeast Asia and the Pacific Islands. Recently a new wave ofO. rhinocerosincursions in Oceania in previously non-infested areas is thought to be related to the presence of low virulence isolates of OrNV or virus tolerant haplotypes of beetles. In this study, chronically infectedO. rhinocerosadults were field collected from the Philippines, Fiji, Papua New Guinea and the Solomon Islands. We extracted total RNA from these samples to investigate the global viral gene expression profiles and comparative genomic analysis of structural variations between the four different populations. Maximum likelihood phylogenic analysis indicated that OrNV strains from the Solomon Islands and the Philippines are closely related to while OrNV strains from PNG and Fiji formed a distinct adjacent clade. We detected several polymorphic sites with a frequency higher than 35% in 892 positions of the viral genome. The highest number of structural variants, including single nucleotide variants (SNV), insertion, deletion and non-synonymous mutations, were found in strains from Fiji and PNG when compared to complete recently sequenced Solomon Islands OrNV reference genome. Non-synonymous mutations were detected in several hypothetical proteins, and 15 nudivirus core genes such asOrNV_gp034(DNA Helicase),lef-8, lef-4andvp91. For examination of the global gene expression profile of OrNV in chronically infected populations, we found limited evidence of variation between geographic populations. Only a few genes such asOrNV_gp01(DNA polymerase B),OrNV_gp022andOrNV_gp107(Pif-3) were differentially expressed among different strains. Additionally, small RNA sequencing from the Solomon Islands population suggests that OrNV is targeted by the host RNA interference (RNAi) response with abundant 21nt small RNAs. Additionally, we identified a highly abundant putative 22 nt miRNA from the 3’ of a pre-miRNA-like hairpin originating fromOrNV-gp-098. These findings provide valuable resources for future studies to improve our understanding of the OrNV genetic variation. Some of these structural changes are specific to the geographic population and could be related to particular phenotypic characteristics of the strain, such as viral pathogenicity or transmissibility, and this requires further investigation.
Ambient air pollutants, meteorological factors and their interactions affect confirmed cases of COVID-19 in 120 Chinese cities
Authors: Zhou Jianli , Qin Linyuan , Liu Nan 
Published: May 2020

AbstractEmerging evidences have confirmed effects of meteorological factors on novel coronavirus disease 2019 (COVID-19). However, few studies verify the impact of air pollutants on this pandemic. This study aims to explore the association of ambient air pollutants, meteorological factors and their interactions effect confirmed case counts of COVID-19 in 120 Chinese cities. Here, we collected total confirmed cases of COVID-19 by combining with meteorological factors and air pollutants data from 15th January 2020 to 18th March 2020 in 120 Chinese cities. Spearman correlation analysis was employed to estimate the association between two variables; univariate and multivariate negative binomial regression analysis were applied to explore the effect of air pollutants and meteorological parameters on the COVID-19 confirmed cases. Positive associations were found between the confirmed cases of COVID-19 and carbon monoxide (CO), aerodynamic particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5), relative humidity (RH) and air pressure (AP). And negative association was found for sulfur dioxide (SO2). In addition, multivariate negative binomial regression analysis suggested that confirmed cases of COVID-19 was positively correlated with ozone (O3) in lag 0 day while it was negatively associated with wind velocity (WV) in lag 14 days, and the pollutants-meteorological factors interactions also associate with COVID-19. In conclusions, air pollutants and meteorological factors and their interactions all associate with COVID-19.