Kuenzel W.J.,University of Arkansas |
Hancock M.,University of Arkansas |
Nagarajan G.,University of Arkansas |
Aman N.A.,University of Arkansas |
And 2 more authors.
Neuroscience Letters | Year: 2016
Previous studies identified SR-49059 as a most effective antagonist of the avian vasotocin 4 receptor (VT4R) compared to other candidate blockers including the Manning compound using in silico 3 dimensional (3D) modeling/docking analysis of the chicken VT4R and an in vitro anterior pituitary cell culture study. The present experiments were designed to validate whether SR-49059 and the Manning compound would likewise be effective in vivo in blocking the VT4R when applied intracerebroventricularly (ICV) to chicks. Two treatments were tested, a stressor (immobilization) and administration of neuropeptide Y (NPY), a potent orexigenic compound. In the first experiment, birds were given the Manning compound, SR-49059 or physiological saline ICV followed by immobilization stress. Blood samples were taken and corticosterone (CORT) was determined by radioimmunoassay. It was hypothesized that both antagonists would reduce the stress response. A second experiment examined the role of the VT4R in food intake regulation. The Manning compound, SR-49059 or physiological saline was administered prior to NPY and food intake was monitored for 1 h. It was hypothesized that each of the two antagonists coupled with NPY would augment food intake above the intake resulting from saline plus NPY administration. Related to the second experiment was a third that examined the difference between the effect of central administration of NPY versus SR-49059 in releasing CORT. Results of the first study showed that the Manning compound or SR-49059 prior to stress decreased CORT levels compared to controls while the second experiment showed that SR-49059 or the Manning compound plus NPY, enhanced food intake above that of the experimental group given saline and NPY. The last study showed that NPY increased plasma CORT above birds given SR-49059 centrally or saline administered controls. Taken together, results suggest that the avian VT4R is involved in the central neuroendocrine stress response as well as functions in appetite regulation by mediating an anorexigenic effect similar to what has been reported in mammals for the V1aR. In conclusion, similar to the past in silico and in vitro tests, the current in vivo experiments showed SR-49059 to be a most efficacious avian vasotocin receptor antagonist. Therefore based upon results of functional tests utilizing a highly specific mammalian antagonist, SR-49059, to the mammalian V1aR that likewise was most effective in blocking the avian VT4R and past reported high sequence homology between the mammalian V1aR and the VT4R, it is recommended that the chicken VT4R be renamed the avian V1aR to facilitate better communication among scientists involved in comparative studies. © 2016 Elsevier Ireland Ltd.
Mari Saez A.,Charite - Medical University of Berlin |
Weiss S.,Robert Koch Institute |
Weiss S.,U.S. Center for Disease Control and Prevention |
Weiss S.,Public Health England |
And 32 more authors.
EMBO Molecular Medicine | Year: 2015
The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2-year-old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free-tailed bats (Mops condylurus). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology. Synopsis: The severe Ebola virus disease epidemic occurring in West Africa likely stems from a single zoonotic transmission event involving a 2-year-old boy in Meliandou, Guinea, who might have been infected by hunting or playing with insectivorous free-tailed bats living in a nearby hollow tree. Monitoring data show that larger wildlife did not experience a recent decline and is therefore unlikely to have served as the source for the Ebola virus disease epidemic in West Africa. Fruit bat hunting and butchering are common activities in southern Guinea, therefore facilitating direct human contact. Children are also exposed to insectivorous bats through hunting in and around villages. No large colony of fruit bats exists in or nearby the index village (Meliandou). The 2-year-old index case may have been infected by playing in a hollow tree housing a colony of insectivorous free-tailed bats (Mops condylurus). The severe Ebola virus disease epidemic occurring in West Africa likely stems from a single zoonotic transmission event involving a 2-year-old boy in Meliandou, Guinea, who might have been infected by hunting or playing with insectivorous free-tailed bats living in a nearby hollow tree. © 2014 The Authors.
Glinz D.,ETH Zurich |
Hurrell R.F.,ETH Zurich |
Ouattara M.,Felix Houphouet-Boigny University |
Zimmermann M.B.,ETH Zurich |
And 10 more authors.
Malaria Journal | Year: 2015
Background: Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. Methods: A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). Results: After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 μg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001). Conclusions: IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions. Trial registration: http://www.clinicaltrials.gov; identifier NCT01634945; registered on July 3, 2012. © 2015 Glinz et al.
Hoppe E.,Robert Koch Institute |
Pauly M.,Robert Koch Institute |
Gillespie T.R.,Emory University |
Akoua-Koffi C.,Alassane Ouattara University |
And 18 more authors.
Molecular biology and evolution | Year: 2015
Human adenoviruses (HAdV; species HAdV-A to -G) are highly prevalent in the human population, and represent an important cause of morbidity and, to a lesser extent, mortality. Recent studies have identified close relatives of these viruses in African great apes, suggesting that some HAdV may be of zoonotic origin. We analyzed more than 800 fecal samples from wild African great apes and humans to further investigate the evolutionary history and zoonotic potential of hominine HAdV. HAdV-B and -E were frequently detected in wild gorillas (55%) and chimpanzees (25%), respectively. Bayesian ancestral host reconstruction under discrete diffusion models supported a gorilla and chimpanzee origin for these viral species. Host switches were relatively rare along HAdV evolution, with about ten events recorded in 4.5 My. Despite presumably rare direct contact between sympatric populations of the two species, transmission events from gorillas to chimpanzees were observed, suggesting that habitat and dietary overlap may lead to fecal-oral cross-hominine transmission of HAdV. Finally, we determined that two independent HAdV-B transmission events to humans occurred more than 100,000 years ago. We conclude that HAdV-B circulating in humans are of zoonotic origin and have probably affected global human health for most of our species lifetime. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Mossoun A.,Felix Houphouet-Boigny University |
Pauly M.,Robert Koch Institute |
Pauly M.,Luxembourg Institute of Health |
Akoua-Koffi C.,Alassane Ouattara University |
And 6 more authors.
EcoHealth | Year: 2015
Elevated exposure levels to non-human primates (NHP) and NHP bushmeat represent major risk factors for zoonotic disease transmission in sub-Saharan Africa. Demography can affect personal nutritional behavior, and thus rates of contact to NHP bushmeat. Here, we analyzed demographic and NHP contact data from 504 participants of differing demographic backgrounds living in proximity to the Taï National Park in Western Côte d’Ivoire (CI) to identify factors impacting the risk of NHP exposure. Overall, participants’ contact rates to NHP were high, and increased along a gradient of bushmeat processing (e.g., 7.7% hunted, but 61.9% consumed monkeys). Contact to monkeys was significantly more frequent than to chimpanzees, most likely a reflection of meat availability and hunting effort. 17.2% of participants reported previous interaction with NHP pets. Generalized linear mixed model analysis revealed significant effects of sex, country of birth or ethnicity on rates of NHP bushmeat contact, with male participants from CI being at particular risk of exposure to NHP. The presence of zoonotic pathogens in humans and NHP in Taï further highlights the risk for zoonotic disease emergence in this region. Our results are relevant for formulating prevention strategies to reduce zoonotic pathogen burden in tropical Africa. © 2015, International Association for Ecology and Health.