The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest. Following its well-cited 2010 critical review, the Health Effects Institute (HEI) ...appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected adverse health outcomes. Health outcomes were selected based on evidence of causality for general air pollution (broader than TRAP) cited in authoritative reviews, relevance for public health and policy, and resources available.
The Panel used a systematic approach to search the literature, select studies for inclusion in the review, assess study quality, summarize results, and reach conclusions about the confidence in the evidence. An extensive search was conducted of literature published between January 1980 and July 2019 on selected health outcomes. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP.
In total, 353 studies were included in the review. Respiratory effects in children (118 studies) and birth outcomes (86 studies) were the most commonly studied outcomes. Fewer studies investigated cardiometabolic effects (57 studies), respiratory effects in adults (50 studies), and mortality (48 studies).
The findings from the systematic review, meta-analyses, and evaluation of the quality of the studies and potential biases provided an overall high or moderate-to-high level of confidence in an association between long-term exposure to TRAP and the adverse health outcomes all-cause, circulatory, ischemic heart disease and lung cancer mortality, asthma onsetin chilldren and adults, and acute lower respiratory infections in children. The evidence was considered moderate, low or very low for the other selected outcomes.
In light of the large number of people exposed to TRAP – both in and beyond the near-road environment - the Panel concluded that the overall high or moderate-to-high confidence in the evidence for an association between long-term exposure to TRAP and several adverse health outcomes indicates that exposures to TRAP remain an important public health concern and deserve greater attention from the public and from policymakers.
Selecting particles from digital micrographs is an essential step in single-particle electron cryomicroscopy (cryo-EM). As manual selection of complete datasets-typically comprising thousands of ...particles-is a tedious and time-consuming process, numerous automatic particle pickers have been developed. However, non-ideal datasets pose a challenge to particle picking. Here we present the particle picking software crYOLO which is based on the deep-learning object detection system You Only Look Once (YOLO). After training the network with 200-2500 particles per dataset it automatically recognizes particles with high recall and precision while reaching a speed of up to five micrographs per second. Further, we present a general crYOLO network able to pick from previously unseen datasets, allowing for completely automated on-the-fly cryo-EM data preprocessing during data acquisition. crYOLO is available as a standalone program under http://sphire.mpg.de/ and is distributed as part of the image processing workflow in SPHIRE.
Elimination of suitable leaving groups from 3-substituted indoles under basic or acidic conditions readily provides alkylideneindolenine intermediates that may react with a large variety of ...nucleophilic reagents. This article highlights some recent developments of this synthetic approach for the preparation of functionalized indole derivatives.
Proline strikes again: The intermolecular enamine‐catalyzed asymmetric “formal” α‐alkylation of aldehydes is described. Alkylating reagent 1 generates a highly stabilized carbocation, which can ...readily intercept the enamine intermediate. L‐Proline proved to be the best catalyst, providing an easy route to relevant 3‐indolyl derivatives 2 with high diastereo‐ and enantiocontrol.
Neurogenesis persists in the adult brain and can contribute to learning and memory processes and potentially to regeneration and repair of the affected nervous system. Deregulated neurogenesis has ...been observed in neuropathological conditions including neurodegenerative diseases, trauma and stroke. However, the survival of neural precursor cells (NPCs) and newly born neurons is adversely affected by the inflammatory environment that arises as a result of microglial activation associated with injury or disease processes. In the present study, we have investigated the mechanisms by which microglia affect NPC proliferation and survival. Importantly, we demonstrate that interleukin-1β (IL-1β) produced by lipopolysaccharide/interferon-γ-activated microglia is necessary to induce cell cycle arrest and apoptosis in NPCs in vitro. Mechanistically, we show that IL-1β activates the tumor suppressor p53 through an oxidative stress-dependent mechanism resulting in p53-mediated induction of the cyclin-dependent kinase inhibitor p21 and the proapoptotic Bcl-2 (B-cell lymphoma-2) family members Puma (p53-upregulated modulator of apoptosis) and Noxa. Furthermore, we demonstrate that cell cycle arrest and apoptosis induced by recombinant IL-1β or activated microglia is attenuated in p53-deficient NPCs. Finally, we have determined that IL-1β induces NPC death via the p53-dependent induction of Puma leading to the activation of a Bax (Bcl-2-associated X protein)-mediated mitochondrial apoptotic pathway. In summary, we have elucidated a novel role for p53 in the regulation of NPC proliferation and survival during neuroinflammatory conditions that could be targeted to promote neurogenesis and repair in a number of neurological conditions.
Summary
B‐1 and B‐2 B cell subsets carry out a diverse array of functions that range broadly from responding to innate stimuli, antigen presentation, cytokine secretion and antibody production. In ...this review, we first cover the functional roles of the major murine B cell subsets. We then highlight emerging evidence, primarily in preclinical rodent studies, to show that select B cell subsets are a therapeutic target in obesity and its associated co‐morbidities. High fat diets promote accumulation of select murine B cell phenotypes in visceral adipose tissue. As a consequence, B cells exacerbate inflammation and thereby insulin sensitivity through the production of autoantibodies and via cross‐talk with select adipose resident macrophages, CD4+ and CD8+ T cells. In contrast, interleukin (IL)‐10‐secreting regulatory B cells counteract the proinflammatory profile and improve glucose sensitivity. We subsequently review data from rodent studies that show pharmacological supplementation of obesogenic diets with long chain n‐3 polyunsaturated fatty acids or specialized pro‐resolving lipid mediators synthesized from endogenous n‐3 polyunsaturated fatty acids boost B cell activation and antibody production. This may have potential benefits for improving inflammation in addition to combating the increased risk of viral infection that is an associated complication of obesity and type II diabetes. Finally, we propose potential underlying mechanisms throughout the review by which B cell activity could be differentially regulated in response to high fat diets.
Abstract Background Fruit and vegetable (F/V) intake assessment tools that are valid, reliable, brief, and easy to administer and code are vital to the field of public health nutrition. Objective To ...evaluate three short F/V intake screeners (ie, a 2-item serving tool, a 2-item cup tool, and a 16-item F/V intake screener) among adults using multiple 24-hour dietary recalls (24-hour recalls) as the reference instrument and evaluate test–retest reliability of the screeners across a 2- to 3-week time period. Design Validity and reliability study. Participants/setting Two hundred forty-four adults for the validity study and 335 adults for test–retest reliability. Statistical analyses performed Median values for F/V intakes were calculated for the screeners and 24-hour recalls. The Wilcoxon signed rank test was used to compare screeners with the 24-hour recalls. Deattenuated Pearson correlations were reported for validity and intraclass correlation coefficient used for reliability. Results The estimated median daily servings/cups of F/V for the 2-item serving screener was lower, for the 2-item cup screener was equivalent for men but higher for women, and for the 16-item F/V intake screener were about the same when compared with 24-hour recall values. The deattenuated correlations comparing the 24-hour recalls with the screeners were positive but weak for the 2-item serving screener, and were positive and moderate in strength for the 2-item cup and 16-item F/V intake screeners. The test–retest intraclass correlation coefficients were all positive and fairly strong for all of the screeners. Conclusions Although dietary screeners offer a more cost-effective, less burdensome way to obtain gross estimates to rank individuals with regard to F/V intake, these methods are not recommended for assessing precise intake levels.
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•Optical and dielectric properties of l-valine doped ADP crystal.•The SHG efficiency is found to be 1.92 times that of KDP crystal.•High transparency is useful for optoelectronics ...applications.•The lower dielectric characteristics were ascertained from dielectric measurements.•Third order nonlinearity shows its applications for optical limiting and sensor devices.
Single crystal of l-valine doped ammonium dihydrogen phosphate has been grown by slow evaporation method at room temperature. The crystalline nature of the grown crystal was confirmed using powder X-ray diffraction technique. The different functional groups of the grown crystal were identified using Fourier transform infrared analysis. The UV–visible studies were employed to examine the high optical transparency and influential optical constants for tailoring materials suitability for optoelectronics applications. The cutoff wavelength of the title crystal was found to be 280nm with wide optical band gap of 4.7eV. The dielectric measurements were carried to determine the dielectric constant and dielectric loss at room temperature. The grown crystal has been characterized by thermogravimetric analysis. The second harmonic generation efficiency of the grown crystal was determined by the classical Kurtz powder technique and it is found to be 1.92 times that of potassium dihydrogen phosphate. The grown crystal was identified as third order nonlinear optical material employing Z-scan technique using He–Ne laser operating at 632.8nm.
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