bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiota induces aging-related leaky gut and inflammation by dampening mucin barriers and butyrate-FFAR2/3 signaling
Authors: Mishra Sidharth P , Wang Bo , Wang Shaohua , Nagpal Ravinder , Miller Brandi , Jain Shalini , Lee Jea Young , Borlongan Cesar , Taraphdar Subhash , Rane Sushil G. , Yadav Hariom 
Published: August 2021

ABSTRACTIncreased chronic inflammation is one of the key risk factors of aging-related disorders although its precise etiology remains elusive. Here, we demonstrate that aged, but not young, microbiota triggers inflammation by promoting gut permeability (leaky gut) via disruption of mucus barriers. Levels of the beneficial short-chain fatty acid, butyrate, are suppressed in the aged gut. Consistent with feedback regulation, the expression of butyrate-sensing receptors, free fatty acid receptor 2/3 (FFAR2/3), are also reduced in aged gut. Butyrate treatment of aged mice revereses the reduced mucin production, increased gut permeability and inflammation associated with low butyrate levels. In agreement, intestine-specific FFAR2/3 knockout mice manifest a compromised gut phenotype typically seen in aged mice,, such as increased gut permeability and inflammation with reduced mucin production. Taken together, our results demonstrate that an aged gut microbiota causally instigates inflammation by increasing gut permeability due to reduced butyrate levels, FFAR2/3 expression, and mucin barriers. Thus, butyrate-FFAR2/3 agonism could ameliorate the deleterious effects seen in aged gut and their implications on metabolic health.
Effects of the exercise-inducible myokine irisin on proliferation and malignant properties of ovarian cancer cells through the HIF-1 α signaling pathway
Authors: Zarei Marziyeh Alizadeh , Hosseini Elahe Seyed , Kashani Hamed Haddad , Ahmad Ejaz , Nikzad Hossein 
Published: August 2021

AbstractBackgroundExercise has been shown to be associated with reduced risk and improving outcomes of several types of cancers. Irisin −a novel exercise-related myokine- has been proposed to exert beneficial effects in metabolic disorders including cancer. No previous studies have investigated whether irisin may regulate malignant characteristics of ovarian cell lines.MethodsIn the present study, we aimed to explore the effect of irisin on viability and proliferation of ovarian cancer cells which was examined by MTT assay. Then, we evaluated migratory and invasive ability of the cells via transwell assays. Moreover, the percentage of apoptosis induction was determined by flowcytometery. Furthermore, the mRNA expression level of genes related to the aerobic respiration (HIF-1α, c-Myc, LDHA, PDK1 and VEGF) were detected by real-time PCR.ResultsOur data revealed that irisin treatment significantly attenuated the proliferation, migration and invasion of ovarian cancer cells. Besides, irisin induced apoptosis in ovarian cancer cells. We also observed that irisin regulated the expression of genes involved in aerobic respiration of ovarian cancer cells.ConclusionOur results indicate that irisin may play a crucial role in inhibition of cell growth and malignant characteristics of ovarian cancer. This findings may open up avenues for future studies to identify the further therapeutic use of irisin in ovarian cancer management.
Mapping Vegetation Species Succession in a Mountainous Grassland ecosystem using Landsat and Sentinel-2 data
Authors: Adagbasa G.E , Mukwada G 
Published: August 2021

AbstractVegetation species succession and composition are significant factors determining the rate of ecosystem biodiversity recovery after being disturbed and subsequently vital for sustainable and effective natural resource management and biodiversity. The succession and composition of grasslands ecosystems worldwide have significantly been affected by the accelerated changes in the environment due to natural and anthropogenic activities. Therefore, understanding spatial data on the succession of grassland vegetation species and communities through mapping and monitoring is essential to gain knowledge on the ecosystem and other ecosystem services. This study used a random forest machine learning classifier on the Google Earth Engine platform to classify grass vegetation species with Landsat 7 ETM+ and ASTER multispectral imager (MI) data resampled with the current Sentinel-2 MSI data to map and estimate the changes in vegetation species succession. The results indicate that ASTER IM has the least accuracy of 72%, Landsat 7 ETM+ 84%, and Sentinel-2 had the highest of 87%. The result also show that other species had replaced four dominant grass species totaling an area of about 49 km2 throughout the study.
Poly-gamma-glutamic acid secretion protects Bacillus subtilis from zinc and copper intoxication
Authors: Deol Reina , Louis Ashweetha , Glazer Harper Lee , Hosseinion Warren , Chandrangsu Pete 
Published: August 2021

AbstractZinc and copper are essential micronutrients that serve as a cofactors for numerous enzymes. However, when present at elevated concentrations, zinc and copper are highly toxic to bacteria. To combat the effects of zinc and copper excess, bacteria have evolved a wide array of defense mechanisms. Here, we show that the Gram positive soil bacterium, Bacillus subtilis, produces the extracellular polymeric substance, poly-gamma-glutamate (γ-PGA) as a protective mechanism in response to zinc and copper excess. Furthermore, we provide evidence that zinc and copper dependent γ-PGA production is independent of the DegS-DegQ two component regulatory system and likely occurs at a post-transcriptional level. These data provide new insight into bacterial metal resistance mechanisms and contribute to our understanding of the regulation of bacterial γ-PGA biosynthesis.ImportanceZinc and copper are potent antimicrobial compounds. As such, bacteria have evolved a diverse range of tools to prevent metal intoxication. Here, we show that the Gram-positive model organism, Bacillus subtilis, produces poly-gamma-glutamic acid (γ-PGA) as a protective mechanism against zinc and copper intoxication and that zinc and copper dependent γ-PGA production occurs by a yet undefined mechanism independent of known γ-PGA regulation pathways.
Identifying Therapeutic Strategies in IgA Nephropathy through Comprehensive Transcriptomic Characterization
Authors: Ofori Kenneth , Yakubu Amin , Rai Alex J. 
Published: August 2021

AbstractIgA nephropathy (IgAN) is an autoimmune disease and the most common primary glomerulonephritis. The four-hit hypothesis describes mechanism of the disease, from synthesis of galactose deficient IgA (GD-IgA), to recognition of GD-IgA by anti-glycan antibodies and deposition of the formed immune complex in the mesangium. Complement and coagulation cascade activation ensues, resulting in mesangial activation and cytokine release, podocyte injury, mesangial sclerosis and tubulointerstitial damage. Currently, there is no disease cure, and 30-40% of patients progress to end stage renal disease.Using complementary bioinformatic approaches, we demonstrate different levels of deviation of the transcriptome of the glomerulus in IgAN from normal, with the aim of identifying therapeutic targets. Approaches used herein include, deconvolution of the transcriptome to estimate immune constitution, co-regulation-based functional analysis of differentially expressed genes, modular co-expression analysis, network analysis of metabolic pathways and differential gene correlation analysis.We describe the immune composition in IgAN and the relatively low fold changes of the abundance of different immune cells and strength of immune signatures compared with control. Additionally, we identify enrichment of the intestinal network for IgA synthesis, repression of expression and dysregulation of networks of amino acid metabolism and PPAR signaling pathways in IgAN glomeruli. We also find loss of correlation between expression of matrix synthesizing and matrix degrading genes in IgAN.We conclude by discussing how therapies based on some nodes in these altered pathways described have been shown to be efficacious in IgAN and/or other inflammatory diseases and the potential of others in effective treatment.
Goal-centered representations in the human hippocampus
Authors: Crivelli-Decker Jordan , Clarke Alex , Park Seongmin A. , Huffman Derek J. , Boorman Erie , Ranganath Charan 
Published: August 2021

AbstractRecent work in cognitive and systems neuroscience has suggested that the hippocampus might support planning, imagination, and navigation by forming “cognitive maps” that capture the structure of physical spaces, tasks, and situations. Critically, navigation involves planning within a context and disambiguating similar contexts to reach a goal. We examined hippocampal activity patterns in humans during a goal-directed navigation task to examine how contextual and goal information are incorporated in the construction and execution of navigational plans. Results demonstrate that, during planning, the hippocampus carries a context-specific representation of a future goal. Importantly, this effect could not be explained by stimulus or spatial information alone. During navigation, we observed reinstatement of activity patterns in the hippocampus ahead of participants’ required actions, which was strongest for behaviorally relevant points in the sequence. These results suggest that, rather than simply representing overlapping associations, hippocampal activity patterns are powerfully shaped by context and goals.
In vivo hemostatic capability of a novel Tetra-PEG hydrogel
Authors: Okata Shinya , Hoshina Katsuyuki , Hanada Kazumasa , Kamata Hiroyuki , Fujisawa Ayano , Yoshikawa Yuki , Sakai Takamasa 
Published: August 2021

AbstractTetraStat is a novel synthetic sealant created with a tetra-armed polyethylene glycol (PEG) hydrogel. It has no risk of infection from biological pathogens and has a hemostatic mechanism independent of the blood coagulation pathway and controllable gelation. We evaluated the hemostatic effect of TetraStat in ex vivo and in vivo experiments for future clinical application. In ex vivo experiments using a circulatory system filled with phosphate-buffered saline under high pressure, needle punctures were astricted with TetraStat and two commercially available hemostatic agents (SURGICEL and TachoSil). For in vivo experiments, rat vena cavae were punctured with 14, 18, and 20 gauge needles, and hemorrhage occurred for several seconds. A porous PEG sponge soaked with TetraStat was applied as a hemostatic system for the massive hemorrhage. In the ex vivo experiment, punctures were sealed completely after 1 min astriction with TetraStat gel; in contrast, SURGICEL and TachoSil failed to seal the hole. In vivo experiments demonstrated that TetraStat successfully caused hemostasis in the punctured vena cava within 1 min of application in a dose-dependent manner. For SURGICEL and TachoSil, successful hemostasis occurred after 5 min astriction but was less frequent after 1 min astriction. Ex vivo and in vivo experiments revealed TetraStat’s high hemostatic ability under high pressure and in rat vena cava injuries under massive hemorrhage. A porous PEG sponge soaked with TetraStat is a promising advancement in hemostatic systems.
The IgE production is initially induced in subcutaneous fat and depends on extrafollicular B cells
Authors: Chudakov Dmitrii Borisovich , Fattakhova Gulnar Vaisovna , Konovalova Mariya Vladimirovna , Tsaregorotseva Daria Sergeevna , Shevchenko Marina Alexandrovna , Kotsareva Olga Dmitrievna , Sergeev Anton Andreevich , Svrshcehvskaya Elena Victorovna 
Published: August 2021

AbstractBackgroundGrowing body of evidence indicates that IgE production can be developed by mechanisms that differ from those responsible for IgG and IgA production. One potential possibility is generation of IgE producing cells from tissue-associated B-cells and/or through extrafollicular pathway. But the role of subcutaneous fat-associated B-cells in this process is poorly investigated. The aim of the present study was to investigate the role of different B- and T- cell subpopulations after long-term antigen administration in IgE response.MethodsBALB/c mice were immunized 3 times a eeks for 4 weeks in withers region enriched with subcutaneous fat with high and low antigen doses as well as by intraperitoneal route in region enriched with visceral fat for comparison.ResultsAfter long-term antigen administration that promotes the type of immune response which is more similar to one observed in young allergic children, subcutaneous fat tissue B-cells generates more rapid and active IgE class switched and IgE-produced cells. Although IgE production at later time points was initiated also in regional lymph nodes, the early IgE production was exclusively linked with subcutaneous fat. We observed that low-dose induced strong IgE production accompanied by minimal IgG1 production was linked with extrafollicular B-2 derived plasmablasts as well as extrafollicular T- helpers accumulation. Delayed IgE class switching in regional lymph nodes and visceral fat tissue was characterized by the absence of both stable plasmablasts and T-extrafollicular helpers accumulation.ConclusionExtrafollicular B- and T-cell responses in subcutaneous fat are necessary for early IgE class switching and sensitization process in the case of allergen penetration through skin.
Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens
Authors: Counoupas Claudio , Pino Paco , Stella Alberto O. , Ashley Caroline , Lukeman Hannah , Bhattacharyya Nayan D. , Tada Takuya , Anchisi Stephanie , Metayer Charles , Martinis Jacopo , Aggarwal Anupriya , Dcosta Belinda M. , Kint Joeri , Wurm Maria J , Landau Nathaniel R. , Steain Megan , Turville Stuart G , Wurm Florian M , David Sunil A. , Triccas James A. 
Published: August 2021

ABSTRACTGlobal control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern.
Single amino-acid mutation in a Drosophila melanogaster ribosomal protein: an insight in uL11 transcriptional activity
Authors: Grunchec Héloïse , Deraze Jérôme , Dardalhon-Cuménal Delphine , Ribeiro Valérie , Coléno-Costes Anne , Dias Karine , Bloyer Sébastien , Mouchel-Vielh Emmanuèle , Peronnet Frédérique , Thomassin Hélène 
Published: August 2021

ABSTRACTThe ribosomal protein uL11 is located at the basis of the ribosome P-stalk and plays a paramount role in translational efficiency. In addition, no mutant for uL11 is available suggesting that this gene is haplo-insufficient as many other Ribosomal Protein Genes (RPGs). We have previously shown that overexpression of Drosophila melanogaster uL11 enhances the transcription of many RPGs and Ribosomal Biogenesis genes (RiBis) suggesting that uL11 might globally regulate the level of translation through its transcriptional activity. Moreover, uL11 trimethylated on lysine 3 (uL11K3me3) interacts with the chromodomain of the Enhancer of Polycomb and Trithorax Corto, and both proteins co- localize with RNA Polymerase II at many sites on polytene chromosomes. These data have led to the hypothesis that the N-terminal end of uL11, and more particularly the trimethylation of lysine 3, supports the extra-ribosomal activity of uL11 in transcription. To address this question, we mutated the lysine 3 codon using a CRISPR/Cas9 strategy and obtained several lysine 3 mutants. We describe here the first mutants of D. melanogaster uL11. Unexpectedly, the uL11K3A mutant, in which the lysine 3 codon is replaced by an alanine, displays a genuine Minute phenotype known to be characteristic of RPG deletions (longer development, low fertility, high lethality, thin and short bristles) whereas the uL11K3Y mutant, in which the lysine 3 codon is replaced by a tyrosine, is unaffected. In agreement, the rate of translation decreases in uL11K3A but not in uL11K3Y. Co-immunoprecipitation experiments show that the interaction between uL11 and the Corto chromodomain is impaired by both mutations. RNA- seq analysis from wing imaginal discs shows enrichment in the GO categories “glutathione metabolism” for up-regulated genes in both uL11K3A and uL11K3Y mutants and “regulation of transcription” for down-regulated genes in uL11K3A only. Analysis of the cis-regulatory sequences of these genes suggests that uL11 might regulate transcription of target genes in concert with the couple of transcription factors Mad/Med that mediate response to the Bone Morphogenetic Protein (BMP) signaling pathway.
Data Matrix Normalization and Merging Strategies Minimize Batch-specific Systemic Variation in scRNA-Seq Data
Authors: Babcock Benjamin R. , Kosters Astrid , Yang Junkai , White Mackenzie L. , Ghosn Eliver E. B. 
Published: August 2021

AbstractSingle-cell RNA sequencing (scRNA-seq) can reveal accurate and sensitive RNA abundance in a single sample, but robust integration of multiple samples remains challenging. Large-scale scRNA-seq data generated by different workflows or laboratories can contain batch-specific systemic variation. Such variation challenges data integration by confounding sample-specific biology with undesirable batch-specific systemic effects. Therefore, there is a need for guidance in selecting computational and experimental approaches to minimize batch-specific impacts on data interpretation and a need to empirically evaluate the sources of systemic variation in a given dataset. To uncover the contributions of experimental variables to systemic variation, we intentionally perturb four potential sources of batch-effect in five human peripheral blood samples. We investigate sequencing replicate, sequencing depth, sample replicate, and the effects of pooling libraries for concurrent sequencing. To quantify the downstream effects of these variables on data interpretation, we introduced a new scoring metric, the Cell Misclassification Statistic (CMS), which identifies losses to cell type fidelity that occur when merging datasets of different batches. CMS reveals an undesirable overcorrection by popular batch-effect correction and data integration methods. We show that optimizing gene expression matrix normalization and merging can reduce the need for batch-effect correction and minimize the risk of overcorrecting true biological differences between samples.
Src acts with WNT/FGFRL signaling to pattern the planarian anteroposterior axis
Authors: Bonar Nicolle A. , Gittin David I. , Petersen Christian P. 
Published: August 2021

AbstractTissue identity determination is critical for regeneration, and the planarian anteroposterior (AP) axis uses positional control genes expressed from bodywall muscle to determine body regionalization. Canonical Wnt signaling establishes anterior versus posterior pole identities through notum and wnt1 signaling, and two Wnt/FGFRL signaling pathways control head and trunk domains, but their downstream signaling mechanisms are not fully understood. Here we identify a planarian Src homolog that restricts head and trunk identities to anterior positions. src-1(RNAi) animals formed enlarged brains and ectopic eyes and also duplicated trunk tissue, similar to a combination of Wnt/FGFRL RNAi phenotypes. src-1 was required for establishing territories of positional control gene expression, indicating it acts at an upstream step in patterning the AP axis. Double RNAi experiments and eye regeneration assays suggest src-1 can act in parallel to at least some Wnt and FGFRL factors. Co-inhibition of src-1 with other posterior-promoting factors led to dramatic patterning changes and a reprogramming of Wnt/FGFRLs into controlling new positional outputs. These results identify src-1 as a factor that promotes robustness of the AP positional system that instructs appropriate regeneration.HighlightsSrc-1 suppresses head and trunk identitySrc-1 can regulate positional control gene domainsSrc-1 likely acts independently of notum/Wnt and FGFRL signalsSrc-1 inhibition broadly sensitizes animals to AP pattern disruption
A method for high throughput image based antifungal screening
Authors: Sabburg Rosalie , Gregson Aphrika , Urquhart Andrew S. , Aitken Elizabeth A. B. , Smith Linda , Thatcher Louise F. , Gardiner Donald M. 
Published: August 2021

AbstractRobust antifungal screening is technically challenging particularly for filamentous fungi. We present a method for undertaking antifungal screening assays that builds upon existing broth dilution protocols and incorporates time resolved image-based assessment of fungal growth. We show that the method performs with different fungi, particularly those for which spores can be used as inoculum, and with different compound classes, can accurately assess susceptibility or otherwise in only few hours, performs well even without replication and can even account for differences in inherent growth properties of strains.