Patent: Dual Function Proteins for Treating Metabolic Disorders

The present invention relates to new proteins comprising fibroblast growth factor 2 1 (FGF21 ) and other metabolic regulators known to improve metabolic profiles in subjects to whom they are administered

Oxidative damage is influenced by diet but unaffected by selection for early age of oviposition in the Marula fly, ceratitis cosyra (Diptera: Tephritidae)

The expression of life-history traits, such as lifespan or reproductive effort, is tightly correlated with the amount and blend of macronutrients that individuals consume. In a range of herbivorous insects, consuming high protein to carbohydrate ratios (P:C) decreases lifespan but increases female fecundity. In other words, females face a resourcebased trade-off between lifespan and fecundity. Redox metabolism may help mediate this trade-off, if oxidative damage is elevated by reproductive investment and if this damage, in turn, reduces lifespan. Here, we test how diets varying in P:C ratio affect oxidative damage and antioxidant protection in female and male of the marula fly, Ceratitis cosyra (Diptera: Tephritidae). We use replicated lines that have been subjected to experimental evolution and differ in their lifespan and reproductive scheduling. We predicted that high fecundity would be associated with high oxidative damage and reduced antioxidant defences, while longer lived flies would show reduced damage and elevated antioxidant defences. However, higher levels of oxidative damage were observed in longlived control lines than selection lines, but only when fed the diet promoting lifespan. Flies fed diets promoting female fecundity (1:4 and 1:2 P:C) suffered greater oxidative damage to lipids than flies fed the best diet (0:1 P:C) for lifespan. Total antioxidant capacity was not affected by the selection regime or nutrition. Our results reiterate the importance of nutrition in affecting life-history traits, but suggest that in C. cosyra, reactive oxygen species play a minimal role in mediating dietary trade-offs between lifespan and reproduction.A National Research Foundation Competitive Programme for Rated Researchers.https://www.frontiersin.org/journals/physiologydm2022Zoology and Entomolog

A Pandemic Instrument Can Start Turning Collective Problems into Collective Solutions by Governing the Common-Pool Resource of Antimicrobial Effectiveness

To address the complex challenge of global antimicrobial resistance (AMR), a pandemic treaty should include mechanisms that 1) equitably address the access gap for antimicrobials, diagnostic technologies, and alternative therapies; 2) equitably conserve antimicrobials to sustain effectiveness and access across time and space; 3) equitably finance the investment, discovery, development, and distribution of new technologies; and 4) equitably finance and establish greater upstream and midstream infection prevention measures globally. Biodiversity, climate, and nuclear governance offer lessons for addressing these challenges

Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management:A GRADE assessment and international consensus approach

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against &gt;15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.</p

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

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

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