Fever-like temperature modification differentially affects in vitro signaling of bradykinin B-1 and B-2 receptors

The bradykinin (BK) B-2 and B-1 receptors (B2R, B1R) belong to the rhodopsin-like G protein-coupled receptors (GPCRs) and are involved in (patho)physiological processes such as blood pressure regulation or inflammation. They mediate the effects of the pro-inflammatory peptides bradykinin/kallidin and desArg(9)-BK/desArg(10)-kallidin, respectively. Whereas the B2R is constitutively expressed and gets internalized upon activation, the B1R is especially induced by inflammatory mediators and responds to stimulation with increased surface receptor numbers. Stimulation of both receptors activates phospholipase C beta (PLC beta) and mitogen activated protein kinase (MAPK) signaling. Because inflammatory processes are characterized by heat (fever), we analyzed the effect of increased temperature (41 degrees C vs. 37 degrees C) on B1R and B2R signaling in HEK 293 and IMR 90 cells. Our results show that signaling of both receptors is temperature-sensitive, however to a different extent and with regard to the investigated pathways. Comparing PLCb activity and Ca2+-regulated signals, a temperature-dependent increase was only observed for B1R but not for B2R activation, whereas MAPK activities were doubled at 41 degrees C for both receptors. Taken together, our findings suggest that the observed temperature sensitivity of B1R-induced PLCb activation is B1R-specific. In contrast, the enhanced stimulation of MAPK activity under hyperthermic conditions appears to be a common phenomenon for GPCRs

»Die Universität – ein Nukleus für eine Belebung des kulturellen und intellektuellen Lebens der Region« : Frankfurt und seine Potenziale – Wo wird die Main-Metropole im Jahre 2030 stehen?

Im Gespräch: Prof. Albert Speer, Dr. Olaf Kaltenborn, Prof. Klaus Ring und Prof. Werner Müller-Esterl

An approach to construct a three-dimensional isogeometric model from µ-CT scan data with an application to the bridge of a violin

We present an algorithm to build a ready to use isogeometric model from scan data gained by a µ-CT scan. Based on a three-dimensional multi-patch reference geometry, which includes the major topological features, we fit the outline, then the cross-section and finally the three-dimensional geometry. The key step is to fit the outline, where a non-linear least squares problem is solved with a Gauss-Newton approach presented by Borges and Pastva (2002). We extend this approach by a regularisation and a precise interpolation of selected data points. The resulting NURBS geometry is ready for applying isogeometric analysis tools for efficient numerical simulations. As a particular example we examine the scan data of a violin bridge and present the complete workflow from the µ-CT scan up to the numerical simulation based on isogeometric mortar methods. We illustrate the relevance of the constructed geometry with a vibro-acoustical application

On the Shell Structure of Nuclear Bubbles

We investigate the shell structure of spherical nuclear bubbles in simple phenomenological shell model potentials. The shell correction energies for doubly magic bubbles may be as large as -40 MeV and probably imply a very long lifetime against spontaneous fission. Beta-stability occurs for ratios of the neutron number N to the proton number Z which differ markable from the beta-stability valley of ordinary compact nuclei. The alpha-decay probability is shown to be very small for proton rich bubbles with a moderately large outer radius. Metastable islands of nuclear bubbles are shown to exist for nucleon in the range A=450 - 3000.Comment: 37 pages, latex, 27 figures in the eps format include

Stability of bubble nuclei through Shell-Effects

We investigate the shell structure of bubble nuclei in simple phenomenological shell models and study their binding energy as a function of the radii and of the number of neutron and protons using Strutinsky's method. Shell effects come about, on the one hand, by the high degeneracy of levels with large angular momentum and, on the other, by the big energy gaps between states with a different number of radial nodes. Shell energies down to -40 MeV are shown to occur for certain magic nuclei. Estimates demonstrate that the calculated shell effects for certain magic numbers of constituents are probably large enough to produce stability against fission, alpha-, and beta-decay. No bubble solutions are found for mass number A < 450.Comment: 9 pages and 9 figures in the eps format include

Effect of feeding practices and manure quality on CH4_{4} and N2_{2}O emissions from uncovered cattle manure heaps in Kenya

Countries in sub-Saharan Africa (SSA) rely on IPCC emission factors (EF) for GHG emission reporting. However, these were derived for industrialized livestock farms and do not represent conditions of smallholder farms (small, low-producing livestock breeds, poor feed quality, feed scarcity). Here, we present the first measurements of CH$_{4}$ and N$_{2}$O emissions from cattle-manure heaps representing feeding practices typical for smallholder farms in the highlands of East Africa: 1) cattle fed below maintenance energy requirements to represent feed scarcity, and 2) cattle fed tropical forage grasses (Napier, Rhodes, Brachiaria). Sub-maintenance feeding reduced cumulative manure N$_{2}$O emissions compared to cattle receiving sufficient feed but did not change EF$_{N2O}$. Sub-maintenance feeding did not affect cumulative manure CH$_{4}$ emissions or EF$_{CH4}$. When cattle were fed tropical forage grasses, cumulative manure N$_{2}$O emissions did not differ between diets, but manure EF$_{N2O}$ from Brachiaria and Rhodes diets were lower than the IPCC EF$_{N2O}$ for solid storage (1%, 2019 Refinement of IPCC Guidelines). Manure CH$_{4}$ emissions were lower in the Rhodes grass diet than when feeding Napier or Brachiaria, and manure EF$_{CH4}$ from all three grasses were lower than the IPCC default (4.4 g CH$_{4}$ kg$^{-1}$ VS, 2019 Refinement of IPCC Guidelines). Regression analysis revealed that manure N concentration and C:N were important drivers of N$_{2}$O emissions, with low N concentrations and high C:N reducing N$_{2}$O emissions. Our results show that IPCC EFs overestimate excreta GHG emissions, which calls for additional measurements to develop localized EFs for smallholder livestock systems in SSA

Acupuncture in acute herpes zoster pain therapy (ACUZoster) - design and protocol of a randomised controlled trial

Background: Acute herpes zoster is a prevalent condition. One of its major symptoms is pain, which can highly influence patient's quality of life. Pain therapy is limited. Acupuncture is supposed to soften neuropathic pain conditions and might therefore act as a therapeutic alternative. Objective of the present study is to investigate whether a 4 week semi-standardised acupuncture is non-inferior to sham laser acupuncture and the anticonvulsive drug gabapentine in the treatment of pain associated with herpes zoster. Methods/Design: Three-armed, randomised, placebo-controlled trial with a total follow-up time of 6 months. Up to estimated 336 patients (interim analyses) with acute herpes zoster pain (VAS > 30 mm) will be randomised to one of three groups (a) semi-standardised acupuncture (168 patients); (b) gabapentine with individualised dosage between 900-3600 mg/d (84 patients); (c) sham laser acupuncture. Intervention takes place over 4 weeks, all patients will receive analgesic therapy (non-opioid analgesics: metamizol or paracetamol and opioids: tramadol or morphine). Therapy phase includes 4 weeks in which group (a) and (c) consist of 12 sessions per patient, (b) visits depend on patients needs. Main outcome measure is to assess the alteration of pain intensity before and 1 week after treatment sessions (visual analogue scale VAS 0-100 mm). Secondary outcome measure are: alteration of pain intensity and frequency of pain attacks; alteration of different aspects of pain evaluated by standardised pain questionnaires (NPI, PDI, SES); effects on quality of life (SF 36); analgesic demand; alteration of sensoric perception by systematic quantitative sensory testing (QST); incidence of postherpetic neuralgia; side effects and cost effectiveness. Credibility of treatments will be assessed. Discussion: This study is the first large-scale randomised placebo controlled trial to evaluate the efficacy of acupuncture compared to gabapentine and sham treatment and will provide valuable new information about the clinical and physiological effects of acupuncture and gabapentine in the treatment of acute herpes zoster pain. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if acupuncture can be shown to be an effective treatment strategy in acute herpes zoster pain