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41.
42.
An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants 总被引:26,自引:0,他引:26
Rose NF Marx PA Luckay A Nixon DF Moretto WJ Donahoe SM Montefiori D Roberts A Buonocore L Rose JK 《Cell》2001,106(5):539-549
We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection. 相似文献
43.
Clarke TR Hoshiya Y Yi SE Liu X Lyons KM Donahoe PK 《Molecular endocrinology (Baltimore, Md.)》2001,15(6):946-959
Signal reception of Müllerian inhibiting substance (MIS) in the mesenchyme around the embryonic Müllerian duct in the male is essential for regression of the duct. Deficiency of MIS or of the MIS type II receptor, MISRII, results in abnormal reproductive development in the male due to the maintenance of the duct. MIS is a member of the transforming growth factor-beta (TGFbeta) superfamily of secreted protein hormones that signal through receptor complexes of type I and type II serine/threonine kinase receptors. To investigate candidate MIS type I receptors, we examined reporter construct activation by MIS. The bone morphogenetic protein (BMP)-responsive Tlx2 and Xvent2 promoter-driven reporter constructs were stimulated by MIS but the TGFbeta/activin-induced p3TP-lux or CAGA-luc reporter constructs were not. The induction of Tlx2-luc was dependent upon the kinase activity of MISRII and was blocked by a dominant negative truncated ALK2 (tALK2) receptor but not by truncated forms of the other BMP type I receptors ALK1, ALK3, or ALK6. MIS induced activation of a Gal4DBD-Smad1 but not a Gal4DBD-Smad2 fusion protein. This activation could also be blocked by tALK2. The BMP-induced inhibitory Smad, Smad6, was up-regulated by MIS endogenously in Leydig cell-derived lines and is expressed in male but not female Müllerian duct mesenchyme. ALK6 has been shown to function as an MIS type I receptor. Investigation of the pattern of ALK2, MISRII, and ALK6 in the developing urogenital system demonstrated overlapping expression of ALK2 and MISRII in the mesenchyme surrounding the duct while ALK6 was observed only in the epithelium. Examination of ALK6 -/- male animals revealed no defect in duct regression. The reporter construct analysis, pattern of expression of the receptors, and analysis of ALK6-deficient animals suggest that ALK2 is the MIS type I receptor involved in Müllerian duct regression. 相似文献
44.
45.
JS Osombause SNM Mandiki JA-P Ulyel J-C Micha P Kestemont 《African Journal of Aquatic Science》2019,44(1):61-70
Distichodus antonii is an endemic fish species of the Congo River basin in which the stocks of wild populations are threatened by overfishing pressure. Knowledge of its reproductive biology would be useful in consideration of conservation and management options for the species. Therefore, this study investigated changes in ovarian activity and levels of steroid profiles in wild populations in relation to variation in temperature and rainfall. Adult females (n = 101, body weight of 3 183 ± 14.75 g, SE) were captured monthly over one year (2013–2014). Apart from evaluation of oocyte diameters and gonad developmental stages, gonado-, hepato-, lipososomatic indices (GSI, HSI, LSI) and plasma levels of sex steroids (testosterone-T, estradiol-17β-E2) were determined. The results suggested a synchronous development of oocytes with two annual reproductive seasons over the one-year study. Plasma T and E2 levels peaked during spawning periods likely reflecting active oogenesis. The highest values of morphosomatic indices were observed during the longest rainfall period in September, and were associated with high steroidogenic activity evidenced by increased E2 production. In addition, more vitellogenic oocytes (September and October) were observed during the latter season than during the short rainy season (in May). 相似文献
46.
Donahoe JW 《Behavioural processes》2002,57(2-3):241-259
Darwin proposed a powerful functional principle-natural selection-to interpret phylogenetic diversity and complexity. Nevertheless, some 70 years elapsed before even biologists embraced his account. The triumph of natural selection required two additional factors: (a) biological mechanisms that implemented the functional principle (i.e. genetics); and (b) quantitative procedures that traced its cumulative effects (i.e. population genetics). Thorndike and, later, Skinner proposed a functional principle-selection by reinforcement-that interpreted ontogenetic diversity and complexity. This principle has been substantially refined by subsequent experimental and theoretical work and now provides an equally powerful functional account. However, a purely functional principle has once again not persuaded most scientists (apart from the behavior-analytic minority) that complex behavior can be understood by a selection principle. If the history of ontogeny recapitulates the history of phylogeny, the biological mechanisms that implement selection by reinforcement must be discovered and quantitative techniques that trace its effects must be devised. In short, the triumph of reinforcement may await the integration of behavior analysis with the neurosciences and the development of coordinated quantitative procedures. This article identifies specific interrelations with neuroscience that form the basis for a behavior-analytically faithful interpretation of reinforcement using neural-network techniques. Implications for the architecture of networks and for the learning algorithm are emphasized. 相似文献
47.
Surendra Kumar ?smund Skj?veland Russell JS Orr P?l Enger Torgeir Ruden Bj?rn-Helge Mevik Fabien Burki Andreas Botnen Kamran Shalchian-Tabrizi 《BMC bioinformatics》2009,10(1):357
Background
Large multigene sequence alignments have over recent years been increasingly employed for phylogenomic reconstruction of the eukaryote tree of life. Such supermatrices of sequence data are preferred over single gene alignments as they contain vastly more information about ancient sequence characteristics, and are thus more suitable for resolving deeply diverging relationships. However, as alignments are expanded, increasingly numbers of sites with misleading phylogenetic information are also added. Therefore, a major goal in phylogenomic analyses is to maximize the ratio of information to noise; this can be achieved by the reduction of fast evolving sites. 相似文献48.
OLF Weyl MK Schirrmann JS Hargrove T Bodill ER Swartz 《African Journal of Aquatic Science》2017,42(4):359-365
Largemouth bass Micropterus salmoides are a popular North American angling species that was introduced into South Africa in 1928. To enhance the largemouth bass fisheries, Florida bass Micropterus floridanus were introduced into KwaZulu Natal, South Africa, in 1980. Knowledge on the status of M. floridanus in South Africa is required, because it lives longer and reaches larger sizes than M. salmoides, which may result in heightened impacts on native biota. Because M. floridanus are morphologically similar, but genetically distinct from M. salmoides, the distribution of this species was assessed by genetically screening 185 Micropterus sp. individuals sampled from 20 localities across South Africa using the mitochondrial ND2 gene. Individuals with mitochondrial DNA matching M. salmoides were recovered from 16 localities, whereas M. floridanus mitochondrial DNA was recovered from 13 localities. At nine localities (45%), the mitochondrial DNA of both species was detected. These results demonstrate M. floridanus dispersal to multiple sites across South Africa. 相似文献
49.
Growth hormone restores aged diaphragm myosin composition and performance after chronic undernutrition. 总被引:2,自引:0,他引:2
B T Ameredes J F Watchko M J Daood J F Rosas M P Donahoe R M Rogers 《Journal of applied physiology》1999,87(4):1253-1259
The effects of growth hormone (GH) on diaphragm muscle myosin heavy chain (MHC) composition and mechanical performance were investigated in Fischer 344 male rats aged to senescence (24.5 mo of age). Chronic undernutrition (UN), refeeding (RF), and RF+GH were compared with ad libitum feeding by using a model of UN that produced a 50% decrease in body weight over a 12-mo period. The effect of aging was assessed by comparing MHC composition of ad libitum-fed rats at 12 and 24.5 mo of age. At senescence, significant decreases in slow type I (-23%) and fast type IIA (-31%) MHC had occurred with aging. Conversely, UN over this aging period increased types I (32-73%) and IIA (22-23%) MHC and decreased fast types IIB (32-54%) and IIX (30-31%) MHC. RF and RF+GH reversed these shifts back toward control values. At senescence, maximal specific force, maximal velocity, and specific power capacity were not different across treatment groups. During repetitive isotonic contraction trials, the diaphragms of UN rats maintained power production over time (54% of initial power at 60 s), whereas the power production of diaphragms of ad libitum-fed rats fell to 0% (P < 0.05). In comparison with UN rats, the diaphragms of RF and RF+GH rats produced 23 (not significant) and 11% (P < 0.05) of initial power, respectively, suggesting that RF+GH treatment restored performance characteristics after UN. We conclude that RF+GH can reverse alterations in MHC composition and mechanical performance produced by chronic UN in the aged rat diaphragm. 相似文献
50.
A characteristic feature of the sperm P1 protamines of eutherian mammals is
the constant presence of six to nine cysteine residues per molecule. During
spermiogenesis these residues become oxidized to form a three-dimensional
network of disulfide bridges between, and within, protamine molecules in
the sperm chromatin. This covalent cross linking strongly stabilizes
eutherian sperm nuclei. In contrast, protamines sequenced from teleost
fish, birds, monotremes, and marsupials all lack cysteine residues and
their sperm nuclei, without the stabilizing cross links, are easily
decondensed in vitro. We have now found that one genus of tiny, shrewlike
dasyurid marsupials, the Planigales, possess P1 protamines containing five
to six cysteine residues. These residues appear to have evolved since the
divergence of Planigales from other members of the family Dasyuridae, such
as the marsupial mouse, Sminthopsis crassicaudata. We believe this
constitutes a case of convergent evolution in a subfamily of dasyurid
marsupials toward the cysteine-rich eutherian form of sperm protamine P1.
相似文献