Argonaute2 regulates the pancreatic β-cell secretome

Argonaute2 (Ago2) is an established component of the microRNA-induced silencing complex. Similar to miR-375 loss-of-function studies, inhibition of Ago2 in the pancreatic beta-cell resulted in enhanced insulin release underlining the relationship between these two genes. Moreover, as the most abundant microRNA in pancreatic endocrine cells, miR-375 was also observed to be enriched in Ago2-associated complexes. Both Ago2 and miR-375 regulate the pancreatic beta-cell secretome and we identified using quantitative mass spectrometry the enhanced release of a set of proteins or secretion signature in response to a glucose stimulus using the murine beta-cell line, MIN6. In addition, loss of Ago2 resulted in the increased expression of miR-375 target genes, including gephyrin and ywhaz. These targets positively contribute to exocytosis indicating they may mediate the functional role of both miR-375 and Ago proteins in the pancreatic beta-cell by influencing the secretory pathway. This study specifically addresses the role of Ago2 in the systemic release of proteins from beta-cells and highlights the contribution of the microRNA pathway to the function of this cell type

Initiation and Polymer Density of Conjugated Polymer Brushes

The growth mechanism and polymer density in conjugated polymer brush (CPB) films composed of poly(3-methylthiophene) (P3MT) are characterized. X-ray photoelectron spectroscopy experiments show that the initiation of aryl halide monolayers by Pd(PtBu3)2 produces disproportionated monolayer initiators. Unlike disproportionated species formed during the solution-phase initiation of aryl halides, which cannot mediate polymerization, the surface-bound initiators catalyze polymerization to form CPB films with a high grafting density (1.2 nm-2). Rutherford backscattering spectrometry (RBS) experiments show that P3MT CPB films have a characteristic monomer volume density (3.7 nm-3) that is indistinguishable from the volume density of spuncast poly(3-hexylthiophene) films. Using these RBS and XPS results, characteristics of P3MT CPB growth are obtained, including the turnover frequency (7.5 h-1) and polymer molecular weight (300 g/mol·nm)

Dynamical effects of the nanometer-sized polarized domains in Pb(Zn1/3Nb2/3)O3

Recent neutron scattering measurements performed on the relaxor ferroelectric Pb[(Zn1/3Nb2/3)0.92Ti0.08]O3 (PZN-8%PT) in its cubic phase at 500 K, have revealed an anomalous ridge of inelastic scattering centered ~0.2 A-1 from the zone center (Gehring et al., Phys. Rev. Lett. 84, 5216 (2000)). This ridge of scattering resembles a waterfall when plotted as a phonon dispersion diagram, and extends vertically from the transverse acoustic (TA) branch near 4 meV to the transverse optic (TO) branch near 9 meV. No zone center optic mode was found. We report new results from an extensive neutron scattering study of pure PZN that exhibits the same waterfall feature. We are able to model the dynamics of the waterfall using a simple coupled-mode model that assumes a strongly q-dependent optic mode linewidth Gamma1(q) that increases sharply near 0.2 A-1 as one approaches the zone center. This model was motivated by the results of Burns and Dacol in 1983, who observed the formation of a randomly-oriented local polarization in PZN at temperatures far above its ferroelectric phase transition temperature. The dramatic increase in Gamma1 is believed to occur when the wavelength of the optic mode becomes comparable to the size of the small polarized micro-regions (PMR) associated with this randomly-oriented local polarization, with the consequence that longer wavelength optic modes cannot propagate and become overdamped. Below Tc=410 K, the intensity of the waterfall diminishes. At lowest temperatures ~30 K the waterfall is absent, and we observe the recovery of a zone center transverse optic mode near 10.5 meV.Comment: 8 pages, 9 figures (one color). Submitted to Physical Review

Seroincidence of SARS-CoV-2 infection prior to and during the rollout of vaccines in a community-based prospective cohort of U.S. adults

This study used repeat serologic testing to estimate infection rates and risk factors in two overlapping cohorts of SARS-CoV-2 N protein seronegative U.S. adults. One mostly unvaccinated sub-cohort was tracked from April 2020 to March 2021 (pre-vaccine/wild-type era, n = 3421), and the other, mostly vaccinated cohort, from March 2021 to June 2022 (vaccine/variant era, n = 2735). Vaccine uptake was 0.53% and 91.3% in the pre-vaccine and vaccine/variant cohorts, respectively. Corresponding seroconversion rates were 9.6 and 25.7 per 100 person-years. In both cohorts, sociodemographic and epidemiologic risk factors for infection were similar, though new risk factors emerged in the vaccine/variant era, such as having a child in the household. Despite higher incidence rates in the vaccine/variant cohort, vaccine boosters, masking, and social distancing were associated with substantially reduced infection risk, even through major variant surges

Phenomenology of the Lense-Thirring effect in the Solar System

Recent years have seen increasing efforts to directly measure some aspects of the general relativistic gravitomagnetic interaction in several astronomical scenarios in the solar system. After briefly overviewing the concept of gravitomagnetism from a theoretical point of view, we review the performed or proposed attempts to detect the Lense-Thirring effect affecting the orbital motions of natural and artificial bodies in the gravitational fields of the Sun, Earth, Mars and Jupiter. In particular, we will focus on the evaluation of the impact of several sources of systematic uncertainties of dynamical origin to realistically elucidate the present and future perspectives in directly measuring such an elusive relativistic effect.Comment: LaTex, 51 pages, 14 figures, 22 tables. Invited review, to appear in Astrophysics and Space Science (ApSS). Some uncited references in the text now correctly quoted. One reference added. A footnote adde

Prediction of major depressive disorder following beta-blocker therapy in patients with cardiovascular diseases

Incident depression has been reported to be associated with poor prognosis in patients with cardiovascular disease (CVD), which might be associated with beta-blocker therapy. Because early detection and intervention can alleviate the severity of depression, we aimed to develop a machine learning (ML) model predicting the onset of major depressive disorder (MDD). A model based on L1 regularized logistic regression was trained against the South Korean nationwide administrative claims database to identify risk factors for the incident MDD after beta-blocker therapy in patients with CVD. We identified 50,397 patients initiating beta-blockers for CVD, with 774 patients developing MDD within 365 days after initiating beta-blocker therapy. An area under the receiver operating characteristic curve (AUC) of 0.74 was achieved. A history of non-selective beta-blockers and factors related to anxiety disorder, sleeping problems, and other chronic diseases were the most strong predictors. AUCs of 0.62–0.71 were achieved in the external validation conducted on six independent electronic health records and claims databases in the USA and South Korea. In conclusion, an ML model that identifies patients at high-risk for incident MDD was developed. Application of ML to identify susceptible patients for adverse events of treatment may serve as an important approach for personalized medicine

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe