Tau is implicated in more than 20 neurodegenerative diseases, including Alzheimer's disease. Under pathological conditions, Tau dissociates from axonal microtubules and missorts to pre- and postsynaptic terminals. Patients suffer from early synaptic dysfunction prior to Tau aggregate formation, but the underlying mechanism is unclear. Here we show that pathogenic Tau binds to synaptic vesicles via its N-terminal domain and interferes with presynaptic functions, including synaptic vesicle mobility and release rate, lowering neurotransmission in fly and rat neurons. Pathological Tau mutants lacking the vesicle binding domain still localize to the presynaptic compartment but do not impair synaptic function in fly neurons. Moreover, an exogenously applied membrane-permeable peptide that competes for Tau-vesicle binding suppresses Tau-induced synaptic toxicity in rat neurons. Our work uncovers a presynaptic role of Tau that may be part of the early pathology in various Tauopathies and could be exploited therapeutically.
Purpose – The purpose of this paper is to build a comprehensive model and examine the relationship among green brand positioning (GBP), green brand knowledge (GBK), attitude toward green brand (AGB), and green purchase intention (GPI). Design/methodology/approach – A questionnaire survey was deployed to collect data from the members of Taiwan's Lifestyles of Health and Sustainability (LOHAS) Club, obtaining 425 valid samples which were analyzed with structural equation modeling. Findings – GBP and GBK influence green brand attitudes separately. GBK affects green brand attitudes. Meanwhile, green brand attitudes influence GPIs. Another finding indicates that the mediating effects exist. Research limitations/implications – By applying the environmental knowledge-attitude-intention paradigm to green brand research, it was empirically supported the existence of a GBK-attitude-intention hierarchy in the context of GPIs. Practical implications – GBP can be used as brand marketing strategy to improve consumers’ GBK and form positive green brand attitudes as well as enhance GPIs. Originality/value – Proposing two novel concepts, i.e. GBK and green brand attitude to develop and test the framework of this study.
Dissecting the pathogenesis of classical Hodgkin lymphoma (cHL), a common cancer in young adults, remains challenging because of the rarity of tumor cells in involved tissues (usually <5%). Here, we analyzed the coding genome of cHL by microdissecting tumor and normal cells from 34 patient biopsies for a total of ∼50 000 singly isolated lymphoma cells. We uncovered several recurrently mutated genes, namely, (32% of cases), (24%), (18%), and (16%), and document the functional role of mutant STAT6 in sustaining tumor cell viability. Mutations of genetically and functionally cooperated with disruption of, a JAK-STAT pathway inhibitor, to promote cHL growth. Overall, 87% of cases showed dysregulation of the JAK-STAT pathway by genetic alterations in multiple genes (also including ,, ,, and ), attesting to the pivotal role of this pathway in cHL pathogenesis and highlighting its potential as a new therapeutic target in this disease.
Synaptic dysfunction is an early pathological feature of neurodegenerative diseases associated with Tau, including Alzheimer's disease. Interfering with early synaptic dysfunction may be therapeutically beneficial to prevent cognitive decline and disease progression, but the mechanisms underlying synaptic defects associated with Tau are unclear. In disease conditions, Tau mislocalizes into pre- and postsynaptic compartments; here we show that, under pathological conditions, Tau binds to presynaptic vesicles in Alzheimer's disease patient brain. We define that the binding of Tau to synaptic vesicles is mediated by the transmembrane vesicle protein Synaptogyrin-3. In fly and mouse models of Tauopathy, reduction of Synaptogyrin-3 prevents the association of presynaptic Tau with vesicles, alleviates Tau-induced defects in vesicle mobility, and restores neurotransmitter release. This work therefore identifies Synaptogyrin-3 as the binding partner of Tau on synaptic vesicles, revealing a new presynapse-specific Tau interactor, which may contribute to early synaptic dysfunction in neurodegenerative diseases associated with Tau.
Anthracnose caused by Colletotrichum is one of the most severe diseases that can afflict Camellia sinensis. However, research on the diversity and geographical distribution of Colletotrichum in China remain limited. In this study, 106 Colletotrichum isolates were collected from diseased leaves of Ca. sinensis cultivated in the 15 main tea production provinces in China. Multi-locus phylogenetic analysis coupled with morphological identification showed that the collected isolates belonged to 11 species, including 6 known species (C. camelliae, C. cliviae, C. fioriniae, C. fructicola, C. karstii, and C. siamense), 3 new record species (C. aenigma, C. endophytica, and C. truncatum), 1 novel species (C. wuxiense), and 1 indistinguishable strain, herein described as Colletotrichum sp. Of these species, C. camelliae and C. fructicola were the dominant species causing anthracnose in Ca. sinensis. In addition, our study provided further evidence that phylogenetic analysis using a combination of ApMat and GS sequences can be used to effectively resolve the taxonomic relationships within the C. gloeosporioides species complex. Finally, pathogenicity tests suggested that C. camelliae, C. aenigma, and C. endophytica are more invasive than other species after the inoculation of the leaves of Ca. sinensis.
Sugar plays an essential role in plant cold acclimation (CA), but the interaction between CA and sugar remains unclear in tea plants. In this study, during the whole winter season, we investigated the variations of sugar contents and the expression of a large number of sugar-related genes in tea leaves. Results indicated that cold tolerance of tea plant was improved with the development of CA during early winter season. At this stage, starch was dramatically degraded, whereas the content of total sugars and several specific sugars including sucrose, glucose and fructose were constantly elevated. Beyond the CA stage, the content of starch was maintained at a low level during winter hardiness (WH) period and then was elevated during de-acclimation (DC) period. Conversely, the content of sugar reached a peak at WH stage followed by a decrease during DC stage. Moreover, gene expression results showed that, during CA period, sugar metabolism-related genes exhibited different expression pattern, in which beta-amylase gene (CsBAM), invertase gene (CsINV5) and raffinose synthase gene (CsRS2) engaged in starch, sucrose and raffinose metabolism respectively were solidly up-regulated; the expressions of sugar transporters were stimulated in general except the down-regulations of CsSWEET2, 3, 16, CsERD6.7 and CsINT2; interestingly, the sugar-signaling related CsHXK3 and CsHXK2 had opposite expression patterns at the early stage of CA. These provided comprehensive insight into the effects of CA on carbohydrates indicating that sugar accumulation contributes to tea plant cold tolerance during winter season, and a simply model of sugar regulation in response to cold stimuli is proposed.
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