On the population genetics of beta2-glycoprotein I.

Beta2-glycoprotein I typings on 152 healthy Germans and 150 patients with atopic diseases did not show any differences in the serum protein concentrations or in the phenotype and gene frequencies. Compared to these German samples, Philippinos (n = 88) as well as healthy Negroes from South Africa (n = 192) revealed statistically significant lower concentrations of this serum protein. They differ also from the Germans with regard to phenotype and gene frequencies. A most striking result was found in the comparison of healthy and leprous Negroes (n = 250) from South Africa. In these, quite different and statistically significant beta 2-Glycoprotein I concentrations, respectively, phenotype and gene frequencies were seen, which may be due to this disease. The possible reasons for these observations as well as for the observed population differences are discussed.     

Surgical Management of Epilepsy

Therapy with anticonvulsant drugs reduces the frequency and severity of seizures in many but not all epileptic patients. Unfortunately, in a significant number control remains poor even when maximal doses of multiple anticonvulsant drugs are given. Some of these patients are candidates for surgical treatment of epilepsy. The operative management of convulsive disorders is a well-established technique and is available in some centers. In selected cases, such operations are both safe and effective, with good longterm improvement or complete control in 76 percent of patients. We have summarized the 24-year experience with surgical operation for epilepsy at the University of Washington Medical Center.     

Finger ridge-count variation among various Subsaharan African groups

This paper addresses the question of the extent to which finger ridge-count data are useful features with which to study population variation in Subsaharan Africa. Each subject was represented by a vector of 20 ridge-counts, a radial and an ulnar count for each digit. Such data were available from 11 African groups, nine of which were indigenous Africans, and two, the South African Colored and South African Indians, contained a portion of non-African ancestory. The ridge-counts were first transformed to principal component scores and these were subjected to multivariate analysis of variance and distance analysis to elucidate intergroup variation. The primary findings were that ridgecounts provide a good reflection of variation on at least two levels, that of African versus non-African, and variation among Africans. Also, the principal components that reveal variation at these two levels are very different. We conclude that ridge-counts can only be useful in population studies if full account is taken of their multicomponent nature.     

On the Combined Analysis of H and N/H Solid-State NMR Data for Determination of Transmembrane Peptide Orientation and Dynamics

The dynamics of membrane-spanning peptides have a strong affect on the solid-state NMR observables. We present a combined analysis of ²H-alanine quadrupolar splittings together with ¹⁵N/¹H dipolar couplings and ¹⁵N chemical shifts, using two models to treat the dynamics, for the systematic evaluation of transmembrane peptides based on the GWALP23 sequence (acetyl-GGALW(LA)₆LWLAGA-amide). The results indicate that derivatives of GWALP23 incorporating diverse guest residues adopt a range of apparent tilt angles that span 5°–35° in lipid bilayer membranes. By comparing individual and combined analyses of specifically ²H- or ¹⁵N-labeled peptides incorporated in magnetically or mechanically aligned lipid bilayers, we examine the influence of data-set size/identity, and of explicitly modeled dynamics, on the deduced average orientations of the peptides. We conclude that peptides with small apparent tilt values (<∼10°) can be fitted by extensive families of solutions, which can be narrowed by incorporating additional ¹⁵N as well as ²H restraints. Conversely, peptides exhibiting larger tilt angles display more narrow distributions of tilt and rotation that can be fitted using smaller sets of experimental constraints or even with ²H or ¹⁵N data alone. Importantly, for peptides that tilt significantly more than 10° from the bilayer-normal, the contribution from rigid body dynamics can be approximated by a principal order parameter.     

Novel 2′-Deoxy Pyrazine C-Nucleosides Synthesized VIA Palladium-Catalyzed Cross-Couplings

Abstract

The palladium-catalyzed cross-couplings of 2-chloro-3,5-diamino-6-iodopyrazine (1a) and methyl 3-amino-6-iodopyrazine-2-carboxylate (1b) with 1,4-anhydro-3,5-O-bis[(tert-butyl)dimethylsilyl]-2-deoxy-D-erythro-pent-1-enitol (2) followed by desilylation and stereospecific reduction of the 2′-deoxy-3′-keto adduct leads to the formation of 2-chloro-6-(2-deoxy-ß-D-ribofuranosyl)-3,5-diaminopyrazine (4a) and methyl 3-amino-6-(2-deoxy-ß-D-ribofuranosyl)pyrazine-2-carboxylate (4b) in 58% yield and 21% yield, respectively. These are the first syntheses of the heretofore unknown 2′-deoxy pyrazine C-nucleosides and demonstrate the utility of a convergent approach for the synthesis of pyrazine C-nucleosides.     

The spatial segregation of pericentric cohesin and condensin in the mitotic spindle

In mitosis, the pericentromere is organized into a spring composed of cohesin, condensin, and a rosette of intramolecular chromatin loops. Cohesin and condensin are enriched in the pericentromere, with spatially distinct patterns of localization. Using model convolution of computer simulations, we deduce the mechanistic consequences of their spatial segregation. Condensin lies proximal to the spindle axis, whereas cohesin is radially displaced from condensin and the interpolar microtubules. The histone deacetylase Sir2 is responsible for the axial position of condensin, while the radial displacement of chromatin loops dictates the position of cohesin. The heterogeneity in distribution of condensin is most accurately modeled by clusters along the spindle axis. In contrast, cohesin is evenly distributed (barrel of 500-nm width × 550-nm length). Models of cohesin gradients that decay from the centromere or sister cohesin axis, as previously suggested, do not match experimental images. The fine structures of cohesin and condensin deduced with subpixel localization accuracy reveal critical features of how these complexes mold pericentric chromatin into a functional spring.