Introduction:

Understanding patients’ perspectives about their diabetes and what causes those perspectives to shift is critical to building a treatment strategy with the patient and facilitating patient self-management behavior. Key "turning points" can provide crucial opportunities to enact a change in perspective. The goal of this study is to identify "turning points" that have significance to diabetes-related health.

Arrestin-1 is the arrestin family member responsible for inactivation of the G protein–coupled receptor rhodopsin in photoreceptors. Arrestin-1 is also well-known to interact with additional protein partners and to affect other signaling cascades beyond phototransduction. In this study, we investigated one of these alternative arrestin-1 binding partners, the glycolysis enzyme enolase-1, to map the molecular contact sites between these two proteins and investigate how the binding of arrestin-1 affects the catalytic activity of enolase-1. Using fluorescence quench protection of strategically placed fluorophores on the arrestin-1 surface, we observed that arrestin-1 primarily engages enolase-1 along a surface that is opposite of the side of arrestin-1 that binds photoactivated rhodopsin. Using this information, we developed a molecular model of the arrestin-1–enolase-1 complex, which was validated by targeted substitutions of charge-pair interactions. Finally, we identified the likely source of arrestin's modulation of enolase-1 catalysis, showing that selective substitution of two amino acids in arrestin-1 can completely remove its effect on enolase-1 activity while still remaining bound to enolase-1. These findings open up opportunities for examining the functional effects of arrestin-1 on enolase-1 activity in photoreceptors and their surrounding cells.

ABSTRACT

Interspecific hybridization can drive evolutionary adaptation to novel environments. The Saccharomycotina clade of budding yeasts includes many hybrid lineages, and hybridization has been proposed as a source for new pathogenic species. Candida orthopsilosis is an emerging opportunistic pathogen for which most clinical isolates are hybrids, each derived from one of at least four independent crosses between the same two parental lineages. To gain insight into the transcriptomic aftermath of hybridization in these pathogens, we analyzed allele-specific gene expression in two independently formed hybrid strains and in a homozygous strain representative of one parental lineage. Our results show that the effect of hybridization on overall gene expression is rather limited, affecting ~4% of the genes studied. However, we identified a larger effect in terms of imbalanced allelic expression, affecting ~9.5% of the heterozygous genes in the hybrids. This effect was larger in the hybrid with more extensive loss of heterozygosity, which may indicate a tendency to avoid loss of heterozygosity in these genes. Consistently, the number of shared genes with allele-specific expression in the two independently formed hybrids was higher than random expectation, suggesting selective retention. Some of the imbalanced genes have functions related to pathogenicity, including zinc transport and superoxide dismutase activities. While it remains unclear whether the observed imbalanced genes play a role in virulence, our results suggest that differences in allele-specific expression may add an additional layer of phenotypic plasticity to traits related to virulence in C. orthopsilosis hybrids.

IMPORTANCE How new pathogens emerge is an important question that remains largely unanswered. Some emerging yeast pathogens are hybrids originated through the crossing of two different species, but how hybridization contributes to higher virulence is unclear. Here, we show that hybrids selectively retain gene regulation plasticity inherited from the two parents and that this plasticity affects genes involved in virulence.

Childbirth at any age confers a transient increased risk for breast cancer in the first decade postpartum and this window of adverse effect extends over two decades in women with late-age first childbirth (>35 years of age). Crossover to the protective effect of pregnancy is dependent on age at first pregnancy, with young mothers receiving the most benefit. Furthermore, breast cancer diagnosis during the 5- to 10-year postpartum window associates with high risk for subsequent metastatic disease. Notably, lactation has been shown to be protective against breast cancer incidence overall, with varying degrees of protection by race, multiparity, and lifetime duration of lactation. An effect for lactation on breast cancer outcome after diagnosis has not been described. We discuss the most recent data and mechanistic insights underlying these epidemiologic findings. Postpartum involution of the breast has been identified as a key mediator of the increased risk for metastasis in women diagnosed within 5–10 years of a completed pregnancy. During breast involution, immune avoidance, increased lymphatic network, extracellular matrix remodeling, and increased seeding to the liver and lymph node work as interconnected pathways, leading to the adverse effect of a postpartum diagnosis. We al discuss a novel mechanism underlying the protective effect of breastfeeding. Collectively, these mechanistic insights offer potential therapeutic avenues for the prevention and/or improved treatment of postpartum breast cancer.

Premier industry experts also share an overview of the first quarter of the year, as well as brief market forecasts.

Once the ‘go-to guy for feckless losers’, the actor is now spearheading Apple’s assault on British TV. He talks about flops, racism, chest hair – and Laurence Fox

In October 2005, Rafe Spall was starring in the role he thought he was born to play. Only 21 at the time, he’d bagged a part in Anna Mackmin’s reimagining of Francis Beaumont’s 1607 comedy The Knight of the Burning Pestle at the Barbican. The play isn’t just any old Renaissance play in the Spall household, it’s a hallowed text.

His father (Timothy Spall, you might have heard of him) had played the same part in a 1981 RSC version that changed his life for ever. It was while playing that role he met his wife, Shane, and the pair loved the play so much they decided to give their first child the name of the character his father played: Rafe. To make it seem even more preordained, it was Rafe’s grandmother’s favourite ever performance by his father. No pressure, then.

Even before the COVID-19 shutdown, venture funding rounds and total deal volume of VC funding for esports were down noticeably from the year prior. The space received a lot of attention in 2017 and 2018 as leagues formed, teams raised money and surging popularity fostered a whole ecosystem of new companies. Last year featured some […]

As the infrastructure for developing games becomes more advanced, studios have turned to buying best-in-class technology from others instead of building everything from scratch (often with inferior quality). This shift underpinned Unity’s rise as the most popular game engine. The current focus on games as ever-evolving social hubs that can remain popular for a decade […]

Hulu debuts Solar Opposites, a new animated sitcom created by Rick and Morty's Justin Roiland and Mike McMahan, but don't expect more of the same.

Sierra Leone's president Julius Maada Bio has accused the main opposition party of orchestrating a spate of violent incidents, deepening a political standoff that risks undermining the country's efforts to contain a coronavirus outbreak.

Environmental campaigners against electric plant and pipeline say Samir Flores Soberanes’s murder is a ‘political crime’

A Mexican environmental activist has been murdered before a referendum on a controversial thermal-electric plant and pipeline that he opposed.

Samir Flores Soberanes, an indigenous Náhuatl, was killed in his home during the early hours of Wednesday in the town of Amilcingo in Morelos state, 80 miles south of Mexico City. He was a human rights activist, producer for a community radio station and long-time opponent of the Proyecto Integral Morelos (the integral project for Morelos) – which includes the plant and pipeline.

Read our live coronavirus updates HERE

Coronavirus: the symptoms Read our LIVE updates on the coronavirus here

Most Brits are against ending the coronavirus lockdown this week, with less than one in five thinking the time is right to reopen pubs, restaurants, stadiums and schools, a new survey shows.

Felix Project volunteer Lauren Graham shares her story You can donate at virginmoneygiving.com/fund/FoodforLondonNOW

Myan Mode, a garment factory on the outskirts of Yangon, Myanmar, produces men's jackets, women's blazers and coats for Western fashion companies like Mango and Zara. Since the start of the coronavirus pandemic, it has seen a decrease in orders from international retailers.That was why it let go almost half of its 1,274 workers in late March, the factory's managing director said in response to protesters who arrived at the factory's doors to denounce the dismissals.Three fired sewing operators, however, said the factory was taking an opportunity to punish workers engaged in union activity. In an interview, the operators -- Maung Moe, Ye Yint and Ohnmar Myint -- said that of the 571 who had been dismissed, 520 had belonged to the factory's union, one of 20 that make up the Federation of Garment Workers Myanmar. About 700 workers who did not belong to the union kept their jobs, they said.Myan Mode's South Korean-based owner did not respond to requests for comment, and did not provide details about the firings.Moe, 27, was the factory union's president and had organized several strikes. Yint, 30, was the union's secretary, while Myint, 34, had been a union member since its founding in June 2018."The bosses used COVID as an opportunity to get rid of us because they hated our union," Moe said. He said he and other union members had been in discussions with the factory managers before the firings, demanding personal protective equipment and that workers be farther apart on the factory floor. "They thought we caused them constant headaches by fighting for our rights and those of our fellow workers."Union-busting -- practices undertaken to prevent or disrupt the formation of trade unions or attempts to expand membership -- has been a serious problem across the fashion supply chain for decades. But with the global spread of COVID-19 placing fresh pressures on the industry, it is a particular issue in South Asia, where about 40 million garment workers have long grappled with poor working conditions and wages."Union-busting is not a COVID-specific issue for the garment industry -- it happens all the time," said Luke Smitham of the sustainability consultancy Kumi Consulting.Zara's parent company, Inditex, which is supplied by Myan Mode, said its code of conduct for manufacturers expressly prohibited any discrimination against worker representatives. The company said in an email that it was "actively following the situation" at Myan Mode, and would "try to achieve the best possible solution for workers."Mango, which has started to reopen its stores in Europe, said in an emailed statement that it "understood the need to ensure that the human rights of factory workers are respected." The company added that it was maintaining "a continuous" dialogue with suppliers.Roughly 2% of garment workers in Myanmar, where the minimum wage is roughly $3.50 a day, and 0.5% of garment workers in Bangladesh belong to a union, according to affiliate data estimates collected by the global trade union IndustriALL. While Cambodia's workforce is more unionized than others in the region -- around 80% -- the unions there are fragmented, meaning successful collective bargaining negotiations can be difficult.Tear gas, water cannons, police brutality and imprisonment were some of the tools used by the governments of Bangladesh, Cambodia, India and Myanmar to punish striking garment workers and union members last year, according to the International Trade Union Confederation, an umbrella group for unions around the world. It noted that many workers in those countries who tried to form a union were dismissed from jobs or blacklisted by factories. And the number of countries that exclude workers from the right to establish or join a trade union increased to 107 in 2019 from 92 in 2018.Andrew Tillett-Saks, a labor organizer in Yangon, said he had seen a surge in unionizing by garment workers in Myanmar over the last 18 months -- and a reaction from factory owners. Before the pandemic, he said, some garment factories with fledgling unions were abruptly closing and firing union members, then reopening weeks later to supply the same brands under a slightly different name with a new group of nonunionized workers.Tillett-Saks said that much of the focus had been on whether brands would pay wages for workers during the pandemic, or for orders that had already been produced. But factory owners "taking this as an opportunity to break down labor movements in the supply chain could be an even bigger issue."Some brands, like H&M, have tried to facilitate union activity in supplier factories by signing ACT, an agreement brokered by IndustriALL and designed to secure fair wages for workers through collective bargaining and building guarantees of labor rights into purchasing agreements. But there are still hurdles. Before the International Labor Organization, a U.N. agency, can take action, allegations of mistreatment must be sent in writing from a national or international trade union organization and then reviewed internally by the agency -- a complicated process even before the pandemic."We have heard allegations of anti-union discrimination in recent weeks," said John Ritchotte, a specialist in social dialogue and labor administration in Asia for the International Labor Organization. "However, it is currently more difficult than usual for us to verify those allegations through our usual procedures because of travel restrictions and local lockdowns."In the weeks since the Myan Mode layoffs, around 15,000 jobs in the textile industry have been lost and about 40 factories closed across Asia, said Khaing Zar Aung, president of Industrial Workers Federation of Myanmar.Moe said the fired Myan Mode workers had protested outside the factory for weeks, watching as daily wage workers entered and scores of exhausted former colleagues left at midnight after overtime shifts. Eventually, management offered severance but not re-employment to the 571 fired workers, plus 49 employees who had walked out in solidarity. All but 79 eventually took the severance pay.The Garment Manufacturers Association in Cambodia said about 60% of its factories -- where union members have also been targeted -- had been severely affected by canceled orders of ready-made garment exports because of the pandemic.On March 31, several dozen union workers at the Superl leatherwear factory on the outskirts of Phnom Penh -- which produces handbags for brands like Michael Kors, Tory Burch and Kate Spade -- were told they were being let go. One was a woman who was six months pregnant.Soy Sros, a factory shop steward and the local president of the Collective Union of Movement of Workers, wrote about the company's actions on Facebook, stating it violated a March 6 appeal from the Cambodian government saying COVID should not be used as a chance to discriminate against union members.Twenty-four hours later, Sros was forced by factory management to take down her post and make a thumbprint on a warning letter accusing her of defamation. On April 2, she was removed from the factory floor by the police and charged with posting fake information on social media. She is now in jail.Superl, which is headquartered in Hong Kong, did not respond to requests for comment, nor did Michael Kors and Tory Burch, who regularly place orders at the factory. Another customer, Tapestry, the owner of Kate Spade, declined to comment.In Myanmar, Moe, Yint and Myint all said they did not regret joining the union despite the difficulties they had faced. They said the loss of jobs was proof that worker representation was needed."I worry for the future of garment workers here without representatives," Myint said, referring to both the firings at Myan Mode and other factories across Asia. "But for now, I worry about providing for my family and getting food on the table."This article originally appeared in The New York Times.(C) 2020 The New York Times Company

Cybertip.ca, an online sexual exploitation of children tipline, says it saw a 66 per cent spike in reports in April.

My brother's death last month caused great pain. COVID-19 and its restrictions, which have delayed his funeral, made grieving so much harder.

'I've realized my comments on risks around opening schools have confused and upset people'

Brighton have become the first Premier League club to publicly oppose proposals to play matches at neutral venues if and when the season resumes.

Crystal Palace chairman Steve Parish has warned the bottom six clubs opposing the resumption of the Premier League in neutral grounds that they are not taking the financial threat to the league seriously enough.

Gladys Berejiklian has again ruled out the prospect of pill testing at music festivals despite a leaked draft coroner's report recommending the move.

Televangelist Jim Bakker is being sued over his promotion of a coronavirus cure. Then there's Scalar Light, a Florida company that says it can "disassemble pathogens" at the quantum level.

Climate experts say the way Australia chooses to rebuild its economy after the COVID-19 pandemic will seal its climate change fate.

The modelling predicts more than a quarter of a million jobs could be lost in Victoria due to the coronavirus pandemic in what Premier Daniel Andrews says is the perhaps the "biggest economic and employment challenge" in the state's history.

New Zealand's careful climb out of Covid-19 restrictions has been a tale of two journeys.To envious overseas eyes, we have been a smooth success story and a source of hope to others. At home, the reaction has been a lot more mixed.We...

But if he wants to avoid being the target of their protests both before and—if he’s elected—after November, he’ll need to earn more than just their votes.

With major sporting competitions on hold because of coronavirus, now is the time to reassess how we approach the sport-lifestyle balance of professional athletes and even how they are recruited, writes Richard Hinds.

By: Daniel Dwyer and Daniel Logan On March 27, 2020, the President signed into law the Coronavirus Aid, Relief, and Economic Security Act, or “CARES” Act (Pub. Law 116-136), which includes a comprehensive revision of the rules governing over-the-counter (OTC) drugs currently marketed under monographs published by the Food and Drug Administration (FDA).  This law

The post New Opportunities for OTC Monograph Drugs under the CARES Act appeared first on Kleinfeld Kaplan & Becker LLP.

Today, Chairs of the House Committees that oversee the Department of Health and Human Services (HHS) voiced their strong opposition to a harmful Trump Administration rule that would roll back Affordable Care Act (ACA) nondiscrimination protections. In a letter, House Energy and Commerce Committee Chairman Frank Pallone, Jr. (D-NJ), House Ways and Means Committee Chairman Richard E. Neal (D-MA), House Education and Labor Committee Chairman Bobby Scott (D-VA), and House Oversight and Reform Committee Chairwoman Carolyn B. Maloney (D-NY) urged HHS Secretary Alex Azar not to finalize this troubling rule and to instead focus on responding to the COVID-19 pandemic. The rule would overturn core protections for marginalized communities including LGBTQ+ people, women, individuals with limited English proficiency, and individuals with disabilities, and eliminate many health care programs and activities from coverage of the Affordable Care Act’s nondiscrimination requirements. “At a time when the United States is grappling with the 2019 coronavirus (COVID-19) pandemic and access to health care services is so critical, we are disappointed that this Administration is once again taking steps to limit access to health care and embolden discrimination against some of the most vulnerable among us,” the Chairs wrote. “If finalized, this dangerous rule would open the door to discrimination against patients in express contradiction to the plain language and intent of the law, and would therefore be illegal. Undermining protections for marginalized individuals at any time is unacceptable, but it is particularly egregious to do so during the worst global pandemic in over a century.” Read the full letter to Secretary Azar HERE. ###

In May of 2017 the Board of Directors of the Association of Clinical Research Organizations, which represents the world’s leading clinical research...

A British citizen was charged in connection with the operation of a series of fraudulent business opportunities on March 10, 2009, by a Miami federal grand jury. Sirtaj Mathauda was indicted on charges that he and his co-conspirators purported to sell vending machine, beverage and greeting card business opportunities, including assistance in establishing, maintaining and operating such businesses. The charges form part of the government’s continued nationwide crackdown on business opportunity fraud.

A Miami federal grand jury has charged two South Florida men with conspiracy, mail and wire fraud in connection with the operation of a fraudulent ATM business opportunity. The criminal charges are part of the government’s continued nationwide crackdown on business opportunity fraud.

A Tampa federal grand jury has charged a Florida man with criminal contempt of a federal court order in connection with the operation of a fraudulent vending machine business opportunity. The criminal charges form part of the government’s continued nationwide crackdown on business opportunity fraud.

A British citizen charged in connection with the operation of a series of fraudulent business opportunities was arrested Thursday evening in Miami following his indictment by a Miami federal grand jury on June 9, 2009.

On Aug.11, 2009, two individuals were sentenced in connection with South Florida business opportunity scams. Stewart Pope was sentenced in connection with his participation in fraudulent business opportunity sales at a Miami firm called Global Resources (“Global”).

On Jan. 13, 2010, Dilraj Mathauda entered a guilty plea in federal district court in Miami Federal to one count of an indictment pending against him, charging conspiracy to commit mail and wire fraud.

Stephen Schultz entered a guilty plea in federal district court in Miami to 12 counts of an indictment pending against him.

The Department entered into a settlement agreement with the Monroe City School District to address the educational inequities between schools serving virtually all black student populations and those schools that serve most of the district’s white students.

The Justice Department announced today that it has reached an out-of-court settlement in the matter of J.L. v. Mohawk Central School District, a lawsuit which the United States sought to join to address alleged violations of the Equal Protection Clause of the Fourteenth Amendment to the United States Constitution and Title IX of the Education Amendments of 1972, both of which prohibit discrimination based on sex, including discrimination based on gender stereotypes

Defendant Stephen Schultz was sentenced in connection with a series of Costa Rica-based business opportunity fraud ventures.

A federal court has ordered the Walthall County, Miss., School District to eliminate policies that have resulted in significant racial segregation among students in the school district.

Dilraj “Rosh” Mathauda was sentenced yesterday by U.S. District Court Judge Joan A. Lenard in Miami to a term of 115 months in prison and five years of supervised release for illegally operating a series of Costa Rica-based business opportunity fraud ventures.