A study of GPR3, GPR6, of GPR12 as novel molecular targets for cannabidiol.

The G protein-coupled receptors 3, 6, and 12 (GPR3, GPR6, and GPR12) comprise a family of closely related orphan receptors with no confirmed endogenous ligands. These receptors are constitutively active, capable of signaling through G protein and non-G protein mediated mechanisms. These orphan receptors have previously been reported to play important roles in many normal physiological functions and to be involved in a variety of pathological conditions. Although they are orphans, GPR3, GPR6, and GPR12 are phylogenetically most closely related to the cannabinoid receptors. Using β-arrestin2 recruitment and cAMP accumulation assays, we have recently found that the non-psychoactive phytocannabinoid cannabidiol (CBD) is an inverse agonist for GPR3, GPR6, and GPR12. This discovery highlights these orphan receptors as potential new molecular targets for CBD, provides novel mechanisms of action, and suggests new therapeutic uses of CBD for illnesses such as Alzheimer’s disease, Parkinson’s disease, cancer, and infertility. Furthermore, identification of CBD as a new inverse agonist for GPR3, GPR6, and GPR12 provides the initial chemical scaffolds upon which potent and efficacious agents acting on these receptors can be developed, with the goal of developing chemical tools for studying these orphan receptors and ultimately new therapeutic agents

Detection of fractures of hand and forearm in whole-body CT for suspected polytrauma in intubated patients

Background: The aim of this study was to evaluate the potential of whole-body CT for diagnosis of hand and forearm fractures in intubated patients with suspected polytrauma. Methods: We performed a retrospective analysis on data collected from two trauma centres in Germany, including demographics, ISS, clinical symptoms, depiction in whole-body CT, and time to diagnosis. Results: Out of 426 patients included in the study, 66 (15.5%) suffered a hand or forearm fracture. The total number of fractures was 132, the whole-body CT report mentioned 98 (74.2%). 16 (12,1%) fractures of 12 patients were diagnosed later than 24 h after admission. Late diagnoses of fractures of the hand occurred more often if the hand was not fully included in the CT scan field. The sensitivity of whole-body CT for cases with fractures of hand and/or forearm with full inclusion of the corresponding area in the scan field was 80.2%. Conclusions: This study shows that whole-body CT is a valuable diagnostic tool for hand fractures in polytrauma patients. Hands should be evaluated regardless of clinical presentation in intubated patients after suspected polytrauma if they are included in the whole-body CT. © 2020 The Author(s)

Implementation of kriging methods in mobile GIS to estimate damage to buildings in crisis scenarios

In the paper an example for the application of kriging methods to estimate damage to buildings in crisis scenarios is introduced. Furthermore, the Java implementations for Ordinary and Universal Kriging on mobile GIS are presented. As variogram models an exponential, a Gaussian and a spherical variogram are tested in detail. Different test constellations are introduced with various information densities. As test data set, public data from the analysis of the 2010 Haiti earthquake by satellite images are pre-processed and visualized in a Geographic Information System. As buildings, topography and other external influences cannot be seen as being constant for the whole area under investigation, semi variograms are calculated by consulting neighboured classified buildings using the so called moving window method. The evaluation of the methods shows that the underlying variogram model is the determining factor for the quality of the interpolation rather than the choice of the kriging method or increasing the information density of a random sample. The implementation is completely realized with the programming language Java. Thereafter, the implemented software component is integrated into GeoTech Mobile, a mobile GIS Android application based on the processing of standardized spatial data representations defined by the Open Geospatial Consortium (OGC). As a result the implemented methods can be used on mobile devices, i.e. they may be transferred to other application fields. That is why we finally point out further research with new applications in the Dubai region

Aging (Albany NY)

The combination of functional genomics with next generation sequencing facilitates new experimental strategies for addressing complex biological phenomena. Here, we report the identification of a gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1p) via whole-genome re-sequencing of a dominantSaccharomyces cerevisiae mutant obtained by chemical mutagenesis. Yeast strain K6001, a screening system for lifespan phenotypes, was treated with ethyl methanesulfonate (EMS). We isolated an oxidative stress-resistant mutant (B7) which transmitted this phenotype in a background-independent, monogenic and dominant way. By massive parallel pyrosequencing, we generated an 38.8 fold whole-genome coverage of the strains, which differed in 12,482 positions from the reference (S288c) genome. Via a subtraction strategy, we could narrow this number to 13 total and 4 missense nucleotide variations that were specific for the mutant. Via expression in wild type backgrounds, we show that one of these mutations, exchanging a residue in the peroxiredoxin Tsa1p, was responsible for the mutant phenotype causing background-independent dominant oxidative stress-resistance. These effects were not provoked by altered Tsa1p levels, nor could they be simulated by deletion, haploinsufficiency or over-expression of the wild-type allele. Furthermore, via both a mother-enrichment technique and a micromanipulation assay, we found a robust premature aging phenotype of this oxidant-resistant strain. Thus, TSA1-B7 encodes for a novel dominant form of peroxiredoxin, and establishes a new connection between oxidative stress and aging. In addition, this study shows that the re-sequencing of entire genomes is becoming a promising alternative for the identification of functional alleles in approaches of classic molecular genetics

GRAVITY: getting to the event horizon of Sgr A*

We present the second-generation VLTI instrument GRAVITY, which currently is in the preliminary design phase. GRAVITY is specifically designed to observe highly relativistic motions of matter close to the event horizon of Sgr A*, the massive black hole at center of the Milky Way. We have identified the key design features needed to achieve this goal and present the resulting instrument concept. It includes an integrated optics, 4-telescope, dual feed beam combiner operated in a cryogenic vessel; near infrared wavefront sensing adaptive optics; fringe tracking on secondary sources within the field of view of the VLTI and a novel metrology concept. Simulations show that the planned design matches the scientific needs; in particular that 10 microarcsecond astrometry is feasible for a source with a magnitude of K=15 like Sgr A*, given the availability of suitable phase reference sources.Comment: 13 pages, 11 figures, to appear in the conference proceedings of SPIE Astronomical Instrumentation, 23-28 June 2008, Marseille, Franc

The control of translational accuracy is a determinant of healthy ageing in yeast

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing

An overview of the mid-infrared spectro-interferometer MATISSE: science, concept, and current status

MATISSE is the second-generation mid-infrared spectrograph and imager for the Very Large Telescope Interferometer (VLTI) at Paranal. This new interferometric instrument will allow significant advances by opening new avenues in various fundamental research fields: studying the planet-forming region of disks around young stellar objects, understanding the surface structures and mass loss phenomena affecting evolved stars, and probing the environments of black holes in active galactic nuclei. As a first breakthrough, MATISSE will enlarge the spectral domain of current optical interferometers by offering the L and M bands in addition to the N band. This will open a wide wavelength domain, ranging from 2.8 to 13 um, exploring angular scales as small as 3 mas (L band) / 10 mas (N band). As a second breakthrough, MATISSE will allow mid-infrared imaging - closure-phase aperture-synthesis imaging - with up to four Unit Telescopes (UT) or Auxiliary Telescopes (AT) of the VLTI. Moreover, MATISSE will offer a spectral resolution range from R ~ 30 to R ~ 5000. Here, we present one of the main science objectives, the study of protoplanetary disks, that has driven the instrument design and motivated several VLTI upgrades (GRA4MAT and NAOMI). We introduce the physical concept of MATISSE including a description of the signal on the detectors and an evaluation of the expected performances. We also discuss the current status of the MATISSE instrument, which is entering its testing phase, and the foreseen schedule for the next two years that will lead to the first light at Paranal.Comment: SPIE Astronomical Telescopes and Instrumentation conference, June 2016, 11 pages, 6 Figure

Black Hole Mass Estimates Based on CIV are Consistent with Those Based on the Balmer Lines

Using a sample of high-redshift lensed quasars from the CASTLES project with observed-frame ultraviolet or optical and near-infrared spectra, we have searched for possible biases between supermassive black hole (BH) mass estimates based on the CIV, Halpha and Hbeta broad emission lines. Our sample is based upon that of Greene, Peng & Ludwig, expanded with new near-IR spectroscopic observations, consistently analyzed high S/N optical spectra, and consistent continuum luminosity estimates at 5100A. We find that BH mass estimates based on the FWHM of CIV show a systematic offset with respect to those obtained from the line dispersion, sigma_l, of the same emission line, but not with those obtained from the FWHM of Halpha and Hbeta. The magnitude of the offset depends on the treatment of the HeII and FeII emission blended with CIV, but there is little scatter for any fixed measurement prescription. While we otherwise find no systematic offsets between CIV and Balmer line mass estimates, we do find that the residuals between them are strongly correlated with the ratio of the UV and optical continuum luminosities. Removing this dependency reduces the scatter between the UV- and optical-based BH mass estimates by a factor of approximately 2, from roughly 0.35 to 0.18 dex. The dispersion is smallest when comparing the CIV sigma_l mass estimate, after removing the offset from the FWHM estimates, and either Balmer line mass estimate. The correlation with the continuum slope is likely due to a combination of reddening, host contamination and object-dependent SED shapes. When we add additional heterogeneous measurements from the literature, the results are unchanged.Comment: Accepted for publication in The Astrophysical Journal. 37 text pages + 8 tables + 23 figures. Updated with comments by the referee and with a expanded discussion on literature data including new observation