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1.
Chemistry ; 24(56): 15096-15103, 2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30016561

RESUMO

Introducing phenylphosphonic acid (H2 PPA) into the Ag/tBuSH assembly system has produced a family of nanoscale-sized, high-atom number, silver thiolate/PPA nests (SD/Ag45 a, SD/Ag66 a, and SD/Ag73 a) with impressive core-shell features. SD/Ag45 a is a 45-atom ellipsoid comprised of an Ag36 shell trapping an Ag9 S2 three-bladed rotor inside. SD/Ag66 a comprises an inner rod-like Ag20 core and an outer Ag44 shell, giving a 64-atom nest. These Ag64 nests are further extended by Ag(CN)2 linkers to form a one-dimensional chain structure. SD/Ag73 a is a three-shell 73-nucleus silver nest with a central silver atom enclosed in a rhombicuboctahedron of 24 silver atoms, which is itself enclosed in the outermost shell of a rectified version of a 48-Ag octahedral Goldberg 2,0 cage. The solution behaviors and optical absorption properties of the three nests are described in detail. Of note, SD/Ag45 a and SD/Ag73 a emit in the near-infrared region and show different luminescent thermochromic behavior. This work demonstrates that the participation of H2 PPA strongly influences the structures of silver thiolate nests, thus providing a new route to fabricate and modify them in a more rational way.

2.
Proc Natl Acad Sci U S A ; 114(46): 12132-12137, 2017 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-29087328

RESUMO

Buckminsterfullerene (C60) represents a perfect combination of geometry and molecular structural chemistry. It has inspired many creative ideas for building fullerene-like nanopolyhedra. These include other fullerenes, virus capsids, polyhedra based on DNA, and synthetic polynuclear metal clusters and cages. Indeed, the regular organization of large numbers of metal atoms into one highly complex structure remains one of the foremost challenges in supramolecular chemistry. Here we describe the design, synthesis, and characterization of a Ag180 nanocage with 180 Ag atoms as 4-valent vertices (V), 360 edges (E), and 182 faces (F)--sixty 3-gons, ninety 4-gons, twelve 5-gons, and twenty 6-gons--in agreement with Euler's rule V - E + F = 2. If each 3-gon (or silver Trigon) were replaced with a carbon atom linked by edges along the 4-gons, the result would be like C60, topologically a truncated icosahedron, an Archimedean solid with icosahedral (Ih) point-group symmetry. If C60 can be described mathematically as a curling up of a 6.6.6 Platonic tiling, the Ag180 cage can be described as a curling up of a 3.4.6.4 Archimedean tiling. High-resolution electrospray ionization mass spectrometry reveals that {Ag3}n subunits coexist with the Ag180 species in the assembly system before the final crystallization of Ag180, suggesting that the silver Trigon is the smallest building block in assembly of the final cage. Thus, we assign the underlying growth mechanism of Ag180 to the Silver-Trigon Assembly Road (STAR), an assembly path that might be further employed to fabricate larger, elegant silver cages.

3.
Structure ; 22(10): 1385-98, 2014 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-25220471

RESUMO

Like many double-stranded DNA viruses, tumor gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus withstand high internal pressure. Bacteriophage HK97 uses covalent chainmail for this purpose, but how this is achieved noncovalently in the much larger gammaherpesvirus capsid is unknown. Our cryoelectron microscopy structure of a gammaherpesvirus capsid reveals a hierarchy of four levels of organization: (1) Within a hexon capsomer, each monomer of the major capsid protein (MCP), 1,378 amino acids and six domains, interacts with its neighboring MCPs at four sites. (2) Neighboring capsomers are linked in pairs by MCP dimerization domains and in groups of three by heterotrimeric triplex proteins. (3) Small (∼280 amino acids) HK97-like domains in MCP monomers alternate with triplex heterotrimers to form a belt that encircles each capsomer. (4) One hundred sixty-two belts concatenate to form noncovalent chainmail. The triplex heterotrimer orchestrates all four levels and likely drives maturation to an angular capsid that can withstand pressurization.


Assuntos
Proteínas do Capsídeo/química , Capsídeo/química , Rhadinovirus/química , Sequência de Aminoácidos , Animais , Microscopia Crioeletrônica , Dimerização , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Terciária de Proteína
4.
Proc Natl Acad Sci U S A ; 111(8): 2920-5, 2014 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-24516137

RESUMO

The three known classes of convex polyhedron with equal edge lengths and polyhedral symmetry--tetrahedral, octahedral, and icosahedral--are the 5 Platonic polyhedra, the 13 Archimedean polyhedra--including the truncated icosahedron or soccer ball--and the 2 rhombic polyhedra reported by Johannes Kepler in 1611. (Some carbon fullerenes, inorganic cages, icosahedral viruses, geodesic structures, and protein complexes resemble these fundamental shapes.) Here we add a fourth class, "Goldberg polyhedra," which are also convex and equilateral. We begin by decorating each of the triangular facets of a tetrahedron, an octahedron, or an icosahedron with the T vertices and connecting edges of a "Goldberg triangle." We obtain the unique set of internal angles in each planar face of each polyhedron by solving a system of n equations and n variables, where the equations set the dihedral angle discrepancy about different types of edge to zero, and the variables are a subset of the internal angles in 6gons. Like the faces in Kepler's rhombic polyhedra, the 6gon faces in Goldberg polyhedra are equilateral and planar but not equiangular. We show that there is just a single tetrahedral Goldberg polyhedron, a single octahedral one, and a systematic, countable infinity of icosahedral ones, one for each Goldberg triangle. Unlike carbon fullerenes and faceted viruses, the icosahedral Goldberg polyhedra are nearly spherical. The reasoning and techniques presented here will enable discovery of still more classes of convex equilateral polyhedra with polyhedral symmetry.


Assuntos
Fulerenos/química , Matemática/métodos , Modelos Teóricos , Conformação Molecular , Vírus/ultraestrutura
5.
Nat Struct Mol Biol ; 20(1): 105-10, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23241927

RESUMO

Regulated by pH, membrane-anchored proteins E and M function during dengue virus maturation and membrane fusion. Our atomic model of the whole virion from cryo-electron microscopy at 3.5-Å resolution reveals that in the mature virus at neutral extracellular pH, the N-terminal 20-amino-acid segment of M (involving three pH-sensing histidines) latches and thereby prevents spring-loaded E fusion protein from prematurely exposing its fusion peptide. This M latch is fastened at an earlier stage, during maturation at acidic pH in the trans-Golgi network. At a later stage, to initiate infection in response to acidic pH in the late endosome, M releases the latch and exposes the fusion peptide. Thus, M serves as a multistep chaperone of E to control the conformational changes accompanying maturation and infection. These pH-sensitive interactions could serve as targets for drug discovery.


Assuntos
Vírus da Dengue/química , Vírus da Dengue/metabolismo , Proteínas do Envelope Viral/química , Proteínas da Matriz Viral/química , Ligação Viral , Aedes/virologia , Animais , Linhagem Celular , Microscopia Crioeletrônica , Cristalografia por Raios X , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Proteínas de Membrana/metabolismo , Conformação Proteica , Proteínas do Envelope Viral/metabolismo , Proteínas da Matriz Viral/metabolismo , Rede trans-Golgi/metabolismo , Rede trans-Golgi/virologia
6.
Vis Neurosci ; 28(1): 3-16, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21272390

RESUMO

L and M cones, divided into two groups by absorption spectra, have not been distinguished by structure. Here, we report what may be such a difference. We reconstructed the synaptic terminals of 16 non-S cones and the dendritic arbors of their ON and OFF midget bipolar cells from high-magnification electron micrographs of serial thin sections of a small region of macaque fovea. Each cone terminal contacted a similar number (~16) of invaginating central elements provided by its ON midget bipolar cell. By contrast, the numbers of connections between a cone terminal and its OFF midget bipolar cell were grouped into two clusters: 30-37 versus 43-50 basal contacts in the triad-associated position and 41-47 versus 61-74 Outer Densities within those basal contacts. The coefficients of variation of these distributions were all in the range of 10% or lower, characteristic of single populations. If these two clusters correspond to M- and L-cone circuits, the results reveal structural differences between M and L cones and between their corresponding OFF midget bipolar cells.


Assuntos
Fóvea Central/fisiologia , Células Bipolares da Retina/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Sinapses/fisiologia , Animais , Diferenciação Celular , Macaca fascicularis , Masculino , Microscopia Eletrônica de Varredura , Terminações Pré-Sinápticas/fisiologia , Terminações Pré-Sinápticas/ultraestrutura , Células Bipolares da Retina/ultraestrutura , Células Fotorreceptoras Retinianas Cones/ultraestrutura , Sinapses/ultraestrutura , Fixação de Tecidos
7.
Vis Neurosci ; 28(1): 17-28, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21272391

RESUMO

As described in the companion paper, the synaptic terminal of a cone photoreceptor in macaque monkey makes an average of 35 or 46 basal contacts with the tips of the dendrites of its OFF midget bipolar cell. Each basal contact has one or more symmetrically thickened dense regions. These "Outer Densities," averaging 48 or 67 in number, harbor clusters of ionotropic glutamate receptors and are ~0.8 µm (and ~1-ms diffusion time) from active zones associated with synaptic ribbons. Here, we show similarly appearing "Inner Densities," averaging 53 or 74 in number, located more proximally on the dendrites of these OFF midget bipolar cells, ~0.4 µm inward from the tips of the dendrites and out of contact with the basal surface of the cone terminal. Compared to desmosome-like junctions, Inner Densities are closer to the terminal and are less dense and less thick. Each Inner Density is shared with another cell, the partners including diffuse bipolar cells, ON midget bipolar cells, and horizontal cells. Given the diversity of the partners, the OFF midget bipolar cells are unlikely to be in a synaptic relationship with the partners. Instead, Inner Densities are near enough to the active zones associated with synaptic ribbons to receive pulses of glutamate at concentrations effective for glutamate receptors. The role of Inner Densities is not known, but they might represent additional clusters of glutamate receptors.


Assuntos
Dendritos/fisiologia , Fóvea Central/fisiologia , Células Bipolares da Retina/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Sinapses/fisiologia , Animais , Dendritos/ultraestrutura , Fóvea Central/citologia , Fóvea Central/ultraestrutura , Ácido Glutâmico/metabolismo , Processamento de Imagem Assistida por Computador , Macaca fascicularis , Masculino , Microscopia Eletrônica , Modelos Neurológicos , Terminações Pré-Sinápticas/fisiologia , Terminações Pré-Sinápticas/ultraestrutura , Receptores de Superfície Celular/fisiologia , Receptores Ionotrópicos de Glutamato/fisiologia , Células Bipolares da Retina/ultraestrutura , Células Fotorreceptoras Retinianas Cones/ultraestrutura , Sinapses/ultraestrutura
8.
Science ; 329(5995): 1038-43, 2010 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-20798312

RESUMO

Construction of a complex virus may involve a hierarchy of assembly elements. Here, we report the structure of the whole human adenovirus virion at 3.6 angstroms resolution by cryo-electron microscopy (cryo-EM), revealing in situ atomic models of three minor capsid proteins (IIIa, VIII, and IX), extensions of the (penton base and hexon) major capsid proteins, and interactions within three protein-protein networks. One network is mediated by protein IIIa at the vertices, within group-of-six (GOS) tiles--a penton base and its five surrounding hexons. Another is mediated by ropes (protein IX) that lash hexons together to form group-of-nine (GON) tiles and bind GONs to GONs. The third, mediated by IIIa and VIII, binds each GOS to five surrounding GONs. Optimization of adenovirus for cancer and gene therapy could target these networks.


Assuntos
Adenovírus Humanos/química , Adenovírus Humanos/ultraestrutura , Proteínas do Capsídeo/química , Adenovírus Humanos/genética , Adenovírus Humanos/metabolismo , Capsídeo/química , Capsídeo/ultraestrutura , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/ultraestrutura , Microscopia Crioeletrônica , Genoma Viral , Processamento de Imagem Assistida por Computador , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Vírion/química , Vírion/ultraestrutura
9.
Proc Natl Acad Sci U S A ; 107(14): 6292-7, 2010 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-20332209

RESUMO

Bluetongue virus (BTV) is transmitted by blood-feeding insects (Culicoides sp.) and causes hemorrhagic diseases in livestock. BTV is a nonenveloped, double-stranded RNA (dsRNA) virus with two capsids: a well-studied, stable core enclosing the dsRNA genome and a highly unstable, poorly studied coat responsible for host cell attachment and entry. Here, based on cryo-electron microscopy (cryoEM), we report a 7-A resolution structure of the infectious BTV virion, including the coat proteins. We show that unlike other dsRNA viruses, the VP2 attachment trimer has a triskelion shape composed of three tip domains branching from a central hub domain. We identify three putative sialic acid-binding pockets in the hub and present supporting biochemical data indicating sugar moiety binding is important for BTV infection. Despite being a nonenveloped virus, the putative VP5 membrane penetration trimer, located slightly inward of the VP2 attachment trimer, has a central coiled-coil alpha-helical bundle, similar to the fusion proteins of many enveloped viruses (e.g., HIV, herpesviruses, vesicular stomatitis virus, and influenza virus). Moreover, mapping of the amino acid sequence of VP5 to the secondary structural elements identified by cryoEM locates 15 amphipathic alpha-helical regions on the external surface of each VP5 trimer. The cryoEM density map also reveals few, weak interactions between the VP5 trimer and both the outer-coat VP2 trimer and the underlying core VP7 trimer, suggesting that the surface of VP5 could unfurl like an umbrella during penetration and shedding of the coat to release the transcriptionally active core particle.


Assuntos
Vírus Bluetongue/química , Proteínas do Capsídeo/química , Ácido N-Acetilneuramínico/química , Multimerização Proteica , Proteínas Virais de Fusão/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Vírus Bluetongue/metabolismo , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/ultraestrutura , Linhagem Celular , Cricetinae , Microscopia Crioeletrônica , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Ácido N-Acetilneuramínico/metabolismo , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Virais de Fusão/metabolismo , Proteínas Virais de Fusão/ultraestrutura , Replicação Viral
10.
Science ; 327(5966): 689-93, 2010 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-20133572

RESUMO

Vesicular stomatitis virus (VSV) is a bullet-shaped rhabdovirus and a model system of negative-strand RNA viruses. Through direct visualization by means of cryo-electron microscopy, we show that each virion contains two nested, left-handed helices: an outer helix of matrix protein M and an inner helix of nucleoprotein N and RNA. M has a hub domain with four contact sites that link to neighboring M and N subunits, providing rigidity by clamping adjacent turns of the nucleocapsid. Side-by-side interactions between neighboring N subunits are critical for the nucleocapsid to form a bullet shape, and structure-based mutagenesis results support this description. Together, our data suggest a mechanism of VSV assembly in which the nucleocapsid spirals from the tip to become the helical trunk, both subsequently framed and rigidified by the M layer.


Assuntos
Proteínas do Nucleocapsídeo/química , RNA Viral/química , Vesiculovirus/química , Vesiculovirus/ultraestrutura , Proteínas da Matriz Viral/química , Microscopia Crioeletrônica , Cristalografia por Raios X , Processamento de Imagem Assistida por Computador , Bicamadas Lipídicas , Modelos Moleculares , Mutagênese , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/ultraestrutura , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Subunidades Proteicas/química , RNA Viral/ultraestrutura , Vesiculovirus/fisiologia , Proteínas da Matriz Viral/ultraestrutura , Vírion/química , Vírion/ultraestrutura , Montagem de Vírus
11.
J Mol Biol ; 387(2): 363-75, 2009 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-19356592

RESUMO

Fullerene cages have n trivalent vertices, 12 pentagonal faces, and (n-20)/2 hexagonal faces. The smallest cage in which all of the pentagons are surrounded by hexagons and thus isolated from each other has 60 vertices and is shaped like a soccer ball. The protein clathrin self-assembles into fullerene cages of a variety of sizes and shapes, including smaller ones with adjacent pentagons as well as larger ones, but the variety is limited. To explain the range of clathrin architecture and how these fullerene cages self-assemble, we proposed a hypothesis, the "head-to-tail exclusion rule" (the "Rule"). Of the 5769 small clathrin cage isomers with n< or =60 vertices and adjacent pentagons, the Rule permits just 15, three identified in 1976 and 12 others. A "weak version" of the Rule permits another 99. Based on cryo-electron tomography, Cheng et al. reported six raw clathrin fullerene cages. One was among the three identified in 1976. Here, (1) we identify the remaining five. (2) Four are new and are among the 12 others permitted by the Rule. (3) One, also new, is among the 99 weak version cages. (4) Of particular note, none of the remaining 5565 excluded cages has been identified. These findings provide powerful experimental confirmation of the Rule and the principle on which it is based. (5) Surprisingly, the newly identified clathrin cages are among the least symmetric of those permitted. (6) By devising a method for counting assembly paths, (7) we show that asymmetric cages can be assembled by larger numbers of paths, thus providing a kinetic explanation for the prevalence of asymmetric cages. (8) Finally, we show that operation during cage growth of the Rule greatly increases the likelihood of producing a closed fullerene cage, specifically one of those permitted, but efficient assembly still appears to require internal remodeling.


Assuntos
Clatrina/química , Fulerenos/química , Modelos Moleculares , Estereoisomerismo
12.
Proc Natl Acad Sci U S A ; 105(49): 19142-7, 2008 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-19050075

RESUMO

Carbon atoms self-assemble into the famous soccer-ball shaped Buckminsterfullerene (C(60)), the smallest fullerene cage that obeys the isolated-pentagon rule (IPR). Carbon atoms self-assemble into larger (n > 60 vertices) empty cages as well-but only the few that obey the IPR-and at least 1 small fullerene (n 60, the head-to-tail exclusion rule permits only (and all) fullerene cages and nanotubes that obey the IPR. We therefore suggest that self-assembly that obeys the IPR may be explained by the head-to-tail exclusion rule, a geometric constraint.


Assuntos
Clatrina/química , Fulerenos/química , Modelos Químicos , Nanotubos/química , Estereoisomerismo
13.
Biophys J ; 94(3): 938-57, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-17921208

RESUMO

In the companion article, we proposed that fullerene cages with head-to-tail dihedral angle discrepancies do not self-assemble. Here we show why. If an edge abuts a pentagon at one end and a hexagon at the other, the dihedral angle about the edge increases, producing a dihedral angle discrepancy (DAD) vector. The DADs about all five/six edges of a central pentagonal/hexagonal face are determined by the identities-pentagon or hexagon-of its five/six surrounding faces. Each "Ring"-central face plus specific surrounding faces-may have zero, two, or four edges with DAD. In most Rings, the nonplanarity induced by DADs is shared among surrounding faces. However, in a Ring that has DADs arranged head of one to tail of another, the nonplanarity cannot be shared, so some surrounding faces would be especially nonplanar. Because the head-to-tail exclusion rule is an implicit geometric constraint, the rule may operate either by imposing a kinetic barrier that prevents assembly of certain Rings or by imposing an energy cost that makes those Rings unlikely to last in an equilibrium circumstance. Since Rings with head-to-tail DADs would be unlikely to self-assemble or last, fullerene cages with those Rings would be unlikely to self-assemble.


Assuntos
Cristalização/métodos , Fulerenos/química , Modelos Químicos , Modelos Moleculares , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Simulação por Computador , Substâncias Macromoleculares/química , Conformação Molecular
14.
Biophys J ; 94(3): 958-76, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-17921209

RESUMO

Clathrin triskelia and carbon atoms alike self-assemble into a limited selection of fullerene cages (with n three connected vertices, 3n/2 edges, 12 pentagonal faces, and (n-20)/2 hexagonal faces). We show that a geometric constraint-exclusion of head-to-tail dihedral angle discrepancies (DADs)-explains this limited selection as well as successful assembly into such closed cages in the first place. An edge running from a pentagon to a hexagon has a DAD, since the dihedral angles about the edge broaden from its pentagon (tail) end to its hexagon (head) end. Of the 21 configurations of a central face and surrounding faces, six have such DAD vectors arranged head-to-tail. Of the 5770 mathematically possible fullerene cages for n

Assuntos
Cristalização/métodos , Fulerenos/química , Modelos Químicos , Modelos Moleculares , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Simulação por Computador , Substâncias Macromoleculares/química , Conformação Molecular
15.
Biophys J ; 91(9): 3257-67, 2006 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-16920838

RESUMO

A rod transmits absorption of a single photon by what appears to be a small reduction in the small number of quanta of neurotransmitter (Q(count)) that it releases within the integration period ( approximately 0.1 s) of a rod bipolar dendrite. Due to the quantal and stochastic nature of release, discrete distributions of Q(count) for darkness versus one isomerization of rhodopsin (R*) overlap. We suggested that release must be regular to narrow these distributions, reduce overlap, reduce the rate of false positives, and increase transmission efficiency (the fraction of R* events that are identified as light). Unsurprisingly, higher quantal release rates (Q(rates)) yield higher efficiencies. Focusing here on the effect of small changes in Q(rate), we find that a slightly higher Q(rate) yields greatly reduced efficiency, due to a necessarily fixed quantal-count threshold. To stabilize efficiency in the face of drift in Q(rate), the dendrite needs to regulate the biochemical realization of its quantal-count threshold with respect to its Q(count). These considerations reveal the mathematical role of calcium-based negative feedback and suggest a helpful role for spontaneous R*. In addition, to stabilize efficiency in the face of drift in degree of regularity, efficiency should be approximately 50%, similar to measurements.


Assuntos
Dendritos/fisiologia , Modelos Neurológicos , Fótons , Células Bipolares da Retina/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Transmissão Sináptica/fisiologia , Animais , Simulação por Computador , Dendritos/efeitos da radiação , Humanos , Luz , Células Bipolares da Retina/efeitos da radiação , Células Fotorreceptoras Retinianas Bastonetes/efeitos da radiação , Transmissão Sináptica/efeitos da radiação
16.
Biophys J ; 89(6): 3931-49, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16169984

RESUMO

We can see at light intensities much lower than an average of one photon per rod photoreceptor, demonstrating that rods must be able to transmit a signal after absorption of a single photon. However, activation of one rhodopsin molecule (Rh*) hyperpolarizes a mammalian rod by just 1 mV. Based on the properties of the voltage-dependent Ca2+ channel and data on [Ca2+] in the rod synaptic terminal, the 1 mV hyperpolarization should reduce the rate of release of quanta of neurotransmitter by only 20%. If quantal release were Poisson, the distributions of quantal count in the dark and in response to one Rh* would overlap greatly. Depending on the threshold quantal count, the overlap would generate too frequent false positives in the dark, too few true positives in response to one Rh*, or both. Therefore, quantal release must be regular, giving narrower distributions of quantal count that overlap less. We model regular release as an Erlang process, essentially a mechanism that counts many Poisson events before release of a quantum of neurotransmitter. The combination of appropriately narrow distributions of quantal count and a suitable threshold can give few false positives and appropriate (e.g., 35%) efficiency for one Rh*.


Assuntos
Canais de Cálcio/fisiologia , Potenciais da Membrana/fisiologia , Modelos Neurológicos , Neurotransmissores/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Canais de Cálcio/efeitos da radiação , Simulação por Computador , Luz , Potenciais da Membrana/efeitos da radiação , Modelos Químicos , Modelos Estatísticos , Células Fotorreceptoras Retinianas Bastonetes/efeitos da radiação , Sinapses/efeitos da radiação , Transmissão Sináptica/efeitos da radiação
17.
J Neurosci ; 24(38): 8366-78, 2004 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-15385619

RESUMO

A rule of retinal wiring is that many receptors converge onto fewer bipolar cells and still fewer ganglion cells. However, for each S cone in macaque fovea, there are two S-cone ON bipolar cells and two blue-yellow (BY) ganglion cells. To understand this apparent rule reversal, we reconstructed synaptic patterns of divergence and convergence and determined the basic three-tiered unit of connectivity that repeats across the retina. Each foveal S cone diverges to four S-cone ON bipolar cells but contacts them unequally, providing 1-16 ribbon synapses per cell. Next, each bipolar cell diverges to two BY ganglion cells and also contacts them unequally, providing approximately 14 and approximately 28 ribbon synapses per cell. Overall, each S cone diverges to approximately six BY ganglion cells, dominating one and contributing more modestly to the others. Conversely, of each pair of BY ganglion cells, one is dominated by a single S cone and one is diffusely driven by several. This repeating circuit extracts blue/yellow information on two different spatiotemporal scales and thus parallels the circuits for achromatic, spatial vision, in which each cone dominates one narrow-field ganglion cell (midget) and contributes some input to several wider-field ganglion cells (parasol). Finally, because BY ganglion cells have coextensive +S and -(L+M) receptive fields, and each S cone contributes different weights to different BY ganglion cells, the coextensive receptive fields must be already present in the synaptic terminal of the S cone. The S-cone terminal thus constitutes the first critical locus for BY color vision.


Assuntos
Percepção de Cores/fisiologia , Fóvea Central/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/fisiologia , Animais , Contagem de Células , Fóvea Central/citologia , Macaca fascicularis , Masculino , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Células Fotorreceptoras Retinianas Cones/citologia , Células Ganglionares da Retina/citologia , Sinapses/fisiologia
18.
J Neurosci ; 23(30): 9881-7, 2003 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-14586017

RESUMO

Psychophysical results suggest that the primate visual system is equally sensitive to both the onset and offset of short-wavelength light and that these responses are carried by separate pathways. However, physiological studies of cells in the retina and lateral geniculate nucleus find far fewer OFF-center than ON-center cells whose receptive-field centers are driven by short-wavelength-sensitive (S) cones. To determine whether S cones contact ON and OFF midget bipolar cells as well as (ON) "blue-cone bipolar" cells (Mariani, 1984), we examined 118 contiguous cone terminals and their bipolar cells in electron micrographs of serial sections from macaque foveal retina. Five widely spaced cone terminals do not contact ON midget bipolar cells. These five cone terminals contact the dendrites of "blue-cone bipolar" cells instead, showing that they are the terminals of S cones. These S-cone terminals are smaller and contain more synaptic ribbons than other terminals. Like neighboring cones, each S cone contacts its own OFF midget bipolar cell via triad-associated (flat) synaptic contacts. Moreover, each S-cone OFF midget bipolar cell has a synaptic terminal in the outer half of the inner plexiform layer, where it contacts an OFF midget ganglion cell.


Assuntos
Macaca fascicularis/fisiologia , Retina/citologia , Células Fotorreceptoras Retinianas Cones/citologia , Vias Visuais/citologia , Animais , Masculino , Terminações Pré-Sinápticas/ultraestrutura , Retina/fisiologia , Retina/ultraestrutura , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Fotorreceptoras Retinianas Cones/ultraestrutura , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/fisiologia , Vias Visuais/fisiologia
19.
Vis Neurosci ; 20(2): 189-209, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12916740

RESUMO

We examine the assumptions that the fovea contains equal numbers of inner (invaginating or ON) and outer (flat or OFF) midget bipolar cells and equal numbers of inner and outer diffuse bipolar cells. Based on reconstruction from electron photomicrographs of serial thin sections through the fovea of a macaque monkey, we reject both assumptions. First, every foveal L and M cone is presynaptic to one inner and one outer midget bipolar cell; however, S cones are presynaptic to one outer but no inner midget bipolar cell. Second, we measure the density of all foveal cells in the same patch of fovea, affording accurate cell density ratios. For each foveal cone pedicle, at a density of 26,500 mm(-2), there is close to one (0.88) outer diffuse bipolar cell but only 0.40 inner diffuse bipolar cells. This asymmetry may be related to differences in resolution and sensitivity for light increments and decrements. We also find one (1.01) Müller cell, one (1.01) amacrine cell in the inner nuclear layer, and close to one (0.83) horizontal cell for each cone pedicle. In addition, for each S cone, there are two inner S-cone bipolar cells and two small bistratified ganglion cells. In total, there are 3.4 cone bipolar cells per cone but only 2.6 ganglion cells per cone. The latter ratio is enough to accommodate one midget ganglion cell for each midget bipolar cell.


Assuntos
Fóvea Central/citologia , Macaca/anatomia & histologia , Animais , Contagem de Células , Processamento de Imagem Assistida por Computador , Microscopia Eletrônica , Células Fotorreceptoras Retinianas Cones/citologia , Células Ganglionares da Retina/citologia
20.
Am J Ophthalmol ; 136(2): 231-8, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12888043

RESUMO

PURPOSE: To conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON). DESIGN: Observational population cohort study. METHODS: A prospective investigation of an entire Brazilian LHON family. SETTING: A field investigation by an international team conducted in a remote part of Brazil. STUDY POPULATION: We evaluated 265 (both eyes) of the 328 living family members of this LHON pedigree. Only members of this pedigree were studied. Those entering the pedigree as spouses were used as controls. OBSERVATION PROCEDURES: We conducted epidemiologic interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmologic examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for mitochondrial genetic analysis. RESULTS: We reconstructed a seven-generation maternal lineage descended from a common ancestor dating to the 1870s. All maternally related family members were invariably homoplasmic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are still living. With each subsequent generation, there was a progressive decrease of penetrance, and only males were affected in the last two generations. A significant exposure (greater than 95% confidence intervals) to a variety of environmental risk factors characterized the affected individuals, with smoking as the most common (P <.01). Both affected and carriers (95% confidence intervals) presented with a significantly lower incidence of hypertension and high cholesterol compared with the control group (P <.05). CONCLUSIONS: Almost 95% of a 328-living-member pedigree with LHON 11778/J haplogroup was comprehensively studied. Our initial results indicate the strong influence of environmental risk factors. The remarkably reduced incidence of cardiovascular risk in the maternal lineage is discussed. Further genetic analysis may reveal a role for the nuclear genome.


Assuntos
Haplótipos , Atrofia Óptica Hereditária de Leber/epidemiologia , Atrofia Óptica Hereditária de Leber/genética , Adolescente , Brasil/epidemiologia , Estudos de Coortes , Percepção de Cores , Sensibilidades de Contraste , Análise Mutacional de DNA , DNA Mitocondrial/genética , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Fatores de Risco , Acuidade Visual , Campos Visuais
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