Modification of stem cell states by alcohol and acetaldehyde.

Ethanol (EtOH) is a recreationally ingested compound that is both teratogenic and carcinogenic in humans. Because of its abundant consumption worldwide and the vital role of stem cells in the formation of birth defects and cancers, delineating the effects of EtOH on stem cell function is currently an active and urgent pursuit of scientific investigation to explicate some of the mechanisms contributing to EtOH toxicity. Stem cells represent a primordial, undifferentiated phase of development; thus encroachment on normal physiologic processes of differentiation into terminal lineages by EtOH can greatly alter the function of progenitors and terminally differentiated cells, leading to pathological consequences that manifest as fetal alcohol spectrum disorders and cancers.

Different Effects of Knockouts in ALDH2 and ACSS2 on Embryonic Stem Cell Differentiation.

Background: Ethanol (EtOH) is a teratogen that causes severe birth defects, but the mechanisms by which EtOH affects stem cell differentiation are unclear. Our goal here is to examine the effects of EtOH and its metabolites, acetaldehyde (AcH) and acetate, on embryonic stem cell (ESC) differentiation.

Methods: We designed ESC lines in which aldehyde dehydrogenase (ALDH2, NCBI#11669) and acyl-CoA synthetase short-chain family member 2 (ACSS2, NCBI#60525) were knocked out by CRISPR-Cas9 technology.

Ethanol promotes differentiation of embryonic stem cells through retinoic acid receptor-γ.

Ethanol (EtOH) is a teratogen, but its teratogenic mechanisms are not fully understood. The alcohol form of vitamin A (retinol/ROL) can be oxidized to all--retinoic acid (RA), which plays a critical role in stem cell differentiation and development. Using an embryonic stem cell (ESC) model to analyze EtOH's effects on differentiation, we show here that EtOH and acetaldehyde, but not acetate, increase differentiation-associated mRNA levels, and that EtOH decreases pluripotency-related mRNAs.

Coupled ion binding and structural transitions along the transport cycle of glutamate transporters.

Membrane transporters that clear the neurotransmitter glutamate from synapses are driven by symport of sodium ions and counter-transport of a potassium ion. Previous crystal structures of a homologous archaeal sodium and aspartate symporter showed that a dedicated transport domain carries the substrate and ions across the membrane. Here, we report new crystal structures of this homologue in ligand-free and ions-only bound outward- and inward-facing conformations.

Wnt of the two horizons: putting stem cell self-renewal and cell fate determination into context.

The canonical Wnt/β-catenin pathway has long been associated with self-renewal and expansion of embryonic stem cells (ESCs). Recent studies have brought into question some earlier assumptions concerning the functional role that canonical Wnt signaling plays in self-renewal mechanisms by demonstrating clear effects on differentiation. In addition, Wnt is crucial for cell fate determination during embryogenesis.

Epigenetic changes brought about by perinatal stressors: a brief review of the literature.

Introduction: Numerous studies employing various animal models have found that perinatal stress, encountered in utero during sensitive developmental stages or shortly after birth, disrupts both sexual differentiation and sexual behavior in offspring. The biochemical, cellular, genetic and epigenetic events which are involved in the organismal response to perinatal stress are currently under investigation.

Methods, Results And Discussion: In this review, the reader is introduced to perinatal stressors as a toxicological phenomenon, and several recently characterized epigenetic responses to said stressors are discussed.

Toward an integrative analysis of the tumor microenvironment in ovarian epithelial carcinoma.

Ovarian epithelial carcinomas are heterogeneous malignancies exhibiting great diversity in histological phenotypes as well as genetic and epigenetic aberrations. A general early event in tumorigenesis is regional dissemination into the peritoneal cavity. Initial spread to the peritoneum is made possible by cooperative signaling between a wide array of molecules constituting the tissue microenvironment in the coelomic epithelium.

Unraveling the mysteries of aging through a Hutchinson-Gilford progeria syndrome model.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, deadly laminopathy. Research into its nature has provided valuable insights into understanding molecular mechanisms underlying cell senescence. Phenotypic changes in nuclear structure and heterochromatin, resulting from increased progerin production following overuse of a cryptic splice site in the LMNA gene have profound effects on cell cycle progression and DNA repair mechanisms.

Acute delirium associated with combined diphenhydramine and linezolid use.

Objective: To report a case of delirium with hallucinations presumably caused by the combination of diphenhydramine and linezolid.

Case Summary: A 56-year-old white man was receiving diphenhydramine 300 mg/d for 2 days to treat pruritus caused by a bullous rash possibly induced by vancomycin. He subsequently developed visual and auditory hallucinations, with erratic, aggressive behavior persisting for 3 days.

Infliximab treatment of sarcoidosis.

Objective: To determine whether there is sufficient evidence in the literature to support the use of infliximab in the treatment of sarcoidosis.

Data Sources And Selection: Literature was accessed through MEDLINE (1966-August 2002), OVID (2001-January 2003), and bibliographic searches. Additional databases were also searched.