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Lee D  Park SJ  Sung KS  Park J  Lee SB  Park SY  Lee HJ  Ahn JW  Choi SJ  Lee SG  Kim SH  Kim DH  Kim J  Kim Y  Choi CY 《EMBO reports》2012,13(2):163-169
The Ras effector NORE1 is frequently silenced in primary adenocarcinomas, although the significance of this silencing for tumorigenesis is unclear. Here we show that NORE1 induces polyubiquitination and proteasomal degradation of oncoprotein HIPK1 by facilitating its interaction with the Mdm2 E3 ubiquitin ligase. Endogenous HIPK1 is stabilized in Nore1-deficient mouse embryonic fibroblasts, and depletion of HIPK1 in NORE1-silenced lung adenocarcinoma cells inhibits anchorage-independent cell growth and tumour formation in nude mice. These findings indicate that the control of HIPK1 stability by Mdm2-NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization.  相似文献   
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Background

Timely presentation to appropriate health service provider of sick animals/humans from zoonotic diseases like rabies is important for early case/outbreak detection and management. However, data on community’s health seeking practice for rabies in Ethiopia is limited. Therefore the objective of this study was to determine community’s health seeking behavior on rabies, Southwest Ethiopia.

Methods

A cross-sectional survey was conducted from January 16-February 14, 2015 to collect data from 808 respondents where the respondents were selected using multistage sampling technique. Data were collected using interviewer administered structured questionnaire by trained epidemiology graduate level students. Data were entered to Epidata version 3.1 and analyzed using SPSS version 20 for windows.

Result

Eight hundred three (99.4%) respondents participated in the study. Out of 28 respondents who reported their family members’ exposure to rabies, 8 of them replied that the exposed family members sought treatment from traditional healers. More than nine in ten respondents perceived that humans and domestic animals with rabies exposure should seek help of which 85% of them suggested modern health care facilities as the preferred management option for the sick humans and domestic animals. However, among those who reported sick domestic animals, near to 72% of them had either slaughtered for human consumption, sold immediately, visited traditional healer, given home care or did nothing for the sick domestic animals.

Conclusion

Majority of the respondents had favorable perception of seeking treatment from modern health care facilities for rabies. However, significant number of them had managed inappropriately for the sick domestic animals from rabies. Hence, raising awareness of the community about management of sick domestic animals from rabies and the need for reporting to both human and animal health service providers is needed.  相似文献   
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BackgroundThe numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions.MethodsA longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25+ cells.Results30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25+ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25+ cells to CD25+ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25+ cells either before or after treatment. Depleting CD25+ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25+ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25+ cells.ConclusionThe findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25+ cells. Our results suggest that the suppressive function of Tregs in ENL is intact despite ENL being associated with reduced numbers of Tregs. The lack of difference in IL-10 response in control PBMCs and CD25+ depleted PBMCs in individuals with LL and the increased IL-10 response following the depletion of CD25+ cells in individuals with untreated ENL suggest that the mechanism of immune regulation by Tregs in leprosy appears independent of IL-10 or that other cells may be responsible for IL-10 production in leprosy. The present findings highlight mechanisms of T cell regulation in LL and ENL and provide insights into the control of peripheral immune tolerance, identifying Tregs as a potential therapeutic target.  相似文献   
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A new phenylanthrone, named knipholone cyclooxanthrone and a dimeric anthraquinone, 10-methoxy-10,7′-(chrysophanol anthrone)-chrysophanol were isolated from the roots of Kniphofia foliosa together with the rare naphthalene glycoside, dianellin. The structures were determined by NMR and mass spectroscopic techniques. The compounds showed antiplasmodial activities against the chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum with 10-methoxy-10,7′-(chrysophanol anthrone)-chrysophanol being the most active with IC50 values of 1.17 ± 0.12 and 4.07 ± 1.54 μg/ml, respectively.  相似文献   
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The RASSF family proteins were identified as tumor suppressors in a variety of human cancers, and evidenced distinct subcellular localization patterns among their subfamilies and isoforms. In this study, we showed that NORE1A was exported actively via its nuclear export signal (NES) in the C-terminus (residues 372-379). Substitutions of three lysine residues of NORE1A NES to alanines (L372, 376, 379A) showed its localization to the dot structures of the nucleus, which was similar to the NORE1A localizations observed after the administration to cells of Leptomycin B, a nuclear export inhibitor. The NORE1A NES mutant inhibited caspase-mediated apoptosis, whereas wild-type NORE1A induced caspase-3 activation. Furthermore, the NORE1A NES mutant did not co-localize with GFP-MST1, the direct downstream target of NORE1A. These results show that the nuclear export of NORE1A via NES is involved in the NORE1A-mediated induction of apoptosis.  相似文献   
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A range of activities are currently underway to improve access to malaria prevention and control interventions. As disease control strategies change over time, it is crucial to understand the health-seeking behaviour and the local socio-cultural context in which the changes in interventions operate. This paper reflects on how people in an area of seasonal malaria perceive the causes and transmission of the disease, and what prevention and treatment measures they practise to cope with the disease. It also highlights some of the challenges of malaria treatment for health care providers. The study was undertaken in 2003 in Adami Tulu District in south-central Ethiopia, where malaria is a major health problem. Pre-tested structured questionnaires and focus group discussions were conducted among men and women. Malaria, locally known as busa, was perceived as the most important cause of ill health in the area. Respondent's perception and knowledge about the cause and transmission of the disease were relatively high. The newly introduced insecticide-treated nets were not popular in the area, and only 6.4% of households possessed at least one. The results showed that patients use multiple sources of health care for malaria treatment. Public health facilities, private clinics and community health workers were the main providers of malaria treatment. Despite higher treatment costs, people preferred to use private health care providers for malaria treatment due to the higher perceived quality of care they offer. In conclusion, effort in the prevention and control of malaria should be intensified through addressing not only public facilities, but also the private sector and community-based control interventions. Appropriate and relevant information on malaria should be disseminated to the local community. The authors propose the provision of effective antimalarial drugs and malaria prevention tools such as subsidized or free insecticide-treated nets.  相似文献   
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The population dynamics of the white wax scale, Ceroplastes destructor Newstead, was studied intensively in four easy-peel citrus orchards in the Western Cape Province of South Africa over three consecutive years (1997-1999). Key factor analysis was used to determine and quantify the contribution of individual mortality factors to the total generation mortality. Key stage mortality, determined from a cohort life table, was in the third instar and pre-ovipositing female stages. Mortality of C. destructor was caused primarily by parasitoids, predators and miscellaneous factors. Parasitoids and miscellaneous factors acted as density-dependent regulatory agents during the pre-ovipositional and first instar stages respectively. This has implications for biological control of C. destructor. Some of the mortality factors acted either randomly with no reference to the population densities or in an inverse density-dependent manner during the egg-crawler, second or third instar stages.  相似文献   
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