Polyglutamine-expanded ATXN7 alters a specific epigenetic signature underlying photoreceptor identity gene expression in SCA7 mouse retinopathy.

Background: Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder that primarily affects the cerebellum and retina. SCA7 is caused by a polyglutamine expansion in the ATXN7 protein, a subunit of the transcriptional coactivator SAGA that acetylates histone H3 to deposit narrow H3K9ac mark at DNA regulatory elements of active genes. Defective histone acetylation has been presented as a possible cause for gene deregulation in SCA7 mouse models.

Metabolism-associated molecular classification of gastric adenocarcinoma.

Most gastric cancers (GC) are adenocarcinomas, whereas GC is a highly heterogeneous disease due to its molecular heterogeneity. However, traditional morphology-based classification systems, including the WHO classification and Lauren's classification, have limited utility in guiding clinical treatment. We performed nonnegative matrix factorization (NMF) clustering based on 2752 metabolism-associated genes.

GenIDA: an international participatory database to gain knowledge on health issues related to genetic forms of neurodevelopmental disorders.

Intellectual disability with or without manifestations of autism and/or epilepsy affects 1-2% of the population, and it is estimated that more than 30-50% of these cases have a single genetic cause. More than 1000 genes and recurrent chromosomal abnormalities are involved in these genetic forms of neurodevelopmental disorders, which often remain insufficiently described in terms of clinical spectrum, associated medical problems, etc., due to their rarity and the often-limited number of patients' phenotypes reported.

Analytic modeling of inhomogeneous-resolution maps in cryo-electron microscopy and crystallography.

Refinement of macromolecular atomic models versus experimental maps in crystallography and cryo-electron microscopy is a critical step in structure solution. For an appropriate comparison, model maps should mimic the imperfections in the experimental maps, mainly atomic disorder and limited resolution, which are often inhomogeneous over the molecular region. In the suggested method, these model maps are calculated as the sum of atomic contributions expressed through a specifically designed function describing a solitary spherical wave.

An Enhancer Demethylator Phenotype Converged to Immune Dysfunction and Resistance to Immune Checkpoint Inhibitors in Clear-Cell Renal Cell Carcinomas.

Purpose: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of patients with clear-cell renal cell carcinomas (ccRCC). Although analyses of transcriptome, genetic alterations, and the tumor microenvironment (TME) have shed light into mechanisms of response and resistance to these agents, the role of epigenetic alterations in this process remains fully unknown.

Experimental Design: We investigated the methylome of six ccRCC cohorts as well as one cell line dataset.

Characterization of Two Mouse Heterozygous Loss-of-Function Models Shows Dysgenesis of the Corpus Callosum and Previously Unreported Features of CHARGE Syndrome.

CHARGE syndrome is a rare congenital disorder frequently caused by mutations in the chromodomain helicase DNA-binding protein-7 . Here, we developed and systematically characterized two genetic mouse models with identical, heterozygous loss-of-function mutation of the gene engineered on inbred and outbred genetic backgrounds. We found that both models showed consistent phenotypes with the core clinical manifestations seen in CHARGE syndrome, but the phenotypes in the inbred model were more severe, sometimes having reduced penetrance and included dysgenesis of the corpus callosum, hypoplasia of the hippocampus, abnormal retrosplenial granular cortex, ventriculomegaly, hyperactivity, growth delays, impaired grip strength and repetitive behaviors.

Selective transduction of cerebellar Purkinje and granule neurons using delivery of AAV-PHP.eB and AAVrh10 vectors at axonal terminal locations.

Adeno-associated virus (AAV)-based brain gene therapies require precision without off-targeting of unaffected neurons to avoid side effects. The cerebellum and its cell populations, including granule and Purkinje cells, are vulnerable to neurodegeneration; hence, conditions to deliver the therapy to specific cell populations selectively remain challenging. We have investigated a system consisting of the AAV serotypes, targeted injections, and transduction modes (direct or retrograde) for targeted delivery of AAV to cerebellar cell populations.

The impact of lockdown on young people with genetic neurodevelopmental disabilities: a study with the international participatory database GenIDA.

Background: Previous publications suggested that lockdown is likely to impact daily living issues of individuals with intellectual disabilities. The authors notably suspected an intensification of behavioural, eating and sleep problems.

Methods: To test these hypotheses, we conducted an international online survey about the impact of COVID-19-associated first lockdown on people with genetic neurodevelopmental disorders.

Cloning of nine glucocorticoid receptor isoforms from the slender African lungfish (Protopterus dolloi).

We wanted to clone the glucocorticoid receptor (GR) from slender African lungfish (Protopterus dolloi) for comparison to the P. dolloi mineralocorticoid receptor (MR), which we had cloned and were characterizing, as well as for comparison to the GRs from humans, elephant shark and zebrafish. However, although sequencing of the genome of the Australian lungfish (Neoceratodus forsteri), as well as, that of the West African lungfish (Protopterus annectens) were reported in the first three months of 2021, we could not retrieve a GR sequence with a BLAST search of GenBank, when we submitted our research for publication in July 2021.

Genetic landscape of indolent and aggressive Kaposi sarcomas.

Background: Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown.

Objectives: To explore the tumour mutational burden in indolent and aggressive KS.

Macrophages and monocytes mediated activation of oxidative phosphorylation implicated the prognosis and clinical therapeutic strategy of Wilms tumour.

Wilms tumour is the fourth leading cause of paediatric malignancy, but the detailed relationship between the tumour microenvironment and prognosis remains largely unclear. In this research, gene expression profile and clinical information from TARGET and the First Affiliated Hospital of Anhui Medical University were collected. After comparing the prognostic value of the associated immune cells, we established a nomogram to predict the prognosis of Wilms tumour based on monocyte infiltration, macrophage infiltration, stage, and sex.

Is RsfS a Hibernation Factor or a Ribosome Biogenesis Factor?

Solving the structures of bacterial, archaeal, and eukaryotic ribosomes by crystallography and cryo-electron microscopy has given an impetus for studying intracellular regulatory proteins affecting various stages of protein translation. Among them are ribosome hibernation factors, which have been actively investigated during the last decade. These factors are involved in the regulation of protein biosynthesis under stressful conditions.

Dynamin-2 reduction rescues the skeletal myopathy of a SPEG-deficient mouse model.

Striated preferentially expressed protein kinase (SPEG), a myosin light chain kinase, is mutated in centronuclear myopathy (CNM) and/or dilated cardiomyopathy. No precise therapies are available for this disorder, and gene replacement therapy is not a feasible option due to the large size of SPEG. We evaluated the potential of dynamin-2 (DNM2) reduction as a potential therapeutic strategy because it has been shown to revert muscle phenotypes in mouse models of CNM caused by MTM1, DNM2, and BIN1 mutations.

Innovative approach to lymphadenectomy in breast sarcoma.

Unlabelled: Lymphatic dissemination is thought to be a rare event in breast sarcomas. The decision to perform axillary clearance is challenging. In our prospective cohort, we aimed to evaluate the frequency and factors determining lymph node (LN) involvement in breast sarcomas, with the aim of proposing a decision tree/algorithm for the realization of LN clearance in breast sarcomas.

Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the locus.

How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We traced nearly all transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter-enhancer interaction frequencies or topological domain organization.

An integrative ultrasound-pathology approach to improve preoperative phyllodes tumor classification: A pilot study.

Objective: Preoperative diagnosis of phyllodes tumor (PT) is challenging, core-needle biopsy (CNB) has a significant rate of understaging, resulting in suboptimal surgical planification. We hypothesized that the association of imaging data to CNB would improve preoperative diagnostic accuracy compared to biopsy alone.

Methods: In this retrospective pilot study, we included 59 phyllodes tumor with available preoperative imaging, CNB and surgical specimen pathology.

[ORF19.2286 Gene: Isolation and Purification of Deoxyhypusine Hydroxylase from the Human Pathogenic Yeast Candida albicans].

Candida albicans (C. albicans) is a fungal pathogen that causes infections of the wet body surfaces and the blood in immunocompromised patients or individuals with imbalanced microflora. Since the cases of clinically meaningful candidosis are on the rise, efficient С.

Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome.

Neurodevelopmental disorders are highly heterogenous conditions resulting from abnormalities of brain architecture and/or function. FBXW7 (F-box and WD-repeat-domain-containing 7), a recognized developmental regulator and tumor suppressor, has been shown to regulate cell-cycle progression and cell growth and survival by targeting substrates including CYCLIN E1/2 and NOTCH for degradation via the ubiquitin proteasome system. We used a genotype-first approach and global data-sharing platforms to identify 35 individuals harboring de novo and inherited FBXW7 germline monoallelic chromosomal deletions and nonsense, frameshift, splice-site, and missense variants associated with a neurodevelopmental syndrome.

DNA circles promote yeast ageing in part through stimulating the reorganization of nuclear pore complexes.

The nuclear pore complex (NPC) mediates nearly all exchanges between nucleus and cytoplasm, and in many species, it changes composition as the organism ages. However, how these changes arise and whether they contribute themselves to ageing is poorly understood. We show that SAGA-dependent attachment of DNA circles to NPCs in replicatively ageing yeast cells causes NPCs to lose their nuclear basket and cytoplasmic complexes.

Biallelic variants in TRAPPC10 cause a microcephalic TRAPPopathy disorder in humans and mice.

The highly evolutionarily conserved transport protein particle (TRAPP) complexes (TRAPP II and III) perform fundamental roles in subcellular trafficking pathways. Here we identified biallelic variants in TRAPPC10, a component of the TRAPP II complex, in individuals with a severe microcephalic neurodevelopmental disorder. Molecular studies revealed a weakened interaction between mutant TRAPPC10 and its putative adaptor protein TRAPPC2L.