Cleavage of endogenous gamma ENaC and elevated abundance of alpha ENaC are associated with increased Na+ transport in response to apical fluid volume expansion in human H441 airway epithelial cells

Using human H441 airway epithelial cells cultured at air–liquid interface (ALI), we have uniquely correlated the functional response to apical fluid volume expansion with the abundance and cleavage of endogenous α- and γENaC proteins in the apical membrane. Monolayers cultured at ALI rapidly elevated I(sc) when inserted into fluid-filled Ussing chambers. The increase in I(sc) was not significantly augmented by the apical addition of trypsin, and elevation was abolished by the protease inhibitor aprotinin and an inhibitor of the proprotein convertase, furin. These treatments also increased the IC(50) amiloride indicating that the effect was via inhibition of highly Na(+)-selective ENaC channels. Apical fluid, 5–500 μl for 1 h in culture, increased the spontaneous starting I(sc) in a dose-dependent manner, whilst maximal fluid-induced I(sc) in the Ussing chamber was unchanged. Apical fluid expansion increased the abundance of 63–65-kDa αENaC proteins in the apical membrane. However, this could not be attributed to increased cleavage as protease inhibitors had no effect on the ratio of cleaved to non-cleaved (90 kDa) αENaC proteins. Instead, fluid expansion increased αENaC abundance in the membrane. In contrast, function correlated well with γENaC cleavage at known sites by furin and extracellular proteases. Interestingly, cleavage of γENaC was associated with increased retrieval from the membrane via the proteosomal pathway. Thus, the response to apical fluid volume expansion in H441 airway epithelial cells involves cleavage of γENaC, and changes in α- and γENaC protein abundance at the apical membrane. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00424-011-0982-x) contains supplementary material, which is available to authorized users

Mobile consumer behaviour on apps usage: The effects of perceived values, rating, and cost

The rapid development of technology and the use of smartphones and mobile applications (apps) have become significant and influential in today’s living. Despite the growing amount of research on mobile app usage, little is known on the role they play in shaping the behaviour of the mobile consumer. By deploying the framework, this study revises Sheth’s fundamental propositions of consumption values. While the fit of values has been recognised by many behavioural studies, insight into the theoretical interface in the mobile communication studies remains unsubstantiated. Therefore, this study explores the perceived consumption values on mobile apps behaviour and investigates the role of the rating of the apps and cost in influencing the behaviour. A total of 392 questionnaires were collected through an online survey with 9 hypotheses examined. The analysis of the structural equation modelling determined a final model with four significant factors (functional, social, emotional, and conditional values). It confirmed that the usage is influenced by the apps rating and cost towards a certain degree. This study indicates the potential significance variables in mobile consumer literature and sheds light on mobile communication marketing in the area of apps marketing, specifically in designing an effective user-experience (UX) apps for mobile consumers

Pengaruh Pengetahuan Pajak, Sosialisasi Pajak, dan Insentif Pajak Terhadap Kepatuhan Wajib Pajak Penggiat UMKM di Kecamatan Periuk.

Penulisan skripsi ini dijalankan guna menilai besarnya dampak dari pemberian pengetahuan pajak, sosialisasi pajak, dan insentif pajak terhadap kepatuhan wajib pajak pelaku umkm di kecamatan periuk populasi dari penelitian ini ialah UMKM di Kecamatan Periuk. Sampel kajian ini mempergunakan metode Insidental Sampling, data dalam kajian ini dikumpulkan dengan cara menyebarkan kuesioner, serts mempunyai 150 responden. Metode analisa kajian yang dipergunakan ialah regresi linear berganda serta mempergunakan SPSS 24. Berdasarkan dari hasil analisa memperlihatkan bahwa sosialisasi pajak berdampak positif dan signifikan terhadap kepatuhan wajib pajak. Sedangkan pengetahuan pajak tidak berdampak signifikan terhadap kepatuhan wajib pajak pelaku UMKM

Neuroinflammation and Neuronal Loss Precede Aβ Plaque Deposition in the hAPP-J20 Mouse Model of Alzheimer's Disease

Recent human trials of treatments for Alzheimer's disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-βAβ? plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust stereological methods, we found there is no neuron loss in the hippocampal CA3 region at any age. However loss of neurons from the hippocampal CA1 region begins as early as 12 weeks of age. The extent of neuron loss increases with age, correlating with the number of activated microglia. Gliosis was also present, but plateaued during aging. Increased hyperactivity and spatial memory deficits occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric Aβ were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD mouse model is engineered to over-expresses Aβ. Our data raises the possibility that plaque load may not be the best marker for early AD and suggests that activated microglia could be a valuable marker to track disease progression. © 2013 Wright et al

Effects of fibre content and textile structure on dynamic-mechanical and shape-memory properties of ELO/flax biocomposites

Biocomposites were prepared using epoxidized linseed oil (ELO) and flax fibre reinforcements in different assemblies. ELO was cured by two different anhydrides to check how its thermomechanical properties can be influenced. As reinforcements nonwoven mat, twill weave and quasi-unidirectional textile fabrics with two different yarn finenesses were used. Their reinforcing effect was determined in dynamic mechanical analysis (DMA) in flexure. DMA served also to determine the glass transition temperature (Tg). Shape memory properties were derived from quasiunconstrained flexural tests performed near to the Tg of the ELO and its biocomposites. Flax reinforcement reduced the Tg that was attributed to off-stoichiometry owing to chemical reaction between the hydroxyl groups of flax and anhydride hardener. The shape memory parameters were moderate or low. They were affected by both textile content and type

Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8+ T Cell Response against Toxoplasma gondii

CD8+ T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8+ T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related γ-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8+ T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8+ T cell response. This impairment is characterized by reduction in CD44 expression, IFN-γ production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8+ T cells. Interestingly, the absence of both cytokines did not impair initial CD8+ T cell generation but affected their survival and differentiation into memory phenotype IL-7Rαhi cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8+ T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15−/− mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8+ T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8+ T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported

Gastrointestinal tissue‐based molecular biomarkers: A practical categorization based on the 2019 WHO Classification of Epithelial Digestive Tumours

Molecular biomarkers have come to constitute one of the cornerstones of oncological pathology. The method of classification not only directly affects the manner in which patients are diagnosed and treated, but also guides the development of drugs and of artificial intelligence tools. The aim of this article is to organise and update gastrointestinal molecular biomarkers in order to produce an easy-to-use guide for routine diagnostics. For this purpose, we have extracted and reorganised the molecular information on epithelial neoplasms included in the 2019 World Health Organization classification of tumours. Digestive system tumours, 5th edn

Learning and innovative elements of strategy adoption rules expand cooperative network topologies

Cooperation plays a key role in the evolution of complex systems. However, the level of cooperation extensively varies with the topology of agent networks in the widely used models of repeated games. Here we show that cooperation remains rather stable by applying the reinforcement learning strategy adoption rule, Q-learning on a variety of random, regular, small-word, scale-free and modular network models in repeated, multi-agent Prisoners Dilemma and Hawk-Dove games. Furthermore, we found that using the above model systems other long-term learning strategy adoption rules also promote cooperation, while introducing a low level of noise (as a model of innovation) to the strategy adoption rules makes the level of cooperation less dependent on the actual network topology. Our results demonstrate that long-term learning and random elements in the strategy adoption rules, when acting together, extend the range of network topologies enabling the development of cooperation at a wider range of costs and temptations. These results suggest that a balanced duo of learning and innovation may help to preserve cooperation during the re-organization of real-world networks, and may play a prominent role in the evolution of self-organizing, complex systems.Comment: 14 pages, 3 Figures + a Supplementary Material with 25 pages, 3 Tables, 12 Figures and 116 reference