microRNA-142-mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance

Tregs play a fundamental role in immune tolerance via control of self-reactive effector T cells (Teffs). This function is dependent on maintenance of a high intracellular cAMP concentration. A number of microRNAs are implicated in the maintenance of Tregs. In this study, we demonstrate that peripheral immune tolerance is critically dependent on posttranscriptional repression of the cAMP-hydrolyzing enzyme phosphodiesterase-3b (Pde3b) by microRNA-142-5p (miR-142-5p). In this manner, miR-142-5p acts as an immunometabolic regulator of intracellular cAMP, controlling Treg suppressive function. Mir142 was associated with a super enhancer bound by the Treg lineage-determining transcription factor forkhead box P3 (FOXP3), and Treg-specific deletion of miR-142 in mice (TregΔ142) resulted in spontaneous, lethal, multisystem autoimmunity, despite preserved numbers of phenotypically normal Tregs. Pharmacological inhibition and genetic ablation of PDE3B prevented autoimmune disease and reversed the impaired suppressive function of Tregs in TregΔ142 animals. These findings reveal a critical molecular switch, specifying Treg function through the modulation of a highly conserved, cell-intrinsic metabolic pathway. Modulation of this pathway has direct relevance to the pathogenesis and treatment of autoimmunity and cancer

Analytical Pluralism in Qualitative Research: A Meta-Study

Recent interest in analytical pluralism – the application of more than one qualitative analytical method to a single data set – has demonstrated its potential to produce multiple, complex and varied understandings of phenomena. However tensions remain regarding the commensurability of findings produced from diverse theoretical frameworks, the practical application of multiple methods of analysis and the capacity of pluralism to contribute to knowledge in psychology. This study addresses these issues, through a critical interpretation of existing qualitative studies that utilised analytical pluralism. Using a meta-study design, we examined the use of theory, application of methods and production of findings in studies that had adopted qualitative analytical pluralism. Following comprehensive database searches, 10 articles were included in the analysis. Epistemological and ontological considerations, the influence of decisions made in the practical application of pluralism and approaches to interpreting findings produced from multiple analyses are discussed, and implications for future research are considered

Arctic marine secondary organic aerosol contributes significantly to summertime particle size distributions in the Canadian Arctic Archipelago

Summertime Arctic aerosol size distributions are strongly controlled by natural regional emissions. Within this context, we use a chemical transport model with sizeresolved aerosol microphysics (GEOS-Chem-TOMAS) to interpret measurements of aerosol size distributions from the Canadian Arctic Archipelago during the summer of 2016, as part of the "NETwork on Climate and Aerosols: Addressing key uncertainties in Remote Canadian Environments" (NETCARE) project. Our simulations suggest that condensation of secondary organic aerosol (SOA) from precursor vapors emitted in the Arctic and near Arctic marine (ice-free seawater) regions plays a key role in particle growth events that shape the aerosol size distributions observed at Alert (82.5° N, 62.3° W), Eureka (80.1° N, 86.4° W), and along a NETCARE ship track within the Archipelago. We refer to this SOA as Arctic marine SOA (AMSOA) to reflect the Arctic marine-based and likely biogenic sources for the precursors of the condensing organic vapors. AMSOA from a simulated flux (500 μgm-2 day-1, north of 50° N) of precursor vapors (with an assumed yield of unity) reduces the summertime particle size distribution model-observation mean fractional error 2- to 4-fold, relative to a simulation without this AMSOA. Particle growth due to the condensable organic vapor flux contributes strongly (30 %-50 %) to the simulated summertime-mean number of particles with diameters larger than 20 nm in the study region. This growth couples with ternary particle nucleation (sulfuric acid, ammonia, and water vapor) and biogenic sulfate condensation to account for more than 90% of this simulated particle number, which represents a strong biogenic influence. The simulated fit to summertime size-distribution observations is further improved at Eureka and for the ship track by scaling up the nucleation rate by a factor of 100 to account for other particle precursors such as gas-phase iodine and/or amines and/or fragmenting primary particles that could be missing from our simulations. Additionally, the fits to the observed size distributions and total aerosol number concentrations for particles larger than 4 nm improve with the assumption that the AMSOA contains semivolatile species: the model-observation mean fractional error is reduced 2- to 3-fold for the Alert and ship track size distributions. AMSOA accounts for about half of the simulated particle surface area and volume distributions in the summertime Canadian Arctic Archipelago, with climaterelevant simulated summertime pan-Arctic-mean top-of-theatmosphere aerosol direct (-0:04Wm-2) and cloud-albedo indirect (-0:4Wm-2) radiative effects, which due to uncertainties are viewed as an order of magnitude estimate. Future work should focus on further understanding summertime Arctic sources of AMSOA

Some Rare Indo-Pacific Coral Species Are Probable Hybrids

Background: coral reefs worldwide face a variety of threats and many coral species are increasingly endangered. It is often assumed that rare coral species face higher risks of extinction because they have very small effective population sizes, a predicted consequence of which is decreased genetic diversity and adaptive potential.\ud \ud Methodology/Principal Findings: here we show that some Indo-Pacific members of the coral genus Acropora have very small global population sizes and are likely to be unidirectional hybrids. Whether this reflects hybrid origins or secondary hybridization following speciation is unclear.\ud \ud Conclusions/Significance: the interspecific gene flow demonstrated here implies increased genetic diversity and adaptive potential in these coral species. Rare Acropora species may therefore be less vulnerable to extinction than has often been assumed because of their propensity for hybridization and introgression, which may increase their adaptive potential

Bird pollination of Canary Island endemic plants

The Canary Islands are home to a guild of endemic, threatened bird pollinated plants. Previous work has suggested that these plants evolved floral traits as adaptations to pollination by flower specialist sunbirds, but subsequently they appear to be have co-opted passerine birds as sub-optimal pollinators. To test this idea we carried out a quantitative study of the pollination biology of three of the bird pollinated plants, Canarina canariensis (Campanulaceae), Isoplexis canariensis (Veronicaceae) and Lotus berthelotii (Fabaceae), on the island of Tenerife. Using colour vision models, we predicted the detectability of flowers to bird and bee pollinators. We measured pollinator visitation rates, nectar standing crops, as well as seed set and pollen removal and deposition. These data showed that the plants are effectively pollinated by non-flower specialist passerine birds that only occasionally visit flowers. The large nectar standing crops and extended flower longevities (>10days) of Canarina and Isoplexis suggests that they have evolved bird pollination system that effectively exploits these low frequency non-specialist pollen vectors and is in no way suboptimal. Seed set in two of the three species was high, and was significantly reduced or zero in flowers where pollinator access was restricted. In L. berthelotii, however, no fruit set was observed, probably because the plants were self incompatible horticultural clones of a single genet. We also show that, while all three species are easily detectable for birds, the orange Canarina and the red Lotus (but less so the yellow-orange Isoplexis) should be difficult to detect for insect pollinators without specialised red receptors, such as bumblebees. Contrary to expectations if we accept that the flowers are primarily adapted to sunbird pollination, the chiffchaff (Phylloscopus canariensis) was an effective pollinator of these species

Методи управління екологічними ризиками в системі забезпечення економічного розвитку регіону

Метою статті є дослідження методів управління екологічними ризиками в системі забезпечення економічного розвитку регіону

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein

User fees in private non-for-profit hospitals in Uganda: a survey and intervention for equity

BACKGROUND: In developing countries, user fees may represent an important source of revenues for private-non-for-profit hospitals, but they may also affect access, use and equity. METHODS: This survey was conducted in ten hospitals of the Uganda Catholic Medical Bureau to assess differences in user fees policies and to propose changes that would better fit with the social concern explicitly pursued by the Bureau. Through a review of relevant hospital documents and reports, and through interviews with key informants, health workers and users, hospital and non-hospital cost was calculated, as well as overall expenditure and revenues. Lower fees were applied in some pilot hospitals after the survey. RESULTS: The percentage of revenues from user fees varied between 6% and 89% (average 40%). Some hospitals were more successful than others in getting external aid and government subsidies. These hospitals were applying lower fees and flat rates, and were offering free essential services to encourage access, as opposed to the fee-for-service policies implemented in less successful hospitals. The wide variation in user fees among hospitals was not justified by differences in case mix. None of the hospitals had a policy for exemption of the poor; the few users that actually got exempted were not really poor. To pay hospital and non-hospital expenses, about one third of users had to borrow money or sell goods and property. The fee system applied after the survey, based on flat and lower rates, brought about an increase in access and use of hospital services. CONCLUSION: Our results confirm that user fees represent an unfair mechanism of financing for health services because they exclude the poor and the sick. To mitigate this effect, flat rates and lower fees for the most vulnerable users were introduced to replace the fee-for-service system in some hospitals after the survey. The results are encouraging: hospital use, especially for pregnancy, childbirth and childhood illness, increased immediately, with no detrimental effect on overall revenues. A more equitable user fees system is possible