Ups and downs of lysosomal pH: conflicting roles of LAMP proteins?

The acidic pH of lysosomes is critical for catabolism in eukaryotic cells and is altered in neurodegenerative disease including Alzheimer and Parkinson. Recent reports using Drosophila and mammalian cell culture systems have identified novel and, at first sight, conflicting roles for the lysosomal associated membrane proteins (LAMPs) in the regulation of the endolysosomal system. AD: Alzheimer disease; LAMP: lysosomal associated membrane protein; LTR: LysoTracker; PD: Parkinson disease; TMEM175: transmembrane protein 175; V-ATPase: vacuolar-type H-translocating ATPase.

Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity.

The time of day strongly influences adaptive behaviors like long-term memory, but the correlating synaptic and molecular mechanisms remain unclear. The circadian clock comprises a canonical transcription-translation feedback loop (TTFL) strictly dependent on the BMAL1 transcription factor. We report that BMAL1 rhythmically localizes to hippocampal synapses in a manner dependent on its phosphorylation at Ser [pBMAL1(S42)].

Circulating Microvesicles Are Elevated Acutely following Major Burns Injury and Associated with Clinical Severity.

Microvesicles are cell-derived signaling particles emerging as important mediators and biomarkers of systemic inflammation, but their production in severe burn injury patients has not been described. In this pilot investigation, we measured circulating microvesicle levels following severe burns, with severe sepsis patients as a comparator group. We hypothesized that levels of circulating vascular cell-derived microvesicles are elevated acutely following burns injury, mirroring clinical severity due to the early onset and prevalence of systemic inflammatory response syndrome (SIRS) in these patients.

eLearning to facilitate the education and implementation of the Chelsea Critical Care Physical Assessment: a novel measure of function in critical illness.

Objective: To evaluate the efficacy of eLearning in the widespread standardised teaching, distribution and implementation of the Chelsea Critical Care Physical Assessment (CPAx) tool-a validated tool to assess physical function in critically ill patients.

Design: Prospective educational study. An eLearning module was developed through a conceptual framework, using the four-stage technique for skills teaching to teach clinicians how to use the CPAx.

The responsiveness of the Chelsea Critical Care Physical Assessment tool in measuring functional recovery in the burns critical care population: an observational study.

Introduction: Severe burn leads to a state of hypercatabolism, resulting in rapid muscle loss and long-term disability. As survival rates from severe burn are improving, early rehabilitation is essential to facilitate functional recovery. However, there is no way of measuring the degree of disability in the acute stages, and hence, no marker of functional recovery.

Construct validity of the Chelsea critical care physical assessment tool: an observational study of recovery from critical illness.

Introduction: Intensive care unit-acquired weakness (ICU-AW) is common in survivors of critical illness, resulting in global weakness and functional deficit. Although ICU-AW is well described subjectively in the literature, the value of objective measures has yet to be established. This project aimed to evaluate the construct validity of the Chelsea Critical Care Physical Assessment tool (CPAx) by analyzing the association between CPAx scores and hospital-discharge location, as a measure of functional outcome.

Reactive oxygen species and p38 mitogen-activated protein kinase mediate tumor necrosis factor α-converting enzyme (TACE/ADAM-17) activation in primary human monocytes.

Tumor necrosis factor α-converting enzyme (TACE) is responsible for the shedding of cell surface TNF. Studies suggest that reactive oxygen species (ROS) mediate up-regulation of TACE activity by direct oxidization or modification of the protein. However, these investigations have been largely based upon nonphysiological stimulation of promonocytic cell lines which may respond and process TACE differently from primary cells.

Mathematical modelling of the acid-base chemistry and oxygenation of blood: a mass balance, mass action approach including plasma and red blood cells.

Mathematical models of the acid-base chemistry of blood based upon mass action and mass balance equations have become popular as diagnostic tools in intensive care. The reference models using this approach are those based on the strong ion approach, but these models do not currently take into account the effects of oxygen on the buffering characteristics of haemoglobin. As such these models are limited in their ability to simulate physiological situations involving simultaneous changes of O(2) and CO(2) levels in the blood.