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1.
Western lifestyle plays an important role in the prevalence of type 2 diabetes by causing insulin resistance and pancreatic
β-cell dysfunction, a prerequisite for the development of diabetes. High fat diet and alcohol are major components of the
western diet. The aim of the present study was to investigate the effects of ethanol and fatty acids on β-cell survival and
metabolism. We treated the rat β-cell line RINm5F with ethanol, a mixture of palmitic and oleic acids, or both. Reactive oxygen
species (ROS) were determined by (5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate) (CM-H2DCFDA) fluorescence
assay, and mitochondrial activity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction
assay and by determining ATP production. Cell viability was assessed with a cell counter and trypan blue exclusion, and the
mode of cell death by Hoechst33342 and propidium iodide staining. With both ethanol and fatty acid treatments, MTT reduction
and ATP production decreased, whereas ROS production increased. Ethanol treatment had no effect on cell number, whereas fatty
acid treatment reduced the cell number. Cell incubation with ethanol, fatty acids, or both increased the number of Hoechst
33342-positive nuclei. However, the majority of nuclei from fatty acid-treated cells were stained with propidium iodide, indicating
a loss of plasma membrane integrity. We conclude that both ethanol and fatty acids generate cellular oxidative stress, and
affect mitochondrial function in RINm5F β-cells. However, ethanol causes β-cell death by apoptosis, whereas fatty acids cause
cell death predominantly by necrosis. It is not known whether these results are applicable to human β-cells. 相似文献
2.
Sanoussi Bamani Jonathan D. King Mamadou Dembele Famolo Coulibaly Dieudonne Sankara Yaya Kamissoko Jim Ting Lisa A. Rotondo Paul M. Emerson 《PLoS neglected tropical diseases》2010,4(7)
Objectives
A national survey in 1997 demonstrated that trachoma was endemic in Mali. Interventions to control trachoma including mass drug administration (MDA) with azithromycin were launched in the regions of Kayes and Koulikoro in 2003. MDA was discontinued after three annual rounds in 2006, and an impact survey conducted. We resurveyed all districts in Kayes and Koulikoro in 2009 to reassess trachoma prevalence and determine intervention objectives for the future. In this paper we present findings from both the 2006 and 2009 surveys.Methods
Population-based cluster surveys were conducted in each of the nine districts in Koulikoro in 2006 and 2009, whilst in Kayes, four of seven districts in 2006 and all seven districts in 2009 were surveyed. Household members present were examined for clinical signs of trachoma.Results
Overall, 29,179 persons from 2,528 compounds, in 260 clusters were examined in 2006 and 32,918 from 7,533 households in 320 clusters in 2009. The prevalence of TF in children aged 1–9 years in Kayes and Koulikoro was 3.9% (95%CI 2.9–5.0%, range by district 1.2–5.4%) and 2.7% (95%CI 2.3–3.1%, range by district 0.1–5.0%) respectively in 2006. In 2009 TF prevalence was 7.26% (95%CI 6.2–8.2%, range by district 2.5–15.4%) in Kayes and 8.19% (95%CI 7.3–9.1%, range by district 1.7–17.2%) in Koulikoro among children of the same age group. TT in adults 15 years of age and older was 2.37% (95%CI 1.66–3.07%, range by district 0.30–3.54%) in 2006 and 1.37% (95%CI 1.02–1.72%, range by district 0.37–1.87%) in 2009 in Kayes and 1.75% (95%CI 1.31–2.23%, range by district 1.06–2.49%) in 2006 and 1.08% (95%CI 0.86–1.30%, range by district 0.34–1.78%) in 2009 in Koulikoro.Conclusions
Using WHO guidelines for decision making, four districts, Bafoulabe in Kayes Region; and Banamba, Kolokani and Koulikoro in Koulikoro Region, still meet criteria for district-wide implementation of the full SAFE strategy as TF in children exceeds 10%. A community-by-community approach to trachoma control may now be required in the other twelve districts. Trichiasis surgery provision remains a need in all districts and should be enhanced in six districts in Kayes and five in Koulikoro where the prevalence exceeded 1.0% in adults. Since 1997 great progress has been observed in the fight against blinding trachoma; however, greater effort is required to meet the elimination target of 2015. 相似文献3.
Raveau M Lignon JM Nalesso V Duchon A Groner Y Sharp AJ Dembele D Brault V Hérault Y 《PLoS genetics》2012,8(5):e1002724
Down syndrome (DS) leads to complex phenotypes and is the main genetic cause of birth defects and heart diseases. The Ts65Dn DS mouse model is trisomic for the distal part of mouse chromosome 16 and displays similar features with post-natal lethality and cardiovascular defects. In order to better understand these defects, we defined electrocardiogram (ECG) with a precordial set-up, and we found conduction defects and modifications in wave shape, amplitudes, and durations in Ts65Dn mice. By using a genetic approach consisting of crossing Ts65Dn mice with Ms5Yah mice monosomic for the App-Runx1 genetic interval, we showed that the Ts65Dn viability and ECG were improved by this reduction of gene copy number. Whole-genome expression studies confirmed gene dosage effect in Ts65Dn, Ms5Yah, and Ts65Dn/Ms5Yah hearts and showed an overall perturbation of pathways connected to post-natal lethality (Coq7, Dyrk1a, F5, Gabpa, Hmgn1, Pde10a, Morc3, Slc5a3, and Vwf) and heart function (Tfb1m, Adam19, Slc8a1/Ncx1, and Rcan1). In addition cardiac connexins (Cx40, Cx43) and sodium channel sub-units (Scn5a, Scn1b, Scn10a) were found down-regulated in Ts65Dn atria with additional down-regulation of Cx40 in Ts65Dn ventricles and were likely contributing to conduction defects. All these data pinpoint new cardiac phenotypes in the Ts65Dn, mimicking aspects of human DS features and pathways altered in the mouse model. In addition they highlight the role of the App-Runx1 interval, including Sod1 and Tiam1, in the induction of post-natal lethality and of the cardiac conduction defects in Ts65Dn. These results might lead to new therapeutic strategies to improve the care of DS people. 相似文献
4.
5.
Dembele K Yao XH Chen L Nyomba BL 《American journal of physiology. Regulatory, integrative and comparative physiology》2006,291(3):R796-R802
Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life. 相似文献
6.
In this paper, we introduce a model of malaria, a disease that involves a complex life cycle of parasites, requiring both human and mosquito hosts. The novelty of the model is the introduction of periodic coefficients into the system of one-dimensional equations, which account for the seasonal variations (wet and dry seasons) in the mosquito birth and death rates. We define a basic reproduction number R(0) that depends on the periodic coefficients and prove that if R(0)<1 then the disease becomes extinct, whereas if R(0)>1 then the disease is endemic and may even be periodic. 相似文献
7.
Fugier C Klein AF Hammer C Vassilopoulos S Ivarsson Y Toussaint A Tosch V Vignaud A Ferry A Messaddeq N Kokunai Y Tsuburaya R de la Grange P Dembele D Francois V Precigout G Boulade-Ladame C Hummel MC Lopez de Munain A Sergeant N Laquerrière A Thibault C Deryckere F Auboeuf D Garcia L Zimmermann P Udd B Schoser B Takahashi MP Nishino I Bassez G Laporte J Furling D Charlet-Berguerand N 《Nature medicine》2011,17(6):720-725
Myotonic dystrophy is the most common muscular dystrophy in adults and the first recognized example of an RNA-mediated disease. Congenital myotonic dystrophy (CDM1) and myotonic dystrophy of type 1 (DM1) or of type 2 (DM2) are caused by the expression of mutant RNAs containing expanded CUG or CCUG repeats, respectively. These mutant RNAs sequester the splicing regulator Muscleblind-like-1 (MBNL1), resulting in specific misregulation of the alternative splicing of other pre-mRNAs. We found that alternative splicing of the bridging integrator-1 (BIN1) pre-mRNA is altered in skeletal muscle samples of people with CDM1, DM1 and DM2. BIN1 is involved in tubular invaginations of membranes and is required for the biogenesis of muscle T tubules, which are specialized skeletal muscle membrane structures essential for excitation-contraction coupling. Mutations in the BIN1 gene cause centronuclear myopathy, which shares some histopathological features with myotonic dystrophy. We found that MBNL1 binds the BIN1 pre-mRNA and regulates its alternative splicing. BIN1 missplicing results in expression of an inactive form of BIN1 lacking phosphatidylinositol 5-phosphate-binding and membrane-tubulating activities. Consistent with a defect of BIN1, muscle T tubules are altered in people with myotonic dystrophy, and membrane structures are restored upon expression of the normal splicing form of BIN1 in muscle cells of such individuals. Finally, reproducing BIN1 splicing alteration in mice is sufficient to promote T tubule alterations and muscle weakness, a predominant feature of myotonic dystrophy. 相似文献
8.
Mehmood T Schneider A Sibille J Sibillec J Marques Pereira P Pannetier S Ammar MR Dembele D Thibault-Carpentier C Rouach N Hanauer A 《Human genetics》2011,129(3):255-269
Coffin–Lowry syndrome (CLS) is a syndromic form of mental retardation caused by loss of function mutations in the X-linked
RPS6KA3 gene, which encodes RSK2, a serine/threonine kinase acting in the MAPK/ERK pathway. The mouse invalidated for the Rps6ka3 (Rsk2-KO) gene displays learning and long-term spatial memory deficits. In the current study, we compared hippocampal gene expression
profiles from Rsk2-KO and normal littermate mice to identify changes in molecular pathways. Differential expression was observed for 100 genes
encoding proteins acting in various biological pathways, including cell growth and proliferation, cell death and higher brain
function. The twofold up-regulated gene (Gria2) was of particular interest because it encodes the subunit GLUR2 of the AMPA glutamate receptor. AMPA receptors mediate most
fast excitatory synaptic transmission in the central nervous system. We provide evidence that in the hippocampus of Rsk2-KO mice, expression of GLUR2 at the mRNA and at the protein levels is significantly increased, whereas basal AMPA receptor-mediated
transmission in the hippocampus of Rsk2-KO mice is significantly decreased. This is the first time that such deregulations have been demonstrated in the mouse model
of the Coffin–Lowry syndrome. Our findings suggest that a defect in AMPA neurotransmission and plasticity contribute to mental
retardation in CLS patients. 相似文献
9.
Housseini Dolo Yaya I. Coulibaly Benoit Dembele Siaka Konate Siaka Y. Coulibaly Salif S. Doumbia Abdallah A. Diallo Lamine Soumaoro Michel E. Coulibaly Seidina A. S. Diakite Aldiouma Guindo Michael P. Fay Simon Metenou Thomas B. Nutman Amy D. Klion 《PLoS neglected tropical diseases》2012,6(11)
Background
Wuchereria bancrofti (Wb) and Mansonella perstans (Mp) are blood-borne filarial parasites that are endemic in many countries of Africa, including Mali. The geographic distribution of Wb and Mp overlaps considerably with that of malaria, and coinfection is common. Although chronic filarial infection has been shown to alter immune responses to malaria parasites, its effect on clinical and immunologic responses in acute malaria is unknown.Methodology/Principal Findings
To address this question, 31 filaria-positive (FIL+) and 31 filaria-negative (FIL−) children and young adults, matched for age, gender and hemoglobin type, were followed prospectively through a malaria transmission season. Filarial infection was defined by the presence of Wb or Mp microfilariae on calibrated thick smears performed between 10 pm and 2 am and/or by the presence of circulating filarial antigen in serum. Clinical malaria was defined as axillary temperature ≥37.5°C or another symptom or sign compatible with malaria infection plus the presence of asexual malaria parasites on a thick blood smear. Although the incidence of clinical malaria, time to first episode, clinical signs and symptoms, and malaria parasitemia were comparable between the two groups, geometric mean hemoglobin levels were significantly decreased in FIL− subjects at the height of the transmission season compared to FIL+ subjects (11.4 g/dL vs. 12.5 g/dL, p<0.01). Plasma levels of IL-1ra, IP-10 and IL-8 were significantly decreased in FIL+ subjects at the time of presentation with clinical malaria (99, 2145 and 49 pg/ml, respectively as compared to 474, 5522 and 247 pg/ml in FIL− subjects).Conclusions/Significance
These data suggest that pre-existent filarial infection attenuates immune responses associated with severe malaria and protects against anemia, but has little effect on susceptibility to or severity of acute malaria infection. The apparent protective effect of filarial infection against anemia is intriguing and warrants further study in a larger cohort. 相似文献10.
Catherine Ky‐Dembele Mulualem Tigabu Jules Bayala Sibiri Jean Ouédraogo Per Christer Odén 《African Journal of Ecology》2008,46(4):602-611
An understanding of the proportion of true seedlings, seedling sprouts and root suckers in the forest is essential for directing the genetic composition of the future crop. We conducted a study to determine the difference between these plantlets of Detarium microcarpum based on morphological characters and carbohydrate contents in leaves and roots. For individuals ≤50 cm in height, root suckers had the highest values for height, stem length, internode number, root diameter, rachis length and leaflet number. The concentrations of starch and total nonstructural carbohydrates in the roots of seedling sprouts were superior. Plantlets did not differ in the concentration of leaf carbohydrates. For individuals >50 cm in height, root suckers had larger values for stem length, root diameter, leaflet length and width. Roots of seedling sprouts showed higher concentrations of soluble sugars and total soluble sugars. True seedlings were distinguished from seedling sprouts and root suckers using all morphological traits except collar diameter and leaflet number. Root suckers and seedling sprouts showed a closer morphological resemblance; thus resulted in slightly more than 50% discrimination success. In conclusion, discrimination between seedling sprouts and root suckers appeared to be more difficult than between true seedlings and clonal plantlets. 相似文献