ABSTRACT

Reversible repression of HIV-1 5' long terminal repeat (5'-LTR)-mediated transcription represents the main mechanism for HIV-1 to maintain latency. Identification of host factors that modulate LTR activity and viral latency may help develop new antiretroviral therapies. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are known to regulate gene expression and possess multiple physiological functions. hnRNP family members have recently been identified as the sensors for viral nucleic acids to induce antiviral responses, highlighting the crucial roles of hnRNPs in regulating viral infection. A member of the hnRNP family, X-linked RNA-binding motif protein (RBMX), has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5'-LTR-driven transcription of viral genome in CD4⁺ T cells. Mechanistically, RBMX binds to HIV-1 proviral DNA at the LTR downstream region and maintains the repressive trimethylation of histone H3 lysine 9 (H3K9me3), leading to a blockage of the recruitment of the positive transcription factor phosphorylated RNA polymerase II (RNA pol II) and consequential impediment of transcription elongation. This RBMX-mediated modulation of HIV-1 transcription maintains viral latency by inhibiting viral reactivation from an integrated proviral DNA. Our findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.

IMPORTANCE HIV-1 latency featuring silence of transcription from HIV-1 proviral DNA represents a major obstacle for HIV-1 eradication. Reversible repression of HIV-1 5'-LTR-mediated transcription represents the main mechanism for HIV-1 to maintain latency. The 5'-LTR-driven HIV gene transcription can be modulated by multiple host factors and mechanisms. The hnRNPs are known to regulate gene expression. A member of the hnRNP family, RBMX, has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5'-LTR-driven transcription of viral genome in CD4⁺ T cells and maintains viral latency. These findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.

Decades of rallying cries from professional societies, medical education and training programs, and government stakeholders have distilled the conversation of social determinants of health (SDOH) from theoretical proposals into practical solutions [1-3]. No longer standing on the precipice of change, we are now in the trenches. The nation's health care system recognizes SDOH as important drivers of health and is taking steps to address them in the practice environment.

More widespread action and attention by the health care system drives the need to train the next generation of physicians in the concepts and actions related to SDOH. This includes SDOH as a core part of the medical curriculum, offering clinical and research experiences and service in the community [4-5]. Unfortunately, to date only a handful of programs have brought this vision to fruition. Across the country, most programs offer educational content that is largely didactic and provided in short or one-time sessions [6]. Though a start, such approaches are insufficient to prepare the next generation of physicians for their important work ahead.

In New Orleans, the NOLA Hotspotters are an interdisciplinary group of medical, public health, nursing, and pharmacy students inspired by the work out of Camden, New Jersey, to "hot spot" patients with high utilization, which is often related to social needs [7]. While the results of the Camden program have been widely discussed following publication of their work, we argue the benefit of such a program exists beyond reduced emergency department visits or health care spending [8]. The...

Objective

To use the variations in neurology consultations requested by emergency department (ED) physicians to identify opportunities to implement multidisciplinary interventions in an effort to reduce ED overcrowding.

Live streaming isn’t a trend; it’s fast becoming the dominant form of communication in the connected age. In fact, 78% of online audiences are already […]

The post How to Bring Your Live Events to the Next Level with Interactive Video Streaming appeared first on e-Learning Feeds.

Watch everything unfold in real time, rather than reading about it later.

As a very ugly standoff develops between legacy cinemas and legacy studios, Disney appears to be playing its cards close to its chest.

DJ D-Nice, Miley Cyrus, Ben Gibbard, and a lot of Diplo.

Today, Microsoft and Ebb Studios revealed that Xbox Series X would be getting the launch exclusivity for Scorn

As novel coronavirus spreads throughout the United States, millions of Americans are spending more time at home.MORE: Here's everything coming to Disney+ in AprilBut whether you're doing so because of a job loss, working from home situation or otherwise taking part in the mass effort to stay safe, chances are you've been bored once or twice while living under quarantine.Thankfully, some very talented people have been creating extra-special performances and experiences that you can enjoy to help you cope with the new normal and that don't break any social distancing rules. ...

With cinemas closed and major titles delaying their release, the Academy has changed its rules to welcome some streaming titles. Will they regret it?

‘What about the Oscars?” might not be the question at the top of your mind as you consider the manifold uncertainties raised by the coronavirus pandemic. A Hollywood awards ceremony scheduled for the end of February 2021, one might think, has fewer immediate concerns than most cultural institutions do right now. Yet panic has been rising within the Academy: the show itself may go on, but with cinemas closed for the foreseeable future and dozens of major titles either rescheduling or indefinitely delaying their release dates, will it have have enough standout films to celebrate?

For some weeks now, the joke around the industry has been that Leigh Whannell’s hit psychothriller The Invisible Man – one of the few popular and critical successes to be released in the year’s early months – may as well collect its gongs now. But a crucial rule change announced on Tuesday by Academy CEO Dawn Hudson and president David Rubin has ensured that it will face some competition after all, even if its rivals never see the inside of a cinema.

Elizabeth Sankey’s fine documentary on the genre, premiering on Mubi, could be the perfect spark for your own romantic comedy love-in

Romantic comedies are a perennially undervalued genre: even very fine ones are often described as “guilty pleasures”. That’s always a nonsense term, given that no pleasure is without value or grace – least of all these days. Under lockdown, don’t you find yourself more inclined towards romantic comedies both great and mediocre, to sink yourself in the familiar warmth of stories driven by love and tenderness, where everything tends to turn out fine?

Mubi has thus chosen an opportune moment to premiere Romantic Comedy, a spry, affectionate documentary by musician turned film-maker Elizabeth Sankey that gives this maligned genre its due. A short, accessible film essay that did the festival rounds last year, it cuts to the heart of why romcoms have to work harder to be taken seriously – hint: they tend to prioritise the female viewer – and unpicks their history of flawed gender politics and heteronormative bias. But it’s a loving exercise, overlaid with droll personal commentary, and one that will have you jotting down a playlist of films to watch right after.

Twitch is doubling down on esports in this new era of social distancing as a number of traditional sporting events have been cancelled. The company this week introduced a new esports directory on its site that will make it easier for viewers to find live matches, information on players, games with active competition leagues, a […]

UFC returns to action this weekend with an action-packed card of action from Florida.The mixed martial arts organisation comes back after a coronavirus-enforced hiatus on Saturday night in Jacksonville with a 11-fight bill headlined by Tony Ferguson’s clash against Justin Gaethje for the interim lightweight title.

The real house from ‘The Conjuring’ movie set to be...

The post The Real House From ‘The Conjuring’ To Be Live-Streamed For A Week appeared first on Man's World India.

Dealmaster also has deals on Kindles, our top Thunderbolt 3 dock, and more.

Follow our live coronavirus updates HERE Coronavirus: the symptoms

Streamed films will be eligible for next year's Oscars due to the Covid-19 impact on the industry.

The Supreme Court, for the first time, livestreamed its oral argument on Monday. It has discussed whether generic terms can become protected trademarks by the addition of a dot-com domain.

The Bengaluru turn up on dissonance and retain prog flavors on their latest song

The post Exclusive Stream: Tangents Bring Twisted Metal on ‘IGOR’ appeared first on My Site.

What is Value Stream Management? Value Stream Management (VSM) is the TLA du jour among software development tools, so is it relevant…

First and last names, email addresses, gender and sexual orientation, and credit card information of models and users was left on an insecure server

Celebrate VE Day with Mike Newell's 2018 WW2 film.

From a mysterious toilet flush to Justice Ruth Bader Ginsburg speaking from the hospital, here are the highlights — including audio clips — from a historic week for the high court.

Coronavirus pandemic has caused production shutdowns and delays

There are loads of titles you didn't know were on the streaming service

The latest in our series of writers recommending hidden films available to stream is a invite to travel back to 1932 for a brutal thriller

Some film tropes get wheeled out so often they create their own furrow. Perhaps that’s why the timeworn premise of “man hunting man” has evolved into its own disreputable but seemingly indestructible mini-genre. This year has already seen the deferred release of scattershot satire The Hunt, a button-pushing thriller from the Blumhouse production line in which snooty US liberals kidnap and stalk blue-collar “deplorables” in a customised paddock sited far from flyover country.

Related: 'My favourite forgotten film' – you recommend your best streaming gems

The stylist's partner found himself in shot during a Facebook live

From learning Spanish to playing music, Happity is helping to keep toddlers occupied at home

Netflix is cutting down traffic to ease internet capacity as more people work from home. Here’s what it means for Australians’ streaming experience

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Netflix has agreed to reduce the data it uses to stream movies and TV shows across Australia as more and more people are working from home due to the coronavirus shutdown. But what will it mean for your viewing habits while you’re staying at home?

Related: Australian government asks Netflix and Stan to reduce data to avoid broadband overload

Related: As cinemas go dark, the film industry may go straight to Netflix

While global sport remains at a standstill due to the coronavirus pandemic, 20 players from some of European football's biggest clubs will substitute their boots for controllers as they compete in the EA Sports's Fifa 20 Stay and Play Cup.

Football has been suspended for the foreseeable future due to the coronavirus pandemic.

Football has been suspended for the foreseeable future due to the coronavirus pandemic.

With the Premier League on hold, players will be swapping their boots for controllers as they take to battle on FIFA 20 in the inaugural ePremier League Invitational tournament starting today (April 21).

Football fans will have the chance to embark upon a nostalgic journey over the next few weeks as ITV screen the 1996 European Championships in their entirety.

Football fans will finally have some live action to watch on Friday, when the South Korean K-League returns from its coronavirus shutdown.

As fans of European clubs nervously wait to find out when the beautiful game is returning across the continent, the prospect of any live football is a godsend.

As fans of European clubs nervously wait to find out when the beautiful game is returning across the continent, the prospect of any live football is a godsend.

Welcome to Standard Sport's LIVE coverage of the K-League openers between Jeonbuk Hyundai Motors and the Suwon Samsung Bluewings

Gaming on Twitch is largely a one-way affair. You can join a Marbles on Stream race or play a slightly delayed Jackbox Party Pack game, but the service is largely meant for passive viewing. Amazon aims to fix that before long, however. The company tells the New York Times that it's developing games both Twitch streamers and their viewers can play together in "real time." While details are scarce, you should see games become available throughout the summer.

If you're devoted enough to livestreaming that you want the kind of features you'd expect from a TV studio, Blackmagic might have your back. It's releasing the ATEM Mini Pro, an enhanced version of the ATEM Mini switcher that's focused on the most elaborate streaming setups. There's now a hardware streaming engine that lets the Pro stream directly to Twitch, Facebook and YouTube through an Ethernet connection, with no special software required. You can also save recordings for posterity to USB flash drives, and multiview on the HDMI output lets you monitor all inputs on one screen.

Numerous internet services have offered help to creators who may be struggling during the COVID-19 pandemic, but Microsoft's Mixer might have one of the simpler solutions: direct cash infusions. The livestreaming service is giving all of its partnered members $100 to help them get through any financial hardships while the outbreak lasts. Given that anyone sufficiently committed to Mixer to reach partner status depends at least partly on the service to make a living, that may be a welcome gesture.

Demonstrators gathered after the death of Sean Reed

For the final night of its ‘Night at the Movies’ events to benefit people who work in the movie industry, Lionsgate is planning to stream John Wick tonight. The live stream will kick off at 9 PM ET on YouTube, hosted by Jamie Lee Curtis. The event is...

Hacienda Classical will perform at the second stay-at-home rave from the legendary club and United We Stream

Under siege from much cheaper rivals and with lenders unwilling to support it, pay TV operator Foxtel is increasingly looking like a threatened species.

A polar vortex event will bring record lows and May snow to the east this weekend, even as the west coast bakes. Here's why.

Stars like Saffron Barker, Big Narstie and Yammy take part in a four-hour event to raise money.

Tekashi just streamed from in-home incarceration, setting an Instagram Live record with 2 million people tuning in. 6ix9ine trolled off the bat, bumping "Bad Boys" while toying with a pair of handcuffs. Tekashi got a lot off his plate ... admitting…

StreamLink Software began as nonprofit executives saw a need for solutions to common management issues. When it became clear there was gap in quality, affordable products, StreamLink Software was formed to develop them.

"This is a direct result of what we heard from tribal leaders at the department's listening session. Tribal leaders have made it clear that a single application would significantly improve their ability to apply and receive critical federal funding, which so many of their communities depend on," said Associate Attorney General Perrelli.