Title: Work Stress, Poor Sleep, High Blood Pressure a Deadly Trio
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM

Title: As Sense of Smell Fades, Does Death Come Closer?
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: AHA News: A Father's Death at 37 Reveals a Hidden History of Cholesterol
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 5/1/2019 12:00:00 AM

Title: U.S. Teen Opioid Deaths Soaring
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 5/1/2019 12:00:00 AM

Title: Not Just Opioids: Deaths Tied to Cocaine, Meth Are Soaring, Too
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: Nanotechnology Might Help Fight Deadly 'Cytokine Storm' of COVID-19
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM

Title: AHA News: Traumatic Childhood Increases Lifelong Risk for Heart Disease, Early Death
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM

Title: COVID-19 Pandemic May Lead to 75,000 'Deaths of Despair'
Category: Health News
Created: 5/8/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Title: Pneumonia More Deadly Than Hip Fractures for Hospitalized Seniors
Category: Health News
Created: 4/23/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM

Title: Allow Dead Men to Be Sperm Donors, Medical Ethicists Say
Category: Health News
Created: 1/22/2020 12:00:00 AM
Last Editorial Review: 1/22/2020 12:00:00 AM

Title: Religion Helps Protect Against 'Deaths of Despair': Study
Category: Health News
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM

Title: U.S. Deaths From High Blood Pressure Soar, Especially in the South: Study
Category: Health News
Created: 3/23/2020 12:00:00 AM
Last Editorial Review: 3/24/2020 12:00:00 AM

Title: Got Flu? Deal Quickly With Complications
Category: Health News
Created: 2/2/2020 12:00:00 AM
Last Editorial Review: 2/3/2020 12:00:00 AM

Title: Many Car Crash Deaths Involve Alcohol Levels Below Legal Limit: Study
Category: Health News
Created: 3/16/2020 12:00:00 AM
Last Editorial Review: 3/17/2020 12:00:00 AM

TNF-related apoptosis-inducing ligand (TRAIL) and an agonistic antibody against the death-inducing TRAIL receptor 5, DR5, are thought to selectively induce tumor cell death and therefore, have gained attention as potential therapeutics currently under investigation in several clinical trials. However, some tumor cells are resistant to TRAIL/DR5–induced cell death, even though they express DR5. Previously, we reported that DR5 is transported into the nucleus by importin β1, and knockdown of importin β1 upregulates cell surface expression of DR5 resulting in increased TRAIL sensitivity in vitro. Here, we examined the impact of importin β1 knockdown on agonistic anti-human DR5 (hDR5) antibody therapy. Drug-inducible importin β1 knockdown sensitizes HeLa cells to TRAIL-induced cell death in vitro, and exerts an antitumor effect when combined with agonistic anti-hDR5 antibody administration in vivo. Therapeutic importin β1 knockdown, administered via the atelocollagen delivery system, as well as treatment with the importin β inhibitor, importazole, induced regression and/or eradication of two human TRAIL-resistant tumor cells when combined with agonistic anti-hDR5 antibody treatment. Thus, these findings suggest that the inhibition of importin β1 would be useful to improve the therapeutic effects of agonistic anti-hDR5 antibody against TRAIL-resistant cancers.

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

ABSTRACT

Fungal infections are a major contributor to infectious disease-related deaths worldwide. Recently, global emergence of the fungal pathogen Candida auris has caused considerable concern because most C. auris isolates are resistant to fluconazole, the most commonly administered antifungal, and some isolates are resistant to drugs from all three major antifungal classes. To identify novel agents with bioactivity against C. auris, we screened 2,454 compounds from a diversity-oriented synthesis collection. Of the five hits identified, most shared a common rocaglate core structure and displayed fungicidal activity against C. auris. These rocaglate hits inhibited translation in C. auris but not in its pathogenic relative Candida albicans. Species specificity was contingent on variation at a single amino acid residue in Tif1, a fungal member of the eukaryotic initiation factor 4A (eIF4A) family of translation initiation factors known to be targeted by rocaglates. Rocaglate-mediated inhibition of translation in C. auris activated a cell death program characterized by loss of mitochondrial membrane potential, increased caspase-like activity, and disrupted vacuolar homeostasis. In a rocaglate-sensitized C. albicans mutant engineered to express translation initiation factor 1 (Tif1) with the variant amino acid that we had identified in C. auris, translation was inhibited but no programmed cell death phenotypes were observed. This surprising finding suggests divergence between these related fungal pathogens in their pathways of cellular responses to translation inhibition. From a therapeutic perspective, the chemical biology that we have uncovered reveals species-specific vulnerability in C. auris and identifies a promising target for development of new, mechanistically distinct antifungals in the battle against this emerging pathogen.

IMPORTANCE Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within the medical community and the public at large. This pathogen is unusually resistant to antifungals, threatening to overwhelm current management options. By screening a library of structurally diverse molecules, we found that C. auris is surprisingly sensitive to translation inhibition by a class of compounds known as rocaglates (also known as flavaglines). Despite the high level of conservation across fungi in their protein synthesis machinery, these compounds inhibited translation initiation and activated a cell death program in C. auris but not in its relative Candida albicans. Our findings highlight a surprising divergence across the cell death programs operating in Candida species and underscore the need to understand the specific biology of a pathogen in attempting to develop more-effective treatments against it.

Drivers with blood-alcohol levels below legal limits cause 15% of all crash deaths that involve alcohol, a study in the March issue of the American Journal of Preventive Medicine finds.

Pedestrian fatalities from vehicle impacts in 2019 were the highest in the U.S. in over three decades, a February report finds.

N-terminal (Nt) acetylation (NTA) is an ample and irreversible cotranslational protein modification catalyzed by ribosome-associated Nt-acetyltransferases. NTA on specific proteins can act as a degradation signal (called an Ac/N-degron) for proteolysis in yeast and mammals. However, in plants, the biological relevance of NTA remains largely unexplored. In this study, we reveal that Arabidopsis (Arabidopsis thaliana) SIGMA FACTOR-BINDING PROTEIN1 (SIB1), a transcription coregulator and a positive regulator of salicylic acid-primed cell death, undergoes an absolute NTA on the initiator Met; Nt-acetyltransferase B (NatB) partly contributes to this modification. While NTA results in destabilization of certain target proteins, our genetic and biochemical analyses revealed that plant NatB-involved NTA instead renders SIB1 more stable. Given that the ubiquitin/proteasome system stimulates SIB1 degradation, it seems that the NTA-conferred stability ensures the timely expression of SIB1-dependent genes, mostly related to immune responses. Taking our findings together, here we report a noncanonical NTA-driven protein stabilization in land plants.

A wide variety of intrinsic and extrinsic cues lead to cell death with unclear mechanisms. The infertility of some death mutants often hurdles the classical suppressor screens for death regulators. We have developed a transient RNA interference (RNAi)-based screen using a virus-induced gene silencing approach to understand diverse cell death pathways in Arabidopsis (Arabidopsis thaliana). One death pathway is due to the depletion of a MAP kinase (MAPK) cascade, consisting of MAPK kinase kinase 1 (MEKK1), MKK1/2, and MPK4, which depends on a nucleotide-binding site Leu-rich repeat (NLR) protein SUMM2. Silencing of MEKK1 by virus-induced gene silencing resembles the mekk1 mutant with autoimmunity and defense activation. The RNAi-based screen toward Arabidopsis T-DNA insertion lines identified SUMM2, MEKK2, and Calmodulin-binding receptor-like cytoplasmic kinase 3 (CRCK3) to be vital regulators of RNAi MEKK1-induced cell death, consistent with the reports of their requirement in the mekk1-mkk1/2-mpk4 death pathway. Similar with MEKK2, overexpression of CRCK3 caused dosage- and SUMM2-dependent cell death, and the transcripts of CRCK3 were up-regulated in mekk1, mkk1/2, and mpk4. MEKK2-induced cell death depends on CRCK3. Interestingly, CRCK3-induced cell death also depends on MEKK2, consistent with the biochemical data that MEKK2 complexes with CRCK3. Furthermore, the kinase activity of CRCK3 is essential, whereas the kinase activity of MEKK2 is dispensable, for triggering cell death. Our studies suggest that MEKK2 and CRCK3 exert concerted functions in the control of NLR SUMM2 activation and MEKK2 may play a structural role, rather than function as a kinase, in regulating CRCK3 protein stability.

Programmed death-ligand 1 (PD-L1/B7-H1) serves as a cosignaling molecule in cell-mediated immune responses and contributes to chronicity of inflammation and the escape of tumor cells from immunosurveillance. Here, we investigated the molecular mechanisms leading to PD-L1 upregulation in human oral carcinoma cells and in primary human gingival keratinocytes in response to infection with Porphyromonas gingivalis (P. gingivalis), a keystone pathogen for the development of periodontitis. The bacterial cell wall component peptidoglycan uses bacterial outer membrane vesicles to be taken up by cells. Internalized peptidoglycan triggers cytosolic receptors to induce PD-L1 expression in a myeloid differentiation primary response 88 (Myd88)-independent and receptor-interacting serine/threonine-protein kinase 2 (RIP2)-dependent fashion. Interference with the kinase activity of RIP2 or mitogen-activated protein (MAP) kinases interferes with inducible PD-L1 expression.

Background and objectives

Uromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD.

Cell death is an invariant feature throughout our life span, starting with extensive scheduled cell death during morphogenesis and continuing with death under homeostasis in adult tissues. Additionally, cells become victims of accidental, unscheduled death following injury and infection. Cell death in each of these occasions triggers specific and specialized responses in the living cells that surround them or are attracted to the dying/dead cells. These responses sculpt tissues during morphogenesis, replenish lost cells in homeostasis to maintain tissue/system function, and repair damaged tissues after injury. Wherein lies the information that sets in motion the cascade of effector responses culminating in remodeling, renewal, or repair? Here, we attempt to provide a framework for thinking about cell death in terms of the specific effector responses that accompanies various modalities of cell death. We also propose an integrated threefold "cell death code" consisting of information intrinsic to the dying/dead cell, the surroundings of the dying cell, and the identity of the responder.

Background:

New technologies are being developed for early detection of multiple types of cancer simultaneously. To quantify the potential benefit, we estimated reductions in absolute cancer–related deaths that could occur if cancers diagnosed after metastasis (stage IV) were instead diagnosed at earlier stages.

“Dear Designer” is a blog series on orienting novice practitioners to the discipline of instructional design and learning experience design.

The post Dear Designer: 3 Considerations for Length When Shifting to VILT appeared first on e-Learning Feeds.

Yell at yer friends in 1-4 player co-op while working under time pressure to serve up meals to an unforgiving god in Overc—er sorry, Cannibal Cuisine. It’s certainly got a familiar vibe to it, so if you liked the frantic food prep of that other friendship-ender perhaps you’ll like doing it with a new secret […]

A centenarian who tested positive for COVID-19 has become the oldest local resident to die from the virus. The woman in her 100s was a resident of a long-term care or retirement home. She died on Thursday, the Windsor-Essex County Health Unit reported during its end-of-week epidemic data summary on Friday. “I would like to […]

Chinese telecomms firm Huawei will be allowed to provide technology for key parts of the UK's super-fast 5G infrastructure, prime minister Boris Johnson has said, despite opposition from the US

Pandemics of the past can teach us about the current one, says John Troyer, who studies how we use technology to alter the experience of death

Why? Because that’s our reality here in the year 2020.

A South Dakota teenager has admitted to slaying a 16-year-old girl who “ran away” from home to live with him after they met on an online dating website, authorities said.

Michael Campbell, 17, pleaded guilty to first-degree manslaughter on Thursday for the death of Shayna Ritthaler, a 16-year-old from Moorcroft, Wyoming, who was reported missing from a local coffee shop on Oct. 3. Less than a week later, her body was found in the basement bedroom of Campbell’s home.

“We got into an argument and then I shot her,” Campbell said during a change-of-plea hearing on Thursday, before referring to the teenager as his girlfriend, according to the Associated Press. “I shot her in the head.”

Read more at The Daily Beast.

Campaigns and consultants have spent the last four years worrying about the Trump campaign’s digital operation. Even before COVID-19 upended the election and forced candidates online, the Trump campaign was geofencing campaign rallies, micro-targeting digital ads, and amplifying deepfake videos.

And now, as both the crisis and the general election enter their third month, panic is beginning to set in about the startling digital gap between the two parties, amplified by the recent Trump campaign announcement of both a new app experience and the start of a $10 million digital push against Joe Biden. 

President Trump’s campaign manager has called what he’s built a “juggernaut” and is likening his digital infrastructure to a Death Star. In reality, what he's built is a trap.  

Read more at The Daily Beast.

This post contains spoilers for Dead to Me Season 2.

Maybe it’s the surreality of, well, everything lately—or maybe it’s just aged like the fine wines all of its characters toss back by the bottle. Whatever the reason, Dead to Me Season 2 hits even better than Season 1—fighting off a sophomore slump with a fresh batch of twists, dramatic ironies, and, most importantly, some more Christina Applegate angsting out to metal. Perhaps this season’s smartest move, however, is a trope pulled straight out of Soapy Dramas 101: Bringing James Marsden back to play his own twin.

Series creator Liz Feldman was sending the usual thank-you notes back and forth with cast and crew after Season 1 wrapped when she received a particularly amusing message from Marsden.

Read more at The Daily Beast.

Thousands of dead satellites and chunks of debris in orbit are a threat to active satellites, but rockets that launch clouds of talcum powder may prevent a disastrous collision

The machine would use an “alphabet of human thoughts” and rules to combine them

What’s going to get Jen first: the discovery of what’s happening in her garage, or the guilt over what she hasn’t told her BFF?

What feels like a victory to Jen doesn’t carry the same sense of relief for Judy.

“Today, the world has lost one of the greats of magic, but I have lost my best friend,” Siegfried Fischbacher said in a statement.

After finding common ground, Jen and Judy split up to spend time with new friends who could end up being something more.

His cause of death is unknown.

This RPG Cast was recorded in the dark before a dead studio audience. Josh fails at Fire Emblem. Jonathan becomes a rock star. Kelley pines for Garrus. Chris gets spooked. And Anna Marie harvests squid poop. Yeah it's a weird show.

Peter, Kelley, Chris, and Anna Marie are joined by Alice this week; while she didn’t deliver any missiles, large robots may be a part of the podcast in unexpected ways! We discuss cheating on the stalk market, the news of the week, and your feedback. Now to wait for our copies of Persona 5 Royal to arrive...hurry up already!

Keep up to date with all the latest coronavirus news from Glasgow, Scotland and beyond - LIVE

People who attended religious services at least once a week were significantly less likely to die from 'deaths of despair,' including deaths related to suicide, drug overdose, and alcohol poisoning, according to new research.

Marisa Bardach Ramel is co-author of “The Goodbye Diaries: A Mother-Daughter Memoir,” written with her mother Sally Bardach. As Mother’s Day approaches, I long to sit beside you, pour you some tea and talk about all the things.