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1.
In response to the low levels of skilled birth attendance in rural Pakistan, the government introduced a new cadre of community midwives (CMWs) in 2006. Assessments to-date have found that these CMWs have yet to emerge as significant providers for a number of sociocultural, geographic and financial reasons. However, a small number of CMWs have managed to establish functional practices in the private sector in conservative, infrastructure-challenged rural contexts. With an objective to highlight “what are the successful CMWs doing right given their context?” this paper adopts an asset-based approach to explore the experiences of the Pakistani CMWs who have managed to overcome the barriers and practice. We drew upon ethnographic data that was collected as part of a larger mixed methods study conducted in 2011–2012 in districts Jhelum and Layyah, Pakistan. Thirty eight CMWs, 45 other health care providers, 20 policymakers, 78 women, 35 husbands and 23 older women were interviewed. CMW clinics and practices were observed. Our data showed that only eight 8 out of 38 CMWs sampled were active providers. Poverty as a push factor to work and intrinsic individual-level characteristics that enabled the CMWs to respond successfully to the demands of the midwifery profession in the private sector emerged as the two key themes. Household poverty pushed the CMWs to work in this perceived low-status occupation. Their families supported them since they became the breadwinners. The successful CMWs also had an intrinsic sense of what was required to establish a private practice; they exhibited professionalism, had strong business sense and provided respectful maternity care. The study provides insight into how the program might improve its functioning by adapting its recruitment criteria to ensure selection of right candidates. 相似文献
2.
Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite 总被引:2,自引:0,他引:2
Singh AP Buscaglia CA Wang Q Levay A Nussenzweig DR Walker JR Winzeler EA Fujii H Fontoura BM Nussenzweig V 《Cell》2007,131(3):492-504
The liver stages of malaria are clinically silent but have a central role in the Plasmodium life cycle. Liver stages of the parasite containing thousands of merozoites grow inside hepatocytes for several days without triggering an inflammatory response. We show here that Plasmodium uses a PEXEL/VTS motif to introduce the circumsporozoite (CS) protein into the hepatocyte cytoplasm and a nuclear localization signal (NLS) to enter its nucleus. CS outcompetes NFkappaB nuclear import, thus downregulating the expression of many genes controlled by NFkappaB, including those involved in inflammation. CS also influences the expression of over one thousand host genes involved in diverse metabolic processes to create a favorable niche for the parasite growth. The presence of CS in the hepatocyte enhances parasite growth of the liver stages in vitro and in vivo. These findings have far reaching implications for drug and vaccine development against the liver stages of the malaria parasite. 相似文献
3.
Mark-release-recapture experiments were undertaken in order to investigate the movement of adult Diabrotica virgifera virgifera LeConte from accidental introduction points towards suitable habitats, such as its host plant, Zea mays L. In Hungary in 2003 and 2004, nine mark-release-recapture experiments were carried out in a grass steppe area and lucerne field, in which two small maize fields (10x10 m) had been planted 300 m distant from the central release point. After each release of 5500 to 6000 marked D. v. virgifera, beetle recaptures were recorded three times using non-baited yellow sticky traps placed on 30, 105, 205 and 305 m radii around the release point. In seven out of 15 recapture periods (47%), beetle populations showed no directional movements, and their movements towards any particular habitat cannot be predicted. During five recapture periods (33%), beetle populations showed a uni-directional movement, and in three cases (20%) a bi-directional movement was observed. In 10 out of 15 recapture periods (67%), the released populations moved in a direction that was comparable with the mean wind direction during these periods; thus, beetle movements were slightly correlated with wind direction. On average over sites and years, beetles were not preferentially moving towards the two small maize fields (located 300 m from the release point) compared to other directions. However, beetles moved significantly more frequently in the direction of naturally-occurring maize fields within a radius of 1500 m than towards other habitats. Beetles stayed more frequently within flowering lucerne fields out to a radius of 300 and 600 m than in non-flowering lucerne or other habitats. On average, 2.8% (SD 3.2) of all recaptured beetles arrived in one of the two small maize fields located 300 m from their release point indicating that there is a high risk of a founder population establishing. Habitat management cannot be suggested as a means of preventing the beetle's initial dispersal because movement was usually non-directional, and alternative food plants were used prior to reaching maize. 相似文献
4.
Abstract: The Western Corn Rootworm, Diabrotica virgifera virgifera LeConte (Col., Chrysomelidae), is an invasive alien pest of maize, Zea mays , in Europe. The suitability of 14 fluorescent powders for mass-marking the adults was studied in laboratory and in field cages. The visual discrimination between remaining spots of each colour on the beetles was investigated under ultraviolet (UV) light, as well as their retention time and the influences of those colours on the beetle survival and flight take-off response. The two best recognizable orange colours (i.e. of Radiant Colour and of Fiesta Colours Swada) were proposed for field experiments in first priority, followed by an orange and a yellow (both Magruder Colour), another yellow (Fiesta) and a pink (Radiant), as all did not affect beetle survival and flight take-off response and were recognizable under UV light for at least 10 days in the field. In contrast, the colours yellow and green (Radiant), red and blue (Magruder), yellow (Ciba Geigy) and pink (Fiesta) were unsuitable, because they either quickly disappeared from the beetles or adversely affected beetle survival or flight take-off response. For mass releases with differently marked beetles, only the use of a single orange colour together with a single yellow colour or the use of a pink colour together with a yellow colour can be used since few spots can clearly be discriminated from each other under UV light. 相似文献
5.
Narayanan V Sandiford SL Wang Q Keren-Raifman T Levay K Slepak VZ 《Biochemistry》2007,46(23):6859-6870
The R7 family of RGS proteins (RGS6, -7, -9, -11) is characterized by the presence of three domains: DEP, GGL, and RGS. The RGS domain interacts with Galpha subunits and exhibits GAP activity. The GGL domain permanently associates with Gbeta5. The DEP domain interacts with the membrane anchoring protein, R7BP. Here we provide evidence for a novel interaction within this complex: between the DEP domain and Gbeta5. GST fusion of the RGS7 DEP domain (GST-R7DEP) binds to both native and recombinant Gbeta5-RGS7, recombinant Gbetagamma complexes, and monomeric Gbeta5 and Gbeta1 subunits. Co-immunoprecipitation and FRET assays supported the GST pull-down experiments. GST-R7DEP reduced FRET between CFP-Gbeta5 and YFP-RGS7, indicating that the DEP-Gbeta5 interaction is dynamic. In transfected cells, R7BP had no effect on the Gbeta5/RGS7 pull down by GST-R7DEP. The DEP domain of RGS9 did not bind to Gbeta5. Substitution of RGS7 Glu-73 and Asp-74 for the corresponding Ser and Gly residues (ED/SG mutation) of RGS9 diminished the DEP-Gbeta5 interaction. In the absence of R7BP both the wild-type RGS7 and the ED/SG mutant attenuated muscarinic M3 receptor-mediated Ca2+ mobilization. In the presence of R7BP, wild-type RGS7 lost this inhibitory activity, whereas the ED/SG mutant remained active. Taken together, our results are consistent with the following model. The Gbeta5-RGS7 molecule can exist in two conformations: "closed" and "open", when the DEP domain and Gbeta5 subunit either do or do not interact. The closed conformation appears to be less active with respect to its effect on Gq-mediated signaling than the open conformation. 相似文献
6.
Rosenzweig DH Nair KS Levay K Peshenko IV Crabb JW Dizhoor AM Slepak VZ 《The Biochemical journal》2009,417(3):803-812
Vertebrate phototransduction is mediated by cGMP, which is generated by retGC (retinal guanylate cyclase) and degraded by cGMP phosphodiesterase. Light stimulates cGMP hydrolysis via the G-protein transducin, which directly binds to and activates phosphodiesterase. Bright light also causes relocalization of transducin from the OS (outer segments) of the rod cells to the inner compartments. In the present study, we show experimental evidence for a previously unknown interaction between G(alphat) (the transducin alpha subunit) and retGC. G(alphat) co-immunoprecipitates with retGC from the retina or from co-transfected COS-7 cells. The retGC-G(alphat) complex is also present in cones. The interaction also occurs in mice lacking RGS9 (regulator of G-protein signalling 9), a protein previously shown to associate with both G(alphat) and retGC. The G(alphat)-retGC interaction is mediated primarily by the kinase homology domain of retGC, which binds GDP-bound G(alphat) stronger than the GTP[S] (GTPgammaS; guanosine 5'-[gamma-thio]triphosphate) form. Neither G(alphat) nor G(betagamma) affect retGC-mediated cGMP synthesis, regardless of the presence of GCAP (guanylate cyclase activating protein) and Ca2+. The rate of light-dependent transducin redistribution from the OS to the inner segments is markedly accelerated in the retGC-1-knockout mice, while the migration of transducin to the OS after the onset of darkness is delayed. Supplementation of permeabilized photoreceptors with cGMP does not affect transducin translocation. Taken together, these results suggest that the protein-protein interaction between G(alphat) and retGC represents a novel mechanism regulating light-dependent translocation of transducin in rod photoreceptors. 相似文献
7.
Liapis E Sandiford S Wang Q Gaidosh G Motti D Levay K Slepak VZ 《Journal of neurochemistry》2012,122(3):568-581
The R7 family of regulators of G protein signaling (RGS) is involved in many functions of the nervous system. This family includes RGS6, RGS7, RGS9, and RGS11 gene products and is defined by the presence of the characteristic first found in Disheveled, Egl-10, Pleckstrin (DEP), DEP helical extension (DHEX), Gγ-like, and RGS domains. Herein, we examined the subcellular localization of RGS7, the most broadly expressed R7 member. Our immunofluorescence studies of retinal and dorsal root ganglion neurons showed that RGS7 concentrated at the plasma membrane of cell bodies, in structures resembling lamellipodia or filopodia along the processes, and at the dendritic tips. At the plasma membrane of dorsal root ganglia neurons, RGS7 co-localized with its known binding partners R7 RGS binding protein (R7BP), Gαo, and Gαq. More than 50% of total RGS7-specific immunofluorescence was present in the cytoplasm, primarily within numerous small puncta that did not co-localize with R7BP. No specific RGS7 or R7BP immunoreactivity was detected in the nuclei. In transfected cell lines, ectopic RGS7 had both diffuse cytosolic and punctate localization patterns. RGS7 also localized in centrosomes. Structure-function analysis showed that the punctate localization was mediated by the DEP/DHEX domains, and centrosomal localization was dependent on the DHEX domain. 相似文献
8.
Ames JB Levay K Wingard JN Lusin JD Slepak VZ 《The Journal of biological chemistry》2006,281(48):37237-37245
Recoverin, a member of the neuronal calcium sensor branch of the EF-hand superfamily, serves as a calcium sensor that regulates rhodopsin kinase (RK) activity in retinal rod cells. We report here the NMR structure of Ca(2+)-bound recoverin bound to a functional N-terminal fragment of rhodopsin kinase (residues 1-25, called RK25). The overall main-chain structure of recoverin in the complex is similar to structures of Ca(2+)-bound recoverin in the absence of target (<1.8A root-mean-square deviation). The first eight residues of recoverin at the N terminus are solvent-exposed, enabling the N-terminal myristoyl group to interact with target membranes, and Ca(2+) is bound at the second and third EF-hands of the protein. RK25 in the complex forms an amphipathic helix (residues 4-16). The hydrophobic face of the RK25 helix (Val-9, Val-10, Ala-11, Ala-14, and Phe-15) interacts with an exposed hydrophobic groove on the surface of recoverin lined by side-chain atoms of Trp-31, Phe-35, Phe-49, Ile-52, Tyr-53, Phe-56, Phe-57, Tyr-86, and Leu-90. Residues of recoverin that contact RK25 are highly conserved, suggesting a similar target binding site structure in all neuronal calcium sensor proteins. Site-specific mutagenesis and deletion analysis confirm that the hydrophobic residues at the interface are necessary and sufficient for binding. The recoverin-RK25 complex exhibits Ca(2+)-induced binding to rhodopsin immobilized on concanavalin-A resin. We propose that Ca(2+)-bound recoverin is bound between rhodopsin and RK in a ternary complex on rod outer segment disk membranes, thereby blocking RK interaction with rhodopsin at high Ca(2+). 相似文献
9.
Balasubramanian N Levay K Keren-Raifman T Faurobert E Slepak VZ 《Biochemistry》2001,40(42):12619-12627
In vertebrate photoreceptors, photoexcited rhodopsin interacts with the G protein transducin, causing it to bind GTP and stimulate the enzyme cGMP phosphodiesterase. The rapid termination of the active state of this pathway is dependent upon a photoreceptor-specific regulator of G protein signaling RGS9-1 that serves as a GTPase activating protein (GAP) for transducin. Here, we show that, in preparations of photoreceptor outer segments (OS), RGS9-1 is readily phosphorylated by an endogenous Ser/Thr protein kinase. Protein kinase C and MAP kinase inhibitors reduced labeling by about 30%, while CDK5 and CaMK II inhibitors had no effect. cAMP-dependent protein kinase (PKA) inhibitor H89 reduced RGS9-1 labeling by more than 90%, while dibutyryl-cAMP stimulated it 3-fold, implicating PKA as the major kinase responsible for RGS9-1 phosphorylation in OS. RGS9-1 belongs to an RGS subfamily also including RGS6, RGS7, and RGS11, which exist as heterodimers with the G protein beta subunit Gbeta5. Phosphorylated RGS9-1 remains associated with Gbeta5L, a photoreceptor-specific splice form, which itself was not phosphorylated. RGS9-1 immunoprecipitated from OS was in vitro phosphorylated by exogenous PKA. The PKA catalytic subunit could also phosphorylate recombinant RGS9-1, and mutational analysis localized phosphorylation sites to Ser(427) and Ser(428). Substitution of these residues for Glu, to mimic phosphorylation, resulted in a reduction of the GAP activity of RGS9-1. In OS, RGS9-1 phosphorylation required the presence of free Ca(2+) ions and was inhibited by light, suggesting that RGS9-1 phosphorylation could be one of the mechanisms mediating a stronger photoresponse in dark-adapted cells. 相似文献
10.