Determination of concerted or stepwise mechanism of hydrogen tunneling from isotope effects: Departure between experiment and theory.

Isotope substitution is an important experimental technique that offers deep insight into reaction mechanisms, as the measured kinetic isotope effects (KIEs) can be directly compared with theory. For multiple proton transfer processes, there are two types of mechanisms: stepwise transfer and concerted transfer. The Bell-Limbach model provides a simple theory to determine whether the proton transfer mechanism is stepwise or concerted from KIEs.

Hypermethylation and reduced expression of Gtl2, Rian and Mirg at the Dlk1-Dio3 imprinted locus as a marker for poor developmental potential of mouse embryonic stem cells.

Mouse embryonic stem cells (ESCs) have played a crucial role in biomedical research where they can be used to elucidate gene function through the generation of genetically modified mice. A critical requirement for the success of this technology is the ability of ESCs to contribute to viable chimaeras with germ-line transmission of the genetically modified allele. We have identified several ESC clones that cause embryonic death of chimaeras at mid to late gestation stages.

Current and future directions in clinical fatigue management: An update for emergency medicine practitioners.

Physicians worldwide are working round the clock to meet the demands of healthcare systems, especially in acute medical settings such as EDs. Demanding shift work schedules cause fatigue and thus deterioration in mood and motor performance. This article explores the effects of sleep deprivation, focusing on cognition, executive decision-making and the implications for clinical care.

Atrial fibrillation in Indigenous and non-Indigenous Australians: a cross-sectional study.

Objective: To examine the prevalence of atrial fibrillation (AF) and cardiac structural characteristics in Indigenous and non-Indigenous Australians.

Design: Retrospective cross-sectional study linking clinical, echocardiography and administrative databases over a 10-year period.

Setting: A tertiary, university teaching hospital in Adelaide, Australia.

Single site-specific integration targeting coupled with embryonic stem cell differentiation provides a high-throughput alternative to in vivo enhancer analyses.

Comprehensive analysis of cis-regulatory elements is key to understanding the dynamic gene regulatory networks that control embryonic development. While transgenic animals represent the gold standard assay, their generation is costly, entails significant animal usage, and in utero development complicates time-course studies. As an alternative, embryonic stem (ES) cells can readily be differentiated in a process that correlates well with developing embryos.

Temporal and comparative outcomes of cardiac electrophysiology abstracts.

Although conferences are important vehicles for discussing scientific findings, the translation of presented research into peer-reviewed manuscripts is a crucial subsequent step in the research process. Given the evolving subspecialization of cardiology, we sought to characterize the temporal and comparative outcomes of abstracts presented at a subspecialty cardiac electrophysiology conference. Abstracts presented at the Heart Rhythm Society conference (1994 through 2006; HRS abstracts) and abstracts presented at the American Heart Association conference (2003; AHA abstracts) were studied.

LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease.

Activating mutations in the tyrosine kinase Janus kinase 2 (JAK2) cause myeloproliferative neoplasms, clonal blood stem cell disorders with a propensity for leukaemic transformation. Leukaemia inhibitory factor (LIF) signalling through the JAK-signal transducer and activator of transcription (STAT) pathway enables self-renewal of embryonic stem (ES) cells. Here we show that mouse ES cells carrying the human JAK2V617F mutation were able to self-renew in chemically defined conditions without cytokines or small-molecule inhibitors, independently of JAK signalling through the STAT3 or phosphatidylinositol-3-OH kinase pathways.

Gfi1 expression is controlled by five distinct regulatory regions spread over 100 kilobases, with Scl/Tal1, Gata2, PU.1, Erg, Meis1, and Runx1 acting as upstream regulators in early hematopoietic cells.

The growth factor independence 1 (Gfi1) gene was originally discovered in the hematopoietic system, where it functions as a key regulator of stem cell homeostasis, as well as neutrophil and T-cell development. Outside the blood system, Gfi1 is essential for inner-ear hair and intestinal secretory cell differentiation. To understand the regulatory hierarchies within which Gfi1 operates to control these diverse biological functions, we used a combination of comparative genomics, locus-wide chromatin immunoprecipitation assays, functional validation in cell lines, and extensive transgenic mouse assays to identify and characterize the complete ensemble of Gfi1 regulatory elements.