2020 Honda Pilot vs. 2020 Ford Explorer: Compare Crossover SUVs Two of the bestselling three-row SUVs, the 2020 Honda Pilot and 2020 Ford Explorer, go about their family business a bit differently. Pickup trucks outsell cars for the first time, and it may not be temporary The Ford F-150, Ram 1500, and Chevy Silverado have been the best-selling...

Review update: The 2020 Mercedes-Benz AMG GLC 43 SUV "nose" the right spice level These are halcyon days for fleet-footed crossover SUVs. Saucy ‘utes like the 2020 Mercedes-Benz GLC 43 AMG hardly look like they’re just as quick as their smaller siblings but stopwatches don’t lie. 5 things to know about Uconnect 5 Uconnect 5, the...

2020 Mercedes-Benz A-Class vs 2020 Mercedes-Benz CLA-Class: Compare Cars If you can’t get the lord to buy you a Mercedes-Benz, you have to do it yourself, and that can really stretch the budget. Mercedes answers that issue with its two lowest-priced cars, the A-Class and CLA-Class. IIHS reports that new Jeep Wrangler SUV rolled over on its...

Tidal energy developer Atlantis Resources remains on track to deliver power to the Scottish power grid from the MeyGen site in the coming year, according to an end-of-year statement issued by the company earlier this week.

As a general rule of data privacy protection in Hong Kong, personal data should be used only for the original purpose for which the data was collected, or a directly related purpose. One exception is where the data user obtains the consent from the ...

1. Introduction 1.1 The Charity Commission has recently released detailed guidance for charities on their connections to non-charities, highlighting that whilst such connections can bring benefits they can also present risks and challenges. Common s...

Title: AHA News: Hearing Loss and the Connection to Alzheimer's Disease, Dementia
Category: Health News
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM

Title: AHA News: The Often-Overlooked Connection Between Sleep Troubles and Stroke
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Lipid rafts are highly ordered regions of the plasma membrane that are enriched in cholesterol and sphingolipids and play important roles in many cells. In hematopoietic stem and progenitor cells (HSPCs), lipid rafts house receptors critical for normal hematopoiesis. Lipid rafts also can bind and sequester kinases that induce negative feedback pathways to limit proliferative cytokine receptor cycling back to the cell membrane. Modulation of lipid rafts occurs through an array of mechanisms, with optimal cholesterol efflux one of the major regulators. As such, cholesterol homeostasis also regulates hematopoiesis. Increased lipid raft content, which occurs in response to changes in cholesterol efflux in the membrane, can result in prolonged receptor occupancy in the cell membrane and enhanced signaling. In addition, certain diseases, like diabetes, may contribute to lipid raft formation and affect cholesterol retention in rafts. In this review, we explore the role of lipid raft-related mechanisms in hematopoiesis and CVD (specifically, atherosclerosis) and discuss how defective cholesterol efflux pathways in HSPCs contribute to expansion of lipid rafts, thereby promoting myelopoiesis and thrombopoiesis. We also discuss the utility of cholesterol acceptors in contributing to lipid raft regulation and disruption, and highlight the potential to manipulate these pathways for therapeutic gain in CVD as well as other disorders with aberrant hematopoiesis.

ABSTRACT

Protein homeostasis is critical for proliferation and viability of all organisms. For Candida albicans, protein homeostasis also modulates the transition between yeast and filamentous forms, which is critical for virulence. A key regulator of morphogenesis is the molecular chaperone Hsp90, which mediates proteostasis under physiological and stress conditions. Hsp90 regulates morphogenesis by repressing cyclic AMP-protein kinase A (cAMP-PKA) signaling, such that inhibition of Hsp90 causes filamentation in the absence of an inducing cue. We explored the effect of perturbation of another facet of protein homeostasis and discovered that morphogenesis is also regulated by the proteasome, a large 33-subunit protein complex consisting of a 20S catalytic core and two 19S regulatory particles, which controls degradation of intracellular proteins. We identified a conserved role of the proteasome in morphogenesis as pharmacological inhibition of the proteasome induced filamentation of C. albicans and the related species Candida dubliniensis, Candida tropicalis, Candida krusei, and Candida parapsilosis. For C. albicans, genetic depletion of any of 29 subunits of the 19S or 20S particle induced filamentation. Filaments induced by inhibition of either the proteasome or Hsp90 have shared structural characteristics, such as aberrant nuclear content, and shared genetic dependencies, such as intact cAMP-PKA signaling. Consistent with a functional connection between these facets of protein homeostasis that modulate morphogenesis, we observed that proteasome inhibition results in an accumulation of ubiquitinated proteins that overwhelm Hsp90 function, relieving Hsp90-mediated repression of morphogenesis. Together, our findings provide a mechanism whereby interconnected facets of proteostasis regulate C. albicans morphogenesis.

IMPORTANCE Fungi cause life-threatening infections and pose a serious threat to human health as there are very few effective antifungal drugs. Candida albicans is a major human fungal pathogen and cause of morbidity and mortality in immunocompromised individuals. A key trait that enables C. albicans virulence is its ability to transition between yeast and filamentous forms. Understanding the mechanisms regulating this virulence trait can facilitate the development of much-needed, novel therapeutic strategies. A key regulator of morphogenesis is the molecular chaperone Hsp90, which is crucial for proteostasis. Here, we expanded our understanding of how proteostasis regulates fungal morphogenesis and identified the proteasome as a repressor of filamentation in C. albicans and related species. Our work suggests that proteasome inhibition overwhelms Hsp90 function, thereby inducing morphogenesis. This work provides a foundation for understanding the role of the proteasome in fungal virulence and offers potential for targeting the proteasome to disarm fungal pathogens.

Finding common ground and building trust between local stakeholders could help prevent violent encounters between police and young black men, new research finds.

New Delhi, May 9: Mahendra Singh Dhoni's manic following just keeps on increasing with India and Chennaiyin FC midfielder Anirudh Thapa being the latest to join the bandwagon of his awestruck fans. Dhoni is one of the co-owners of Chennaiyin

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.

Millions of people had difficulty accessing the internet yesterday as Virgin Media had a series of outages across the country.

Most of us get high-speed internet via a wired connection. But not everyone has access, like in rural areas. 5G could broaden those broadband options.

For the first in our new series of letters capturing tales and thoughts during lockdown, Amira Hashish finds comfort in her neighbour's act of kindness...

New version of the classic doll, which can chat with children, makes her debut at New York Toy Fair.

Health news and commentary from around the Web gathered by the ALLMedPage Today staff

A Minnesota man was arrested today on charges related to an alleged Ponzi scheme involving commodity pools. Charles “Chuck” E. Hays, of Rosemount, Minn., was charged in a criminal complaint filed in the District of Minnesota with one count of wire fraud and one count of mail fraud.

Carlos Serrano, 64, of Glendale, Calif., was sentenced to 18 months in a community correctional facility in connection with a $1.3 million scheme to defraud the First International Bank of Connecticut (FIB) and the Export-Import Bank of the United States (Ex-Im Bank). In addition to his prison sentence, Serrano was placed on five years of probation and ordered to pay restitution of $924,569 to the Ex-Im Bank.

A British citizen was charged in connection with the operation of a series of fraudulent business opportunities on March 10, 2009, by a Miami federal grand jury. Sirtaj Mathauda was indicted on charges that he and his co-conspirators purported to sell vending machine, beverage and greeting card business opportunities, including assistance in establishing, maintaining and operating such businesses. The charges form part of the government’s continued nationwide crackdown on business opportunity fraud.

A former contract employee of the U.S. Army Corps of Engineers and a dirt, sand and gravel subcontractor were both convicted on charges of conspiracy and bribery in connection with a $16 million hurricane protection project for the reconstruction of the Lake Cataouatche Levee, south of New Orleans.

Lazare Kabaya Kobagaya, 82, of Topeka, Kan., was arrested today on charges of naturalization fraud and misuse of an alien registration card. According to the indictment, Kobagaya allegedly participated in genocidal activities during the 1994 Rwandan conflict including mobilizing attackers to commit arson and murder. Kobagaya is alleged to have failed to disclose his alleged participation in these activities during his immigration and naturalization processes.

A Miami federal grand jury has charged two South Florida men with conspiracy, mail and wire fraud in connection with the operation of a fraudulent ATM business opportunity. The criminal charges are part of the government’s continued nationwide crackdown on business opportunity fraud.

Novo Nordisk A/S (Novo), a Danish corporation based in Bagsvaerd, Denmark, has agreed to pay a $9 million penalty for illegal kickbacks paid to the former Iraqi government.

A defense contractor has pleaded guilty to wire fraud and has admitted to engaging in other bribery-related conduct in connection with contracts in Iraq. According to the plea agreement filed in the U.S. District Court in the District of Columbia on Dec. 18, 2007, and unsealed today, Diana Bakir Demilta, a U.S. citizen, pleaded guilty to one count of wire fraud.

Sims Lawson Jr., a resident of Killen, Ala., pleaded guilty yesterday to filing false tax returns for years 2002 through 2004. Lawson appeared before Judge R. David Proctor in Birmingham, Ala., and admitted that he failed to pay federal income taxes of $369,038 and state income taxes of $50,938.

A Tampa federal grand jury has charged a Florida man with criminal contempt of a federal court order in connection with the operation of a fraudulent vending machine business opportunity. The criminal charges form part of the government’s continued nationwide crackdown on business opportunity fraud.

A British citizen charged in connection with the operation of a series of fraudulent business opportunities was arrested Thursday evening in Miami following his indictment by a Miami federal grand jury on June 9, 2009.

On Aug.11, 2009, two individuals were sentenced in connection with South Florida business opportunity scams. Stewart Pope was sentenced in connection with his participation in fraudulent business opportunity sales at a Miami firm called Global Resources (“Global”).

A former sand and gravel subcontractor was sentenced today to serve five years in prison and to pay a $5,000 criminal fine by U.S. District Judge Carl J. Barbier after being convicted by a federal jury of conspiracy and bribery in connection with a $16 million hurricane protection project for the reconstruction a New Orleans levee.

An Oklahoma man pleaded guilty today for his role in a scheme to solicit kickbacks in connection with the award of a private security services subcontract to protect U.S. government personnel and contractors in Afghanistan. Bryan Lee Burrows, 42, of Wagoner, Okla., pleaded guilty today before U.S. District Court Judge Leonie M. Brinkema in the Eastern District of Virginia to one count of conspiracy to solicit a kickback.

The former director of sales and marketing for Pacific Consolidated Industries LP (PCI) pleaded guilty today to charges related to the bribery of a U.K. Ministry of Defense (UK-MOD) official in order to obtain lucrative equipment contracts with the U.K. Royal Air Force, in violation of the Foreign Corrupt Practices Act (FCPA).

Daniel Earl Danforth, 30, of Minden, La., has been indicted by a federal grand jury for hate crime violations and obstruction of justice charges stemming from a cross-burning in Athens, La., last year near the home of an interracial couple. Danforth was arrested today following the return of the indictment on Sept. 25, 2009.

AGCO Corp., a U.S. corporation based in Duluth, Ga., has agreed to pay a $1.6 million penalty for illegal kickbacks paid to the former government of Iraq.

Ryan Scott McMonigle, 37, of Ponca City, Okla., was indicted today for his alleged role in a scheme to solicit kickbacks in connection with the award of a security services subcontract to protect U.S. government personnel and contractors in Afghanistan.

Sims Lawson Jr., a resident of Killen, Ala., was sentenced to 70 months in prison by Judge R. David Proctor.

Two Chicago men have been arrested on federal charges for their alleged roles in conspiracies to provide material support and/or to commit terrorist acts against overseas targets.

John A. Campbell, a resident of Portage, Mich., was sentenced to 60 months in prison today by the Honorable Janet T. Neff of the U.S. District Court in the Western District of Michigan for conspiring to defraud the United States.

A civil lawsuit was filed today against a former U.S. Army officer and three contracting firms related to an alleged bribery scheme in connection with the awarding of contracts for services in Kuwait.

Scott Anthony Walker, 36, of Australia, pleaded guilty in the Eastern District of Virginia to one count of conspiracy to solicit a kickback.

Detroit-area residents Baskaran Thangarasan, Sandeep Aggarwal and Wayne Smith pleaded guilty this week for their roles in connection with several Detroit-area health care fraud schemes.

The forfeiture is the largest ever entered against an entity for IEEPA violations.

On Jan. 13, 2010, Dilraj Mathauda entered a guilty plea in federal district court in Miami Federal to one count of an indictment pending against him, charging conspiracy to commit mail and wire fraud.

Daniel Earl Danforth of Minden, La., was convicted by a jury in Shreveport, La., of a civil rights conspiracy, use of fire in the commission of a federal felony, and obstruction of justice in connection with a cross-burning near the home of an interracial couple in Athens, La.

Stephen Schultz entered a guilty plea in federal district court in Miami to 12 counts of an indictment pending against him.