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Friday, October 7, 2022

NIH scientists shed light on how genetic architecture determines gene expression, tissue-specific function, and disease phenotype in blinding diseases.

National Eye Institute researchers mapped the organization of human retinal cell chromatin, the fibers that package 3 billion nucleotide-long DNA molecules into compact structures that fit into chromosomes within each cells nucleus. The resulting comprehensive gene regulatory network provides insights into regulation of gene expression in general, and in retinal function, in both rare and common eye diseases. The study published in Nature Communications.

This is the first detailed integration of retinal regulatory genome topology with genetic variants associated with age-related macular degeneration (AMD) and glaucoma, two leading causes of vision loss and blindness, said the studys lead investigator, Anand Swaroop, Ph.D., senior investigator and chief of the Neurobiology Neurodegeneration and Repair Laboratory at the NEI, part of the National Institutes of Health.

Adult human retinal cells are highly specialized sensory neurons that do not divide, and are therefore relatively stable for exploring how the chromatins three-dimensional structure contributes to the expression of genetic information.

Chromatin fibers package long strands of DNA, which are spooled around histone proteins and then repeatedly looped to form highly compact structures. All those loops create multiple contact points where genetic sequences that code for proteins interact with gene regulatory sequences, such as super enhancers, promoters, and transcription factors.

Such non-coding sequences were long considered junk DNA. But more advanced studies demonstrate ways these sequences control which genes get transcribed and when, shedding light on the specific mechanisms by which non-coding regulatory elements exert control even when their location on a DNA strand is remote from the genes they regulate.

Using deep Hi-C sequencing, a tool used for studying 3D genome organization, the researchers created a high-resolution map that included 704 million contact points within retinal cell chromatin. Maps were constructed using post-mortem retinal samples from four human donors.

The researchers then integrated that chromatin topology map with datasets on retinal genes and regulatory elements. What emerged was a dynamic picture of interactions within chromatin over time, including gene activity hot spots and areas with varying degrees of insulation from other regions of DNA.

They found distinct patterns of interaction at retinal genes suggesting how chromatins 3D organization plays an important role in tissue-specific gene regulation.

Having such a high-resolution picture of genomic architecture will continue to provide insights into the genetic control of tissue-specific functions, Swaroop said.

Furthermore, similarities between mice and human chromatin organization suggest conservation across species, underscoring the relevance of chromatin organizational patterns for retinal gene regulation. More than a third (35.7%) of gene pairs interacting through a chromatin loop in mice also did so in human retina.

The researchers integrated the chromatin topology map with data on genetic variants identified from genome-wide association studies for their involvement in AMD and glaucoma, two leading causes of vision loss and blindness. The findings point to specific candidate causal genes involved in those diseases.

The integrated genome regulatory map will also assist in evaluating genes associated with other common retina-associated diseases such as diabetic retinopathy, determining missing heritability and understanding genotype-phenotype correlations in inherited retinal and macular diseases.

The study was supported by the NEI Intramural Research Program, grants ZIAEY000450 and ZIAEY000546.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research. To learn more about basic research, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.

NEI leads the federal governments efforts to eliminate vision loss and improve quality of life through vision researchdriving innovation, fostering collaboration, expanding the vision workforce, and educating the public and key stakeholders. NEI supports basic and clinical science programs to develop sight-saving treatments and to broaden opportunities for people with vision impairment. For more information, visit https://www.nei.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Marchal C, Singh N, Batz Z, Advani J, Jaeger C, Corso-Diaz X, and Swaroop A. High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci. Published October 7, 2022, Nature Communications. DOI:10.1038/s41467-022-33427-1.

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3D map reveals DNA organization within human retina cells - nih.gov

Attorney-General and Minister for Justice, Minister for Women and Minister for the Prevention of Domestic and Family ViolenceThe Honourable Shannon Fentiman

The Palaszczuk Government has released the final report following the review of the Queensland operations of The Star Entertainment Group, along with its response.

Attorney-General and Minister for Justice Shannon Fentiman said the independent expert review conducted by the Honourable Robert Gotterson AO KC made 12 recommendations to enhance the integrity, minimise the potential for harm, ensure probity and restore public confidence in the operations of Queensland casinos.

Making sure Queensland casinos operate lawfully is a priority for the Government, the Attorney said.

Thats why I am pleased to announce that the Palaszczuk Government supports in principle all recommendations of this review.

I would like to thank Mr Gotterson andCounsel Assisting Dr Jonathon Horton KC and Ms Angela Hellewellfor their work in conducting this important review.

The Government instigated the review in June 2022 to examine serious issues with the operation and governance arrangements of the Star Group.

Mr Gottersons inquiries were informed by public hearings, the findings of the independent review of The Star Pty Ltd conducted by Mr Bell SC in NSW, and the Queensland regulators investigations and compliance work.

The Attorney said the review examined a broad range of issues, and highlights major failings and concerns, including:

As a result of these findings, and the findings of Mr Bell SCs Inquiry in NSW, Mr Gotterson found that the actions of The Star left open a finding of unsuitability to hold a casino licence in Queensland.

Considering the serious and concerning findings of the Gotterson Review and his advice regarding suitability, I have formed the view that The Star is unsuitable to hold a licence in Queensland, the Attorney said.

In accordance with the legislation, once aformal determination of unsuitability is made, The Star will be given the opportunity to respond to that finding through a show cause process.

Following the show cause process, a range of remedial actions will be available to Government, including fines, suspending or cancelling licenses, and as recommended by Mr Gotterson, appointing a special manager, as has been done in Victoria.

The Queensland Government supports in principle all 12 recommendations of the Gotterson review, these include:

The Government has also determined to raise the maximum penalty that can be imposed on a casino to a proposed $100 million.

Mr Gotterson found no suggestion of any inappropriate interference by the Minister of the day or Government in regulatory decisions relating to The Star. Similarly, Mr Gotterson did not find sufficient justification to change fundamentally the structure of the Queensland regulator.

However, in regard to the Queens Wharf Financial Commitment Agreement regulatory restrictions and compensation clauses, he noted that the State legislature should not be fettered in its capacity to impose controls on casinos or compensate them in any way for having done so.

Government has agreed with Mr Gottersons advice and will act accordingly.

The report can be found online here: https://www.justice.qld.gov.au/initiatives/external-review-qld-operations-star-entertainment-group

ENDS

Media contact: Phoenix Campbell 0439 949 719

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Government responds to The Star review - Ministerial Media Statements - Media Statements

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As one of the most famous athletes in the world,LeBron Jamesis used to having his every move scrutinized by the media. But after years of feeling misrepresented, the NBA star decided to take matters into his own hands by launching his own media company.

With over$300 million earned from the NBAalone, the business-savvy athlete has used his platform and influence to create content that tells his story in his own words.

James is not new to the business world. The NBA star has committed to numerous endorsement deals and business ventures. However, James entrance into the media world is perhaps his most impressive.

In 2014, the 37-year-old teamed up with business partner Maverick Carter to launch Uninterrupted, a digital media company that produces content focused on athletes and their stories. The multimedia platform allows athletes to connect with their fans by giving testimonials regarding their experiences without the interference of traditional media.

James and Carter chose the name Uninterrupted because they wanted to create a space where athletes could connect with their fans and uninterruptedly tell their stories and experiences.

In an interview withSports Illustrated, James explains that he wants to be able to tell his story, in his own words, not just for himself but for his family too. I got tired of media altering the narrative or picking whatever suits their narrative regarding what I was doing, James explained. He feels that if the public and the media will fashion an image for you and your family, it is best to control it rather than watch it play out.

This sentiment is echoed in his statement about wanting to play in the NBA with his sons. After James floated the idea, most people began speculating about his future. However, with Uninterrupted, the media had no chance to miss coverage or provide false narratives about what he said.

Instead, LeBron was able to tell his story on his terms. In addition to providing athletes with a platform to share their stories, Uninterrupted has produced various content. The company has released severaldocumentariesand web series.

In addition to Uninterrupted, James also has five other notable business ventures. These include a Beats by Dre partnership, production company SpringHill Entertainment, and investments in various companies likeBlaze PizzaandLiverpool Football Club. Hes also invested in Boston Red Sox and Fenway Sports Group. Recently, James added anew Pepsi Productto his ever-expanding business portfolio.

While some may see the Ohio natives business ventures as another way to make money, its clear the NBA star is using his platform and influence to create opportunities for himself and others. With Uninterrupted, hes enabled the production of various projects, including The Shop. Initially available on HBO, LeBron and his team have moved the unscripted series to YouTube to reach a wider audience. Other projects produced through Uninterrupted includeFate of a Sport, Road to Discovery, HBCUs Rising and more.

With multiple successful ventures under James belt, there is no telling what he will do next. But one thing is for sure: He will continue to tell his story on his terms.

RELATED: Ray Allen Completely Dismisses LeBron James as the GOAT: He Aint Even Great In All Those Categories

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LeBron James Launched His Own Media Company When the NBA Star Realized He Needs to Control His Own Narrative - Sportscasting

Social media use exploded with COVID-19s lockdowns and contact restrictions. Millions turned to Facebook, TikTok, Twitter, and other platforms to escape feelings of isolation, anxiety, and hopelessness.

However, excessive screen time has led to addictive behaviors, stronger emotional attachment to social media, and deeper mental anguish for many people.

Researchers at the Ruhr-Universittt in Bochum, Germany investigated the effects of reducing social media use (SMU) and increasing physical activity, or both, on emotional well-being and tobacco consumption.

Julia Brailosvskaia, Ph.D., an assistant professor at the universitys Mental Health Research and Treatment Center, led the two-week experiment.

Brailosvskaia and her team observed that the interventions they suggested may have helped enhance participants satisfaction with life. At a 6-month follow-up, the subjects continued to report spending less time on social media, maintaining physical activity, feeling happier, and smoking fewer cigarettes.

The Journal of Public Health recently published these findings.

The studys authors noted that mental health consists of two interrelated but separate dimensions: positive and negative.

With this paradigm, they hypothesized that the positive dimension of their intervention would increase life satisfaction and subjective happiness. The negative dimension would decrease depression symptoms and addictive tendencies of SMU.

Medical News Today discussed this study with Dr.Sheldon Zablow, an author and nutritional psychiatrist. He was not involved in the research.

When asked about the effects of social media on mental health, Dr. Zablow asserted:

If activities interfere with customary basic age-appropriate milestones of economic self-sufficiency, socialization, or health maintenance, then they are detrimental. The activities could be alcohol use, substance use, dietary choices, exercise choices, or entertainment choicesspecifically social media.

Dr. Zablow warned that excessive social media use weakens social interpersonal bonds, which can negatively impact mental health.

MNT also spoke with Dr. David A. Merrill, adult and geriatric psychiatrist and director of the Pacific Neuroscience Institutes Pacific Brain Health Center at Providence Saint Johns Health Center in Santa Monica, CA, regarding the present study. He was not involved in the research.

Dr. Merrill argued that the term social media is a misnomer thats almost like a bait and switch, designed to increase user engagement.

Too much social media use, he said, could end up exacerbating mental issues for people with behavioral health conditions or addictive vulnerabilities.

Theres the brain reward system that you get from clicking or scrolling or maintaining the use of the social media, Dr. Merrill said.

I think [that the authors are] demonstrating causally that you both need to have a conscious awareness of the need to limit the self-soothing aspect of social media use, and you also need to have alternatives, so you need to have some other way to bring joy into your life, and especially during the pandemic.

As a psychiatrist, Dr. Zablow emphasized that the essential part of any treatment program recommended is exercise. Psychotherapy and, when indicated, medication, will not work well if a person does not exercise.

Dr. Zablow added that exercise increases the production of neurotransmitters, the brains natural antidepressants and antianxiety molecules.

Consequently, more exercise can build mental health, while less activity due to social media overuse can curtail healthy brain chemistry.

Dr. Brailosvskaia and her colleagues reasoned that a conscious and controlled reduction of time spent on SMU as well as an increase of time spent on physical activity could causally reduce negative mental health consequences of the COVID-19 situation. They also believed that combining both interventions might amplify this effect.

The professor mentioned that the methods can easily fit into everyday life with little cost, effort, or risk of violating COVID-19 protocols.

Further, the scientists expected their experiment to reduce stress caused by COVID-19 and diminish smoking behavior.

The researchers recruited 642 healthy adult social media users and placed them in 4 experimental groups.

The social media (SM) group had 162 individuals, the physical activity (PA) group of 161, a combination group of 159, and a control group of 160.

Over 2 weeks, the SM subjects reduced their daily SMU time by 30 minutes and the PA group increased their daily physical activity by 30 minutes. The combination group applied both interventions, while the control did not change their behaviors.

Following the World Health Organizations physical activity recommendations for adults, the first three groups increased their exercise time by 30 minutes.

The participants completed online surveys and daily compliance diaries at the start of the trial, 1 week later, and after the 2-week period. They also submitted follow-up surveys at 1, 3, and 6 months post-experiment.

Dr. Brailosvskaia and her team concluded that their interventions helped people decrease the time they spend with SM.

Even 6 months after the experiment, the participants had reduced their daily initial SM time by about 37 minutes in the SM group, by about 33 minutes in the PA group, and by about 46 minutes in the combination group.

Moreover, participants reported having a decreased emotional bond with social media.

All the interventions encouraged more physical activity as well. Six months later, our participants had enhanced their initial weekly physical activity time for 26 minutes in the SM group, for 40 minutes in the PA group, and for 1 hour 39 minutes in the combination group, the authors wrote.

Even the control group increased their activity by 20 minutes.

Dr. Merrill was impressed with the studys striking findings with the combination of reducing social media with increasing physical activity. He agreed with the notion that SMU restrictions need a complementing activity that brings joy or a sense of achievement.

According to the studys authors, the experimental longitudinal design of their present research allowed them to establish causality.

However, the study population lacked diversity. All the participants were young, female, German, Caucasian, and highly educated.

Dr. Merrill felt that, while it would be interesting to replicate this investigation in the United States with a more diverse group, the results would likely be similar.

The study did not consider which form of SMU the subjects were using or specify which type of physical activity the participants engaged in. The researchers hope that future work will focus more on these factors.

Dr. Brailosvskaias research suggests that modest changes in SMU and physical activity could help protect and enhance mental health conveniently and affordably.

The professor and her team recognize how SMU can minimize isolation and help spread information.

From time to time, it is important to consciously limit ones online accessibility and to go back to the human roots [] a physically active lifestyle to stay happy and healthy in the age of digitalization, the researchers wrote.

Excerpt from:
Mental health benefits of replacing social media with exercise - Medical News Today