The fifth season of the ABB FIA Formula E Championship has kicked off in style in December 2018 with the SAUDIA Ad Diriyah E-Prix. Since then, the Championship’s 22 participating Gen2 electric cars and drivers have been crisscrossing the planet in 13...

Twitter used to be full of cat memes and had a culture of sharing. Now, I pay a company to make sure my presence on the site is extremely limited, writes Annalee Newitz

Entropy is the physicist’s magic word, invoked to answer to some of the biggest questions in cosmology. Yet a quantum rethink may be needed to tell us what it actually is

Bamboo is a renewable material that when microwaved becomes stronger by weight than steel or concrete – which could make it ideal for constructing buildings, cars and planes

Title: Health Tip: Make Microwave Cooking Safe
Category: Health News
Created: 5/1/2013 8:35:00 AM
Last Editorial Review: 5/1/2013 12:00:00 AM

Title: More Cases of Tick-Borne Powassan Disease Expected in U.S. This Year
Category: Health News
Created: 5/3/2017 12:00:00 AM
Last Editorial Review: 5/4/2017 12:00:00 AM

Title: Could Cellphone, Microwave Radiation During Pregnancy Raise ADHD Risk?
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 12:00:00 AM

Title: Researchers Move Toward Once-Yearly Treatment for HIV
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

ABSTRACT

Viral diseases cause significant losses in aquaculture. Prophylactic measures, such as immune priming, are promising control strategies. Treatment of the Pacific oyster (Crassostrea gigas) with the double-stranded RNA analog poly(I·C) confers long-term protection against infection with ostreid herpesvirus 1, the causative agent of Pacific oyster mortality syndrome. In a recent article in mBio, Lafont and coauthors (M. Lafont, A. Vergnes, J. Vidal-Dupiol, J. de Lorgeril, et al., mBio 11:e02777-19, 2020, https://doi.org/10.1128/mBio.02777-19) characterized the transcriptome of oysters treated with poly(I·C). This immune stimulator induced genes related to the interferon and apoptosis pathways. This response overlaps the response to viral infection, and high expression levels of potential effector genes are maintained for up to 4 months. This work opens the door to characterization of the phenomena of immune priming in a poorly studied invertebrate model. It also highlights the importance of interferon-like responses for invertebrate antiviral immunity.

ABSTRACT

Hepatitis C virus (HCV) infects millions of people worldwide, causing chronic liver disease that can lead to cirrhosis, hepatocellular carcinoma, and liver transplant. In the last several years, the advent of direct-acting antivirals, including NS3/4A protease inhibitors (PIs), has remarkably improved treatment outcomes of HCV-infected patients. However, selection of resistance-associated substitutions and polymorphisms among genotypes can lead to drug resistance and in some cases treatment failure. A proactive strategy to combat resistance is to constrain PIs within evolutionarily conserved regions in the protease active site. Designing PIs using the substrate envelope is a rational strategy to decrease the susceptibility to resistance by using the constraints of substrate recognition. We successfully designed two series of HCV NS3/4A PIs to leverage unexploited areas in the substrate envelope to improve potency, specifically against resistance-associated substitutions at D168. Our design strategy achieved better resistance profiles over both the FDA-approved NS3/4A PI grazoprevir and the parent compound against the clinically relevant D168A substitution. Crystallographic structural analysis and inhibition assays confirmed that optimally filling the substrate envelope is critical to improve inhibitor potency while avoiding resistance. Specifically, inhibitors that enhanced hydrophobic packing in the S4 pocket and avoided an energetically frustrated pocket performed the best. Thus, the HCV substrate envelope proved to be a powerful tool to design robust PIs, offering a strategy that can be translated to other targets for rational design of inhibitors with improved potency and resistance profiles.

IMPORTANCE Despite significant progress, hepatitis C virus (HCV) continues to be a major health problem with millions of people infected worldwide and thousands dying annually due to resulting complications. Recent antiviral combinations can achieve >95% cure, but late diagnosis, low access to treatment, and treatment failure due to drug resistance continue to be roadblocks against eradication of the virus. We report the rational design of two series of HCV NS3/4A protease inhibitors with improved resistance profiles by exploiting evolutionarily constrained regions of the active site using the substrate envelope model. Optimally filling the S4 pocket is critical to avoid resistance and improve potency. Our results provide drug design strategies to avoid resistance that are applicable to other quickly evolving viral drug targets.

In recent years, North Carolina has attracted significant national attention due to numerous health care reforms underway across government and the private sector. These reforms encompass new incentives, new partnerships, and new models of delivering care, and collectively, they have important implications for health care data.

North Carolina is developing a unique and innovative infrastructure to support integrated physical, behavioral, and social health care. Efforts by the North Carolina Department of Health and Human Services, the Foundation for Health Leadership & Innovation, Cone Health, Atrium Health, and the One Charlotte Health Alliance advance our understanding of how to best operationalize the design and payment of integrated services. Best practices such as the collaborative care and primary care behavioral health models reduce inefficiencies and disparities by bringing together teams of primary care and behavioral health care providers.

The question of the relative evolutionary roles of adaptive and nonadaptive processes has been a central debate in population genetics for nearly a century. While advances have been made in the theoretical development of the underlying models, and statistical methods for estimating their parameters from large-scale genomic data, a framework for an appropriate null model remains elusive. A model incorporating evolutionary processes known to be in constant operation, genetic drift (as modulated by the demographic history of the population) and purifying selection, is lacking. Without such a null model, the role of adaptive processes in shaping within- and between-population variation may not be accurately assessed. Here, we investigate how population size changes and the strength of purifying selection affect patterns of variation at "neutral" sites near functional genomic components. We propose a novel statistical framework for jointly inferring the contribution of the relevant selective and demographic parameters. By means of extensive performance analyses, we quantify the utility of the approach, identify the most important statistics for parameter estimation, and compare the results with existing methods. Finally, we reanalyze genome-wide population-level data from a Zambian population of Drosophila melanogaster, and find that it has experienced a much slower rate of population growth than was inferred when the effects of purifying selection were neglected. Our approach represents an appropriate null model, against which the effects of positive selection can be assessed.

Efficient delivery of antigenic cargo to trigger protective immune responses is critical to the success of vaccination. Genetically engineered microorganisms, including virus, bacteria, and protozoa, can be modified to carry and deliver heterologous antigens to the host immune system. The biological vectors can induce a broad range of immune responses and enhance heterologous antigen-specific immunological outcomes. The protozoan genus Eimeria is widespread in domestic animals, causing serious coccidiosis. Eimeria parasites with strong immunogenicity are potent coccidiosis vaccine candidates and offer a valuable model of live vaccines against infectious diseases in animals. Eimeria parasites can also function as a vaccine vector. Herein, we review recent advances in design and application of recombinant Eimeria as a vaccine vector, which has been a topic of ongoing research in our laboratory. By recapitulating the establishment of an Eimeria transfection platform and its application, it will help lay the foundation for the future development of effective parasite-based vaccine delivery vectors and beyond.

Premature infants have a higher incidence of indirect hyperbilirubinemia than term infants. Management of neonatal indirect hyperbilirubinemia in late preterm and term neonates has been well addressed by recognized, consensus-based guidelines. However, the extension of these guidelines to the preterm population has been an area of uncertainty because of limited evidence. This leads to variation in clinical practice and lack of recognition of the spectrum of bilirubin-induced neurologic dysfunction (BIND) in this population. Preterm infants are metabolically immature and at higher risk for BIND at lower bilirubin levels than their term counterparts. Early use of phototherapy to eliminate BIND and minimize the need for exchange transfusion is the goal of treatment in premature neonates. Although considered relatively safe, phototherapy does have side effects, and some NICUs tend to overuse phototherapy. In this review, we describe the epidemiology and pathophysiology of BIND in preterm neonates, and discuss our approach to standardized management of indirect hyperbilirubinemia in the vulnerable preterm population. The proposed treatment charts suggest early use of phototherapy in preterm neonates with the aim of reducing exposure to high irradiance levels, minimizing the need for exchange transfusions, and preventing BIND. The charts are pragmatic and have additional curves for stopping phototherapy and escalating its intensity. Having a standardized approach would support future research and quality improvement initiatives that examine dose and duration of phototherapy exposure with relation to outcomes.

A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice.

Technology in bioanalysis, -omics, and computation have evolved over the past half century to allow for comprehensive assessments of the molecular to whole body pharmacology of diverse corticosteroids. Such studies have advanced pharmacokinetic and pharmacodynamic (PK/PD) concepts and models that often generalize across various classes of drugs. These models encompass the "pillars" of pharmacology, namely PK and target drug exposure, the mass-law interactions of drugs with receptors/targets, and the consequent turnover and homeostatic control of genes, biomarkers, physiologic responses, and disease symptoms. Pharmacokinetic methodology utilizes noncompartmental, compartmental, reversible, physiologic [full physiologically based pharmacokinetic (PBPK) and minimal PBPK], and target-mediated drug disposition models using a growing array of pharmacometric considerations and software. Basic PK/PD models have emerged (simple direct, biophase, slow receptor binding, indirect response, irreversible, turnover with inactivation, and transduction models) that place emphasis on parsimony, are mechanistic in nature, and serve as highly useful "top-down" methods of quantitating the actions of diverse drugs. These are often components of more complex quantitative systems pharmacology (QSP) models that explain the array of responses to various drugs, including corticosteroids. Progressively deeper mechanistic appreciation of PBPK, drug-target interactions, and systems physiology from the molecular (genomic, proteomic, metabolomic) to cellular to whole body levels provides the foundation for enhanced PK/PD to comprehensive QSP models. Our research based on cell, animal, clinical, and theoretical studies with corticosteroids have provided ideas and quantitative methods that have broadly advanced the fields of PK/PD and QSP modeling and illustrates the transition toward a global, systems understanding of actions of diverse drugs.

To date, more than 200 monogenic, often devastating, skin diseases have been described. Because of unmet medical needs, development of long-lasting and curative therapies has been consistently attempted, with the aim of correcting the underlying molecular defect. In this review, we will specifically address the few combined cell and gene therapy strategies that made it to the clinics. Based on these studies, what can be envisioned for the future is a patient-oriented strategy, built on the specific features of the individual in need. Most likely, a combination of different strategies, approaches, and advanced therapies will be required to reach the finish line at the end of the long and winding road hampering the achievement of definitive treatments for genodermatoses.

Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. Studies have shown an increase in the risk of developing specific cancer types in the presence of a germline PTEN mutation. Furthermore, outside of the familial setting, somatic variants of PTEN occur in numerous malignancies. Here we introduce and discuss the prospect of moving toward a systems pathology approach for PTEN diagnostics, incorporating clinical and molecular pathology data with the goal of improving the clinical management of patients with a PTEN mutation. Detection of a germline PTEN mutation can inform cancer surveillance and in the case of somatic mutation, have value in predicting disease course. Given that PTEN functions in the PI3K/AKT/mTOR pathway, identification of a PTEN mutation may highlight new therapeutic opportunities and/or inform therapeutic choices.

Twitter used to be full of cat memes and had a culture of sharing. Now, I pay a company to make sure my presence on the site is extremely limited, writes Annalee Newitz

Bamboo is a renewable material that when microwaved becomes stronger by weight than steel or concrete – which could make it ideal for constructing buildings, cars and planes

I was not surprised either that it took two-plus months for arrests to come of two men and murder charges in the case. This only after the GBI was rightly called in.

Experts representing a diversity of views on autonomous weapons systems collaborate on a realistic policy roadmap

This is the Popcorn Popping Lid with Butter Vents available from Uncommon Goods ($11). You just fill a microwave-safe 10-inch bowl with your choice of popping corn, set the lid on top, add a pat of butter to each of the lid's butter vents, and let the microwaving begin! Of course if you're anything like me you'll balance as much butter as you can atop each of those vents because, I don't know if you knew this about me, but I love butter. I don't really like it cold but *microwave beeping* sometimes when I'm really feeling down I'll just melt two sticks and drink it. Keep going for a couple more shots because they exist.

Study highlights industry failures and calls for shift in consumer attitudes

The fashion industry needs to fundamentally change in order to mitigate the environmental impact of fast fashion, experts have said.

Clothes rental, better recycling processes, pollution control technology and the innovative use of offcuts are among measures that could help, they said.

Researchers have announced the isolation and characterization of a unique antibody that can bind to the virus that causes COVID-19 (SARS-CoV-2). The team has established that the antibody binds to a conserved epitope on the spike protein of SARS-CoV-2.

Antibodies in blood taken from people who recovered from COVID-19 are widely seen as a key to developing a possible cure for the disease

The crisis over shortages of vital protective clothing for doctors and nurses was laid bare today with the leak of plans to start re-using disposable equipment.

Air-burning plasma thruster may be competitive with jet engines.

Comet had prompted excitement as astronomers expected it to be visible to the naked eye – but it has since broken up and is getting dimmer

Researchers suggest unusual rapid shift is due to competing patches of magnetic field

Emily Berch

The post Iowa’s Republican Governor Sacrifices Citizens to Trump appeared first on The Nation.

Coronavirus crisis has forced musicians and others to adapt, says founder of platform

Musicians, artists and writers have turned to crowdfunding sites to make up for lost opportunities in lockdown, and their audiences have followed them, leading to a rise in contributions through platforms such as Patreon.

Since mid-March more than 70,000 extra creators have joined Patreon, which allows fans to give monthly payments to artists in exchange for exclusive content or simply out of a desire to support someone whose work they appreciate.

McGowan previously called her 'Charmed' co-star Alyssa Milano a 'fraud' for endorsing Biden

Former Premier League referee Howard Webb has revealed the one decision he wishes he could have reversed in his career, admitting: 'I knew within seconds I was wrong'.

Farmers are entitled to a new, one-off payment from the Federal Government to help them decide if their farm is sustainable or could be sold.

Don Lemon came through with a word!

Shadow, a tech developer started by veterans of Hillary Clinton's 2016 presidential run, built the app being blamed for delaying Iowa Democratic caucus results.

The Iowa caucuses teach a lesson that sometimes technology makes things worse.

Cyber security experts and the State Opposition say there are still questions to be answered after an article published in the New York Times claimed an Israeli software company found hackers with links to China had sent malware in an email sent to the Premier's office in January.

Here's a look at the number of coronavirus cases in Iowa and the latest news about the COVID-19 outbreak.

Agency moves toward more accelerated reviews

2018 was a busy and productive year for ACRO’s European Scientific & Regulatory Committee, which meets quarterly in London. While the Committee focused largely on the continuing implementation of the EU Clinical Trial Regulation, there were also opportunities to engage with regulators on other topics ranging from European regulatory strategy to Advanced Therapies to the urgent challenges of Brexit.

The United States has sued a Clive, Iowa, couple to bar them from preparing federal tax returns for others. According to the government complaint, Jill Schwartz-Musin, her husband Howard Musin, and their business, SSC Services, prepare fraudulent federal income tax returns for small business owners.

The United States has brought suit in federal court against Gayle Lemmon of Humboldt, Iowa. The lawsuit seeks to bar her and her firm from preparing federal tax returns for others. According to the government complaint in the case, Lemmon’s firm, Gayle’s Bookkeeping and Tax Service Inc., prepares federal income tax returns for customers that unlawfully understate tax liabilities by claiming improper deductions for the business use of the home and for non-deductible personal expenses.

Justin Hanson, 21, of Mason City, Iowa, pleaded guilty today in federal court in Cedar Rapids to violating the civil rights of an African-American family.

"With power and wealth must come responsibility and caring. You must realize that you possess real and symbolic power as lawyers and understand that you can change the whole of America for the better."