5,273,810 results match your criteria: "Genetics & Genomics University of Georgia Athens Georgia.[Affiliation]"

The analysis of circulating tumour DNA (ctDNA) through minimally invasive liquid biopsies is promising for early multi-cancer detection and monitoring minimal residual disease. Most existing methods focus on targeted deep sequencing, but few integrate multiple data modalities. Here, we develop a methodology for ctDNA detection using deep (80x) whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive approach than bisulphite sequencing, which permits the simultaneous analysis of genomic and methylomic data.

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Biomethanation is a crucial process occurring in natural and engineered systems which can reduce carbon dioxide to methane impacting the global carbon cycle. However, little is known about the effect of on-and-off gaseous provision and micronutrients on bioconversion. Here, anaerobic microbiomes underwent intermittent feeding with incremental starvations and selective metal supplementation to assess the impact of hydrogen and carbon dioxide availability on microbial physiology.

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The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is an intronic GC repeat expansion in C9orf72. The repeats undergo bidirectional transcription to produce sense and antisense repeat RNA species, which are translated into dipeptide repeat proteins (DPRs). As toxicity has been associated with both sense and antisense repeat-derived RNA and DPRs, targeting both strands may provide the most effective therapeutic strategy.

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Tetrahydrocannabinol (THC) is the principal psychoactive compound derived from the cannabis plant Cannabis sativa and approved for emetic conditions, appetite stimulation and sleep apnea relief. THC's psychoactive actions are mediated primarily by the cannabinoid receptor CB. Here, we determine the cryo-EM structure of HU210, a THC analog and widely used tool compound, bound to CB and its primary transducer, G.

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Protein translocation across cellular membranes is an essential and nano-scale dynamic process. In the bacterial cytoplasmic membrane, the core proteins in this process are a membrane protein complex, SecYEG, corresponding to the eukaryotic Sec61 complex, and a cytoplasmic protein, SecA ATPase. Despite more than three decades of extensive research on Sec proteins, from genetic experiments to cutting-edge single-molecule analyses, no study has visually demonstrated protein translocation.

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ATR plays key roles in cellular responses to DNA damage and replication stress, a pervasive feature of cancer cells. ATR inhibitors (ATRi) are in clinical development for treating various cancers, including those with high replication stress, such as is elicited by ARID1A deficiency, but the cellular mechanisms that determine ATRi efficacy in such backgrounds are unclear. Here, we have conducted unbiased genome-scale CRISPR screens in ARID1A-deficient and proficient cells treated with ATRi.

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One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) which are often essential for viral replication, transcription, or translation. In this report, we discovered a series of coumarin derivatives that bind to a four-way RNA helix called SL5 in the 5' UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a sequencing-based method namely cgSHAPE-seq, in which an acylating probe was directed to crosslink with the 2'-OH group of ribose at the binding site to create read-through mutations during reverse transcription.

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The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes X and Y, we create a small variant benchmark set with 111,725 variants for the Genome in a Bottle HG002 reference material. We develop an active evaluation approach to demonstrate the benchmark set reliably identifies errors in challenging genomic regions and across short and long read callsets.

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The 22q11.2 deletion is a risk factor for multiple psychiatric disorders including schizophrenia and also increases vulnerability to middle-ear problems that can cause hearing impairment. Up to 60% of deletion carriers experience hearing impairment and ~30% develop schizophrenia in adulthood.

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Multidrug resistance-associated protein 2 (MRP2) is an ATP-powered exporter important for maintaining liver homeostasis and a potential contributor to chemotherapeutic resistance. Using cryogenic electron microscopy (cryo-EM), we determine the structures of human MRP2 in three conformational states: an autoinhibited state, a substrate-bound pre-translocation state, and an ATP-bound post-translocation state. In the autoinhibited state, the cytosolic regulatory (R) domain plugs into the transmembrane substrate-binding site and extends into the cytosol to form a composite ATP-binding site at the surface of nucleotide-binding domain 2.

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An abnormal expansion of a GGGGCC (GC) hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we develop here a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform curbed the expression of the GC repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci, reduced the production of a dipeptide repeat protein, and reversed transcriptional deficits.

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Structural basis of RNA polymerase complexes in African swine fever virus.

Nat Commun

January 2025

State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

African swine fever virus is highly contagious and causes a fatal infectious disease in pigs, resulting in a significant global impact on pork supply. The African swine fever virus RNA polymerase serves as a crucial multifunctional protein complex responsible for genome transcription and regulation. Therefore, it is essential to investigate its structural and functional characteristics for the prevention and control of African swine fever.

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Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase that unwinds DNA during S-phase. Here, we report the reconstitution of human DNA licensing using purified proteins.

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Predicting cell morphological responses to perturbations using generative modeling.

Nat Commun

January 2025

Department of Computational Health, Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.

Advancements in high-throughput screenings enable the exploration of rich phenotypic readouts through high-content microscopy, expediting the development of phenotype-based drug discovery. However, analyzing large and complex high-content imaging screenings remains challenging due to incomplete sampling of perturbations and the presence of technical variations between experiments. To tackle these shortcomings, we present IMage Perturbation Autoencoder (IMPA), a generative style-transfer model predicting morphological changes of perturbations across genetic and chemical interventions.

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Protein lactylation is an emerging field. To advance the exploration of its biological functions, here we develop a comprehensive workflow that integrates proteomics to identify lactylated sites, genetic code expansion (GCE) for the expression of site-specifically lactylated proteins in living cells, and an integrated functional analysis (IFA) platform to evaluate their biological effects. Using a combined wet-and-dry-lab proteomics strategy, we identify a conserved lactylation at ALDOA-K147, which we hypothesize plays a significant biological role.

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Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution.

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Uncertainty remains regarding the role of diet in colorectal cancer development. We examined associations of 97 dietary factors with colorectal cancer risk in 542,778 Million Women Study participants (12,251 incident cases over 16.6 years), and conducted a targeted genetic analysis in the ColoRectal Transdisciplinary Study, Colon Cancer Family Registry, and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO).

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Physical unclonable functions (PUFs) are considered the most promising approach to address the global issue of counterfeiting. Current PUF devices are often based on a single stochastic process, which can be broken, especially since their practical encoding capacities can be significantly lower than the theoretical value. Here we present stochastic PUF devices with features across multiple length scales, which incorporate semiconducting polymer nanoparticles (SPNs) as fluorescent taggants.

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Integrating genomic, hyperspectral imaging (HSI), and environmental data enhances wheat yield predictions, with HSI providing detailed spectral insights for predicting complex grain yield (GY) traits. Incorporating HSI data with single nucleotide polymorphic markers (SNPs) resulted in a substantial improvement in predictive ability compared to the conventional genomic prediction models. Over the course of several years, the prediction ability varied due to diverse weather conditions.

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As the role of primary care providers (PCPs) in genetic medicine increases, there is a need for training related to the integration of genetics into primary care. However, little is known about PCPs' attitudes towards and perceived needs for such training. We conducted semi-structured interviews with nine PCPs to capture information about their perceptions of their role in genetics and their continuing medical educational needs related to genetics in primary care, and we conducted thematic analysis.

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Classical genomic prediction approaches rely on statistical associations between traits and markers rather than their biological significance. Biologically informed selection of genomic regions can help prioritize polymorphisms by considering underlying biological processes, making prediction models robust and accurate. Gene ontology (GO) terms can be used for this purpose, and the information can be integrated into genomic prediction models through marker categorization.

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In an attempt to stimulate further theory and research on only children, we introduce two conceptual distinctions: Only children as independent variables vs. only children as dependent variables; and only children by choice vs. only children by circumstances.

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Dual targeting of HSP90 and BCL-2 in breast cancer cells using inhibitors BIIB021 and ABT-263.

Breast Cancer Res Treat

January 2025

Rafet Kayış Faculty of Engineering, Department of Genetics and Bioengineering, Alanya Alaaddin Keykubat University, Antalya, Turkey.

Purpose: The incidence of breast cancer has been increasing in recent years, and monotherapy approaches are not sufficient alone in the treatment of breast cancer. In the combined therapy approach, combining two or three different agents in lower doses can mitigate the side effects on living cells and tissues caused by high doses of chemical agents used alone. ABT-263 (navitoclax), a clinically tested Bcl-2 family protein inhibitor, has shown limited success in clinical trials due to the development of resistance to monotherapy in breast cancer cells.

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Algal-bacterial bioremediation of cyanide-containing wastewater in a continuous stirred photobioreactor.

World J Microbiol Biotechnol

January 2025

The Biotechnology Center, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.

This study reports the isolation and characterization of highly resistant bacterial and microalgal strains from an Egyptian wastewater treatment station to cyanide-containing compounds. The bacterial strain was identified as Bacillus licheniformis by 16S rRNA gene sequencing. The isolate removed up to 1 g L potassium cyanide, 3 g L benzonitrile, and 1 g L sodium salicylate when incubated as 10% v/v in MSM at 30 ℃.

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Enhancing salt tolerance genetically through defining the genetic and physiological mechanisms intergenerational and transgenerational stress memory that contributes to sustainable agriculture by reducing the reliance on external inputs such as irrigation and improving the adaptability of barley to changing climate conditions. Salinity stress poses a substantial challenge to barley production worldwide, adversely affecting crop yield, quality, and agricultural sustainability. To address this, the present study utilized a genome-wide association san (GWAS) to identify genetic associations underlying intergenerational and transgenerational stress memory in response to salinity in a diverse panel of 138 barley accessions.

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