A Mouse Amidase Specific for N-terminal Asparagine: the gene, the enzyme, and their function in the N-end rule pathway

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In both fungi and mammals, the tertiary destabilizing N-terminal residues asparagine and glutamine function through their conversion, by enzymatic deamidation, into the secondary destabilizing residues aspartate and glutamate, whose destabilizing activity requires their enzymatic conjugation to arginine, one of the primary destabilizing residues. We report the isolation and analysis of a mouse cDNA and the corresponding gene (termed Ntan1) that encode a 310-residue amidohydrolase (termed NtN-amidase) specific for N-terminal asparagine. The ~17-kilobase pair Ntan1 gene is located in the proximal region of mouse chromosome 16 and contains 10 exons ranging from 54 to 177 base pairs in length. The ~1.4-kilobase pair Ntan1 mRNA is expressed in all of the tested mouse tissues and cell lines and is down-regulated upon the conversion of myoblasts into myotubes. The Ntan1 promoter is located ~500 base pairs upstream of the Ntan1 start codon. The deduced amino acid sequence of mouse NtN-amidase is 88% identical to the sequence of its porcine counterpart, but bears no significant similarity to the sequence of the NTA1-encoded N-terminal amidohydrolase of the yeast Saccharomyces cerevisiae, which can deamidate either N-terminal asparagine or glutamine. The expression of mouse NtN-amidase in S. cerevisiae nta1Delta was used to verify that NtN-amidase retains its asparagine selectivity in vivo and can implement the asparagine-specific subset of the N-end rule. Further dissection of mouse Ntan1, including its null phenotype analysis, should illuminate the functions of the N-end rule, most of which are still unknown

Novel genetic markers improve measures of atrial fibrillation risk prediction

Aims Atrial fibrillation (AF) is associated with adverse outcome. Whether recently discovered genetic risk markers improve AF risk prediction is unknown. Methods and results We derived and validated a novel AF risk prediction model from 32 possible predictors in the Women's Health Study (WHS), a cohort of 20 822 women without cardiovascular disease (CVD) at baseline followed prospectively for incident AF (median: 14.5 years). We then created a genetic risk score (GRS) comprised of 12 risk alleles in nine loci and assessed model performance in the validation cohort with and without the GRS. The newly derived WHS AF risk algorithm included terms for age, weight, height, systolic blood pressure, alcohol use, and smoking (current and past). In the validation cohort, this model was well calibrated with good discrimination [C-index (95% CI) = 0.718 (0.684-0.753)] and improved all reclassification indices when compared with age alone. The addition of the genetic score to the WHS AF risk algorithm model improved the C-index [0.741 (0.709-0.774); P = 0.001], the category-less net reclassification [0.490 (0.301-0.670); P < 0.0001], and the integrated discrimination improvement [0.00526 (0.0033-0.0076); P < 0.0001]. However, there was no improvement in net reclassification into 10-year risk categories of <1, 1-5, and 5+% [0.041 (−0.044-0.12); P = 0.33]. Conclusion Among women without CVD, a simple risk prediction model utilizing readily available risk markers identified women at higher risk for AF. The addition of genetic information resulted in modest improvements in predictive accuracy that did not translate into improved reclassification into discrete AF risk categorie

Novel genetic markers improve measures of atrial fibrillation risk prediction

Aims Atrial fibrillation (AF) is associated with adverse outcome. Whether recently discovered genetic risk markers improve AF risk prediction is unknown. Methods and results We derived and validated a novel AF risk prediction model from 32 possible predictors in the Women's Health Study (WHS), a cohort of 20 822 women without cardiovascular disease (CVD) at baseline followed prospectively for incident AF (median: 14.5 years). We then created a genetic risk score (GRS) comprised of 12 risk alleles in nine loci and assessed model performance in the validation cohort with and without the GRS. The newly derived WHS AF risk algorithm included terms for age, weight, height, systolic blood pressure, alcohol use, and smoking (current and past). In the validation cohort, this model was well calibrated with good discrimination [C-index (95% CI) = 0.718 (0.684–0.753)] and improved all reclassification indices when compared with age alone. The addition of the genetic score to the WHS AF risk algorithm model improved the C-index [0.741 (0.709–0.774); P = 0.001], the category-less net reclassification [0.490 (0.301–0.670); P < 0.0001], and the integrated discrimination improvement [0.00526 (0.0033–0.0076); P < 0.0001]. However, there was no improvement in net reclassification into 10-year risk categories of <1, 1–5, and 5+% [0.041 (−0.044–0.12); P = 0.33]. Conclusion: Among women without CVD, a simple risk prediction model utilizing readily available risk markers identified women at higher risk for AF. The addition of genetic information resulted in modest improvements in predictive accuracy that did not translate into improved reclassification into discrete AF risk categories

The Northwest Tropical Atlantic Station (NTAS) : NTAS-1 mooring deployment cruise report

A surface mooring outfitted for meteorological and oceanographic measurement was deployed near 14°50'N, 51°00'W in the northwest tropical Atlantic on 30 March 2001. This was the initial deployment of the Northwest Tropical Atlantic Station (NTAS) project for air–sea flux measurement. These observations will be used to investigate air–sea interaction processes related to climate variability. The deployment was done on R/V Oceanus Cruise 365, Leg 5 by the Upper Ocean Processes Group (UOP) of the Woods Hole Oceanographic Institution. The 3-meter discus buoy was outfitted with two Air–Sea Interaction Meteorology (ASIMET) systems. Each system measures, records, and transmits via Argos satellite the surface meteorological variables necessary to compute air–sea fluxes of heat, moisture and momentum. The upper 120 m of the mooring line was outfitted with oceanographic sensors for the measurement of temperature and velocity. This report describes the initial deployment of the NTAS mooring (NTAS-1), including some of the pre-cruise buoy preparations and post cruise data comparisons.Funding was provided by the National Oceanic and Atmospheric Administration (NOAA) through the Cooperative Institute for Climate and Ocean Research (CICOR) under Grant No. NA87RJ0445

Temporal Patterns of Arrest in a Cohort of Adults Receiving Mental Health Services: The Massachusetts Mental Health / Criminal Justice Cohort Study

Criminal Justice Involvement among Clientele is a Major Concern for State Mental Health Agencies. Mental health and criminal justice systems provide services at various points along the interface of these systems to reduce offending and re-offending, including: - Diversion programs - Mental Health Courts - Re-Entry Little information about scope of offending to guide service development. This study provides data on the prevalence, type and temporal patterns of arrest for a large sample of adults followed for roughly 9.5 years

Serious Mental Illness and Chronic Crimial Justice Involvement: Findings from The Massachusetts Mental Healthy / Criminal Justice Cohort Study

Presents findings from 1990 through 2000 from The Massachusetts Mental Health/Criminal Justice Cohort Study

Effect of Long-Term Marine Omega-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Background: Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine omega-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose related. Methods: The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012 and December 31, 2020 in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine omega-3 fatty acids that reported results for AF, either as pre-specified outcome, adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median followup of at least one year were included. RCTs specifically examining shorter term effects of omega-3 fatty acids on recurrent AF in patients with established AF or post-operative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was metaanalyzed using random-effects model with Knapp-Hartung adjustment and evaluated a doseresponse relationship with a meta-regression model. Results: Of 4049 screened records, seven studies were included in the meta-analysis. Of those, five were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81,210 patients from 7 trials, 58,939 (72.6%) were enrolled in trials testing ≤1gram per day (g/d) and 22,271 (27.4%) in trials testing >1g/d of omega-3 fatty acids. The mean age was 65 years and 31,842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine omega-3 fatty acid supplements was associated with an increased risk of AF (n=2,905; HR 1.25, 95%CI 1.07-1.46, P=0.013). In analyses stratified by dose, the HR was greater in the trials testing >1g/d (HR 1.49, 95%CI 1.04-2.15, P=0.042) as compared with those testing ≤1 g/d (HR 1.12, 95%CI 1.03-1.22, P=0.024, P for interaction1g/d

The Northwest Tropical Atlantic Station (NTAS) : NTAS-2 mooring turnaround cruise report

The Northwest Tropical Atlantic Station (NTAS) was established to address the need for accurate air-sea flux estimates and upper ocean measurements in a region with strong sea surface temperature anomalies and the likelihood of significant local air–sea interaction on interannual to decadal timescales. The approach is to maintain a surface mooring outfitted for meteorological and oceanographic measurements at a site near 15°N, 51°W by successive mooring turnarounds. These observations will be used to investigate air–sea interaction processes related to climate variability. Deployment of the first NTAS mooring (NTAS-1) at 14°50′ N, 51°00′ W on 30 March 2001 was documented in a previous report (Plueddemann et al., 2001). This report documents recovery of the NTAS-1 mooring and deployment of the NTAS-2 mooring at the same site. Both moorings used 3-meter discus buoys as the surface element. These buoys were outfitted with two Air–Sea Interaction Meteorology (ASIMET) systems. Each system measures, records, and transmits via Argos satellite the surface meteorological variables necessary to compute air–sea fluxes of heat, moisture and momentum. The upper 120 m of the NTAS-1 mooring line, and the upper 150 m of the NTAS-2 mooring line, were outfitted with oceanographic sensors for the measurement of temperature and velocity. The mooring turnaround was done on the NOAA Ship Ronald H. Brown, Cruise RB-02-02, by the Upper Ocean Processes Group of the Woods Hole Oceanographic Institution. The cruise took place between 2 and 8 March 2002. A SeaBeam bathymetry survey of the site was done first, followed by deployment of the NTAS-2 mooring on 4 March at approximately 14°44.3′ N, 50°56.8′ W in 5043 m of water. A 24-hour intercomparison period followed, after which the NTAS-1 mooring was recovered. This report describes these operations, as well as some of the pre-cruise buoy preparations.Funding was provided by the National Oceanic and Atmospheric Administration and the Cooperative Institute for Climate and Ocean Research (CICOR) under Grant No. NA17RJ1223