Malaria risk and access to prevention and treatment in the paddies of the Kilombero Valley, Tanzania

Background: The Kilombero Valley is a highly malaria-endemic agricultural area in south-eastern Tanzania. Seasonal flooding of the valley is favourable to malaria transmission. During the farming season, many households move to distant field sites (shamba in Swahili) in the fertile river floodplain for the cultivation of rice. In the shamba, people live for several months in temporary shelters, far from the nearest health services. This study assessed the impact of seasonal movements to remote fields on malaria risk and treatment-seeking behaviour. Methods: A longitudinal study followed approximately 100 randomly selected farming households over six months. Every household was visited monthly and whereabouts of household members, activities in the fields, fever cases and treatment seeking for recent fever episodes were recorded. Results: Fever incidence rates were lower in the shamba compared to the villages and moving to the shamba did not increase the risk of having a fever episode. Children aged 1-4 years, who usually spend a considerable amount of time in the shamba with their caretakers, were more likely to have a fever than adults (odds ratio = 4.47, 95 confidence interval 2.35-8.51). Protection with mosquito nets in the fields was extremely good (98 antimalarials was uncommon. Despite the long distances to health services, 55.8 health facility, while home-management was less common (37 17.4-50.5). Conclusion: Living in the shamba does not appear to result in a higher fever-risk. Mosquito nets usage and treatment of fever in health facilities reflect awareness of malaria. Inability to obtain drugs in the fields may contribute to less irrational use of drugs but may pose an additional burden on poor farming households. A comprehensive approach is needed to improve access to treatment while at the same time assuring rational use of medicines and protecting fragile livelihoods

Inherent Structural Disorder and Dimerisation of Murine Norovirus NS1-2 Protein

Human noroviruses are highly infectious viruses that cause the majority of acute, non-bacterial epidemic gastroenteritis cases worldwide. The first open reading frame of the norovirus RNA genome encodes for a polyprotein that is cleaved by the viral protease into six non-structural proteins. The first non-structural protein, NS1-2, lacks any significant sequence similarity to other viral or cellular proteins and limited information is available about the function and biophysical characteristics of this protein. Bioinformatic analyses identified an inherently disordered region (residues 1–142) in the highly divergent N-terminal region of the norovirus NS1-2 protein. Expression and purification of the NS1-2 protein of Murine norovirus confirmed these predictions by identifying several features typical of an inherently disordered protein. These were a biased amino acid composition with enrichment in the disorder promoting residues serine and proline, a lack of predicted secondary structure, a hydrophilic nature, an aberrant electrophoretic migration, an increased Stokes radius similar to that predicted for a protein from the pre-molten globule family, a high sensitivity to thermolysin proteolysis and a circular dichroism spectrum typical of an inherently disordered protein. The purification of the NS1-2 protein also identified the presence of an NS1-2 dimer in Escherichia coli and transfected HEK293T cells. Inherent disorder provides significant advantages including structural flexibility and the ability to bind to numerous targets allowing a single protein to have multiple functions. These advantages combined with the potential functional advantages of multimerisation suggest a multi-functional role for the NS1-2 protein

What determines cell size?

AbstractFirst paragraph (this article has no abstract) For well over 100 years, cell biologists have been wondering what determines the size of cells. In modern times, we know all of the molecules that control the cell cycle and cell division, but we still do not understand how cell size is determined. To check whether modern cell biology has made any inroads on this age-old question, BMC Biology asked several heavyweights in the field to tell us how they think cell size is controlled, drawing on a range of different cell types. The essays in this collection address two related questions - why does cell size matter, and how do cells control it

Levels of a subpopulation of platelets, but not circulating endothelial cells, predict early treatment failure in prostate cancer patients after prostatectomy

BACKGROUND: Angiogenesis is one of the hallmarks of cancer driving tumour growth and ultimately metastasis. Circulating endothelial cells (CECs) and circulating endothelial progenitor (CEPs) cells have been reported as candidate surrogate markers for tumour vascularisation. Our aim was to investigate the potential use of these circulating cells levels as predictors of prostate cancer treatment failure and metastasis. METHODS: We examined the levels of CD31(+)CD45(-) cells (CECs) and CD31(+)CD45(-)CD117(+) (CEPs) in s.c. and orthotopic models of human prostate cancers and correlated measurements with tumour size, volume and microvessel density (MVD). We then performed a prospective cohort study in 164 men with localised prostate cancer undergoing prostatectomy. The CD31(+)CD45(-), CD31(+)CD45(-)CD146(+) (CECs) and CD31(+)CD45(intermediate)CD133(+) (CEPs) populations were quantified and subsequently enriched for further characterisation. RESULTS: In preclinical models, levels of CD31(+)CD45(-) cells, but not CEPs, were significantly elevated in tumour-bearing mice and correlated with tumour size, volume and MVD. In our human prospective cohort study, the levels of CD31(+)CD45(-) cells were significantly higher in men who experienced treatment failure within the first year, and on logistic regression analysis were an independent predictor of treatment failure, whereas neither levels of CECs or CEPs had any prognostic utility. Characterisation of the isolated CD31(+)CD45(-) cell population revealed an essentially homogenous population of large, immature platelets representing <0.1% of circulating platelets. CONCLUSION: Elevated levels of a distinct subpopulation of circulating platelets were an independent predictor for early biochemical recurrence in prostate cancer patients within the first year from prostatectomy