NKR-P1A is a target-specific receptor that activates natural killer cell cytotoxicity.

NKR-P1A is a lectinlike surface molecule expressed on rat natural killer (NK) cells. NKR-P1A has structural and functional features of an activating NK cell receptor, but a requirement for NKR-P1A in target cell lysis has not been determined. To define the role of NKR-P1A in natural killing, we have generated a mutant of the rat NK cell line, RNK-16, lacking expression of all members of the NKR-P1 receptor family. Although these NKR-P1-deficient NK cells were able to kill many standard tumor targets, including YAC-1, they were selectively deficient in the lysis of IC-21 macrophage, B-16 melanoma, and C1498 lymphoma targets. Reexpression of a single member of the NKR-P1 family, NKR-P1A, on mutant cells restored lysis of IC-21, and killing of IC-21 targets through rat NKR-P1A was completely blocked by F(ab')2 anti-NKR-P1A. Reexpression of NKR-P1A also restored transmembrane signaling to IC-21, as assessed by the generation of inositol-1,4,5-trisphosphate. The generation of inositol-1,4,5-trisphosphate was also restored in response to B-16 targets, but both B-16 and C1498 cells remained resistant to lysis, indicating that other NK cell molecules, perhaps within the NKR-P1 family, are required for the efficient killing of these tumors. These results are the first to demonstrate that NKR-P1A is a target-specific receptor that activates natural killing

Molecular cloning of the cDNA encoding pp36, a tyrosine-phosphorylated adaptor protein selectively expressed by T cells and natural killer cells.

Activation of T and natural killer (NK) cells leads to the tyrosine phosphorylation of pp36 and to its association with several signaling molecules, including phospholipase Cgamma-1 and Grb2. Microsequencing of peptides derived from purified rat pp36 protein led to the cloning, in rat and man, of cDNA encoding a T- and NK cell-specific protein with several putative Src homology 2 domain-binding motifs. A rabbit antiserum directed against a peptide sequence from the cloned rat molecule recognized tyrosine phosphorylated pp36 from pervanadate-treated rat thymocytes. When expressed in 293T human fibroblast cells and tyrosine-phosphorylated, pp36 associated with phospholipase Cgamma-1 and Grb2. Studies with GST-Grb2 fusion proteins demonstrated that the association was specific for the Src homology 2 domain of Grb-2. Molecular cloning of the gene encoding pp36 should facilitate studies examining the role of this adaptor protein in proximal signaling events during T and NK cell activation

Dorsal and ventral stimuli in cell–material interactions: effect on cell morphology

Cells behave differently between bidimensional (2D) and tridimensional (3D) environments. While most of the in vitro cultures are 2D, most of the in vivo extracellular matrices are 3D, which encourages the development of more relevant culture conditions, seeking to provide more physiological models for biomedicine (e.g., cancer, drug discovery and tissue engineering) and further insights into any dimension-dependent biological mechanism. In this study, cells were cultured between two protein coated surfaces (sandwich-like culture). Cells used both dorsal and ventral receptors to adhere and spread, undergoing morphological changes with respect to the 2D control. Combinations of fibronectin and bovine serum albumin on the dorsal and ventral sides led to different cell morphologies, which were quantified from bright field images by calculating the spreading area and circularity. Although the mechanism underlying these differences remains to be clarified, excitation of dorsal receptors by anchorage to extracellular proteins plays a key role on cell behavior. This approach—sandwich-like culture—becomes therefore a versatile method to study cell adhesion in well-defined conditions in a quasi 3D environment

Short-scale turbulent fluctuations driven by the electron-temperature gradient in the national spherical torus experiment

Measurements with coherent scattering of electromagnetic waves in plasmas of the National Spherical Torus Experiment indicate the existence of turbulent fluctuations in the range of wave numbers k(perpendicular to)rho(e)=0.1-0.4, corresponding to a turbulence scale length nearly equal to the collisionless skin depth. Experimental observations and agreement with numerical results from a linear gyrokinetic stability code support the conjecture that the observed turbulence is driven by the electron-temperature gradient.X1155sciescopu

The Role of Deontic Logic in the Specification of Information Systems

In this paper we discuss the role that deontic logic plays in the specification of information systems, either because constraints on the systems directly concern norms or, and even more importantly, system constraints are considered ideal but violable (so-called `soft¿ constraints).\ud To overcome the traditional problems with deontic logic (the so-called paradoxes), we first state the importance of distinguishing between ought-to-be and ought-to-do constraints and next focus on the most severe paradox, the so-called Chisholm paradox, involving contrary-to-duty norms. We present a multi-modal extension of standard deontic logic (SDL) to represent the ought-to-be version of the Chisholm set properly. For the ought-to-do variant we employ a reduction to dynamic logic, and show how the Chisholm set can be treated adequately in this setting. Finally we discuss a way of integrating both ought-to-be and ought-to-do reasoning, enabling one to draw conclusions from ought-to-be constraints to ought-to-do ones, and show by an example the use(fulness) of this

Rate of Decline in Serum PFOA Concentrations after Granular Activated Carbon Filtration at Two Public Water Systems in Ohio and West Virginia

Drinking water in multiple water districts in the Mid-Ohio Valley has been contaminated with perfluorooctanoic acid (PFOA), which was released by a nearby DuPont chemical plant. Two highly contaminated water districts began granular activated carbon filtration in 2007.To determine the rate of decline in serum PFOA, and its corresponding half-life, during the first year after filtration.Up to six blood samples were collected from each of 200 participants from May 2007 until August 2008. The primary source of drinking water varied over time for some participants; our analyses were grouped according to water source at baseline in May-June 2007.For Lubeck Public Service District customers, the average decrease in serum PFOA concentrations between May-June 2007 and May-August 2008 was 32 ng/mL (26%) for those primarily consuming public water at home (n = 130), and 16 ng/mL (28%) for those primarily consuming bottled water at home (n = 17). For Little Hocking Water Association customers, the average decrease in serum PFOA concentrations between November-December 2007 and May-June 2008 was 39 ng/mL (11%) for consumers of public water (n = 39) and 28 ng/mL (20%) for consumers of bottled water (n = 11). The covariate-adjusted average rate of decrease in serum PFOA concentration after water filtration was 26% per year (95% confidence interval, 2528% per year).The observed data are consistent with first-order elimination and a median serum PFOA half-life of 2.3 years. Ongoing follow-up will lead to improved half-life estimation

Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes

Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy

Inner wellbeing: concept and validation of a new approach to subjective perceptions of wellbeing-India

© The Author(s) 2013. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This paper describes the conceptual development of a multi-domain, psychosocial model of 'Inner Wellbeing' (IWB) and assesses the construct validity of the scale designed to measure it. IWB expresses what people think and feel they are able to be and do. Drawing together scholarship in wellbeing and international development it is grounded in field research in marginalised, rural communities in the global South. Results from research in India at two points in time (2011 and 2013) are reported. At Time 1 (n = 287), we were unable to confirm an eight-factor, correlated model as distinct yet interrelated domains. However, at Time 2 (n = 335), we were able to confirm a revised, seven-factor correlated model with economic confidence, agency and participation, social connections, close relationships, physical and mental health, competence and self-worth, and values and meaning (five items per domain) as distinct yet interrelated domains. In particular, at Time 2, a seven-factor, correlated model provided a significantly better fit to the data than did a one-factor model.This work is supported by the Economic and Social Research Council/Department for International Development Joint Scheme for Research on International Development (Poverty Alleviation) grant number RES-167-25-0507 ES/H033769/1. Special thanks are due to Chaupal and Gangaram Paikra, Pritam Das, Usha Kujur, Kanti Minjh, Susanna Siddiqui, and Dinesh Tirkey

Patient information leaflets (PILs) for UK randomised controlled trials : a feasibility study exploring whether they contain information to support decision making about trial participation

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