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21.
Bolajoko Jatau Yohanna Avong Olumide Ogundahunsi Safieh Shah Katherine Tayler Smith Rafael Van den Bergh Rony Zachariah Johan van Griensven Ernest Ekong Patrick Dakum 《PloS one》2015,10(6)
Background
The World Health Organisation (WHO) introduced the twelve early warning indicators for monitoring and evaluating drug Procurement and Supply management (PSM) systems, intended to prevent drug stock-outs and overstocking. Nigeria- one of the high Multi Drug Resistant Tuberculosis (MDR-TB) burden countries, scaled-up treatment in 2012 with the concurrent implementation of a PSM system.Method
We evaluated how well this system functioned using the WHO indicators, including all seven MDR-TB treatment centres in the country that were functional throughout 2013.Results
The quantity of MDR-TB drugs ordered for 2013 matched the annual forecast and all central orders placed during the year were delivered in full and on time. Drug consumption was 81%–106% of the quantity allocated for routine consumption. Timely submission of complete inventory reports ranged from 86–100%, late submissions being 5–15 days late. Forty to 71% of treatment centres placed a drug order when stock was below the minimum level of three months. The proportion of drug orders received at the treatment centres in full and on time ranged from 29–80%, late orders being 1–19 days late.Conclusion
The PSM was found to be performing well in terms of forecasting and procurement of MDR-TB drugs, but there were shortcomings in drug distribution, reporting at treatment centre level and in drug order placements. Despite these gaps, there were no stock outs. These findings indicate that where it matters most, namely ensuring that no drug stock outs affect patient management, the PSM system is effective. Addressing the observed shortcomings will help to strengthen the existing PSM system in anticipation of a growing MDR-TB case burden in the country. 相似文献22.
Emmie Dornez Evi Croes Kurt Gebruers Sebastien Carpentier Rony Swennen Kris Laukens Erwin Witters Martin Urban Jan A. Delcour Christophe M. Courtin 《Proteomics》2010,10(12):2303-2319
Wheat contains three different classes of proteinaceous xylanase inhibitors (XIs), i.e. Triticum aestivum xylanase inhibitors (TAXIs) xylanase‐inhibiting proteins (XIPs), and thaumatin‐like xylanase inhibitors (TLXIs) which are believed to act as a defensive barrier against phytopathogenic attack. In the absence of relevant data in wheat kernels, we here examined the response of the different members of the XI protein population to infection with a ΔTri5 mutant of Fusarium graminearum, the wild type of which is one of the most important wheat ear pathogens, in early developing wheat grain. Wheat ears were inoculated at anthesis, analyzed using 2‐D DIGE and multivariate analysis at 5, 15, and 25 days post anthesis (DPA), and compared with control samples. Distinct abundance patterns could be distinguished for different XI forms in response to infection with F. graminearum ΔTri5. Some (iso)forms were up‐regulated, whereas others were down‐regulated. This pathogen‐specific regulation of proteins was mostly visible at five DPA and levelled off in the samples situated further from the inoculation point. Furthermore, it was shown that most identified TAXI‐ and XIP‐type XI (iso)forms significantly increased in abundance from the milky (15 DPA) to the soft dough stages (25 DPA) on a per kernel basis, although the extent of increase differed greatly. Non‐glycosylated XIP forms increased more strongly than their glycosylated counterparts. 相似文献
23.
Population Dynamics and Metabolite Target Analysis of Lactic Acid Bacteria during Laboratory Fermentations of Wheat and Spelt Sourdoughs 总被引:3,自引:1,他引:2 下载免费PDF全文
Roel Van der Meulen Ilse Scheirlinck Ann Van Schoor Geert Huys Marc Vancanneyt Peter Vandamme Luc De Vuyst 《Applied microbiology》2007,73(15):4741-4750
Four laboratory sourdough fermentations, initiated with wheat or spelt flour and without the addition of a starter culture, were prepared over a period of 10 days with daily back-slopping. Samples taken at all refreshment steps were used for determination of the present microbiota. Furthermore, an extensive metabolite target analysis of more than 100 different compounds was performed through a combination of various chromatographic methods including liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. The establishment of a stable microbial ecosystem occurred through a three-phase evolution within a week, as revealed by both microbiological and metabolite analyses. Strains of Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus rossiae, Lactobacillus brevis, and Lactobacillus paraplantarum were dominating some of the sourdough ecosystems. Although the heterofermentative L. fermentum was dominating one of the wheat sourdoughs, all other sourdoughs were dominated by a combination of obligate and facultative heterofermentative taxa. Strains of homofermentative species were not retrieved in the stable sourdough ecosystems. Concentrations of sugar and amino acid metabolites hardly changed during the last days of fermentation. Besides lactic acid, ethanol, and mannitol, the production of succinic acid, erythritol, and various amino acid metabolites, such as phenyllactic acid, hydroxyphenyllactic acid, and indolelactic acid, was shown during fermentation. Physiologically, they contributed to the equilibration of the redox balance. The biphasic approach of the present study allowed us to map some of the interactions taking place during sourdough fermentation and helped us to understand the fine-tuned metabolism of lactic acid bacteria, which allows them to dominate a food ecosystem. 相似文献
24.
Burgermeister E Chuderland D Hanoch T Meyer M Liscovitch M Seger R 《Molecular and cellular biology》2007,27(3):803-817
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascade plays a central role in intracellular signaling by many extracellular stimuli. One target of the ERK cascade is peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that promotes differentiation and apoptosis. It was previously demonstrated that PPARgamma activity is attenuated upon mitogenic stimulation due to phosphorylation of its Ser84 by ERKs. Here we show that stimulation by tetradecanoyl phorbol acetate (TPA) attenuates PPARgamma's activity in a MEK-dependent manner, even when Ser84 is mutated to Ala. To elucidate the mechanism of attenuation, we found that PPARgamma directly interacts with MEKs, which are the activators of ERKs, but not with ERKs themselves, both in vivo and in vitro. This interaction is facilitated by MEKs' phosphorylation and is mediated by the basic D domain of MEK1 and the AF2 domain of PPARgamma. Immunofluorescence microscopy and subcellular fractionation revealed that MEK1 exports PPARgamma from the nucleus, and this finding was supported by small interfering RNA knockdown of MEK1 and use of a cell-permeable interaction-blocking peptide, which prevented TPA-induced export of PPARgamma from the nucleus. Thus, we show here a novel mode of downregulation of PPARgamma by its MEK-dependent redistribution from the nucleus to the cytosol. This unanticipated role for the stimulation-induced nuclear shuttling of MEKs shows that MEKs can regulate additional signaling components besides the ERK cascade. 相似文献
25.
Huys R Llewellyn-Hughes J Conroy-Dalton S Olson PD Spinks JN Johnston DA 《Molecular phylogenetics and evolution》2007,43(2):368-378
Copepods exhibit an astounding variety of lifestyles, host associations and morphology, to the extent that their crustacean affinities may be obscured. Relationships among the ten copepod orders based on morphological characters remain equivocal. Here we test the ordinal status of the enigmatic Monstrilloida using SSU rDNA gene sequences, comparative morphological data (antennulary sensory interface) and ontogenetic data (caudal ramus setation patterns). Bayesian analysis unexpectedly revealed the Monstrilloida are nested within a fish-parasitic clade of the Siphonostomatoida and share a common ancestor with the stem species of the caligiform families (sea-lice). This unforeseen relationship is congruent with both antennulary and caudal ramus morphology. The divergence of the monstrilloids from an ectoparasitic, vertebrate-associated ancestor involved radical changes in host utilization, body plan and life cycle strategy, a combination rarely observed and probably unique in metazoan parasites. Adult monstrilloids secondarily returned to a free-living, predator-exposed mode of life and we postulate the pressure on maintaining a functional approaching-predator detection system has progenetically delayed the suppression (as in post-copepodid caligiform instars) of the 5-point antennulary sensory array. The homoplastic evolution of the frontal filament in Siphonostomatoida is discussed. 相似文献
26.
Disentangling the roles of approach, activation and valence in instrumental and pavlovian responding
Huys QJ Cools R Gölzer M Friedel E Heinz A Dolan RJ Dayan P 《PLoS computational biology》2011,7(4):e1002028
Hard-wired, Pavlovian, responses elicited by predictions of rewards and punishments exert significant benevolent and malevolent influences over instrumentally-appropriate actions. These influences come in two main groups, defined along anatomical, pharmacological, behavioural and functional lines. Investigations of the influences have so far concentrated on the groups as a whole; here we take the critical step of looking inside each group, using a detailed reinforcement learning model to distinguish effects to do with value, specific actions, and general activation or inhibition. We show a high degree of sophistication in Pavlovian influences, with appetitive Pavlovian stimuli specifically promoting approach and inhibiting withdrawal, and aversive Pavlovian stimuli promoting withdrawal and inhibiting approach. These influences account for differences in the instrumental performance of approach and withdrawal behaviours. Finally, although losses are as informative as gains, we find that subjects neglect losses in their instrumental learning. Our findings argue for a view of the Pavlovian system as a constraint or prior, facilitating learning by alleviating computational costs that come with increased flexibility. 相似文献
27.
Gracia P. González-Porter Frank Hailer Oscar Flores-Villela Rony García-Anleu Jesús E. Maldonado 《Conservation Genetics》2011,12(5):1229-1242
We conducted a phylogeographic analysis of the strictly aquatic and critically endangered Central American river turtle, Dermatemys mawii, as part of a conservation management program for the species. We sampled 238 individuals from 15 different localities throughout
the species range. Using sequence fragments from the mtDNA Cyt b and ND4 genes, we identified 16 different haplotypes. Overall, our results reveal a signal of phylogeographic structure throughout
the range, which appears to have been secondarily blurred by extensive gene flow. Notably, this also applies to genetic structuring
across three major hydrological basins that pose biogeographic breaks in other aquatic taxa. Divergence times of mtDNA haplotypes
in D. mawii suggest that the main lineages split in the Pliocene–Pleistocene (3.73–0.227 MA) and demographic tests indicate that the
species has undergone drastic demographic size fluctuations since this time period. One ancient haplotype (1D) was found to
exhibit sequence divergence of up to 2% from other haplogroups. Divergence of this magnitude is indicative of species level
differentiation in other turtle genera. Haplotype 1D was found in only two localities, Sarstun and Salinas, but specimens
with other haplotypes were also found in those localities. It is not known whether the individuals with the 1D haplotype interbreed
with non-1D individuals. Our results suggest that human activity, such as harvesting and long distance transport of animals,
may have influenced the current patterns of genetic diversity. For more than 2000 years, D. mawii has been consumed by people from Middle American cultures, and the archeological record contains strong evidence that the
Mayans transported animals between villages and far away from their natural distribution range. Therefore, the large-scale
pattern of haplotype sharing even across hydrological barriers, the observed low haplotype diversity in some populations and
the contemporary absence of a pronounced phylogeographic pattern is likely due to a combination of population expansions,
gene flow, extensive human-mediated-movements and recent bottlenecks resulting from over-harvesting. 相似文献
28.
29.
Bidet M Joubert O Lacombe B Ciantar M Nehmé R Mollat P Brétillon L Faure H Bittman R Ruat M Mus-Veteau I 《PloS one》2011,6(9):e23834
Background
Sonic hedgehog (Shh) signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Methodology/Principal Findings
Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol) from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Conclusion/Significance
Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation. 相似文献30.
BmBKTx1, a novel Ca2+-activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch 总被引:1,自引:0,他引:1
Xu CQ Brône B Wicher D Bozkurt O Lu WY Huys I Han YH Tytgat J Van Kerkhove E Chi CW 《The Journal of biological chemistry》2004,279(33):34562-34569
BmBKTx1 is a novel short chain toxin purified from the venom of the Asian scorpion Buthus martensi Karsch. It is composed of 31 residues and is structurally related to SK toxins. However, when tested on the cloned rat SK2 channel, it only partially inhibited rSK2 currents, even at a concentration of 1 microm. To screen for other possible targets, BmBKTx1 was then tested on isolated metathoracic dorsal unpaired median neurons of Locusta migratoria, in which a wide variety of ion channels are expressed. The results suggested that BmBKTx1 could specifically block voltage-gated Ca(2+)-activated K(+) currents (BK-type). This was confirmed by testing the BmBKTx1 effect on the alpha subunits of BK channels of the cockroach (pSlo), fruit fly (dSlo), and human (hSlo), heterologously expressed in HEK293 cells. The IC(50) for channel blocking by BmBKTx1 was 82 nm for pSlo and 194 nm for dSlo. Interestingly, BmBKTx1 hardly affected hSlo currents, even at concentrations as high as 10 microm, suggesting that the toxin might be insect specific. In contrast to most other scorpion BK blockers that also act on the Kv1.3 channel, BmBKTx1 did not affect this channel as well as other Kv channels. These results show that BmBKTx1 is a novel kind of blocker of BK-type Ca(2+)-activated K(+) channels. As the first reported toxin active on the Drosophila Slo channel dSlo, it will also greatly facilitate studying the physiological role of BK channels in this model organism. 相似文献