Title: Trouble With Sense of Direction May Be Linked to Early Alzheimer's: Study
Category: Health News
Created: 4/26/2016 12:00:00 AM
Last Editorial Review: 4/27/2016 12:00:00 AM

Title: Some Antibiotics Linked to Miscarriage Risk
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM

Title: Raw Oysters From British Columbia Linked to Norovirus Outbreaks
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM

Title: Device Might Detect Breast Cancer-Linked Swelling Sooner
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

Title: Vampire Facials at New Mexico Spa Linked to HIV Infections
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/1/2019 12:00:00 AM

Title: Breast Implants Linked to Cancer Can Still be Sold in U.S.: FDA
Category: Health News
Created: 5/3/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: COVID-19 Now Linked With Strokes in Young Patients
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM

Title: Screen Time for Tiniest Tots Linked to Autism-Like Symptoms
Category: Health News
Created: 4/20/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM

Title: Heavy Pot Use Linked to Mental Problems, Even After Quitting
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

ABSTRACT

The multifunctional nature of viral proteins is essentially driven by posttranslational modifications (PTMs) and is key for the successful outcome of infection. For influenza A viruses (IAVs), a composite pattern of PTMs regulates the activity of viral proteins. However, almost none are known that target the PB2 replication protein, except for inducing its degradation. We show here that PB2 undergoes a nonproteolytic ubiquitination during infection. We identified E3 ubiquitin ligases catalyzing this ubiquitination as two multicomponent RING-E3 ligases based on cullin 4 (CRL4s), which are both contributing to the levels of ubiquitinated forms of PB2 in infected cells. The CRL4 E3 ligase activity is required for the normal progression of the viral cycle and for maximal virion production, indicating that the CRL4s mediate a ubiquitin signaling that promotes infection. The CRL4s are recruiting PB2 through an unconventional bimodal interaction with both the DDB1 adaptor and DCAF substrate receptors. While able to bind to PB2 when engaged in the viral polymerase complex, the CRL4 factors do not alter transcription and replication of the viral segments during infection. CRL4 ligases catalyze different patterns of lysine ubiquitination on PB2. Recombinant viruses mutated in the targeted lysines showed attenuated viral production, suggesting that CRL4-mediated ubiquitination of PB2 contributes to IAV infection. We identified K29-linked ubiquitin chains as main components of the nonproteolytic PB2 ubiquitination mediated by the CRL4s, providing the first example of the role of this atypical ubiquitin linkage in the regulation of a viral infection.

IMPORTANCE Successful infection by influenza A virus, a pathogen of major public health importance, involves fine regulation of the multiple functions of the viral proteins, which often relies on post-translational modifications (PTMs). The PB2 protein of influenza A viruses is essential for viral replication and a key determinant of host range. While PTMs of PB2 inducing its degradation have been identified, here we show that PB2 undergoes a regulating PTM signaling detected during infection, based on an atypical K29-linked ubiquitination and mediated by two multicomponent E3 ubiquitin ligases. Recombinant viruses impaired for CRL4-mediated ubiquitination are attenuated, indicating that ubiquitination of PB2 is necessary for an optimal influenza A virus infection. The CRL4 E3 ligases are required for normal viral cycle progression and for maximal virion production. Consequently, they represent potential candidate host factors for antiviral targets.

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.

ABSTRACT

All enterococci produce a complex polysaccharide called the enterococcal polysaccharide antigen (EPA). This polymer is required for normal cell growth and division and for resistance to cephalosporins and plays a critical role in host-pathogen interaction. The EPA contributes to host colonization and is essential for virulence, conferring resistance to phagocytosis during the infection. Recent studies revealed that the "decorations" of the EPA polymer, encoded by genetic loci that are variable between isolates, underpin the biological activity of this surface polysaccharide. In this work, we investigated the structure of the EPA polymer produced by the high-risk enterococcal clonal complex Enterococcus faecalis V583. We analyzed purified EPA from the wild-type strain and a mutant lacking decorations and elucidated the structure of the EPA backbone and decorations. We showed that the rhamnan backbone of EPA is composed of a hexasaccharide repeat unit of C2- and C3-linked rhamnan chains, partially substituted in the C3 position by α-glucose (α-Glc) and in the C2 position by β-N-acetylglucosamine (β-GlcNAc). The so-called "EPA decorations" consist of phosphopolysaccharide chains corresponding to teichoic acids covalently bound to the rhamnan backbone. The elucidation of the complete EPA structure allowed us to propose a biosynthetic pathway, a first essential step toward the design of antimicrobials targeting the synthesis of this virulence factor.

IMPORTANCE Enterococci are opportunistic pathogens responsible for hospital- and community-acquired infections. All enterococci produce a surface polysaccharide called EPA (enterococcal polysaccharide antigen) required for biofilm formation, antibiotic resistance, and pathogenesis. Despite the critical role of EPA in cell growth and division and as a major virulence factor, no information is available on its structure. Here, we report the complete structure of the EPA polymer produced by the model strain E. faecalis V583. We describe the structure of the EPA backbone, made of a rhamnan hexasaccharide substituted by Glc and GlcNAc residues, and show that teichoic acids are covalently bound to this rhamnan chain, forming the so-called "EPA decorations" essential for host colonization and pathogenesis. This report represents a key step in efforts to identify the structural properties of EPA that are essential for its biological activity and to identify novel targets to develop preventive and therapeutic approaches against enterococci.

Although enteroviruses are associated with a wide variety of diseases and conditions, their mode of replication is well conserved. Their genome is carried as a single, positive-sense RNA strand. At the 5' end of the strand is an approximately 90-nucleotide self-complementary region called the 5' cloverleaf, or the oriL. This noncoding region serves as a platform upon which host and virus proteins, including the 3B, 3C, and 3D virus proteins, assemble in order to initiate replication of a negative-sense RNA strand. The negative strand in turn serves as a template for synthesis of multiple positive-sense RNA strands. Building on structural studies of individual RNA stem-loops, the structure of the intact 5' cloverleaf from rhinovirus has recently been determined via nuclear magnetic resonance/small-angle X-ray scattering (NMR/SAXS)-based methods, while structures have also been determined for enterovirus 3A, 3B, 3C, and 3D proteins. Analysis of these structures, together with structural and modeling studies of interactions between host and virus proteins and RNA, has begun to provide insight into the enterovirus replication mechanism and the potential to inhibit replication by blocking these interactions.

Monoubiquitinated FANCI and FANCD2 constitute the ID complex, which forms a sliding clamp on DNA.

Gastric cancer (GC) is the fifth-ranked cancer type by associated mortality. The proportion of early diagnosis is low, and most patients are diagnosed at the advanced stages. First-line therapy standardly includes fluoropyrimidines and platinum compounds with trastuzumab for HER2-positive cases. For recurrent disease, there are several alternative options including ramucirumab, a monoclonal therapeutic antibody that inhibits VEGF-mediated tumor angiogenesis by binding with VEGFR2, alone or in combination with other cancer drugs. However, overall response rate following ramucirumab or its combinations is 30%–80% of the patients, suggesting that personalization of drug prescription is needed to increase efficacy of treatment. We report here original tumor RNA sequencing profiles for 15 advanced GC patients linked with data on clinical response to ramucirumab or its combinations. Three genes showed differential expression in the tumors for responders versus nonresponders: CHRM3, LRFN1, and TEX15. Of them, CHRM3 was up-regulated in the responders. Using the bioinformatic platform Oncobox we simulated ramucirumab efficiency and compared output model results with actual tumor response data. An agreement was observed between predicted and real clinical outcomes (AUC ≥ 0.7). These results suggest that RNA sequencing may be used to personalize the prescription of ramucirumab for GC and indicate potential molecular mechanisms underlying ramucirumab resistance. The RNA sequencing profiles obtained here are fully compatible with the previously published Oncobox Atlas of Normal Tissue Expression (ANTE) data.

BACKGROUND AND PURPOSE:

Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results.

The majority of these children have tested positive for the virus or seem to carry antibodies from an earlier infection.

A 7-year-old boy from Westchester County is the second child in New York state to die from pediatric multi-symptom inflammatory syndrome tied to COVID-19 since the pandemic began. A 5-year-old boy died earlier in the week from the same syndrome at Mount Sinai Kravis Children’s Hospital in New York City.

The childhood ailment has affected at least 73 children in New York state and authorities are now looking for other potential cases across the country. Cases have also been reported in Washington, D.C., California, Delaware, Louisiana, Massachusetts, Pennsylvania, Washington state and New Jersey, where a 4-year-old died with symptoms last month.

It has been previously thought that children are less likely to suffer any serious complications from the coronavirus.

Read more at The Daily Beast.

Scientists set out to investigate a potential role of the gut microbiota in the development of cardio-metabolic diseases. They ended up identifying the common cholesterol-lowering drug statins as a potential microbiota-modulating therapeutic.

Obese Europeans who are treated with cholesterol lowering drugs have not only lower values of blood LDL cholesterol and markers of inflammation but in addition a more healthy gut bacteria profile than those obese who are not prescribed statins.

New research finds that sleep problems in a baby's first 12 months may not only precede an autism diagnosis, but also may be associated with altered growth trajectory in a key part of the brain, the hippocampus.

An analysis of the daily steps taken by about 5000 people in the US has found that a higher step count is linked to a lower yearly risk of death, although the effect tails off above 12,000 steps

Following China’s switch to a two-child policy, there has been a slight rise in congenital anomalies, perhaps because parents are older on average at conception

As Quebec prepares to reopen schools, doctors are poring over 15-20 cases of children with what seems to be the same illnesses reported in U.S. and Europe

According to many observations, certain virus infections may play a part in the autoimmune attack that leads to type 1 diabetes. Researchers have now produced a vaccine for these viruses in the hope that it could provide protection against the disease.

A new study has found an association between low average levels of vitamin D and high numbers of COVID-19 cases and mortality rates across 20 European countries.

People with body integrity dysphoria (BID) often feel as though one of their healthy limbs isn't meant to be a part of their bodies. They may act as though the limb is missing or even seek its amputation 'to feel complete.' Now, researchers have found that these feelings that a limb doesn't belong are mirrored in the brains of people with this condition.

Hackers linked to Iran have targeted staff at U.S. drugmaker Gilead Sciences Inc in recent weeks, according to publicly-available web archives reviewed by Reuters and three cybersecurity researchers, as the company races to deploy a treatment for the COVID-19 virus.

Read our live coronavirus updates HERE Coronavirus: The symptoms

Read our live coronavirus updates HERE

Detectives investigating a gang responsible for trafficking young women from Brazil to work in brothels in north London have made two arrests.

A UK police force has upped patrols around 5G masts in a bid to stop further attacks linked to coronavirus conspiracy theories.

Some children have died of a new illness that could be linked to coronavirus, the Health Secretary has said.

There is now an outbreak of COVID-19 linked to Canada Post's main plant in Calgary, according to Alberta Health Services.

Hackers linked to Iran have targeted staff at U.S. drugmaker Gilead Sciences Inc in recent weeks, according to publicly-available web archives reviewed by Reuters and three cybersecurity researchers, as the company races to deploy a treatment for the COVID-19 virus. In one case, a fake email login page designed to steal passwords was sent in April to a top Gilead executive involved in legal and corporate affairs, according to an archived version on a website used to scan for malicious web addresses. Ohad Zaidenberg, lead intelligence researcher at Israeli cybersecurity firm ClearSky, who closely tracks Iranian hacking activity and has investigated the attacks, said the attempt was part of an effort by an Iranian group to compromise email accounts of staff at the company using messages that impersonated journalists.

'By expanding our thinking of how oceans behaved in the past, we could gain some insights into oceans today,' says scientist at Stanford University

In addition to the QAnon accounts, Facebook also removed accounts linked to VDARE, a U.S. website known for posting anti-immigration content.

Valencia midfielder Geoffrey Kondogbia could be available for around €30 million this summer amid reported interest from Tottenham.

It is no secret that Chelsea are on the lookout for new signings, with Frank Lampard looking for both quality and quantity in attack this summer.

Gabriel Veron is a player in demand with Everton and Arsenal in pursuit, according to recent reports.

Nnamdi Collins is the latest talented young footballer linked with a Premier League switch, with Chelsea and Manchester City reportedly interested in the 16-year-old defender.

James Rodriguez has been linked with a sensational switch to David Beckham's MLS franchise, Inter Miami.

Arsenal have been linked with a move for Feyenoord's young midfielder Orkun Kokcu, who has been tipped for a big future after an impressive breakout season in the Netherlands.

Arsenal are reportedly planning a summer move to capture Bayern Munich youngster Angelo Stiller.

Moderate, daily coffee consumption does not trigger incident heart arrhythmias, according to an analysis of prospectively collected data from nearly 300,000 residents of the United Kingdom.
Medscape Medical News

Although rare, health authorities advise any children presenting with Kawasaki-like symptoms be taken immediately to a specialist in pediatric infectious disease, rheumatology, or critical care.
Medscape Medical News

12 children have fallen ill across the UK with a new and potentially fatal combination of symptoms linked to COVID-19.

A former member of the Bosnian Serb Army has left the United States to return to Serbia after a federal judge ordered his denaturalization based on concealment during his application for U.S. citizenship that he served in the military during the Bosnian war.