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1.
Sci Adv ; 8(47): eabo4856, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36417517

RESUMO

Perseverance's Mastcam-Z instrument provides high-resolution stereo and multispectral images with a unique combination of spatial resolution, spatial coverage, and wavelength coverage along the rover's traverse in Jezero crater, Mars. Images reveal rocks consistent with an igneous (including volcanic and/or volcaniclastic) and/or impactite origin and limited aqueous alteration, including polygonally fractured rocks with weathered coatings; massive boulder-forming bedrock consisting of mafic silicates, ferric oxides, and/or iron-bearing alteration minerals; and coarsely layered outcrops dominated by olivine. Pyroxene dominates the iron-bearing mineralogy in the fine-grained regolith, while olivine dominates the coarse-grained regolith. Solar and atmospheric imaging observations show significant intra- and intersol variations in dust optical depth and water ice clouds, as well as unique examples of boundary layer vortex action from both natural (dust devil) and Ingenuity helicopter-induced dust lifting. High-resolution stereo imaging also provides geologic context for rover operations, other instrument observations, and sample selection, characterization, and confirmation.

2.
J Immunol ; 176(7): 4075-82, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16547243

RESUMO

Immunoproteasomes comprise a specialized subset of proteasomes that is defined by the presence of three catalytic immunosubunits: LMP2, MECL-1 (LMP10), and LMP7. Proteasomes in general serve many cellular functions through protein degradation, whereas the specific function of immunoproteasomes has been thought to be largely, if not exclusively, optimization of MHC class I Ag processing. In this report, we demonstrate that T cells from double knockout mice lacking two of the immunosubunits, MECL-1 and LMP7, hyperproliferate in vitro in response to various polyclonal mitogens. We observe hyperproliferation of both CD4(+) and CD8(+) T cell subsets and demonstrate accelerated cell cycling. We do not observe hyperproliferation of T cells lacking only one of these subunits, and thus hyperproliferation is independent of either reduced MHC class I expression in LMP7(-/-) mice or reduced CD8(+) T cell numbers in MECL-1(-/-) mice. We observe both of these latter two phenotypes in MECL-1/LMP7(-/-) mice, which indicates that they also are independent of each other. Finally, we provide evidence of in vivo T cell dysfunction by demonstrating increased numbers of central memory phenotype CD8(+) T cells in MECL-1/LMP7(-/-) mice. In summary, this novel phenotype of hyperproliferation of T cells lacking both MECL-1 and LMP7 implicates a specific role for immunoproteasomes in T cell proliferation that is not obviously connected to MHC class I Ag processing.


Assuntos
Cisteína Endopeptidases/metabolismo , Mitógenos/imunologia , Complexos Multienzimáticos/metabolismo , Complexo de Endopeptidases do Proteassoma/imunologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cisteína Endopeptidases/deficiência , Cisteína Endopeptidases/genética , Regulação da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/metabolismo , Imunidade Inata , Memória Imunológica , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Camundongos , Camundongos Knockout , Mitógenos/farmacologia , Complexos Multienzimáticos/deficiência , Complexos Multienzimáticos/genética , Fenótipo , Subunidades Proteicas/deficiência , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Baço/imunologia , Baço/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
3.
J Clin Endocrinol Metab ; 90(4): 2364-9, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15671095

RESUMO

Ionizing radiation is a well-known risk factor for thyroid cancer in human populations. Chromosomal rearrangements involving the RET gene, known as RET/PTC, are prevalent in thyroid papillary carcinomas from patients with radiation history. We studied the generation of RET/PTC in HTori-3 immortalized human thyroid cells exposed to a range of doses of gamma-radiation and harvested 2, 5-6, and 9 d later. RET/PTC1 and RET/PTC3 were detected by RT-PCR followed by Southern blotting and hybridization with internal oligonucleotide probes. No RET/PTC was found in cells harvested 2 and 5-6 d after irradiation, whereas 59 RET/PTC events were detected in cells collected 9 d after exposure. The average rate of RET/PTC induction was 0.1 x 10(-6) after exposure to 0.1 Gy, 1.6 x 10(-6) after 1 Gy, 3.0 x 10(-6) after 5 Gy, and 0.9 x 10(-6) after 10 Gy. When adjusted for cell survival, the rate after 10 Gy was comparable with those after 5 Gy. RET/PTC1 was more common than RET/PTC3 after each dose, comprising 80% of all rearrangements. In this study, we demonstrate a dose-dependent induction of RET/PTC rearrangements in human thyroid cells after exposure to 0.1-10 Gy gamma-radiation. This provides additional evidence for a direct link between this genetic event and radiation exposure and offers a powerful experimental system for studying radiation-induced carcinogenesis in the thyroid gland.


Assuntos
Rearranjo Gênico , Neoplasias Induzidas por Radiação/etiologia , Proteínas Oncogênicas/genética , Glândula Tireoide/efeitos da radiação , Neoplasias da Glândula Tireoide/etiologia , Proliferação de Células/efeitos da radiação , Células Cultivadas , Relação Dose-Resposta à Radiação , Raios gama , Humanos , Neoplasias Induzidas por Radiação/genética , Proteínas de Fusão Oncogênica , Proteínas Tirosina Quinases , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética
4.
Am J Surg Pathol ; 26(8): 1016-23, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12170088

RESUMO

A PAX8-PPARgamma rearrangement has been recently identified in follicular thyroid carcinomas, but not in follicular adenomas or other thyroid tumors. We report here the analyses of PAX8-PPARgamma in a series of 118 thyroid tumors using a newly developed RT-PCR assay to detect this rearrangement in frozen and paraffin-embedded tissues and using immunostaining with a PPARgamma antibody. PAX8-PPARgamma was detected by RT-PCR in eight of 15 (53%) follicular carcinomas and two of 25 (8%) follicular adenomas but not in 35 papillary carcinomas (including 12 follicular variants), 12 Hurthle cell carcinomas, 12 Hurthle cell adenomas, two anaplastic carcinomas, one poorly differentiated carcinoma, or 16 hyperplastic nodules. The prevalence was higher in follicular carcinomas from patients with a history of radiation exposure (three of three). Strong, diffuse nuclear immunostaining with the PPARgamma antibody correlated with the presence of PAX8-PPARgamma detected by RT-PCR. Most sporadic follicular carcinomas positive for PAX8-PPARgamma were overtly invasive, whereas tumors lacking the rearrangement were predominantly minimally invasive. The two follicular adenomas positive for PAX8-PPARgamma had trabecular growth pattern and thick capsule, but no invasion, and thus may represent "pre-invasive" follicular carcinomas. The absence of PAX8-PPARgamma rearrangements in Hurthle cell tumors and papillary thyroid carcinomas highlights the differences in the molecular pathogenesis of these thyroid tumors.


Assuntos
Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Proteínas Nucleares , Receptores Citoplasmáticos e Nucleares/genética , Neoplasias da Glândula Tireoide/genética , Transativadores/genética , Fatores de Transcrição/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/patologia , Adenoma Oxífilo/genética , Adenoma Oxífilo/patologia , Carcinoma/genética , Carcinoma/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Humanos , Imuno-Histoquímica , Fator de Transcrição PAX8 , Fatores de Transcrição Box Pareados , Reação em Cadeia da Polimerase , Neoplasias da Glândula Tireoide/patologia
5.
Int J Surg Pathol ; 10(1): 15-22, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11927965

RESUMO

The relationship between Hashimoto's thyroiditis (HT) and follicular cell-derived thyroid cancer remains unclear. Recently, 2 studies reported a 95% prevalence of RET/PTC rearrangements in histologically benign tissue affected by HT, suggesting that multiple occult tumors exist in HT patients with high frequency. We tested the prevalence of RET/PTC rearrangements in 26 HT, in 6 papillary carcinomas arising in the background of HT, and in 27 papillary carcinomas not associated with HT. We detected no RET/PTC rearrangements in HT or papillary carcinomas arising in the background of HT, in contrast to a 33% prevalence among papillary carcinomas not associated with HT. However, the expression of wild-type RET was found in more than half of papillary carcinomas. These results suggest that, if the association between HT and thyroid cancer exists, its molecular basis is different from RET/PTC rearrangement.


Assuntos
Carcinoma Papilar, Variante Folicular/genética , Rearranjo Gênico , Proteínas de Fusão Oncogênica/análise , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Neoplasias da Glândula Tireoide/genética , Tireoidite Autoimune/genética , Carcinoma Papilar, Variante Folicular/complicações , Secções Congeladas , Humanos , Inclusão em Parafina , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas c-ret , RNA Mensageiro/análise , Receptores Proteína Tirosina Quinases/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/complicações , Tireoidite Autoimune/complicações
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