The single-stranded DNA-binding factor SUB1/PC4 alleviates replication stress at telomeres and is a vulnerability of ALT cancer cells.

To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies.

Diagnosis and mitigation of the systemic impact of genome reduction in DGF-298.

Unlabelled: Microorganisms with simplified genomes represent interesting cell chassis for systems and synthetic biology. However, genome reduction can lead to undesired traits, such as decreased growth rate and metabolic imbalances. To investigate the impact of genome reduction on strain DGF-298, a strain in which ~ 36% of the genome has been removed, we reconstructed a strain-specific metabolic model (AC1061), investigated the regulation of gene expression using iModulon-based transcriptome analysis, and performed adaptive laboratory evolution to let the strain correct potential imbalances that arose during its simplification.

Repression of pervasive antisense transcription is the primary role of fission yeast RNA polymerase II CTD serine 2 phosphorylation.

The RNA polymerase II carboxy-terminal domain (CTD) consists of conserved heptapeptide repeats that can be phosphorylated to influence distinct stages of the transcription cycle, including RNA processing. Although CTD-associated proteins have been identified, phospho-dependent CTD interactions have remained elusive. Proximity-dependent biotinylation (PDB) has recently emerged as an alternative approach to identify protein-protein associations in the native cellular environment.

Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes.

Reduced insulin sensitivity (insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM). We conducted transcriptomic profiling of 434 human placentas and identified a positive association between insulin-like growth factor binding protein 1 gene (IGFBP1) expression in the placenta and insulin sensitivity at ~26 weeks gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which, together with high gene expression levels in our placenta samples, suggests a placental or decidual source.

Placental RNA sequencing implicates IGFBP1 in insulin sensitivity during pregnancy and in gestational diabetes.

Reduced insulin sensitivity (or greater insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM) pathophysiology. We conducted transcriptomic profiling of 434 human placentas and identified a strong positive association between insulin-like growth factor binding protein 1 gene () expression in the placenta and insulin sensitivity at ~ 26 weeks' gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which together with high placental gene expression levels, suggests a placental source.

Higher Maternal Body Mass Index Is Associated With Lower Placental Expression of EPYC: A Genome-Wide Transcriptomic Study.

Context: Elevated body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. The placental transcriptome may elucidate molecular mechanisms underlying these associations.

Objective: We examined the association of first-trimester maternal BMI with the placental transcriptome in the Gen3G prospective cohort.

Pulse-SILAC and Interactomics Reveal Distinct DDB1-CUL4-Associated Factors, Cellular Functions, and Protein Substrates.

Cullin-RING finger ligases represent the largest family of ubiquitin ligases. They are responsible for the ubiquitination of ∼20% of cellular proteins degraded through the proteasome, by catalyzing the transfer of E2-loaded ubiquitin to a substrate. Seven cullins are described in vertebrates.

Motif conservation, stability, and host gene expression are the main drivers of snoRNA expression across vertebrates.

Small nucleolar RNAs (snoRNAs) are structured noncoding RNAs present in multiple copies within eukaryotic genomes. snoRNAs guide chemical modifications on their target RNA and regulate processes like ribosome assembly and splicing. Most human snoRNAs are embedded within host gene introns, the remainder being independently expressed from intergenic regions.

Enabling low-cost and robust essentiality studies with high-throughput transposon mutagenesis (HTTM).

Transposon-insertion sequencing (TIS) methods couple high density transposon mutagenesis with next-generation sequencing and are commonly used to identify essential or important genes in bacteria. However, this approach can be work-intensive and sometimes expensive depending on the selected protocol. The difficulty to process a high number of samples in parallel using standard TIS protocols often restricts the number of replicates that can be performed and limits the deployment of this technique to large-scale projects studying gene essentiality in various strains or growth conditions.

The mutational impact of Illudin S on human cells.

Illudin S (ILS) is a fungal sesquiterpene secondary metabolite with potent genotoxic and cytotoxic properties. Early genetic studies and more recent genome-wide CRISPR screens showed that Illudin-induced lesions are preferentially repaired by transcription-coupled nucleotide excision repair (TC-NER) with some contribution from post-replication repair pathways. In line with these results, Irofulven, a semi-synthetic ILS analog was recently shown to be particularly effective on cell lines and patient-derived xenografts with impaired NER (e.

First Trimester Plasma MicroRNA Levels Predict Risk of Developing Gestational Diabetes Mellitus.

Aims: Our objective is to identify first-trimester plasmatic miRNAs associated with and predictive of GDM.

Methods: We quantified miRNA using next-generation sequencing in discovery (Gen3G: n = 443/GDM = 56) and replication (3D: n = 139/GDM = 76) cohorts. We have diagnosed GDM using a 75-g oral glucose tolerance test and the IADPSG criteria.

Maternal Body Mass Index Is Associated with Profile Variation in Circulating MicroRNAs at First Trimester of Pregnancy.

Many women enter pregnancy with overweight and obesity, which are associated with complications for both the expectant mother and her child. MicroRNAs (miRNAs) are short non-coding RNAs that regulate many biological processes, including energy metabolism. Our study aimed to identify first trimester plasmatic miRNAs associated with maternal body mass index (BMI) in early pregnancy.

Investigating the role of RNA structures in transcriptional pausing using in vitro assays and in silico analyses.

Transcriptional pausing occurs across the bacterial genome but the importance of this mechanism is still poorly understood. Only few pauses were observed during the previous decades, leaving an important gap in understanding transcription mechanisms. Using the well-known and pause sites as models, we describe here the relation of pause sites with upstream RNA structures suspected to stabilize pausing.

First trimester plasma microRNAs levels predict Matsuda Index-estimated insulin sensitivity between 24th and 29th week of pregnancy.

Introduction: Gestational diabetes mellitus (GDM) is a consequence of an imbalance between insulin sensitivity (IS) and secretion during pregnancy. MicroRNAs (miRNAs) are small and secreted RNA molecules stable in blood and known to regulate physiological processes including glucose homeostasis. The aim of this study was to identify plasmatic miRNAs detectable in early pregnancy predicting IS at 24th-29th week of pregnancy.

CanDIG: Federated network across Canada for multi-omic and health data discovery and analysis.

We present the Canadian Distributed Infrastructure for Genomics (CanDIG) platform, which enables federated querying and analysis of human genomics and linked biomedical data. CanDIG leverages the standards and frameworks of the Global Alliance for Genomics and Health (GA4GH) and currently hosts data for five pan-Canadian projects. We describe CanDIG's key design decisions and features as a guide for other federated data systems.

Inactivation of the riboswitch-controlled GMP synthase GuaA in is associated with severe growth defects and poor infectivity in a mouse model of infection.

is the main cause of nosocomial antibiotic-associated diarrhoea. There is a need for new antimicrobials to tackle this pathogen. Guanine riboswitches have been proposed as promising new antimicrobial targets, but experimental evidence of their importance in is missing.

MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights.

Since its first release over a decade ago, the MetaboAnalyst web-based platform has become widely used for comprehensive metabolomics data analysis and interpretation. Here we introduce MetaboAnalyst version 5.0, aiming to narrow the gap from raw data to functional insights for global metabolomics based on high-resolution mass spectrometry (HRMS).