12/15-Lipoxygenase Is Required for the Early Onset of High Fat Diet-Induced Adipose Tissue Inflammation and Insulin Resistance in Mice

Recent understanding that insulin resistance is an inflammatory condition necessitates searching for genes that regulate inflammation in insulin sensitive tissues. 12/15-lipoxygenase (12/15LO) regulates the expression of proinflammatory cytokines and chemokines and is implicated in the early development of diet-induced atherosclerosis. Thus, we tested the hypothesis that 12/15LO is involved in the onset of high fat diet (HFD)-induced insulin resistance.Cells over-expressing 12/15LO secreted two potent chemokines, MCP-1 and osteopontin, implicated in the development of insulin resistance. We assessed adipose tissue inflammation and whole body insulin resistance in wild type (WT) and 12/15LO knockout (KO) mice after 2-4 weeks on HFD. In adipose tissue from WT mice, HFD resulted in recruitment of CD11b(+), F4/80(+) macrophages and elevated protein levels of the inflammatory markers IL-1beta, IL-6, IL-10, IL-12, IFNgamma, Cxcl1 and TNFalpha. Remarkably, adipose tissue from HFD-fed 12/15LO KO mice was not infiltrated by macrophages and did not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. WT mice developed severe whole body (hepatic and skeletal muscle) insulin resistance after HFD, as measured by hyperinsulinemic euglycemic clamp. In contrast, 12/15LO KO mice exhibited no HFD-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output during clamp studies. Insulin-stimulated Akt phosphorylation in muscle tissue from HFD-fed mice was significantly greater in 12/15LO KO mice than in WT mice.These results demonstrate that 12/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding

Osteopontin Is Required for the Early Onset of High Fat Diet-Induced Insulin Resistance in Mice

Insulin resistance is manifested in muscle, adipose tissue, and liver and is associated with adipose tissue inflammation. The cellular components and mechanisms that regulate the onset of diet-induced insulin resistance are not clearly defined.We initially observed osteopontin (OPN) mRNA over-expression in adipose tissue of obese, insulin resistant humans and rats which was normalized by thiazolidinedione (TZD) treatment in both species. OPN regulates inflammation and is implicated in pathogenic maladies resulting from chronic obesity. Thus, we tested the hypothesis that OPN is involved in the early development of insulin resistance using a 2-4 week high fat diet (HFD) model. OPN KO mice fed HFD for 2 weeks were completely protected from the severe skeletal muscle, liver and adipose tissue insulin resistance that developed in wild type (WT) controls, as determined by hyperinsulinemic euglycemic clamp and acute insulin-stimulation studies. Although two-week HFD did not alter body weight or plasma free fatty acids and cytokines in either strain, HFD-induced hyperleptinemia, increased adipose tissue inflammation (macrophages and cytokines), and adipocyte hypertrophy were significant in WT mice and blunted or absent in OPN KO mice. Adipose tissue OPN protein isoform expression was significantly altered in 2- and 4-week HFD-fed WT mice but total OPN protein was unchanged. OPN KO bone marrow stromal cells were more osteogenic and less adipogenic than WT cells in vitro. Interestingly, the two differentiation pathways were inversely affected by HFD in WT cells in vitro.The OPN KO phenotypes we report reflect protection from insulin resistance that is associated with changes in adipocyte biology and adipose tissue inflammatory status. OPN is a key component in the development of HFD-induced insulin resistance

CSF biomarkers for dementia

Although cerebrospinal fluid (CSF) biomarker testing is incorporated into some current guidelines for the diagnosis of dementia (such as England's National Institute for Health and Care Excellence (NICE)), it is not widely accessible for most patients for whom biomarkers could potentially change management. Here we share our experience of running a clinical cognitive CSF service and discuss recent developments in laboratory testing including the use of the CSF amyloid-β 42/40 ratio and automated assay platforms. We highlight the importance of collaborative working between clinicians and laboratory staff, of preanalytical sample handling, and discuss the various factors influencing interpretation of the results in appropriate clinical contexts. We advocate for broadening access to CSF biomarkers by sharing clinical expertise, protocols and interpretation with colleagues working in psychiatry and elderly care, especially when access to CSF may be part of a pathway to disease-modifying treatments for Alzheimer's disease and other forms of dementia

Surface gravity waves in deep fluid at vertical shear flows

Special features of surface gravity waves in deep fluid flow with constant vertical shear of velocity is studied. It is found that the mean flow velocity shear leads to non-trivial modification of surface gravity wave modes dispersive characteristics. Moreover, the shear induces generation of surface gravity waves by internal vortex mode perturbations. The performed analytical and numerical study provides, that surface gravity waves are effectively generated by the internal perturbations at high shear rates. The generation is different for the waves propagating in the different directions. Generation of surface gravity waves propagating along the main flow considerably exceeds the generation of surface gravity waves in the opposite direction for relatively small shear rates, whereas the later wave is generated more effectively for the high shear rates. From the mathematical point of view the wave generation is caused by non self-adjointness of the linear operators that describe the shear flow.Comment: JETP, accepte

[CII] 158 micron Luminosities and Star Formation Rate in Dusty Starbursts and AGN

Results are presented for [CII] 158 micron line fluxes observed with the Herschel PACS instrument in 112 sources with both starburst and AGN classifications, of which 102 sources have confident detections. Results are compared with mid-infrared spectra from the Spitzer Infrared Spectrometer and with L(IR) from IRAS fluxes; AGN/starburst classifications are determined from equivalent width of the 6.2 micron PAH feature. It is found that the [CII] line flux correlates closely with the flux of the 11.3 micron PAH feature independent of AGN/starburst classification, log [f([CII] 158 micron)/f(11.3 micron PAH)] = -0.22 +- 0.25. It is concluded that [CII] line flux measures the photodissociation region associated with starbursts in the same fashion as the PAH feature. A calibration of star formation rate for the starburst component in any source having [CII] is derived comparing [CII] luminosity L([CII]) to L(IR) with the result that log SFR = log L([CII)]) - 7.08 +- 0.3, for SFR in solar masses per year and L([CII]) in solar luminosities. The decreasing ratio of L([CII]) to L(IR) in more luminous sources (the "[CII] deficit") is shown to be a consequence of the dominant contribution to L(IR) arising from a luminous AGN component because the sources with largest L(IR) and smallest L([CII])/L(IR) are AGN.Comment: Accepted for publication in The Astrophysical Journa

30 days wild: development and evaluation of a large-scale nature engagement campaign to improve well-being

There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature

Adoption of Global Investment Performance Standards: Case of ASEAN

Research on voluntary compliance with accepted international standards has paid overwhelming attention to financial reporting standards, but not to investment performance standards. Previous research on the adoption of the Global Investment Performance Standards has overlooked the unique region of the Association of Southeast Asian Nations. Using 17 years (1999 to 2015) worth of data from all ten countries, which generates 170 country-year observations for each variable of the study, this paper evaluates whether, and how, social and economic pressures influence the adoption of GIPS in the region in the Institutional Theory lens. The results suggest that social pressure is more impactful than economic pressure on the adoption of GIPS. The findings have generated useful contributions and implications in this vein, and several future research directions have been identified. Keywords: Global Investment Performance Standards (GIPS); ASEAN; investment profession; regional integration; voluntary adoption; sustainability reporting; Chartered Financial Analyst (CFA). JEL classification: G11, G15, N95, P1

Cerebrospinal fluid in the differential diagnosis of Alzheimer's disease: clinical utility of an extended panel of biomarkers in a specialist cognitive clinic.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias. METHODS: We used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls. Patients fulfilled consensus criteria for AD (n = 156), DLB (n = 20), behavioural variant frontotemporal dementia (bvFTD; n = 45), progressive non-fluent aphasia (PNFA; n = 17), and semantic dementia (SD; n = 7); approximately 10% were pathology/genetically confirmed (n = 26). Global tests based on generalised least squares regression were used to determine differences between groups. Non-parametric receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses were used to quantify how well each biomarker discriminated AD from each of the other diagnostic groups (or combinations of groups). CSF cut-points for the major biomarkers found to have diagnostic utility were validated using an independent cohort which included causes of AD (n = 104), DLB (n = 5), bvFTD (n = 12), PNFA (n = 3), SD (n = 9), and controls (n = 10). RESULTS: There were significant global differences in Aβ1-42, T-tau, T-tau/Aβ1-42 ratio, P-tau-181, NFL, AβX-42, AβX-42/X-40 ratio, APPα, and APPβ between groups. At a fixed sensitivity of 85%, AβX-42/X-40 could differentiate AD from controls, bvFTD, and SD with specificities of 93%, 85%, and 100%, respectively; for T-tau/Aβ1-42 these specificities were 83%, 70%, and 86%. AβX-42/X-40 had similar or higher specificity than Aβ1-42. No biomarker or ratio could differentiate AD from DLB or PNFA with specificity > 50%. Similar sensitivities and specificities were found in the independent validation cohort for differentiating AD and other dementias and in a pathology/genetically confirmed sub-cohort. CONCLUSIONS: CSF AβX-42/X-40 and T-tau/Aβ1-42 ratios have utility in distinguishing AD from controls, bvFTD, and SD. None of the biomarkers tested had good specificity at distinguishing AD from DLB or PNFA

Evidence for the exclusive decay Bc+- to J/psi pi+- and measurement of the mass of the Bc meson

We report first evidence for a fully reconstructed decay mode of the B_c^{\pm} meson in the channel B_c^{\pm} \to J/psi \pi^{\pm}, with J/psi \to mu^+mu^-. The analysis is based on an integrated luminosity of 360 pb$^{-1} in p\bar{p} collisions at 1.96 TeV center of mass energy collected by the Collider Detector at Fermilab. We observe 14.6 \pm 4.6 signal events with a background of 7.1 \pm 0.9 events, and a fit to the J/psi pi^{\pm} mass spectrum yields a B_c^{\pm} mass of 6285.7 \pm 5.3(stat) \pm 1.2(syst) MeV/c^2. The probability of a peak of this magnitude occurring by random fluctuation in the search region is estimated as 0.012%.Comment: 7 pages, 3 figures. Version 3, accepted by PR

Top quark mass measurement using the template method at CDF

We present a measurement of the top quark mass in the lepton+jets and dilepton channels of $t\bar{t}$ decays using the template method. The data sample corresponds to an integrated luminosity of 5.6 fb$^{-1}$ of $p\bar{p}$ collisions at Tevatron with $\sqrt{s}=1.96$ TeV, collected with the CDF II detector. The measurement is performed by constructing templates of three kinematic variables in the lepton+jets and two kinematic variables in the dilepton channel. The variables are two reconstructed top quark masses from different jets-to-quarks combinations and the invariant mass of two jets from the $W$ decay in the lepton+jets channel, and a reconstructed top quark mass and $m_{T2}$, a variable related to the transverse mass in events with two missing particles, in the dilepton channel. The simultaneous fit of the templates from signal and background events in the lepton+jets and dilepton channels to the data yields a measured top quark mass of $M_{top} = 172.1 \pm 1.1(stat) \pm 0.9(syst).$Comment: submitted to Phys. Rev.