СHANGES OF IMMUNOREGULATORY INDEXES IN CHILDREN EXPOSED TO STRONTIUM

Evaluation of the immune system parameters can be used in order to assess capacity to adapt under conditions of increased external chemical load, including exposure to metals, which can exert either activating and inhibitory effects upon immune regulation parameters. The aim of this work was the analysis of immunoregulatory markers in a children’s population who consumed water with high strontium content (a sample from the Perm region). We carried out immunological evaluation of the children aged 7 to 12 years, living at a territory with a high strontium content in the drinking water. The comparison group included children from the conventionally clean region. We studied differential changes in cellular immunity (phagocytosis rates), humoral factors of immune defense (serum immunoglobulins), development of specific sensitization for strontium, as well as the processes of apoptosis triggering and regulation. A 3.68-fold increase in strontium levels was shown in fresh water within observation area, and the average  blood strontium content in the children of appropriate observation group was 1.55-fold higher than in children of the comparison group. At the same time, 1.2-fold increase in phagocytic activity determined as phagocytic number and phagocytic index was found, as compared to the control group. In 80% of the subjects, a reduction in serum IgG level was observed when compared to physiological norm, as well as a significant decrease in IgG and enhance in IgM production against the levels found in the comparison group. Wehave also shown an enhanced total sensitization in 55.0% of the observation group as shown by the total IgE test compared with normal age ranges, as well as excessive specific sensitization to strontium by 2.49 times, according to the IgG criterion. Disturbance in apoptosis triggering was associated with decreased number of CD95+ lymphocytes and TNFR1+ cells (2.8-fold compared to reference values), shifted balance in apoptogenic proteins, an average of 2.6-fold decrease in Bcl-2 expression, a 2.8-fold reduction of the p53 transcription factor expression relative to the reference interval. Thus, we have shown an ability of strontium excess in drinking water to influence the most important indices of immune regulation in pediatric population. These changes may serve as indices of populational health status under of external strontium exposure

EXPERIMENTAL MODELING OF APOPTOSIS UNDER CONDITIONS OF STABLE STRONTIUM EXPOSURE

Apoptosis is defined as a highly regulated form of programmed cell death with typical morphological and biochemical features. A variety of factors, including heavy metals, may influence the intensity of programmed cell death. The aim of the work was to simulate apoptosis in an in vitrosystem under the conditions of stable strontium exposure. The children’s population consuming drinking water with high strontium (Sr2+) content (n = 49) was observed. The level of lymphocyte apoptosis was determined with flow cytometry technique, by means of labeled annexin V-FITC conjugate (AnnV-FITC) and propidium iodide (PI) staining. AnnV-FITC+PI- cells were regarded as early apoptotic forms, whereas late apoptotic and/or necrotic cells were AnnV-FITC+PI+. The isolated leukocytes were incubated with Sr2+ at a concentration of 7.0 mg/l, the maximal permitted concentration (MPC) for water of aqueous objects, for 4 hours at 37 ºC. Expression of CD95 and p53 apoptosis markers was performed by flow cytometry using labeled monoclonal antibodies.In vitroexposure to strontium was associated with significantly decreased expression of apoptosisregulating factors, i.e., membrane marker CD95 and intracellular transcription protein p53, 1.56- and 1.68-fold, respectively. Meanwhile, we revealed a significantly (4.68-fold) decreased amounts of AnnV-FITC+PI--cells, as well as a statistically significant (1.35-fold) increase of the AnnV-FITC+PI+-cells. Moreover, the amounts of AnnV-FITC+ PI--lymphocytes in all samples were below the physiological ranges and control values. The number of samples with higher contents of AnnV-FITC+PI+-lymphocyte exceeding the established standards and control values, was 30.8%. Thus, it has been experimentally proven that strontium, at a concentration corresponding to MPC for water objects may significantly inhibit cell death along apoptotic pathways, with switching to necrotic cell death mechanisms, according to phosphatidylserine contents, as detected by annexin V binding test. The data have revealed an ability of strontium to have a significant effect upon the parameters of regulation and maintenance of cellular homeostasis, by influencing the apoptosis intensity, due to shifting a balance towards necrosis and reducing expression of apoptosis-regulating factors. The results of this study may be used in order to identify some marker indexes of immune disorders potentially induced by external influence of strontium upon human health under specific environmental factors

Directional Sensitivity of the NEWSdm Experiment to Cosmic Ray Boosted Dark Matter

We present a study of a directional search for Dark Matter boosted forward when scattered by cosmic-ray nuclei, using a module of the NEWSdm experiment. The boosted Dark Matter flux at the edge of the Earth's atmosphere is expected to be pointing to the Galactic Center, with a flux 15 to 20 times larger than in the transverse direction. The module of the NEWSdm experiment consists of a 10 kg stack of Nano Imaging Trackers, i.e.~newly developed nuclear emulsions with AgBr crystal sizes down to a few tens of nanometers. The module is installed on an equatorial telescope. The relatively long recoil tracks induced by boosted Dark Matter, combined with the nanometric granularity of the emulsion, result in an extremely low background. This makes an installation at the INFN Gran Sasso laboratory, both on the surface and underground, viable. A comparison between the two locations is made. The angular distribution of nuclear recoils induced by boosted Dark Matter in the emulsion films at the surface laboratory is expected to show an excess with a factor of 3.5 in the direction of the Galactic Center. This excess allows for a Dark Matter search with directional sensitivity. The surface laboratory configuration prevents the deterioration of the signal in the rock overburden and it emerges as the most powerful approach for a directional observation of boosted Dark Matter with high sensitivity. We show that, with this approach, a 10 kg module of the NEWSdm experiment exposed for one year at the Gran Sasso surface laboratory can probe Dark Matter masses between 1 keV/c$^2$ and 1 GeV/c$^2$ and cross-section values down to $10^{-30}$~cm$^2$ with a directional sensitive search.Comment: 15 pages, 14 figures, updated references, clarified discussion in intro section. Submitted to JCA

SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b

BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection

Treatment aims and philosophy in the treatment of adolescent anorexia nervosa in Europe

This study describes the range of service provision and explores differences in treatment approaches and therapeutic aims, in the 12 countries participating in the European Union collaborative COST B6 Adolescent Project into the treatment of adolescent anorexia nervosa (AN). Following a number of group meetings, two questionnaires were administered, completed and returned by e-mail. The first questionnaire examined features of the services provided, including details of the numbers of patients seen, inpatient admission criteria and aspects of patient management. The second questionnaire contained a list Of 13 therapeutic aims, asking respondents to rank in order the six they considered most important in the first weeks of treatment. There was broad agreement between services concerning the need to offer a full spectrum of services in a range of settings. Nevertheless, there were significant differences in approaches, chiefly concerning the readiness to admit to hospital, the use of (individual or family) day units and the focus on weight restoration as opposed to therapeutic engagement. Copyright (C) 2002 John Wiley & Sons, Ltd and Eating Disorders Association

Treatment aims and philosophy in the treatment of adolescent anorexia nervosa in Europe

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThis study describes the range of service provision and explores differences in treatment approaches and therapeutic aims, in the 12 countries participating in the European Union collaborative COST B6 Adolescent Project into the treatment of adolescent anorexia nervosa (AN). Following a number of group meetings, two questionnaires were administered, completed and returned by e-mail. The first questionnaire examined features of the services provided, including details of the numbers of patients seen, inpatient admission criteria and aspects of patient management. The second questionnaire contained a list of 13 therapeutic aims, asking respondents to rank in order the six they considered most important in the first weeks of treatment. There was broad agreement between services concerning the need to offer a full spectrum of services in a range of settings. Nevertheless, there were significant differences in approaches, chiefly concerning the readiness to admit to hospital, the use of (individual or family) day units and the focus on weight restoration as opposed to therapeutic engagement