bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of land-use intensity, productivity, and aboveground richness on seed rain in temperate grasslands
Authors: Klinger Y.P. , Kunze S. , Hölzel N. , Freitag M. , Klaus V.H. , Kleinebecker T. , Prati D. , Neuenkamp L 
Published: October 2024

AbstractSeed rain, the amount of seeds reaching an area via primary or secondary dispersal, affects the regeneration of plant communities and shapes the trajectory of future community composition. In agricultural grasslands, the composition and density in seed rain are mainly driven by land use, but drivers of seed rain quality and quantity along land-use gradients are poorly understood. We studied the effects of land-use intensity (LUI), its components (i.e. fertilization, mowing, and grazing), productivity, and aboveground vegetation composition and richness on seed rain.We collected the seed rain over a five-month period in 142 grasslands and identified emerging seedlings. Grass seedlings dominated seed rain most likely due to their high abundance in vegetation and intense and early seed set. Only ten species accounted for approximately 80 % of seedlings, with grasses such asLolium perenneandAlopecurus pratensisbeing most abundant. Forbs such asCerastium holosteoidesandVeronica arvensiswere abundant in seed rain despite lower cover, probably due to early and prolonged flowering and high seed production.Seed rain of grasses and forbs reacted differently to LUI and vegetation richness, LUI effects on grass seed rain mainly determined total seed density. Seed rain richness first increased with LUI, but decreased at higher LUI levels. Consequently, seed rain richness consistently increased with vegetation richness. This is reflected by a decrease in the abundance of stress strategists and an increase in ruderals in seed rain with increasing LUI and decreasing vegetation richness.Among LUI components, fertilization intensity most strongly affected seed rain density and composition, with negative effects at intermediate fertilization intensities. Mowing once a year increased seed rain density, whereas it decreased at higher mowing frequencies. Grazing intensity reduced overall seed density and richness by reducing grass seed density, while forb seed density remained unaffected.Synthesis: Land-use intensity and aboveground productivity significantly influence the species composition and seed densities in the seed rain of temperate agricultural grasslands. Higher land-use intensity and productivity increased seed production but reduced taxonomic and functional diversity in seed rain and may negatively impact ecosystem stability and resilience.
AMPK activation promotes transcriptional activation of TFEB through its dephosphorylation
Authors: Negoita Florentina , Bringas Conchita Fraguas , Hellberg Kristina , Luda Katarzyna M. , Liu Hongling , Cuenco Joyceline , Zhao Jin-Feng , Sathe Gajanan , Sapkota Gopal , Sakamoto Kei 
Published: October 2024

AbstractTranscription Factor EB (TFEB) is a critical regulator of lysosomal biogenesis, autophagy and energy homeostasis through controlling expression of genes belonging to the coordinated lysosomal expression and regulation network. AMP-activated protein kinase (AMPK) has been reported to phosphorylate TFEB at three conserved C-terminal serine residues (S466, S467, S469) and these phosphorylation events were essential for transcriptional activation of TFEB. In sharp contrast to this proposition, here we demonstrate that AMPK activation leads to dephosphorylation of the C-terminal sites, and that AMPK is dispensable for mTORC1-mediated/torin1-sensitive TFEB activation. We show that a synthetic peptide encompassing C-terminal serine residues of TFEB is a poor substrate of AMPK. Treatment of cells with AMPK activator (MK-8722) or mTOR inhibitor (torin1) robustly dephosphorylated TFEB not only at mTORC1-targeted N-terminal serine sites, but also at the C-terminal sites. Loss of function of AMPK abrogated MK-8722-but not torin1-induced dephosphorylation and induction of the vast majority of TFEB target genes.
Genome-wide variant analysis reveals divergent genetic signatures inAedes aegyptiand its morphological variantAedes aegyptivar.luciensis
Authors: Gupta Bhavna , Pandiyan G Navaneetha , Sumitha Melveettil Kishor , Paramasivan Rajaiah , Kalimuthu Mariapillai 
Published: October 2024

AbstractIn this study, we analysed the genetic diversity between the two morphotypes ofAedes aegyptiby identifying and characterizing genomic variants from low-coverage resequencing data. Four samples from each morphotype were sequenced, and high-quality variants were identified. Variants from the four samples of each morphotype were combined, considering only those present in all samples (missing variants were excluded). This resulted in 7,181 variants in the normal type and 4,513 in the variant type, with only 1,180 shared variants identified between the two morphotypes. Most variants in both types were found in non-coding regions. Chromosomal distribution showed comparable variant frequencies between morphotypes, with similar transition/transversion ratios. The neighbor-joining tree indicated distinct genetic clusters for each morphotype, likely driven by different demographic histories. We have not obtained much data on variations in the coding regions, probably due to low sequencing coverage. However, the significant genetic differentiation between the two morphotypes indicates important evolutionary processes at play. Understanding these variations is crucial from an epidemiological perspective, as they may lead to differences in vector competence for pathogens, potentially affecting transmission dynamics and disease risk.
Unraveling the diversity of protein-carbohydrate interfaces: insights from a multi-scale study
Authors: Gheeraert Aria , Guyon Frédéric , Pérez Serge , Galochkina Tatiana 
Published: October 2024

ABSTRACTProtein-carbohydrate interactions play a crucial role in numerous fundamental biological processes. Thus, description and comparison of the carbohydrate binding site (CBS) architecture is of great importance for understanding of the underlying biological mechanisms. However, traditional approaches for carbohydrate-binding protein analysis and annotation rely primarily on the sequence-based methods applied to specific protein classes. The recently released DIONYSUS database aims to fill this gap by providing tools for CBS comparison at different levels: both in terms of protein properties and classification, as well as in terms of atomistic CBS organization. In the current study, we explore DIONYSUS content using a combination of the suggested approaches in order to evaluate the diversity of the currently resolved non-covalent protein-carbohydrate interfaces at different scales. Notably, our analysis reveals evolutionary convergence of CBS in proteins with distinct folds and coming from organisms across different kingdoms of life. Furthermore, we demonstrate that a CBS structure based approach has the potential to facilitate functional annotation for the proteins with missing information in the existing databases. In particular, it provides reliable information for numerous carbohydrate-binding proteins from rapidly evolving organisms, whose analysis is particularly challenging for classical sequence-based methods.
Mechanoreceptors initiate innate immunity in response to microbial infections
Authors: Stucchi Giulia , Marongiu Laura , Rocca Giuseppe , Galli Marco , Celant Anna , Cozzi Stefano , Polissi Alessandra , Martorana Alessandra Maria , Vai Marina , Orlandi Ivan , Innocenti Metello , Granucci Francesca 
Published: October 2024

AbstractHow mammals mount an effective immune response against infectious agents remains an unresolved fundamental issue in biology. Here, we discovered an unforeseen two-tier mechanism of neutrophil recruitment during infections, in which mechanosensing is key to initiating innate immunity. Leveraging a skin infection model and pathogenic bacteria and fungi, we demonstrate that the early recruitment of neutrophils is mainly danger-driven and partly reminiscent of sterile inflammation. Mechanistically, neutrophil recruitment is initiated by a mechanosensor-dependent pathway, involving the activation of PIEZO1 channels. This leads to LTB4production, which, along with IL-1⍺, induces the release of CXCL1, promoting neutrophil arrival to the site of infection. In contrast, later neutrophil recruitment is TLR- and CXCL2-dependent, highlighting a shift towards a pathogen-driven response to sustain inflammation. These findings advance our understanding of innate immunity by uncovering that mechanical and biochemical signals integrate into a circuit that initiates innate immune responses to microbial infections.
Loss of long-chain acyl-CoA dehydrogenase protects against acute kidney injury
Authors: Chiba Takuto , Oda Akira , Zhang Yuxun , Bons Joanna , Bharathi Sivakama S , Pfister Katherine E. , Zhang Bob B. , Richert Adam C. , Schilling Birgit , Goetzman Eric S. , Sims-Lucas Sunder 
Published: October 2024

ABSTRACTProximal tubular epithelial cells (PTECs) are particularly vulnerable to acute kidney injury (AKI). While fatty acids are the preferred energy source for PTECs via fatty acid oxidation (FAO), FAO-mediated H2O2production in mitochondria has been shown to be a major source of oxidative stress. We have previously shown that a mitochondrial flavoprotein, long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes a key step in mitochondrial FAO, directly produces H2O2in vitro. Further we have established that loss of a lysine deacylase, Sirtuin 5 (Sirt5−/−), induces hypersuccinylation and inhibition of mitochondrial FAO genes to stimulate peroxisomal FAO and to protect against AKI. However, the role of LCAD has yet to be determined.Mass spectrometry data acquisition revealed that LCAD is hypersuccinylated inSirt5−/−kidneys after AKI. Following two distinct models of AKI, cisplatin treatment or renal ischemia/reperfusion (IRI), LCAD knockout mice (LCAD−/−) demonstrated renoprotection against AKI. Specifically,LCAD−/−kidneys displayed mitigated renal tubular injury, decreased oxidative stress, preserved mitochondrial function, enhanced peroxisomal FAO, and decreased ferroptotic cell death.LCAD deficiency confers protection against two distinct models of AKI. This suggests a therapeutically attractive mechanism whereby preserved mitochondrial respiration as well as enhanced peroxisomal FAO by loss of LCAD mediates renoprotection against AKI.
Development and validation of versatile species-specific primer assays for eDNA monitoring and authentication of 10 commercially important Peruvian marine species
Authors: Marín Alan , Alfaro Ruben , Reyes-Flores Lorenzo E. , Ingar Claudia , Santos-Rojas Luis E. , Alvarez-Jaque Irina B. , Rodríguez-Bernales Karen , Carbajal Cleila , Yon-Utrilla Angel , Zelada-Mázmela Eliana 
Published: October 2024

AbstractMolecular identification assays provide crucial support in the research and regulation of aquatic resources. Among them, species-specific primers provide strong discriminatory power for fast and simultaneous differentiation between closely related species. In this study, we used interspecific variations detected in two mitochondrial genes to develop species-specific primers for eDNA monitoring and identifying 10 fish and shellfish species commercially available within the Peruvian seafood sector. To ensure versatility and high specificity, our primers were subjected to PCR, qPCR, and sequencing methods, coupled with robust validation assays that included a) an in-silico stage using self-generated and public DNA sequences, b) an in-vitro stage using target species belonging to vouchered specimens, fresh and cooked commercial samples, early life stages, and broad taxa of non-target species, and c) an in-situ stage using eDNA samples from different Peruvian marine ecosystems. Our novel species-specific primers successfully passed the validation process with high efficiency and specificity in unequivocally identifying all target species with 100% accuracy and without cross-species amplifications, thereby making them valuable tools for eDNA monitoring, seafood authentication, and to identify and combat illegal, unreported and unregulated fishing. The identification assays presented herein can be used to support effective fishery management and conservation efforts not only in the Peruvian fishery sector but also in other countries where our target species also occur or are available as imported commodities.
Biocontrol efficiency and mechanism of novelStreptomyces luomodiensisSCA4-21 against bananaFusariumwilt
Authors: Liu Qiao , Zou Liangping , Chen Yufeng , Feng Junting , Wei Yongzan , Miaoyi Zhang , Li Kai , Zhao Yankun , Zhou Dengbo , Wang Wei , Qi Dengfeng , Xie Jianghui 
Published: October 2024

ABSTRACTThe soil-borne fungiFusarium oxysporumf. sp.cubensetropical race 4 (Foc TR4) causes bananaFusariumwilt, which seriously threats global banana production. Biocontrol has been considered viable alternative method to manage bananaFusariumwilt. In previous study, we found that novelS. luomodiensisSCA4-21 exhibited antifungal activity. Here, we revealed that the extracts of strain SCA4-21 significantly inhibited the growth of Foc TR4 hyphae and spore germination, severely disrupting the ultrastructure of Foc TR4 hyphal cells and spore morphology. These extracts also exhibited broad-spectrum antifungal activity against eight other phytopathogenic fungi. Furthermore, we demonstrated that strain SCA4-21 produce 32 volatile organic compounds, including five antifungal compounds. In a pot experiment, we discovered that the inoculation of strain SCA4-21 significantly inhibited the infection of Foc TR4 in banana seedling corms, achieving a biocontrol efficiency of 59.3%, and promoted the growth of banana seedlings. Additionally, this inoculation significantly enhanced the abundances of beneficial bacterial generaStreptomyces,Bacillus,Sphingomonas, andMassilia, as well as fungal generaMortierella,Purpureocillium,Gibellulopsis, andXenomyrothecium, while significantly reduced the abundances of pathogenic bacteria genusPantoeaand fungal genusFusarium, in the banana rhizosphere soil. Moreover, the inoculation of strain SCA4-21 significantly increased the enrichment of pathways such as carbohydrate metabolism, amino acid metabolism, and metabolism of terpenoids and polyketides. Therefore, we postulated that strain SCA4-21 may synergistically combat bananaFusariumwilt by producing antifungal compounds and enriching beneficial bacteria and fungi. Our findings present a promising biocontrol agent for the management of bananaFusariumwilt.IMPORTANCEBanana (Musaspp.) is one of the most popular fruit crops and the fourth largest food crop in developing countries within tropical and subtropical regions. However, the emergence and rapid spread of strain Foc TR4 seriously hinder the development of banana industry. Currently, there is no effective control measure available. Biological control holds potential due to its safety and effectiveness. Here, we found that the extracts ofS. luomodiensisSCA4-21 exhibited significant inhibitory effects on the hyphal growth and spore germination of Foc TR4, as well as severe destructive effects on its cell morphology and ultrastructure, and broad-spectrum antifungal activity. We also discovered that the inoculation of strain SCA4-21 significantly inhibited the infection of Foc TR4 in banana seedling corms, reduced the incidence index of bananaFusariumwilt, promoted the growth of banana seedlings, and enhances beneficial microbes and metabolic pathways, suggesting that strain SCA4-21 is a promising biocontrol agent.
Type-I IFNs induce GBPs and lysosomal defense in hepatocytes to control malaria
Authors: Marques-da-Silva Camila , Schmidt-Silva Clyde , Bowers Carson , Charles-Chess Essel , Shiau Justine C. , Park Eui-Soon , Yuan Zhongyu , Kim Bae-Hoon , Kyle Dennis E. , Harty John T. , MacMicking John D. , Kurup Samarchith P. 
Published: October 2024

AbstractPlasmodiumparasites undergo development and replication within the hepatocytes before infecting the erythrocytes and initiating clinical malaria. Although type-I interferons (IFNs) are known to hinderPlasmodiuminfection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers a pathway of lysosomal fusion with the parasitophorous vacuole (PV) to help clearPlasmodium. Second, guanylate-binding protein (GBP) 1 disruption of the PV activates caspase-1 inflammasome, inducing pyroptosis to remove the infected host cells. Remarkably, both human and mouse hepatocytes enlist these cell-autonomous immune programs to eliminatePlasmodium; their pharmacologic or genetic inhibition led to profound malarial susceptibility, and are essentialin vivo. In addition to identifying the IFN-I-mediated cell-autonomous immune circuits controllingPlasmodiuminfection in the hepatocytes, this study extends our understanding of how non-immune cells are integral to protective immunity against malaria.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) elicited dose-dependent shifts in the murine urinary metabolome associated with hepatic AHR-mediated differential gene expression
Authors: Sink Warren J. , Fling Russell , Yilmaz Ali , Nault Rance , Goniwiecha Delanie , Harkema Jack R. , Graham Stewart F. , Zacharewski Timothy 
Published: October 2024

ABSTRACTEpidemiological evidence suggests an association between dioxin and dioxin-like compound (DLC) exposure and human liver disease. The prototypical DLC, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been shown to induce the progression of reversible hepatic steatosis to steatohepatitis with periportal fibrosis and biliary hyperplasia in mice. Although the effects of TCDD toxicity are mediated by aryl hydrocarbon receptor (AHR) activation, the underlying mechanisms of TCDD-induced hepatotoxicity are unresolved. In the present study, male C57BL/6NCrl mice were gavaged every 4 days for 28 days with 0.03 - 30 μg/kg TCDD and evaluated for liver histopathology and gene expression as well as complementary 1-dimensional proton magnetic resonance (1D-1H NMR) urinary metabolic profiling. Urinary trimethylamine (TMA), trimethylamineN-oxide (TMAO), and 1-methylnicotinamide (1MN) levels were altered by TCDD at doses ≤ 3 μg/kg; other urinary metabolites, like glycolate, urocanate, and 3-hydroxyisovalerate, were only altered at doses that induced moderate to severe steatohepatitis. Bulk liver RNA-seq data suggested altered urinary metabolites correlated with hepatic differential gene expression corresponding to specific metabolic pathways. In addition to evaluating whether altered urinary metabolites were liver-dependent, published single-nuclear RNA-seq (snRNA-seq), AHR ChIP-seq, and AHR knockout gene expression datasets provide further support for hepatic cell-type and AHR-regulated dependency, respectively. Overall, TCDD-induced liver effects were preceded by and occurred with changes in urinary metabolite levels due to AHR-mediated changes in hepatic gene expression.
When to Trust Epigenetic Clocks: Avoiding False Positives in Aging Interventions
Authors: Borrus Daniel S. , Sehgal Raghav , Armstrong Jenel Fraij , Kasamoto Jessica , Gonzalez John , Higgins-Chen Albert 
Published: October 2024

AbstractRecent human studies have suggested that aging interventions can reduce aging biomarkers related to morbidity and mortality risk. Such biomarkers may potentially serve as early, rapid indicators of effects on healthspan. An increasing number of studies are measuring intervention effects on epigenetic clocks, commonly used aging biomarkers based on DNA methylation profiles. However, with dozens of clocks to choose from, different clocks may not agree on the effect of an intervention. Furthermore, changes in some clocks may simply be the result of technical noise causing a false positive result. To address these issues, we measured the variability between 6 popular epigenetic clocks across a range of longitudinal datasets containing either an aging intervention or an age-accelerating event. We further compared them to the same clocks re-trained to have high test-retest reliability. We find the newer generation of clocks, trained on mortality or rate-of-aging, capture aging events more reliably than those clocks trained on chronological age, as these show consistent effects (or lack thereof) across multiple clocks including high-reliability versions, and including after multiple testing correction. In contrast, clocks trained on chronological age frequently show sporadic changes that are not replicable when using high-reliability versions of those same clocks, or when using newer generations of clocks and these results do not survive multiple-testing correction. These are likely false positive results, and we note that some of these clock changes were previously published, suggesting the literature should be re-examined. This work lays the foundation for future clinical trials that aim to measure aging interventions with epigenetic clocks, by establishing when to attribute a given change in biological age to abona fidechange in the aging process.
Learning antibody sequence constraints from allelic inclusion
Authors: Jagota Milind , Hsu Chloe , Mazumder Thomas , Sung Kevin , DeWitt William S. , Listgarten Jennifer , Matsen Frederick A. , Ye Chun Jimmie , Song Yun S. 
Published: October 2024

AbstractAntibodies and B-cell receptors (BCRs) are produced by B cells, and are built of a heavy chain and a light chain. Although each B cell could express two different heavy chains and four different light chains, usually only a unique pair of heavy chain and light chain is expressed—a phenomenon known asallelic exclusion. However, a small fraction of naive-B cells violate allelic exclusion by expressing two productive light chains, one of which has impaired function; this has been calledallelic inclusion. We demonstrate that these B cells can be used to learn constraints on antibody sequence. Using large-scale single-cell sequencing data from humans, we find examples of light chain allelic inclusion in thousands of naive-B cells, which is an order of magnitude larger than existing datasets. We train machine learning models to identify the abnormal sequences in these cells. The resulting models correlate with antibody properties that they were not trained on, including polyreactivity, surface expression, and mutation usage in affinity maturation. These correlations are larger than what is achieved by existing antibody modeling approaches, indicating that allelic inclusion data contains useful new information. We also investigate the impact of similar selection forces on the heavy chain in mouse, and observe that pairing with the surrogate light chain significantly restricts heavy chain diversity.