Ejectosome of bacteriophage ΦM1.

Podophages that infect gram-negative bacteria, such as pathogen ΦM1, encode tail assemblies too short to extend across the complex gram-negative cell wall. To overcome this, podophages encode a large protein complex (ejectosome) packaged inside the viral capsid and correspondingly ejected during infection to form a transient channel that spans the periplasmic space. Here, we describe the ejectosome of bacteriophage ΦM1 to a resolution of 3.

Characterization of Brain-Penetrant Pyrimidine-Containing Molecules with Differential Microtubule-Stabilizing Activities Developed as Potential Therapeutic Agents for Alzheimer's Disease and Related Tauopathies.

The microtubule (MT)-stabilizing protein tau disengages from MTs and forms intracellular inclusions known as neurofibrillary tangles in Alzheimer's disease and related tauopathies. Reduced tau binding to MTs in tauopathies may contribute to neuronal dysfunction through decreased MT stabilization and disrupted axonal transport. Thus, the introduction of brain-penetrant MT-stabilizing compounds might normalize MT dynamics and axonal deficits in these disorders.

Survival as medical registrar on call: remember the doughnut.

Life as a medical registrar presents many challenges and concern is growing that a downwards trend in recruitment to General Medicine is the direct result of a perception by junior doctors that the role of the medical registrar is excessively demanding and results in poor work-life balance. A solution-focused approach (SFA) can be used successfully to find a satisfying outcome for both registrar and patient in many of the situations encountered during an on-call, as well as carrying over benefits into life outside of work. We explore the origins of SFA and the ways in which it can be successfully applied to clinical medicine, providing case studies from the author's own experience to illustrate the principles of this way of thinking.

Inserting tunnelled hemodialysis catheters using elective guidewire exchange from nontunnelled catheters: is there a greater risk of infection when compared with new-site replacement?

The objective is to evaluate bacteremia outcomes and survival rates when using guidewire exchange to place tunnelled hemodialysis catheter (THDC) compared with a new-site replacement. Retrospectively, all patients were identified who received a THDC between January 1, 2000 and January 1, 2007. Any THDC having received antibiotic line locks or tunnel-to-tunnel exchange were excluded.

Markers of oxidative stress in the skeletal muscle of patients on haemodialysis.

Background: Increased oxidative stress may play a role in morbidity and mortality of patients with renal failure. Most studies have examined serum markers of oxidation, but it is unclear whether oxidative stress is involved in skeletal muscle atrophy.

Methods: This study examined markers of oxidative stress in the skeletal muscle of 10 haemodialysed patients and 10 control subjects.

Abnormal mitochondrial function and muscle wasting, but normal contractile efficiency, in haemodialysed patients studied non-invasively in vivo.

Background: Muscle dysfunction, which contributes to morbidity in patients on haemodialysis, has several manifestations and a number of possible causes. We applied the non-invasive techniques of (31)P-magnetic resonance spectroscopy ((31)P-MRS), magnetic resonance imaging (MRI) and near-infrared spectroscopy (NIRS) to calf muscle of dialysed patients to define the abnormalities in muscle cross-sectional area (CSA), contractile efficiency, mitochondrial function and vascular O(2) supply.

Methods: We performed (31)P-MRS/NIRS/MRI studies on the lateral gastrocnemius during isometric plantarflexion and recovery in 23 male patients on haemodialysis (age 24-71 years; haemoglobin 9.

The antiproteinuric effect of losartan is systemic blood pressure dependent.

Background: It has been suggested that high doses of angiotensin II receptor antagonists (AIIAs) may reduce proteinuria by a non-haemodynamic action additional to their effect on systemic blood pressure.

Methods: We tested this for the AIIA losartan using a prospective single-blind randomized design in patients with proteinuria (>1 g/24 h) due to non-diabetic chronic renal failure (stable creatinine clearance >20 ml/min) and mild to moderate hypertension (130/80 < blood pressure < 160/110 mmHg). Twenty-one patients were randomized into two groups: group A received losartan 50 mg daily for 4 weeks, then 100 mg daily for 4 weeks; group B received losartan 50 mg daily for 8 weeks.

A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114.

Proteinaceous inclusions with amyloidogenic properties are a common link between many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Histological and in vitro studies of amyloid fibrils have advanced the understanding of protein aggregation, and provided important insights into pathogenic mechanisms of these neurodegenerative brain amyloidoses. The classical amyloid dyes Congo Red (CR) and thioflavin T and S, have been used extensively to detect amyloid inclusions in situ.