Although substantial progress has been made in depicting the molecular pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection, the comprehensive mechanism of HIV-1 latency and the most promising therapeutic strategies to effectively reactivate the HIV-1 latent reservoir to achieve a functional cure for AIDS remain to be systematically illuminated. Here, we demonstrated that piwi (P element-induced Wimpy)-like RNA-mediated gene silencing 4 (PIWIL4) played an important role in suppressing HIV-1 transcription and contributed to the latency state in HIV-1-infected cells through its recruitment of various suppressive factors, including heterochromatin protein 1α/β/, SETDB1, and HDAC4. The knockdown of PIWIL4 enhanced HIV-1 transcription and reversed HIV-1 latency in both HIV-1 latently infected Jurkat T cells and primary CD4⁺ T lymphocytes and resting CD4⁺ T lymphocytes from HIV-1-infected individuals on suppressive combined antiretroviral therapy (cART). Furthermore, in the absence of PIWIL4, HIV-1 latently infected Jurkat T cells were more sensitive to reactivation with vorinostat (suberoylanilide hydroxamic acid, or SAHA), JQ1, or prostratin. These findings indicated that PIWIL4 promotes HIV-1 latency by imposing repressive marks at the HIV-1 5' long terminal repeat. Thus, the manipulation of PIWIL4 could be a novel strategy for developing promising latency-reversing agents (LRAs).

IMPORTANCE HIV-1 latency is systematically modulated by host factors and viral proteins. During this process, the suppression of HIV-1 transcription plays an essential role in promoting HIV-1 latency. In this study, we found that PIWIL4 repressed HIV-1 promoter activity and maintained HIV-1 latency. In particular, we report that PIWIL4 can regulate gene expression through its association with the suppressive activity of HDAC4. Therefore, we have identified a new function for PIWIL4: it is not only a suppressor of endogenous retrotransposons but also plays an important role in inhibiting transcription and leading to latent infection of HIV-1, a well-known exogenous retrovirus. Our results also indicate a novel therapeutic target to reactivate the HIV-1 latent reservoir.

The Department of Justice announced today that, in order for VeriFone Systems Inc. to complete its acquisition of Hypercom Corp., it must divest Hypercom’s U.S. point-of-sale terminals business to an entity sponsored by Gores Group LLC, a private equity fund.

Edward Arakelyan, 21, and Arman Vardanyan, 22, were each charged in a criminal information filed on March 5, 2012, in U.S. District Court in Oakland, Calif., with one count of conspiracy to commit bank fraud, one count of bank fraud, and one count of aggravated identity theft.

Eduard Arakelyan, 21, and Arman Vardanyan, 23, were each sentenced yesterday to serve 36 months in prison on bank fraud and conspiracy charges, and an additional, consecutive 24 months in prison for the identity theft charge.

BP Products North America, Inc. will pay a $210,000 penalty and implement an enhanced oil spill response program at its oil terminals nationwide, as well as a comprehensive compliance audit to resolve alleged violations of oil spill response regulations at its Curtis Bay Terminal in Maryland.

Hospice of the Comforter Inc. (HOTCI) has agreed to pay $3 million to resolve allegations that it violated the False Claims Act by submitting false claims to the Medicare program for hospice services provided to patients who were not eligible for the Medicare hospice benefit.

In vitro and rodent studies suggest ophiopogonin D could help prevent doxorubicin-induced cardiotoxicity.

Did we say we hate concrete? Just the new stuff. This kind of concrete should be buffed, polished and treasured.

A Mulund railway yard master, who retired from his 35-year-old job recently, was so busy in the last working month of his career, that he ended up staying at the rail terminus for a month, to handle despatching essential commodity trains, giving priority to supplies for citizens over his family.

Vilas V Pagare, 60, who retired on April 30, joined the railways around 1984 and had been posted at Central Railway in various designations. His earlier posting was at Vasind station. He retired as Chief Yard Master at Mulund Container Terminal. "The lockdown has been the most challenging time of my career. It was supposed to be my retirement month, but as the lockdown came into effect, more and more trains with essentials needed to be despatched. I decided to stay at the Mulund Container Terminal from March 23 the day the lockdown of the railways was announced, to April 22 to handle the growing number of freight trains and loading and unloading at the terminal," a proud Pagare told mid-day.

His family comprises two grown up sons and his wife. "The railways have given me everything and this was the least I could give back not just to the railways, but to society," he said, of prioritising work over family. During this time, he handled 40 trains, their deformation, loading and unloading and re-formation.

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Australian Survivor star Sharn Coombes has shared her heartbreak over her father's terminal cancer diagnosis. 

Mavis Torrance, from Bishopbriggs, told STV she displayed a high temperature days after her daughter Angela Grubb and son-in-law Gus started to show symptoms of Covid-19.

Tony Stevens, from Royal Wootton Bassett, Wiltshire, and his partner Trisha Nation split up after doctors said an STI was the cause of his night sweats and weight loss.

Jet2 axed the trip for children and carers from Martin House Children's Hospice in Wetherby claiming they had not been told the level of medical care the children would need.

North Korean refugees suspected of having caught coronavirus during their escape to China have been quarantined among terminal tuberculosis patients. Pictured: Pyongyang Hospital.

Christine Meaney, 60, and Desmond Codona, 59, who live in Hemlington, Middlesbrough, married at their home, after Desmond was told that he could have just weeks to live.

The original Nursing and Midwifery Council [NMC] tribunal heard Stacey Worsley gambled the money - meant for Toby Nye's neuroblastoma treatment - over a 15-month period.

Gatwick Airport looked almost empty after passenger numbers on planes, trains and the London Undergound slumped due to coronavirus.

Hannah Toohill, from Dingwall in Scotland, began experiencing crippling back and chest pain four months into her pregnancy before she was diagnosed with multiple myeloma.

In the second part of her interview that aired on Wednesday, Doherty said she kept it secret for so long because she did not people to look at her and think 'dead man walking'.

My husband is terminally ill now. Will I receive any of his state pension when he dies? This is Money's pensions columnist, Steve Webb, explains how the rules work according to a couple's ages.

ON THE ROAD: Paul takes a quick glance at his watch and lets out a heavy sigh. 'A season or two ago, this place would have been rammed by now,' he says.

On Tuesday, the Reserve Bank of India (RBI) released a notification on Frequently Asked Questions (FAQs) on cash withdrawal facility at point of sale (PoS) terminals. The facility allows a bank account holder to walk into a shop and withdraw money

Tornio Manga LNG terminal

LNG Terminal India

L&T’s container terminal project

Railway Terminals

Regasification Terminal

Onshore Gas Terminal

Kochi terminal

LNG Terminal Project

LNG Regasification Terminal

Terminal 2

LNG Re-Gasification Terminal

Kochi LNG terminal

New Liquid Terminal at JNPT

LNG Import Terminal India

LNG Terminal Kochi

LNG terminals

Australia's state of Victoria on Wednesday became the first in the country to legalize euthanasia for the terminally ill as the law on voluntary assisted death (VAD) entered into force.

Dewey Library - HD8039.R36 W37 2019

Online Resource

Online Resource

Rotch Library - DT449.Z27 N53 2004