DNA methylation dynamic in male rat germ cells during gametogenesis.

In mammals, a near complete resetting of DNA methylation (DNAme) is observed during germline establishment. This wave of epigenetic reprogramming is sensitive to the environment, which could impair the establishment of an optimal state of the gamete epigenome, hence proper embryo development. Yet, we lack a comprehensive understanding of DNAme dynamics during spermatogenesis, especially in rats, the model of choice for toxicological studies.

Evidence of Motor Skill Learning in Acute Stroke Patients Without Lesions to the Thalamus and Internal Capsule.

Background: It is currently unknown whether motor skill learning (MSkL) with the paretic upper limb is possible during the acute phase after stroke and whether lesion localization impacts MSkL. Here, we investigated MSkL in acute (1-7 days post) stroke patients compared with healthy individuals (HIs) and in relation to voxel-based lesion symptom mapping.

Methods: Twenty patients with acute stroke and 35 HIs were trained over 3 consecutive days on a neurorehabilitation robot measuring speed, accuracy, and movement smoothness variables.

Discovery and Development of TMPRSS6 Inhibitors Modulating Hepcidin Levels in Human Hepatocytes.

Iron overload disorders are characterized by the body's inability to regulate iron absorption and its storage which can lead to organ failures. Accumulated evidence has revealed that hepcidin, the master regulator of iron homeostasis, is negatively modulated by TMPRSS6 (matriptase-2), a liver-specific type II transmembrane serine protease (TTSP). Here, we report that treatment with a peptidomimetic inhibitor affecting TMPRSS6 activity increases hepcidin production in hepatic cells.

Transcriptome analysis reveals TMPRSS6 isoforms with distinct functionalities.

TMPRSS6 (matriptase-2) is a type II transmembrane serine protease involved in iron homoeostasis. At the cell surface of hepatocytes, TMPRSS6 cleaves haemojuvelin (HJV) and regulates the BMP/SMAD signalling pathway leading to production of hepcidin, a key regulator of iron absorption. Although four TMPRSS6 human isoforms and three mice Tmprss6 isoforms are annotated in databases (Ensembl and RefSeq), their relative expression or activity has not been studied.