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2.
Nat Biotechnol ; 34(1): 25-30, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26744974
4.
Nat Biotechnol ; 27(8): 705-9, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19668174

RESUMEN

After a decade of significant challenges, biotech's long-term sustainability depends on making fundamental changes to its traditional business model.


Asunto(s)
Biotecnología/economía , Comercio/economía , Industria Farmacéutica/economía , Mercadotecnía/economía , Innovación Organizacional/economía
6.
Nat Biotechnol ; 24(11): 1335-40, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17093473

RESUMEN

Contrary to conventional thinking, there are compelling reasons for investors to consider early-stage life science ventures, especially in the context of a maturing biotech business 'ecosystem'.


Asunto(s)
Biotecnología/economía , Financiación del Capital/economía , Industria Farmacéutica/economía , Inversiones en Salud/economía , Biotecnología/tendencias , Financiación del Capital/tendencias , Industria Farmacéutica/tendencias , Competencia Económica , Inversiones en Salud/tendencias , Estados Unidos
7.
J Immunol ; 175(7): 4618-26, 2005 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-16177107

RESUMEN

CTL play a critical role in the control of HIV and SIV. However, intrinsic genetic instability enables these immunodeficiency viruses to evade detection by CTL through mutation of targeted antigenic sites. These mutations can impair binding of viral epitopes to the presenting MHC class I molecule or disrupt TCR-mediated recognition. In certain regions of the virus, functional constraints are likely to limit the capacity for variation within epitopes. Mutations elsewhere in the protein, however, might still enable immune escape through effects on Ag processing. In this study, we describe the coincident emergence of three mutations in a highly conserved region of Nef during primary HIV-1 infection. These mutations (R69K, A81G, and H87R) flank the HLA B*35-restricted VY8 epitope and persisted to fixation as the early CTL response to this Ag waned. The variant form of Nef showed a reduced capacity to activate VY8-specific CTL, although protein stability and expression levels were unchanged. This effect was associated with altered processing by the proteasome that caused partial destruction of the VY8 epitope. Our data demonstrate that a variant HIV genotype can significantly impair proteasomal epitope processing and substantiate the concept of immune evasion through diminished Ag generation. These observations also indicate that the scale of viral escape may be significantly underestimated if only intraepitope variation is evaluated.


Asunto(s)
Presentación de Antígeno , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/genética , Productos del Gen nef/metabolismo , VIH-1/metabolismo , Mutación , Complejo de la Endopetidasa Proteasomal/fisiología , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Presentación de Antígeno/genética , Línea Celular , ADN Intergénico , Epítopos de Linfocito T/fisiología , Productos del Gen nef/genética , Infecciones por VIH/inmunología , VIH-1/genética , Antígenos HLA-B/metabolismo , Humanos , Masculino , Datos de Secuencia Molecular , Procesamiento Proteico-Postraduccional , Linfocitos T Citotóxicos/inmunología , Productos del Gen nef del Virus de la Inmunodeficiencia Humana
10.
Nat Rev Drug Discov ; 2(10): 838-41, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14526387

RESUMEN

By combining innovative science with years of massive investment, drug makers seek to turn newly discovered chemicals into revolutionary blockbuster drugs that generate billions of dollars in revenue. So every year, they collectively spend tens of billions of dollars on the high-risk pursuit of the next Prozac or Viagra. But should they? This article analyses key themes around differentiation that we have found to be common among blockbusters, and examines the implications for creating future billion-dollar drugs.


Asunto(s)
Aprobación de Drogas , Costos de los Medicamentos/tendencias , Diseño de Fármacos , Industria Farmacéutica/economía , Resultado del Tratamiento , Evaluación de Medicamentos , Humanos , Seguridad
12.
Viral Immunol ; 15(1): 193-6, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-11952141

RESUMEN

Cytotoxic T lymphocytes (CTLs) play a key role in the control of persistent viral infections. Differences in the quality of this cellular immune response influence the long-term outcome of such infections, but the factors that determine which virus-derived peptide epitopes are targeted by CTLs remain poorly understood. Here, we examine the antigen-processing requirements of three human leukocyte antigen (HLA) A*0201-restricted HIV-1 CTL epitopes. Each of these three peptides appears to be generated by a distinct proteolytic pathway, despite presentation on the cell surface in association with the same HLA class I molecule. Presentation of the commonly immunodominant SLYNTVATL (HIV-1 p17 Gag; residues 77-85) epitope was unaffected by inhibition of the proteasome with lactacystin, but was dependent on the presence of the beta-subunit LMP7. These findings are consistent with emerging data on the complexity of peptide epitope generation, and suggest that differences in antigen processing might contribute to patterns of CTL recognition in vivo.


Asunto(s)
Epítopos de Linfocito T , VIH-1/inmunología , Antígeno HLA-A2/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Presentación de Antígeno , Cisteína Endopeptidasas/fisiología , Transcriptasa Inversa del VIH/inmunología , Complejos Multienzimáticos/fisiología , Complejo de la Endopetidasa Proteasomal , Ratas
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