Identification of RHCE and KEL alleles in large cohorts of Afro-Caribbean and Comorian donors by multiplex SNaPshot and fragment assays: a transfusion support for sickle cell disease patients.

To lower the alloimmunization risk following transfusion in blacks, we developed two genotyping assays for large-scale screening of Comorian and Afro-Caribbean donors. One was a multiplex SNaPshot assay designed to identify ce(s) (340), ceMO/AR/EK/BI/SM, ce(s) , ce(s) (1006) and KEL*6/*7 alleles. The other was a multiplex fragment assay designed to detect RHD, RHDψ and RHCE*C and 455A>C transversion consistent with (C)ce(s) Type 1 and DIII Type5 ce(s) . Variant RHCE*ce alleles or RH haplotypes were detected in 58·69% of Comorians and 41·23% of Afro-Caribbeans. The ce(s) allele, (C)ce(s) Type 1, and DIII Type 5 ce(s) haplotypes were identified respectively in 39·13%, 14·67% and 4·88% of Comorians and 32·23%, 5·28% and 1·76% of Afro-Caribbeans. Genotypes consistent with partial D, C, c and/or e antigen expression were observed in 26·08% of Comorians and 14·69% of Afro-Caribbeans. No homozygous genotype corresponding to the RH:-18, -34, and -46 phenotypes were found. However, over 50% of genotypes produced low-prevalence antigens at risk for negative recipients, i.e., V, VS, JAL, and/or KEL6. One new variant RHCE*ce(s) (712) allele was identified. This is the first determination of variant RHCE and KEL allele frequencies. Results indicate the most suitable targets for molecular assay screening to optimize use of compatible blood units and lower immunization risk.

Circadian rhythms of oxidative phosphorylation: effects of rotenone and melatonin on isolated rat brain mitochondria.

Mitochondrial experiments are of increasing interest in different fields of research. Inhibition of mitochondrian activities seems to play a role in Parkinson's disease and in this regard several animal models have used inhibitors of mitochondrial respiration such as rotenone or MPTP. Most of these experiments were done during the daytime. However, there is no reason for mitochondrial respiration to be constant during the 24 h. This study investigated the circadian variation of oxidative phosphorylation in isolated rat brain mitochondria and the administration-time-dependent effect of rotenone and melatonin. The respiratory control ratio, state 3 and state 4, displayed a circadian fluctuation. The highest respiratory control ratio value (3.01) occurred at 04:00 h, and the lowest value (2.63) at 08:00 h. The highest value of state 3 and state 4 oxidative respiration occurred at 12:00 h and the lowest one at 20:00 h. The 24 h mean decrease in the respiratory control ratio following incubation with melatonin and rotenone was 7 and 32%, respectively; however, the exact amount of the inhibition exerted by these agents varied according to the time of the mitochondria isolation. Our results show the time of mitochondrial isolation could lead to interindividual variability. When studies require mitochondrial isolation from several animals, the time between animal experiments has to be minimized. In oxidative phosphorylation studies, the time of mitochondria isolation must be taken into account, or at least specified in the methods section.

Genetic diversity on the Comoros Islands shows early seafaring as major determinant of human biocultural evolution in the Western Indian Ocean.

The Comoros Islands are situated off the coast of East Africa, at the northern entrance of the channel of Mozambique. Contemporary Comoros society displays linguistic, cultural and religious features that are indicators of interactions between African, Middle Eastern and Southeast Asian (SEA) populations. Influences came from the north, brought by the Arab and Persian traders whose maritime routes extended to Madagascar by 700-900 AD. Influences also came from the Far East, with the long-distance colonisation by Austronesian seafarers that reached Madagascar 1500 years ago. Indeed, strong genetic evidence for a SEA, but not a Middle Eastern, contribution has been found on Madagascar, but no genetic trace of either migration has been shown to exist in mainland Africa. Studying genetic diversity on the Comoros Islands could therefore provide new insights into human movement in the Indian Ocean. Here, we describe Y chromosomal and mitochondrial genetic variation in 577 Comorian islanders. We have defined 28 Y chromosomal and 9 mitochondrial lineages. We show the Comoros population to be a genetic mosaic, the result of tripartite gene flow from Africa, the Middle East and Southeast Asia. A distinctive profile of African haplogroups, shared with Madagascar, may be characteristic of coastal sub-Saharan East Africa. Finally, the absence of any maternal contribution from Western Eurasia strongly implicates male-dominated trade and religion as the drivers of gene flow from the North. The Comoros provides a first view of the genetic makeup of coastal East Africa.

[Manufacturing waste of hemodialyzers decreases oxidative phosphorylation of mitochondria isolated from rats]. / Les résidus de fabrication des hémodialyseurs diminuent la phosphorylation oxydative des mitochondries isolées de rat.

INTRODUCTION: The persistence of manufacturing waste in hemodialysers is a neglected aspect of lack of hemodialysis biocompatibility. The effect of waste was tested on mitochondria isolated from rat liver. MATERIAL AND METHODS: After throwing the first two liters of the rinse solution of hemodialysers, the third liter is lyophilized. The waste is placed in the presence of mitochondria. The parameter V3 is the synthesis of ATP, the respiratory control (RC) is the ability to activate phosphorylation in the presence of ADP, ADP/O is the ratio of ADP used on oxygen consumption. The study was conducted on two hemodialyzers sterilized with gamma rays (Tricea and APS) and one hemodialyzer sterilized with flowing steam (FX60). RESULTS: The respiratory parameters in the presence of waste are expressed as percentage of values obtained in the presence of control (sterile water). The respective values with Tricea, APS and the FX are for V3: 67±14, 79±10, and 81±8% (T vs A p=0.02; T vs F p=0.01; A vs F p=0.68) ; for CR : 44±6, 63±7, and 74±9% (T vs A p<0.001; T vs X p<0.001; A vs F p=0.004) ; for ADP/O : 75±11, 90±19, 91±11% (T vs A p=0.16; T vs F p=0.01; A vs F p=0.68). The dose-response curves confirm the differences concerning V3 and RC but not concerning ADP/O. CONCLUSION: The hemodialyzers contain waste which has toxic effects on isolated mitochondria. This waste impairs the oxidative phosphorylation. The fact that this waste is still present in the dialyzers despite rinsing with two liters should alert users about the importance of extensive rinsing and manufacturers about the importance of effective procedures in order to eliminate manufacturing waste.

Improving minority blood donation: anthropologic approach in a migrant community.

BACKGROUND: As a result of blood group polymorphism, distinctive blood types have evolved in populations around the world. In countries with large migrant populations, finding rare blood types for transfusion can be challenging. This is especially true for sub-Saharan African immigrants living in countries with predominantly European populations. This problem is further compounded by hereditary disorders such as sickle cell disease and by traditional cultural values that discourage routine donation. STUDY DESIGN AND METHODS: The purpose of this report is to describe the drive to recruit more safe rare blood type donors in a Comorian immigrant community living in Marseilles, France. With a culturally adapted message developed on an anthropologic approach and working in close collaboration with scientific and medical members of the Comorian community, it is proposed that this population be sensitized with the gift of blood. RESULTS: Targeted collection of specific sub-Saharan African blood types was achieved. Taking into account the high rate of infectious markers among products collected in this targeted collection, however, it was decided to promote blood donation in this minority by addressing people directly toward our principal blood center site. Since setup of this adapted communication, regular donors present themselves spontaneously without community pressure. Infectious markers rate is then equal to general blood donor population's rate. CONCLUSION: The results of this drive demonstrate the utility of an anthropologic approach and cultural mediation in identifying donors with specific blood types in migrant communities and recruiting second-generation donors. The techniques described in this study could also be applied to collection of other tissues including organs and peripheral blood progenitor cells in minorities.