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1.
Neuron ; 46(1): 37-49, 2005 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-15820692

RESUMO

Rhythmic limb movements are controlled by pattern-generating neurons within the ventral spinal cord, but little is known about how these locomotor circuits are assembled during development. At early stages of embryogenesis, motor neurons are spontaneously active, releasing acetylcholine that triggers the depolarization of adjacent cells in the spinal cord. To investigate whether acetylcholine-driven activity is required for assembly of the central pattern-generating (CPG) circuit, we studied mice lacking the choline acetyltransferase (ChAT) enzyme. Our studies show that a rhythmically active spinal circuit forms in ChAT mutants, but the duration of each cycle period is elongated, and right-left and flexor-extensor coordination are abnormal. In contrast, blocking acetylcholine receptors after the locomotor network is wired does not affect right-left or flexor-extensor coordination. These findings suggest that the cholinergic neurotransmitter pathway is involved in configuring the CPG during a transient period of development.


Assuntos
Acetilcolina/metabolismo , Colina O-Acetiltransferase/deficiência , Neurônios Motores/metabolismo , Vias Neurais/embriologia , Medula Espinal/embriologia , Potenciais de Ação/fisiologia , Animais , Ataxia/etiologia , Eletrofisiologia , Embrião de Mamíferos , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Mutantes , Atividade Motora/fisiologia , Vias Neurais/enzimologia , Técnicas de Cultura de Órgãos
2.
Curr Biol ; 12(15): 1301-11, 2002 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-12176358

RESUMO

BACKGROUND: RNA interference (RNAi) is a newly discovered cellular defense system that is known to suppress replication of genomic parasites in model organisms. It has been widely conjectured that RNAi may also serve as an antiviral system in vertebrates. RESULTS: Retroviral infection could be initiated by electroporation of cloned Rous sarcoma virus (RSV) proviral DNA into the developing chick neural tube. Coelectroporation of proviral DNA and short double-stranded RNAs matching sequences of avain retroviruses, which were designed to induce RNAi against RSV, inhibited viral replication. Replication of RSV after electroporation resulted in disruption of embryonic development and early death, but this, too, could be suppressed by RNAi against the RSV genome. RNAi could also inhibit the growth of RSV and HIV in cell culture. Analysis of the step of the retroviral life cycle that is inhibited by RNAi revealed that it primarily prevented accumulation of the viral RNAs synthesized late during infection. RNA genomes introduced in viral particles early during infection were less sensitive. CONCLUSIONS: RNAi can block retroviral infection in vertebrates. The tissue electroporation method described here should allow RNAi to be used widely to study gene function and control of infection in vertebrate animals.


Assuntos
Interferência de RNA , Retroviridae/genética , Retroviridae/patogenicidade , Animais , Vírus do Sarcoma Aviário/genética , Vírus do Sarcoma Aviário/patogenicidade , Sequência de Bases , Embrião de Galinha , Técnicas de Transferência de Genes , Proteínas de Fluorescência Verde , Proteínas Luminescentes/metabolismo , Sistema Nervoso/embriologia , Oligonucleotídeos/química , RNA Mensageiro/genética , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Viral/genética , Proteínas Recombinantes de Fusão/metabolismo , Retroviridae/fisiologia , Virulência/genética , Replicação Viral/genética
3.
Inorg Chem ; 41(6): 1652-7, 2002 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-11896736

RESUMO

The first monomeric antimony alkoxides, Sb(OC(6)H(3)Me(2))(3) (1) and Sb(OEt)(5) x NH(3) (2), have been crystallographically characterized. The former adopts a trigonal pyramidal geometry, while the latter is octahedral about antimony; hydrogen bonding between NH(3) and SbOEt groups in Sb(OEt)(5) small middle dotNH(3) creates a one-dimensional lattice arrangement. Reaction of pyridine with SbCl(5) in EtOH/hexane yields the salt [Hpy(+)](9)[Sb(2)Cl(11)(5)(-)][Cl(-)](4) (3), which has also been crystallographically characterized. Crystallographic data: 1, C(24)H(27)O(3)Sb, a = 10.9080(2), b = 11.9660(2), c = 17.7260(4) A, alpha = 109.740(1) degrees, monoclinic P2(1)/c (unique axis a), Z = 4; 2, C(10)H(28)NO(5)Sb, a = 7.7220(1), b = 19.0700(2), c = 21.6800(3) A, beta = 93.4960(7) degrees, monoclinic P2(1)/c, Z = 8; 3, C(45)H(54)Cl(15)N(9)Sb(2), a = 13.4300(2), b = 14.4180(2), c = 17.4180(3) A, alpha = 82.7650(7), beta = 77.5570(7), gamma = 70.7670(7) degrees, triclinic P1, Z = 2.

4.
Inorg Chem ; 41(20): 5052-8, 2002 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-12354037

RESUMO

A series of tris(N,N-dialkylcarbamato)antimony(III) complexes, Sb(O(2)CNR(2))(3) (R = Me, Et, Pr(i)()), have been synthesized and are the first members of this class of compound to have been crystallographically characterized. Sb(O(2)CNMe(2))(3) (1) exists as a weakly bound dimer, whereas its diethyl and diisopropyl analogues (2, 3) are monomeric. In addition, tetrakis(N,N-diethylcarbamato)tin(IV) (4) has been prepared for comparison and shown by single-crystal X-ray analysis to exhibit the relatively rare SnO(8) coordination. Crystallographic data: for 1, a = 8.7520(5) A, b = 14.2970(8) A, c = 11.8150(7) A, beta = 108.029(2) degrees, monoclinic, P2(1)/c, Z = 4; for 2, a = b = 14.4690(2) A, c = 16.6740(2) A, trigonal, Rthremacr;, Z = 6; for 3, a = 11.9881(2) A, b = 11.6521(3) A, c = 19.8780(6) A, beta = 90.401(1) degrees, monoclinic, P2(1)/n, Z = 4; for 4, a = 13.9654(2) A, b = 12.0817(2) A, c = 16.6752(2) A, beta = 108.1960(7) degrees, monoclinic, C2/c, Z = 4. Sb(O(2)CNMe(2))(3) has been used as a single-source precursor in the low-pressure chemical vapor deposition of the senarmonite form of Sb(2)O(3).

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