2,096 research outputs found
Similarities and differences in structure, expression, and functions of VLDLR and ApoER2
Very Low Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2) are important receptors in the brain for mediating the signaling effects of the extracellular matrix protein Reelin, affecting neuronal function in development and in the adult brain. VLDLR and ApoER2 are members of the low density lipoprotein family, which also mediates the effects of numerous other extracellular ligands, including apolipoprotein E. Although VLDLR and ApoER2 are highly homologous, they differ in a number of ways, including structural differences, expression patterns, alternative splicing, and binding of extracellular and intracellular proteins. This review aims to summarize important aspects of VLDLR and ApoER2 that may account for interesting recent findings that highlight the unique functions of each receptor
How to Block Cartel Formation and Price-Fixing
Abstract written by the AEI-Brookings Joint Center: Allowing foreign buyers of goods produced by international cartels to pursue civil antitrust damages in U.S. courts would better deter cartel formation and price-fixing than do sanctions currently imposed by global criminal and civil justice systems.Technology and Industry, Regulatory Reform, Other Topics
Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model
Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban area in Los Angeles. Male C57BL/6J mice were exposed to either re-aerosolized nPM or filtered air for 5 hours/day, 3 days/week, for 10 weeks (150 hours; n = 18/group). Microglia were characterized by immunohistochemical double staining of ionized calcium-binding protein-1 (Iba-1) with inducible nitric oxide synthase (iNOS) to identify pro-inflammatory cells, and Iba-1 with arginase-1 (Arg) to identify anti-inflammatory/ homeostatic cells. Myelin injury was assessed by degraded myelin basic protein (dMBP). Oligodendrocyte cell counts were evaluated by oligodendrocyte transcription factor 2 (Olig2). Axonal injury was assessed by axonal neurofilament marker SMI-312. iNOS-expressing microglia were significantly increased in the corpus callosum of mice exposed to nPM when compared to those exposed to filtered air (2.2 fold increase; p\u3c0.05). This was accompanied by an increase in dMBP (1.4 fold increase; p\u3c0.05) immunofluorescent density, a decrease in oligodendrocyte cell counts (1.16 fold decrease; p\u3c0.05), and a decrease in neurofilament SMI-312 (1.13 fold decrease; p\u3c0.05) immunofluorescent density. Exposure to nPM results in increased inflammatory microglia, white matter injury, and axonal degradation in the corpus callosum of adult male mice. iNOS-expressing microglia release cytokines and reactive oxygen/ nitrogen species which may further contribute to the white matter damage observed in this model
Impact of Temperature Relative Humidity and Absolute Humidity on the Incidence of Hospitalizations for Lower Respiratory Tract Infections Due to Influenza, Rhinovirus, and Respiratory Syncytial Virus: Results from Community-Acquired Pneumonia Organization (CAPO) International Cohort Study
Abstract
Background: Transmissibility of several etiologies of lower respiratory tract infections (LRTI) may vary based on outdoor climate factors. The objective of this study was to evaluate the impact of outdoor temperature, relative humidity, and absolute humidity on the incidence of hospitalizations for lower respiratory tract infections due to influenza, rhinovirus, and respiratory syncytial virus (RSV).
Methods: This was a secondary analysis of an ancillary study of the Community Acquired Pneumonia Organization (CAPO) database. Respiratory viruses were detected using the Luminex xTAG respiratory viral panel. Climate factors were obtained from the National Weather Service. Adjusted Poisson regression models with robust error variance were used to model the incidence of hospitalization with a LRTI due to: 1) influenza, 2) rhinovirus, and 3) RSV (A and/or B), separately.
Results: A total of 467 hospitalized patients with LRTI were included in the study; 135 (29%) with influenza, 41 (9%) with rhinovirus, and 27 (6%) with RSV (20 RSV A, 7 RSV B). The average, minimum, and maximum absolute humidity and temperatur e variables were associated with hospitalization due to influenza LRTI, while the relative humidity variables were not. None of the climate variables were associated with hospitalization due to rhinovirus or RSV.
Conclusions: This study suggests that outdoor absolute humidity and temperature are associated with hospitalizations due to influenza LRTIs, but not with LRTIs due to rhinovirus or RSV. Understanding factors contributing to the transmission of respiratory viruses may assist in the prediction of future outbreaks and facilitate the development of transmission prevention interventions
Characterization of an Fe≡N−NH_2 Intermediate Relevant to Catalytic N_2 Reduction to NH_3
The ability of certain transition metals to mediate the reduction of N_2 to NH_3 has attracted broad interest in the biological and inorganic chemistry communities. Early transition metals such as Mo and W readily bind N_2 and mediate its protonation at one or more N atoms to furnish M(N_xH_y) species that can be characterized and, in turn, extrude NH_3. By contrast, the direct protonation of Fe–N_2 species to Fe(N_xH_y) products that can be characterized has been elusive. Herein, we show that addition of acid at low temperature to [(TPB)Fe(N_2)][Na(12-crown-4)] results in a new S = 1/2 Fe species. EPR, ENDOR, Mössbauer, and EXAFS analysis, coupled with a DFT study, unequivocally assign this new species as [(TPB)Fe≡N–NH_2]^+, a doubly protonated hydrazido(2−) complex featuring an Fe-to-N triple bond. This unstable species offers strong evidence that the first steps in Fe-mediated nitrogen reduction by [(TPB)Fe(N_2)][Na(12-crown-4)] can proceed along a distal or “Chatt-type” pathway. A brief discussion of whether subsequent catalytic steps may involve early or late stage cleavage of the N–N bond, as would be found in limiting distal or alternating mechanisms, respectively, is also provided
Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma
Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion
Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations
Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I
Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I
Elevated Depression Symptoms, Antidepressant Medicine Use, and Risk of Developing Diabetes During the Diabetes Prevention Program
OBJECTIVE—To assess the association between elevated depression symptoms or antidepressant medicine use on entry to the Diabetes Prevention Program (DPP) and during the study and the risk of developing diabetes during the study.
RESEARCH DESIGN AND METHODS—DPP participants (n = 3,187) in three treatment arms (intensive lifestyle [ILS], metformin [MET], and placebo [PLB]) completed the Beck Depression Inventory (BDI) and reported their use of antidepressant medication at randomization and throughout the study (average duration in study 3.2 years).
RESULTS—When other factors associated with the risk of developing diabetes were controlled, elevated BDI scores at baseline or during the study were not associated with diabetes risk in any arm. Baseline antidepressant use was associated with diabetes risk in the PLB (hazard ratio 2.25 [95% CI 1.38–3.66]) and ILS (3.48 [1.93–6.28]) arms. Continuous antidepressant use during the study (compared with no use) was also associated with diabetes risk in the same arms (PLB 2.60 [1.37–4.94]; ILS 3.39 [1.61–7.13]), as was intermittent antidepressant use during the study in the ILS arm (2.07 [1.18–3.62]). Among MET arm participants, antidepressant use was not associated with developing diabetes.
CONCLUSIONS—A strong and statistically significant association between antidepressant use and diabetes risk in the PLB and ILS arms was not accounted for by measured confounders or mediators. If future research finds that antidepressant use independently predicts diabetes risk, efforts to minimize the negative effects of antidepressant agents on glycemic control should be pursued
Understanding the effect of sheared flow on microinstabilities
The competition between the drive and stabilization of plasma
microinstabilities by sheared flow is investigated, focusing on the ion
temperature gradient mode. Using a twisting mode representation in sheared slab
geometry, the characteristic equations have been formulated for a dissipative
fluid model, developed rigorously from the gyrokinetic equation. They clearly
show that perpendicular flow shear convects perturbations along the field at a
speed we denote by (where is the sound speed), whilst parallel
flow shear enters as an instability driving term analogous to the usual
temperature and density gradient effects. For sufficiently strong perpendicular
flow shear, , the propagation of the system characteristics is
unidirectional and no unstable eigenmodes may form. Perturbations are swept
along the field, to be ultimately dissipated as they are sheared ever more
strongly. Numerical studies of the equations also reveal the existence of
stable regions when , where the driving terms conflict. However, in both
cases transitory perturbations exist, which could attain substantial amplitudes
before decaying. Indeed, for , they are shown to exponentiate
times. This may provide a subcritical route to turbulence in
tokamaks.Comment: minor revisions; accepted to PPC
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