The ability of Leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. However, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. To elucidate nutrient stress response pathways in Leishmania donovani, we have used purine starvation as the paradigm. The salvage of purines from the host milieu is obligatory for parasite replication; nevertheless, purine-starved parasites can persist in culture without supplementary purine for over three months, indicating that the response to purine starvation is robust and engenders parasite survival under conditions of extreme scarcity. To understand metabolic reprogramming during purine starvation we have employed global approaches. Whole proteome comparisons between purine-starved and purine-replete parasites over a 6–48 h span have revealed a temporal and coordinated response to purine starvation. Purine transporters and enzymes involved in acquisition at the cell surface are upregulated within a few hours of purine removal from the media, while other key purine salvage components are upregulated later in the time-course and more modestly. After 48 h, the proteome of purine-starved parasites is extensively remodeled and adaptations to purine stress appear tailored to deal with both purine deprivation and general stress. To probe the molecular mechanisms affecting proteome remodeling in response to purine starvation, comparative RNA-seq analyses, qRT-PCR, and luciferase reporter assays were performed on purine-starved versus purine-replete parasites. While the regulation of a minority of proteins tracked with changes at the mRNA level, for many regulated proteins it appears that proteome remodeling during purine stress occurs primarily via translational and/or post-translational mechanisms. 相似文献
Erectile dysfunction (ED) has emerged as an important marker of cardiovascular and overall health, independent of other known conventional risk factors. ED often precedes coronary artery disease in half of affected subjects, and could indicate the presence of cardiovascular pathology. The pathophysiology and role of androgens in sexual function are described, along with the relevant literature on the effects of aging in erectile and gonadal function. The concept of testosterone supplementation (TST) in men with ED is reviewed. The authors utilize clinical vignettes to discuss the appropriate management of two clinical cases of men at different life stages who have ED in the setting of hypogonadism and propose a treatment algorithm. In patients of all ages, proper identification of the underlying pathophysiology of decreased libido and erectile function is paramount in choosing between the use of TST, phosphodiesterase type 5 inhibitors, or both, in the management of these disorders.Key words: Erectile dysfunction, Testosterone supplementation, Hypogonadism, Phosphodiesterase type 5 inhibitorsErectile dysfunction (ED) has emerged as an important marker of cardiovascular and overall health, independent of other known conventional risk factors. Because ED often precedes coronary artery disease (CAD) in half of affected subjects, it may be considered a harbinger of indolent cardiovascular pathology.1,2 The modulation of erectile function by testosterone is well known,3,4 and in men with both hypogonadism and ED a treatment strategy necessitating management of both conditions is required.Phosphodiesterase type 5 inhibitors (PDE5i) and testosterone supplementation therapy (TST) are established treatment strategies for ED and hypogonadism, respectively. Using a PDE5i in combination with TST has the potential for improving efficacy in men with concurrent ED and hypogonadism compared with the use of either agent alone. However, in light of the recent evidence associating testosterone with cardiovascular risk in elderly men,5,6 TST should be used judiciously in the management of ED in older men. 相似文献
The present study of genetic analysis is an attempt to precisely characterize diverse temperature-sensitive genic male-sterile
(TGMS) lines so as to explore the possibilities of utilizing the most promising in large-scale hybrid seed production. Genetical
studies revealed that the TGMS segregants derived from crosses involving TGMS lines ID24 and SA2 expressed differential fertility
levels at low-temperature conditions. A majority of these progenies expressed transgressive segregation towards either sterility
of fertility, causing instability of sterility and low reversibilty of fertility which may be due to large numbers of single-locus
QTLs and their epistatic interactions. We identified two putative genes imparting temperature-sensitive male sterility after
observing crosses involving diverse TGMS sources. To identify suitable molecular markers closely linked to the trait we used
RAPD, AFLP and microsatellites which generated polymorphism through bulked segregant analysis. AFLP analysis using a smaller
genome kit resulted in enormous polymorphism, out of which the combination EAA/MCAG amplified a 330-bp fragment, which closely
segregated with the gene at a distance of 5.3 cM. This fragment was eluted for cloning and from the sequence a STS primer
(TS200) was developed which produced a dominant polymorphism specific to TGMS. The microsatellite RM257, located earlier on
chromosome 9, was linked with the TGMS trait in SA2 at a distance of 6.2 cM. RM257 produced a codominant polymorphism with
145-bp (sterile) and 132-bp (fertile) products. Both individually and collectively, the markers TS200 and RM257 located on
either side of the TGMS locus are very useful for marker-assisted selection.
Received: 10 April 1999 / Accepted: 29 July 1999 相似文献
Ascorbic acid (20.4 g l-1 in 50 h) was synthesized directly from glucose by Xanthomonas campestris as an adaptive response to induced free-radicals through HOCl treatment. Identity of ascorbic acid was confirmed through IR and NMR spectroscopy. 相似文献
Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India. 相似文献
and
1986. The surface topography and ultrastructure of the tegument and haptor of Pricea multae (Monogenea). International Journal for Parasitology 16: 581–589. Pricea multae is a gill parasite of Scomberomorus spp. In the present study, the surface specialization and ultrastructure of the tegument and haptor were examined in detail. The buccal cavity and the preoral pit bear uniciliated sensory endings. The genital atrium opens on the ventral surface whereas the vaginal pore opens on the dorsal surface of the anterior region. The general body surface is elevated by pits and folds together with papillae-like uniciliated sensory endings. Microvilli are uncommon.
The syncytium of the tegument is bounded by apical and basal plasma membranes. Some electron-dense granules and electron-lucent vesicles were observed exocytosing at the apical surface. The tegumental perikarya lie amongst the muscle blocks underneath the basal lamina. The body wall muscle fibres are non-striated consisting of thick and thin myofilaments. Each muscle fibre is limited by a sarcolemma and separated from neighbouring fibres by interstitial material.
The haptor possesses two rows of pincer-type clamps. The clamps may be withdrawn by muscles into cavity-like depressions. Electron-dense fibrils are embedded within the clamp sclerite matrix. The intrinsic muscles of the clamp include radial muscles enclosed within the basal lamina. The muscle fibres enclosed within the basal lamina of the clamp appear to differ from the body wall muscles by the absence of interstitial material, the possession of well defined gap junctions between the sarcolemma of adjacent muscle fibres, abundant sarcoplasmic reticulum and numerous mitochondria. The extrinsic muscles of the clamp presumably arise from the dorso-lateral surface of the haptor and are apparently connected to the tendon of the clamp. A cluster of gland cells occurs in the haptor beneath each clamp. The haptor is richly supplied with nerve fibres which are associated with groups of neurones. Each axon is non-myelinated and contains presumed neurosecretory granules. The peripheries of some of the large axons are subdivided by invaginations of the axon wall. 相似文献
Glucose oxidase-negative (gox-) mutants of Phanerochaete chrysosporium were isolated after exposing conidia to UV irradiation. The gox- mutants exhibited little or no ability to degrade lignin (2-[14C]-synthetic lignin to 14CO2); however, they retained other secondary metabolic features such as the ability to conidiate and produce veratryl alcohol, suggesting that they are not pleiotropic for secondary metabolism. Lignin degradation activity was restored in gox+ revertants. These results, in support of earlier evidence, indicate that glucose oxidase activity plays an important role in lignin degradation by P. chrysosporium. 相似文献
Attempts were made to manipulate specific responses of baboons to protect them from infection with Schistosoma mansoni. In Experiment 1, eosinophilia was induced in naive baboons with Trichinella spiralis larvae given intravenously before intraperitoneal injection of globulin fractions from S. mansoni-infected baboon sera and subsequent percutaneous exposure to S. mansoni cercariae. In Experiment 2, baboons with 8- or 32-week-old primary S. mansoni infections received T. spiralis i.v. before an S. mansoni challenge. In experiments 3 to 5 respectively, naive baboons received intramuscularly before challenge: formalin-fixed S. mansoni schistosomula, with Bordetella pertussis as an adjuvant; a preparation of S. mansoni adult worm teguments; and a preparation of IgE-immune complexes obtained from S. mansoni-infected rat sera, with Freunds Complete Adjuvant. Minor, but statistically insignificant, protection was obtained in Experiments 2 (32-week infections) and 3, but was far less than that given by intact, irradiated living vaccines. There are signs on the horizon of non-living vaccines protecting rodents against S. mansoni infection and it would be prudent, as with drugs, to test these in primates before proceeding to man. The results of our experiments, though essentially negative, should help the design of any future vaccine trials in primates. 相似文献
Lablab bean (Lablab purpureus) is a popular vegetable crop in Bangladesh, but farmers growing this crop experience significant losses to insect pests despite heavy reliance on conventional insecticides. We conducted field studies to improve pest management in lablab bean by testing biorational insecticides as alternatives to conventional insecticides for the control of pod borers (Maruca vitrata) and aphids (Aphis craccivora), and characterizing flower-inhabiting thrips as an emerging pest in this crop. In field experiments, spinosad was the most promising biorational we tested, suppressing pod-boring caterpillars more effectively than thiamethoxam or quinalphos. In contrast, azadirachtin (neem) did not significantly suppress any of the insect pests we measured, although target aphid populations were generally low at our research site. Using DNA barcoding at the coxI locus combined with morphological identification, we found eight thrips taxa inhabiting lablab bean flowers, dominated by Megalurothrips usitatus and M. distalis/peculiaris. A preliminary regression analysis indicated that these flower-inhabiting thrips reduced lablab bean yield. Our results suggest that spinosad may be useful within lablab bean IPM programs, and that these programs will likely need to incorporate tactics against thrips to effectively protect yield. Finally, we found that DNA barcoding was a valuable tool for pest identification in an understudied crop and region, but that to reach its full potential will require an investment in more comprehensive reference libraries. 相似文献