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141.
Gillespie GM Stewart-Jones G Rengasamy J Beattie T Bwayo JJ Plummer FA Kaul R McMichael AJ Easterbrook P Dong T Jones EY Rowland-Jones SL 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(6):3893-3902
HLA-B*57 is associated with slower disease progression to AIDS, and CD8+ T cell responses to B*57-restricted epitopes are thought to contribute to this protective effect. In this study, we evaluate the B*57-restricted p24 KAFSPEVIPMF (KF11) immune response which is immunodominant during chronic infection. Previously, we observed that the KF11 clade variants KGFNPEVIPMF [A2G,S4N] and KAFNPEIIMPF [S4N,V7I], sharing a position 4 mutation, are differentially recognized by KF11-specific T cells. By combining structural and cellular studies, we now demonstrate that the KF11 and [A2G,S4N] epitopes induce distinct functional responses in [A2G,S4N] and KF11-specific T cells, respectively, despite minimal structural differences between the individual B*57-peptide complexes. Recently, we also elucidated the highly distinct structure of KF11 in complex with B*5703, and have now characterized the CD8+ T cell repertoire recognizing this epitope. We now report striking features of TCR conservation both in terms of TCR Valpha and Vbeta chain usage, and throughout the hypervariable region. Collectively, our findings highlight unusual features of the B*5701/B*5703-KF11-specific immune responses which could influence disease progression and that might be important to consider when designing future vaccine regimens. 相似文献
142.
Bim plays a crucial role in synergistic induction of apoptosis by the histone deacetylase inhibitor SBHA and TRAIL in melanoma cells 总被引:3,自引:0,他引:3
Gillespie S Borrow J Zhang XD Hersey P 《Apoptosis : an international journal on programmed cell death》2006,11(12):2251-2265
The wide variation in sensitivity of cancer cells to TRAIL- or histone deacetylase (HDAC) inhibitor – induced apoptosis precludes
successful treatment of cancer with these agents. We report here that TRAIL and SBHA synergistically induce apoptosis of melanoma
cells as revealed by quantitative analysis using the normalized isobologram method. This is supported by enhanced activation
of caspase-3 and cleavage of its substrates, PARP and ICAD. Co-treatment with SBHA and TRAIL did not enhance formation of
the death-inducing signaling complex (DISC) and processing of caspase-8 and Bid, but potentiated activation of Bax and release
of Cytochrome C and Smac/DIABLO from mitochondria into the cytosol. SBHA down-regulated Bcl-XL, Mcl-1 and XIAP, but up-regulated Bax, Bak, and the BH3-only protein BimEL. Up-regulation of the latter by SBHA was attenuated by the presence of TRAIL, which was inhibitable by the pan-caspase inhibitor
z-VAD-fmk. Inhibition of Bim by siRNA attenuated conformational changes of Bax, mitochondrial apoptotic events, and activation
of caspase-3, leading to marked inhibition of the synergy between SBHA and TRAIL. Thus, Bim plays an essential role in synergistic
induction of apoptosis by SBHA and TRAIL in melanoma.
This work was supported by the NSW State Cancer Council, the Melanoma and Skin Cancer Research Institute Sydney, the Hunter
Melanoma Foundation, NSW, and the National Health and Medical Research Council, Australia. X.D. Zhang is a Cancer Institute
NSW Fellow. 相似文献
143.
Thomas R. Gillespie 《International journal of primatology》2006,27(4):1129-1143
Recent evidence of emerging human diseases with origins or likely transmission to humans, or both, that involve primates and a greater recognition of the risk of human pathogen transmission to free-ranging primates have raised awareness of the potential impact of zoonotic pathogen transmission on primate conservation and nonhuman primate and human health. As human population density continues to increase exponentially, speeding the reduction and fragmentation of primate habitats, greater human-primate contact is inevitable and even higher rates of pathogen transmission are likely. Thus interest has grown in collecting baseline data on patterns of parasitic infections in wild primate populations to provide an index of population health and to begin to assess and, to manage disease risks. Primatologists traditionally have been involved with such surveys through noninvasive assessment of gastrointestinal parasites. Unfortunately, previous studies have tended toward divergent methodologies, compromising the potential for longitudinal and comparative work. Here, I provide practical guidelines and standardized methodologies for the noninvasive assessment of gastrointestinal parasites of primates.
相似文献
Thomas R. GillespieEmail: |
144.
Adult male red colobus (Procolobus tephrosceles) were observed capturing and killing an owl (Glaucidium perlatum) in the Rurama forest fragment near Kibale National Park in western Uganda. The owl was not subsequently eaten by the colobus, their conspecifics, or the other primates present during the attack. Because the incident was preceded by an agonistic encounter with a raptor, the event is best interpreted as a misdirected antipredator behavior. Although antipredator behaviors are not unknown in red colobus, this is the first such incident directed against a raptor to be documented. 相似文献
145.
Relationships of Exodontiella, a non-alysiine, exodont member of the family Braconidae (Insecta, Hymenoptera) 总被引:1,自引:0,他引:1
Robert A. Wharton Matthew J. Yoder Joseph J. Gillespie John C. Patton & Rodney L. Honeycutt 《Zoologica scripta》2006,35(4):323-340
The placement of Exodontiella Wharton is re-examined in light of the discovery of four additional individuals. Genomic DNA was extracted from one of the individuals, the D2 expansion segment of the 28S rRNA gene was sequenced, and the sequence compared to selected taxa within the Braconidae. Based on the molecular data and the morphological study, Exodontiella is formally transferred from the Opiinae to the Gnamptodontinae. The genus and its included species are redescribed. 相似文献
146.
All developmental stages of Tanystylum bealensis are described. This is the first complete developmental series of a pycnogonid species collected from a natural, rather than a laboratory-reared population. Development proceeds through a series of nine instars from egg to adult, with major defining characteristics of the instars being the addition of walking legs, loss of chelifores, and modification of larval appendages into adult palps and ovigers. All stages are free-living on the hydroid Plumularia setacea, except for the first instar (protonymphon), which remains on the ovigers of the adult male for a short time after hatching. Development in T. bealensis is compared to development in both the closely related species T. orbiculare and to the more distantly related Achelia alaskensis. 相似文献
147.
148.
Markert JM Cody JJ Parker JN Coleman JM Price KH Kern ER Quenelle DC Lakeman AD Schoeb TR Palmer CA Cartner SC Gillespie GY Whitley RJ 《Journal of virology》2012,86(9):5304-5313
Herpes simplex virus 1 (HSV-1) mutants that lack the γ(1)34.5 gene are unable to replicate in the central nervous system but maintain replication competence in dividing cell populations, such as those found in brain tumors. We have previously demonstrated that a γ(1)34.5-deleted HSV-1 expressing murine interleukin-12 (IL-12; M002) prolonged survival of immunocompetent mice in intracranial models of brain tumors. We hypothesized that M002 would be suitable for use in clinical trials for patients with malignant glioma. To test this hypothesis, we (i) compared the efficacy of M002 to three other HSV-1 mutants, R3659, R8306, and G207, in murine models of brain tumors, (ii) examined the safety and biodistribution of M002 in the HSV-1-sensitive primate Aotus nancymae following intracerebral inoculation, and (iii) determined whether murine IL-12 produced by M002 was capable of activating primate lymphocytes. Results are summarized as follows: (i) M002 demonstrated superior antitumor activity in two different murine brain tumor models compared to three other genetically engineered HSV-1 mutants; (ii) no significant clinical or magnetic resonance imaging evidence of toxicity was observed following direct inoculation of M002 into the right frontal lobes of A. nancymae; (iii) there was no histopathologic evidence of disease in A. nancymae 1 month or 5.5 years following direct inoculation; and (iv) murine IL-12 produced by M002 activates A. nancymae lymphocytes in vitro. We conclude that the safety and preclinical efficacy of M002 warrants the advancement of a Δγ(1)34.5 virus expressing IL-12 to phase I clinical trials for patients with recurrent malignant glioma. 相似文献
149.
Species formation during adaptive radiation often occurs in the context of a changing environment. The establishment and arrangement of populations, in space and time, sets up ecological and genetic processes that dictate the rate and pattern of differentiation. Here, we focus on how a dynamic habitat can affect genetic structure, and ultimately, differentiation among populations. We make use of the chronology and geographical history provided by the Hawaiian archipelago to examine the initial stages of population establishment and genetic divergence. We use data from a set of 6 spider lineages that differ in habitat affinities, some preferring low elevation habitats with a longer history of connection, others being more specialized for high elevation and/or wet forest, some with more general habitat affinities. We show that habitat preferences associated with lineages are important in ecological and genetic structuring. Lineages that have more restricted habitat preferences are subject to repeated episodes of isolation and fragmentation as a result of lava flows and vegetation succession. The initial dynamic set up by the landscape translates over time into discrete lineages. Further work is needed to understand how genetic changes interact with a changing set of ecological interactions amongst a shifting mosaic of landscapes to achieve species formation. 相似文献
150.
Human thermal comfort assessments pertaining to exercise while in outdoor environments can improve urban and recreational
planning. The current study applied a simple four-segment skin temperature approach to the COMFA (COMfort FormulA) outdoor
energy balance model. Comparative results of measured mean skin temperature (
[`(T)]\nolimitsMsk \mathop{{\bar{T}}}\nolimits_{{Msk}} ) with predicted
[`(T)]\nolimitssk \mathop{{\bar{T}}}\nolimits_{{sk}} indicate that the model accurately predicted
[`(T)]\nolimitssk \mathop{{\bar{T}}}\nolimits_{{sk}} , showing significantly strong agreement (r = 0.859, P < 0.01) during outdoor exercise (cycling and running). The combined 5-min mean variation of the
[`(T)]\nolimitssk \mathop{{\bar{T}}}\nolimits_{{sk}} RMSE was 1.5°C, with separate cycling and running giving RMSE of 1.4°C and 1.6°C, respectively, and no significant difference
in residuals. Subjects’ actual thermal sensation (ATS) votes displayed significant strong rank correlation with budget scores
calculated using both measured and predicted
[`(T)]\nolimitssk \mathop{{\bar{T}}}\nolimits_{{sk}} (r
s
= 0.507 and 0.517, respectively, P < 0.01). These results show improved predictive strength of ATS of subjects as compared to the original and updated COMFA
models. This psychological improvement, plus
[`(T)]\nolimitssk \mathop{{\bar{T}}}\nolimits_{{sk}} and T
c validations, enables better application to a variety of outdoor spaces. This model can be used in future research studying
linkages between thermal discomfort, subsequent decreases in physical activity, and negative health trends. 相似文献