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Evolution of the extracellular space in immature nervous tissue 总被引:3,自引:0,他引:3
56.
Voltage-gated potassium channels such as Shaker help to control electrical signalling in neurons by regulating the passage of K+ across cell membranes. Ion flow is controlled by a voltage-dependent gate at the intracellular side of the pore, formed by the crossing of four alpha-helices--the inner-pore helices. The prevailing model of gating is based on a comparison of the crystal structures of two bacterial channels--KcsA in a closed state and MthK in an open state--and proposes a hinge motion at a conserved glycine that splays the inner-pore helices wide open. We show here that two types of intersubunit metal bridge, involving cysteines placed near the bundle crossing, can occur simultaneously in the open state. These bridges provide constraints on the open Shaker channel structure, and on the degree of movement upon opening. We conclude that, unlike predictions from the structure of MthK, the inner-pore helices of Shaker probably maintain the KcsA-like bundle-crossing motif in the open state, with a bend in this region at the conserved proline motif (Pro-X-Pro) not found in the bacterial channels. A narrower opening of the bundle crossing in Shaker K+ channels may help to explain why Shaker has an approximately tenfold lower conductance than its bacterial relatives. 相似文献
57.
Delépine M Nicolino M Barrett T Golamaully M Lathrop GM Julier C 《Nature genetics》2000,25(4):406-409
Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis and growth retardation occur at a later age. Other frequent multisystemic manifestations include hepatic and renal dysfunction, mental retardation and cardiovascular abnormalities. On the basis of two consanguineous families, we mapped WRS to a region of less than 3 cM on chromosome 2p12, with maximal evidence of linkage and homozygosity at 4 microsatellite markers within an interval of approximately 1 cM. The gene encoding the eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) resides in this interval; thus we explored it as a candidate. We identified distinct mutations of EIF2AK3 that segregated with the disorder in each of the families. The first mutation produces a truncated protein in which the entire catalytic domain is missing. The other changes an amino acid, located in the catalytic domain of the protein, that is highly conserved among kinases from the same subfamily. Our results provide evidence for the role of EIF2AK3 in WRS. The identification of this gene may provide insight into the understanding of the more common forms of diabetes and other pathologic manifestations of WRS. 相似文献
58.
Gleyzes S Kuhr S Guerlin C Bernu J Deléglise S Busk Hoff U Brune M Raimond JM Haroche S 《Nature》2007,446(7133):297-300
A microscopic quantum system under continuous observation exhibits at random times sudden jumps between its states. The detection of this quantum feature requires a quantum non-demolition (QND) measurement repeated many times during the system's evolution. Whereas quantum jumps of trapped massive particles (electrons, ions or molecules) have been observed, this has proved more challenging for light quanta. Standard photodetectors absorb light and are thus unable to detect the same photon twice. It is therefore necessary to use a transparent counter that can 'see' photons without destroying them. Moreover, the light needs to be stored for durations much longer than the QND detection time. Here we report an experiment in which we fulfil these challenging conditions and observe quantum jumps in the photon number. Microwave photons are stored in a superconducting cavity for times up to half a second, and are repeatedly probed by a stream of non-absorbing atoms. An atom interferometer measures the atomic dipole phase shift induced by the non-resonant cavity field, so that the final atom state reveals directly the presence of a single photon in the cavity. Sequences of hundreds of atoms, highly correlated in the same state, are interrupted by sudden state switchings. These telegraphic signals record the birth, life and death of individual photons. Applying a similar QND procedure to mesoscopic fields with tens of photons should open new perspectives for the exploration of the quantum-to-classical boundary. 相似文献
59.
Silvia Peppicelli Elena Andreucci Jessica Ruzzolini Anna Laurenzana Francesca Margheri Gabriella Fibbi Mario Del Rosso Francesca Bianchini Lido Calorini 《Cellular and molecular life sciences : CMLS》2017,74(15):2761-2771
Although surgical excision, chemo-, and radio-therapy are clearly advanced, tumors may relapse due to cells of the so-called “minimal residual disease”. Indeed, small clusters of tumor cells persist in host tissues after treatment of the primary tumor elaborating strategies to survive and escape from immunological attacks before their relapse: this variable period of remission is known as “cancer dormancy”. Therefore, it is crucial to understand and consider the major concepts addressing dormancy, to identify new targets and disclose potential clinical strategies. Here, we have particularly focused the relationships between tumor microenvironment and cancer dormancy, looking at a re-appreciated aspect of this compartment that is the low extracellular pH. Accumulating evidences indicate that acidity of tumor microenvironment is associated with a poor prognosis of tumor-bearing patients, stimulates a chemo- and radio-therapy resistant phenotype, and suppresses the tumoricidal activity of cytotoxic lymphocytes and natural killer cells, and all these aspects are useful for dormancy. Therefore, this review discusses the possibility that acidity of tumor microenvironment may provide a new, not previously suggested, adequate milieu for “dormancy” of tumor cells. 相似文献
60.
Aurelio Ramírez-Bautista América L. Ortíz-Cruz M. Del Coro Arizmendi Jorge Campos 《西北部美国博物学家》2011,65(2)
We studied the reproductive characteristics of 2 syntopic lizard species, Sceloporus gadoviae and Sceloporus jalapae (Phrynosomatidae). Specimens of S. gadoviae ( N = 105) and S. jalapae ( N = 41) were collected in a tropical arid forest from Tehuacán Valley, Puebla, México. Males of S. gadoviae reached sexual maturity at the same snoutvent length (SVL; 45.0 mm) as S. jalapae , and a similar pattern occurred in females of both species (SVL; 41.0 and 42.0 mm, respectively). Males of S. gadoviae exhibited reproductive activity throughout the year, with a longer activity during the dry (November to May) and part of the wet season (June to September). In contrast, reproductive activity in S. jalapae males occurred during the wet season (July to September). Females of S. gadoviae showed continuous reproduction, whereas females of S. jalapae exhibited seasonal reproduction. Mean SVL of sexually mature females was higher for S. gadoviae ( ̄ x ± s ̄x = 50.4 ± 0.52) than for S. jalapae (46.0 ± 0.54, P S. gadoviae was lower (3.9 ± 0.14 eggs) than for S. jalapae (5.6 ± 0.43). There was no significant correlation between snout-vent length of females and clutch size of S. gadoviae ( r 2 = 0.22, P > 0.05) or S. jalapae ( r 2 = 0.48, P > 0.05). Our study suggests that although both species inhabit the same environment, they have different reproductive characteristics. 相似文献