bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity causes irreversible mitochondria failure in visceral adipose tissue despite successful anti-obesogenic lifestyle-based interventions
Authors: Gonzalez-Franquesa Alba , Gama-Perez Pau , Kulis Marta , Dahdah Norma , Moreno-Gomez Sonia , Latorre-Pellicer Ana , Fernández-Ruiz Rebeca , Aguilar-Mogas Antoni , Monelli Erika , Samino Sara , Miró Joan , Oemer Gregor , Duran Xavier , Sanchez-Rebordelo Estrella , Schneeberger Marc , Obach Merce , Montane Joel , Castellano Giancarlo , Chapaprieta Vicente , Navarro Lourdes , Prieto Ignacio , Castaño Carlos , Novials Anna , Gomis Ramon , Monsalve Maria , Claret Marc , Graupera Mariona , Soria Guadalupe , Vendrell Joan , Fernandez-Veledo Sonia , Enríquez Jose Antonio , Carracedo Angel , Perales José Carlos , Nogueiras Rubén , Herrero Laura , Keller Markus A. , Yanes Oscar , Sales-Pardo Marta , Guimerà Roger , Martín-Subero José Ignacio , Garcia-Roves Pablo M. 
Published: July 2020

AbstractMetabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most pathological features were successfully reverted, we observed a high degree of metabolic dysfunction irreversibility in visceral white adipose tissue, characterised by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and apparent global phenotypic recovery, obesity specifically triggered in visceral adipose a cascade of events progressing from mitochondrial metabolic and proteostatic defects to widespread cellular stress, which compromises its biosynthetic and recycling capacity. Our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in white adipose tissue, becoming a significant milestone in disease progression.
Long-range GABAergic inhibition modulates spatiotemporal dynamics of the output neurons in the olfactory bulb
Authors: Villar Pablo S. , Hu Ruilong , Araneda Ricardo C. 
Published: July 2020

SUMMARYLocal interneurons of the olfactory bulb (OB) are densely innervated by long-range GABAergic neurons from the basal forebrain (BF), suggesting that this top-down inhibition regulates early processing in the olfactory system. However, how GABAergic inputs modulate the OB output neurons, the mitral/tufted cells, is unknown. Here, in acute brain slices, we show that optogenetic activation of BF GABAergic inputs produced distinct local circuit effects that can influence the activity of mitral/tufted cells in the spatiotemporal domains. Activation of the GABAergic axons produced a fast disinhibition of mitral/tufted cells consistent with a rapid and synchronous release of GABA onto local interneurons in the glomerular and inframitral circuits of the OB, which also reduced the spike precision of mitral/tufted cells in response to simulated stimuli. In addition, BF GABAergic inhibition modulated local oscillations in a layer-specific manner. The intensity of locally evokedθoscillations was decreased upon activation of top-down inhibition in the glomerular circuit, while evokedγoscillations were reduced by inhibition of granule cells. Furthermore, BF GABAergic input reduced dendrodendritic inhibition in mitral/tufted cells. Together, these results suggest that long-range GABAergic neurons from the BF are well suited to influence temporal and spatial aspects of processing by OB circuits.
Chronic high glyphosate exposure delays individual worker bee (Apis melliferaL.) development under field conditions
Authors: Odemer Richard , Alkassab Abdulrahim T. , Bischoff Gabriela , Frommberger Malte , Wernecke Anna , Wirtz Ina P. , Pistorius Jens , Odemer Franziska 
Published: July 2020

ABSTRACTThe ongoing debate about glyphosate-based herbicides (GBH) and their implications for beneficial arthropods give rise to controversy. This research was carried out to cover possible sublethal GBH effects on brood and colony development, adult survival, and overwintering success of honey bees (Apis melliferaL.) under field conditions. Residues in bee relevant matrices such as nectar, pollen and plants were measured in addition. To address these questions, we adopted four independent study approaches. For brood effects and survival, we orally exposed mini-hives housed in the “Kieler mating-nuc” system to sublethal concentrations of 4.8 mg glyphosate/kg (T1, low) and 137.6 mg glyphosate/kg (T2, high) over the period of one brood cycle (21 days). Brood development and colony conditions were assessed after a modified OECD method (No. 75). For adult survival, we weighed and labeled freshly emerged workers from exposed colonies and introduced them into non-contaminated mini-hives to monitor life span for 25 consecutive days. Results from these experiments showed a trivial effect of GBH on colony conditions and survival of individual workers, even though hatching weight was reduced in T2. The brood termination rate (BTR) in the T2 treatment, however, was more than doubled (49.84%) when compared to the control (22.11%) or T1 (20.69%). This was surprising as T2 colonies gained similar weight and similar numbers of bees per colony compared to the control, indicating equal performance. Obviously, the brood development in T2 was not “terminated” as expected by the OECD method terminology but rather “slowed down” for an unknown period of time. In light of these findings, we suggest that chronic high GBH exposure is capable of delaying worker brood development to a significant extent while no further detrimental effects seem to appear at the colony level. Against this background, we discuss additional results and possible consequences of GBH for honey bee health.
DIET INFLUENCES PERIPHERAL AMYLOID β METABOLISM: A ROLE FOR CIRCULATING INSULIN-LIKE GROWTH FACTOR I
Authors: Herrero-Labrador R. , Trueba-Saiz A. , Martinez-Rachadell L. , de Sevilla E. Fernandez , Diaz-Pacheco S. , Fernandez Ana F. , Torres Aleman I. 
Published: July 2020

AbstractObesity is a risk factor for Alzheimer’s disease (AD), but underlying mechanisms are not clear. We analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact on brain Aβ load, a major landmark of AD pathology. Overweight mice showed increased peripheral Aβ clearance by the liver, the major site of elimination of systemic Aβ, but unaltered brain Aβ levels. Since circulating insulin-like growth factor I (IGF-I) modulates brain Aβ clearance, and is increased in serum of overweight mice, we determined whether it affects peripheral Aβ clearance. We found that Aβ uptake by hepatocytes is stimulated by IGF-I. Moreover, mice with low serum IGF-I levels show reduced peripheral Aβ clearance. In the brain, IGF-I favored association of its receptor (IGF-IR) with Aβ precursor protein (APP), and at the same time stimulated non-amyloidogenic processing of APP in astrocytes, as indicated by an increased sAPPα/sAPPβ ratio after IGF-I treatment. Since serum IGF-I enters into the brain in an activity-dependent manner, we analyzed in overweight mice the effect of brain activation by environmental enrichment (EE) on brain IGF-IR phosphorylation and its association to APP, as a readout of IGF-I activity. After EE, significantly less activation of brain IGF-IR phosphorylation and APP/IGF-IR association was found in overweight mice as compared to lean controls. Collectively, these results indicate that diet influences peripheral clearance of Aβ without affecting brain Aβ load. Increased serum IGF-I likely contributes to enhanced peripheral Aβ clearance in overweight mice, without affecting brain Aβ clearance probably because its brain entrance is reduced.
Evidence for reduced immune gene diversity and activity during the evolution of termites
Authors: He Shulin , Sieksmeyer Thorben , Che Yanli , Esparza Mora M. Alejandra , Stiblik Petr , Banasiak Ronald , Harrison Mark C. , Šobotník Jan , Wang Zongqing , Johnston Paul R. , McMahon Dino P. 
Published: July 2020

AbstractThe evolution of biological complexity is associated with the emergence of bespoke immune systems that maintain and protect organism integrity. Unlike the well studied immunity at the cell and individual level, little is known about the origins of immunity during the transition to eusociality, a major evolutionary transition comparable to the evolution of multicellular organisms from single-celled ancestors. We tackle this by characterizing the immune gene repertoire of 18 cockroach and termite species, spanning the spectrum of solitary, subsocial and eusocial lifestyles. We identified five significant immune gene family contractions and one immune gene family expansion along the spine of a time-calibrated phylogeny, correlating with key transitions in termite sociality. In cross-species comparisons of immune gene expression, we find that termites appear to have evolved a caste-specific social defense system at the expense of individual immune protection. Our study indicates that a major transition in organismal complexity entailed a fundamental reshaping of the immune system optimized for group over individual defense.
Severely ill COVID-19 patients display augmented functional properties in SARS-CoV-2-reactive CD8+T cells
Authors: Kusnadi Anthony , Ramírez-Suástegui Ciro , Fajardo Vicente , Chee Serena J , Meckiff Benjamin J , Simon Hayley , Pelosi Emanuela , Seumois Grégory , Ay Ferhat , Vijayanand Pandurangan , Ottensmeier Christian H 
Published: July 2020

ABSTRACTThe molecular properties of CD8+T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+T cells from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+T cell response to SARS-CoV-2 was ‘exhausted’ or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the non-exhausted subsets from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8+T cell memory responses in patients with severe COVID-19 illness. CD8+T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features. Cells with such features were mostly absent in SARS-CoV-2 responsive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+T cells responding to SARS-CoV-2.
Large genetic diversity and strong positive selection in F-box and GPCR genes among the wild isolates ofCaenorhabditis elegans
Authors: Ma Fuqiang , Lau Chun Yin , Zheng Chaogu 
Published: July 2020

AbstractThe F-box and chemosensory GPCR (csGPCR) gene families are greatly expanded in nematodes, including the model organismCaenorhabditis elegans, compared to insects and vertebrates. However, the intraspecific evolution of these two gene families in nematodes remain unexamined. In this study, we analyzed the genomic sequences of 330 recently sequenced wild isolates ofC. elegansusing a range of population genetics approaches. We found that F-box and csGPCR genes, especially theSrwfamily csGPCRs, showed much more diversity than other gene families. Population structure analysis and phylogenetic analysis divided the wild strains into eight non-Hawaiian and three Hawaiian subpopulations. Some Hawaiian strains appeared to be more ancestral than all other strains. F-box and csGPCR genes maintained a great amount of the ancestral variants in the Hawaiian subpopulation and their divergence among the non-Hawaiian subpopulations contributed significantly to population structure. F-box genes are mostly located at the chromosomal arms and high recombination rate correlates with their large polymorphism. Moreover, using both neutrality tests and Extended Haplotype Homozygosity analysis, we identified signatures of strong positive selection in the F-box and csGPCR genes among the wild isolates, especially in the non-Hawaiian population. Accumulation of high-frequency derived alleles in these genes was found in non-Hawaiian population, leading to divergence from the ancestral genotype. In summary, we found that F-box and csGPCR genes harbour a large pool of natural variants, which may be subjected to positive selection. These variants are mostly mapped to the substrate-recognition domains of F-box proteins and the extracellular and intracellular regions of csGPCRs, possibly resulting in advantages during adaptation by affecting protein degradation and the sensing of environmental cues, respectively.Significance statementThe small nematodeCaenorhabditis eleganshas emerged as an important organism in studying the genetic mechanisms of evolution. F-box and chemosensory GPCR proteins are two of the largest gene families inC. elegans. However, their intraspecific evolution withinC. eleganswas not studied before. In this work, using the nonsynonymous SNV (single nucleotide variant) data of 330C. eleganswild isolates, we found that F-box and chemosensory GPCR genes showed larger polymorphisms and stronger positive selection than other genes. The large diversity is likely the result of rapid gene family expansion, high recombination rate, and gene flow. Analysis of subpopulation suggests that positive selection of these genes occurred most strongly in the non-Hawaiian population, which underwent a selective sweep possibly linked to human activities.
Aedes albopictus(Skuse) susceptibility status to agrochemical-insecticides used in durian plantating systems in southern Thailand
Authors: Ratisupakorn Sakda , Lorn Sokchan , Dada Nsa , Ngampongsai Aran , Chaivisit Pawit , Ritthison Wanapa , Tainchum Krajana 
Published: July 2020

ABSTRACTHigh rates of dengue, chikungunya, and zika morbidity occur in southern Thailand. The intensive application of insecticides in orchards could impact not only agricultural insect pests, but also non-target insects, such as mosquitoes, or non-target beneficial insects. In this study, the population density and insecticide susceptibility ofAedes albopictuspopulations to field application concentrations of four agrochemical insecticides – cypermethrin, chlorpyrifos, carbaryl, and imidacloprid were examined. Mosquito eggs were collected from durian cultivation sites in five provinces in southern Thailand and hatched and allowed to develop to the adult stage. The study sites were categorized into three groups based on insecticide application; intensive-application of insecticides (IA), less-application of insecticides (LA), and no application of insecticides (NA). Twenty ovitraps were deployed for at least three consecutive days at each study site to collect mosquito eggs and to determine theAe. albopictuspopulation density then WHO tube assays being used to determine the susceptibility of adult mosquitoes to selected insecticides. This study represents the first report of the agrochemical insecticide susceptibility status ofAe. albopictuscollected from durian orchards in southern Thailand. The study found that the populations ofAe. albopictuswere susceptible to chlorpyrifos, but showed reduced mortality following exposure to lambda-cyhalothrin, carbaryl, and imidacloprid which is suggestive of the existence of resistance. These findings provide new insights into mosquito insecticide resistance focusing onAe. albopictuspopulations and has important implications for mosquito and mosquito-borne disease control in Thailand as well as providing baseline data on which future studies can develop.
Loss of Cdk5rap2 triggers cellular senescence via β-catenin-mediated downregulation of WIP1
Authors: Wang Xidi , Sipila Patrick , Si Zizhen , Rosales Jesusa L. , Gao Xu , Lee Ki-Young 
Published: July 2020

AbstractLoss-of-function mutations in Cdk5rap2 is associated with the developmental disorders, primary microcephaly and primordial dwarfism, but the underlying molecular link remains obscure. Here, we show that Cdk5rap2 loss in BJ-5ta human fibroblasts triggers senescence that is associated with proliferation defect, which is manifested as small body size in Cdk5rap2an/anmice. In fibroblasts, Cdk5rap2 loss induces p53 Ser15 phosphorylation that correlates with decreased level of the p53 phosphatase, WIP1. Ectopic WIP1 expression reverses senescence in Cdk5rap2-depleted cells, linking senescence to WIP1 downregulation. Cdk5rap2 interacts with GSK3β, increasing inhibitory Ser9 phosphorylation in GSK3β, which phosphorylates and tags β-catenin for degradation. Thus, Cdk5rap2 loss decreases GSK3β Ser9 phosphorylation and increases GSK3β activity, reducing β-catenin that affects expression of NF-κB target genes, including WIP1. Consequently, Cdk5rap2 or β-catenin depletion downregulates WIP1. GSK3β Inhibition in Cdk5rap2-depleted cells restores β-catenin and WIP1 levels, reducing p53 Ser15 phosphorylation and preventing senescence. Conversely, WIP1 inhibition increases p53 Ser15 phosphorylation and senescence in Cdk5rap2-depleted cells lacking GSK3β activity. Senescence through GSK3β/β-catenin downregulation of WIP1 may contribute to the developmental disorders associated with Cdk5rap2 loss-of-function.
Assessment of endemic northern swamp deer (Rucervus duvaucelii duvaucelii) distribution and identification of priority conservation areas through modeling and field surveys across north India
Authors: Paul Shrutarshi , Sarkar Debanjan , Patil Abhilash , Ghosh Tista , Talukdar Gautam , Kumar Mukesh , Habib Bilal , Nigam Parag , Mohan Dhananjai , Pandav Bivash , Mondol Samrat 
Published: July 2020

AbstractRecent declines in large herbivores have led to significant conservation efforts globally. However, the niche-specific megaherbivores residing outside protected areas face more imminent extinction threats. Swamp deer, the obligate grassland-dwelling endemic cervid is the most extinction-prone megaherbivore in the Indian subcontinent. Limited information on distribution and habitat status pose significant conservation and management challenges for the remaining fragmented populations in north, north-east and central India. To this end, we combined exhaustive field surveys and Maximum Entropy (MaxEnt) modeling to generate the most detailed distribution map for the northern swamp deer subspecies. We used primary data from more than 6000 km2field surveys and eight ecologically relevant covariates for model predictions. Grassland cover, annual mean temperature and distance from water were the major factors that predicted the species distribution. Models predicted swamp deer distribution in only ~3% of the entire landscape, covering both protected (~1.4%) as well as non-protected (~1.6%) areas. Our validation surveys in some of these predicted areas confirmed swamp deer presence and indicated ~85% model accuracy. Finally, we identified four ‘Priority Conservation Areas’ still retaining adequate grassland habitat and species presence that require immediate attention to ensure population connectivity across this landscape. These results highlight the importance of the marginalized grassland ecosystems of northern India that still retains high biodiversity. We suggest a swamp deer-centric conservation approach to protect these human-dominated habitats and emphasize in generating such information for other endemic, habitat-specialist species across the globe.
Activation of the pro-resolving receptors Fpr2/3 attenuate lipopolysaccharide-induced inflammatory microglial activation
Authors: Wickstead Edward S. , Elliott Bradley T. , Biggs Christopher , Getting Stephen J. , McArthur Simon 
Published: July 2020

AbstractNeuroinflammation driven primarily by microglia directly contributes to neuronal death in many neurodegenerative diseases. Classical anti-inflammatory approaches aim to suppress pro-inflammatory mediator production, but exploitation of inflammatory resolution, the active endogenous process whereby inflammation is terminated, may also be of benefit. A key driver of peripheral inflammatory resolution, formyl peptide receptors 2/3 (Fpr2/3), is expressed by microglia, but its therapeutic potential in neurodegeneration remains unclear. Here, we sought to provide a proof-of-principle that Fpr2/3 targeting could reverse inflammatory microglial activation induced by the potent bacterial inflammogen lipopolysaccharide (LPS). Stimulation of murine BV2 microglia with LPS triggered release of nitric oxide, TNFα and IL-10, upregulated surface expression of CD38 and CD40 and suppressed CD206, all of which were reduced by subsequent treatment with the Fpr2/3 ligand C43. Cellular exposure to LPS also stimulated NADPH oxidase and mitochondrial derived reactive oxygen species production, effects reversed by C43 treatment. Mechanistic studies showed C43 to act through p38 MAPK phosphorylation and reduction of LPS-induced NFκB nuclear translocation through prevention of IκBα degradation. Here, we provide proof-of-concept data indicating exploitation of the pro-resolving receptor Fpr2/3 as a promising therapeutic strategy in neuroinflammatory conditions.
COCOA: Coordinate covariation analysis of epigenetic heterogeneity
Authors: Lawson John T. , Smith Jason P. , Bekiranov Stefan , Garrett-Bakelman Francine E. , Sheffield Nathan C. 
Published: July 2020

AbstractA key challenge in epigenetics is to determine the biological significance of epigenetic variation among individuals. Here, we present Coordinate Covariation Analysis (COCOA), a computational framework that uses covariation of epigenetic signals across individuals and a database of region sets to annotate epigenetic heterogeneity. COCOA is the first such tool for DNA methylation data and can also analyze any epigenetic signal with genomic coordinates. We demonstrate COCOA’s utility by analyzing DNA methylation, ATAC-seq, and multi-omic data in supervised and unsupervised analyses, showing that COCOA provides new understanding of inter-sample epigenetic variation. COCOA is available as a Bioconductor R package (http://bioconductor.org/packages/COCOA).