Identification of transmembrane domains that regulate spatial arrangements and activity of prokineticin receptor 2 dimers

The chemokine prokineticin 2 (PK2) activates its cognate G protein-coupled receptor (GPCR) PKR2 to elicit various downstream signaling pathways involved in diverse biological processes. Many GPCRs undergo dimerization that can modulate a number of functions including membrane delivery and signal transduction. The aim of this study was to elucidate the interface of PKR2 protomers within dimers by analyzing the ability of PKR2 transmembrane (TM) deletion mutants to associate with wild type (WT) PKR2 in yeast using co-immunoprecipitation and mammalian cells using bioluminescence resonance energy transfer. Deletion of TMs 5-7 resulted in a lack of detectable association with WT PKR2, but could associate with a truncated mutant lacking TMs 6-7 (TM1-5). Interestingly, TM1-5 modulated the distance, or organization, between protomers and positively regulated Gαs signaling and surface expression of WT PKR2. We propose that PKR2 protomers form type II dimers involving TMs 4 and 5, with a role for TM5 in modulation of PKR2 function

TRAIL, DR5 and Caspase 3-dependent Apoptosis in Vessels of Diseased Human Temporomandibular Joint Disc. An Immunohistochemical Study

To evaluate the apoptosis involvement in the angiogenesis as a self-limiting process in patients with temporomandibular joint (TMJ) degenerated disc vessels, we assessed, by immunohistochemistry, the detection of TRAIL, its death receptor DR5 and caspase 3. TRAIL, its death receptor DR5 and caspase 3 expression were studied by immunohistochemistry in 15 TMJ discs displaced without reduction and in 4 unaffected discs. These apoptosis molecules were detected in the intima and media layers of newly formed vessels affected discs. In conclusion, vessels apoptosis activation in TMJ disc with ID could be regarded as a self-limiting process that try to leads to vessel regression; in this way an inhibition of angiogenic vessels may prove a key strategy in limiting pathological angiogenesis, by cutting off blood supply to tumors, or by reducing harmful inflammation

What Works for Aboriginal and Torres Strait Islander Men? A Systematic Review of the Literature

Aboriginal and Torres Strait Islander men experience significantly higher rates of suicide, trauma, alcohol related deaths and unemployment than other Australian men. Despite significant levels of government intervention, rates of family violence, unemployment and incarceration continue to increase in Aboriginal and Torres Strait Islander communities. As a subset of the Aboriginal and Torres Strait Islander population, there has been a lesser focus on how to meaningfully improve the wellbeing of Aboriginal and Torres Strait Islander men. This systematic review seeks to understand what interventions, programs and activities are successful in improving the wellbeing of Aboriginal and Torres Strait Islander men and thereby the wellbeing of their communities. A thorough search of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifteen studies met the inclusion criteria. Analysis of the programs, activities and interventions evaluated in these studies indicated two prominent themes that were successful in improving the wellbeing of Aboriginal and Torres Strait Islander men: strengthening identity and increasing social connection. The mechanisms contributing to these outcomes are discussed, as are implications for policy and future research

Which Way From Here? An Exploration of Local Perspectives on Strengths, Needs and Goals in the Aurukun Community

Aurukun is a small Aboriginal community located in remote Cape York, Far North Queensland. This study explores local perspectives on the goals, strengths and areas of need in the community, and perceptions of the role of a man in Aurukun. Seventeen individuals from the Aurukun community were informally interviewed. The sample comprised eight community elders (four female, four male) and nine community members (six male, three female). A reference group comprising local community members and elders guided the research project. Results indicated that the communities’ main strength was their connection to culture, the areas most needing improvement were violence, alcohol use, over incarceration, poor support for mental health and a lack of employment opportunities. Participants saw the best way forward as being through more employment and better communication. The interconnectedness of these themes as well as their implications for successful program development and evaluation are discussed

SO2 flux from Stromboli during the 2007 eruption: Results from the FLAME network and traverse measurements

SO2 fluxes emitted by Stromboli during the 27th February – 2nd April 2007 effusive eruption were regularly measured both by an automatic network of scanning ultraviolet spectrometers and by traverse easurements conducted by boat and helicopter. The results from both methodologies agree reasonably well, providing a validation for the automatic flux calculations produced by the network. Approximately 22,000 tonnes of SO2 were degassed during the course of the 35 day eruption at an average rate of 620 tonnes per day. Such a degassing rate is much higher than that normally observed (150-200 t/d), because the cross-sectional area occupied by ascending degassed magma is much greater than normal during the effusion, as descending, degassed magma that would normally occupy a large volume of the conduit is absent. We propose that the hydrostatically controlled magma level within Stromboli’s conduit is the main control on eruptive activity, and that a high effusion rate led to the depressurisation of an intermediate magma reservoir, creating a decrease in the magma level until it dropped beneath the eruptive fissure, causing the rapid end of the eruption. A significant decrease in SO2 flux was observed prior to a paroxysm on 15th March 2007, suggesting that choking of the gas flowing in the conduit may have induced a coalescence event, and consequent rapid ascent of gas and magma that produced the explosion

New insights into volcanic processes at Stromboli from Cerberus, a remote-controlled open-path FTIR scanner system

The ordinary, low intensity, activity of Stromboli volcano is sporadically interrupted by more energetic events termed, depending on their intensity, “major explosions” and “paroxysms”. These short-lived energetic episodes represent a potential risk to visitors to the highly accessible summit of Stromboli. Observations made at Stromboli over the last decade have shown that the composition of gas emitted from the summit craters may change prior to such explosions, allowing the possibility that such changes may be used to forecast these potentially dangerous events. In 2008 we installed a novel, remote-controlled, open-path FTIR scanning system called Cerberus at the summit of Stromboli, with the objective of measuring gas compositions from individual vents within the summit crater terrace of the volcano with high temporal resolution and for extended periods. In this work we report the first results from the Cerberus system, collected in August-September 2009, November 2009 and May-June 2010. We find significant, fairly consistent, intra-crater variability for CO2/SO2 and H2O/CO2 ratios, and relatively homogeneous SO2/HCl ratios. In general, the southwest crater is richest in CO2, and the northeast crater poorest, while the central crater is richest in H2O. It thus appears that during the measurement period the southwest crater had a somewhat more direct connection to a primary, deep degassing system; whilst the central and northeast craters reflect a slightly more secondary degassing nature, with a supplementary, shallow H2O source for the central crater, probably related to puffing activity. Such water-rich emissions from the central crater can account for the lower crystal content of its eruption products, and emphasise the role of continual magma supply to the shallowest levels of Stromboli's plumbing system. Our observations of heterogeneous crater gas emissions and high H2O/CO2 ratios do not agree with models of CO2-flushing, and we show that simple depressurisation during magma ascent to the surface is a more likely model for H2O loss at Stromboli. We highlight that alternative explanations other than CO2 flushing are required to explain distributions of H2O and CO2 amounts dissolved in melt inclusions. We detected fairly systematic increases in CO2/SO2 ratio some weeks prior to major explosions, and some evidence of a decrease in this ratio in the days immediately preceding the explosions, with periods of low, stable CO2/SO2 ratios between explosions otherwise. Our measurements, therefore, confirm the medium term (~ weeks) precursory increases previously observed with MultiGas instruments, and, in addition, reveal new, short-term precursory decreases in CO2/SO2 ratios. immediately prior to the major explosions. Such patterns, if shown to be systematic, may be of great utility for hazard management at Stromboli's summit. Our results suggest that intra-crater CO2/SO2 variability may produce short-term peaks and troughs in CO2/SO2 time series measured with in-situ MultiGas instruments, due simply to variations in wind direction

Novel retrieval of volcanic SO2 abundance from ultraviolet spectra

The recent development of fixed networks of scanning ultraviolet spectrometers for automatic determination of volcanic SO2 fluxes has created tremendous opportunities for monitoring volcanoes but has brought new challenges in processing of the substantial data flow they produce. A particular difficulty in standard implantation of differential optical absorption (DOAS) methods is the requirement for a clear-sky (plume-free) background spectrum. Our experience after four years of measurements with two UV scanner networks on Etna and Stromboli shows that wide plumes are frequently observed precluding simple selection of clear-sky spectra. We have therefore developed a retrieval approach based on simulation of the background spectrum. We describe the method here and tune it empirically by collecting clear, zenith sky spectra using calibration cells containing known amounts of SO2. We then test the performance of this optimised retrieval using clear-sky spectra collected with the same calibration cells but for variable scan angles, time of day, and season (through the course of 1 year). We find in all cases acceptable results (maximum ~12% error) for SO2 column amounts. The method is therefore very suitable for automated SO2-plume monitoring

Current molecular and clinical insights into uveal melanoma (Review)

Uveal melanoma (UM) represents the most prominent primary eye cancer in adults. With an incidence of approximately 5 cases per million individuals annually in the United States, UM could be considered a relatively rare cancer. The 90.95% of UM cases arise from the choroid. Diagnosis is based mainly on a clinical examination and ancillary tests, with ocular ultrasonography being of greatest value. Differential diagnosis can prove challenging in the case of indeterminate choroidal lesions and, sometimes, monitoring for documented growth may be the proper approach. Fine needle aspiration biopsy tends to be performed with a prognostic purpose, often in combination with radiotherapy. Gene expression profiling has allowed for the grading of UMs into two classes, which feature different metastatic risks. Patients with UM require a specialized multidisciplinary management. Primary tumor treatment can be either enucleation or globe preserving. Usually, enucleation is reserved for larger tumors, while radiotherapy is preferred for small/medium melanomas. The prognosis is unfavorable due to the high mortality rate and high tendency to metastasize. Following the development of metastatic disease, the mortality rate increases to 80% within one year, due to both the absence of an effective treatment and the aggressiveness of the condition. Novel molecular studies have allowed for a better understanding of the genetic and epigenetic mechanisms involved in UM biological activity, which differs compared to skin melanomas. The most commonly mutated genes are GNAQ, GNA11 and BAP1. Research in this field could help to identify effective diagnostic and prognostic biomarkers, as well as novel therapeutic targets