Oxidative Stress and Microglial Cells in Parkinson's Disease

Significant evidence has now been accumulated that microglial cells play a central role in the degeneration of DA neurons in animal models of PD. The oxidative stress response by microglial cells, most notably the activity of the enzyme NADPH oxidase, appears to play a central role in the pathology of PD. This oxidative stress response occurs in microglia through the activation of the ERK signaling pathway by proinflammatory stimuli, leading to the phosphorylation and translocation of the p47phox and p67phox cytosolic subunits, the activation of membrane-bound PHOX, and the production of ROS. Therapeutic anti-inflammatories which prevent DA neurodegeneration in PD, including anti-inflammatory cytokines, morphinan compounds, NADPH oxidase inhibitors, NF-κB inhibitors, and β2-AR agonists, all function to inhibit the activation of the PHOX in microglial cells. These observations suggest a central role for the oxidative stress response in microglial cells as a mediator or regulator of DA neurodegeneration in PD

Food resources of stream macroinvertebrates determined by natural-abundance stable C and N isotopes and a 15N tracer addition

Trophic relationships were examined using natural-abundance 13C and 15N analyses and a 15N-tracer addition experiment in Walker Branch, a 1st-order forested stream in eastern Tennessee. In the 15N-tracer addition experiment, we added 15NH4, to stream water over a 6-wk period In early spring, and measured 15N:14N ratios in different taxa and biomass compartments over distance and time. Samples collected from a station upstream from the 15N addition provided data on natural-abundance 13C:12C and 15N:14N ratios. The natural-abundance 15N analysis proved to be of limited value in identifying food resources of macroinvertebrates because 15N values were not greatly different among food resources. In general, the natural-abundance stable isotope approach was most useful for determining whether epilithon or detritus were important food resources for organisms that may use both (e.g., the snail Elimia clavaeformis), and to provide corroborative evidence of food resources of taxa for which the 15N tracer results were not definitive. The 15N tracer results showed that the mayflies Stenonema spp. and Baetis spp. assimilated primarily epilithon, although Baetis appeared to assimilate a portion of the epilithon (e.g., algal cells) with more rapid N turnover than the bulk pool sampled. Although Elimia did not reach isotopic equilibrium during the tracer experiment, application of a N-turnover model to the field data suggested that it assimilated a combination of epilithon and detritus. The amphipod Gammarus minus appeared to depend mostly on fine benthic organic matter (FBOM), and the coleopteran Anchytarsus bicolor on epixylon. The caddisfly Diplectrona modesta appeared to assimilate primarily a fast N-turnover portion of the FBOM pool, and Simuliidae a fast N- turnover component of the suspended particulate organic matter pool rather than the bulk pool sampled. Together, the natural-abundance stable C and N isotope analyses and the experimental 15N tracer approach proved to be very useful tools for identifying food resources in this stream ecosystem

NITROGEN CYCLING IN A FOREST STREAM DETERMINED BY A 15N TRACER ADDITION

Nitrogen uptake and cycling was examined using a six‐week tracer addition of 15N‐labeled ammonium in early spring in Walker Branch, a first‐order deciduous forest stream in eastern Tennessee. Prior to the 15N addition, standing stocks of N were determined for the major biomass compartments. During and after the addition, 15N was measured in water and in dominant biomass compartments upstream and at several locations downstream. Residence time of ammonium in stream water (5–6 min) and ammonium uptake lengths (23–27 m) were short and relatively constant during the addition. Uptake rates of NH4 were more variable, ranging from 22 to 37 μg N·m−2·min−1 and varying directly with changes in streamwater ammonium concentration (2.7–6.7 μg/L). The highest rates of ammonium uptake per unit area were by the liverwort Porella pinnata, decomposing leaves, and fine benthic organic matter (FBOM), although epilithon had the highest N uptake per unit biomass N. Nitrification rates and nitrate uptake lengths and rates were determined by fitting a nitrification/nitrate uptake model to the longitudinal profiles of 15N‐NO3 flux. Nitrification was an important sink for ammonium in stream water, accounting for 19% of the total ammonium uptake rate. Nitrate production via coupled regeneration/nitrification of organic N was about one‐half as large as nitrification of streamwater ammonium. Nitrate uptake lengths were longer and more variable than those for ammonium, ranging from 101 m to infinity. Nitrate uptake rate varied from 0 to 29 μg·m−2·min−1 and was ∼1.6 times greater than assimilatory ammonium uptake rate early in the tracer addition. A sixfold decline in instream gross primary production rate resulting from a sharp decline in light level with leaf emergence had little effect on ammonium uptake rate but reduced nitrate uptake rate by nearly 70%. At the end of the addition, 64–79% of added 15N was accounted for, either in biomass within the 125‐m stream reach (33–48%) or as export of 15N‐NH4 (4%), 15N‐NO3 (23%), and fine particulate organic matter (4%) from the reach. Much of the 15N not accounted for was probably lost downstream as transport of particulate organic N during a storm midway through the experiment or as dissolved organic N produced within the reach. Turnover rates of a large portion of the 15N taken up by biomass compartments were high (0.04–0.08 per day), although a substantial portion of the 15N in Porella (34%), FBOM (21%), and decomposing wood (17%) at the end of the addition was retained 75 d later, indicating relatively long‐term retention of some N taken up from water. In total, our results showed that ammonium retention and nitrification rates were high in Walker Branch, and that the downstream loss of N was primarily as nitrate and was controlled largely by nitrification, assimilatory demand for N, and availability of ammonium to meet that demand. Our results are consistent with recent 15N tracer experiments in N‐deficient forest soils that showed high rates of nitrification and the importance of nitrate uptake in regulating losses of N. Together these studies demonstrate the importance of 15N tracer experiments for improving our understanding of the complex processes controlling N cycling and loss in ecosystems

Measuring Population Transmission Potential for HIV: An Alternative Metric of Transmission Risk in Men who have Sex with Men (MSM) in the US

Background Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities. Methods and Findings Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. …See full text for complete abstract

Multi-Player Quantum Games

Recently the concept of quantum information has been introduced into game theory. Here we present the first study of quantum games with more than two players. We discover that such games can possess a new form of equilibrium strategy, one which has no analogue either in traditional games or even in two-player quantum games. In these `pure' coherent equilibria, entanglement shared among multiple players enables new kinds of cooperative behavior: indeed it can act as a contract, in the sense that it prevents players from successfully betraying one-another.Comment: 5 pages, 2 figs. Substantial revisons inc. new result

The Comparability of Men Who Have Sex With Men Recruited From Venue-Time-Space Sampling and Facebook: A Cohort Study

Background: Recruiting valid samples of men who have sex with men (MSM) is a key component of the US human immunodeficiency virus (HIV) surveillance and of research studies seeking to improve HIV prevention for MSM. Social media, such as Facebook, may present an opportunity to reach broad samples of MSM, but the extent to which those samples are comparable with men recruited from venue-based, time-space sampling (VBTS) is unknown. Objective: The objective of this study was to assess the comparability of MSM recruited via VBTS and Facebook. Methods: HIV-negative and HIV-positive black and white MSM were recruited from June 2010 to December 2012 using VBTS and Facebook in Atlanta, GA. We compared the self-reported venue attendance, demographic characteristics, sexual and risk behaviors, history of HIV-testing, and HIV and sexually transmitted infection (STI) prevalence between Facebook- and VTBS-recruited MSM overall and by race. Multivariate logistic and negative binomial models estimated age/race adjusted ratios. The Kaplan-Meier method was used to assess 24-month retention. Results: We recruited 803 MSM, of whom 110 (34/110, 30.9% black MSM, 76/110, 69.1% white MSM) were recruited via Facebook and 693 (420/693, 60.6% black MSM, 273/693, 39.4% white MSM) were recruited through VTBS. Facebook recruits had high rates of venue attendance in the previous month (26/34, 77% among black and 71/76, 93% among white MSM; between-race P=.01). MSM recruited on Facebook were generally older, with significant age differences among black MSM (P=.02), but not white MSM (P=.14). … See full text for complete abstract

Development and Evaluation of an Online, Patient-Driven, Family Outreach Intervention to Facilitate Sharing of Genetic Risk Information in Families with Lynch Syndrome

Departments of Gastroenterology Research, Behavioral Science, and Gastroenterology, Hepatology, and Nutrition This article has been accepted for publication in the Journal of Medical Genetics, 2021 following peer review, and the Version of Record can be accessed online at https://doi.org/10.1136/jmedgenet-2020-107615https://openworks.mdanderson.org/mdacc_ghn_pubs/1000/thumbnail.jp

The Sloan Digital Sky Survey Reverberation Mapping Project: Velocity Shifts of Quasar Emission Lines

Quasar emission lines are often shifted from the systemic velocity due to various dynamical and radiative processes in the line-emitting region. The level of these velocity shifts depends both on the line species and on quasar properties. We study velocity shifts for the line peaks of various narrow and broad quasar emission lines relative to systemic using a sample of 849 quasars from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project. The coadded (from 32 epochs) spectra of individual quasars have sufficient signal-to-noise ratio (SNR) to measure stellar absorption lines to provide reliable systemic velocity estimates, as well as weak narrow emission lines. The sample also covers a large dynamic range in quasar luminosity (~2 dex), allowing us to explore potential luminosity dependence of the velocity shifts. We derive average line peak velocity shifts as a function of quasar luminosity for different lines, and quantify their intrinsic scatter. We further quantify how well the peak velocity can be measured for various lines as a function of continuum SNR, and demonstrate there is no systematic bias in the line peak measurements when the spectral quality is degraded to as low as SNR~3 per SDSS pixel. Based on the observed line shifts, we provide empirical guidelines on redshift estimation from [OII]3728, [OIII]5008, [NeV]3426, MgII, CIII], HeII1640, broad Hbeta, CIV, and SiIV, which are calibrated to provide unbiased systemic redshifts in the mean, but with increasing intrinsic uncertainties of 46, 56, 119, 205, 233, 242, 400, 415, and 477 km/s, in addition to the measurement uncertainties. These more realistic redshift uncertainties are generally much larger than the formal uncertainties reported by the redshift pipelines for spectroscopic quasar surveys, and demonstrate the infeasibility of measuring quasar redshifts to better than ~200 km/s with only broad lines.Comment: matched to the published version; minor changes and conclusions unchange

The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen

This work is licensed under a Creative Commons Attribution 4.0 International License.Caenorhabditis elegans are soil-dwelling nematodes and models for understanding innate immunity and infection. Previously, we developed a novel fluorescent dye (KR35) that accumulates in the intestine of C. elegans and reports a dynamic wave in intestinal pH associated with the defecation motor program. Here, we use KR35 to show that mutations in the Ca2+-binding protein, PBO-1, abrogate the pH wave, causing the anterior intestine to be constantly acidic. Surprisingly, pbo-1 mutants were also more susceptible to infection by several bacterial pathogens. We could suppress pathogen susceptibility in pbo-1 mutants by treating the animals with pH-buffering bicarbonate, suggesting the pathogen susceptibility is a function of the acidity of the intestinal pH. Furthermore, we use KR35 to show that upon infection by pathogens, the intestinal pH becomes neutral in a wild type, but less so in pbo-1 mutants. C. elegans is known to increase production of reactive oxygen species (ROS), such as H2O2, in response to pathogens, which is an important component of pathogen defense. We show that pbo-1 mutants exhibited decreased H2O2 in response to pathogens, which could also be partially restored in pbo-1 animals treated with bicarbonate. Ultimately, our results support a model whereby PBO-1 functions during infection to facilitate pH changes in the intestine that are protective to the host