Prostaglandins facilitate peptide release from rat sensory neurons by activating the adenosine 3',5'-cyclic monophosphate transduction cascade

Prostaglandins sensitize sensory neurons to activation by mechanical, thermal and chemical stimuli. This sensitization also results in an increase in the stimulus-evoked release of the neuroactive peptides, substance P and calcitonin gene-related peptide from sensory neurons. The cellular transduction cascade underlying the prostaglandin-induced augmentation of peptide release is not known. Therefore, we examined whether the sensitizing action of prostaglandins on peptide release from sensory neurons grown in culture is mediated by the second messenger, adenosine 3', 5' cyclic monophosphate (cAMP). Prostaglandin E2 and carba prostacyclin (a stable analog of prostaglandin I2) significantly increase the content of cAMP-like immunoreactive substance (icAMP) in the sensory neuron cultures at concentrations that also augment the bradykinin- or capsaicin-evoked release of peptides. Furthermore, pretreating sensory neurons with agents that increase intracellular cAMP mimics the sensitizing action of prostaglandins. Exposing cultures to either forskolin (0.1-10 microM), cholera toxin (1.5 micrograms), or 8-bromo-cAMP (100 microM) results in a significant enhancement of the bradykinin- or capsaicin-stimulated release of both substance P-like and calcitonin gene-related peptide-like immunoreactive substances. Pretreating sensory neurons with the adenylyl cyclase inhibitor, 9-tetrahydro-2-furyl adenine (5 mM), abolishes the prostaglandin-induced increases in icAMP content and attenuates the prostaglandin E2 or carba prostacyclin enhancement of the evoked release of calcitonin gene-related peptide-like immunoreactive substance. These results demonstrate that the cAMP transduction cascade mediates the sensitizing actions of prostaglandins on peptide release from sensory neurons

JIRAM, the Jovian Infrared Auroral Mapper

JIRAM is an imager/spectrometer on board the Juno spacecraft bound for a polar orbit around Jupiter. JIRAM is composed of IR imager and spectrometer channels. Its scientific goals are to explore the Jovian aurorae and the planet's atmospheric structure, dynamics and composition. This paper explains the characteristics and functionalities of the instrument and reports on the results of ground calibrations. It discusses the main subsystems to the extent needed to understand how the instrument is sequenced and used, the purpose of the calibrations necessary to determine instrument performance, the process for generating the commanding sequences, the main elements of the observational strategy, and the format of the scientific data that JIRAM will produce

The influence of media violence on youth

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83429/1/2003.Anderson_etal.InfluenceofMediaViolenceonYouth.PsychologicalScienceinthePublicInterest.pd

Co-limitation towards lower latitudes shapes global forest diversity gradients

The latitudinal diversity gradient (LDG) is one of the most recognized global patterns of species richness exhibited across a wide range of taxa. Numerous hypotheses have been proposed in the past two centuries to explain LDG, but rigorous tests of the drivers of LDGs have been limited by a lack of high-quality global species richness data. Here we produce a high-resolution (0.025° × 0.025°) map of local tree species richness using a global forest inventory database with individual tree information and local biophysical characteristics from ~1.3 million sample plots. We then quantify drivers of local tree species richness patterns across latitudes. Generally, annual mean temperature was a dominant predictor of tree species richness, which is most consistent with the metabolic theory of biodiversity (MTB). However, MTB underestimated LDG in the tropics, where high species richness was also moderated by topographic, soil and anthropogenic factors operating at local scales. Given that local landscape variables operate synergistically with bioclimatic factors in shaping the global LDG pattern, we suggest that MTB be extended to account for co-limitation by subordinate drivers

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Bone turnover in elderly females and males using bisphosphonate treatment-A pilot study


We undertook a 2 year pilot study in premenopausal and postmenopausal females and male partners in which the subjects were administered a bisphosphonate, alendronate, for 6 months. The aim ot the study was to determine how lead isotopes and lead concentrations changed in relation to bone remodelling processes. Each subject had blood and urine samples collected for markers of bone turnover and for lead isotope studies monthly for $7-9$ months before and then 3 monthly during and for up to 6 months after treatment with alendronate as an agent for inhibiting bone resorption. There were significant decreases in the lead isotope ratio, $^{206}$Pb/$^{204}$Pb, for the migrant subjects cluring treatment compared with thepre-treatment period ($\rm p<0.01$). The average bloodlead concentrations in migrant subjects decreased by about 20% during the treatment compared with the pre-treatment period ($\rm p<0.01$). The changes in lead isotopic composition and lead concentration are consistent with a decrease m bone résorption and associated mobilisation of lead during alendronate therapy