Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

The European Commission has recently published its Public Procurement Guidance for Practitioners on the avoidance of the most common errors in projects funded by the European Structural and Investment Funds ("the Guide"). We have helped...

Why is getting it right important? Each year statutory undertakers are engaged in hundreds of thousands of street works activities across the country to keep our key utilities and infrastructure running. They must all comply with the New Roads and S...

In its concern to block tax avoidance, HMRC is planning to make Stamp Duty Land Tax (SDLT) ever more complicated, as two recent consultations show. Residential properties held by companies The first consultation proposes the imposition of SDLT on ...

The European guide to strikes and other industrial action has been created by Eversheds Sutherland to provide you with a quickand easy reference when responding to threats of industrial action in 15 European countries. Click here to download the pub...

As the shipping community is truly internationally based, issues can often arise when a formal claim is issued in the English High Court that then has to be served outside the UK jurisdiction.  For example, if a dispute arises between a ship ow...

1

1

Technology is a critical aspect of improving the availability and accessibility of clean water around the world.

Asia’s economies have generally maintained sound macroeconomic policies that can help the region withstand this latest challenge and emerge even stronger.

The COVID-19 pandemic could be an opportunity to take a more holistic approach to health and well-being, invest in health systems and in resilient supply chains.

With timely and well-targeted programs, policy makers can prevent the health crisis from deepening into a wider economic and financial crisis. This could sow the seeds of economic recovery.  

Blue tits and great tits don’t need to taste unpleasant foods to avoid them – they can learn not to try them by seeing another bird’s disgusted response, even if it’s only on video

In Washington State and Boston, two initiatives are helping prevent potatoes from being thrown out and milk from being poured down the drain. Gavino Garay has more.

We are already seeing the pandemic's effects on mental health, and we need to act urgently to avoid a full-blown crisis, says Sam Howells  

Wealth Enhancement Group's Nicole Webb says small cap stocks make good bets emerging from a recession but not amid the current market volatility.

In Washington State and Boston, two initiatives are helping prevent potatoes from being thrown out and milk from being poured down the drain. Gavino Garay has more.

Title: Health Tip: Foods to Avoid If You Have Ulcerative Colitis
Category: Health News
Created: 4/28/2010 8:10:00 AM
Last Editorial Review: 4/28/2010 12:00:00 AM

Title: Health Tip: Avoid Emotional Eating
Category: Health News
Created: 5/2/2013 8:35:00 AM
Last Editorial Review: 5/2/2013 12:00:00 AM

Title: Focus on Healthy Foods, Not Avoiding 'Bad' Ones, for Heart Health: Study
Category: Health News
Created: 4/25/2016 12:00:00 AM
Last Editorial Review: 4/25/2016 12:00:00 AM

Title: Health Tip: Avoid Alcohol While Nursing
Category: Health News
Created: 4/29/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM

Title: Many Manly Men Avoid Needed Health Care
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM

Title: Health Tip: Avoid Concentrated Caffeine
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

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.

Blue-light-induced chloroplast movements play an important role in maximizing light utilization for photosynthesis in plants. Under a weak light condition, chloroplasts accumulate to the cell surface to capture light efficiently (chloroplast accumulation response). Conversely, chloroplasts escape from strong light and move to the side wall to reduce photodamage (chloroplast avoidance response). The blue light receptor phototropin (phot) regulates these chloroplast movements and optimizes leaf photosynthesis by controlling other responses in addition to chloroplast movements. Seed plants such as Arabidopsis (Arabidopsis thaliana) have phot1 and phot2. They redundantly mediate phototropism, stomatal opening, leaf flattening, and the chloroplast accumulation response. However, the chloroplast avoidance response is induced by strong blue light and regulated primarily by phot2. Phots are localized mainly on the plasma membrane. However, a substantial amount of phot2 resides on the chloroplast outer envelope. Therefore, differentially localized phot2 might have different functions. To determine the functions of plasma membrane- and chloroplast envelope-localized phot2, we tethered it to these structures with their respective targeting signals. Plasma membrane-localized phot2 regulated phototropism, leaf flattening, stomatal opening, and chloroplast movements. Chloroplast envelope-localized phot2 failed to mediate phototropism, leaf flattening, and the chloroplast accumulation response but partially regulated the chloroplast avoidance response and stomatal opening. Based on the present and previous findings, we propose that phot2 localized at the interface between the plasma membrane and the chloroplasts is required for the chloroplast avoidance response and possibly for stomatal opening as well.

Human adenoviruses have many attractive features for gene therapy applications. However, the high prevalence of preexisting immunity against these viruses in general populations worldwide has greatly limited their clinical utility. In addition, the most commonly used human adenovirus, human adenovirus subgroup C serotype 5 (HAd5), when systemically administered, triggers systemic inflammation and toxicity, with the liver being the most severely affected organ. Here, we evaluated the utility and safety of a new low-seroprevalence gorilla adenovirus (GAd; GC46) as a gene transfer vector in mice. Biodistribution studies revealed that systemically administered GAd had a selective and robust lung endothelial cell (EC) tropism with minimal vector expression throughout many other organs and tissues. Administration of a high dose of GAd accomplished extensive transgene expression in the lung yet elicited no detectable inflammatory histopathology in this organ. Furthermore, GAd, unlike HAd5, did not exhibit hepatotropism or induce liver inflammatory toxicity in mice, demonstrating the exceptional safety profile of the vector vis-à-vis systemic utility. We further demonstrated that the GAd capsid fiber shared the flexibility of the HAd5 equivalent for permitting genetic modification; GAd with the pan-EC-targeting ligand myeloid cell-binding peptide (MBP) incorporated in the capsid displayed a reduced lung tropism and efficiently retargeted gene expression to vascular beds in other organs.

IMPORTANCE In the aggregate, our mouse studies suggest that GAd is a promising gene therapy vector that utilizes lung ECs as a source of therapeutic payload production and a highly desirable toxicity profile. Further genetic engineering of the GAd capsid holds the promise of in vivo vector tropism modification and targeting.

[Having appointment with real estate experts #5] While buying a home is quite easy for high-income households, it is another story for the middle-class. With a wise and specific financial plan, the chances of owning a home can still lie within reach even if an average income.

For almost first-time home buyers, owning a home can be a very rewarding experience. With a little caution and some attention to detail, you can avoid costly mistakes.

As home sellers commonly propose to state a lower price in the sale contract than the actual transaction value, home buyers have to bear additional risks from such real estate transactions.

For a smooth and profitable deal, you should avoid these four common and costly home selling mistakes before your home hits the market.

If you make a mistake during the listing process, you might end up getting less than your home is worth or find that it takes significantly longer to sell your home than it should.

Home selling can be an emotional process, so don’t make it even tougher by letting your emotions run the process. Make sure that you don’t fall into any of these four of the most common home selling mistakes.

As with other types of investment, real estate investors need a good vision and smart strategies to make it profitable. Here are 6 important guides for investors to avoid loss and gain profit from their real estate investment.

"I just couldn't be more proud of you and the prospect of your presidency," Newsom told Biden Friday during a campaign event.

There's been a spike in scam calls, emails and texts

We are already seeing the pandemic's effects on mental health, and we need to act urgently to avoid a full-blown crisis, says Sam Howells  

False information about the pandemic is rampant; here’s how experts say you can identify what news to trust and what might be faulty

Follow our live coronavirus updates here Coronavirus: the symptoms

Follow our live Covid-19 updates HERE Coronavirus: The symptoms

Coronavirus: The symptoms

Pub visits should be avoided when social distancing measures are eased, one of the UK's top medics has said.