A noncanonical role of roX RNAs in autosomal epigenetic repression.

Long noncoding RNAs known as roX (RNA on the X) are crucial for male development in Drosophila, as their loss leads to male lethality from the late larval stages. While roX RNAs are recognized for their role in sex-chromosome dosage compensation, ensuring balanced expression of X-linked genes in both sexes, their potential influence on autosomal gene regulation remains unexplored. Here, using an integrative multi-omics approach, we show that roX RNAs not only govern the X chromosome but also target genes on autosomes that lack male-specific lethal (MSL) complex occupancy, together with Polycomb repressive complexes (PRCs).

Generation and characterization of CRISPR-Cas9-mediated XPC gene knockout in human skin cells.

Xeroderma pigmentosum group C (XPC) is a versatile protein crucial for sensing DNA damage in the global genome nucleotide excision repair (GG-NER) pathway. This pathway is vital for mammalian cells, acting as their essential approach for repairing DNA lesions stemming from interactions with environmental factors, such as exposure to ultraviolet (UV) radiation from the sun. Loss-of-function mutations in the XPC gene confer a photosensitive phenotype in XP-C patients, resulting in the accumulation of unrepaired UV-induced DNA damage.

A hitchhiker's guide to single-cell epigenomics: Methods and applications for cancer research.

Genetic mutations are well known to influence tumorigenesis, tumor progression, treatment response and relapse, but the role of epigenetic variation in cancer progression is still largely unexplored. The lack of epigenetic understanding in cancer evolution is in part due to the limited availability of methods to examine such a heterogeneous disease. However, in the last decade the development of several single-cell methods to profile diverse chromatin features (chromatin accessibility, histone modifications, DNA methylation, etc.

Identification of a sorting motif for Tspan3 to MHCII compartments in human B cells.

Tetraspanins are four-transmembrane proteins that play fundamental roles in the immune system by enabling processes like migration, proliferation, signaling and protein trafficking. While the importance of cell surface tetraspanins has been established, the function of intracellular tetraspanins is less well understood. Here, we investigated the role of tetraspanin 3 (Tspan3) in lymphocytes.

The farnesoid X receptor activates transcription independently of RXR at non-canonical response elements.

The farnesoid X receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with the retinoid X receptor (RXR). FXR is expressed as four isoforms (α1-α4) that drive transcription from IR-1 (inverted repeat-1) response elements (REs). Recently, we found that FXR isoforms α2/α4 also activate transcription from non-canonical ER-2 (everted repeat-2) REs, mediating most metabolic effects of general FXR activation.

HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia.

KMT2A::MLLT3 acute myelomonocytic leukemia (AML) comes in two clinically and biologically different subtypes. One is characterized by inferior outcome, older age, and MECOM oncogene expression. The other is mainly observed in children and young adults, associates with better clinical outcome, but lacks MECOM.

Characterization of DNA methylation reader proteins in .

In plants, cytosine DNA methylation (mC) is largely associated with transcriptional repression of transposable elements, but it can also be found in the body of expressed genes, referred to as gene body methylation (gbM). gbM is correlated with ubiquitously expressed genes; however, its function, or absence thereof, is highly debated. The different outputs that mC can have raise questions as to how it is interpreted-or read-differently in these sequence and genomic contexts.

Endothelial eNOS deficiency causes podocyte injury through NFAT2 and heparanase in diabetic mice.

The pivotal role of endothelial nitric oxide synthase (eNOS) in diabetic nephropathy (DN) has been demonstrated using global eNOS knockout (eNOSGKO) mice. However, the precise role of endothelially expressed eNOS and how its deficiency advances DN are still unclear. Here, we targeted endothelial eNOS expression (E-eNOSKO) after the onset of diabetes using the floxed eNOS and endSCL-CreER alleles.

UGT8 mediated sulfatide synthesis modulates BAX localization and dictates apoptosis sensitivity of colorectal cancer.

Elevated de novo lipid synthesis is a remarkable adaptation of cancer cells that can be exploited for therapy. However, the role of altered lipid metabolism in the regulation of apoptosis is still poorly understood. Using thermal proteome profiling, we identified Manidipine-2HCl, targeting UGT8, a key enzyme in the synthesis of sulfatides.

Different dynamics of soluble inflammatory mediators after clearance of respiratory SARS-CoV-2 versus blood-borne hepatitis C virus infections.

Viral infections can be acute or chronic, with the immune system pivotal in immunopathogenesis. The potential reversibility of inflammation post-viral elimination is of current interest. This study compares the dynamics of soluble inflammatory mediators (SIM) during and after respiratory infections with SARS-CoV-2 and blood-borne acute and chronic hepatitis C virus (HCV) infections.

Disruption of survivin protein expression by treatment with YM155 accelerates the resolution of neutrophilic inflammation.

Background And Purpose: Prolonged survival of neutrophils is essential for determining the progression and severity of inflammatory and immune-mediated disorders, including gouty arthritis. Survivin, an anti-apoptotic molecule, has been described as a regulator of cell survival. This study aims to examine the effects of YM155 treatment, a survivin selective suppressant, in maintaining neutrophil survival in vitro and in vivo experimental settings of neutrophilic inflammation.

The commitment of the human cell atlas to humanity.

The Human Cell Atlas (HCA) is a global partnership "to create comprehensive reference maps of all human cells-the fundamental units of life - as a basis for both understanding human health and diagnosing, monitoring, and treating disease." ( https://www.humancellatlas.

Proceedings of a membrane update symposium: advancements, scientific insights, and future trends for dialysis membranes for enhanced clinical outcomes in end stage kidney disease patients.

Purpose Of Symposium: From September 6 - 8 2022, the Life/2022 Membrane Symposium was held in Frankfurt, Germany, and transmitted live to a worldwide internet audience. The event was part of the Life/Nephrology Campus initiative, a continuous educational platform for the nephrology community to expand knowledge and share expertise on contemporary topics in chronic kidney disease. We describe recent questions and advances in the field, and we underline challenges in the care of dialysis patients and opportunities for integration of new findings into clinical practice to improve patient outcomes in end stage kidney disease patients.

Food antigens suppress small intestinal tumorigenesis.

Food components suppressing small intestinal tumorigenesis are not well-defined partly because of the rarity of this tumor type compared to colorectal tumors. Using mice, a mouse model for intestinal tumorigenesis, and antigen-free diet, we report here that food antigens serve this function in the small intestine. By depleting Peyer's patches (PPs), immune inductive sites in the small intestine, we found that PPs have a role in the suppression of small intestinal tumors and are important for the induction of small intestinal T cells by food antigens.

A novel whole blood assay to quantify the release of T cell associated cytokines in response to Bordetella pertussis antigens.

Background: Bordetella pertussis continues to cause whooping cough globally even in countries with high immunisation coverage. Booster vaccinations with acellular pertussis vaccines are thus used in children, adolescents, and adults. T cell immunity is crucial for orchestrating the immune response after vaccination.

Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo.

In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3.

IMPRESS: Improved methylation profiling using restriction enzymes and smMIP sequencing, combined with a new biomarker panel, creating a multi-cancer detection assay.

Background: Despite the worldwide progress in cancer diagnostics, more sensitive diagnostic biomarkers are needed. The methylome has been extensively investigated in the last decades, but a low-cost, bisulfite-free detection method for multiplex analysis is still lacking.

Methods: We developed a methylation detection technique called IMPRESS, which combines methylation-sensitive restriction enzymes and single-molecule Molecular Inversion Probes.