Characterization of Fine Particulate Matter (PM) and Secondary PM Precursor Gases in Mexico City

This project was one of three collaborating grants designed to understand the atmospheric chemistry and aerosol particle microphysics impacting air quality in the Mexico City Metropolitan Area (MCMA) and its urban plume. The overall effort, titled MCMA- 2006, focused on: 1) the primary emissions of fine particles and precursor gases leading to photochemical production of atmospheric oxidants and secondary aerosol particles and 2) the measurement and analysis of secondary oxidants and secondary fine particular matter (PM) production, with particular emphasis on secondary organic aerosol (SOA). MCAM-2006 pursued it goals through three main activities: 1) performance and publication of detailed analyses of extensive MCMA trace gas and fine PM measurements made by the collaborating groups and others during earlier MCMA field campaigns in 2002 and 2003; 2) deployment and utilization of extensive real-time trace gas and fine PM instrumentation at urban and downwind MCMA sites in support of the MAX-Mex/MILAGRO field measurements in March, 2006; and, 3) analyses of the 2006 MCMA data sets leading to further publications that are based on new data as well as insights from analysis and publication of the 2002/2003 field data. Thirteen archival publications were coauthored with other MCMA-2003 participants. Documented findings included a significantly improved speciated emissions inventory from on-road vehicles, a greatly enhanced understanding of the sources and atmospheric loadings of volatile organic compounds, a unique analysis of the high fraction of ambient formaldehyde from primary emission sources, a much more extensive knowledge of the composition, size distributions and atmospheric mass loadings of both primary and secondary fine PM, including the fact that the rate of MCMA SOA production greatly exceeded that predicted by current atmospheric models, and evaluations of significant errors that can arise from standard air quality monitors for ozone and nitrogen dioxide. Deployment of the Aerodyne mobile laboratory, equipped with instruments from five collaborating laboratories, at the T0 urban supersite, four downwind sites and the Tula industrial area yielded unique trace gas and fine PM data sets during the March 2006 MAXMex/MILAGRO campaign. In addition, on-road measurements as the mobile laboratory moved between sites provided extensive data on 2006 MCMA fleet averaged vehicle emissions. Analyses of 2006 data sets have yielded the identification of a close correlation between the rate of production of SOA and “Odd Oxygen” (O3 + NO2) and primary organic PM with CO in the MCMA urban plume, a more sophisticated understanding of the interplay between nitrogen oxide speciation and ozone production, the identification of significant vehicular emission sources of HCN and CH3CN (usually associated with biomass burning), characterization of the aging of primary carbonaceous PM, and updated 2006 MCMA fleet on-road trace gas and fine PM emissions. Results from analyses of 2002/2003 and 2006 emissions and ambient measurements have conveyed to Mexican air quality managers who are using these data to devise and assess air quality management strategies. All data sets and published analyses are available to DOE/ASP researchers evaluating the impact of urban emissions on regional climate

ATTR amyloidosis during the COVID-19 pandemic: insights from a global medical roundtable

BACKGROUND: The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing the ongoing coronavirus disease 2019 (COVID-19) pandemic has raised serious concern for patients with chronic disease. A correlation has been identified between the severity of COVID-19 and a patient's preexisting comorbidities. Although COVID-19 primarily involves the respiratory system, dysfunction in multiple organ systems is common, particularly in the cardiovascular, gastrointestinal, immune, renal, and nervous systems. Patients with amyloid transthyretin (ATTR) amyloidosis represent a population particularly vulnerable to COVID-19 morbidity due to the multisystem nature of ATTR amyloidosis. MAIN BODY: ATTR amyloidosis is a clinically heterogeneous progressive disease, resulting from the accumulation of amyloid fibrils in various organs and tissues. Amyloid deposition causes multisystem clinical manifestations, including cardiomyopathy and polyneuropathy, along with gastrointestinal symptoms and renal dysfunction. Given the potential for exacerbation of organ dysfunction, physicians note possible unique challenges in the management of patients with ATTR amyloidosis who develop multiorgan complications from COVID-19. While the interplay between COVID-19 and ATTR amyloidosis is still being evaluated, physicians should consider that the heightened susceptibility of patients with ATTR amyloidosis to multiorgan complications might increase their risk for poor outcomes with COVID-19. CONCLUSION: Patients with ATTR amyloidosis are suspected to have a higher risk of morbidity and mortality due to age and underlying ATTR amyloidosis-related organ dysfunction. While further research is needed to characterize this risk and management implications, ATTR amyloidosis patients might require specialized management if they develop COVID-19. The risks of delaying diagnosis or interrupting treatment for patients with ATTR amyloidosis should be balanced with the risk of exposure in the health care setting. Both physicians and patients must adapt to a new construct for care during and possibly after the pandemic to ensure optimal health for patients with ATTR amyloidosis, minimizing treatment interruptions

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Afferents to the midbrain auditory center in the bullfrog, Rana catesbeiana

Horseradish peroxidase (HRP) histochemistry was used to visualize cells afferent to the bullfrog torus semicircularis. These afferent cells are located in several sensory and nonsensory nuclei. The sensory structures which project to the torus are mainly auditory nuclei, with the major input coming from the ipsilateral superior olive. A very small contralateral projection is also present. In addition, afferents arise from the contralateral, and to a lesser extent ipsilateral, dorsal acoustic nucleus and nucleus caudalis, both primary eighth nerve nuclei. A vestibular input is also apparent in that HRP-positive cells were seen in the magnocellular vestibular nucleus and among elongated bipolar cells at the ventral border of the eighth nerve nuclei. In addition, the torus receives somatosensory input from the contralateral perisolitary band. Afferents from spinal cord cells proved difficult to visualize. Nonsensory areas throughout the brain innervate the torus as well. In the medulla, HRP-positive cells were present bilaterally in both medial and lateral reticular areas. The tegmentum contributes a major input from the superficial isthmal reticular nucleus and a minor input from the tegmental fields. Commissural toral projections are also present. Descending forebrain input arises from the pretectal gray bilaterally, the ventral half of the ipsilateral lateral pretectal nucleus, and, possibly, from the ipsilateral posterior thalamic nucleus. HRP-positive cells were also occasionally seen in the posterior tuberculum, ventral hypothalamus, and caudal suprachiasmatic preoptic area. Finally, a telencephalic projection from the ipsilateral anterior entopeduncular nucleus is present.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50015/1/901980304_ftp.pd

Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population

Background: Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP).   Methods: A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods. Results: Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p&lt;0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p&lt;0.001), alcohol intake (p = 0.003) and CRP (p&lt;0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p&lt;0.001).   Conclusions: In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP  Original Publication: Peter Garvin, Lennart Nilsson, John Carstensen, Lena Jonasson and Margareta Kristenson, Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population, 2008, PLoS ONE, (3), 3, e1774. http://dx.doi.org/10.1371/journal.pone.0001774 Licensee: Public Library of Science (PLoS) http://www.plos.org/</p

Implication of NOD1 and NOD2 for the Differentiation of Multipotent Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood

Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are known to trigger an innate immune response against microbial infection. Although studies suggest that activation of TLRs modulate the function of mesenchymal stem cells (MSCs), little is known about the role of NLRs on the MSC function. In this study, we investigated whether NOD1 and NOD2 regulate the functions of human umbilical cord blood-derived MSCs (hUCB-MSCs). The genes of TLR2, TLR4, NOD1, and NOD2 were expressed in hUCB-MSCs. Stimulation with each agonist (Pam3CSK4 for TLR2, LPS for TLR4, Tri-DAP for NOD1, and MDP for NOD2) led to IL-8 production in hUCB-MSC, suggesting the expressed receptors are functional in hUCB-MSC. CCK-8 assay revealed that none of agonist influenced proliferation of hUCB-MSCs. We next examined whether TLR and NLR agonists affect osteogenic-, adipogenic-, and chondrogenic differentiation of hUCB-MSCs. Pam3CSK4 and Tri-DAP strongly enhanced osteogenic differentiation and ERK phosphorylation in hUCB-MSCs, and LPS and MDP also slightly did. Treatment of U0126 (MEK1/2 inhibitor) restored osteogenic differentiation enhanced by Pam3CSK4. Tri-DAP and MDP inhibited adipogenic differentiation of hUCB-MSCs, but Pam3CSK4 and LPS did not. On chondrogenic differentiation, all TLR and NLR agonists could promote chondrogenesis of hUCB-MSCs with difference in the ability. Our findings suggest that NOD1 and NOD2 as well as TLRs are involved in regulating the differentiation of MSCs

Regression with Empirical Variable Selection: Description of a New Method and Application to Ecological Datasets

Despite recent papers on problems associated with full-model and stepwise regression, their use is still common throughout ecological and environmental disciplines. Alternative approaches, including generating multiple models and comparing them post-hoc using techniques such as Akaike's Information Criterion (AIC), are becoming more popular. However, these are problematic when there are numerous independent variables and interpretation is often difficult when competing models contain many different variables and combinations of variables. Here, we detail a new approach, REVS (Regression with Empirical Variable Selection), which uses all-subsets regression to quantify empirical support for every independent variable. A series of models is created; the first containing the variable with most empirical support, the second containing the first variable and the next most-supported, and so on. The comparatively small number of resultant models (n = the number of predictor variables) means that post-hoc comparison is comparatively quick and easy. When tested on a real dataset – habitat and offspring quality in the great tit (Parus major) – the optimal REVS model explained more variance (higher R2), was more parsimonious (lower AIC), and had greater significance (lower P values), than full, stepwise or all-subsets models; it also had higher predictive accuracy based on split-sample validation. Testing REVS on ten further datasets suggested that this is typical, with R2 values being higher than full or stepwise models (mean improvement = 31% and 7%, respectively). Results are ecologically intuitive as even when there are several competing models, they share a set of “core” variables and differ only in presence/absence of one or two additional variables. We conclude that REVS is useful for analysing complex datasets, including those in ecology and environmental disciplines

Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3(-/-) mice, but not wildtype mice.

Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3(-/-) mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3(-/-)) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not. Per3(-/-) mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3(-/-) nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3(-/-) phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light