A Novel Soluble Immune-Type Receptor (SITR) in Teleost Fish: Carp SITR Is Involved in the Nitric Oxide-Mediated Response to a Protozoan Parasite

Background- The innate immune system relies upon a wide range of germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors. Different Ig-like immune receptor families have been reported in mammals, birds, amphibians and fish. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Ig-like domains and their regulation of effector functions is mediated intracellularly by distinct stimulatory or inhibitory pathways. Methodology/Principal Findings - Carp SITR was found in a substracted cDNA repertoire from carp macrophages, enriched for genes up-regulated in response to the protozoan parasite Trypanoplasma borreli. Carp SITR is a type I protein with two extracellular Ig domains in a unique organisation of a N-proximal V/C2 (or I-) type and a C-proximal V-type Ig domain, devoid of a transmembrane domain or any intracytoplasmic signalling motif. The carp SITR C-proximal V-type Ig domain, in particular, has a close sequence similarity and conserved structural characteristics to the mammalian CD300 molecules. By generating an anti-SITR antibody we could show that SITR protein expression was restricted to cells of the myeloid lineage. Carp SITR is abundantly expressed in macrophages and is secreted upon in vitro stimulation with the protozoan parasite T. borreli. Secretion of SITR protein during in vivo T. borreli infection suggests a role for this IgSF receptor in the host response to this protozoan parasite. Overexpression of carp SITR in mouse macrophages and knock-down of SITR protein expression in carp macrophages, using morpholino antisense technology, provided evidence for the involvement of carp SITR in the parasite-induced NO production. Conclusion/Significance - We report the structural and functional characterization of a novel soluble immune-type receptor (SITR) in a teleost fish and propose a role for carp SITR in the NO-mediated response to a protozoan parasite

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Genetic variants linked to education predict longevity

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members’ polygenic profile score for education to predict their parents’ longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total ndeaths = 79,702) and ∼2.4% lower risk for fathers (total ndeaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity.</p

High Resolution Beam Orbit Measurement Electronics based on Compensated Diode Detectors

A high resolution beam position monitor (BPM) electronics based on diode peak detectors has been developed at CERN. The circuit processes the BPM electrode signals independently, converting the short beam pulses into slowly varying signals which can be digitized with high resolution ADCs operating in the kHz range or even measured with a DC voltmeter. For signals with peak amplitudes larger than some hundred mV the non-linear forward voltage of the diodes is compensated by a simple network using signals from two peak detectors, one with a single and the second with two diodes in series. This contribution presents results obtained with the first prototype in the laboratory and with the CERN-SPS beam. Ongoing development and possible future applications of the technique are also discussed

BPM Electronics based on Compensated Diode Detectors – Results from development Systems

High resolution beam position monitor (BPM) electronics based on diode peak detectors is being developed for processing signals from button BPMs embedded into future LHC collimators. Its prototypes were measured in a laboratory as well as with beam signals from the collimator BPM installed on the SPS and with LHC BPMs. Results from these measurements are presented and discussed

LHC Beam Stability and Performance of the Q/Q' Diagnostic Instrumentation

The BBQ tune (Q) and chromaticity (Q’) diagnostic systems played a crucial role during the LHC commissioning while establishing circulating beam and first ramps. Early on, they allowed identifying issues such as residual tune stability, beam spectrum interferences and beam-beam effects – all of which may impact beam life-times and thus are being addressed in view of nominal LHC operation. This contribution discusses the initial beam stability in relation to the achieved instrumentation sensitivity, corresponding tune frequency and Q’ resolution

First Results from the LHC BBQ Tune and Chromaticity Systems

This note summarises the performance and early results obtained with the base-line LHC Tune Measurements System during the first days of LHC operation. Initial tune, coupling and chromaticity measurements as well as initial tune correction are presented

Continuous Measurement and Control of Beta-Beating in the LHC

The beta function has a fundamental impact on the LHC performance and on the functioning of its machine protection and collimation systems. A new beta-beat diagnostic system, prototyped at the SPS, has been used to verify the time-dependent variations of the LHC lattice with unprecedented 1% beta-beta resolution and at a measurement bandwidth of about 1 Hz. This contribution discusses the first results of local continuous beta-function measurements in the LHC collimation region, the systematic measurement errors and their compensation. The impact on nominal LHC operation and the potential to provide an input for an automated local feedback control of the beta-function are presented

Commissioning and Initial Performance of the LHC Beam-Based Feedback Systems

The LHC deploys a comprehensive suite of beam-based feedbacks for safe and reliable machine operation. This contribution summarises the commissioning and early results of the LHC feedback control systems on orbit, tune, chromaticity, and energy. Their performance – strongly linked to the associated beam instrumentation, external beam perturbation sources and optics uncertainties – is evaluated and compared with the initial feedback design assumption