Human Ubc9 Contributes to Production of Fully Infectious Human Immunodeficiency Virus Type 1 Virions

Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, trafficking, and Env incorporation. The Gag-mediated assembly of virus particles and protease-mediated processing of Gag and Gag-Pol were unchanged in the absence of Ubc9. However, the stability of the cell-associated Env glycoprotein was decreased and Env incorporation into released virions was altered. Interestingly, overexpression of the Ubc9 trans-dominant-negative mutant C93A, which is a defective E2-SUMO-1 conjugase, suggests that this activity may not be required for interaction with Gag, virion assembly, or infectivity. This finding demonstrates that Ubc9 plays an important role in the production of infectious HIV-1 virions

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The problem of constitutional legitimation: what the debate on electoral quotas tells us about the legitimacy of decision-making rules in constitutional choice

Proponents of electoral quotas have a ‘dependent interpretation’ of democracy, i.e. they have formed an opinion on which decision-making rules are fair on the basis of their prior approval of the outcomes these rules are likely to generate. The article argues that this position causes an irresolvable problem for constitutional processes that seek to legitimately enact institutional change. While constitutional revision governed by formal equality allows the introduction of electoral quotas, this avenue is normatively untenable for proponents of affirmative action if they are consistent with their claim that formal equality reproduces biases and power asymmetries at all levels of decision-making. Their critique raises a fundamental challenge to the constitutional revision rule itself as equally unfair. Without consensus on the decision-making process by which new post-constitutional rules can be legitimately enacted, procedural fairness becomes an issue impossible to resolve at the stage of constitutional choice. This problem of legitimation affects all instances of constitutional choice in which there are opposing views not only about the desired outcome of the process but also about the decision-making rules that govern constitutional choice

Hernia recurrence following inguinal hernia repair in children

Purpose: We aimed to describe the incidence, timing, and predictors of recurrence following inguinal hernia repair (IHR) in children.Methods: We used the TRICARE claims database, a national cohort of \u3e3 million child dependents of members of the U.S. Armed Forces. We abstracted data on children (2005-2014). Our primary outcome was recurrence (ICD9-CM diagnosis codes). We calculated incidence rates for the population and stratified by age, time from repair to recurrence, and multivariable logistic regression to determine predictors.Results: Nine thousand nine hundred ninety-three children met inclusion criteria. Age at time of IHR was ≤1y in 37%, 2-3y in 23%, 4-5y in 16%, and 5-12y in 24%. Median follow-up time was 3.5y (IQR:1.6-6.1). 137 patients recurred (1.4%), with an incidence of 3.46 per 1000 person-years. Over half occurred in children 0-1y at repair (60%). The majority occurred within a year following repair (median 209 days [IQR:79-486]). Children 0-1y had 2.53 times greater odds of recurrence (compared to \u3e5y). Children with multiple comorbidities had 5.45 times greater odds compared to those with no comorbidities.Conclusions: The incidence of recurrence following IHR is 3.46 per 1000 person-years. The majority occurred within a year of repair. Children ≤1y and those with multiple comorbidities were at increased risk.Level of evidence: Prognosis Study, Level II

EC91-219 Nebraska Swine Report

This 1991 Nebraska Swine Report was prepared by the staff in Animal Science and cooperating departments for use in the Extension and Teaching programs at the University of Nebraska-Lincoln. Authors from the following areas contributed to this publication: Swine Nutrition, swine diseases, pathology, economics, engineering, swine breeding, meats, agronomy, and diagnostic laboratory. It covers the following areas: breeding, disease control, feeding, nutrition, economics, housing and meats

Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease

We aimed to identify genetic variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F(2) crosses between spontaneously hypertensive heart failure (SHHF) rats and reference strains. We combined linkage analyses with genome-wide expression profiling and identified Ephx2 as a heart failure susceptibility gene in SHHF rats. Specifically, we found that cis variation at Ephx2 segregated with heart failure and with increased transcript expression, protein expression and enzyme activity, leading to a more rapid hydrolysis of cardioprotective epoxyeicosatrienoic acids. To confirm our results, we tested the role of Ephx2 in heart failure using knockout mice. Ephx2 gene ablation protected from pressure overload-induced heart failure and cardiac arrhythmias. We further demonstrated differential regulation of EPHX2 in human heart failure, suggesting a cross-species role for Ephx2 in this complex disease