Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene

Mutations in the X-linked Plp gene lead to dysmyelinating phenotypes and oligodendrocyte cell death. Here, we exploit the X inactivation phenomenon to show that a hierarchy exists in the influence of different mutant Plp alleles on oligodendrocyte survival. We used compound heterozygote mice to study the long-term fate of oligodendrocytes expressing either the jimpy or rumpshaker allele against a background of cells expressing a Plp-null allele. Although mutant and null oligodendrocytes were generated in equal numbers, the proportion expressing the mutant allele subsequently declined, but whereas those expressing the rumpshaker allele formed a reduced but stable population, the number of jimpy cells fell progressively. The age of decline in the jimpy cells in different regions of the CNS correlated with the temporal sequence of myelination. In compound heterozygotes expressing rumpshaker and jimpy alleles, oligodendrocytes expressing the former predominated and were more abundant than when the rumpshaker and null alleles were in competition. Thus, oligodendrocyte survival is not determined solely by cell intrinsic factors, such as the conformation of the misfolded PLP, but is influenced by neighboring cells, possibly competing for cell survival factors

Role of transmembrane pH gradient and membrane binding in nisin pore formation

Nisin is a cationic antimicrobial peptide that belongs to the group of lantibiotics. It is thought to form oligomeric pores in the target membrane by a mechanism that requires the transmembrane electrical potential (Delta psi) and that involves local pertubation of the lipid bilayer structure. Here me show that nisin does not form exclusively voltage dependent pores: even in the absence of a Delta psi, nisin is able to dissipate the transmembrane pH gradient (Delta pH) in sensitive Lactococcus lactis cells and proteoliposomes. The rate of dissipation increases with the magnitude of the Delta pH. Nisin forms pores only when the Delta pH is inside alkaline. The efficiency of Delta psi-induced pore formation is strongly affected by the external pH, whereas Delta pH-induced pore formation is rather insensitive to the external pH. Nisin(1-12), an amino-terminal fragment of nisin, and (des-Delta Ala(5))-nisin(1-32) amide have a strongly reduced capacity to dissipate the Delta psi and Delta pH in cytochrome c oxidase proteoliposomes and L. lactis cells, Both variants bind with reduced efficiency to liposomes containing negatively charged phospholipids, suggesting that both ring A and rings C to E play a role in membrane binding, Nisin(1-12) competes with nisin for membrane binding and antagonizes pore formation. These findings are consistent with the wedge model of nisin-induced pore formation (A, J. M. Driessen et al., Biochemistry 34:1606-1614, 1995).</p

An Earth-system prediction initiative for the twenty-first century

International audienceSome scientists have proposed the Earth-System Prediction Initiative (EPI) at the 2007 GEO Summit in Cape Town, South Africa. EPI will draw upon coordination between international programs for Earth system observations, prediction, and warning, such as the WCRP, WWRP, GCOS, and hence contribute to GEO and the GEOSS. It will link with international organizations, such as the International Council for Science (ICSU), Intergovernmental Oceanographic Commission (IOC), UNEP, WMO, and World Health Organization (WHO). The proposed initiative will provide high-resolution climate models that capture the properties of regional high-impact weather events, such as tropical cyclones, heat wave, and sand and dust storms associated within multi-decadal climate projections of climate variability and change. Unprecedented international collaboration and goodwill are necessary for the success of EPI

Integrated motor drives: state of the art and future trends

With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system. This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

L'admirable Crichton : fantaisie en quatre actes

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