Histone H3 N-terminal recognition by the PHD finger of PHRF1 is required for proper DNA damage response.

Plant homeodomain (PHD) fingers are critical effectors of histone post-translational modifications (PTMs), acting as regulators of gene expression and genome integrity, and frequently presenting in human disease. While most PHD fingers recognize unmodified and methylated states of histone H3 lysine 4 (H3K4), the specific functions of many of the over 100 PHD finger-containing proteins in humans remain poorly understood, despite their significant implications in disease processes. In this study, we undertook a comprehensive analysis of one such poorly characterized PHD finger-containing protein, PHRF1.

Cancer-associated DNA hypermethylation of Polycomb targets requires DNMT3A dual recognition of histone H2AK119 ubiquitination and the nucleosome acidic patch.

During tumor development, promoter CpG islands that are normally silenced by Polycomb repressive complexes (PRCs) become DNA-hypermethylated. The molecular mechanism by which de novo DNA methyltransferase(s) [DNMT(s)] catalyze CpG methylation at PRC-regulated regions remains unclear. Here, we report a cryo-electron microscopy structure of the DNMT3A long isoform (DNMT3A1) amino-terminal region in complex with a nucleosome carrying PRC1-mediated histone H2A lysine-119 monoubiquitination (H2AK119Ub).

Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of Histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch.

During tumor development, promoter CpG islands (CGIs) that are normally silenced by Polycomb repressive complexes (PRCs) become DNA hypermethylated. The molecular mechanism by which DNA methyltransferase(s) catalyze CpG methylation at PRC-regulated regions remains unclear. Here we report a cryo-EM structure of the DNMT3A long isoform (DNMT3A1) N-terminal region in complex with a nucleosome carrying PRC1-mediated histone H2A lysine 119 monoubiquitination (H2AK119Ub).

Nucleosome conformation dictates the histone code.

Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' that are read by specialized regions (reader domains) in chromatin-associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP: histone PTM] specificities, and thus decipher the histone code and guide epigenetic therapies.

An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability.

In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.

Heat Release by Isolated Mouse Brain Mitochondria Detected with Diamond Thermometer.

The production of heat by mitochondria is critical for maintaining body temperature, regulating metabolic rate, and preventing oxidative damage to mitochondria and cells. Until the present, mitochondrial heat production has been characterized only by methods based on fluorescent probes, which are sensitive to environmental variations (viscosity, pH, ionic strength, quenching, etc.).

Structure and flexibility of the yeast NuA4 histone acetyltransferase complex.

The NuA4 protein complex acetylates histones H4 and H2A to activate both transcription and DNA repair. We report the 3.1-Å resolution cryo-electron microscopy structure of the central hub of NuA4, which flexibly tethers the histone acetyltransferase (HAT) and Trimer Independent of NuA4 involved in Transcription Interactions with Nucleosomes (TINTIN) modules.

Influence of lamina vastoadductoria dissection on the outcomes of femoral artery extensive lesion stenting: A pilot randomised investigation.

Objective: Aim of the study was to improve the immediate and long-term results of stenting of the superficial femoral artery in extended lesions with the changing of the biomechanics of superficial ffemoral artery and of the first portion of the popliteal artery.

Methods: Pilot randomized prospective single-center study were included 70 patients. Patients were randomized into two groups in 1 × 1 format for 35 people using the envelope method.

Editor's Choice - Hybrid vs. Open Surgical Reconstruction for Iliofemoral Occlusive Disease: A Prospective Randomised Trial.

Objective: The aim of this non-inferiority randomised trial was to compare the short and midterm safety and efficacy of hybrid repair (HR) and open reconstruction (OR) for patients with co-existing iliac and common femoral artery (CFA) occlusive disease.

Methods: The study was registered on the ClinicalTrials.gov register (identifier: NCT02580084).

Fecal Microbiota Analysis in Cats with Intestinal Dysbiosis of Varying Severity.

Recent studies have shown that the gut microbiota plays an important role in the pathogenesis of gastrointestinal diseases in various animal species. There are only limited data on the microbiome in cats with varying grades of dysbiosis. The purpose of the study was a detailed analysis of the quantitative and qualitative fecal microbiota spectrum in cats with intestinal dysbiosis of varying severity.

The dCypher Approach to Interrogate Chromatin Reader Activity Against Posttranslational Modification-Defined Histone Peptides and Nucleosomes.

Bulk chromatin encompasses complex sets of histone posttranslational modifications (PTMs) that recruit (or repel) the diverse reader domains of Chromatin-Associated Proteins (CAPs) to regulate genome processes (e.g., gene expression, DNA repair, mitotic transmission).

Unifying mechanism behind the onset of acquired epilepsy.

Acquired epilepsy (AE) can result from a number of brain insults and neurological diseases with wide etiological diversity sharing one common outcome of brain epileptiform activity. This implies that despite their disparity, all these initiating pathologies affect the same fundamental brain functions underlying network excitability. Identifying such mechanisms and their availability as therapeutic targets would help develop an effective strategy for epileptogenesis prevention.

A trivalent nucleosome interaction by PHIP/BRWD2 is disrupted in neurodevelopmental disorders and cancer.

Mutations in the chromatin regulator cause the human neurodevelopmental disorder Chung-Jansen syndrome, while alterations in expression are linked to cancer. Precisely how PHIP functions in these contexts is not fully understood. Here we demonstrate that PHIP is a chromatin-associated CRL4 ubiquitin ligase substrate receptor and is required for CRL4 recruitment to chromatin.

A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization.

Nuclear receptor-binding SET domain-containing 2 (NSD2) is the primary enzyme responsible for the dimethylation of lysine 36 of histone 3 (H3K36), a mark associated with active gene transcription and intergenic DNA methylation. In addition to a methyltransferase domain, NSD2 harbors two proline-tryptophan-tryptophan-proline (PWWP) domains and five plant homeodomains (PHDs) believed to serve as chromatin reading modules. Here, we report a chemical probe targeting the N-terminal PWWP (PWWP1) domain of NSD2.

Randomized Controlled Trial of Conventional Versus MicroNet-Covered Stent in Carotid Artery Revascularization.

Objectives: The aim of this study was to compare procedure-related ipsilateral cerebral embolism with a conventional (Acculink, Abbott Vascular) versus a MicroNet-covered (CGuard, InspireMD) stent in carotid artery stenting (CAS).

Background: The MicroNet-covered stent may reduce periprocedural cerebral embolism in CAS, but level 1 evidence is lacking.

Methods: A total of 100 consecutive patients were randomized 1:1 to filter-protected CAS using the Acculink or the CGuard device.

Food Intolerance: The Role of Histamine.

Histamine is a natural amine derived from L-histidine. Although it seems that our knowledge about this molecule is wide and diverse, the importance of histamine in many regulatory processes is still enigmatic. The interplay between different types of histamine receptors and the compound may cause ample effects, including histamine intoxication and so-called histamine intolerance or non-allergic food intolerance, leading to disturbances in immune regulation, manifestation of gastroenterological symptoms, and neurological diseases.

Novel Ex Vivo Zymography Approach for Assessment of Protease Activity in Tissues with Activatable Antibodies.

Proteases are involved in the control of numerous physiological processes, and their dysregulation has been identified in a wide range of pathologies, including cancer. Protease activity is normally tightly regulated post-translationally and therefore cannot be accurately estimated based on mRNA or protein expression alone. While several types of zymography approaches to estimate protease activity exist, there remains a need for a robust and reliable technique to measure protease activity in biological tissues.

Aβ initiates brain hypometabolism, network dysfunction and behavioral abnormalities via NOX2-induced oxidative stress in mice.

A predominant trigger and driver of sporadic Alzheimer's disease (AD) is the synergy of brain oxidative stress and glucose hypometabolism starting at early preclinical stages. Oxidative stress damages macromolecules, while glucose hypometabolism impairs cellular energy supply and antioxidant defense. However, the exact cause of AD-associated glucose hypometabolism and its network consequences have remained unknown.

Hydrogen sulfide content in pregnant women with preeclampsia in late gestation and their newborns.

We examined 70 women who were 22-40 weeks pregnant and their newborns. Of these, 15 women with moderate PE made up group 1, 22 women with severe PE-group 2, and 55 women with uncomplicated pregnancy without hypertensive disorders - the control group. Blood was collected from women when they were admitted to the clinic, and blood was taken from newborns for 3-5 days of life.

Two competing mechanisms of DNMT3A recruitment regulate the dynamics of de novo DNA methylation at PRC1-targeted CpG islands.

Precise deposition of CpG methylation is critical for mammalian development and tissue homeostasis and is often dysregulated in human diseases. The localization of de novo DNA methyltransferase DNMT3A is facilitated by its PWWP domain recognizing histone H3 lysine 36 (H3K36) methylation and is normally depleted at CpG islands (CGIs). However, methylation of CGIs regulated by Polycomb repressive complexes (PRCs) has also been observed.

Evaluation of oxidative stress and antioxidant activity in women with moderate and severe preeclampsia in the third trimester of pregnancy and their newborns.

We examined 66 women who were 22-40 weeks pregnant and their newborns. Of these, 15 women with moderate PE were in group 1, 22 women with severe PE were in group 2, and 55 women with uncomplicated pregnancy without hypertensive disorders were in the control group. Blood was taken from women when they were admitted to the clinic, and newborns ' blood was taken for 3-5 days of life.

Overall survival in patients with metastatic renal cell carcinoma in Russia, Kazakhstan, and Belarus: a report from the RENSUR3 registry.

Background: Real-world data describing outcomes of treatment among metastatic renal cell carcinoma (mRCC) patients are limited and heterogeneous.

Aim: RENSUR3 registry study assessed real-world data on the use of therapies in mRCC and overall survival (OS) in Russia, Kazakhstan, and Belarus.

Methods: Patients were included in the retrospective multicenter registry study.

Is it possible to prevent cerebral embolization by improving the design and technology of carotid stent implantation?

Introduction: The prevention of atherosclerotic plaque fragmentation during carotid artery stenting is a fundamental problem in decreasing the risk of disability of patients. The goal of this review is to clarify whether the stent design can have a decisive impact on the rate of intraoperative and postoperative complications.

Areas Covered: Different designs of the carotid stents are briefed and the advantages and disadvantages of different stent designs are discussed as well as the results of their clinical use.

Size of canine hepatocellular carcinoma as an adverse prognostic factor for surgery.

Objective: Liver neoplasms are problematic among small domestic animals. The etiological cause of hepatocellular carcinomas in domestic animals is still unknown although it is believed that chronic infections and toxic substances can affect the development of this type of tumor. This study aimed to analyze the clinical and morphological characteristics of canine hepatocellular carcinoma.