Multiple parallel cell lineages in the developing mammalian cerebral cortex

Science Advances, Journal Year: 2024, Volume and Issue: 10(13)

Published: March 27, 2024

Cortical neurogenesis follows a simple lineage: apical radial glia cells (RGCs) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones folded cortex, such as human, remains unclear. We used single-cell RNA sequencing from individual cortical ferret barcoded lineage tracking to determine the molecular diversity of progenitor their lineages. identified multiple RGC classes that initiate parallel lineages, converging onto common class newborn neuron. Parallel transcriptomic trajectories were repeated across conserved but not mouse. Neurons followed differentiation gyrus sulcus, different expressions human malformation genes. Progenitor cell multiplicity is mammalian cerebral cortex.

Language: Английский

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Network toxicology and molecular docking for the toxicity analysis of food contaminants: A case of Aflatoxin B1

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 188, P. 114687 - 114687

Published: April 23, 2024

Language: Английский

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Variations in rumen microbiota and host genome impacted feed efficiency in goat breeds

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 29, 2025

Introduction Improving feed efficiency (FE) is a significant goal in animal breeding programs. Variations FE and its relationship with rumen microbiota remain poorly understood across different goat breeds. Methods This study assessed the influence of microbiome host genome on 10 Shami (SH) goats Zaraibi (ZA) goats, all which were fed same diet. The animals genotyped using Illumina 65KSNP chip arrays v2 , their bacteria archaea investigated PCR-amplicon sequencing 16S rRNA gene. Results results showed that ZA exhibited higher than SH ( p < 0.05) greater relative abundance bacterial groups are involved degradation cellulose hemicelluloses, such as Bacteroidota Fibrobacterota, along genera Prevotella Lachnospiraceae AC2044 group, NK3A20 Succiniclasticum linked to carbohydrate nitrogen metabolism pathways. In addition, breed differences found affect proportions milk fatty acids. association analysis identified 26 windows containing several putative candidate genes, TMEM241 AP4S1 FTO HYAL2 BBS2 CD52 CRYBG2 PIGV WDTC1 EEF1A2 GBA2 FNIP1 ACSL6 STARD10 VPS26B ACAD8 GLB1L3 NRN1L LCAT SLC7A6 . These genes contributed traits Egyptian they obesity, metabolism, transport energy, vitamins, acids, proteins, lipids through diverse biological Discussion suggests specific genetic markers microbial could be used identify high-efficient individuals breeds, improving strategies for FE.

Language: Английский

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Machine Learning‐Enabled Drug‐Induced Toxicity Prediction

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Unexpected toxicity has become a significant obstacle to drug candidate development, accounting for 30% of discovery failures. Traditional assessment through animal testing is costly and time‐consuming. Big data artificial intelligence (AI), especially machine learning (ML), are robustly contributing innovation progress in toxicology research. However, the optimal AI model different types usually varies, making it essential conduct comparative analyses methods across domains. The diverse sources also pose challenges researchers focusing on specific studies. In this review, 10 categories drug‐induced examined, summarizing characteristics applicable ML models, including both predictive interpretable algorithms, striking balance between breadth depth. Key databases tools used prediction highlighted, toxicology, chemical, multi‐omics, benchmark databases, organized by their focus function clarify roles prediction. Finally, strategies turn into opportunities analyzed discussed. This review may provide with valuable reference understanding utilizing available resources bridge mechanistic insights, further advance application drugs‐induced

Language: Английский

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DNA methylation in cocaine use disorder–An epigenome-wide approach in the human prefrontal cortex

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 14, 2023

Cocaine use disorder (CUD) is characterized by a loss of control over cocaine intake and associated with structural, functional, molecular alterations in the human brain. At level, epigenetic are hypothesized to contribute higher-level functional structural brain changes observed CUD. Most evidence cocaine-associated comes from animal studies while only few have been performed using tissue.We investigated epigenome-wide DNA methylation (DNAm) signatures CUD post-mortem tissue Brodmann area 9 (BA9). A total N = 42 BA9 samples were obtained 21 individuals without diagnosis. We an association study (EWAS) analyzed CUD-associated differentially methylated regions (DMRs). To assess role differential methylation, we Gene Ontology (GO) enrichment analyses co-methylation networks weighted correlation network analysis. further age clocks for assessment biological age.While no cytosine-phosphate-guanine (CpG) site was at significance BA9, detected 20 DMRs. After annotation DMRs genes, identified Neuropeptide FF Receptor 2 (NPFFR2) Kalirin RhoGEF Kinase (KALRN) which previous behavioral response rodents known. Three four modules functionally related neurotransmission neuroplasticity. Protein-protein interaction (PPI) derived module hub genes revealed several addiction-related as highly connected nodes such Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), Nuclear Subfamily 3 Group Member 1 (NR3C1), Jun Proto-Oncogene, AP-1 Transcription Factor (JUN). In trend toward acceleration (EAA) remaining stable even after adjustment covariates.Results our highlight that differences DNAm levels particularly synaptic signaling This supports findings report on strong impact neurocircuits prefrontal cortex (PFC). Further needed follow up focusing integration transcriptomic proteomic data.

Language: Английский

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Genomic variant benchmark: if you cannot measure it, you cannot improve it

Genome biology, Journal Year: 2023, Volume and Issue: 24(1)

Published: Oct. 5, 2023

Abstract Genomic benchmark datasets are essential to driving the field of genomics and bioinformatics. They provide a snapshot performances sequencing technologies analytical methods highlight future challenges. However, they depend on technology, reference genome, available benchmarking methods. Thus, creating genomic dataset is laborious highly challenging, often involving multiple technologies, different variant calling tools, manual curation. In this review, we discuss their utility. Additionally, focus most recent genes with medical relevance challenging complexity.

Language: Английский

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Genome-wide landscape of runs of homozygosity and differentiation across Egyptian goat breeds

BMC Genomics, Journal Year: 2023, Volume and Issue: 24(1)

Published: Sept. 26, 2023

Understanding the genomic features of livestock is essential for successful breeding programs and conservation. This information scarce local goat breeds in Egypt. In current study, regions with selection signatures were identified as well runs homozygosity (ROH), inbreeding coefficients (FROH) fixation index (FST) detected Egyptian Nubian, Damascus, Barki Boer breeds. A total 46,268 SNP markers 337 animals available analyses. On average, 145.44, 42.02, 87.90 126.95 ROHs per individual autosomal genome respective The mean accumulative ROH lengths ranged from 46.5 Mb Damascus to 360 Nubian. short segments (< 2 Mb) most frequent all breeds, while longest (> 16 exclusively found highest average FROH was observed Nubian (~ 0.12) followed by 0.11), lowest 0.05) breed 0.03). estimated FST 0.14 (Egyptian Boer), 0.077 Barki), 0.075 Damascus), 0.071 (Barki 0.064 (Damascus 0.015 each pair Interestingly, multiple SNPs that accounted high values on chromosome 6 harboring ALPK1 KCNIP4. Genomic overlapping both harbor genes related immunity (IL4R, PHF23, GABARAP, GPS2, CD68), reproduction (SPATA2L, TNFSF12, TMEM95, RNF17), embryonic development (TCF25 SOX15) adaptation (MC1R, KDR, KIT), suggesting potential genetic adaptations environmental conditions. Our results contribute understanding architecture different may provide valuable effective preservation

Language: Английский

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Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer’s and coronary disease pathways

iScience, Journal Year: 2023, Volume and Issue: 26(4), P. 106408 - 106408

Published: March 14, 2023

Identification of proteins dysregulated by COVID-19 infection is critically important for better understanding its pathophysiology, building prognostic models, and identifying new targets. Plasma proteomic profiling 4,301 was performed in two independent datasets tested the association three outcomes (infection, ventilation, death). We identified 1,449 consistently associated both with any these outcomes. subsequently created highly accurate models that distinctively predict infection, death. These were enriched specific biological processes including cytokine signaling, Alzheimer's disease, coronary artery disease. Mendelian randomization gene network analyses eight causal 141 connected hub 35 known drug Our findings provide distinctive biomarkers severe outcomes, reveal their relationship to disease identify potential therapeutic targets

Language: Английский

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Synthetic and Medicinal Chemistry Approaches Toward WEE1 Kinase Inhibitors and Its Degraders

ACS Omega, Journal Year: 2023, Volume and Issue: 8(23), P. 20196 - 20233

Published: June 2, 2023

WEE1 is a checkpoint kinase critical for mitotic events, especially in cell maturation and DNA repair. Most cancer cells' progression survival are linked with elevated levels of kinase. Thus, has become new promising druggable target. A few classes inhibitors designed by rationale or structure-based techniques optimization approaches to identify selective acting anticancer agents. The discovery the inhibitor AZD1775 further emphasized as Therefore, current review provides comprehensive data on medicinal chemistry, synthetic approaches, methods, interaction profile inhibitors. In addition, PROTAC degraders their procedures, including list noncoding RNAs necessary regulation WEE1, also highlighted. From standpoint contents this compilation serve an exemplar design, synthesis, WEE1-targeted

Language: Английский

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Multi-trait GWAS for diverse ancestries: mapping the knowledge gap

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 17, 2024

Abstract Background Approximately 95% of samples analyzed in univariate genome-wide association studies (GWAS) are European ancestry. This bias toward ancestry populations screening also exists for other analyses and methods that often developed tested on only. However, existing data non-European populations, which modest sample size, could benefit from innovative approaches as recently illustrated the context polygenic risk scores. Methods Here, we extend assess potential limitations gains our multi-trait GWAS pipeline, JASS (Joint Analysis Summary Statistics), analysis ancestries. To this end, conducted joint 19 hematological traits glycemic across five ancestries (European (EUR), admixed American (AMR), African (AFR), East Asian (EAS), South-East (SAS)). Results We detected 367 new significant associations (15 Admixed 72 (AFR) 280 (EAS)). New represent 5%, 17% 13% AFR, AMR EAS respectively. Overall, testing increases replication associated loci by 15%. Pleiotropic effects were highly similar at (e.g. mean correlation between genetic EUR was 0.88). For traits, strong discrepancies tied to known evolutionary divergences: ARKC1 loci, is adaptive overcome p.vivax induced malaria. Conclusions Multi-trait can be a valuable tool narrow knowledge gap populations.

Language: Английский

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