Defining the chromatin signature of inducible genes in T cells

BACKGROUND Specific chromatin characteristics, especially the modification status of the core histone proteins, are associated with active and inactive genes. There is growing evidence that genes that respond to environmental or developmental signals may possess distinct chromatin marks. Using a T cell model and both genome-wide and gene-focused approaches, we examined the chromatin characteristics of genes that respond to T cell activation. RESULTS To facilitate comparison of genes with similar basal expression levels, we used expression-profiling data to bin genes according to their basal expression levels. We found that inducible genes in the lower basal expression bins, especially rapidly induced primary response genes, were more likely than their non-responsive counterparts to display the histone modifications of active genes, have RNA polymerase II (Pol II) at their promoters and show evidence of ongoing basal elongation. There was little or no evidence for the presence of active chromatin marks in the absence of promoter Pol II on these inducible genes. In addition, we identified a subgroup of genes with active promoter chromatin marks and promoter Pol II but no evidence of elongation. Following T cell activation, we find little evidence for a major shift in the active chromatin signature around inducible gene promoters but many genes recruit more Pol II and show increased evidence of elongation. CONCLUSIONS These results suggest that the majority of inducible genes are primed for activation by having an active chromatin signature and promoter Pol II with or without ongoing elongation

Defining the chromatin signature of inducible genes in T cells

Inducible genes in T cells show the chromatin characteristics of active genes, suggesting they are primed for transcription

Racial variation in baseline characteristics and wait times among patients undergoing bariatric surgery

BACKGROUND: Although bariatric surgery is the most effective treatment for obesity and weight-related comorbid diseases, utilization rates are disproportionately low among non-white patients. We sought to understand if variation in baseline characteristics or access to care exists between white and non-white patients. METHODS: Using a statewide bariatric-specific data registry, we evaluated all patients who underwent bariatric surgery between 2006 and 2020 and completed a preoperative baseline questionnaire, which included a question about self-identification of race. Patient characteristics, co-morbidities, and time from initial preoperative clinic evaluation to date of surgery were compared among racial groups. RESULTS: A total of 73,141 patients met inclusion criteria with 18,741 (25.5%) self-identified as non-white. These included Black/African American (n = 11,904), Hispanic (n = 3448), Asian (n = 121), Native Hawaiian/Pacific Islander (n = 41), Middle Eastern (n = 164), Multiple (n = 2047) and other (n = 608). Non-white males were the least represented group, accounting for only 4% of all bariatric cases performed. Non-white patients were more likely to be younger (43.0 years vs. 46.6 years, p \u3c 0.0001), disabled (16% vs. 11.4%, p \u3c 0.0001) and have Medicaid (8.4% vs. 3.8%, p \u3c 0.0001) when compared to white patients, despite having higher rates of college education (78.0% vs. 76.6, p \u3c 0.0001). In addition, median time from initial evaluation to surgery was also longer among non-white patients (157 days vs. 127 days, p \u3c 0.0001), despite having higher rates of patients with a body mass index above 50 kg/m(2) (39.0% vs. 33.2%, p \u3c 0.0001). CONCLUSIONS: Non-white patients undergoing bariatric surgery represent an extremely diverse group of patients with more socioeconomic disadvantages and longer wait times when compared to white patients despite presenting with higher rates of severe obesity. Current guidelines and referral patterns for bariatric surgery may not be equitable and need further examination when considering the management of obesity within diverse populations to reduce disparities in care-of which non-white males are particularly at risk

EFFECTS OF INTENSIVE DIET AND EXERCISE ON KNEE JOINT LOADS, INFLAMMATION, AND CLINICAL OUTCOMES AMONG OVERWEIGHT AND OBESE ADULTS WITH KNEE OSTEOARTHRITIS

Importance Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. Objective To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. Design, Setting, and Participants Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. Interventions Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. Main Outcomes and Measures Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). Results Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ]exercise vs diet = 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δexercise vs diet + exercise = 0.39 pg/mL; 95% CI, −0.03 to 0.81; P = .007; Δexercise vs diet = 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δexercise vs diet + exercise = 1.02; 95% CI, 0.33 to 1.71; Ppain = .004; 18.4; 95% CI, 16.9 to 19.9; Δexercise vs diet + exercise, 4.29; 95% CI, 2.07 to 6.50; Pfunction < .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δexercise vs diet + exercise = −2.81; 95% CI, −4.76 to −0.86; P = .005). Conclusions and Relevance Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group

High-Altitude MMIC Sounding Radiometer for the Global Hawk Unmanned Aerial Vehicle

Microwave imaging radiometers operating in the 50-183 GHz range for retrieving atmospheric temperature and water vapor profiles from airborne platforms have been limited in the spatial scales of atmospheric structures that are resolved not because of antenna aperture size, but because of high receiver noise masking the small variations that occur on small spatial scales. Atmospheric variability on short spatial and temporal scales (second/ km scale) is completely unresolved by existing microwave profilers. The solution was to integrate JPL-designed, high-frequency, low-noise-amplifier (LNA) technology into the High-Altitude MMIC Sounding Radiometer (HAMSR), which is an airborne microwave sounding radiometer, to lower the system noise by an order of magnitude to enable the instrument to resolve atmospheric variability on small spatial and temporal scales. HAMSR has eight sounding channels near the 60-GHz oxygen line complex, ten channels near the 118.75-GHz oxygen line, and seven channels near the 183.31-GHz water vapor line. The HAMSR receiver system consists of three heterodyne spectrometers covering the three bands. The antenna system consists of two back-to-back reflectors that rotate together at a programmable scan rate via a stepper motor. A single full rotation includes the swath below the aircraft followed by observations of ambient (roughly 0 C in flight) and heated (70 C) blackbody calibration targets located at the top of the rotation. A field-programmable gate array (FPGA) is used to read the digitized radiometer counts and receive the reflector position from the scan motor encoder, which are then sent to a microprocessor and packed into data files. The microprocessor additionally reads telemetry data from 40 onboard housekeeping channels (containing instrument temperatures), and receives packets from an onboard navigation unit, which provides GPS time and position as well as independent attitude information (e.g., heading, roll, pitch, and yaw). The raw data files are accessed through an Ethernet port. The HAMSR data rate is relatively low at 75 kbps, allowing for real-time access over the Global Hawk high-data-rate downlink. Once on the ground, the raw data are unpacked and processed through two levels of processing. The Level 1 product contains geo-located, time-stamped, calibrated brightness temperatures for the Earth scan. These data are then input to a lD variational retrieval algorithm to produce temperature, water vapor, and cloud liquid water profiles, as well as several derived products such as potential temperature and relative humidity

RCT of web-based personalized normative feedback for college drinking prevention: Are typical student norms good enough?

Objectives: Personalized normative feedback (PNF) interventions are generally effective at correcting normative misperceptions and reducing risky alcohol consumption among college students. However, research has yet to establish what level of reference group specificity is most efficacious in delivering PNF. This study compared the efficacy of a web-based PNF intervention employing eight increasingly-specific reference groups against a Web-BASICS intervention and a repeated-assessment control in reducing risky drinking and associated consequences. Method: Participants were 1663 heavy drinking Caucasian and Asian undergraduates at two universities. The referent for web-based PNF was either the typical same-campus student, or a same-campus student at one (either gender, race, or Greek-affiliation), or a combination of two (e.g., gender and race), or all three levels of specificity (i.e., gender, race, and Greek-affiliation). Hypotheses were tested using quasi-Poisson generalized linear models fit by generalized estimating equations. Results: The PNF intervention participants showed modest reductions in all four outcomes (average total drinks, peak drinking, drinking days, and drinking consequences) compared to control participants. No significant differences in drinking outcomes were found between the PNF group as a whole and the Web-BASICS group. Among the eight PNF conditions, participants receiving typical student PNF demonstrated greater reductions in all four outcomes compared to those receiving PNF for more specific reference groups. Perceived drinking norms and discrepancies between individual behavior and actual norms mediated the efficacy of the intervention. Conclusions: Findings suggest a web-based PNF intervention using the typical student referent offers a parsimonious approach to reducing problematic alcohol use outcomes among college students

RCT of Web-based Personalized Normative Feedback for College Drinking Prevention: Are Typical Student Norms Good Enough?

Objectives Personalized normative feedback (PNF) interventions are generally effective at correcting normative misperceptions and reducing risky alcohol consumption among college students. However, research has yet to establish what level of reference group specificity is most efficacious in delivering PNF. This study compared the efficacy of a web-based PNF intervention employing eight increasingly-specific reference groups against a Web-BASICS intervention and a repeated-assessment control in reducing risky drinking and associated consequences. Method Participants were 1663 heavy drinking Caucasian and Asian undergraduates at two universities. The referent for web-based PNF was either the typical same-campus student, or a same-campus student at one (either gender, race, or Greek-affiliation), or a combination of two (e.g., gender and race), or all three levels of specificity (i.e., gender, race, and Greek-affiliation). Hypotheses were tested using quasi-Poisson generalized linear models fit by generalized estimating equations. Results The PNF intervention participants showed modest reductions in all four outcomes (average total drinks, peak drinking, drinking days, and drinking consequences) compared to control participants. No significant differences in drinking outcomes were found between the PNF group as a whole and the Web-BASICS group. Among the eight PNF conditions, participants receiving typical student PNF demonstrated greater reductions in all four outcomes compared to those receiving PNF for more specific reference groups. Perceived drinking norms and discrepancies between individual behavior and actual norms mediated the efficacy of the intervention. Conclusions Findings suggest a web-based PNF intervention using the typical student referent offers a parsimonious approach to reducing problematic alcohol use outcomes among college students