Family Relationship,Water Contact and Occurrence of Buruli Ulcer in Benin

Background

Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities.

Objectives

This study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU).

Design

Case control study.

Setting

Department of Atlantique, Benin.

Subjects

BU-confirmed cases that were diagnosed and followed up at the BU detection and treatment center (CDTUB) of Allada (Department of the Atlantique, Benin) during the period from January 1st, 2006, to June 30th, 2008, with three matched controls (persons who had no signs or symptoms of active or inactive BU) for age, gender and village of residence per case.

Main Outcomes Measured

Contact with natural water sources, BU history in the family and the practice of consanguineous marriages.

Results

A total of 416 participants were included in this study, including 104 cases and 312 controls. BU history in the family (p<0.001), adjusted by daily contact with a natural water source (p = 0.007), was significantly associated with higher odds of having BU (OR; 95% CI = 5.5; 3.0–10.0). The practice of consanguineous marriage was not associated with the occurrence of BU (p = 0.40). Mendelian disorders could explain this finding, which may influence individual susceptibility by impairing immunity.

Conclusion

This study suggests that a combination of genetic factors and behavioral risk factors may increase the susceptibility for developing BU.     

A genomewide admixture mapping study for yield factors and morphological traits in a cultivated cocoa (Theobroma cacao L.) population

The selection of productive varieties of modern Criollo cocoa, showing fine aromatic qualities in their beans, is of major interest for some producing countries, such as Venezuela. Cultivated populations of Modern Criollo or Trinitario varieties may be suitable for admixture mapping analysis, as large blocks of alleles derived from two identified divergent ancestors, recently admixed, are still preserved, after a few generations of recombination, similar to experimental mapping progenies. Two hundred and fifty-seven individuals from a cultivated population of Modern Criollo were selected and analysed with 92 microsatellite markers distributed along the genome. This population exhibited a wide range of variability for yield factors and morphological features. Population structure analysis identified two main subgroups corresponding to the admixture from the two ancestors Criollo and Forastero. Several significant associations between markers and phenotypic data (yield factors and morphological traits) were identified by a least squares general linear model (GLM) taking into account the population structure and the percentage of admixture of each individual. Results were compared with classical QTL analyses previously reported for other cacao populations. Most markers associated to quantitative traits were very close to QTLs detected formerly for the same traits. Associations were also identified between markers and several qualitative traits including the red pigmentation observed in different organs, mainly associated to common markers in linkage group 4.     

Differential responses of proliferative and non-proliferative leukemia cells to oxidative stress

The response of three human leukemia cell lines, the proliferative promonocyte THP-1 and the promyeloid HL60 cells and the non-proliferative phorbol ester-treated HL60 cells (HL60/PMA), to oxidative stress induced by tert-butylhydroperoxide (t-BHP) treatment was analyzed by fluorescence microplate assay, anti-oxidant enzyme activity measurements, high performance liquid chromatography, yopro-1/PI incorporation, poly (ADP-ribose) polymerase and caspase 3 cleavages. After t-BHP treatment, the non-proliferative HL60/PMA cells exhibited a weak increase in reactive oxygen species (ROS) production, a better preservation of thiol content, a decrease of glutathione peroxidase activity and a high ability to undergo necrosis rather than apoptosis. Submitted to the same treatment, the proliferative HL60 and THP-1 cells exhibited a high increase of ROS production, a moderate thiol depletion and a high percentage of apoptosis. Under thiol depleting conditions, the oxidative treatment of the HL60/PMA cells resulted in a high ROS production that reached levels similar to those of the two other cell lines and in cell death mainly by necrosis. In conclusion, these results that show proliferative phenotype is essential for cell response towards oxidative stress, are of particular interest in chemotherapy involving an oxidative mechanism.     

Oxidation of tetrahydrobiopterin by peroxynitrite or oxoferryl species occurs by a radical pathway

The molecular mechanisms of tetrahydrobiopterin (BH₄) oxidation by peroxynitrite (ONOO^-) was studied using ultra-weak chemiluminescence, electron paramagnetic resonance (EPR) and UV-visible diodearray spectrophotometry, and compared to BH₄ oxidation by oxoferryl species produced by the myoglobin/hydrogen peroxide (Mb/H₂O₂) system. The oxidation of BH₄ by ONOO^- produced a weak chemiluminescence, which was altered by addition of 50 mM of the spin trap α-(4-pyridyl-1-oxide)-N-tert butylnitrone (POBN). EPR spin trapping demonstrated that the reaction occurred at least in part by a radical pathway. A mixture of two spectra composed by an intense six-line spectrum and a fleeting weak nine-line one was observed when using ONOO^-. Mb/H₂O₂ produced a short-living light emission that was suppressed by the addition of BH₄. Simultaneous addition of POBN, BH₄ and Mb/H₂O₂ produced the same six-line EPR spectrum, with a signal intensity depending on BH₄ concentration. Spectrophotometric studies confirmed the rapid disappearance of the characteristic peak of ONOO^- (302 nm) as well as substantial modifications of the initial BH₄ spectrum with both oxidant systems. These data demonstrated that BH₄ oxidation, either by ONOO^- or by Mb/H₂O₂, occurred with the production of activated species and by radical pathways.     

Role of gamma-synuclein in microtubule regulation

Gamma-synuclein is a neuronal protein found in peripheral and motor nerve systems. It becomes highly expressed in metastatic but not in primary tumor or normal tissues. The close association between gamma-synuclein expression and cancer spreading has been demonstrated in a broad range of malignancies. Our previous study showed that exogenous expression of gamma-synuclein in ovarian and breast cancer cells significantly enhanced cell migration and resistance to paclitaxel-induced apoptotic death. In our current research, we found that gamma-synuclein can affect microtubule properties and act as a functional microtubule associated protein. In vitro assays revealed that gamma-synuclein can bind and promote tubulin polymerization, induce the microtubule bundling and alter microtubule morphology developed in the presence of microtubule associated protein 2 (MAP2). Using cancer cell lysate, gamma-synuclein protein was found to be localized in both cytosolic compartment and extracted cytoskeleton portion. Immunofluorescence staining demonstrated that gamma-synuclein can colocalize with microtubule in HeLa cells and decrease rigidity of microtubule bundles caused by paclitaxel. In human ovarian cancer epithelial A2780 cells, gamma-synuclein overexpression improved cell adhesion and microtubule structure upon paclitaxel treatment. Importantly, it led to microtubule-dependent mitochondria clustering at perinuclear area. These observations suggest that overexpression of gamma-synuclein may reduce cell chemo-sensitivity of tumor cells through decreasing microtubule rigidity. In summary, our studies suggested that gamma-synuclein can directly participate in microtubule regulation.     

Diversity and spatial clustering of shade trees affect cacao yield and pathogen pressure in Costa Rican agroforests

The importance of the spatial organisation of individuals in explaining species coexistence within a community is widely recognised. However, few analyses of spatial structure have been performed on tropical agroforests.The main objective of this study was to highlight the links between spatial organisation of shade trees on the one hand, and shade tree species richness and cacao yield on the other, using data from 29 cacao agroforests in Costa Rica.A method of spatial statistics, Ripley's K-function, was used to analyse the spatial organisation of shade and cacao trees in the study plots. For each stand, the X and Y coordinates of ≥2.5-m-tall trees were recorded. In each plot we also assessed shade tree species richness and cacao yield (with total number of pods = number of pods damaged by frosty pod rot + number of healthy pods).Three types of stands were identified: the first was characterised by significant clustering of shade trees, the highest shade tree species richness (S = 6), and the highest number of damaged pods (139 pods ha^?1 year^?1). The second type was characterised by random spatial organisation of shade trees. The third type showed a trend towards regular organisation. Species richness of shade trees did not differ significantly between the last two types (S = 4 for both), nor did the number of damaged pods (56 pods ha^?1 year^?1 and 67 pods ha^?1 year^?1 respectively).Although the trends were not statistically significant for all the variables in our data set, the clustered spatial structure appears to favour a synergy between environmental (tree species richness), and provisioning (cacao production) services.     

Triphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels

The present work aims at identifying new ion channel modulators able to target mitochondrial ATP-sensitive potassium channels (mitoK_ATP channels). An innovative approach should consist in fixing a cationic and hydrophobic triphenylphosphonium fragment on the structure of known K_ATP channel openers. Such phosphonium salts are expected to cross the biological membranes and to accumulate into mitochondria.Previous works revealed that the presence of an (R)-1-hydroxy-2-propylamino chain at the 3-position of 4H-1,2,4-benzothiadiazine 1,1-dioxides K_ATP channel openers increased, in most cases, the selectivity towards the pancreatic-type (SUR1/Kir6.2) K_ATP channel. In order to target cardiac mitoK_ATP channels, we decided to introduce a triphenylphosphonium group through an ester link on the SUR1-selective (R)-7-chloro-3-(1-hydroxy-2-propyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide. The new compounds were found to preserve an inhibitory activity on insulin secretion (SUR1-type K_ATP channel openers) while no clear demonstration of an impact on mitochondria from cardiomyocytes (measurement of oxygen consumption, respiratory parameters and ATP production on H9C2 cells) was observed. However, the most active (inhibition of insulin release) compound 17 was found to penetrate the cardiac cells and to reach mitochondria.     

Comparison of the inhibition of human and Trypanosoma cruzi prolyl endopeptidases

Prolyl endopeptidases (PEPs) have been found in numerous species. Inhibitors of human enzyme could correct cognitive deficits in Alzheimer patients while inhibition of Trypanosoma cruzi PEP could prevent invasion phase in Chagas disease. A structure-activity relationship study carried out in a tetrahydroisoquinoline series allowed to obtain potent competitive inhibitors superior to SUAM-1221. Besides, inhibitors expected to act according to an irreversible mechanism revealed to be superior to JPT-4819, for applications linked to human enzyme inhibition.     

Serum concentrations of vitamin D metabolites, vitamins A and E, and carotenoids in six canid and four ursid species at four zoos

Nutritional status for six captive canid species (n=34) and four captive ursid species (n=18) were analyzed. The species analyzed included: African wild dog (Lycaon pictus), arctic fox (Alopex lagopus), gray wolf (Canis lupus), maned wolf (Chrysocyon brachyurus), Mexican wolf (Canis lupus baleiyi), red wolf (Canis rufus), brown bear (Ursus arctos), polar bear (Ursus maritimus), spectacled bear (Tremarctos ornatus), and sun bear (Ursus malayanus). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens, and North Carolina Zoological Park). The nutritional composition of the diet for each species at each institution met probable dietary requirements. Blood samples were collected from each animal and analyzed for vitamin D metabolites 25(OH)D and 1,25(OH)(2)D, vitamin A (retinol, retinyl stearate, retinyl palmitate), vitamin E (alpha-tocopherol and gamma-tocopherol) and selected carotenoids. Family differences were found for 25(OH)D, retinol, retinyl stearate, retinyl palmitate and gamma-tocopherol. Species differences were found for all detectable measurements. Carotenoids were not detected in any species. The large number of animals contributing to these data, provides a substantial base for comparing the nutritional status of healthy animals and the differences among them.