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151.
Severe immunodeficiency has opposite effects on neuronal survival in glutamate-susceptible and -resistant mice: adverse effect of B cells 总被引:1,自引:0,他引:1
Schori H Lantner F Shachar I Schwartz M 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(6):2861-2865
The resistance of rats or mice to glutamate-induced toxicity depends on their ability to spontaneously manifest a T cell-dependent response to the insult. Survival of retinal ganglion cells (RGCs) exposed to glutamate in BALB/c SCID mice (a strain relatively resistant to glutamate toxicity) was significantly worse than in the wild type. In the susceptible C57BL/6J mouse strain, however, significantly more RGCs survived among SCID mutants than in the matched wild type. RGC survival in the SCID mutants of the two strains was similar. These results suggest 1) that immunodeficiency might be an advantage in strains incapable of spontaneously manifesting protective T cell-dependent immunity and 2) that B cells might be destructive in such cases. After exposure of RGCs to toxic glutamate concentrations in three variants of B cell-deficient C57BL/6J mice, namely muMT(-/-) (B cell knockout mice) and Ii(-/-) mice reconstituted with transgenically expressed low levels of Ii p31 isoforms (p31 mice) or Ii p41 isoforms (p41 mice), significantly more RGCs survived in these mice than in the wild type. The improved survival was diminished by replenishment of the B cell-deficient mice with B cells derived from the wild type. It thus seems that B cells have an adverse effect on neuronal recovery after injury, at least in a strain that is unable to spontaneously manifest a T cell-dependent protective mechanism. These findings have clear implications for the design of immune-based therapies for CNS injury. 相似文献
152.
Three independent parameters (eclipse and latent periods, and rate of ripening during the rise period) are essential and sufficient to describe bacteriophage development in its bacterial host. A general model to describe the classical "one-step growth" experiment [Rabinovitch et al. (1999a) J. Bacteriol.181, 1687-1683] allowed their calculations from experimental results obtained with T4 in Escherichia coli B/r under different growth conditions [Hadas et al. (1997) Microbiology143, 179-185]. It is found that all three parameters could be described by their dependence solely on the culture doubling time tau before infection. Their functional dependence on tau, derived by a best-fit analysis, was used to calculate burst size values. The latter agree well with the experimental results. The dependence of the derived parameters on growth conditions can be used to predict phage development under other experimental manipulations. 相似文献
153.
The anaphase promoting complex/cyclosome (APC/C), activated by fzy and fzr, degrades cell cycle proteins that carry RXXL or KEN destruction boxes (d-boxes). APC/C substrates regulate sequential events and must be degraded in the correct order during mitosis and G(1). We studied how d-boxes determine APC/C(fzy)/APC/C(fzr) specificity and degradation timing. Cyclin B1 has an RXXL box and is degraded by both APC/C(fzy) and APC/C(fzr); fzy has a KEN box and is degraded by APC/C(fzr) only. We characterized the degradation of substrates with swapped d-boxes. Cyclin B1 with KEN was degraded by APC/C(fzr) only. Fzy with RXXL could be degraded by APC/C(fzy) and APC/C(fzr). Interestingly, APC/C(fzy)- but not APC/C(fzr)-specific degradation is highly dependent on the location of RXXL. We studied degradation of tagged substrates in real time and observed that APC/C(fzr) is activated in early G(1). These observations demonstrate how d-box specificities of APC/C(fzy) and APC/C(fzr), and the successive activation of APC/C by fzy and fzr, establish the temporal degradation pattern. Our observations can explain further why some endogenous RXXL substrates are degraded by APC/C(fzy), while others are restricted to APC/C(fzr). 相似文献
154.
Tzolovsky G Millo H Pathirana S Wood T Bownes M 《Molecular biology and evolution》2002,19(7):1041-1052
Myosins constitute a superfamily of motor proteins that convert energy from ATP hydrolysis into mechanical movement along the actin filaments. Phylogenetic analysis currently places myosins into 17 classes based on class-specific features of their conserved motor domain. Traditionally, the myosins have been divided into two classes depending on whether they form monomers or dimers. The conventional myosin of muscle and nonmuscle cells forms class II myosins. They are complex molecules of four light chains bound to two heavy chains that form bipolar filaments via interactions between their coiled-coil tails (type II). Class I myosins are smaller monomeric myosins referred to as unconventional myosins. Now, at least 15 other classes of unconventional myosins are known. How many myosins are needed to ensure the proper development and function of eukaryotic organisms? Thus far, three types of myosins were found in budding yeast, six in the nematode Caenorhabditis elegans, and at least 12 in human. Here, we report on the identification and classification of Drosophila melanogaster myosins. Analysis of the Drosophila genome sequence identified 13 myosin genes. Phylogenetic analysis based on the sequence comparison of the myosin motor domains, as well as the presence of the class-specific domains, suggests that Drosophila myosins can be divided into nine major classes. Myosins belonging to previously described classes I, II, III, V, VI, and VII are present. Molecular and phylogenetic analysis indicates that the fruitfly genome contains at least five new myosins. Three of them fall into previously described myosin classes I, VII, and XV. Another myosin is a homolog of the mouse and human PDZ-containing myosins, forming the recently defined class XVIII myosins. PDZ domains are named after the postsynaptic density, disc-large, ZO-1 proteins in which they were first described. The fifth myosin shows a unique domain composition and a low homology to any of the existing classes. We propose that this is classified when similar myosins are identified in other species. 相似文献
155.
Ben-Zeev B Levy-Nissenbaum E Lahat H Anikster Y Shinar Y Brand N Gross-Tzur V MacGregor D Sidi R Kleta R Frydman M Pras E 《Human genetics》2002,111(2):214-218
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive inherited neurological disorder characterized by macrocephaly, deterioration in motor functions and cerebellar ataxia. In Israel the disease is found in an increased frequency among Libyan Jews. The disease is caused by mutations in the MLC1 gene, which encodes a putative CNS membrane transporter. We describe three novel mutations (p.G59E, p.P92S, and 134_136insC) in seven MLC families. One of these mutations, p.G59E, was found in the vast majority of MLC patients in Israel. Screening of 200 normal Libyan Jewish individuals for the p.G59E mutation, revealed a carrier rate of 1/40 compared with an expected carrier rate of 1/81. Several explanations could account for this difference the most likely one is an admixture of the Libyan Jewish population. 相似文献
156.
157.
Francis E Wang N Parag H Halaban R Hebert DN 《The Journal of biological chemistry》2003,278(28):25607-25617
Tyrosinase is a glycoprotein responsible for the synthesis of melanin in melanocytes. A large number of mutations have been identified in tyrosinase, with many leading to its misfolding, endoplasmic reticulum (ER) retention, and degradation. Here we describe the folding and maturation of human tyrosinase (TYR) using an in vitro translation system coupled with ER-derived microsomes or with semipermeabilized cells, as an intact ER source. TYR remained misfolded as determined by its sensitivity to trypsin digestion and its persistent interaction with the ER resident lectin chaperones calnexin and calreticulin when produced in ER-derived microsomes or nonmelanocytic semipermeabilized cells. However, when TYR was translocated into semipermeabilized melanocytes, chaperone interactions were transient, maturation progressed to a trypsin-resistant state, and a TYR homodimer was formed. The use of semipermeabilized mouse melanocytes defective for tyrosinase or other melanocyte-specific proteins as the ER source indicated that proper TYR maturation and oligomerization were greatly aided by the presence of wild type tyrosinase and tyrosinase-related protein 1. These findings suggested that oligomerization is a step in proper TYR maturation within the ER that requires melanocyte-specific factors. 相似文献
158.
Endocranial capacity of the bodo cranium determined from three-dimensional computed tomography 总被引:3,自引:0,他引:3
Conroy GC Weber GW Seidler H Recheis W Zur Nedden D Mariam JH 《American journal of physical anthropology》2000,113(1):111-118
The 600,000-year-old cranium from Bodo, Ethiopia, is the oldest and most complete early Middle Pleistocene hominid skull from Africa. "Virtual endocast" models created by three-dimensional computed tomography (CT) techniques indicate an endocranial capacity of about 1,250 cc for this cranium (with a reasonable range between approximately 1,200-1,325 cc, depending on how missing portions of the basicranial region are reconstructed). From these determinations, several important implications emerge concerning current interpretations of "tempo and mode" in early hominid brain evolution: 1) already by the early Middle Pleistocene, at least one African hominid species, Homo heidelbergensis, had reached an endocranial capacity within the normal range of modern humans; 2) in spite of its large endocranial capacity, estimates of Bodo's encephalization quotient fall below those found in a large sample of Homo sapiens (both fossil and recent) and Neandertals; and 3) the greatest burst of brain expansion in the Homo lineage may not have been in the last several hundred thousand years, but rather much earlier in the Lower to early Middle Pleistocene. 相似文献
159.
Formation of microtubule-based traps controls the sorting and concentration of vesicles to restricted sites of regenerating neurons after axotomy
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Erez H Malkinson G Prager-Khoutorsky M De Zeeuw CI Hoogenraad CC Spira ME 《The Journal of cell biology》2007,176(4):497-507
Transformation of a transected axonal tip into a growth cone (GC) is a critical step in the cascade leading to neuronal regeneration. Critical to the regrowth is the supply and concentration of vesicles at restricted sites along the cut axon. The mechanisms underlying these processes are largely unknown. Using online confocal imaging of transected, cultured Aplysia californica neurons, we report that axotomy leads to reorientation of the microtubule (MT) polarities and formation of two distinct MT-based vesicle traps at the cut axonal end. Approximately 100 microm proximal to the cut end, a selective trap for anterogradely transported vesicles is formed, which is the plus end trap. Distally, a minus end trap is formed that exclusively captures retrogradely transported vesicles. The concentration of anterogradely transported vesicles in the former trap optimizes the formation of a GC after axotomy. 相似文献
160.