Differential sex mortality in a rural nineteenth-century population: Escazu, Costa Rica.

Cross-cultural studies of sex-specific mortality indicate that, whereas males experience their greatest mortality in industrialized societies, females experience their greatest mortality in populations with low life expectancy. The higher mortality of females in low-life-expectancy communities has been interpreted as a reflection of nutritional and health-care discrimination against females. Cross-cultural demographic studies also indicate that males have a higher frequency of violent and accidental deaths, possibly because of more frequent risky behaviors. This study focuses on Escazu, a rural nineteenth-century population from Costa Rica with low life expectancy. I investigate whether Escazu males had higher violent and accidental deaths and whether females had higher diarrhea-related deaths, an indication of nutritional discrimination. An analysis of mortality by cause of death indicates that males and females did not experience significantly different diarrhea-related death rates, although males did experience greater violent mortality. This study illustrates that more anthropological community-specific studies of mortality are needed to elucidate variation of death rates within large national or international regions.     

Serologic cross-reactivities poorly reflect allelic relationships in the HLA-B12 and HLA-B21 groups. Dominant epitopes of the alpha 2 helix.

Previous analysis has emphasized the correlation between primary structures of class I HLA molecules and their patterns of serologic cross-reactivity. Here we describe the structures of two serologic groups of HLA-B alleles for which this is not the case. HLA-B45, an allele associated with black populations, is serologically paired with B44 in the B12 group; its structure, however, is divergent from that of B44 but closely related to B50. The BN21 (B*4005) allele is associated with native Americans and is serologically grouped with B50 in the B21 group; its structure, however, is more closely related to alleles of the B40 group. The B44 and B45 serologically cross-reactive molecules differ at seven functional positions of the Ag recognition site; the B50 and BN21 molecules differ at four such residues. These differences are predicted to alter peptide presentation and be capable of eliciting strong alloreactive T cell responses. For these pairs of B12 and B21 Ag, serology appears dominated by epitopes formed by short sequences of the alpha 2 helix which have been shuffled by recombination between alleles. The implications of these results for HLA matching in transplantation are discussed.     

Fragile X‐associated tremor/ataxia syndrome: Regional decrease of mitochondrial DNA copy number relates to clinical manifestations

Fragile X‐associated tremor/ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder that appears in at least one‐third of adult carriers of a premutation (55‐200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene. Several studies have shown that mitochondrial dysfunction may play a central role in aging and also in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease as well as in FXTAS. It has been recently proposed that mtDNA copy number, measured by the number of mitochondrial genomes per nuclear genome (diploid), could be a useful biomarker of mitochondrial dysfunction. In order to elucidate the role of mtDNA variation in the pathogenesis of FXTAS, mtDNA copy number was quantified by digital droplet Polymerase chain reaction. In human brain samples, mtDNA levels were measured in the cerebellar vermis, dentate nucleus, parietal and temporal cortex, thalamus, caudate nucleus and hippocampus from a female FXTAS patient, a FMR1 premutation male carrier without FXTAS and from three male controls. The mtDNA copy number was further analyzed using this technology in dermal fibroblasts primary cultures derived from three FXTAS patients and three controls as well as in cortex and cerebellum of a CGG knock in FXTAS mice model. Finally, qPCR was carried out in human blood samples. Results indicate reduced mtDNA copy number in the specific brain region associated with disease progression in FXTAS patients, providing new insights into the role of mitochondrial dysfunction in the pathogenesis of FXTAS.     

Linkage of <Emphasis Type="Italic">Patr-AL</Emphasis> to <Emphasis Type="Italic">Patr-A</Emphasis> and-<Emphasis Type="Italic">B</Emphasis> in the major histocompatibility complex of the common chimpanzee (<Emphasis Type="Italic">Pan troglodytes</Emphasis>)

Patr-AL is a recently described gene found only in the common chimpanzee, but closely related in structure to the highly polymorphic Patr-A and HLA-A genes of the chimpanzee and human MHCs, respectively. Unlike Patr-A and HLA-A, the Patr-AL gene has little polymorphism and is not fixed in the chimpanzee genome. To determine whether Patr-AL is located in the MHC or elsewhere, we compared segregation of the Patr-AL gene with segregation of Patr-A and - B alleles in chimpanzee families. The results demonstrate that Patr-AL is an MHC class I gene present on different MHC haplotypes as defined by their combination of Patr-A and B alleles.     

HLA mismatches and hematopoietic cell transplantation: Structural simulations assess the impact of changes in peptide binding specificity on transplant outcome

The success of hematopoietic cell transplantation from an unrelated donor depends in part on the degree of Human Histocompatibility Leukocyte Antigen (HLA) matching between donor and patient. We present a structure-based analysis of HLA mismatching, focusing on individual amino acid mismatches and their effect on peptide binding specificity. Using molecular modeling simulations of HLA-peptide interactions, we find evidence that amino acid mismatches predicted to perturb peptide binding specificity are associated with higher risk of mortality in a large and diverse dataset of patient-donor pairs assembled by the International Histocompatibility Working Group in Hematopoietic Cell Transplantation consortium. This analysis may represent a first step toward sequence-based prediction of relative risk for HLA allele mismatches.     

Limnology of Crater Lakes in Los Tuxtlas,Mexico

Investigations on the abundance, biomass and position of heterotrophic flagellates (HF) in the benthic microbial food web of a melt water stream on King George Island, Antarctic Peninsula, were undertaken during the Antarctic summer from 23rd December 1997 until 13th March 1998. Abundance and biomass of potential HF resources (picophotoautotrophic and non-photoautotrophic bacteria) as well as potential predators on HF (ciliates and meiofauna) were also investigated. HF abundance ranged from approximately 9 × 10³ to 81 × 10³ cells cm^–3, values which fall into the same range as those found in lower latitudes. Numerically important benthic HF were euglenids, kinetoplastids, thaumatomastigids and especially chrysomonads. Most species identified have been shown to have a worldwide distribution. Abundance of the benthic ciliates ranged from 27 to 950 cells cm^–3. Mean bacterial abundance was 1.9 × 10⁷ and 5.2 × 10⁸ cells cm^–3 for picophotoautotrophic and non-photoautotrophic benthos, respectively. The well-developed microbial community was able to support the large number of nematods, gastotrichs, tardigrads and rotifers with abundances reaching more than 1000 individuals cm^–3. The largest portion of heterotrophic biomass was formed by the meiofauna with a mean of 63 g C cm^–3, followed by that of the heterotrophic bacteria with 4.80 g C cm^–3. Picophotoautotrophic bacteria contributed a mean of 1.37 g C cm^–3. HF and ciliates mean biomass was 0.61 and 1.99 g C cm^–3, respectively, with the HF biomass comprising between <10 and 70% of the total protozoan biomass. The data obtained in this study identify the melt water stream as a hot-spot of heterotrophic microbial and meiofaunal activity during the austral summer. The HF in the melt water stream formed a diverse group in terms of taxa and potential feeding types. Chrysomonads, kinetoplastids, euglenids and thaumatomastigida were the most abundant taxa. A classification into feeding types identified an average of 34% of the total HF as bacterivorous while all others were able to utilise other, larger organisms as resources. Potential trophic interactions between HF and bacteria and higher trophic levels are discussed.