Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

Using the SaTScan method to detect local malaria clusters for guiding malaria control programmes

Mpumalanga Province, South Africa is a low malaria transmission area that is subject to malaria epidemics. SaTScan methodology was used by the malaria control programme to detect local malaria clusters to assist disease control planning. The third season for case cluster identification overlapped with the first season of implementing an outbreak identification and response system in the area. SaTScan™ software using the Kulldorf method of retrospective space-time permutation and the Bernoulli purely spatial model was used to identify malaria clusters using definitively confirmed individual cases in seven towns over three malaria seasons. Following passive case reporting at health facilities during the 2002 to 2005 seasons, active case detection was carried out in the communities, this assisted with determining the probable source of infection. The distribution and statistical significance of the clusters were explored by means of Monte Carlo replication of data sets under the null hypothesis with replications greater than 999 to ensure adequate power for defining clusters. SaTScan detected five space-clusters and two space-time clusters during the study period. There was strong concordance between recognized local clustering of cases and outbreak declaration in specific towns. Both Albertsnek and Thambokulu reported malaria outbreaks in the same season as space-time clusters. This synergy may allow mutual validation of the two systems in confirming outbreaks demanding additional resources and cluster identification at local level to better target resources. Exploring the clustering of cases assisted with the planning of public health activities, including mobilizing health workers and resources. Where appropriate additional indoor residual spraying, focal larviciding and health promotion activities, were all also carried out

ICAR: endoscopic skull‐base surgery

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The proteomic response in glioblastoma in young patients

Increasing age is an important prognostic variable in glioblastoma (GBM). We have defined the proteomic response in GBM samples from 7 young patients (mean age 36 years) compared to peritumoural-control samples from 10 young patients (mean age 32 years). 2-Dimensional-gel-electrophoresis, image analysis, and protein identification (LC/MS) were performed. 68 proteins were significantly altered in young GBM samples with 29 proteins upregulated and 39 proteins downregulated. Over 50 proteins are described as altered in GBM for the first time. In a parallel analysis in old GBM (mean age 67 years), an excellent correlation could be demonstrated between the proteomic profile in young GBM and that in old GBM patients (r(2) = 0.95) with only 5 proteins altered significantly (p < 0.01). The proteomic response in young GBM patients highlighted alterations in protein–protein interactions in the immunoproteosome, NFkB signalling, and mitochondrial function and the same systems participated in the responses in old GBM patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11060-014-1474-6) contains supplementary material, which is available to authorized users

Malaria transmission after five years of vector control on Bioko Island, Equatorial Guinea.

BACKGROUND: Malaria is endemic with year-round transmission on Bioko Island. The Bioko Island Malaria Control Project (BIMCP) started in 2004 with the aim to reduce malaria transmission and to ultimately eliminate malaria. While the project has been successful in reducing overall malaria morbidity and mortality, foci of high malaria transmission still persist on the island. Results from the 2009 entomological collections are reported here. METHODS: Human landing collections (HLC) and light trap collections (LTC) were carried out on Bioko Island, Equatorial Guinea in 2009. The HLCs were performed in three locations every second month and LTCs were carried out in 10 locations every second week. Molecular analyses were performed to identify species, detect sporozoites, and identify potential insecticide resistance alleles. RESULTS: The entomological inoculation rates (EIR) on Bioko Island ranged from 163 to 840, with the outdoor EIRs reaching > 900 infective mosquito bites per year. All three human landing collection sites on Bioko Island had an annual EIR exceeding the calculated African average of 121 infective bites per year. The highest recorded EIRs were in Punta Europa in northwestern Bioko Island with human biting rates of 92 and 66 mosquito landings per person per night, outdoors and indoors, respectively. Overall, the propensity for mosquito biting on the island was significantly higher outdoors than indoors (p < 0.001). Both Anopheles gambiae s.s. and An. melas were responsible for malaria transmission on the island, but with different geographical distribution patterns. Sporozoite rates were the highest in An. gambiae s.s. populations ranging from 3.1% in Punta Europa and 5.7% in Riaba in the southeast. Only the L1014F (kdr-west) insecticide resistance mutation was detected on the island with frequencies ranging from 22-88% in An. gambiae s.s. No insecticide resistance alleles were detected in the An. melas populations. CONCLUSIONS: In spite of five years of extensive malaria control and a generalized reduction in the force of transmission, parasite prevalence and child mortality, foci of very high transmission persist on Bioko Island, particularly in the northwestern Punta Europa area. This area is favorable for anopheline mosquito breeding; human biting rates are high, and the EIRs are among the highest ever recorded. Both vector species collected in the study have a propensity to bite outdoors more frequently than indoors. Despite current vector control efforts mosquito densities remain high in such foci of high malaria transmission. To further reduce transmission, indoor residual spraying (IRS) needs to be supplemented with additional vector control interventions