Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multisystemic disease with a multifactorial pathogenesis involving dietary, environmental, and genetic factors. Previous mouse models suggested that circadian misalignment may additionally influence its development as it influences metabolism in diverse organs including the liver. Further, data from sleep questionnaires proved sleep-wake disruption in patients with MASLD.
View Article and Find Full Text PDFUnlabelled: Andean highland soils contain significant quantities of soil organic carbon (SOC); however, more efforts still need to be made to understand the processes behind the accumulation and persistence of SOC and its fractions. This study modeled SOC variables-SOC, refractory SOC (RSOC), and the C isotope composition of SOC (δC)-using machine learning (ML) algorithms in the Central Andean Highlands of Peru, where grasslands and wetlands ("bofedales") dominate the landscape surrounded by Junin National Reserve. A total of 198 soil samples (0.
View Article and Find Full Text PDFApolipoprotein E4 (ApoE4), the strongest genetic risk factor for sporadic Alzheimer's disease, is also a risk factor for microvascular pathologies leading to cognitive impairment, particularly subcortical white matter injury. These effects have been attributed to alterations in the regulation of the brain blood supply, but the cellular source of ApoE4 and the underlying mechanisms remain unclear. In mice expressing human ApoE3 or ApoE4, we report that border-associated macrophages (BAMs), myeloid cells closely apposed to neocortical microvessels, are both sources and effectors of ApoE4 mediating the neurovascular dysfunction through reactive oxygen species.
View Article and Find Full Text PDFWhen adaptive phenotypic variation or quantitative trait loci map within an inverted segment of a chromosome, researchers often despair because the suppression of crossing over will prevent the discovery of selective target genes that established the rearrangement. If an inversion polymorphism is old enough, then the accumulation of gene conversion tracts offers the promise that quantitative trait loci or selected loci within inversions can be mapped. The inversion polymorphism of Drosophila pseudoobscura is a model system to show that gene conversion analysis is a useful tool for mapping selected loci within inversions.
View Article and Find Full Text PDFCover cropping is a promising strategy to improve soil health, but it may also trigger greenhouse gas emissions, especially nitrous oxide (NO). Beyond nitrogen (N) availability, cover crop residue decomposition may accelerate heterotrophic respiration to limit soil O availability, hence promote NO emissions from denitrification under sub-optimal water-filled pore space (WFPS) conditions that are typically not conducive to large NO production. We conducted a 21-day incubation experiment to examine the effects of contrasting cover crop residue (grass vs legume) decomposition on soil O and biogeochemical changes to influence NO and CO emissions from N labeled fertilized soils under 50% and 80% WFPS levels.
View Article and Find Full Text PDFObjectives: To understand patients' experiences with diabetes care during the COVID-19 pandemic, with an emphasis on rural, medically underserved, and/or minoritised racial and ethnic groups in the Midwestern USA.
Design: Community-engaged, semi-structured interviews were conducted by medical student researchers trained in qualitative interviewing. Transcripts were prepared and coded in the language in which the interview was conducted (English or Spanish).
Background: Idiosyncratic drug-induced liver injury (DILI) is a rare, unpredictable hepatic adverse event and the most common cause of acute liver failure in Europe and the US. Ribociclib is a potent Cyclin-dependent kinase 4 and 6 (CDK4/6)-inhibitor administered for advanced hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Previous reports have shown hepatotoxicity without liver necrosis related to ribociclib.
View Article and Find Full Text PDFHypertension (HTN), a disease afflicting over one billion individuals worldwide, is a leading cause of cognitive impairment, the mechanisms of which remain poorly understood. In the present study, in a mouse model of HTN, we find that the neurovascular and cognitive dysfunction depends on interleukin (IL)-17, a cytokine elevated in individuals with HTN. However, neither circulating IL-17 nor brain angiotensin signaling can account for the dysfunction.
View Article and Find Full Text PDFApolipoprotein-E4 (ApoE4), the strongest genetic risk factor for sporadic Alzheimer's disease, is also a risk factor for microvascular pathologies leading to cognitive impairment, particularly subcortical white matter injury. These effects have been attributed to alterations in the regulation of the brain blood supply, but the cellular source of ApoE4 and the underlying mechanisms remain unclear. In mice expressing human ApoE3 or ApoE4 we report that border associated macrophages (BAM), myeloid cells closely apposed to neocortical microvessels, are both the source and the target of the ApoE4 mediating the neurovascular dysfunction through reactive oxygen species.
View Article and Find Full Text PDFAnn Clin Transl Neurol
October 2023
Objective: Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder caused by autosomal-dominant pathogenic variants in either the TSC1 or TSC2 gene, and it is characterized by hamartomas in multiple organs, such as skin, kidney, lung, and brain. These changes can result in epilepsy, learning disabilities, and behavioral complications, among others. The mechanistic link between TSC and the mechanistic target of the rapamycin (mTOR) pathway is well established, thus mTOR inhibitors can potentially be used to treat the clinical manifestations of the disorder, including epilepsy.
View Article and Find Full Text PDFMicro and nanoplastics (MPs and NPs, respectively) in agricultural soil ecosystems represent a pervasive global environmental concern, posing risks to soil biota, hence soil health and food security. This review provides a comprehensive and current summary of the literature on sources and properties of MNPs in agricultural ecosystems, methodology for the isolation and characterization of MNPs recovered from soil, MNP surrogate materials that mimic the size and properties of soil-borne MNPs, and transport of MNPs through the soil matrix. Furthermore, this review elucidates the impacts and risks of agricultural MNPs on crops and soil microorganisms and fauna.
View Article and Find Full Text PDFBackground & Aims: Recurrent somatic mutations of the RPS6KA3 gene encoding for the serine/threonine kinase RSK2 were identified in hepatocellular carcinomas (HCCs), suggesting its tumour-suppressive function. Our goal was to demonstrate the tumour suppressor role of RSK2 in the liver and investigate the functional consequences of its inactivation.
Methods: We analysed a series of 1,151 human HCCs for RSK2 mutations and 20 other driver genetic alterations.
Microplastics (MP) are an abundant, long-lasting, and widespread type of environmental pollution that is of increasing concern as it might pose a serious threat to ecosystems and species. However, these threats are still largely unknown for amphibians. Here, we used the African clawed frog (Xenopus laevis) as a model species to investigate whether polyethylene MP ingestion affects amphibian growth and development and leads to metabolic changes across two consecutive life stages (larvae and juveniles).
View Article and Find Full Text PDFMicroplastics (MPs) and nanoplastics (NPs) from mulch films and other plastic materials employed in vegetable and small fruit production pose a major threat to agricultural ecosystems. For conducting controlled studies on MPs' and NPs' (MNPs') ecotoxicity to soil organisms and plants and fate and transport in soil, surrogate MNPs are required that mimic MNPs that form in agricultural fields. We have developed a procedure to prepare MPs from plastic films or pellets using mechanical milling and sieving, and conversion of the resultant MPs into NPs through wet grinding, both steps of which mimic the degradation and fragmentation of plastics in nature.
View Article and Find Full Text PDFBackground: Certified training courses in all-terrain vehicle (ATV) operation are recommended, but little has been published regarding how they affect riding behaviors. Our objectives were to determine adolescents' ATV riding exposures, crashes and injuries, and the association of completing certified ATV training on riding behaviors.
Methods: Respondents completed an anonymous paper survey at 30 school districts approximately one year after participating in the Safety Tips for ATV Riders (STARs) program.
Soils are the largest organic carbon reservoir and are key to global biogeochemical cycling, and microbes are the major drivers of carbon and nitrogen transformations in the soil systems. Thus, virus infection-induced microbial mortality could impact soil microbial structure and functions. In this study, we recovered 260 viral operational taxonomic units (vOTUs) in samples collected from soil taken from four nitrogen fertilization (N-fertilization) and cover-cropping practices at an experimental site under continuous cotton production evaluating conservation agricultural management systems for more than 40 years.
View Article and Find Full Text PDFBackground: Disparities in objective assessments in graduate medical education such as the In-Training Examination (ITE) that disadvantage women and those self-identifying with race/ethnicities underrepresented in medicine (URiM) are of concern.
Objective: Examine ITE trends longitudinally across post-graduate year (PGY) with gender and race/ethnicity.
Design: Longitudinal analysis of resident ITE metrics at 7 internal medicine residency programs, 2014-2019.
Philos Trans R Soc Lond B Biol Sci
August 2022
DNA within chromosomes in the nucleus is non-randomly organized into chromosome territories, compartments and topologically associated domains (TADs). Chromosomal rearrangements have the potential to alter chromatin organization and modify gene expression leading to selection against these structural variants. has a wealth of naturally occurring gene arrangements that were generated by overlapping inversion mutations caused by two chromosomal breaks that rejoin the central region in reverse order.
View Article and Find Full Text PDFPurpose: To assess the association between internal medicine (IM) residents' race/ethnicity and clinical performance assessments.
Method: The authors conducted a cross-sectional analysis of clinical performance assessment scores at 6 U.S.
Agricultural practices alter the structure and functions of soil microbial community. However, few studies have documented the alterations of bacterial communities in soils under long-term conservation management practices for continuous crop production. In this study, we evaluated soil bacterial diversity using 16S rRNA gene sequencing and soil physical and chemical properties within 12 combinations of inorganic N fertilization, cover cropping, and tillage throughout a cotton production cycle.
View Article and Find Full Text PDFBackground: Brain tumor formation and progression are dictated by cooperative interactions between neoplastic and non-neoplastic cells. This stromal dependence is nicely illustrated by tumors arising in the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome, where children develop low-grade optic pathway gliomas (OPGs). Using several authenticated -OPG murine models, we previously demonstrated that murine -OPG growth is regulated by T cell function and microglia Ccl5 production, such that their inhibition reduces tumor proliferation .
View Article and Find Full Text PDFThe active layer of permafrost in Ny Ålesund, Svalbard (79°N) around the Bayelva River in the Leirhaugen glacier moraine is measured as a small net carbon sink at the brink of becoming a carbon source. In many permafrost-dominating ecosystems, microbes in the active layers have been shown to drive organic matter degradation and greenhouse gas production, creating positive feedback on climate change. However, the microbial metabolisms linking the environmental geochemical processes and the populations that perform them have not been fully characterized.
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