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981.
Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives 总被引:1,自引:0,他引:1
The SIR (susceptible-infectious-resistant) and SIS (susceptible-infectious-susceptible) frameworks for infectious disease have been extensively studied and successfully applied. They implicitly assume the upper and lower limits of the range of possibilities for host immune response. However, the majority of infections do not fall into either of these extreme categories. We combine two general avenues that straddle this range: temporary immune protection (immunity wanes over time since infection), and partial immune protection (immunity is not fully protective but reduces the risk of reinfection). We present a systematic analysis of the dynamics and equilibrium properties of these models in comparison to SIR and SIS, and analyse the outcome of vaccination programmes. We describe how the waning of immunity shortens inter-epidemic periods, and poses major difficulties to disease eradication. We identify a "reinfection threshold" in transmission when partial immunity is included. Below the reinfection threshold primary infection dominates, levels of infection are low, and vaccination is highly effective (approximately an SIR model). Above the reinfection threshold reinfection dominates, levels of infection are high, and vaccination fails to protect (approximately an SIS situation). This association between high prevalence of infection and vaccine failure emphasizes the problems of controlling recurrent infections in high-burden regions. However, vaccines that induce a better protection than natural infection have the potential to increase the reinfection threshold, and therefore constitute interventions with a surprisingly high capacity to reduce infection where reduction is most needed. 相似文献
982.
Mutations in the gene KCNV2 encoding a voltage-gated potassium channel subunit cause "cone dystrophy with supernormal rod electroretinogram" in humans 总被引:1,自引:0,他引:1
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Wu H Cowing JA Michaelides M Wilkie SE Jeffery G Jenkins SA Mester V Bird AC Robson AG Holder GE Moore AT Hunt DM Webster AR 《American journal of human genetics》2006,79(3):574-579
"Cone dystrophy with supernormal rod electroretinogram (ERG)" is an autosomal recessive disorder that causes lifelong visual loss combined with a supernormal ERG response to a bright flash of light. We have linked the disorder to a 0.98-cM (1.5-Mb) region on chromosome 9p24, flanked by rs1112534 and rs1074449, using homozygosity mapping in one large consanguineous pedigree. Analysis of one gene within this region, KCNV2, showed a homozygous nonsense mutation. Mutations were also found in 17 alleles of 10 other unrelated families with the same disorder. In situ hybridization demonstrated KCNV2 expression in human rod and cone photoreceptors. The precise function of KCNV2 in human photoreceptors remains to be determined, although this work suggests that mutations might perturb or abrogate I(KX), the potassium current within vertebrate photoreceptor inner segments, which has been shown to set their resting potential and voltage response. 相似文献
983.
Schaefer H. Martin; Levey Douglas J.; Schaefer Veronika; Avery Michael L. 《Behavioral ecology》2006,17(5):784-789
Fruit color changes during ripening are typically viewed asan adaptation to increase signal efficacy to seed dispersers.Plants can increase signal efficacy by enhancing chromatic (wavelengthrelated) and/or achromatic (intensity related) contrasts betweenfruit and background. To assess how these contrasts determinethe detectability of fruit signals, we conducted 2 experimentswith free-flying crows (Corvus ossifragus) under seminaturalconditions in a 2025 m2 aviary. Crows searched first for artificialred and black fruits and detected red fruits from a larger distance.Because artificial red fruits had higher chromatic and lowerachromatic contrasts against foliage than artificial black fruits,crows apparently prioritized chromatic contrasts. Thus, thecommon change in fruit color from red to black during ripeningdoes not increase signal efficacy to crows. In a second trial,crows searched for UV-reflecting and black blueberries (Vaccinummyrtillus) against backgrounds of foliage and sand. Againstfoliage, UV-reflecting berries had higher chromatic and achromaticcontrasts than black berries, and crows detected them from alarger distance. Against sand, UV-reflecting berries had lowachromatic contrasts and black berries low chromatic contrasts.Crows detected both fruit types equally, suggesting that theyused chromatic contrasts to detect UV-reflecting berries andachromatic contrasts to detect black berries. Birds prioritizedchromatic contrasts when searching for artificial red fruitsin foliage but not when searching for blueberries on sand. Wesuggest that the relative importance of chromatic and achromaticcontrasts is contingent on the chromatic and achromatic varianceof the background. Models of signal perception can be improvedby incorporating background-specific effects. 相似文献
984.
985.
The fixation of a beneficial mutation represents the first step in adaptation, and the average effect of such mutations is therefore a fundamental property of evolving populations. It is nevertheless poorly characterized because the rarity of beneficial mutations makes it difficult to obtain reliable estimates of fitness. We obtained 68 genotypes each containing a single fixed beneficial mutation from experimental populations of Pseudomonas fluorescens, evolving in medium with serine as the sole carbon source and estimated the selective advantage of each by competition with the ancestor. The distribution of selection coefficients is modal and closely resembles the Weibull distribution. The average selection coefficient (2.1) and beneficial mutation rate (3.8x10(-8)) are high relative to previous studies, possibly because the ancestral population grows poorly in serine-limited medium. Our experiment suggests that the initial stages of adaptation to stressful environments will involve the substitution of mutations with large effect on fitness. 相似文献
986.
Selective brain cooling (SBC) is defined as the lowering of brain temperature below arterial blood temperature. Artiodactyls employ a carotid rete, an anatomical heat exchanger, to cool arterial blood shortly before it enters the brain. The survival advantage of this anatomy traditionally is believed to be a protection of brain tissue from heat injury, especially during exercise. Perissodactyls such as horses do not possess a carotid rete, and it has been proposed that their guttural pouches serve the heat-exchange function of the carotid rete by cooling the blood that traverses them, thus protecting the brain from heat injury. We have tested this proposal by measuring brain and carotid artery temperature simultaneously in free-living horses. We found that despite evidence of cranial cooling, brain temperature increased by about 2.5 degrees C during exercise, and consistently exceeded carotid temperature by 0.2-0.5 degrees C. We conclude that cerebral blood flow removes heat from the brain by convection, but since SBC does not occur in horses, the guttural pouches are not surrogate carotid retes. 相似文献
987.
Graham RL Pollock CE O'Loughlin SN Ternan NG Weatherly DB Jackson PJ Tarleton RL McMullan G 《Journal of proteome research》2006,5(11):3145-3153
We report the first large-scale gel-free proteomic analysis of the soluble subproteome of the emerging pathogen Ochrobactrum anthropi. Utilizing our robust offline multidimensional protein identification protocol, a total of 57 280 peptides were initially identified utilizing automated MS/MS analysis software. We describe our investigation of the heuristic protein validation tool PROVALT and demonstrate its ability to increase the speed and accuracy of the curation process of large-scale proteomic datasets. PROVALT reduced our peptide list to 8517 identified peptides and further manual curation of these peptides led to a final list of 984 uniquely identified peptides that resulted in the positive identification of 249 proteins. These identified proteins were functionally classified and physiochemically characterized. A variety of typical "housekeeping" functions identified within the proteome included nucleic acid, amino and fatty acid anabolism and catabolism, glycolysis, TCA cycle, and pyruvate and selenoamino acid metabolism. In addition, a number of potential virulence factors of relevance to both plant and human disease were identified. 相似文献
988.
989.
Cox11p is an integral protein of the inner mitochondrial membrane that is essential for cytochrome c oxidase assembly. The bulk of the protein is located in the intermembrane space and displays high levels of evolutionary conservation. We have analyzed a collection of site-directed and random cox11 mutants in an effort to further define essential portions of the molecule. Of the alleles studied, more than half had no apparent effect on Cox11p function. Among the respiration deficiency-encoding alleles, we identified three distinct phenotypes, which included a set of mutants with a misassembled or partially assembled cytochrome oxidase, as indicated by a blue-shifted cytochrome aa(3) peak. In addition to the shifted spectral signal, these mutants also display a specific reduction in the levels of subunit 1 (Cox1p). Two of these mutations are likely to occlude a surface pocket behind the copper-binding domain in Cox11p, based on analogy with the Sinorhizobium meliloti Cox11 solution structure, thereby suggesting that this pocket is crucial for Cox11p function. Sequential deletions of the matrix portion of Cox11p suggest that this domain is not functional beyond the residues involved in mitochondrial targeting and membrane insertion. In addition, our studies indicate that Deltacox11, like Deltasco1, displays a specific hypersensitivity to hydrogen peroxide. Our studies provide the first evidence at the level of the cytochrome oxidase holoenzyme that Cox1p is the in vivo target for Cox11p and suggest that Cox11p may also have a role in the response to hydrogen peroxide exposure. 相似文献
990.
Control of phage Bxb1 excision by a novel recombination directionality factor 总被引:3,自引:0,他引:3
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Mycobacteriophage Bxb1 integrates its DNA at the attB site of the Mycobacterium smegmatis genome using the viral attP site and a phage-encoded integrase generating the recombinant junctions attL and attR . The Bxb1 integrase is a member of the serine recombinase family of site-specific recombination proteins and utilizes small (<50 base pair) substrates for recombination, promoting strand exchange without the necessity for complex higher order macromolecular architectures. To elucidate the regulatory mechanism for the integration and excision reactions, we have identified a Bxb1-encoded recombination directionality factor (RDF), the product of gene 47 . Bxb1 gp47 is an unusual RDF in that it is relatively large (˜28 kDa), unrelated to all other RDFs, and presumably performs dual functions since it is well conserved in mycobacteriophages that utilize unrelated integration systems. Furthermore, unlike other RDFs, Bxb1 gp47 does not bind DNA and functions solely through direct interaction with integrase–DNA complexes. The nature and consequences of this interaction depend on the specific DNA substrate to which integrase is bound, generating electrophoretically stable tertiary complexes with either attB or attP that are unable to undergo integrative recombination, and weakly bound, electrophoretically unstable complexes with either attL or attR that gain full potential for excisive recombination. 相似文献