Genomewide Multipoint Linkage Analysis of Seven Extended Palauan Pedigrees with Schizophrenia, by a Markov-Chain Monte Carlo Method

Palauans are an isolated population in Micronesia with lifetime prevalence of schizophrenia (SCZD) of 2%, compared to the world rate of approximately 1%. The possible enrichment for SCZD genes, in conjunction with the potential for reduced etiological heterogeneity and the opportunity to ascertain statistically powerful extended pedigrees, makes Palauans a population of choice for the mapping of SCZD genes. We have used a Markov-chain Monte Carlo method to perform a genomewide multipoint analysis in seven extended pedigrees from Palau. Robust multipoint parametric and nonparametric linkage (NPL) analyses were performed under three nested diagnostic classifications-core, spectrum, and broad. We observed four regions of interest across the genome. Two of these regions-on chromosomes 2p13-14 (for which, under core diagnostic classification, NPL=6.5 and parametric LOD=4.8) and 13q12-22 (for which, under broad diagnostic classification, parametric LOD=3.6, and, under spectrum diagnostic classification, parametric LOD=3.5)-had evidence for linkage with genomewide significance, after correction for multiple testing; with the current pedigree resource and genotyping, these regions are estimated to be 4.3 cM and 19.75 cM in size, respectively. A third region, with intermediate evidence for linkage, was identified on chromosome 5q22-qter (for which, under broad diagnostic classification, parametric LOD=2.5). The fourth region of interest had only borderline suggestive evidence for linkage (on 3q24-28; for this region, under broad diagnostic classification, parametric LOD=2.0). All regions exhibited evidence for genetic heterogeneity. Our findings provide significant evidence for susceptibility loci on chromosomes 2p13-14 and 13q12-22 and support both a model of genetic heterogeneity and the utility of a broader set of diagnostic classifications in the population from Palau.     

Further Data on the Mediterranean Sea Tardigrade Fauna

Available information about Mediterranean tardigrades regards mainly the insular and peninsular Italian coasts, but also Malta, the Alboran Sea, Spain, France, Albania, Morocco, Algeria, Tunisia, Cyprus, and Lebanon. The Mediterranean Tardigrades, more than 70 species, are Heterotardigrada, mainly the order Arthrotardigrada with several families, and the order Echiniscoidea with only the family Echiniscoididae. Coralligenous detritus seems to be the most favourable kind of sediment in which the highest values of biodiversity are reached. Halechiniscidae is the most important family in the subtidal zone, whereas Batillipedidae are more frequent in the intertidal zone. A study of 4 submarine cave populations has been carried out. Neoarctidae and Neostygarctidae, considered as the most ancient families, have only been found in the Mediterranean Sea to date. This could mean that Arthrotardigrada originated in the old Thetys Sea from which the basin of the Mediterranean Sea was formed.     

Endogenous fragment of hemoglobin, neokyotorphin, as cell growth factor

It is shown that neokyotorphin (the -globin fragment 137–141) stimulates proliferation of normal cells (murine embryonic fibroblasts, red bone marrow and spleen cells) and tumor cells (murine melanoma and transformed fibroblasts L929) in the absence or in the presence of fetal bovine serum. In contrast to serum deprivation conditions, the ability to potentiate L929 cell growth in the presence of fetal serum is strongly cell density dependent. The peptide also enhances the viability of L929 cells, murine embryonic fibroblasts and of the primary cultures of murine red bone marrow cells and splenocytes under serum-deprivation conditions for at least 72 h. The results of flow cytometry analysis suggest that the effect of neokyotorphin on survival of L929 cells in serum-free culture medium is due to maintenance of cell proliferation in the absence of growth factors. Along with cell cycle progression the peptide induces reversible reduction of L929 cell size.     

Self-Regulation Phenomena Applied to Bacterial Reaction Centers: 2. Nonequilibrium Adiabatic Potential: Dark and Light Conformations Revisited

Experimental and theoretical results in support of nonlinear dynamic behavior of photosynthetic reaction centers under light-activated conditions are presented. Different conditions of light adaptation allow for preparation of reaction centers in either of two different conformational states. These states were detected both by short actinic flashes and by the switching of the actinic illumination level between different stationary state values. In the second method, the equilibration kinetics of reaction centers isolated from Rhodobacter sphaeroides were shown to be inherently biphasic. The fast and slow equilibration kinetics are shown to correspond to electron transfer (charge separation) at a fixed structure and to combined electron-conformational transitions governed by the bounded diffusion along the potential surface, respectively. The primary donor recovery kinetics after an actinic flash revealed a pronounced dependence on the time interval (Δt) between cessation of a lengthy preillumination of a sample and the actinic flash. A pronounced slow relaxation component with a decay half time of more than 50 s was measured for Δt > 10 s. This component corresponds to charge recombination in reaction centers for which light-induced structural changes have not relaxed completely before the flash. The amplitude of this component depended on the conditions of the sample preparation, specifically on the type of detergent used in the preparation. The redox potential parameters as well as the structural diffusion constants were estimated for samples prepared in different ways.     

Patterns of MUC1 tissue expression defined by an anti-MUC1 cytoplasmic tail monoclonal antibody in breast cancer.

Our aim was to determine the pattern of expression of MUC1 mucin cytoplasmic tail (MUC1 CT) in breast carcinoma. A total of 98 invasive breast adenocarcinoma tumor samples were assayed by immunohistochemical (IHC) analysis. The pattern of reaction was classified as membrane, cytoplasmic, or mixed. Subcellular fractions were prepared after SDS-PAGE and Western blotting. The antibodies employed were anti-MUC1 CT (CT2 monoclonal antibody, MAb) and C595 MAb against the extracellular MUC1 core protein. With the CT2 MAb, IHC showed a high percentage of positive staining in 93% of specimens, with membrane staining the most common pattern observed. C595 MAb was reactive in 73% of specimens. Similar percentages of membrane and cytoplasmic staining were found, mainly in a mixed pattern. Western blotting showed different bands. With the CT2 MAb, the membrane fraction showed the most intense reaction; a strong band of reaction was detected at approximately <30 kD. With the C595 MAb, in most cases a double band at 200 kD was found. In breast epithelium, the pattern of MUC1 CT expression may constitute an indicator of MUC1 production because it does not depend on glycosylation. The pattern and extension of MUC1 CT positivity do not vary according to the histopathological subtype of the tumor.     

Melanocyte function and its control by melanocortin peptides.

Melanocytes are cells of neural crest origin. In the human epidermis, they form a close association with keratinocytes via their dendrites. Melanocytes are well known for their role in skin pigmentation, and their ability to produce and distribute melanin has been studied extensively. One of the factors that regulates melanocytes and skin pigmentation is the locally produced melanocortin peptide alpha-MSH. The effects of alpha-MSH on melanogenesis are mediated via the MC-1R and tyrosinase, the rate-limiting enzyme in the melanogenesis pathway. Binding of alpha-MSH to its receptor increases tyrosinase activity and eumelanin production, which accounts for the skin-darkening effect of alpha-MSH. Other alpha-MSH-related melanocortin peptides, such as ACTH1-17 and desacetylated alpha-MSH, are also agonists at the MC-1R and could regulate melanocyte function. Recent evidence shows that melanocytes have other functions in the skin in addition to their ability to produce melanin. They are able to secrete a wide range of signal molecules, including cytokines, POMC peptides, catecholamines, and NO in response to UV irradiation and other stimuli. Potential targets of these secretory products are keratinocytes, lymphocytes, fibroblasts, mast cells, and endothelial cells, all of which express receptors for these signal molecules. Melanocytes may therefore act as important local regulators of a range of skin cells. It has been shown that alpha-MSH regulates NO production from melanocytes, and it is possible that the melanocortins regulate the release of other signalling molecules from melanocytes. Therefore, the melanocortin signaling system is one of the important regulators of skin homeostasis.     

Genetic structure of populations of Calomys laucha (muridae, sigmodontinae) from central Argentina

The genetic structure of populations of the Sigmodontinae rodent Calomys laucha was studied by means of allozyme electrophoresis. This highly opportunistic species is found preferably in periodically perturbed habitats of crop fields in central Argentina, where it can attain very high densities. A total of 17 enzymatic proteins assayed gave information on 25 loci; only four were monomorphic in the seven populations studied. Levels of genetic variability (H_o from 0.144 to 0.171; P_95% from 44% to 56%) were higher than mean values reported for mammals and rodents. These high levels of heterozygosity could be maintained by large populations that do not experience great fluctuations in size, or by a social structure consistent in many small breeding groups that are formed and dissappear every breeding season. Genetic differentiation at a macrogeographical scale (θ=0.018) was low but statistically significant, and showed no correlation with geographic distance between pairs of populations. The pattern of population differentiation found is compatible with a relatively recent range expansion.