The differences between mass concentration (mas con) parameters and standard Stokes coefficient parameters in the recovery of gravity infonnation from gravity recovery and climate experiment (GRACE) ...intersatellite K-band range rate data are investigated. First, mascons are decomposed into their Stokes coefficient representations to gauge the range of solutions available using each of the two types of parameters. Next, a direct comparison is made between two time series of unconstrained gravity solutions, one based on a set of global equal area mascon parameters (equivalent to 4deg x 4deg at the equator), and the other based on standard Stokes coefficients with each time series using the same fundamental processing of the GRACE tracking data. It is shown that in unconstrained solutions, the type of gravity parameter being estimated does not qualitatively affect the estimated gravity field. It is also shown that many of the differences in mass flux derivations from GRACE gravity solutions arise from the type of smoothing being used and that the type of smoothing that can be embedded in mas con solutions has distinct advantages over postsolution smoothing. Finally, a 1 year time series based on global 2deg equal area mascons estimated every 10 days is presented.
Aims/hypothesis
MicroRNAs regulate a broad range of biological mechanisms. To investigate the relationship between microRNA expression and type 2 diabetes, we compared global microRNA expression in ...insulin target tissues from three inbred rat strains that differ in diabetes susceptibility.
Methods
Using microarrays, we measured the expression of 283 microRNAs in adipose, liver and muscle tissue from hyperglycaemic (Goto–Kakizaki), intermediate glycaemic (Wistar Kyoto) and normoglycaemic (Brown Norway) rats (
n
= 5 for each strain). Expression was compared across strains and validated using quantitative RT-PCR. Furthermore, microRNA expression variation in adipose tissue was investigated in 3T3-L1 adipocytes exposed to hyperglycaemic conditions.
Results
We found 29 significantly differentiated microRNAs (
p
adjusted
< 0.05): nine in adipose tissue, 18 in liver and two in muscle. Of these, five microRNAs had expression patterns that correlated with the strain-specific glycaemic phenotype. MiR-222 (
p
adjusted
= 0.0005) and miR-27a (
p
adjusted
= 0.006) were upregulated in adipose tissue; miR-195 (
p
adjusted
= 0.006) and miR-103 (
p
adjusted
= 0.04) were upregulated in liver; and miR-10b (
p
adjusted
= 0.004) was downregulated in muscle. Exposure of 3T3-L1 adipocytes to increased glucose concentration upregulated the expression of miR-222 (
p
= 0.008), miR-27a (
p
= 0.02) and the previously reported miR-29a (
p
= 0.02). Predicted target genes of these differentially expressed microRNAs are involved in pathways relevant to type 2 diabetes.
Conclusion
The expression patterns of miR-222, miR-27a, miR-195, miR-103 and miR-10b varied with hyperglycaemia, suggesting a role for these microRNAs in the pathophysiology of type 2 diabetes, as modelled by the Gyoto–Kakizaki rat. We observed similar patterns of expression of miR-222, miR-27a and miR-29a in adipocytes as a response to increased glucose levels, which supports our hypothesis that altered expression of microRNAs accompanies primary events related to the pathogenesis of type 2 diabetes.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently ...underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
Endogenous retroviruses (ERVs), remnants of ancient germline infections, comprise 8% of the human genome. The most recently integrated includes human ERV-K (HERV-K) where several envelope (env) ...sequences remain intact. Viral pseudotypes decorated with one of those Envs are infectious. Using a recombinant vesicular stomatitis virus encoding HERV-K Env as its sole attachment and fusion protein (VSV-HERVK) we conducted a genome-wide haploid genetic screen to interrogate the host requirements for infection. This screen identified 11 genes involved in heparan sulfate biosynthesis. Genetic inhibition or chemical removal of heparan sulfate and addition of excess soluble heparan sulfate inhibit infection. Direct binding of heparin to soluble HERV-K Env and purified VSV-HERVK defines it as critical for viral attachment. Cell surface bound VSV-HERVK particles are triggered to infect on exposure to acidic pH, whereas acid pH pretreatment of virions blocks infection. Testing of additional endogenous HERV-K env sequences reveals they bind heparin and mediate acid pH triggered fusion. This work reconstructs and defines key steps in the infectious entry pathway of an extinct virus.
Over the past decade, long-duration γ-ray bursts (GRBs)-including the subclass of X-ray flashes (XRFs)-have been revealed to be a rare variety of type Ibc supernova. Although all these events result ...from the death of massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those of ordinary type Ibc supernovae by many orders of magnitude. The essential physical process that causes a dying star to produce a GRB or XRF, and not just a supernova, is still unknown. Here we report radio and X-ray observations of XRF 060218 (associated with supernova SN 2006aj), the second-nearest GRB identified until now. We show that this event is a hundred times less energetic but ten times more common than cosmological GRBs. Moreover, it is distinguished from ordinary type Ibc supernovae by the presence of 1048 erg coupled to mildly relativistic ejecta, along with a central engine (an accretion-fed, rapidly rotating compact source) that produces X-rays for weeks after the explosion. This suggests that the production of relativistic ejecta is the key physical distinction between GRBs or XRFs and ordinary supernovae, while the nature of the central engine (black hole or magnetar) may distinguish typical bursts from low-luminosity, spherical events like XRF 060218.
To develop evidence-based recommendations for the management of fibromyalgia syndrome.
A multidisciplinary task force was formed representing 11 European countries. The design of the study, including ...search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation.
146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made.
Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.
Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 ...s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required.
Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk ...for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.
Ecology Letters (2011) 14: 349–357
The earth’s future climate state is highly dependent upon changes in terrestrial C storage in response to rising concentrations of atmospheric CO2. Here we show ...that consistently enhanced rates of net primary production (NPP) are sustained by a C‐cascade through the root‐microbe‐soil system; increases in the flux of C belowground under elevated CO2 stimulated microbial activity, accelerated the rate of soil organic matter decomposition and stimulated tree uptake of N bound to this SOM. This process set into motion a positive feedback maintaining greater C gain under elevated CO2 as a result of increases in canopy N content and higher photosynthetic N‐use efficiency. The ecosystem‐level consequence of the enhanced requirement for N and the exchange of plant C for N belowground is the dominance of C storage in tree biomass but the preclusion of a large C sink in the soil.
Using a suitably noncommutative flat matrix model, it is shown that the quantum permutation group has free orbitals: that is, a monomial in the generators of the algebra of functions can be zero for ...trivial reasons only. It is shown that any strictly intermediate quantum subgroup between the classical and quantum permutation groups must have free three-orbitals, and this is used to derive some elementary bounds for the Haar state on degree four monomials in such quantum permutation groups. Exploiting the main character, explicit formulae are given in the case of the quantum permutation group.
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