Research Event

Event participants

Tim Jinks, Head of Drug-Resistant Infections Programme, Wellcome
Jim O’Neill, Chair, Review on Antimicrobial Resistance; Chair, Chatham House
Haileyesus Getahun, Director of Global Coordination and Partnership on Antimicrobial Resistance, World Health Organization 
Juan Lubroth, Chief Veterinary Officer, Food and Agriculture Organization (Videolink)
Jyoti Joshi, Head, South Asia, Center for Disease Dynamics, Economics & Policy
Estelle Mbadiwe, Coordinator-Nigeria, Global Antibiotic Resistance Partnership
Charles Clift, Senior Consulting Fellow, Chatham House; Report Author

8 October 2019

A startling lack of progress on critical recommendations to tackle antimicrobial resistance is highlighted in this new global progress report, as well as opportunities for further action and key obstacles that need to be overcome.

Use the Download button to choose either the Research Paper, or the Background and Analysis Paper.

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K₂ subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.

THE Oxford Dictionary describes the environment as "the surroundings or conditions in which a person, animal, or plant lives or operates". Humankind has been reliant on the environment for its existence for as long as humans have been living on earth. In numerous ways, the future survival of humankind will depend on how we take care of our air, soil, rivers, oceans, animals and plants.

(University of Warwick) A microbial community is a complex, dynamic system composed of hundreds of species and their interactions, they are found in oceans, soil, animal guts and plant roots. Each system feeds the Earth's ecosystem and their own growth, as they each have their own metabolism that underpin biogeochemical cycles. Researchers from the School of Life Sciences at the University of Warwick have produced an extendable thermodynamic model for simulating the dynamics of microbial communities.

(Earth Institute at Columbia University) A uniquely resilient organism all but unheard of in the Arabian Sea 20 years ago has been proliferating and spreading at an alarming pace. New research describes how the continued loss of snow over the Himalayan-Tibetan Plateau region is fueling the expansion of this destructive algal bloom.

(The Korea Advanced Institute of Science and Technology (KAIST)) A research team led by Distinguished Professor Sang-Yup Lee reported the production of a microbial strain capable of the massive production of succinic acid with the highest production efficiency to date. This strategy of integrating systems metabolic engineering with enzyme engineering will be useful for the production of industrially competitive bio-based chemicals.

(Institute for Operations Research and the Management Sciences) New research to be published in the INFORMS journal Management Science has found popular rideshare platforms exhibit racial and other biases that penalize under-represented minorities and others seeking to use their services.

The SBDC offers resources and guidance to Harlem’s small businesses amidst the COVID-19 crisis.

Dong-Jae Jun
May 1, 2020; 61:746-757
Research Articles

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K₂ subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.

Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22 producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum Firmicutes, class Clostridia, and order Clostridiales. This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22 and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.

LGBT India Tours offers best and full assurance services to the gay, lesbian and LGBT clients at affordable rates for reveling holidays and tourism packages to various destinations in India.

BOGOTA, Colombia (AP) — A Colombian advertising company is pitching a novel, if morbid, solution to shortages of hospital beds and coffins during the coronavirus pandemic: combine them. ABC Displays has created a cardboard bed with metal...

Around half of trials that supported new cancer drug approvals in Europe between 2014 and 2016 were judged to be at high risk of bias, in a new study. Huseyin Naci,assistant professor of health policy a the London School of Economics joins us to talk about why potential bias may mean potential exaggeration of treatment effects, and could be...

Colombia has more internally displaced persons (IDPs) than any other country in the world, the result of a 52-year civil war. Beyond improving the lives of its 7.3 million IDPs, the country faces a number of crucial migration issues as it works to achieve stability in the wake of an historic peace accord signed in late 2016. This country profile examines historical trends and current and future migration challenges in Colombia.

Samy Suissa
Jan 1, 2018; 41:6-10
Perspectives in Care

A new scientific study published Monday found that global warming is fueling a destructive algal bloom that is disrupting fisheries in the Arabian sea.

You could be forgiven for thinking the television images in the experiment were from 2006. They were really from 1982: Israeli forces were clashing with Arab militants in Lebanon. The world was watching, charges were flying, and the air was thick with grievance, hurt and outrage.

Antiwar liberals last week got to savor the four most satisfying words in the English language: "I told you so."

Long before word recently broke that white referees in the National Basketball Association were calling fouls at a higher rate on black athletes than on white athletes, and long before studies found racial disparities in how black and white applicants get called for job interviews, researchers no...

On Oct. 10, 2002, Hillary Rodham Clinton stood in the Senate to explain why she was authorizing President Bush to use force against Iraq: "In balancing the risks of action versus inaction, I think New Yorkers who have gone through the fires of hell may be more attuned to the risk of not acting. I...

Felipe Muñoz, Advisor to the President of Colombia for the Colombian-Venezuelan Border, discusses how Colombia is coping with the influx of Venezuelan migrants, plans for future policy decisions surrounding this migration, and developments in regional and international cooperation.

Though Colombians displaced by a decades-long civil war found a welcome refuge in Ecuador, life has become more difficult for them in recent years, in part as a result of the influx of Venezuelans seeking safety. This article draws on surveys of migrants in Quito, comparing and contrasting the experiences of Colombians and Venezuelans, and assessing their perceptions of discrimination, victimization, trust in institutions, and hopes for the future.

Aunque colombianos encontraron un refugio cálido en Ecuador después de ser desplazados de su país por una guerra civil que duro décadas, la vida se ha vuelto más difícil para ellos en los últimos años, en parte como resultado del flujo de venezolanos que buscan seguridad. Este artículo se basa en encuestas de migrantes en Quito, comparando y contrastando las experiencias de colombianos y venezolanos, y evaluando sus percepciones de discriminación, victimización y esperanzas para el futuro.

Felipe Muñoz, Advisor to the President of Colombia for the Colombian-Venezuelan Border, discusses how Colombia is coping with the influx of Venezuelan migrants, plans for future policy decisions surrounding this migration, and developments in regional and international cooperation.

Understand how customer brains work - these are the most important cognitive biases for e-commerce marketers.

The post 12 Cognitive Biases E-commerce Marketers Need to Know appeared first on Neuromarketing.

Our weekly round-up of the best psychology coverage from elsewhere on the web

Sex discrimination against women.

London : printed for Knight and Lacey, 1826.

The NHL suspended its season March 12 with 189 regular-season games left.

London : Stacy Bias, 2019.

Mikael Escobar-Bach, Yuri Goegebeur, Armelle Guillou.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1773--1795.

Abstract:
We consider bias-corrected estimation of the stable tail dependence function in the regression context. To this aim, we first estimate the bias of a smoothed estimator of the stable tail dependence function, and then we subtract it from the estimator. The weak convergence, as a stochastic process, of the resulting asymptotically unbiased estimator of the conditional stable tail dependence function, correctly normalized, is established under mild assumptions, the covariate argument being fixed. The finite sample behaviour of our asymptotically unbiased estimator is then illustrated on a simulation study and compared to two alternatives, which are not bias corrected. Finally, our methodology is applied to a dataset of air pollution measurements.

Yuling Yan, Bret Hanlon, Sebastien Roch, Karl Rohe.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1577--1610.

Abstract:
Respondent-driven sampling (RDS) collects a sample of individuals in a networked population by incentivizing the sampled individuals to refer their contacts into the sample. This iterative process is initialized from some seed node(s). Sometimes, this selection creates a large amount of seed bias. Other times, the seed bias is small. This paper gains a deeper understanding of this bias by characterizing its effect on the limiting distribution of various RDS estimators. Using classical tools and results from multi-type branching processes [12], we show that the seed bias is negligible for the Generalized Least Squares (GLS) estimator and non-negligible for both the inverse probability weighted and Volz-Heckathorn (VH) estimators. In particular, we show that (i) above a critical threshold, VH converge to a non-trivial mixture distribution, where the mixture component depends on the seed node, and the mixture distribution is possibly multi-modal. Moreover, (ii) GLS converges to a Gaussian distribution independent of the seed node, under a certain condition on the Markov process. Numerical experiments with both simulated data and empirical social networks suggest that these results appear to hold beyond the Markov conditions of the theorems.