Mechanisms of the Regulation of the Intestinal Na+/H+Exchanger NHE3

A major of Na+ absorptive process in the proximal part of intestine and kidney is electroneutral exchange of Na+ and H+ by Na+/H+ exchanger type 3 (NHE3). During the past decade, significant advance has been achieved in the mechanisms of NHE3 regulation. A bulk of the current knowledge on Na+/H+ exchanger regulation is based on heterologous expression of mammalian Na+/H+ exchangers in Na+/H+ exchanger deficient fibroblasts, renal epithelial, and intestinal epithelial cells. Based on the reductionist's approach, an understanding of NHE3 regulation has been greatly advanced. More recently, confirmations of in vitro studies have been made using animals deficient in one or more proteins but in some cases unexpected findings have emerged. The purpose of this paper is to provide a brief overview of recent progress in the regulation and functions of NHE3 present in the luminal membrane of the intestinal tract

Testing the Task-Media Fit: The Effects of Task Equivocality on Social Presence of Mobile Video-Mediated Communication

Since social presence theory was introduced, many researchers have tried to apply it to various technology-mediated communication media, including E-Mail, videoconferencing, and instant messengers. Yet few researches have investigated the influence of mobile video-mediated communication (VMC) on the social presence despite prevalence in business practices. In this paper, a research model is developed to test the relationship between the mobile VMC (video telephony and video chatting) and the level of social presence. And the task equivocality, whether it’s an intellective task or a negotiation task, is also considered as moderating variables, based on the task-media fit proposition. Hence, mobile video chatting could be suggested as an alternative media of mobile video telephony for less equivocal informative tasks according to this study

Nedd4-2-dependent ubiquitination potentiates the inhibition of human NHE3 by cholera toxin and enteropathogenic Escherichia coli

BACKGROUND & AIMS: Diarrhea is one of the most common illnesses and is often caused by bacterial infection. Recently, we have shown that human Naþ/Hþ exchanger NHE3 (hNHE3), but not non-human NHE3s, interacts with the E3 ubiquitin ligase Nedd4-2. We hypothesize that this property of hNHE3 contributes to the increased severity of diarrhea in humans. METHODS: We used humanized mice expressing hNHE3 in the intestine (hNHE3int) to compare the contribution of hNHE3 and mouse NHE3 to diarrhea induced by cholera toxin (CTX) and enteropathogenic Escherichia coli (EPEC). We measured Naþ/ Hþ exchange activity and fluid absorption. The role of Nedd4-2 on hNHE3 activity and ubiquitination was determined by knockdown in Caco-2bbe cells. The effects of protein kinase A (PKA), the primary mediator of CTX-induced diarrhea, on Nedd4-2 and hNHE3 phosphorylation and their interaction were determined. RESULTS: The effects of CTX and EPEC were greater in hNHE3int mice than in control wild-type (WT) mice, resulting in greater inhibition of NHE3 activity and increased fluid accumulation in the intestine, the hallmark of diarrhea. Activation of PKA increased ubiquitination of hNHE3 and enhanced interaction of Nedd4-2 with hNHE3 via phosphorylation of Nedd4-2 at S342. S342A mutation mitigated the Nedd4-2–hNHE3 interaction and blocked PKA-induced inhibition of hNHE3. Unlike non-human NHE3s, inhibition of hNHE3 by PKA is independent of NHE3 phosphorylation, suggesting a distinct mechanism of hNHE3 regulation. CONCLUSIONS: The effects of CTX and EPEC on hNHE3 are amplified, and the unique properties of hNHE3 may contribute to diarrheal symptoms occurring in humans

Inter-comparison of Radio-Loudness Criteria for Type 1 AGNs in the XMM-COSMOS Survey

Limited studies have been performed on the radio-loud fraction in X-ray selected type 1 AGN samples. The consistency between various radio-loudness definitions also needs to be checked. We measure the radio-loudness of the 407 type 1 AGNs in the XMM-COSMOS quasar sample using nine criteria from the literature (six defined in the rest-frame and three defined in the observed frame): $R_L=\log(L_{5GHz}/L_B)$, $q_{24}=\log(L_{24\mu m}/L_{1.4GHz})$, $R_{uv}=\log(L_{5GHz}/L_{2500\AA})$, $R_{i}=\log(L_{1.4GHz}/L_i)$, $R_X=\log(\nu L_{\nu}(5GHz)/L_X)$, $P_{5GHz}=\log(P_{5GHz}(W/Hz/Sr))$, $R_{L,obs}=\log(f_{1.4GHz}/f_B)$ (observed frame), $R_{i,obs}=\log(f_{1.4GHz}/f_i)$ (observed frame), and $q_{24, obs}=\log(f_{24\mu m}/f_{1.4GHz})$ (observed frame). Using any single criterion defined in the rest-frame, we find a low radio-loud fraction of $\lesssim 5\%$ in the XMM-COSMOS type 1 AGN sample, except for $R_{uv}$. Requiring that any two criteria agree reduces the radio-loud fraction to $\lesssim 2\%$ for about 3/4 of the cases. The low radio-loud fraction cannot be simply explained by the contribution of the host galaxy luminosity and reddening. The $P_{5GHz}=\log(P_{5GHz}(W/Hz/Sr))$ gives the smallest radio-loud fraction. Two of the three radio-loud fractions from the criteria defined in the observed frame without k-correction ($R_{L,obs}$ and $R_{i,obs}$) are much larger than the radio-loud fractions from other criteria.Comment: 12 pages, 7 figures, MNRAS submitte

Differences in intracellular localisation of ANKH mutants that relate to mechanisms of calcium pyrophosphate deposition disease and craniometaphyseal dysplasia

ANKH mutations are associated with calcium pyrophosphate deposition disease and craniometaphyseal dysplasia. This study investigated the effects of these ANKH mutants on cellular localisation and associated biochemistry. We generated four ANKH overexpression-plasmids containing either calcium pyrophosphate deposition disease or craniometaphyseal dysplasia linked mutations: P5L, E490del and S375del, G389R. They were transfected into CH-8 articular chondrocytes and HEK293 cells. The ANKH mutants dynamic differential localisations were imaged and we investigated the interactions with the autophagy marker LC3. Extracellular inorganic pyrophosphate, mineralization, ENPP1 activity expression of ENPP1, TNAP and PIT-1 were measured. P5L delayed cell membrane localisation but once recruited into the membrane it increased extracellular inorganic pyrophosphate, mineralization, and ENPP1 activity. E490del remained mostly cytoplasmic, forming punctate co-localisations with LC3, increased mineralization, ENPP1 and ENPP1 activity with an initial but unsustained increase in TNAP and PIT-1. S375del trended to decrease extracellular inorganic pyrophosphate, increase mineralization. G389R delayed cell membrane localisation, trended to decrease extracellular inorganic pyrophosphate, increased mineralization and co-localised with LC3. Our results demonstrate a link between pathological localisation of ANKH mutants with different degrees in mineralization. Furthermore, mutant ANKH functions are related to synthesis of defective proteins, inorganic pyrophosphate transport, ENPP1 activity and expression of ENPP1, TNAP and PIT-1

A massive proto-cluster of galaxies at a redshift of z {\approx} 5.3

Massive clusters of galaxies have been found as early as 3.9 Billion years (z=1.62) after the Big Bang containing stars that formed at even earlier epochs. Cosmological simulations using the current cold dark matter paradigm predict these systems should descend from "proto-clusters" - early over-densities of massive galaxies that merge hierarchically to form a cluster. These proto-cluster regions themselves are built-up hierarchically and so are expected to contain extremely massive galaxies which can be observed as luminous quasars and starbursts. However, observational evidence for this scenario is sparse due to the fact that high-redshift proto-clusters are rare and difficult to observe. Here we report a proto-cluster region 1 billion years (z=5.3) after the Big Bang. This cluster of massive galaxies extends over >13 Mega-parsecs, contains a luminous quasar as well as a system rich in molecular gas. These massive galaxies place a lower limit of >4x10^11 solar masses of dark and luminous matter in this region consistent with that expected from cosmological simulations for the earliest galaxy clusters.Comment: Accepted to Nature, 16 Pages, 6 figure

A Step Towards Worldwide Biodiversity Assessment: The BIOSCAN-1M Insect Dataset

In an effort to catalog insect biodiversity, we propose a new large dataset of hand-labelled insect images, the BIOSCAN-Insect Dataset. Each record is taxonomically classified by an expert, and also has associated genetic information including raw nucleotide barcode sequences and assigned barcode index numbers, which are genetically-based proxies for species classification. This paper presents a curated million-image dataset, primarily to train computer-vision models capable of providing image-based taxonomic assessment, however, the dataset also presents compelling characteristics, the study of which would be of interest to the broader machine learning community. Driven by the biological nature inherent to the dataset, a characteristic long-tailed class-imbalance distribution is exhibited. Furthermore, taxonomic labelling is a hierarchical classification scheme, presenting a highly fine-grained classification problem at lower levels. Beyond spurring interest in biodiversity research within the machine learning community, progress on creating an image-based taxonomic classifier will also further the ultimate goal of all BIOSCAN research: to lay the foundation for a comprehensive survey of global biodiversity. This paper introduces the dataset and explores the classification task through the implementation and analysis of a baseline classifier