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61.
Identification of an axonal kinesin-3 motor for fast anterograde vesicle transport that facilitates retrograde transport of neuropeptides 总被引:2,自引:0,他引:2
Barkus RV Klyachko O Horiuchi D Dickson BJ Saxton WM 《Molecular biology of the cell》2008,19(1):274-283
A screen for genes required in Drosophila eye development identified an UNC-104/Kif1 related kinesin-3 microtubule motor. Analysis of mutants suggested that Drosophila Unc-104 has neuronal functions that are distinct from those of the classic anterograde axonal motor, kinesin-1. In particular, unc-104 mutations did not cause the distal paralysis and focal axonal swellings characteristic of kinesin-1 (Khc) mutations. However, like Khc mutations, unc-104 mutations caused motoneuron terminal atrophy. The distributions and transport behaviors of green fluorescent protein-tagged organelles in motor axons indicate that Unc-104 is a major contributor to the anterograde fast transport of neuropeptide-filled vesicles, that it also contributes to anterograde transport of synaptotagmin-bearing vesicles, and that it contributes little or nothing to anterograde transport of mitochondria, which are transported primarily by Khc. Remarkably, unc-104 mutations inhibited retrograde runs by neurosecretory vesicles but not by the other two organelles. This suggests that Unc-104, a member of an anterograde kinesin subfamily, contributes to an organelle-specific dynein-driven retrograde transport mechanism. 相似文献
62.
Rosemarie Swanson Ioannis Kagiampakis Jerry W Tsai 《Journal of computational biology》2008,15(1):65-79
We describe an information-theory-based measure of the quality of secondary structure prediction (RELINFO). RELINFO has a simple yet intuitive interpretation: it represents the factor by which secondary structure choice at a residue has been restricted by a prediction scheme. As an alternative interpretation of secondary structure prediction, RELINFO complements currently used methods by providing an information-based view as to why a prediction succeeds and fails. To demonstrate this score's capabilities, we applied RELINFO to an analysis of a large set of secondary structure predictions obtained from the first five rounds of the Critical Assessment of Structure Prediction (CASP) experiment. RELINFO is compared with two other common measures: percent correct (Q3) and secondary structure overlap (SOV). While the correlation between Q3 and RELINFO is approximately 0.85, RELINFO avoids certain disadvantages of Q3, including overestimating the quality of a prediction. The correlation between SOV and RELINFO is approximately 0.75. The valuable SOV measure unfortunately suffers from a saturation problem, and perhaps has unfairly given the general impression that secondary structure prediction has reached its limit since SOV hasn't improved much over the recent rounds of CASP. Although not a replacement for SOV, RELINFO has greater dispersion. Over the five rounds of CASP assessed here, RELINFO shows that predictions targets have been more difficult in successive CASP experiments, yet the predictions quality has continued to improve measurably over each round. In terms of information, the secondary structure prediction quality has almost doubled from CASP1 to CASP5. Therefore, as a different perspective of accuracy, RELINFO can help to improve prediction of protein secondary structure by providing a measure of difficulty as well as final quality of a prediction. 相似文献
63.
De Rose R Fernandez CS Smith MZ Batten CJ Alcântara S Peut V Rollman E Loh L Mason RD Wilson K Law MG Handley AJ Kent SJ 《PLoS pathogens》2008,4(5):e1000055
Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIV(mac251) replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably approximately 10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans. 相似文献
64.
The Neusiedler See – Seewinkel National Park area is confronted with a remarkable increase in tourism and recreational activities during the last years. The “Koppel” area, situated on the eastern shore of the lake, is one of the most important breeding sites for Greylag Geese. Behaviour and distribution of the geese on the breeding site as well as touristic activities on the adjacent road leading along the Koppel were examined to investigate relations and interactions between the Greylag Goose population and tourism. Taking into account the excellent weather and breeding conditions in the year 2000 the results of the survey indicate a stable or even rising Greylag population, increasing numbers of visitors and high disturbance frequencies in the vicinity of the study area. The number of disturbances on the adjacent road seems to affect the suitability of the site in general, leading to a specific temporal and spatial distribution of the birds, whereas different disturbance qualities result in changes of the birds behaviour. 相似文献
65.
Doris Riether Renée Zindell Jennifer A. Kowalski Brian N. Cook Jörg Bentzien Stéphane De Lombaert David Thomson Stanley Z. Kugler Donna Skow Leslie S. Martin Ernest L. Raymond Hnin Hnin Khine Kathy O’Shea Joseph R. Woska Deborah Jeanfavre Rosemarie Sellati Kerry L.M. Ralph Jennifer Ahlberg Gabriel Labissiere Mohammed A. Kashem Hidenori Takahashi 《Bioorganic & medicinal chemistry letters》2009,19(6):1588-1591
Benzamide 1 demonstrated good potency as a selective ITK inhibitor, however the amide moiety was found to be hydrolytically labile in vivo, resulting in low oral exposure and the generation of mutagenic aromatic amine metabolites. Replacing the benzamide with a benzylamine linker not only addressed the toxicity issue, but also improved the cellular and functional potency as well as the drug-like properties. SAR studies around the benzylamines and the identification of 10n and 10o as excellent tools for proof-of-concept studies are described. 相似文献
66.
Elwin G. Smith Rosemarie A. De Clerck-Floate Brian H. Van Hezewijk James R. Moyer Eva Pavlik 《Biological Control》2009,48(3):281-286
The cost of rearing the root-feeding weevil, Mogulones cruciger Herbst, to control the invasive weed houndstongue (Cynoglossum officinale L.) was determined for two managed production methods. Production in an insectary setting provides control over rearing and all adult weevils that emerge can be collected, but required facility investment and high labor input. Mass-rearing in a managed ‘field crop’ setting required less facilities and labor while the insects were multiplying, but capture of the emerged adults was challenging and labor intensive. Estimated per adult weevil production costs were $CDN 2.65 for the insectary approach, and from $CDN 0.10 to $CDN 0.14 for mass-rearing in the managed field crop setting. Even though collection of adult weevils in the field crop production system was challenging, commercial production of M. cruciger should consider use of this mass-rearing method because of its lower cost. 相似文献
67.
A methodological issue in research relating daytime mood to dream content is the question of whether mood congruency effects—that is, recalling more negative events if the current mood is more negative—also play a role in the dream recall process. This study adopted an indirect approach by testing the hypothesis that interindividual differences in mood congruency effects in a memory task carried out in the daytime correlate with mood congruency effects in dream recall (recalling more negative dream emotions, as one would predict on the basis of the current stress level or overall mood state). The findings, however, did not support the hypothesis of mood congruency effects and, thus, rule out that the findings regarding the continuity hypothesis of dreaming are biased by selective recall. Studies with different methodological approaches are necessary to validate this study’s findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
68.
69.
Salama-Cohen P Arévalo MA Grantyn R Rodríguez-Tébar A 《Journal of neurochemistry》2006,97(5):1269-1278
We have previously shown that dendrite morphology of cultured hippocampal neurones is controlled by Notch receptor activation or binding of nerve growth factor (NGF) to its low affinity receptor p75NTR, i.e. processes that up-regulate the expression of the Homologue of enhancer of split 1 and 5. Thus, the increased expression of these genes decreases the number of dendrites, whereas abrogation of Homologue of enhancer of split 1/5 activity stimulates the outgrowth of new dendrites. Here, we show that Neurogenin 3 is a proneural gene that is negatively regulated by Homologue of enhancer of split 1/5. It also influences dendrite morphology. Hence, a deficit of Notch or NGF/p75NTR activation can lead to the production of high levels of Neurogenin 3, which stimulates the outgrowth of new dendrites. Conversely, activation of either Notch or p75NTR depressed Neurogenin 3 expression, which not only decreased the number of dendrites but also favoured inhibitory (GABAergic) synaptogenesis, thereby diminishing the ratios of excitatory/inhibitory inputs. NGF also augmented the levels of mRNA encoding the vesicular inhibitory amino acid transporter, but it did not affect the fraction of GAD65/67-positive neurones. Conversely, overexpression of Neurogenin 3 largely reduced the number of inhibitory synaptic contacts and, consequently, produced a strong increase in the ratios of excitatory/inhibitory synaptic terminals. Our results reveal a hitherto unknown contribution of NGF/p75NTR to dendritic and synaptic plasticity through Neurogenin 3 signalling. 相似文献
70.
Boyden ED Campos-Xavier AB Kalamajski S Cameron TL Suarez P Tanackovic G Tanackovich G Andria G Ballhausen D Briggs MD Hartley C Cohn DH Davidson HR Hall C Ikegawa S Jouk PS König R Megarbané A Nishimura G Lachman RS Mortier G Rimoin DL Rogers RC Rossi M Sawada H Scott R Unger S Valadares ER Bateman JF Warman ML Superti-Furga A Bonafé L 《American journal of human genetics》2011,(6):767-772
Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto-SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that, in spite of being relatively common among skeletal dysplasias, has eluded molecular elucidation so far. We used whole-exome sequencing of five unrelated individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this skeletal condition. Missense mutations affecting one of two adjacent amino acids in the motor domain of KIF22 were present in 20 familial cases from eight families and in 12 other sporadic cases. The skeletal and connective tissue phenotype produced by these specific mutations point to functions of KIF22 beyond those previously ascribed functions involving chromosome segregation. Although we have found Kif22 to be strongly upregulated at the growth plate, the precise pathogenetic mechanisms remain to be elucidated. 相似文献