Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

A longitudinal analysis of the risk factors for diabetes and coronary heart disease in the Framingham Offspring Study

BACKGROUND: The recent trends in sedentary life-styles and weight gain are likely to contribute to chronic conditions such as hypertension, diabetes, and cardiovascular diseases. The temporal sequence and pathways underlying these conditions can be modeled using the knowledge from the biomedical and social sciences. METHODS: The Framingham Offspring Study in the U.S. collected information on 5124 subjects at baseline, and 8, 12, 16, and 20 years after the baseline. Dynamic random effects models were estimated for the subjects' weight, LDL and HDL cholesterol, and blood pressure using 4 time observations. Logistic and probit models were estimated for the probability of diabetes and coronary heart disease (CHD) events. RESULTS: The subjects' age, physical activity, alcohol consumption, and cigarettes smoked were important predictors of the risk factors. Moreover, weight and height were found to differentially affect the probabilities of diabetes and CHD events; body weight was positively associated with the risk of diabetes while taller individuals had lower risk of CHD events. CONCLUSION: The results showed the importance of joint modeling of body weight, LDL and HDL cholesterol, and blood pressure that are risk factors for diabetes and CHD events. Lower body weight and LDL concentrations and higher HDL levels achieved via physical exercise are likely to reduce diabetes and CHD events

Diagnostic thinking and information used in clinical decision-making: a qualitative study of expert and student dental clinicians

<p>Abstract</p> <p>Background</p> <p>It is uncertain whether the range and frequency of Diagnostic Thinking Processes (DTP) and pieces of information (concepts) involved in dental restorative treatment planning are different between students and expert clinicians.</p> <p>Methods</p> <p>We video-recorded dental visits with one standardized patient. Clinicians were subsequently interviewed and their cognitive strategies explored using guide questions; interviews were also recorded. Both visit and interview were content-analyzed, following the Gale and Marsden model for clinical decision-making. Limited tests used to contrast data were t, χ², and Fisher's. Scott's π was used to determine inter-coder reliability.</p> <p>Results</p> <p>Fifteen dentists and 17 senior dental students participated in visits lasting 32.0 minutes (± 12.9) among experts, and 29.9 ± 7.1 among students; contact time with patient was 26.4 ± 13.9 minutes (experts), and 22.2 ± 7.5 (students). The time elapsed between the first and the last instances of the clinician looking in the mouth was similar between experts and students. Ninety eight types of pieces of information were used in combinations with 12 DTPs. The main differences found in DTP utilization had dentists conducting diagnostic interpretations of findings with sufficient certainty to be considered definitive twice as often as students. Students resorted more often to more general or clarifying enquiry in their search for information than dentists.</p> <p>Conclusions</p> <p>Differences in diagnostic strategies and concepts existed within clearly delimited types of cognitive processes; such processes were largely compatible with the analytic and (in particular) non-analytic approaches to clinical decision-making identified in the medical field. Because we were focused on a clinical presentation primarily made up of non-emergency treatment needs, use of other DTPs and concepts might occur when clinicians evaluate emergency treatment needs, complex rehabilitative cases, and/or medically compromised patients.</p

Social network and dominance hierarchy analyses at Chimpanzee Sanctuary Northwest

Different aspects of sociality bear considerable weight on the individual- and group-level welfare of captive nonhuman primates. Social Network Analysis (SNA) is a useful tool for gaining a holistic understanding of the dynamic social relationships of captive primate groups. Gaining a greater understanding of captive chimpanzees through investigations of centrality, preferred and avoided relationships, dominance hierarchy, and social network diagrams can be useful in advising current management practices in sanctuaries and other captive settings. In this study, we investigated the dyadic social relationships, group-level social networks, and dominance hierarchy of seven chimpanzees (Pan troglodytes) at Chimpanzee Sanctuary Northwest. We used focal-animal and instantaneous scan sampling to collect 106.75 total hours of associative, affiliative, and agonistic data from June to September 2016. We analyzed our data using SOCPROG to derive dominance hierarchies and network statistics, and we diagrammed the group\u27s social networks in NetDraw. Three individuals were most central in the grooming network, while two others had little connection. Through agonistic networks, we found that group members reciprocally exhibited agonism, and the group\u27s dominance hierarchy was statistically non-linear. One chimpanzee emerged as the most dominant through agonism but was least connected to other group members across affiliative networks. Our results indicate that the conventional methods used to calculate individuals\u27 dominance rank may be inadequate to wholly depict a group\u27s social relationships in captive sanctuary populations. Our results have an applied component that can aid sanctuary staff in a variety of ways to best ensure the improvement of group welfare

Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

BACKGROUND: Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence or dissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizing hormone (LH/hCG) receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. METHODS: We conducted a study on 13 non-metastasizing (NM) and 10 metastasizing/recurrent (MR) tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR) in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR) complemented by dot blot hybridization. RESULTS: Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10 MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed on those tumors with better clinical outcome. CONCLUSION: Our data suggest that the expression of GATA-6 in human adrenal cortex is not affected by tumorigenesis. GATA-4 expression is more abundant in MR tumors, while NM tumors express more intensely LHR. Further studies with larger cohorts are needed to test whether relative expression levels of LHR or GATA-4 might be used as prognosis predictors

Life-Long Radar Tracking of Bumblebees

This work was supported by European Research Council Advanced Grant no. 339347

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Measurement of the 2νββ decay half-life of 150Nd and a search for 0νββ decay processes with the full exposure from the NEMO-3 detector

We present results from a search for neutrinoless double-β (0νββ) decay using 36.6 g of the isotope 150Nd with data corresponding to a live time of 5.25 y recorded with the NEMO-3 detector. We construct a complete background model for this isotope, including a measurement of the two-neutrino double-β decay half-life of T2ν 1=2 ¼ ½9.34 0.22ðstatÞ þ0.62 −0.60 ðsystÞ × 1018 y for the ground state transition, which represents the most precise result to date for this isotope. We perform a multivariate analysis to search for 0νββ decays in order to improve the sensitivity and, in the case of observation, disentangle the possible underlying decay mechanisms. As no evidence for 0νββ decay is observed, we derive lower limits on half-lives for several mechanisms involving physics beyond the standard model. The observed lower limit, assuming light Majorana neutrino exchange mediates the decay, is T0ν 1=2 > 2.0 × 1022 y at the 90% C.L., corresponding to an upper limit on the effective neutrino mass of hmνi < 1.6–5.3 eV

Kryptoracemates

Racemic crystals normally crystallise in centrosymmetric spacegroups containing equal numbers of enantiomers. More rarely, racemates may crystallise in non-centrosymmetric space-groups having glide symmetry or, even more rarely, in space-groups devoid of a centre of inversion, having no rotary-inversion axes nor glide plane. The latter class of crystals form the subject of the present bibliographic review – a survey of kryptoracemic behaviour. The term kryptoracemic alludes to the presence of a hidden or non-crystallographic centre of inversion between two molecules that might otherwise be expected to crystallise in an achiral space-group, often about a centre of inversion. Herein, examples of molecules with stereogenic centres crystallising in one of the 65 Sohncke space-groups are described. Genuine kryptoracemates, i.e. crystals comprising only enantiomorphous pairs are described followed by an overview of non-genuine kryptoracemates whereby the crystal also contains other species such as solvent and/or counterions. A full range, i.e. one to six, stereogenic centres are noted in genuine kryptoracemates. Examples will also be described whereby there are more that one enantiomeric pair of molecules in the crystallographic asymmetric unit. A more diverse range of examples are available for non-genuine kryptoracemates. There are unbalanced species where in addition to the enantiomeric pair of molecules, there is another enantiomeric molecule present. There are examples of genuine co-crystals, solvated species and of salts. Finally, special examples will be highlighted where the counterions are chiral and where they are disparate, both circumstances promoting kryptoracemic behaviour

Measurement of the branching fraction for B−→D0K∗−B^- \to D^0 K^{*-}

We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}