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61.
Sumpter B Dunham R Gordon S Engram J Hennessy M Kinter A Paiardini M Cervasi B Klatt N McClure H Milush JM Staprans S Sodora DL Silvestri G 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(3):1680-1691
In contrast to HIV-infected humans, naturally SIV-infected sooty mangabeys (SMs) very rarely progress to AIDS. Although the mechanisms underlying this disease resistance are unknown, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To define the correlates of preserved CD4(+) T cell counts in SMs, we conducted a cross-sectional immunological study of 110 naturally SIV-infected SMs. The nonpathogenic nature of the infection was confirmed by an average CD4(+) T cell count of 1,076 +/- 589/mm(3) despite chronic infection with a highly replicating virus. No correlation was found between CD4(+) T cell counts and either age (used as a surrogate marker for length of infection) or viremia. The strongest correlates of preserved CD4(+) T cell counts were a low percentage of circulating effector T cells (CD28(-)CD95(+) and/or IL-7R/CD127(-)) and a high percentage of CD4(+)CD25(+) T cells. These findings support the hypothesis that the level of immune activation is a key determinant of CD4(+) T cell counts in SIV-infected SMs. Interestingly, we identified 14 animals with CD4(+) T cell counts of <500/mm(3), of which two show severe and persistent CD4(+) T cell depletion (<50/mm(3)). Thus, significant CD4(+) T cell depletion does occasionally follow SIV infection of SMs even in the context of generally low levels of immune activation, lending support to the hypothesis of multifactorial control of CD4(+) T cell homeostasis in this model of infection. The absence of AIDS in these "CD4(low)" naturally SIV-infected SMs defines a protective role of the reduced immune activation even in the context of a significant CD4(+) T cell depletion. 相似文献
62.
Vazeille E Codran A Claustre A Averous J Listrat A Béchet D Taillandier D Dardevet D Attaix D Combaret L 《American journal of physiology. Endocrinology and metabolism》2008,295(5):E1181-E1190
Immobilization produces morphological, physiological, and biochemical alterations in skeletal muscle leading to muscle atrophy and long periods of recovery. Muscle atrophy during disuse results from an imbalance between protein synthesis and proteolysis but also between apoptosis and regeneration processes. This work aimed to characterize the mechanisms underlying muscle atrophy and recovery following immobilization by studying the regulation of the mitochondria-associated apoptotic and the ubiquitin-proteasome-dependent proteolytic pathways. Animals were subjected to hindlimb immobilization for 4-8 days (I4 to I8) and allowed to recover after cast removal for 10-40 days (R10 to R40). Soleus and gastrocnemius muscles atrophied from I4 to I8 to a greater extent than extensor digitorum longus and tibialis anterior muscles. Gastrocnemius muscle atrophy was first stabilized at R10 before being progressively reduced until R40. Polyubiquitinated proteins accumulated from I4, whereas the increased ubiquitination rates and chymotrypsin-like activity of the proteasome were detectable from I6 to I8. Apoptosome and caspase-3 or -9 activities increased at I6 and I8, respectively. The ubiquitin-proteasome-dependent pathway was normalized early when muscle stops to atrophy (R10). By contrast, the mitochondria-associated apoptotic pathway was first downregulated below basal levels when muscle started to recover at R15 and completely normalized at R20. Myf 5 protein levels decreased from I4 to I8 and were normalized at R10. Altogether, our results suggest a two-stage process in which the ubiquitin-proteasome pathway is rapidly up- and downregulated when muscle atrophies and recovers, respectively, whereas apoptotic processes may be involved in the late stages of atrophy and recovery. 相似文献
63.
64.
Carrière Audrey Lagarde Damien Jeanson Yannick Portais Jean-Charles Galinier Anne Ader Isabelle Casteilla Louis 《Journal of physiology and biochemistry》2020,76(2):241-250
Journal of Physiology and Biochemistry - Thermogenic (brown and beige) adipose tissues improve glucose and lipid homeostasis and therefore represent putative targets to cure obesity and related... 相似文献
65.
Audrey Coreau Sébastien Treyer Pierre‐Olivier Cheptou John D. Thompson Laurent Mermet 《Oikos》2010,119(8):1364-1376
In a mainly experimental science based traditionally on hypothesis testing such as ecology, studying futures may be difficult. However, in the last few decades, predicting the consequences of global changes on the dynamics and function of ecological systems has become a major challenge in ecological research. To study how ecological scientists deal with potential difficulties in studying futures, we adopted a reflexive viewpoint on how scientists address the study of ecological futures. To do so we questioned a panel of ecological scientists on their practical involvement and point of view. Quantitative and qualitative analyses of their responses showed that predictions or predictive models were the dominant theme. Many quantitative models, based on statistical correlations, empirical rules or processes have been developed and their methodological limitations explored by the researchers we interviewed. In a small proportion of studies, qualitative scenarios have been elaborated to explore the range of possible futures. Interviewees emphasized the problem of dealing with ecological complexity and multiple future possibilities. Specificities of futures compared to past or present events were not fully identified. In fact, researchers studying futures mainly adopted a reductionist approach, trying to simplify complex ecological systems. But methods and tools promoted by such an approach to science may not always be appropriate to deal with future ecological complexity. Indeed, an emphasis on prediction prevents ecologists from acknowledging the multiplicity and undetermined nature of futures. 相似文献
66.
Tino Krell Frédéric Greco Olivier Engel Jean Dubayle Joseline Dubayle Audrey Kennel Benoit Charloteaux Robert Brasseur Michel Chevalier Regis Sodoyer Rapha?lle El Habib 《European journal of biochemistry》2004,271(8):1566-1579
HIV gp41(24-157) unfolds cooperatively over the pH range of 1.0-4.0 with T(m) values of > 100 degrees C. At pH 2.8, protein unfolding was 80% reversible and the DeltaH(vH)/DeltaH(cal) ratio of 3.7 is indicative of gp41 being trimeric. No evidence for a monomer-trimer equilibrium in the concentration range of 0.3-36 micro m was obtained by DSC and tryptophan fluorescence. Glycosylation of gp41 was found to have only a marginal impact on the thermal stability. Reduction of the disulfide bond or mutation of both cysteine residues had only a marginal impact on protein stability. There was no cooperative unfolding event in the DSC thermogram of gp160 in NaCl/P(i), pH 7.4, over a temperature range of 8-129 degrees C. When the pH was lowered to 5.5-3.4, a single unfolding event at around 120 degrees C was noted, and three unfolding events at 93.3, 106.4 and 111.8 degrees C were observed at pH 2.8. Differences between gp41 and gp160, and hyperthermostable proteins from thermophile organisms are discussed. A series of gp41 mutants containing single, double, triple or quadruple point mutations were analysed by DSC and CD. The impact of mutations on the protein structure, in the context of generating a gp41 based vaccine antigen that resembles a fusion intermediate state, is discussed. A gp41 mutant, in which three hydrophobic amino acids in the gp41 loop were replaced with charged residues, showed an increased solubility at neutral pH. 相似文献
67.
1. Dispersal intensity is a key process for the persistence of prey-predator metacommunities. Consequently, knowledge of the ecological mechanisms of dispersal is fundamental to understanding the dynamics of these communities. Dispersal is often considered to occur at a constant per capita rate; however, some experiments demonstrated that dispersal may be a function of local species density. 2. Here we use aquatic experimental microcosms under controlled conditions to explore intra- and interspecific density-dependent dispersal in two protists, a prey Tetrahymena pyriformis and its predator Dileptus sp. 3. We observed intraspecific density-dependent dispersal for the prey and interspecific density-dependent dispersal for both the prey and the predator. Decreased prey density lead to an increase in predator dispersal, while prey dispersal increased with predator density. 4. Additional experiments suggest that the prey is able to detect its predator through chemical cues and to modify its dispersal behaviour accordingly. 5. Density-dependent dispersal suggests that regional processes depend on local community dynamics. We discuss the potential consequences of density-dependent dispersal on metacommunity dynamics and stability. 相似文献
68.
Wang T Ioannidis S Almeida L Block MH Davies AM Lamb ML Scott DA Su M Zhang HJ Alimzhanov M Bebernitz G Bell K Zinda M 《Bioorganic & medicinal chemistry letters》2011,21(10):2958-2961
Synthesis and biological evaluation of a series of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors was reported. Biochemical screening, followed by profile optimization, resulted in JAK2 inhibitors exhibiting good kinase selectivity, pharmacokinetic properties, physical properties and pharmacodynamic effects. 相似文献
69.
Recombination, the precise physical breakage and rejoining of DNA between homologous chromosomes, plays a central role in mediating the orderly segregation of meiotic chromosomes in most eukaryotes. Despite its importance, the factors that control the number and placement of recombination events within a cell remain poorly defined. The rate of recombination exhibits remarkable species specificity, and, within a species, recombination is affected by the physical size of the chromosome, chromosomal location, proximity to other recombination events (i.e., chiasma interference), and, intriguingly, the sex of the transmitting parent. To distinguish between simple genetic and nongenetic explanations of sex-specific recombination differences in mammals, we compared recombination in meiocytes from XY sex-reversed and XO females with that in meiocytes from XX female and XY male mice. The rate and pattern of recombination in XY and XO oocytes were virtually identical to those in normal XX females, indicating that sex, not genotype, is the primary determinant of meiotic recombination patterns in mammals. 相似文献
70.
We conducted an experimental landscape study to test the hypotheses that: (1) habitat removal results in short-term increases in population density in the remaining habitat patches (the crowding effect); (2) following habitat removal, density is higher in landscapes with more, smaller patches and more habitat edge (i.e., a higher level of habitat fragmentation per se) than in less fragmented landscapes, for the same total amount of habitat on the landscapes; (3) this positive effect of fragmentation per se on density is larger in landscapes with smaller inter-patch distances; and (4) these last two effects should be reduced or disappear over time following habitat removal. Our results did not support the first hypothesis, but they provided some support for the other three hypotheses, for two of the four Coccinellid species studied. As in other empirical studies of fragmentation per se on population density, the effects of fragmentation per se were weak and positive (when they did occur). This is the first study to document a transient effect of fragmentation per se on population density, and to show that this effect depends on inter-patch distances. We suggest that fragmentation per se increased the rate of immigration to patches, resulting in higher population densities in more fragmented landscapes. 相似文献