bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptin-mediated suppression of food intake by conserved Glp1r-expressing neurons prevents obesity
Authors: Rupp Alan C. , Tomlinson Abigail J. , Affinati Alison H. , True Cadence , Lindsley Sarah R. , Kirigiti Melissa A. , MacKenzie Alexander , Li Chien , Knudsen Lotte Bjerre , Olson David P. , Kievit Paul , Myers Martin G. 
Published: December 2021

AbstractThe adipose-derived hormone leptin acts via its receptor (LepRb) in the brain to control energy balance. A previously unidentified population of GABAergic hypothalamic LepRb neurons plays key roles in the restraint of food intake and body weight by leptin. To identify markers for candidate populations of LepRb neurons in an unbiased manner, we performed single-nucleus RNA-sequencing of enriched mouse hypothalamic LepRb cells, as well as with total hypothalamic cells from multiple mammalian species. In addition to identifying known LepRb neuron types, this analysis identified several previously unrecognized populations of hypothalamic LepRb neurons. Many of these populations display strong conservation across species, including GABAergic Glp1r-expressing LepRb (LepRbGlp1r) neurons that express more Lepr and respond more robustly to exogenous leptin than other LepRb populations. Ablating LepRb from these cells provoked hyperphagic obesity without impairing energy expenditure. Conversely, reactivating LepRb in Glp1r-expressing cells decreased food intake and body weight in otherwise LepRb-null mice. Furthermore, LepRb reactivation in GABA neurons improved energy balance in LepRb-null mice, and this effect required the expression of LepRb in GABAergic Glp1r-expressing neurons. Thus, the conserved GABAergic LepRbGlp1r neuron population plays crucial roles in the control of food intake and body weight by leptin.
Mouse models of NADK2 deficiency analyzed for metabolic and gene expression changes to elucidate pathophysiology
Authors: Murray G. , Bais P. , Hatton C. , Tadenev A.L.D. , Morelli K.H. , Schroeder D. , Doty R. , Fiehn O. , John S.W.M. , Bult C.J. , Cox G.A. , Burgess R.W. 
Published: December 2021

AbstractNADK2 encodes the mitochondrial isoform of NAD Kinase, which phosphorylates nicotinamide adenine dinucleotide (NAD). Rare recessive mutations in human NADK2 are associated with a syndromic neurological mitochondrial disease that includes metabolic changes such as hyperlysinemia and 2,4 dienoyl CoA reductase (DECR) deficiency. However, the full pathophysiology resulting from NADK2 deficiency is not known. Here we describe two chemically-induced mouse mutations in Nadk2, S326L and S330P, which cause a severe neuromuscular disease and shorten lifespan. The S330P allele was characterized in detail and shown to have marked denervation of neuromuscular junctions by 5 weeks of age and muscle atrophy by 11 weeks of age. Cerebellar Purkinje cells also showed progressive degeneration in this model. Transcriptome profiling on brain and muscle was performed at early and late disease stages. In addition, metabolomic profiling was performed on brain, muscle, liver, and spinal cord at the same ages. Combined transcriptomic and metabolomic analyses identified hyperlysinemia, DECR deficiency, and generalized metabolic dysfunction in Nadk2 mutant mice, indicating relevance to the human disease. We compared findings from the Nadk model to equivalent RNAseq and metabolomic datasets from a mouse model of infantile neuroaxonal dystrophy, caused by recessive mutations in Pla2g6. This enabled us to identify disrupted biological processes that are common between these mouse models of neurological disease, such as translation, and those processes that are gene-specific such as glycolysis and acetylcholine binding. These findings improve our understanding of the pathophysiology of both Nadk2 and Pla2g6 mutations, as well as pathways common to neuromuscular/neurodegenerative diseases.
Phylogenomic analyses of Snodgrassella isolates from honeybees and bumblebees reveals taxonomic and functional diversity
Authors: Cornet Luc , Cleenwerck Ilse , Praet Jessy , Leonard Raphaël R. , Vereecken Nicolas J. , Michez Denis , Smagghe Guy , Baurain Denis , Vandamme Peter 
Published: December 2021

AbstractSnodgrassella is a Betaproteobacteria genus found in the gut of honeybees (Apis spp.) and bumblebees (Bombus spp). It is part of a conserved microbiome that is composed of few core phylotypes and is essential for bee health and metabolism. Phylogenomic analyses using whole genome sequences of 75 Snodgrassella strains from 4 species of honey bees and 14 species of bumblebees showed that these strains formed a monophyletic lineage within the Neisseriaceae family, that Snodgrassella isolates from Asian honeybees diverged early on from the other species in their evolution, that isolates from honeybees and bumblebees were well separated and that this genus consists of at least seven species. We propose to formally name two new Snodgrassella species that were isolated from bumblebees, i.e. Snodgrassella gandavensis sp. nov. and Snodgrassella communis sp. nov. Possible evolutionary scenarios for 107 species or group specific genes revealed very limited evidence for horizontal gene transfer. Functional analyses revealed the importance of small proteins, defense mechanisms, amino acid transport and metabolism, inorganic ion transport and metabolism and carbohydrate transport and metabolism among these 107 specific genes.ImportanceThe microbiome of honeybees (Apis spp.) and bumblebees (Bombus spp.) is highly conserved and represented by few phylotypes. This simplicity in taxon composition makes the bee’s microbiome an emergent model organism for the study of gut microbial communities. Since the description of the Snodgrassella genus, which was isolated from the gut of honeybees and bumblebees in 2013, a single species, i.e. Snodgrassella alvi, has been named. Here we demonstrate that this genus is actually composed of at least seven species, two of them (Snodgrassella gandavensis sp. nov. and Snodgrassella communis sp. nov.) being formally described in the present publication. We also report the presence of 107 genes specific to Snodgrassella species, showing notably the importance of small proteins and defense mechanisms in this genus.Data summaryCornet L and Vandamme P, European Nucleotide Archive (ENA), Project accession: PRJEB47378Cornet L and Vandamme P, European Nucleotide Archive (ENA), Reads accessions: SAMEA9570070 - SAMEA9570078Cornet L and Vandamme P, European Nucleotide Archive (ENA), Genome accessions: GCA_914768015, GCA_914768025, GCA_914768035, GCA_914768045, GCA_914768055, GCA_914768065, GCA_914768075, GCA_914768085, GCA_914768095.
Sequence diversity in the 3’ untranslated region of alphavirus modulates IFIT2-dependent restriction in a cell type-dependent manner
Authors: Hickson Sarah E. , Brekke Eden , Schwerk Johannes , Saluhke Indraneel , Zaver Shivam , Woodward Joshua , Savan Ram , Hyde Jennifer L. 
Published: December 2021

ABSTRACTAlphaviruses (family Togaviridae) are a diverse group of positive-sense RNA (+ssRNA) viruses that are transmitted by arthropods and are the causative agent of several significant human and veterinary diseases. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFITs) are a family of RNA-binding IFN stimulated genes (ISGs) that are highly upregulated following viral infection, and have been identified as potential restrictors of alphaviruses. The mechanism by which IFIT1 restricts RNA viruses is dependent on self and non-self-discrimination of RNA, and alphaviruses evade this recognition via their 5’UTR. However, the role of IFIT2 during alphavirus replication and the mechanism of viral replication inhibition is unclear. In this study, we identify IFIT2 as a restriction factor for Venezuelan equine encephalitis virus (VEEV) and show that IFIT2 binds the 3’ untranslated region (3’UTR) of the virus. We investigated the potential role of variability in the 3’UTR of the virus affecting IFIT2 antiviral activity by studying infection with VEEV. Comparison of recombinant VEEV clones containing 3’UTR sequences derived from epizootic and enzootic isolates exhibited differential sensitivity to IFIT2 restriction in vitro infection studies, suggesting that the alphavirus 3’UTR sequence may function in part to evade IFIT2 restriction. In vitro binding assays demonstrate that IFIT2 binds to the VEEV 3’UTR, however in contrast to previous studies VEEV restriction did not appear to be dependent on the ability of IFIT2 to inhibit translation of viral RNA, suggesting a novel mechanism of IFIT2 restriction. Our study demonstrates that IFIT2 is a restriction factor for alphaviruses and variability in the 3’UTR of VEEV can modulate viral restriction by IFIT2. Ongoing studies are exploring the biological consequences of IFIT2-VEEV RNA interaction in viral pathogenesis and defining sequence and structural features of RNAs that regulate IFIT2 recognition.
Age-specific Contribution of Contacts to Transmission of SARS-CoV-2 in Germany
Authors: Rodiah I. , Vanella P. , Kuhlmann A. , Jaeger V. K. , Harries M. , Krause G. , Bock W. , Lange B. 
Published: December 2021

AbstractIntroductionCurrent estimates of pandemic spread using infectious disease models in Germany for SARS-CoV-2 often do not use age-specific infection parameters and are not always based on known contact matrices of the population. They also do not usually include setting-based information of reported cases and do not account for age-specific underdetection of reported cases. Here, we report likely pandemic spread using an age-structured model to understand the age- and setting-specific contribution of contacts to transmission during all phases of the COVID-19 pandemic in Germany.MethodsWe developed a deterministic SEIRS model using a pre-pandemic contact matrix. The model is optimized to fit reported age-specific SARS-CoV-2 incidences from the Robert Koch Institute, includes information on setting-specific reported cases in schools and integrates age and pandemic period-specific parameters for underdetection of reported cases deduced from a large population-based seroprevalence study.ResultsWe showed that taking underreporting into account, younger adults and teenagers are the main contributors to infections during the first three pandemic waves in Germany. Overall, the contribution of contacts in schools to the total cases in the population was below 10% during the third wave.DiscussionAccounting for the pandemic phase and age-specific underreporting seems important to correctly identify those parts of the population where quarantine, testing, vaccination, and contact-reduction measures are likely to be most effective and efficient. In the future, we will aim to compare current model estimates with currently emerging during-pandemic age-specific contact survey data.
Adult life-course trajectories of psychological distress and economic outcomes in midlife during the COVID-19 pandemic
Authors: Moulton V , Sullivan A , Goodman A , Parsons S , Ploubidis G 
Published: December 2021

AbstractThis study used two British birth cohorts to examine whether pre-pandemic trajectories of psychological distress were associated with a greater risk of changes in financial and employment situation during the pandemic, as well as increased need for government support and use of other methods to mitigate their economic situation. We identified 5 differential life-course trajectories of psychological distress from adolescence to midlife and explored their relation to changes in financial and employment circumstances at different stages during the pandemic from May 2020 to March 2021, applying multinomial logistic regression and controlling for numerous early life covariates. In addition, we ran modified Poisson models with robust standard errors to identify whether different trajectories were more likely to have been supported by the benefit system, payment holidays, borrowing and other methods of mitigating the economic shock. We found that despite the UK governments economic response package economic inequalities for pre-pandemic psychological distress trajectories with differential onset, severity and chronicity across the life-course were exacerbated by the COVID-19 economic shock. Furthermore, the subsequent cut in government support, alongside increases in the cost of living may widen economic inequalities for differential pre-pandemic psychological distress trajectories, which in turn may also worsen mental health. This work highlights, different pre-pandemic trajectories of psychological distress were more vulnerable to economic shock.
A spectrum of recessiveness among Mendelian disease variants in UK Biobank
Authors: Barton Alison R. , Hujoel Margaux L.A. , Mukamel Ronen E. , Sherman Maxwell A. , Loh Po-Ru 
Published: December 2021

AbstractRecent work has found increasing evidence of mitigated, incompletely penetrant phenotypes in heterozygous carriers of recessive Mendelian disease variants. We leveraged whole-exome imputation within the full UK Biobank cohort (N∼500K) to extend such analyses to 3,481 rare variants curated from ClinVar and OMIM. Testing these variants for association with 57 quantitative traits yielded 103 significant associations involving variants previously implicated in 35 different diseases. Notable examples included a POR missense variant implicated in Antley-Bixler syndrome that associated with a 1.76 (s.e. 0.27) cm increase in height, and an ABCA3 missense variant implicated in interstitial lung disease that associated with reduced FEV1/FVC ratio. Association analyses with 1,257 disease traits yielded five additional variant-disease associations. We also observed contrasting levels of recessiveness between two more-common, classical Mendelian diseases. Carriers of cystic fibrosis variants exhibited increased risk of several mitigated disease phenotypes, whereas carriers of spinal muscular atrophy alleles showed no evidence of altered phenotypes. Incomplete penetrance of cystic fibrosis carrier phenotypes did not appear to be mediated by common allelic variation on the functional haplotype. Our results show that many disease-associated recessive variants can produce mitigated phenotypes in heterozygous carriers and motivate further work exploring penetrance mechanisms.
A Qualitative Expert Interview Study: Mobility Health in Indonesia
Authors: Yosia Mikhael , Basrowi Ray Wagiu , Sundjaya Tonny , Masita Bertri Maulidya 
Published: December 2021

AbstractBackgroundIndonesia has an ageing population that can develop mobility health-related problems in the future, including osteoporosis, arthritis, sarcopenia, low back pain, neck pain, and peripheral neuropathy. However, there are limited references and research that look upon mobility health and problems surrounding it in Indonesia.AimsTo improve understanding on issues surrounding mobility health in Indonesia through a semi-structured interview with relevant experts.MethodSemi-structured qualitative interviews via phone calls were conducted with eight different experts. Data were analysed using reflexive thematic analysis. Experts with experience dealing with mobility (bone, muscle, joint, movement) related issues for more than ten years, working in Indonesia, and communicating in English or Bahasa Indonesia were included.ResultsFour themes were then identified across the experts on issues surrounding mobility health in Indonesia; this includes [1] screening and assessment of mobility health, [2] treatment for mobility health problems, [3] awareness campaign, [4] supplement for mobility health.ConclusionsDiagnostic modalities for mobility health are abundant but still expensive. Treatment of mobility health with herbal medicine (jamu) might be beneficial. Fortified food or milk can improve mobility health. Social media can be a promising tool to increase awareness regarding mobility health. In general, there needs to be a change in mindset from curative to prevention in both health care providers and the general population.
learnMET: an R package to apply machine learning methods for genomic prediction using multi-environment trial data
Authors: Westhues Cathy C. , Simianer Henner , Beissinger Timothy M. 
Published: December 2021

ABSTRACTWe introduce the R-package learnMET, developed as a flexible framework to enable a collection of analyses on multi-environment trial (MET) breeding data with machine learning-based models. learnMET allows the combination of genomic information with environmental data such as climate and/or soil characteristics. Notably, the package offers the possibility of incorporating weather data from field weather stations, or can retrieve global meteorological datasets from a NASA database. Daily weather data can be aggregated over specific periods of time based on naive (for instance, non-overlapping 10-day windows) or phenological approaches. Different machine learning methods for genomic prediction are implemented, including gradient boosted trees, random forests, stacked ensemble models, and multi-layer perceptrons. These prediction models can be evaluated via a collection of cross-validation schemes that mimic typical scenarios encountered by plant breeders working with MET experimental data in a user-friendly way. The package is fully open source and accessible on GitHub.
PTEN inhibits AMPK to control collective migration
Authors: Peglion Florent , Capuana Lavinia , Perfettini Isabelle , Braithwaite Ben , Quissac Emie , Forsberg-Nilsson Karin , Llense Flora , Etienne-Manneville Sandrine 
Published: December 2021

ABSTRACTPTEN is one of the most frequently mutated tumor suppressor gene in cancer. PTEN is generally altered in invasive cancers such as glioblastomas, but its function in collective cell migration and invasion is not fully characterized. Herein, we report that the loss of PTEN increases cell speed during collective migration of non-tumourous cells both in vitro and in vivo. We further show that loss of PTEN promotes LKB1-dependent phosphorylation and activation of the major metabolic regulator AMPK. In turn AMPK increases VASP phosphorylation, reduces VASP localization at cell-cell junctions and decreases the interjunctional transverse actin arcs at the leading front, provoking a weakening of cell-cell contacts and increasing migration speed. Targeting AMPK activity not only slows down PTEN-depleted cells, it also limits PTEN-null glioblastoma cell invasion, opening new opportunities to treat glioblastoma lethal invasiveness.
Endothelial-immune crosstalk contributes to vasculopathy in non-alcoholic fatty liver disease
Authors: Ng Chun Yi , Lee Khang Leng , Muthiah Mark D. , Wu Kan-Xing , Chioh Florence W. J. , Tan Konstanze , Soon Gwyneth S. T. , Shabbir Asim , Loo Wai Mun , Low Zun Siong , Chen Qingfeng , Tan Nguan Soon , Ng Huck Hui , Dan Yock Young , Cheung Christine 
Published: December 2021

AbstractThe top cause of mortality in patients with non-alcoholic fatty liver disease (NAFLD) is cardiovascular complications. However, the mechanisms of NAFLD-associated vasculopathy remain understudied. We developed blood outgrowth endothelial cell (BOEC) models from NAFLD and healthy subjects. NAFLD BOECs exhibited global transcriptional upregulation of chemokine hallmarks and human leukocyte antigens. In mouse models of diet-induced NAFLD, we further confirmed enhanced endothelial expressions of CXCL12 in the aortas and liver vasculatures. To elucidate endothelial-immune crosstalk, we performed immunoprofiling by single-cell analysis, uncovering T cell intensification and potentially T-helper type 1 inflammation in NAFLD patients. Functionally, interference of the CXCL12-CXCR4 axis by small molecule AMD3100 selectively modulated the chemotaxis of patient-derived CD4+ T cells and natural killer cells towards NAFLD BOECs, restoring endothelial barrier integrity. Clinically, we detected three folds more circulating damaged endothelial cells in NAFLD patients than healthy controls. Our work provides insights for modulation of interactions with effector immune subsets to mitigate endothelial injury in NAFLD.
The influence of Janthinobacterium sp. strain SLB01 on the cell culture of primmorphs of the sponge Lubomirskia baicalensis
Authors: Chernogor Lubov I. , Eliseikina Marina G. , Petrushin Ivan S. , Chernogor Ekaterina A. , Khanaev Igor V. , Belikov Sergei I. 
Published: December 2021

AbstractSponges (phylum Porifera) are ancient, filtering, multicellular metazoans. Freshwater sponges (Demosponges, Lubomirskiidae) dominate the fauna of the littoral zone of Lake Baikal. Over the last years, there have been mass diseases and death of endemic sponges. Previously, the strain Janthinobacterium sp. SLB01 was isolated from the diseased sponge Lubomirskia baicalensis. The studies of the pathogenicity of the strain Janthinobacterium sp. SLB01 for Baikal sponges has not been carried out. Therefore we infected experimentally in vitro to determine its pathogenicity by the cell culture of the primmorphs with subsequent isolation, sequencing, and analysis of the genomes. The purpose of the study is to show that the strain Janthinobacterium sp. SLB01 isolated from the diseased sponge L. baicalensis is a pathogen for the cell culture of primmorphs. The bacteria from the infected samples of the primmorphs were isolated and identified as strain Janthinobacterium sp. PLB02. A comparative analysis of the genomes of the strains Janthinobacterium sp. SLB01 and Janthinobacterium sp. PLB02 showed that they are practically identical. The genomes of both strains contain genes vioABCDE violacein, flok formation, and strong biofilm, and the type VI secretion system (T6SS), as the primary virulence factor. The bacterial strains Janthinobacterium sp. based on a comparison of complete genomes showed similarity with strain Janthinobacterium lividum MTR. Isolated our strains of Janthinobacterium sp. are pathogens for cell cultures of primmorphs and L. baicalensis sponges. The results of the study will help to expand the understanding of microbial relationships in the development of disease and the death of Baikal sponges.