Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming

Foxp3(+) regulatory T cells (Tregs) maintain immune homoeostasis through mechanisms that remain incompletely defined. Here by two-photon (2P) imaging, we examine the cellular dynamics of endogenous Tregs. Tregs are identified as two non-overlapping populations in the T-zone and follicular regions of the lymph node (LN). In the T-zone, Tregs migrate more rapidly than conventional T cells (Tconv), extend longer processes and interact with resident dendritic cells (DC) and Tconv. Tregs intercept immigrant DCs and interact with antigen-induced DC: Tconv clusters, while continuing to form contacts with activated Tconv. During antigen-specific responses, blocking CTLA4-B7 interactions reduces Treg-Tconv interaction times, increases the volume of DC: Tconv clusters and enhances subsequent Tconv proliferation in vivo. Our results demonstrate a role for altered cellular choreography of Tregs through CTLA4-based interactions to limit T-cell priming

Entropy, time irreversibility and Schroedinger equation in a primarily discrete space-time

In this paper we show that the existence of a primarily discrete space-time may be a fruitful assumption from which we may develop a new approach of statistical thermodynamics in pre-relativistic conditions. The discreetness of space-time structure is determined by a condition that mimics the Heisenberg uncertainty relations and the motion in this space-time model is chosen as simple as possible. From these two assumptions we define a path-entropy that measures the number of closed paths associated with a given energy of the system preparation. This entropy has a dynamical character and depends on the time interval on which we count the paths. We show that it exists an like-equilibrium condition for which the path-entropy corresponds exactly to the usual thermodynamic entropy and, more generally, the usual statistical thermodynamics is reobtained. This result derived without using the Gibbs ensemble method shows that the standard thermodynamics is consistent with a motion that is time-irreversible at a microscopic level. From this change of paradigm it becomes easy to derive a $H-theorem$. A comparison with the traditional Boltzmann approach is presented. We also show how our approach can be implemented in order to describe reversible processes. By considering a process defined simultaneously by initial and final conditions a well defined stochastic process is introduced and we are able to derive a Schroedinger equation, an example of time reversible equation.Comment: latex versio

Intake of caffeine and its association with physical and mental health status among university students

In Western populations, the caffeine intake of young adults has received significant attention in the research literature; our knowledge in other societies remained limited. The objective of this research is to quantify the amount of ingested caffeine and how this is related to measures of physical and mental health in a Bahraini population. A semi-quantitative food frequency questionnaire was used to estimate caffeine intake from coffee, tea, cocoa, soft drinks, energy drinks, chocolates, and over-the-counter medications. Associations between caffeine intake, demographic variables and 25 symptoms measured using the Hopkins Symptoms Checklist-25 were examined. A convenience sample of university students in Bahrain (n = 727) was surveyed. Caffeine, in any form, was consumed by 98% of students. Mean daily caffeine consumption was 268 mg/day, with males consuming more than females. Coffee was the main source of caffeine intake, followed by black tea and energy drinks. Participants consuming 400 mg/day or more showed a statistically and significantly twice as high risk for five symptoms, these were: headaches, spells of terror or panic, feeling trapped or caught, worrying too much about things, and having feelings of worthlessness. The prevalence of caffeine intake among university students in Bahrain is high. The overall mean intake of caffeine from all sources by university students was within levels considered to be acceptable by many dietary recommendations. High caffeine intake was associated with an anxiogenic effect in the surveyed students. View Full-Tex

Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicates that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression. In this study, peri-adolescent female alcohol preferring (P) rats were given binge-like access to water, sucrose (SUC), SUC-NIC, EtOH, or EtOH-NIC for four weeks. The present study determined the effects of these reinforcers on GLT-1, xCT, GLAST, and mGluR1 expression in the nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC). GLT-1 and xCT expression were decreased in the NAc following both SUC-NIC and EtOH-NIC. In addition, only xCT expression was downregulated in the HIP in both of these latter groups. Also, glutathione peroxidase (GPx) activity in the HIP was reduced following SUC, SUC-NIC, EtOH, and EtOH-NIC consumption. Similar to previous work, GLAST expression was not altered in any brain region by any of the reinforcers. However, mGluR1 expression was increased in the NAc in the SUC-NIC, EtOH, and EtOH-NIC groups. These results indicate that peri-adolescent binge-like drinking of EtOH or SUC with or without NIC may exert differential effects on astroglial glutamate transporters and receptors. Our data further parallel some of the previous findings observed in adult rats

The mucosal adjuvant cholera toxin B instructs non-mucosal dendritic cells to promote IgA production via retinoic acid and TGF-β

It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-beta or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-beta signaling inhibitor or neutralizing anti-TGF-beta was added, demonstrating the involvement of RA and TGF-beta in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant

Erratum to: An Entropy Functional for Riemann-Cartan Space-Times

We correct the entropy functional constructed in Int. J. Theor. Phys. 51:362 (2012). The 'on-shell' functional one obtains from this correct functional possesses a holographic structure without imposing any constraint on the spin-angular momentum tensor of matter, in contrast to the conclusion made in the above paper.Comment: 15 pages. These are the preprints of the original paper and its erratum published in Int. J. Theor. Phy

Spatial clustering of emergency department visits by asthmatic children in an urban area: south-western Detroit, Michigan

Objective This ecological study evaluates the correlation of asthma clusters with outdoor air pollution, race, and household income in South-western Detroit, Michigan. Design To attain this objective (1) a geographic information aystem (GIS) is utilized to evaluate the relationships between rates of emergency department (ED) admissions for asthma, race, and socio-economic status at the neighborhood block group level of analysis; (2) cluster statistical analyses are performed using Geomed software; and (3) the asthma risk from industrial air pollution was evaluated with windrose data and Screen3 air pollution model. Sample Data from five major hospitals with ED admissions of asthma patients (code 493), aged 0–15 years, are used to select a region of analysis with good geographical representation based on the catchment areas of hospitals in the study. A total of 2067 of the reported cases between 1 January 1993 and 30 June 1998, are successfully geocoded to a map, generating a no-match rate of 8.4%. Data on racial characteristics, population density, and household income levels are obtained from neighborhood block groups in the 1990 census report. Locations of major polluting industries within the study area are obtained from the Toxics Release Inventory. Results Spatial analysis identified a local asthma cluster roughly 2 km east (the predominant downwind direction) of the second and third largest air polluters (in terms of tonnage) in Wayne County. Evaluation of the industrial pollution with a focused cluster test, Screen3 air pollution model, and windrose figures, displayed weak association between ED asthma admissions and estimated levels of outdoor air pollution from these two facilities. The neighborhood block groups in the local asthma cluster are more closely correlated with high proportions of African Americans and low median household income. Implications for practice This study illustrates the strengths and weaknesses of GIS in the public health arena. It highlights the difficulty of disentangling the effects of exposure to outdoor air pollutants and socio-economic factors on ED asthmatics (reflecting asthma severity) among an urban population. This study also illustrates the need for population-based, as opposed to hospital-based, asthma data, and the need for block-groups, as opposed to zip codes, as a spatial unit of analysis in the evaluation and analysis of asthma-related risk factors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73994/1/j.1467-0658.2001.00143.x.pd

Induction of IL-8(CXCL8) and MCP-1(CCL2) with oxidative stress and its inhibition with N-acetyl cysteine (NAC) in cell culture model using HK-2 cell

Renal transplantation can often be complicated due to delayed graft function, which is a direct sequel of ischaemia reperfusion injury. The adverse outcome of delayed graft function is not only short term but the long-term function of the graft is also affected. Therefore, it is important to understand the mechanisms of ischaemia reperfusion injury. Reactive oxygen species are the key mediators in ischaemia reperfusion injury causing direct cell damage which also initiate inflammation by inducing chemokines. The presence of inflammation is a marker of severe delayed graft function. However, the effect of oxidative stress on the expression of key chemokines has not been fully established yet. Therefore, the aim of this study was to measure the oxidative stress response and the secretion of chemokines in a cell culture model that mimics the effects of ischaemia reperfusion injury in immortalised human renal proximal tubular epithelial cells, HK-2. Cells were treated with varying concentrations of hydrogen peroxide and markers of oxidative stress response and chemokine release were measured. Exposure to hydrogen peroxide induced a significant increase in the activity of the antioxidant enzyme glutathione peroxidase and the levels of the chemokines Interleukin-8 (IL-8; CXCL8) and MCP-1 (CCL2). A dose related increase of chemokine secretion was also observed. The cytokine Interleukin-1β (IL-1β) at 1 ng/ml significantly potentiated the expression of both IL-8 (CXCL8) and MCP-1 (CCL2) which showed synergistic response in the presence of hydrogen peroxide. Pre-incubation of the cells with the anti-oxidant N-acetyl cysteine (NAC) strongly suppressed the induction of both IL-8 and MCP-1 when stimulated with hydrogen peroxide and IL-1β. This study demonstrates the potential of anti-oxidants like N-acetyl cysteine in ameliorating the effects of ischaemia reperfusion injury thus suggesting a new therapeutic approach in renal transplantation. These findings can have potential implications for clinical use to prevent ischaemia reperfusion injury in renal transplantation

Prenatal and Neighborhood Correlates of Oppositional Defiant Disorder (ODD)

This study investigates the link between prenatal exposure to alcohol and drugs, parental perceptions of neighborhood safety and support, and the diagnosis of oppositional defiant disorder (ODD) among a nationally representative sample of youth. A subset of variables from a larger study, the 2001–2004 National Comorbidity Survey-Adolescent Supplement (NCS-A), as well as its supplemental parental surveys, was analyzed in this study. This study used a specific selection of 5,924 adolescents and their parents from the NCS-A. Results suggest a correlation between prenatal caffeine use and a subsequent ODD diagnosis in female adolescents. Overall correlations between neighborhood drug use/sales and minority status and a subsequent diagnosis of ODD in adolescents were also found. Social, environmental, and professional implications of these findings are also discussed