Title: HIV Meds Cut Transmission Risk to Zero, Even Without Condoms: Study
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

The PMC Canada manuscript submission system was released on April 28, 2010. The system will enable researchers funded by the Canadian Institutes of Health Research to deposit their peer-reviewed research publications, in compliance with CIHR's Policy on Access to Research Outputs.

Title: Helping Seniors Manage Meds After Hospital Reduces Readmission: Study
Category: Health News
Created: 3/3/2020 12:00:00 AM
Last Editorial Review: 3/4/2020 12:00:00 AM

ABSTRACT

RepA is a bacterial protein that builds intracellular amyloid oligomers acting as inhibitory complexes of plasmid DNA replication. When carrying a mutation enhancing its amyloidogenesis (A31V), the N-terminal domain (WH1) generates cytosolic amyloid particles that are inheritable within a bacterial lineage. Such amyloids trigger in bacteria a lethal cascade reminiscent of mitochondrial impairment in human cells affected by neurodegeneration. To fulfill all the criteria to qualify as a prion-like protein, horizontal (intercellular) transmissibility remains to be demonstrated for RepA-WH1. Since this is experimentally intractable in bacteria, here we transiently expressed in a murine neuroblastoma cell line the soluble, barely cytotoxic RepA-WH1 wild type [RepA-WH1(WT)] and assayed its response to exposure to in vitro-assembled RepA-WH1(A31V) amyloid fibers. In parallel, murine cells releasing RepA-WH1(A31V) aggregates were cocultured with human neuroblastoma cells expressing RepA-WH1(WT). Both the assembled fibers and donor-derived RepA-WH1(A31V) aggregates induced, in the cytosol of recipient cells, the formation of cytotoxic amyloid particles. Mass spectrometry analyses of the proteomes of both types of injured cells pointed to alterations in mitochondria, protein quality triage, signaling, and intracellular traffic. Thus, a synthetic prion-like protein can be propagated to, and become cytotoxic to, cells of organisms placed at such distant branches of the tree of life as bacteria and mammalia, suggesting that mechanisms of protein aggregate spreading and toxicity follow default pathways.

IMPORTANCE Proteotoxic amyloid seeds can be transmitted between mammalian cells, arguing that the intercellular exchange of prion-like protein aggregates can be a common phenomenon. RepA-WH1 is derived from a bacterial intracellular functional amyloid protein, engineered to become cytotoxic in Escherichia coli. Here, we have studied if such bacterial aggregates can also be transmitted to, and become cytotoxic to, mammalian cells. We demonstrate that RepA-WH1 is capable of entering naive cells, thereby inducing the cytotoxic aggregation of a soluble RepA-WH1 variant expressed in the cytosol, following the same trend that had been described in bacteria. These findings highlight the universality of one of the central principles underlying prion biology: No matter the biological origin of a given prion-like protein, it can be transmitted to a phylogenetically unrelated recipient cell, provided that the latter expresses a soluble protein onto which the incoming protein can readily template its amyloid conformation.

The coronavirus disease 2019 (COVID-19) epidemic, which was first reported in December 2019 in Wuhan, China, has caused 80 904 confirmed cases as of 9 March 2020, with 28 673 cases being reported outside of China. It has been declared a pandemic by the World Health Organization (WHO), has exhibited human-to-human transmissibility and has spread rapidly across countries [1]. Although the Chinese government has taken various measures to control city-to-city transmission (e.g. shutting down cities, extending holidays) and many other countries have implemented measures (such as airport screening and testing patients who have reported symptoms), the number of cases is still increasing quickly throughout the world.

Background

We sought to determine the cumulative incidence of readmissions after a seizure-related hospitalization and identify risk factors and readmission diagnoses.

Replication initiation in eukaryotic cells occurs asynchronously throughout S phase, yielding early- and late-replicating regions of the genome, a process known as replication timing (RT). RT changes during development to ensure accurate genome duplication and maintain genome stability. To understand the relative contributions that cell lineage, cell cycle, and replication initiation regulators have on RT, we utilized the powerful developmental systems available in Drosophila melanogaster. We generated and compared RT profiles from mitotic cells of different tissues and from mitotic and endocycling cells of the same tissue. Our results demonstrate that cell lineage has the largest effect on RT, whereas switching from a mitotic to an endoreplicative cell cycle has little to no effect on RT. Additionally, we demonstrate that the RT differences we observed in all cases are largely independent of transcriptional differences. We also employed a genetic approach in these same cell types to understand the relative contribution the eukaryotic RT control factor, Rif1, has on RT control. Our results demonstrate that Rif1 can function in a tissue-specific manner to control RT. Importantly, the Protein Phosphatase 1 (PP1) binding motif of Rif1 is essential for Rif1 to regulate RT. Together, our data support a model in which the RT program is primarily driven by cell lineage and is further refined by Rif1/PP1 to ultimately generate tissue-specific RT programs.

During meiotic prophase, concurrent transcription, recombination, and chromosome synapsis place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles of topoisomerases I and II (Top1 and Top2) during meiotic prophase in Saccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes, including many meiotic double-strand break (DSB) hotspots. Despite the comparable binding patterns, top1 and top2 mutations have different effects on meiotic recombination. TOP1 disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive top2-1 mutants exhibit a marked delay in meiotic chromosome remodeling and elevated DSB signals on synapsed chromosomes. The problems in chromosome remodeling were linked to altered Top2 binding patterns rather than a loss of Top2 catalytic activity, and stemmed from a defect in recruiting the chromosome remodeler Pch2/TRIP13 to synapsed chromosomes. No chromosomal defects were observed in the absence of TOP1. Our results imply independent roles for Top1 and Top2 in modulating meiotic chromosome structure and recombination.

Human activities and population growth have increased the natural burden of reactive nitrogen (N) in the environment. Excessive N deposition on Earth’s surface leads to adverse feedbacks on ecosystems and humans. Similar to that of air pollution, emission control is recognized as an efficient means to control acid deposition. Control...

Background and Objectives:

The goal of this study was to decrease admission and readmission rate for the 2296 Medicaid patients in our clinic. Our focus was to eliminate patient identified barriers to care that led to decreased quality of care. The identified barriers for our clinic included distance to care, poor same-day access, communication, and fragmented care. A team-based, collaborative approach using members from all aspects of patient care.

OBJECTIVE

To report U.S. national population-based rates and trends in diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) among adults, in both the emergency department (ED) and inpatient settings.

Season 5 of Respawn Entertainment’s hero-based battle royale kicks off next week and it looks like they’re doing more than just blowing up the map. This new Apex Legends trailer shows off what appears to be a horde mode PvE quest initiated by the newest Legend of the bunch: Loba. It looks like you’ll be […]

X-37B? Sorry, I thought you said your name was X Æ A-12.

When asteroid Armageddon is upon us, we can't just call Bruce Willis. Meet the people who really do watch the skies – and make detailed plans for our survival

NASA has selected four potential future missions – to Jupiter’s fiery moon Io, Neptune’s icy moon Triton, and two that would explore the atmosphere and map the surface of Venus

NASA’s InSight lander has been on the surface of Mars for over a year now – here are five of its strangest and most fascinating discoveries from the Red Planet

A private satellite that is low on fuel could survive five more years because another satellite has come to its rescue – a technique that could be used by future service spacecraft

The ExoMars mission, a joint venture between the European and Russian space agencies, will be delayed for two years. It has already been plagued by issues and the coronavirus hasn't helped

SpaceX’s first crewed launch is planned for 27 May and will be run from a mission control with desks set six feet apart to comply with social distancing protocols

Environmental biologists have warned that the potential spread of COVID-19 via sewage 'must not be neglected' in the battle to protect human health.

U.S. Food and Drug Administration Commissioner Stephen Hahn is in self-quarantine for a couple of weeks after coming into contact with someone who tested positive for COVID-19, an FDA spokesman told Reuters late on Friday.

Noida Police Commissioner has written to national carrier Air India, requesting the airline to ensure that pilots and crew involved in repatriation flights should stay back in Delhi.

New Delhi, May 09 (ANI): An Air India flight carrying 129 passengers from Dhaka, Bangladesh has landed at Delhi airport. The stranded Indian nationals are being brought back to the country through government’s initiative, ‘Vande Bharat Mission’.

The novel coronavirus -- which has infected over 3.9 million people worldwide -- has been detected in wastewater, but researchers have been unclear about the transmission risks.

Canadian Football League Commissioner Randy Ambrosie said the most likely scenario is to cancel the season because of the coronavirus pandemic.

Read our live coronavirus updates HERE Coronavirus: The symptoms

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Parents should receive updates today on whether their child has a place

Dominic Raab has warned against relaxing the UK lockdown, saying the number of Covid-19 infections in Germany grew when restrictions were eased.

The Government should avoid reopening schools too early as scientists do not fully understand coronavirus transmission between children, an NHS chief warned.

Air ambulances will be able to touch down at Kensington Palace for refuelling during the coronavirus pandemic after the Duke of Cambridge gave permission for them to use a private lawn.

In a bustling depot in north London filled with donated food, Phoebe Waller-Bridge compared the work of The Felix Project to "a rescue mission".

The space agency announces the companies that will work on landers to return astronauts to the Moon.

Mission is remembered as perhaps Nasa's finest, and most desparate, hour

Imaging specialist produces clearest pictures yet from dramatic Nasa mission

'We propose that Sars-Cov-2 may have the potential to be transmitted via aerosols,' researchers say

Final season picks up where S6's cliffhanger finale left off.

Big East commissioner Val Ackerman discussed the hurdles for sports to return to her league in 2020-21.

With hospitals and cemeteries overwhelmed by the coronavirus, the mayor of Manaus, Brazil's hardest hit city, has appealed to world leaders, including President Trump, for help.

CFL commissioner Randy Ambrosie says the most likely scenario for the league is a cancelled 2020 season during the COVID-19 pandemic.

With major sports leagues preparing for the eventuality of restarting behind closed doors amid the coronavirus pandemic, NBA commissioner Adam Silver reportedly took the concept to the next level on Friday.

"Our best-case scenario for this year is a drastically truncated season," Randy Ambrosie said. "And our most likely scenario is no season at all.''

As New Brunswick and other provincial governments contemplate launching COVID-19 contact-tracing apps, privacy watchdogs from across the country have issued joint guidelines on what they are describing as an "extraordinary" measure, urging transparency and accountability.