Deaths of detainees in the custody of US forces in Iraq and Afghanistan from 2002 to 2005

In light of the large number of detainees who continue to be taken and held in US custody in settings with limited judicial or public oversight, deaths of detainees warrant scrutiny. We have undertaken the task of reviewing all known detainee deaths between 2002 and early 2005 based on reports available in the public domain. Using documents obtained from the Department of Defense through a Freedom of Information Act request, combined with a review of anecdotal published press accounts, 112 cases of death of detainees in United States custody (105 in Iraq, 7 in Afghanistan) during the period from 2002 to early 2005 were identified. Homicide accounted for the largest number of deaths (43) followed by enemy mortar attacks against the detention facility (36). Deaths attributed to natural causes numbered 20. Nine were listed as unknown cause of death, and 4 were reported as accidental or natural. A clustering of 8 deaths ascribed to natural causes in Iraq in August 2003 raises questions about the adequacy and availability of medical care, as well as other conditions of confinement that may have had an impact on the mortality rate.     

Parasite risk factors for stunting in grade 5 students in a community of extreme poverty in Peru

Malnutrition in school-age children is common in developing countries and includes both stunting and underweight. Stunting, which represents a chronic state of nutritional stress, leads to adverse health, educational and cognitive effects. Although much research is focused on preschool-age children, recent studies show both the high prevalence of stunting and the effectiveness of interventions in school-age children. The objectives of the current study were to determine the risk factors for stunting only, and stunting and underweight. A survey was conducted in 1074 grade 5 children (mean age 10 years) from 17 schools in Belen, Peru, a community of extreme poverty. Prevalence of underweight and stunting were 10.5 and 34.5%, respectively, co-prevalence was 9.3%. Based on multivariable logistic regression analyses, significant independent risk factors (odds ratio: OR) for stunting and underweight were: age (per 1 year increment) (OR=1.55; 95% confidence interval (CI): 1.33, 1.81); diarrhoea in the last week (OR=1.96; 95% CI: 1.17, 3.29) and hookworm infection (OR=1.74; 95% CI: 1.05, 2.86). Significant independent risk factors for stunting only were: age (per 1 year increment) (OR=1.51; 95% CI: 1.35, 1.70); anaemia (OR=1.98; 95% CI: 1.26, 3.11); and moderate and heavy Trichuris and Ascaris co-infection (OR=1.95; 95% CI: 1.35, 2.82). Our results indicate a high prevalence of stunting, in addition to other adverse health indicators, in the study population. Due to the interrelation between many of these health and nutrition problems, interventions at both the school and community levels, including de-worming, feeding programs and health and hygiene education, are needed to reduce malnutrition in this and other similar populations living in conditions of extreme poverty.     

Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression

The zebrafish (Danio rerio) has been long advocated as a model for cancer research, but little is known about the real molecular similarities between zebrafish and human tumors. Comparative analysis of microarray data from zebrafish liver tumors with those from four human tumor types revealed molecular conservation at various levels between fish and human tumors. This approach provides a useful strategy for identifying an expression signature that is strongly associated with a disease phenotype.     

Quality assessment and analysis of Biogen Idec compound library

A subset of the compound repository for lead identification at Biogen Idec was characterized for its chemical stability over a 3-year period. Compounds were stored at 4 degrees C as 10 mM DMSO stocks, and a small subset of compounds was stored as lyophilized dry films. Compound integrity of 470 discrete compounds (Compound Set I) and 1917 combinatorial chemistry-derived compounds (Compound Set II) was evaluated by liquid chromatography/mass spectrometry from the time of acquisition into the library collection and after 3 years of storage. Loss of compound integrity over the 3 years of storage was observed across the 2 subsets tested. Of Compound Set I, 63% of samples retained > 80% purity, whereas 57% of samples from Compound Set II had purity greater than 60%. The stability of the lyophilized samples was superior to the samples stored as DMSO solution. Although storage at 4 degrees C as DMSO solution was adequate for the majority of compounds, the authors observed and quantified the level of degradation within the compound collection. Their study provides general insight into compound storage and selection of library subsets for future lead identification activities.     

Reelin regulates differentiation of neural stem cells by activation of notch signaling through Disabled-1 tyrosine phosphorylation

We have previously reported the cross-talk between Reelin and Notch-1 signaling pathways, which are 2 major pathways that regulate brain development. We found that Reelin activated Notch-1 signaling, leading to the expression of brain lipid binding protein (BLBP) and the formation of radial glial cells in human neural progenitor cells (hNPCs). In the current study, we investigated the molecular mechanisms by which Reelin activates Notch-1. We show that Reelin-stimulated Notch-1 activation is dependent on Reelin signaling. The induction of Disabled-1 (Dab-1) tyrosine phosphorylation, and the subsequent activation of Src family kinases, were found to be essential steps for the activation of Notch-1 signaling by Reelin. Reelin treatment increased the interaction between Dab-1 and Notch-1 intracellular domain (NICD), and enhanced NICD translocation to the nucleus. This study advances our knowledge of the regulation of Notch-1 activation by Reelin signaling in hNPCs, as an approach to understanding cell fate determination, differentiation, and neurogenesis during brain development.     

TULIPs: tunable, light-controlled interacting protein tags for cell biology

Naturally photoswitchable proteins offer a means of directly manipulating the formation of protein complexes that drive a diversity of cellular processes. We developed tunable light-inducible dimerization tags (TULIPs) based on a synthetic interaction between the LOV2 domain of Avena sativa phototropin 1 (AsLOV2) and an engineered PDZ domain (ePDZ). TULIPs can recruit proteins to diverse structures in living yeast and mammalian cells, either globally or with precise spatial control using a steerable laser. The equilibrium binding and kinetic parameters of the interaction are tunable by mutation, making TULIPs readily adaptable to signaling pathways with varying sensitivities and response times. We demonstrate the utility of TULIPs by conferring light sensitivity to functionally distinct components of the yeast mating pathway and by directing the site of cell polarization.     

CENP-V is required for centromere organization, chromosome alignment and cytokinesis

The mechanism of mitotic chromosome condensation is poorly understood, but even less is known about the mechanism of formation of the primary constriction, or centromere. A proteomic analysis of mitotic chromosome scaffolds led to the identification of CENP-V, a novel kinetochore protein related to a bacterial enzyme that detoxifies formaldehyde, a by-product of histone demethylation in eukaryotic cells. Overexpression of CENP-V leads to hypercondensation of pericentromeric heterochromatin, a phenotype that is abolished by mutations in the putative catalytic site. CENP-V depletion in HeLa cells leads to abnormal expansion of the primary constriction of mitotic chromosomes, mislocalization and destabilization of the chromosomal passenger complex (CPC) and alterations in the distribution of H3K9me3 in interphase nucleoplasm. CENP-V-depleted cells suffer defects in chromosome alignment in metaphase, lagging chromosomes in anaphase, failure of cytokinesis and rapid cell death. CENP-V provides a novel link between centromeric chromatin, the primary constriction and the CPC.     

FAT AND CARBOHYDRATE METABOLISM IN HUMANS—A Study of Nutritional and Hormonal Effects

As an index to the rate of fat utilization in human subjects, the recovery of all radioactive carbon dioxide in the expired air was measured for one hour following intravenous injection of palmitate-1-C¹⁴. In the normal fasted subject, about 10 per cent of the injected dose was recovered, and the proportion was lowered to about 5 per cent by administration of glucose. With prolonged fasting, the recovery of radioactive carbon dioxide did not change, despite a rising concentration of fatty acids in the serum. This was interpreted as due to the development of a balance between increasing mobilization and oxidation and was thought to indicate increasing fatty acid oxidation.In chronic undernutrition and diabetes mellitus there was increased fatty acid oxidation due presumably to adaptation to a chronic increase in fat utilization for energy.Administration of human growth hormone did not increase fat oxidation but prevented the usual inhibition produced by glucose. This was interpreted to mean that growth hormone increases fat utilization only indirectly by inhibiting the usual preferential utilization of glucose over fat.