Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies

The 14-3-3 protein test has been shown to support the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) when associated with an adequate clinical context, and a high differential potential for the diagnosis of sporadic CJD has been attributed to other cerebrospinal fluid (CSF) proteins such as tau protein, S100b and neuron specific enolase (NSE). So far there has been only limited information available about biochemical markers in genetic transmissible spongiform encephalopathies (gTSE), although they represent 10–15% of human TSEs. In this study, we analyzed CSF of 174 patients with gTSEs for 14-3-3 (n = 166), tau protein (n = 78), S100b (n = 46) and NSE (n = 50). Levels of brain-derived proteins in CSF varied in different forms of gTSE. Biomarkers were found positive in the majority of gCJD (81%) and insert gTSE (69%), while they were negative in most cases of fatal familial insomnia (13%) and Gerstmann-Sträussler-Scheinker syndrome (10%). Disease duration and codon 129 genotype influence the findings in a different way than in sporadic CJD

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries

2-Aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca²⁺ entry but an inconsistent inhibitor of InsP₃-induced Ca²⁺ release

Since its introduction to Ca2+ signaling in 1997, 2-aminoethoxydiphenyl borate (2-APB) has been used in many studies to probe for the involvement of inositol 1,4,5-trisphosphate receptors in the generation of Ca2+ signals. Due to reports of some nonspecific actions of 2-APB, and the fact that its principal antagonistic effect is on CaCa2+ entry rather than Ca2+ release, this compound may not have the utility first suggested. However, 2-APB has thrown up some interesting results, particularly with respect to store-operated Ca2+ entry in nonexcitable cells. These data indicate that although it must be used with caution, 2-APB can be useful in probing certain aspects of Ca2+ signalin

Amino acid sequence analysis of the annexin super-gene family of proteins

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identilied for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 avallable annexin sequences consisting of gg similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondiry structure prediction and conservation analysis to the characterisation of the molecules. The analysiJ clearly shows that the iepeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids withconserved phy_sicochemical properties at22 positions, *ittr otrty Gly at position i3 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conierved helices in"each r.p.ut unit and patterns of conserved hydrophobic amino acids are consistent wilh one face of a helix packing uguitrrt the_protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but co=ntiins a striking pattern of repeat-specifrc residue conservation at position:i, with Arg in repeats + and Clu i " r"p"uit z, but unconserved amino acids in repeats 1 and 3. This suggests repeats Z and, + may interact via a buried saltbridge. The loop between predicted helices a and b of repeit 3 shows features distinct from the equivalent loop in repeats 1,2 and 4, suggesting an important structurai and/or functional role for this region. No compelling evidence emerges from this _ study for uteroglobin and the annexins sharing similar tertiaiy structures, or fo