Essential tremor

Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations (oscillations or twitching movements) of certain muscle groups in one or more body parts of unknown cause. It is typically symmetrical, and affects the arms, hands, or fingers; but sometimes involves the head, vocal cords, or other body parts. Essential tremor is either an action (intention) tremor—it intensifies when one tries to use the affected muscles during voluntary movements such as eating and writing—or it is a postural tremor, present with sustained muscle tone. This means that it is distinct from a resting tremor, such as that caused by Parkinson's disease, which is not correlated with movement. Essential tremor is a progressive neurological disorder, and the most common movement disorder. Its onset is usually after age 40, but it can occur at any age. The cause is unknown. Diagnosis is by observi

Culture of preantral follicles in poly(ethylene) glycol-based, three-dimensional hydrogel: a relationship between swelling ratio and follicular developments

Jeffrey Alan Hubbell, Seung Tae Lee

This study was undertaken to examine how the softness of poly(ethylene) glycol (PEG)-based hydrogels, creating a three-dimensional (3D) microenvironment, influences the in vitro growth of mouse ovarian follicles. Early secondary, preantral follicles of 2week-old mice were cultured in a crosslinked four-arm PEG hydrogel. The hydrogel swelling ratio, which relates to softness, was modified within the range 25.7-15.5 by increasing the reactive PEG concentration in the precursor solution from 5% to 15% w/v, but it did not influence follicular growth to form the pseudoantrum (60-80%; p=0.76). Significant (p21.4 yielded better oocyte maturation than other levels, while the highest competence to develop pronuclear and blastocyst formation was detected at 20.6. In conclusion, gel softness, as reflected in swelling ratio, was one of the essential factors for supporting folliculogenesis in vivo within a hydrogel-based, 3D microenvironment. (c) 2014 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

Wiley-Blackwell2015

Notch1-driven T-ALL chromatin landscape is regulated by Tcf1 in hematopoietic progenitors

Mateusz Waldemar Antoszewski

Notch1 receptor signaling is essential for T cell fate specification and physiological thymic T lymphocyte development. Its dysregulation and oncogenic activation are detected in almost 80% of pediatric patients suffering from T cell acute lymphoblastic leukemia (T-ALL). T-ALL is a hematological neoplasm arising from immature thymocytes. T cell factor 1 (Tcf1) is a crucial well-known transcription factor regulating the early stages of thymocyte maturation and Notch1 directly drives the expression of Tcf1 during normal T cell development. Here we assessed the role of Tcf1 in modulating chromatin topology which enables the initiation of T-ALL at the level of early hematopoietic progenitors. This allows for the discovery of stage-setting epigenetic regulators establishing a leukemia-prone chromatin landscape during Notch1-driven disease initiation. We found Tcf1 to be an essential mediator of Notch1 signaling during T-ALL induction. Inactivation of Tcf1 prevented leukemogenesis despite oncogenic Notch1 activation. Genomic analysis of hematopoietic progenitors revealed T cell lineage specification to be essential in T-ALL initiation prior to the appearance of phenotypic features of T cells. The expression of genes associated with the T cell lineage was dependent on Notch1 and Tcf1. Chromatin accessibility, chromosome conformation capture and ChIP-seq analysis revealed the co-regulatory epigenetic function of Notch1 and Tcf1 in imprinting a leukemic chromatin landscape. Epigenetic modulation of distal enhancers which regulate leukemic oncogenes has been well described in patient-derived T-ALL cells. The Notch1-Myc enhancer region was shown to be indispensable in the process of leukemogenesis. We have identified a novel regulatory locus, dependent on Tcf1 and Notch1, essential for the expression of Myc in pre-T-ALL cells. This genomic region termed Tcf1-regulated Myc enhancer (TMe) was highly conserved across species. TMe was essential for the transition of pre-leukemic cells to a transplantable full-blown T-ALL but was dispensable for the physiological development of T cells. After activation of the enhancer in hematopoietic progenitors, this regulatory site remained accessible and bound by Tcf1 in murine and human T-ALL cells. Tcf1 is therefore required for shaping the epigenetic landscape of hematopoietic progenitors overexpressing oncogenic Notch1, and thus regulates the expression of genes involved in leukemogenesis.

EPFL2021

Notch1-driven T-ALL chromatin landscape is regulated by Tcf1 in hematopoietic progenitors

Mateusz Waldemar Antoszewski

EPFL2021

Culture of preantral follicles in poly(ethylene) glycol-based, three-dimensional hydrogel: a relationship between swelling ratio and follicular developments

Notch1-driven T-ALL chromatin landscape is regulated by Tcf1 in hematopoietic progenitors

Visually-sensitive networks in essential tremor: evidence from structural and functional imaging

Notch1-driven T-ALL chromatin landscape is regulated by Tcf1 in hematopoietic progenitors

Culture of preantral follicles in poly(ethylene) glycol-based, three-dimensional hydrogel: a relationship between swelling ratio and follicular developments

Visually-sensitive networks in essential tremor: evidence from structural and functional imaging