344 research outputs found

    Impact of information presentation modes on online shopping: An empirical evaluation of a broadband interactive shopping service

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    With the increasing cost-effectiveness of communication technologies, online shopping has emerged as one of the most important areas of electronic commerce. A major problem facing online shopping service providers is the heterogeneity of user profile. Unlike organizational systems that have a well-defined universe of users and system boundary, these shopping services are designed for public users with very different cognitive and demographic profiles. The major challenge lies in designing friendly and effective user interfaces for online shoppers. Previous studies on online shopping suggest that a good user interface with an appropriate mode of information presentation is the key to system acceptance. In this article, we report on an empirical study that looks at product information presentation modes in an actual broadband supermarket shopping environment. Four prototypes with different combinations of text and picture displays were developed and evaluated in an experimental setting. The findings suggest that there is a close relation between product familiarity and shopping effectiveness. When the system is used to purchase familiar product items, pictures are better than text in terms of both efficiency and effectiveness. However, when users are not familiar with the product items, the advantages of pictures over text diminish. Implications of the findings and future research areas are discussed.published_or_final_versio

    Pramipexole reduces phosphorylation of α-Synuclein at Serine-129

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    α-Synuclein is a central component of the pathogenesis of Parkinson's disease (PD). Phosphorylation at serine-129 represents an important post-translational modification and constitutes the major form of the protein in Lewy bodies. Several kinases have been implicated in the phosphorylation of α-synuclein. The targeting of kinase pathways as a potential to influence the pathogenesis of PD is an important focus of attention, given that mutations of specific kinases (LRRK2 and PINK1) are causes of familial PD. Pramipexole (PPX) is a dopamine agonist developed for the symptomatic relief of PD. Several in vitro and in vivo laboratory studies have demonstrated that PPX exerts neuroprotective properties in model systems of relevance to PD. The present study demonstrates that PPX inhibits the phosphorylation of α-synuclein and that this is independent of dopamine receptor activation. PPX blocks the increase in phosphorylated α-synuclein induced by inhibition of the ubiquitin proteasomal system. The phosphorylation of α-synuclein occurs in part at least through casein kinase 2, and PPX in turn reduces the phosphorylation of this enzyme, thereby inhibiting its activity. Thus, PPX decreases the phosphorylation of α-synuclein, and this mechanism may contribute to its protective properties in PD models

    The Cytomegalovirus protein pUL37×1 targets mitochondria to mediate neuroprotection

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    There is substantial evidence that mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson disease (PD). This contribution probably encompasses defects of oxidative phosphorylation, mitochondrial turnover (mitophagy), mitochondrial derived oxidative stress, and apoptotic signalling. Human cytomegalovirus immediate-early protein pUL37 × 1 induces Bax mitochondrial translocation and inactivation to prevent apoptosis. Over-expressing pUL37 × 1 in neuronal cells protects against staurosporin and 6-hydroxydopamine induced apoptosis and cell death. Protection is not enhanced by bax silencing in pUL37 × 1 over-expressing cells, suggesting a bax-dependent mechanism of action. pUL37 × 1 increases glycolysis and induces mitochondrial hyperpolarization, a bax independent anti-apoptotic action. pUL37 × 1 increases glycolysis through activation of phosphofructokinase by a calcium-dependent pathway. The dual anti-apoptotic mechanism of pUL37 × 1 may be considered a novel neuroprotective strategy in diseases where mitochondrial dysfunction and apoptotic pathways are involved

    Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models

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    Meclizine is a well-tolerated drug routinely used as an anti-histamine agent in the management of disequilibrium. Recently, meclizine has been assessed for its neuroprotective properties in ischemic stroke and Huntington disease models. We found that meclizine protected against 6-hydroxydopamine-induced apoptosis and cell death in both SH-SY5Y cells and rat primary cortical cultures. Meclizine increases the level of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which activates phosphofructokinase, a rate-determining enzyme of glycolysis. This protection is therefore mediated by meclizine's ability to enhance glycolysis and increase mitochondrial hyperpolarization. Meclizine represents an interesting candidate for further investigation to re-purpose for its potential to be neuroprotective in Parkinson disease

    PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy

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    Mitochondrial fission is essential for the degradation of damaged mitochondria. It is currently unknown how the dynamin-related protein 1 (DRP1)-associated fission machinery is selectively targeted to segregate damaged mitochondria. We show that PTEN-induced putative kinase (PINK1) serves as a pro-fission signal, independently of Parkin. Normally, the scaffold protein AKAP1 recruits protein kinase A (PKA) to the outer mitochondrial membrane to phospho-inhibit DRP1. We reveal that after damage, PINK1 triggers PKA displacement from A-kinase anchoring protein 1. By ejecting PKA, PINK1 ensures the requisite fission of damaged mitochondria for organelle degradation. We propose that PINK1 functions as a master mitophagy regulator by activating Parkin and DRP1 in response to damage. We confirm that PINK1 mutations causing Parkinson disease interfere with the orchestration of selective fission and mitophagy by PINK1

    Classifying rational densities using two one-dimensional cellular automata

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    Given a (finite but arbitrarily long) string of zeros and ones, we report a way to determine if the number of ones is less than, greater than, or equal to a prescribed number by applying two sets of cellular automation rules in succession. Thus, we solve the general one-dimensional density classification problem using two cellular automata.published_or_final_versio

    Whole-genome sequencing of three local rice varieties (Oryza sativa L.) in Vietnam

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    Recently, a new technology, Next-generation sequencing (NGS) has been launched and providing whole-genome sequences that helps identify molecular markers across the genome. DNA markers such as single nucleotides and insertion – deletion (InDel) polymorphisms were widely used for plant breeding particularly to distinguish important traits in rice. These PCR-based markers can be used for the precision detection of polymorphisms. Moreover, PCR-based approaches are simple and effective methods for dealing with the issue of fraudulent labeling and adulteration in the global rice industry. In this study, three local varieties of Oryza sativa L. in Vietnam were sequenced with up to ten times genome depth and at least four times coverage (~83%) using the Illumina HiSeq2000™ system, with an average of 6.5 GB clean data per sample, generated after filtering low-quality data. The data was approximately mapped up to 95% to the reference genome IRGSP 1.0. The results obtained from this study will contribute to a wide range of valuable information for further investigation into this germplasm

    Inpatient emergencies encountered by an infectious disease consultative service

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    The spectrum of infections disease (ID) emergencies in hospitalized patients was assessed in a prospective study of 3,626 inpatient ID consultations in a 1,350-bed teaching hospital. ID emergencies, defined by a need or anticipated need for advanced life support or by irreversible organ damage leading to permanent functional loss, were encountered in 175 patients. Infections of the central nervous system (26.3%), cardiovascular system (14.9%), alimentary system (13.1%), and lower respiratory tract (7.4%) and adverse reactions to antimicrobial agents (7.4%) were most common. In 18.9% of the cases, the referring clinicians were unaware of the emergency at the time of referral. Drug reactions (46.1%), severe alimentary and peritoneal infections (32.0%), upper respiratory tract infections (28.6%), and skin and soft-tissue infections (27.3%) were most frequently missed. The emergency ID conditions were not recognized because they had an atypical presentation (51.5%), were not commonly seen in the referring specialty (24.2%), were due to rare organisms (15.2%), or had unusual anatomical sites of involvement (9.1%). A close liaison between clinicians and the ID team is crucial for recognition of ID emergencies at their early stages so that appropriate investigations and management can be instituted expediently, before the occurrence of irreversible damage.published_or_final_versio

    Mitochondrial and lysosomal biogenesis are activated following PINK1/parkin-mediated mitophagy

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    Impairment of the autophagy-lysosome pathway (ALP) is implicated with the changes in α-synuclein and mitochondrial dysfunction observed in Parkinson's disease (PD). Damaged mitochondria accumulate PINK1, which then recruits parkin, resultingin ubiquitination of mitochondrial proteins. These can then be bound by the autophagic proteins p62/SQSTM1 and LC3, resulting in degradation of mitochondria by mitophagy. Mutations in PINK1 and parkin genes are a cause of familial PD. We found a significant increase in the expression of p62/SQSTM1 mRNA and protein following mitophagy induction in human neuroblastoma SH-SY5Y cells. p62 protein not only accumulated on mitochondria, but was also greatly increased in the cytosol. Increased p62/SQSMT1 expression was prevented in PINK1 knock down (KD) cells, suggesting increased p62 expression was a consequence of mitophagy induction. The transcription factors Nrf2 and TFEB, which play roles in mitochondrial and lysosomal biogenesis, respectively, can regulate p62/SQSMT1. We report that both Nrf2 and TFEB translocate to the nucleus following mitophagy induction and that the increase in p62 mRNA levels was significantly impaired in cells with Nrf2 or TFEB KD.. TFEB translocation also increased expression of itself and lysosomal proteins such as glucocerebrosidase and cathepsin D following mitophagy induction. We also report that cells with increased TFEB protein have significantly higher PGC-1α mRNA levels, a regulator of mitochondrial biogenesis, resulting in increased mitochondrial content. Our data suggests that TFEB is activated following mitophagy to maintain ALP and mitochondrial biogenesis. Therefore strategies to increase TFEB may improve both the clearance of α-synuclein and mitochondrial dysfunction in PD. This article is protected by copyright. All rights reserved

    Triterpenes and triterpene-glycoside from the leaves of Lawsonia inermis.

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    From the leaves of  Lawsonia inermis (syn. L. alba), two triterpenes augustic acid (1) and 1b,2a,3a,19a-tetrahydroxy-12-ursen-28-oic acid (2), and a triterpene-glycoside suavissimoside R1 (3) were isolated by using various chromatoghraphies. Their structures were characterized on the basis of the spectroscopic data (1D-NMR, HSQC, HMBC, ESI-MS) in comparison with the literature. This is the first report of 1 - 3 from Lawsonia species. Keywords: Lawsonia inermis, Lythraceae, Triterpene
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