The ABCF ATPase New1 resolves translation termination defects associated with specific tRNAArg and tRNALys isoacceptors in the P site.

The efficiency of translation termination is determined by the nature of the stop codon as well as its context. In eukaryotes, recognition of the A-site stop codon and release of the polypeptide are mediated by release factors eRF1 and eRF3, respectively. Translation termination is modulated by other factors which either directly interact with release factors or bind to the E-site and modulate the activity of the peptidyl transferase center.

Synthesis, Structure, Biological Activity, and Luminescence Properties of a "Butterfly"-Type Silver Cluster with 3-Benzyl-4-phenyl-1,2,4-triazol-5-thiol.

A new silver(I) cluster [AgL(Py)(Pype)]·4Py·11HO () with 3-benzyl-4-phenyl-1,2,4-triazol-5-thiol (L) was synthesized via the direct reaction of AgNO and L in MeOH, followed by recrystallization from a pyridine-piperidine mixture. The compound was isolated in a monocrystal form and its crystal structure was determined via single crystal X-ray diffraction. The complex forms a "butterfly" cluster with triazol-5-thioles.

PSF toolkit: an R package for pathway curation and topology-aware analysis.

Most high throughput genomic data analysis pipelines currently rely on over-representation or gene set enrichment analysis (ORA/GSEA) approaches for functional analysis. In contrast, topology-based pathway analysis methods, which offer a more biologically informed perspective by incorporating interaction and topology information, have remained underutilized and inaccessible due to various limiting factors. These methods heavily rely on the quality of pathway topologies and often utilize predefined topologies from databases without assessing their correctness.

Transcriptomic Maps of Colorectal Liver Metastasis: Machine Learning of Gene Activation Patterns and Epigenetic Trajectories in Support of Precision Medicine.

The molecular mechanisms of the liver metastasis of colorectal cancer (CRLM) remain poorly understood. Here, we applied machine learning and bioinformatics trajectory inference to analyze a gene expression dataset of CRLM. We studied the co-regulation patterns at the gene level, the potential paths of tumor development, their functional context, and their prognostic relevance.

Atlas of mRNA translation and decay for bacteria.

Regulation of messenger RNA stability is pivotal for programmed gene expression in bacteria and is achieved by a myriad of molecular mechanisms. By bulk sequencing of 5' monophosphorylated mRNA decay intermediates (5'P), we show that cotranslational mRNA degradation is conserved among both Gram-positive and -negative bacteria. We demonstrate that, in species with 5'-3' exonucleases, the exoribonuclease RNase J tracks the trailing ribosome to produce an in vivo single-nucleotide toeprint of the 5' position of the ribosome.

Molecular Analysis of SARS-CoV-2 Lineages in Armenia.

The sequencing of SARS-CoV-2 provides essential information on viral evolution, transmission, and epidemiology. In this paper, we performed the whole-genome sequencing of SARS-CoV-2 using nanopore and Illumina sequencing to describe the circulation of the virus lineages in Armenia. The analysis of 145 full genomes identified six clades (19A, 20A, 20B, 20I, 21J, and 21K) and considerable intra-clade PANGO lineage diversity.

Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics.

PoxtA and OptrA are ATP binding cassette (ABC) proteins of the F subtype (ABCF). They confer resistance to oxazolidinone and phenicol antibiotics, such as linezolid and chloramphenicol, which stall translating ribosomes when certain amino acids are present at a defined position in the nascent polypeptide chain. These proteins are often encoded on mobile genetic elements, facilitating their rapid spread amongst Gram-positive bacteria, and are thought to confer resistance by binding to the ribosome and dislodging the bound antibiotic.

Telomere Maintenance Pathway Activity Analysis Enables Tissue- and Gene-Level Inferences.

Telomere maintenance is one of the mechanisms ensuring indefinite divisions of cancer and stem cells. Good understanding of telomere maintenance mechanisms (TMM) is important for studying cancers and designing therapies. However, molecular factors triggering selective activation of either the telomerase dependent (TEL) or the alternative lengthening of telomeres (ALT) pathway are poorly understood.

Improved computational analysis of ribosome dynamics from 5'P degradome data using fivepseq.

In eukaryotes, 5'-3' co-translation degradation machinery follows the last translating ribosome providing an footprint of its position. Thus, 5' monophosphorylated (5'P) degradome sequencing, in addition to informing about RNA decay, also provides information regarding ribosome dynamics. Multiple experimental methods have been developed to investigate the mRNA degradome; however, computational tools for their reproducible analysis are lacking.

Transcriptome Patterns of - and - Mutated Breast and Ovarian Cancers.

Mutations in the and genes are known risk factors and drivers of breast and ovarian cancers. So far, few studies have been focused on understanding the differences in transcriptome and functional landscapes associated with the disease (breast vs. ovarian cancers), gene ( vs.

Transcriptome-Guided Drug Repositioning.

Drug repositioning can save considerable time and resources and significantly speed up the drug development process. The increasing availability of drug action and disease-associated transcriptome data makes it an attractive source for repositioning studies. Here, we have developed a transcriptome-guided approach for drug/biologics repositioning based on multi-layer self-organizing maps (ml-SOM).

WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene.

Telomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated, however, their relative contribution to TL variability is still understudied. We have used whole genome sequencing data of 250 family trios from the Genome of the Netherlands project to perform computational measurement of TL and a series of regression and genome-wide association analyses to reveal TL inheritance patterns and associated genetic factors.

Telomere Length Maintenance and Its Transcriptional Regulation in Lynch Syndrome and Sporadic Colorectal Carcinoma.

Activation of telomere maintenance mechanisms (TMMs) is a hallmark of most cancers, and is required to prevent genome instability and to establish cellular immortality through reconstitution of capping of chromosome ends. TMM depends on the cancer type. Comparative studies linking tumor biology and TMM have potential impact for evaluating cancer onset and development.

Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome.

We analyzed the blood transcriptome of sepsis framed within community-acquired pneumonia (CAP) and characterized its molecular and cellular heterogeneity in terms of functional modules of co-regulated genes with impact for the underlying pathophysiological mechanisms. Our results showed that CAP severity is associated with immune suppression owing to T-cell exhaustion and HLA and chemokine receptor deactivation, endotoxin tolerance, macrophage polarization, and metabolic conversion from oxidative phosphorylation to glycolysis. We also found footprints of host's response to viruses and bacteria, altered levels of mRNA from erythrocytes and platelets indicating coagulopathy that parallel severity of sepsis and survival.

Growth of Malignant Non-CNS Tumors Alters Brain Metabolome.

Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as "tumor brain.

Autoimmunity and autoinflammation: A systems view on signaling pathway dysregulation profiles.

Introduction: Autoinflammatory and autoimmune disorders are characterized by aberrant changes in innate and adaptive immunity that may lead from an initial inflammatory state to an organ specific damage. These disorders possess heterogeneity in terms of affected organs and clinical phenotypes. However, despite the differences in etiology and phenotypic variations, they share genetic associations, treatment responses and clinical manifestations.

[Dual energy computed tomography in diagnosis of urolithiasis: a new method for determining the chemical composition of urinary stones].

The "gold standard" for the diagnosis and evaluation of urinary stones is native computed tomography, which allows determining stone localization and size of with high accuracy. However, this imaging technique has limited diagnostic usefulness in determining the stone chemical composition. The newly introduced method of dual-energy computed tomography, based on obtaining images at two different energy levels is highly effective in determining the composition of urinary stones.

Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome.

Colorectal cancer (CRC) arising in Lynch syndrome (LS) comprises tumours with constitutional mutations in DNA mismatch repair genes. There is still a lack of whole-genome and transcriptome studies of LS-CRC to address questions about similarities and differences in mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC, and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch repair in LS colonic mucosa and the possible role of immune editing. Here, we provide a first molecular characterization of LS tumours and of matched tumour-distant reference colonic mucosa based on whole-genome DNA-sequencing and RNA-sequencing analyses.

Integration of Telomere Length Dynamics into Systems Biology Framework: A Review.

Telomere length dynamics plays a crucial role in regulation of cellular processes and cell fate. In contrast to epidemiological studies revealing the association of telomere length with age, age-related diseases, and cancers, the role of telomeres in regulation of transcriptome and epigenome and the role of genomic variations in telomere lengthening are not extensively analyzed. This is explained by the fact that experimental assays for telomere length measurement are resource consuming, and there are very few studies where high-throughput genomics, transcriptomics, and/or epigenomics experiments have been coupled with telomere length measurements.

Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases.

Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far.

Quantitative trait association study for mean telomere length in the South Asian genomes.

Motivation: Mean telomere length (MTL) is associated with cancers and age-related diseases, which necessitates identification of genomic and environmental factors that impact telomere length dynamics. Here, we present a pilot genome wide association (GWA) study for MTL in South Asian population using publicly available next generation whole genome sequences (WGS), both for MTL and genotype calculations.

Results: MTL in the studied population was not correlated with age, which is in accordance with previous reports.

Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers.

We systematically studied the expression of more than fifty histone and DNA (de)methylating enzymes in lymphoma and healthy controls. As a main result, we found that the expression levels of nearly all enzymes become markedly disturbed in lymphoma, suggesting deregulation of large parts of the epigenetic machinery. We discuss the effect of DNA promoter methylation and of transcriptional activity in the context of mutated epigenetic modifiers such as EZH2 and MLL2.

PSFC: a Pathway Signal Flow Calculator App for Cytoscape.

Cell signaling pathways are sequences of biochemical reactions that propagate an input signal, such as a hormone binding to a cell-surface receptor, into the cell to trigger a reactive process. Assessment of pathway activities is crucial for determining which pathways play roles in disease versus normal conditions. To date various pathway flow/perturbation assessment tools are available, however they are constrained to specific algorithms and specific data types.

Computel: computation of mean telomere length from whole-genome next-generation sequencing data.

Telomeres are the ends of eukaryotic chromosomes, consisting of consecutive short repeats that protect chromosome ends from degradation. Telomeres shorten with each cell division, leading to replicative cell senescence. Deregulation of telomere length homeostasis is associated with the development of various age-related diseases and cancers.