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41.
Tyrosine phosphorylation of Munc18‐1 inhibits synaptic transmission by preventing SNARE assembly
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Marieke Meijer Bernhard Dörr Hanna CA Lammertse Chrysanthi Blithikioti Jan RT van Weering Ruud FG Toonen Thomas H Söllner Matthijs Verhage 《The EMBO journal》2018,37(2):300-320
Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18‐1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho‐proteomics abolished the stimulatory effect of Munc18‐1 on SNARE complex formation (“SNARE‐templating”) and membrane fusion in vitro. Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18‐1‐null neurons expressing Munc18‐1Y473D. Synaptic transmission was temporarily restored by high‐frequency stimulation, as well as by a Munc18‐1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming. On the other hand, expression of non‐phosphorylatable Munc18‐1 supported normal synaptic transmission. We propose that SFK‐dependent Munc18‐1 phosphorylation may constitute a potent, previously unknown mechanism to shut down synaptic transmission, via direct occlusion of a Synaptobrevin/VAMP2 binding groove and subsequent hindrance of conformational changes in domain 3a responsible for vesicle priming. This would strongly interfere with the essential post‐docking SNARE‐templating role of Munc18‐1, resulting in a largely abolished pool of releasable synaptic vesicles. 相似文献
42.
Hugh A. L. Henry Mehdi Abedi Concepción L. Alados Karen H. Beard Lauchlan H. Fraser Anke Jentsch Juergen Kreyling Andrew Kulmatiski Eric G. Lamb Wei Sun Mathew R. Vankoughnett Susanna Venn Christiane Werner Ilka Beil Irmgard Blindow Sven Dahlke Maren Dubbert Alexandra Effinger Heath W. Garris Maite Gartzia Tobias Gebauer Mohammed A. S. Arfin Khan Andrey V. Malyshev John Morgan Charles Nock Janelle P. Paulson Yolanda Pueyo Holly J. Stover Xuechen Yang 《Ecosystems》2018,21(7):1432-1444
Reduced precipitation treatments often are used in field experiments to explore the effects of drought on plant productivity and species composition. However, in seasonally snow-covered regions reduced precipitation also reduces snow cover, which can increase soil frost depth, decrease minimum soil temperatures and increase soil freeze–thaw cycles. Therefore, in addition to the effects of reduced precipitation on plants via drought, freezing damage to overwintering plant tissues at or below the soil surface could further affect plant productivity and relative species abundances during the growing season. We examined the effects of both reduced rainfall (via rain-out shelters) and reduced snow cover (via snow removal) at 13 sites globally (primarily grasslands) within the framework of the International Drought Experiment, a coordinated distributed experiment. Plant cover was estimated at the species level, and aboveground biomass was quantified at the functional group level. Among sites, we observed a negative correlation between the snow removal effect on minimum soil temperature and plant biomass production the next growing season. Three sites exhibited significant rain-out shelter effects on plant productivity, but there was no correlation among sites between the rain-out shelter effect on minimum soil moisture and plant biomass. There was no interaction between snow removal and rain-out shelters for plant biomass, although these two factors only exhibited significant effects simultaneously for a single site. Overall, our results reveal that reduced snowfall, when it decreases minimum soil temperatures, can be an important component of the total effect of reduced precipitation on plant productivity. 相似文献
43.
铁皮石斛的离体开花 总被引:9,自引:0,他引:9
铁皮石斛(Dendrobium candidum),为一种野生兰科植物,在栽培条件下,从种子萌发到开花通常需要3~4a.研究了多种植物激素和多胺对该种石斛组织培养中花芽形成的影响,结果表明在培养基中加入合适浓度的亚精胺(spermidine)或BA(6-苄基腺嘌呤),或同时加入NAA(萘乙酸)和BA均可诱导原球茎或由之形成的无根小苗在3~6个月开花,频率在31.6%~45.8%.当将原球茎在加有ABA(脱落酸)的培养基上预培养后再移到加有BA的培养基上,花芽形成的频率可提高到平均达82.8%(个别实验中可达100%),这种诱导提早开花的现象也与实验材料的发育阶段(原球茎、无根小苗、已生根的小苗)有关,通常发生在根的形成受到完全或部分抑制的情况中. 相似文献
44.
45.
Efficiencies of different genes and different tree-building methods in recovering a known vertebrate phylogeny 总被引:24,自引:6,他引:18
The relative efficiencies of different protein-coding genes of the
mitochondrial genome and different tree-building methods in recovering a
known vertebrate phylogeny (two whale species, cow, rat, mouse, opossum,
chicken, frog, and three bony fish species) was evaluated. The
tree-building methods examined were the neighbor joining (NJ), minimum
evolution (ME), maximum parsimony (MP), and maximum likelihood (ML), and
both nucleotide sequences and deduced amino acid sequences were analyzed.
Generally speaking, amino acid sequences were better than nucleotide
sequences in obtaining the true tree (topology) or trees close to the true
tree. However, when only first and second codon positions data were used,
nucleotide sequences produced reasonably good trees. Among the 13 genes
examined, Nd5 produced the true tree in all tree-building methods or
algorithms for both amino acid and nucleotide sequence data. Genes Cytb and
Nd4 also produced the correct tree in most tree-building algorithms when
amino acid sequence data were used. By contrast, Co2, Nd1, and Nd41 showed
a poor performance. In general, large genes produced better results, and
when the entire set of genes was used, all tree-building methods generated
the true tree. In each tree-building method, several distance measures or
algorithms were used, but all these distance measures or algorithms
produced essentially the same results. The ME method, in which many
different topologies are examined, was no better than the NJ method, which
generates a single final tree. Similarly, an ML method, in which many
topologies are examined, was no better than the ML star decomposition
algorithm that generates a single final tree. In ML the best substitution
model chosen by using the Akaike information criterion produced no better
results than simpler substitution models. These results question the
utility of the currently used optimization principles in phylogenetic
construction. Relatively simple methods such as the NJ and ML star
decomposition algorithms seem to produce as good results as those obtained
by more sophisticated methods. The efficiencies of the NJ, ME, MP, and ML
methods in obtaining the correct tree were nearly the same when amino acid
sequence data were used. The most important factor in constructing reliable
phylogenetic trees seems to be the number of amino acids or nucleotides
used.
相似文献
46.
采用红外气体分析仪,于2008年10月17-19日连续3个昼夜原位监测了荷木的树干CO_2释放通量、树干温度、木质部液流密度和CO_2浓度.结果表明:树干CO_2释放通量(EA)日变化呈S形曲线,不同径级间差异显著.EA与树干温度呈显著幂函数关系(0.24Abstract: By using a Li-820 infra-red CO_2 gas analyzer, an in situ measurement of Schima super-ba stem CO_2 efflux was conducted for three consecutive days from 17 to 19 October 2008. In the meantime, the stem temperature, xylem sap efflux density, and xylem CO_2 concentration were measured. The stem CO_2 efflux had a diurnal variation of "S" pattern, and differed significantly with stem diameter. There was a significant exponential relationship between stem CO_2 efflux and stem temperature (0. 24 < R~2 < 0. 78). The temperature coefficient (b) and regression coeffi-cient (R~2) were higher at nighttime than at daytime, and the Q_(10) value ranged from 2. 01 to 2. 79. The stem CO_2 efflux correlated significantly with the xylem CO_2 concentration, and the best regression curve was cubic (R~2= 0. 48). Excluding the effects of stem temperature, the stem CO_2 efflux showed a significant negative correlation with xylem sap flux density (r =-0.462). Therefore, only using simple temperature function to estimate stem CO_2 efflux would yield a significant error, and xylem sap flux should be taken into consideration in the stem CO_2 emux estimation. 相似文献
47.
Matthew K. Nock Irving Hwang Nancy Sampson Ronald C. Kessler Matthias Angermeyer Annette Beautrais Guilherme Borges Evelyn Bromet Ronny Bruffaerts Giovanni de Girolamo Ron de Graaf Silvia Florescu Oye Gureje Josep Maria Haro Chiyi Hu Yueqin Huang Elie G. Karam Norito Kawakami Viviane Kovess Daphna Levinson Jose Posada-Villa Rajesh Sagar Toma Tomov Maria Carmen Viana David R. Williams 《PLoS medicine》2009,6(8)
Background
Suicide is a leading cause of death worldwide. Mental disorders are among the strongest predictors of suicide; however, little is known about which disorders are uniquely predictive of suicidal behavior, the extent to which disorders predict suicide attempts beyond their association with suicidal thoughts, and whether these associations are similar across developed and developing countries. This study was designed to test each of these questions with a focus on nonfatal suicide attempts.Methods and Findings
Data on the lifetime presence and age-of-onset of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) mental disorders and nonfatal suicidal behaviors were collected via structured face-to-face interviews with 108,664 respondents from 21 countries participating in the WHO World Mental Health Surveys. The results show that each lifetime disorder examined significantly predicts the subsequent first onset of suicide attempt (odds ratios [ORs] = 2.9–8.9). After controlling for comorbidity, these associations decreased substantially (ORs = 1.5–5.6) but remained significant in most cases. Overall, mental disorders were equally predictive in developed and developing countries, with a key difference being that the strongest predictors of suicide attempts in developed countries were mood disorders, whereas in developing countries impulse-control, substance use, and post-traumatic stress disorders were most predictive. Disaggregation of the associations between mental disorders and nonfatal suicide attempts showed that these associations are largely due to disorders predicting the onset of suicidal thoughts rather than predicting progression from thoughts to attempts. In the few instances where mental disorders predicted the transition from suicidal thoughts to attempts, the significant disorders are characterized by anxiety and poor impulse-control. The limitations of this study include the use of retrospective self-reports of lifetime occurrence and age-of-onset of mental disorders and suicidal behaviors, as well as the narrow focus on mental disorders as predictors of nonfatal suicidal behaviors, each of which must be addressed in future studies.Conclusions
This study found that a wide range of mental disorders increased the odds of experiencing suicide ideation. However, after controlling for psychiatric comorbidity, only disorders characterized by anxiety and poor impulse-control predict which people with suicide ideation act on such thoughts. These findings provide a more fine-grained understanding of the associations between mental disorders and subsequent suicidal behavior than previously available and indicate that mental disorders predict suicidal behaviors similarly in both developed and developing countries. Future research is needed to delineate the mechanisms through which people come to think about suicide and subsequently progress from ideation to attempts. Please see later in the article for Editors'' Summary 相似文献48.
Neuza M Alcantara-Neves Samuel J Badaró Mariese CA dos Santos Lain Pontes-de-Carvalho Maurício L Barreto 《Respiratory research》2010,11(1):114
Background
The elucidation of factors that trigger the development of transient wheezing in early childhood may be an important step toward understanding the pathogenesis of asthma and other allergic diseases later in life. Transient wheezing has been mainly attributed to viral infections, although sensitisation to aeroallergens and food allergens may occur at an early age. In developing countries, intestinal helminthic infections have also been associated with allergy or atopy-related disorders.Objective
The aim of this study was to explore the association of Trichuris trichiura and Ascaris lumbricoides infections with wheezing and atopy in early childhood.Study design
A cross-sectional study using a Portuguese-language ISAAC phase I questionnaire, adapted for preschool-aged children, nested in a cohort study of childhood diarrhoea, was conducted on 682 children. Two faecal samples per child were examined for the presence of intestinal helminthic infection. IgE antibodies against three allergenic preparations (Dermatophagoides pteronyssinus, Blomia tropicalis and common child food), as well as against A. lumbricoides antigens, were measured in a sub-sample of these children, whose parents allowed the procedure. Atopy was defined by the presence of levels of serum IgE antibodies ≥0.35 kU/L against at least one of the three tested allergenic preparations.Results
Active T. trichiura infection but not A. lumbricoides infection was positively associated with wheezing in the total studied children population [adjusted OR = 2.60; CI = 1.54;4.38] and in the atopic children sub-population [adjusted OR = 3.07; CI = 1.00;9.43]. The association with atopy was also positive and statistically significant only in the brute analysis [OR = 2.13; CI = 1.03;4.40]. Anti-A. lumbricoides IgE antibodies, but not current A. lumbricoides infection, were positively associated with wheezing in atopic children [adjusted OR = 2.01; CI = 1.00;4.50] and in non-atopic children [adjusted OR = 3.07; CI = 1.13;8.35] and it was also associated with atopy [adjusted OR = 7.29; CI = 3.90; 13.4]. On the other hands, reports of wheezing were not significantly associated with atopy.Conclusions
These data corroborate previous studies showing that wheezing is predominantly associated with infection in early childhood and shows that anti-A. lumbricoides IgE antibodies, but not active Ascaris infections, are associated with wheezing and atopy. Additionally, the data demonstrate that T. trichiura infection may play a role in the pathogenesis of atopic wheezing in early childhood. 相似文献49.
50.
Ubydul Haque Ricardo J Soares Magalhães Heidi L Reid Archie CA Clements Syed Masud Ahmed Akramul Islam Taro Yamamoto Rashidul Haque Gregory E Glass 《Malaria journal》2010,9(1):120