Lack of direct evidence for a functional role of voltage-operated calcium channels in juxtaglomerular cells

In this study we have examined the role of voltage-gated calcium channels in the regulation of calcium in juxtaglomerular cells. Using a combination of patch-clamp and single-cell calcium measurement we obtained evidence neither for voltage-operated calcium currents nor for changes of the intracellular calcium concentration upon acute depolarizations of the cell membrane. Increases of the extracellular concentration of potassium to 80 mmol/l depolarized the juxtaglomerular cells close to the potassium equilibrium potential, but did not alter the intracellular calcium concentration neither in patch-clamped nor in intact Furaester-loaded cells. Moreover, basal renin secretion from a preparation enriched in mouse juxtaglomerular cells and from rat glomeruli with attached juxtaglomerular cells was not inhibited when extracellular potassium was isoosmotically increased to 56 mmol/l. In mouse kidney slices, however, depolarizing potassium concentrations caused a delayed inhibition at 56 mmol/l and a delayed stimulation of renin secretion at 110 mmol/l. Taken together, our study does not provide direct evidence for a role of voltage-activated calcium channels in the regulation of calcium and renin secretion in renal juxtaglomerular cells

New RPC front-end electronics for hades

Time-of-flight (TOF) detectors are mainly used for both particle identification and triggering. Resistive Plate Chamber (RPC) detectors are becoming widely used because of their excellent TOF capabilities and reduced cost. The new ESTRELA* RPC wall, which is being installed in the HADES detector at Darmstadt GSI, will contain 1024 RPC modules, covering an active area of around 7 m2. It has excellent TOF and good charge resolutions. Its Front-End electronics is based on a 8-layer Mother-Board providing impedance matched paths for the output signals of each of the eight 4-channel Daughter-Boards to the TDC

Verification of electromagnetic calorimeter concept for the HADES spectrometer

The HADES spectrometer currently operating on the beam of SIS18 accelerator in GSI will be moved to a new position in the CBM cave of the future FAIR complex. Electromagnetic calorimeter (ECAL) will enable the HADES@FAIR experiment to measure data on neutral meson production in heavy ion collisions at the energy range of 2-10 A GeVon the beam of the new accelerator SIS100. Calorimeter will be based on 978 massive lead glass modules read out by photomultipliers and a novel front-end electronics. Secondary gamma beam with energies ranging from 81 MeV up to 1399 MeV from MAMI-C Mainz facility was used to verify selected technical solutions. Relative energy resolution was measured using modules with three different types of photomultipliers. Two types of developed front-end electronics as well as energy leakage between neighbouring modules under parallel and declined gamma beams were studied in detail

Interpreting Metabolomic Profiles using Unbiased Pathway Models

Human disease is heterogeneous, with similar disease phenotypes resulting from distinct combinations of genetic and environmental factors. Small-molecule profiling can address disease heterogeneity by evaluating the underlying biologic state of individuals through non-invasive interrogation of plasma metabolite levels. We analyzed metabolite profiles from an oral glucose tolerance test (OGTT) in 50 individuals, 25 with normal (NGT) and 25 with impaired glucose tolerance (IGT). Our focus was to elucidate underlying biologic processes. Although we initially found little overlap between changed metabolites and preconceived definitions of metabolic pathways, the use of unbiased network approaches identified significant concerted changes. Specifically, we derived a metabolic network with edges drawn between reactant and product nodes in individual reactions and between all substrates of individual enzymes and transporters. We searched for “active modules”—regions of the metabolic network enriched for changes in metabolite levels. Active modules identified relationships among changed metabolites and highlighted the importance of specific solute carriers in metabolite profiles. Furthermore, hierarchical clustering and principal component analysis demonstrated that changed metabolites in OGTT naturally grouped according to the activities of the System A and L amino acid transporters, the osmolyte carrier SLC6A12, and the mitochondrial aspartate-glutamate transporter SLC25A13. Comparison between NGT and IGT groups supported blunted glucose- and/or insulin-stimulated activities in the IGT group. Using unbiased pathway models, we offer evidence supporting the important role of solute carriers in the physiologic response to glucose challenge and conclude that carrier activities are reflected in individual metabolite profiles of perturbation experiments. Given the involvement of transporters in human disease, metabolite profiling may contribute to improved disease classification via the interrogation of specific transporter activities

Distributive justice with and without culture

Academic treatments of distributive justice normally adopt a static approach centred on resource allocation among a set of individual agents. The resulting models, expressed in mathematical language, make no allowance for culture, as they never engage with the society’s way of life or the moulding of individuals within society. This paper compares the static approach to distributive justice with a cultural one, arguing that a case for redistribution should rest upon its cultural effects in assisting well-being and social cohesion. Unless we recognise culture, we can have little understanding of why inequalities matter, where they come from, and how they might be reduced. Redistribution may be motivated by universal value judgements taken from external sources, but it also entails internal cultural changes that refashion social relations through cumulative causation. In practical terms, it has to penetrate beyond reallocating resource endowments to bring revised attitudes in a society less tolerant of unequal outcomes. Egalitarian reforms will flourish only if they generate and reflect an egalitarian culture

Adverse events from spinal manipulation in the pregnant and postpartum periods: a critical review of the literature

<p>Abstract</p> <p>Background</p> <p>The safety of spinal manipulation during pregnancy and the postpartum periods has been a matter of debate among manual therapists. Spinal manipulative therapy during these periods is a commonly performed intervention as musculoskeletal pain is common in these patients. To date there has not been an evaluation of the literature on this topic exclusively.</p> <p>Methods</p> <p>A literature search was conducted on PubMed, CINAHL and the Index to Chiropractic Literature along with reference searching for articles published in English and French in the peer-reviewed literature that documented adverse effects of spinal manipulation during either pregnancy or postpartum. Case reports, case series, and any other clinical study designs were deemed acceptable for inclusion, as were systematic reviews. The appropriate Scottish Intercollegiate Guidelines Network (SIGN) tools were used to rate included articles for quality when applicable.</p> <p>Results</p> <p>Five articles identifying adverse events in seven subjects following spinal manipulation were included in this review, along with two systematic reviews. The articles were published between 1978 and 2009. Two articles describing adverse effects from spinal manipulation on two postpartum patients were included, while the remaining three articles on five patients with adverse effects following spinal manipulation were on pregnant patients. Injury severity ranged from minor injury such as increasing pain after treatment that resolved within a few days to more severe injuries including fracture, stroke, and epidural hematoma. SIGN scores of the prospective observational cohort study and systematic reviews indicated acceptable quality.</p> <p>Conclusions</p> <p>There are only a few reported cases of adverse events following spinal manipulation during pregnancy and the postpartum period identified in the literature. While improved reporting of such events is required in the future, it may be that such injuries are relatively rare.</p