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1.
J Neurosci ; 26(20): 5511-23, 2006 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-16707803

RESUMO

Synaptogenesis during early development is thought to follow a canonical program whereby synapses increase rapidly in number and individual axons multiply-innervate nearby targets. Typically, a subset of inputs then out-competes all others through experience-driven processes to establish stable, long-lasting contacts. We investigated the formation of the calyx of Held, probably the largest nerve terminal in the mammalian CNS. Many basic functional and morphological features of calyx growth have not been studied previously, including whether mono-innervation, a hallmark of this system in adult animals, is established early in development. Evoked postsynaptic currents, recorded from neonatal mice between postnatal day 1 (P1) and P4, increased dramatically from -0.14 +/- 0.04 nA at P1 to -6.71 +/- 0.65 nA at P4 with sharp jumps between P2 and P4. These are the first functional assays of these nascent synapses for ages less than P3. AMPA and NMDA receptor-mediated currents were prominent across this age range. Electron microscopy (EM) revealed a concomitant increase, beginning at P2, in the prevalence of postsynaptic densities (16-fold) and adhering contacts (73-fold) by P4. Therefore, both functional and structural data showed that young calyces could form within 2 d, well before the onset of hearing around P8. Convergence of developing calyces onto postsynaptic targets, indicative of competitive processes that precede mono-innervation, was rare (4 of 29) at P4 as assessed using minimal stimulation electrophysiology protocols. Serial EM sectioning through 19 P4 cells further established the paucity (2 of 19) of convergence. These data indicate that calyces of Held follow a noncanonical program to establish targeted innervation that occurs over a rapid time course and precedes auditory experience.


Assuntos
Vias Auditivas/crescimento & desenvolvimento , Diferenciação Celular/fisiologia , Núcleo Coclear/crescimento & desenvolvimento , Terminações Pré-Sinápticas/fisiologia , Rombencéfalo/crescimento & desenvolvimento , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Vias Auditivas/ultraestrutura , Percepção Auditiva/fisiologia , Núcleo Coclear/ultraestrutura , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/fisiologia , Ácido Glutâmico/metabolismo , Camundongos , Microscopia Eletrônica de Transmissão , Plasticidade Neuronal/fisiologia , Técnicas de Patch-Clamp , Terminações Pré-Sinápticas/ultraestrutura , Receptores de AMPA/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Rombencéfalo/ultraestrutura , Membranas Sinápticas/metabolismo , Membranas Sinápticas/ultraestrutura , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/metabolismo , Vesículas Sinápticas/ultraestrutura , Fatores de Tempo
2.
Biochem Mol Biol Educ ; 34(2): 148-54, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21638660

RESUMO

An analysis of the development of human papillomavirus (HPV) vaccines requires a fundamental comprehension of the underlying science of the technology, as well as an appreciation for the business issues essential to successful commercialization. Students analyzing this topic must consider scientific challenges related to the development of these vaccines, as well as the implications for their commercialization. This case study describes the evolution of our understanding of HPV infection and its causative link to cervical cancer, the establishment of viable HPV vaccine candidates, and various issues related to HPV vaccine implementation. Study questions for use in generating class discussion are provided.

3.
J Acquir Immune Defic Syndr ; 32(1): 9-17, 2003 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-12514409

RESUMO

In this study, we investigated the CD4 T-helper response induced by ALVAC-HIV(vCP205) +/- rgp160MN/LAI-2 using a series of 15 overlapping amino acid peptides spanning the entire gp160MN/LAI-2 antigen. CD4 Env-specific T-cell lines were established from three groups of HIV-1-negative HIV vaccine recipients: vCP205 + gp160MN/LAI-2, vCP205 only, and gp160MN/LAI-2 only. CD4 Env-specific T-cell lines established from individuals who received the prime-boost vCP205 + rgp160MN/LAI-2 generated strong and broad T-helper responses scattered across the Env sequence, whereas Env-specific T-cell lines from individuals receiving the vCP205 vaccine alone generated reactivity to only a few peptides. CD4 -specific T-cell lines were also established from HIV-1-infected individuals and demonstrated poor reactogenicity to Env peptides in both breadth and amplitude of response. These results highlight the complexity of major histocompatibility complex class II presentation and CD4 antigen-specific reactivity, emphasizing the need to better understand these crucial T-helper cell responses in the setting of HIV infection and HIV vaccine development.


Assuntos
Vacinas contra a AIDS/imunologia , Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Antígenos HIV/imunologia , Proteína gp160 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , Adulto , Sequência de Aminoácidos , Linfócitos T CD4-Positivos/citologia , Células Cultivadas , Mapeamento de Epitopos , Epitopos de Linfócito T/química , Antígenos HIV/química , Infecções por HIV/virologia , Humanos , Ativação Linfocitária , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Vacinação
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