Activating KIR2DS4 Is Expressed by Uterine NK Cells and Contributes to Successful Pregnancy

Tissue-specific NK cells are abundant in the pregnant uterus and interact with invading placental trophoblast cells that transform the maternal arteries to increase the fetoplacental blood supply. Genetic case-control studies have implicated killer cell Ig-like receptor (KIR) genes and their $\textit{HLA}$ ligands in pregnancy disorders characterized by failure of trophoblast arterial transformation. Activating $\textit{KIR2DS1}$ or $\textit{KIR2DS5}$ (when located in the centromeric region as in Africans) lower the risk of disorders when there is a fetal $\textit{HLA-C}$ allele carrying a C2 epitope. In this study, we investigated another activating $\textit{KIR, KIR2DS4}$, and provide genetic evidence for a similar effect when carried with $\textit{KIR2DS1. KIR2DS4}$ is expressed by ∼45% of uterine NK (uNK) cells. Similarly to KIR2DS1, triggering of KIR2DS4 on uNK cells led to secretion of GM-CSF and other chemokines, known to promote placental trophoblast invasion. Additionally, XCL1 and CCL1, identified in a screen of 120 different cytokines, were consistently secreted upon activation of KIR2DS4 on uNK cells. Inhibitory $\textit{KIR2DL5A}$, carried in linkage disequilibrium with $\textit{KIR2DS1}$, is expressed by peripheral blood NK cells but not by uNK cells, highlighting the unique phenotype of uNK cells compared with peripheral blood NK cells. That KIR2DS4, KIR2DS1, and some alleles of KIR2DS5 contribute to successful pregnancy suggests that activation of uNK cells by KIR binding to HLA-C is a generic mechanism promoting trophoblast invasion into the decidua.This work was supported by the Wellcome Trust, the Centre for Trophoblast Research, the British Heart Foundation, and the Cambridge Philosophical Society

New Rare Earth Element Abundance Distributions for the Sun and Five r-Process-Rich Very Metal-Poor Stars

We have derived new abundances of the rare-earth elements Pr, Dy, Tm, Yb, and Lu for the solar photosphere and for five very metal-poor, neutron-capture r-process-rich giant stars. The photospheric values for all five elements are in good agreement with meteoritic abundances. For the low metallicity sample, these abundances have been combined with new Ce abundances from a companion paper, and reconsideration of a few other elements in individual stars, to produce internally-consistent Ba, rare-earth, and Hf (56<= Z <= 72) element distributions. These have been used in a critical comparison between stellar and solar r-process abundance mixes.Comment: 48 pages, 11 figures, 12 tables: To appear in the Astrophysical Journal Supplemen

Age-specific symptom prevalence in women 35–64 years old: A population-based study

<p>Abstract</p> <p>Background</p> <p>Symptom prevalence is generally believed to increase with age. The aim of this study was to evaluate the age specific prevalence of 30 general symptoms among Swedish middle-aged women.</p> <p>Methods</p> <p>A cross-sectional postal questionnaire study in seven Swedish counties in a random sample of 4,200 women 35–64 years old, with 2,991 responders. Thirty general symptoms included in the Complaint Score subscale of the Gothenburg Quality of Life Instrument were used.</p> <p>Results</p> <p>Four groups of age specific prevalence patterns were identified after adjustment for the influence of educational level, perceived health and mood, body mass index, smoking habits, use of hormone replacement therapy, and use of other symptom relieving therapy. Only five symptoms (insomnia, leg pain, joint pain, eye problems and impaired hearing) increased significantly with age. Eleven symptoms (general fatigue, headache, irritability, melancholy, backache, exhaustion, feels cold, cries easily, abdominal pain, dizziness, and nausea) decreased significantly with age. Two symptoms (sweating and impaired concentration) had a biphasic course with a significant increase followed by a significant decrease. The remaining twelve symptoms (difficulty in relaxing, restlessness, overweight, coughing, breathlessness, diarrhoea, chest pain, constipation, nervousness, poor appetite, weight loss, and difficulty in urinating) had stable prevalence with age.</p> <p>Conclusion</p> <p>Symptoms did not necessarily increase with age instead symptoms related to stress-tension-depression decreased.</p

Delay to celiac disease diagnosis and its implications for health-related quality of life

<p>Abstract</p> <p>Background</p> <p>To determine how the delay in diagnosing celiac disease (CD) has developed during recent decades and how this affects the burden of disease in terms of health-related quality of life (HRQoL), and also to consider differences with respect to sex and age.</p> <p>Methods</p> <p>In collaboration with the Swedish Society for Coeliacs, a questionnaire was sent to 1,560 randomly selected members, divided in equal-sized age- and sex strata, and 1,031 (66%) responded. HRQoL was measured with the EQ-5D descriptive system and was then translated to quality-adjusted life year (QALY) scores. A general population survey was used as comparison.</p> <p>Results</p> <p>The mean delay to diagnosis from the first symptoms was 9.7 years, and from the first doctor visit it was 5.8 years. The delay has been reduced over time for some age groups, but is still quite long. The mean QALY score during the year prior to initiated treatment was 0.66; it improved after diagnosis and treatment to 0.86, and was then better than that of a general population (0.79).</p> <p>Conclusions</p> <p>The delay from first symptoms to CD diagnosis is unacceptably long for many persons. Untreated CD results in poor HRQoL, which improves to the level of the general population if diagnosed and treated. By shortening the diagnostic delay it is possible to reduce this unnecessary burden of disease. Increased awareness of CD as a common health problem is needed, and active case finding should be intensified. Mass screening for CD might be an option in the future.</p

To servitize is to (re)position : utilizing a Porterian view to understand servitization and value systems

Drawing on the case of a global servitizing company in the ship power industry, we use a Porterian toolkit for analyzing the implications of industry power and its consequences on firm vertical (re)positioning within the value system. Whereas repositioning has been seen as a way of moving closer to customers and obtaining new competencies, strategic moves aimed at increasing companies’ sphere of influence were neglected. This chapter illustrates how the power approach to repositioning, through different alternative mechanisms, complements the widespread capability view and contributes to value system analysis in servitization.fi=vertaisarvioitu|en=peerReviewed

Inclusive V0V^0 Production Cross Sections from 920 GeV Fixed Target Proton-Nucleus Collisions

Inclusive differential cross sections $d\sigma_{pA}/dx_F$ and $d\sigma_{pA}/dp_t^2$ for the production of \kzeros, \lambdazero, and \antilambda particles are measured at HERA in proton-induced reactions on C, Al, Ti, and W targets. The incident beam energy is 920 GeV, corresponding to $\sqrt {s} = 41.6$ GeV in the proton-nucleon system. The ratios of differential cross sections \rklpa and \rllpa are measured to be $6.2\pm 0.5$ and $0.66\pm 0.07$, respectively, for \xf $\approx-0.06$. No significant dependence upon the target material is observed. Within errors, the slopes of the transverse momentum distributions $d\sigma_{pA}/dp_t^2$ also show no significant dependence upon the target material. The dependence of the extrapolated total cross sections $\sigma_{pA}$ on the atomic mass $A$ of the target material is discussed, and the deduced cross sections per nucleon $\sigma_{pN}$ are compared with results obtained at other energies.Comment: 17 pages, 7 figures, 5 table

Towards a healthy diet: from nutrition recommendations to dietary advice

The scientific knowledge regarding dietary fat, carbohydrate and protein, and food for the youngest and oldest people, was presented by key scientists in the field at a symposium arranged in Uppsala on 14 December 2006. The quality of fat and carbohydrates, rather than the total amount, was emphasized. It was more difficult, however, to reach conclusions about the preferred type of dietary protein. Recent dietary recommendations, main activities and key messages to the public in the Nordic countries, and a 5 year programme to decrease salt intake in Sweden were also presented. Some practical aspects on how to implement the recommendations in the population were highlighted. In many aspects the Nordic countries join together in similar simplified advice to the population. The symposium is summarized in this report

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Control of the Intracellular Redox State by Glucose Participates in the Insulin Secretion Mechanism

Background: Production of reactive oxygen species (ROS) due to chronic exposure to glucose has been associated with impaired beta cell function and diabetes. However, physiologically, beta cells are well equipped to deal with episodic glucose loads, to which they respond with a fine tuned glucose-stimulated insulin secretion (GSIS). In the present study, a systematic investigation in rat pancreatic islets about the changes in the redox environment induced by acute exposure to glucose was carried out. Methodology/Principal Findings: Short term incubations were performed in isolated rat pancreatic islets. Glucose dose- and time-dependently reduced the intracellular ROS content in pancreatic islets as assayed by fluorescence in a confocal microscope. This decrease was due to activation of pentose-phosphate pathway (PPP). Inhibition of PPP blunted the redox control as well as GSIS in a dose-dependent manner. The addition of low doses of ROS scavengers at high glucose concentration acutely improved beta cell function. The ROS scavenger N-acetyl-L-cysteine increased the intracellular calcium response to glucose that was associated with a small decrease in ROS content. Additionally, the presence of the hydrogen peroxide-specific scavenger catalase, in its membrane-permeable form, nearly doubled glucose metabolism. Interestingly, though an increase in GSIS was also observed, this did not match the effect on glucose metabolism. Conclusions: The control of ROS content via PPP activation by glucose importantly contributes to the mechanisms that couple the glucose stimulus to insulin secretion. Moreover, we identified intracellular hydrogen peroxide as an inhibitor of glucose metabolism intrinsic to rat pancreatic islets. These findings suggest that the intracellular adjustment of the redox environment by glucose plays an important role in the mechanism of GSIS.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)(CAPES) Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazi