Acute inflammatory responses to high-intensity functional training programming: An observational study

Effects of varying types of short duration workouts in high-intensity functional training (HIFT) on inflammatory biomarkers have not been adequately characterized. Objectives: The purpose of this descriptive study was to examine the acute effects of HIFT workouts on biomarkers of inflammation, over time, in two HIFT bouts. Materials and Methods: Ten apparently healthy males (28.1 ± 5 yrs) completed two HIFT sessions (“short bout:” sub-5-minute vs. “long bout:” 15-minute) in a randomized crossover design. Blood was drawn pre and post-exercise, and 1 hour, 3 hours, and 6 hours post-exercise, centrifuged, and plasma frozen for analysis. Inflammation was assessed through plasma interleukin-6 (IL-6), interleukin-10 (IL-10), and tumour necrosis factor alpha (TNF-α). Results: Repeated measures ANOVA revealed a single trial-dependent difference (IL-6, p≤ 0.05), and while statistically significant, this difference may not be biologically significant. The biomarkers IL-6, IL-10, and TNF-α all follow a similar pattern of peaking post-exercise and returning to baseline within 6 hours in both trials. Conclusions: Both temporal responses and concentrations were similar in the short and long bout. A practical implication is that both bouts of a HIFT elicit certain specific physiologic inflammatory responses

JWST Near-Infrared Detectors: Latest Test Results

The James Webb Space Telescope, an infrared-optimized space telescope being developed by NASA for launch in 2013, will utilize cutting-edge detector technology in its investigation of fundamental questions in astrophysics. JWST's near infrared spectrograph, NIRSpec utilizes two 2048 x 2048 HdCdTe arrays with Sidecar ASIC readout electronics developed by Teledyne to provide spectral coverage from 0.6 microns to 5 microns. We present recent test and calibration results for the NIRSpec flight arrays as well as data processing routines for noise reduction and cosmic ray rejection

James Webb Space Telescope Near-Infrared Spectrograph: Dark Performance of the First Flight Candidate Detector Arrays

The James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec) incorporates two 5 micron cutoff (lambda(sub co) = 5 micron) 2048x2048 pixel Teledyne HgCdTe HAWAII-2RG sensor chip assemblies. These detector arrays, and the two Teledyne SIDECAR application specific integrated circuits that control them, are operated in space at T approx. 37 K. This article focuses on the measured performance of the first flight-candidate, and near-flight candidate, detector arrays. These are the first flight-packaged detector arrays that meet NIRSpec's challenging 6 e(-) rms total noise requirement

Selenium, Selenoenzymes, Oxidative Stress and Risk of Neoplastic Progression from Barrett's Esophagus: Results from Biomarkers and Genetic Variants

Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA) and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX) 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1) concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85). SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR) = 3.95, 95% confidence intervals (CI) = 1.42–10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31–32.58), but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12–0.69). Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1 concentrations with the risk of EA and aneuploidy, which warrants further investigation

Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors

Novel therapeutic approaches are urgently required for multiple myeloma (MM). We used a phenotypic screening approach using co-cultures of MM cells with bone marrow stromal cells to identify compounds that overcome stromal resistance. One such compound, BRD9876, displayed selectivity over normal hematopoietic progenitors and was discovered to be an unusual ATP non-competitive kinesin-5 (Eg5) inhibitor. A novel mutation caused resistance, suggesting a binding site distinct from known Eg5 inhibitors, and BRD9876 inhibited only microtubule-bound Eg5. Eg5 phosphorylation, which increases microtubule binding, uniquely enhanced BRD9876 activity. MM cells have greater phosphorylated Eg5 than hematopoietic cells, consistent with increased vulnerability specifically to BRD9876’s mode of action. Thus, differences in Eg5-microtubule binding between malignant and normal blood cells may be exploited to treat multiple myeloma. Additional steps are required for further therapeutic development, but our results indicate that unbiased chemical biology approaches can identify therapeutic strategies unanticipated by prior knowledge of protein targets