Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts and clusters of apoptotic signaling molecule-enriched rafts. The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, LXR agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apoA-I binding protein. Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy.

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.

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.

Activation of microglia and astrocytes secondary to inflammatory processes contributes to the development and perpetuation of pain with a neuropathic phenotype. This pain state presents as a chronic debilitating condition and affects a large population of patients with conditions like rheumatoid arthritis and diabetes, or after surgery, trauma, or chemotherapy. Here, we review the regulation of lipid rafts in glial cells and the role they play as a key component of neuroinflammatory sensitization of central pain signaling pathways. In this context, we introduce the concept of an inflammaraft (i-raft), enlarged lipid rafts harboring activated receptors and adaptor molecules and serving as an organizing platform to initiate inflammatory signaling and the cellular response. Characteristics of the inflammaraft include increased relative abundance of lipid rafts in inflammatory cells, increased content of cholesterol per raft, and increased levels of inflammatory receptors, such as toll-like receptor (TLR)4, adaptor molecules, ion channels, and enzymes in lipid rafts. This inflammaraft motif serves an important role in the membrane assembly of protein complexes, for example, TLR4 dimerization. Operating within this framework, we demonstrate the involvement of inflammatory receptors, redox molecules, and ion channels in the inflammaraft formation and the regulation of cholesterol and sphingolipid metabolism in the inflammaraft maintenance and disruption. Strategies for targeting inflammarafts, without affecting the integrity of lipid rafts in noninflammatory cells, may lead to developing novel therapies for neuropathic pain states and other neuroinflammatory conditions.

Lipid rafts are small, dynamic membrane areas characterized by the clustering of selected membrane lipids as the result of the spontaneous separation of glycolipids, sphingolipids, and cholesterol in a liquid-ordered phase. The exact dynamics underlying phase separation of membrane lipids in the complex biological membranes are still not fully understood. Nevertheless, alterations in the membrane lipid composition affect the lateral organization of molecules belonging to lipid rafts. Neural lipid rafts are found in brain cells, including neurons, astrocytes, and microglia, and are characterized by a high enrichment of specific lipids depending on the cell type. These lipid rafts seem to organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating the homeostasis of the brain. The progressive decline of brain performance along with physiological aging is at least in part associated with alterations in the composition and structure of neural lipid rafts. In addition, neurodegenerative conditions, such as lysosomal storage disorders, multiple sclerosis, and Parkinson’s, Huntington’s, and Alzheimer’s diseases, are frequently characterized by dysregulated lipid metabolism, which in turn affects the structure of lipid rafts. Several events underlying the pathogenesis of these diseases appear to depend on the altered composition of lipid rafts. Thus, the structure and function of lipid rafts play a central role in the pathogenesis of many common neurodegenerative diseases.

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.

Lipid rafts, solid regions of the plasma membrane enriched in cholesterol and glycosphingolipids, are essential parts of a cell. Functionally, lipid rafts present a platform that facilitates interaction of cells with the outside world. However, the unique properties of lipid rafts required to fulfill this function at the same time make them susceptible to exploitation by pathogens. Many steps of pathogen interaction with host cells, and sometimes all steps within the entire lifecycle of various pathogens, rely on host lipid rafts. Such steps as binding of pathogens to the host cells, invasion of intracellular parasites into the cell, the intracellular dwelling of parasites, microbial assembly and exit from the host cell, and microbe transfer from one cell to another all involve lipid rafts. Interaction also includes modification of lipid rafts in host cells, inflicted by pathogens from both inside and outside the cell, through contact or remotely, to advance pathogen replication, to utilize cellular resources, and/or to mitigate immune response. Here, we provide a systematic overview of how and why pathogens interact with and exploit host lipid rafts, as well as the consequences of this interaction for the host, locally and systemically, and for the microbe. We also raise the possibility of modulation of lipid rafts as a therapeutic approach against a variety of infectious agents.

Lipid rafts are organized plasma membrane microdomains, which provide a distinct level of regulation of cellular metabolism and response to extracellular stimuli, affecting a diverse range of physiologic and pathologic processes. This Thematic Review Series focuses on Biology of Lipid Rafts rather than on their composition or structure. The aim is to provide an overview of ideas on how lipid rafts are involved in regulation of different pathways and how they interact with other layers of metabolic regulation. Articles in the series will review the involvement of lipid rafts in regulation of hematopoiesis, production of extracellular vesicles, host interaction with infection, and the development and progression of cancer, neuroinflammation, and neurodegeneration, as well as the current outlook on therapeutic targeting of lipid rafts.

Thematic collection: This article is part of the Exploration 17 collection available at: https://www.lyellcollection.org/cc/exploration-17

We spoke with industry experts to identify what’s preventing developers from fully going green – and it all boils down to lack of finances.

Electric scooters are a nightmare. Rented by the minute, they clog up pavements and are an ungainly eyesore, but we still need them, says Donna Lu

Robots are being developed to help with tasks like fixing the sea cages where fish are farmed, and their size seems to be all that affects how the fish react

Can you really be addicted to your smartphone? Daria Kuss has shown that it is only a problem for a small number of people - and she knows how to help

Please, I implore you: jump on this bandwagon.

On Tuesday the president took his first trip since the coronavirus grounded the country, to a Honeywell factory in battleground state Arizona. This particular Honeywell factory produces N95 masks. Pictures of the trip immediately surfaced on the internet, and they showed a president sporting his usual mango-tinted, ever-tan skin, his usual topiary-structured hair tinted a baffling yellowish, and a pair of clear safety goggles.

But what was missing? What we did not see on the president’s face was a mask. While the rest of us cover our faces as recommended by the CDC, the president does not. In fact, we have never seen a mask on the president, despite the president’s love of masking himself when it comes to his tax returns, his sexual assault allegations, and his financial dealings.   

On Wednesday, when pressed on his decision not to wear a mask at a mask factory, the president responded with the very fishy, “I had a mask on for a period of time, I had it on back, backstage. But they said you didn’t need it, so, I didn’t need it. And by the way, if you noticed, nobody else had it on that was in the group.” Okay. Whatever you say. 

Read more at The Daily Beast.

Einstein’s theory of relativity predicts that fast-spinning objects stretch space and time around them, and we’ve watched that effect make a pair of stars wobble

Extraterrestrial oceans are an obvious place to search for alien life, but getting there and having a look won't be easy, says NASA's Kevin Hand in his book Alien Oceans

Whether for maintenance or augmentation, robots that can use tools on themselves are more independent and capable

This week RPG Cast welcomes Kelley to the show! Together with Anna Marie and Chris, they uncover the truth about Vita DRPGs. They unravel the...

In fact, why not join them?

There's been a spike in scam calls, emails and texts

Trapped in lockdown due to the COVID-19 pandemic, over a thousand migrant workers staying in Hyderabad's Tolichowki took to the streets on Sunday demanding to be taken home.

To fight the new coronavirus, researchers are investigating more than 60 drugs, including remdesivir and hydroxychloroquine and brand new ones. Here’s a breakdown of progress so far

Economic reconstruction is a chance to speed up decarbonisation, and the pandemic has shown a different kind of politics is possible

We’re already being swamped with ideas about “reforms” needed to recover from the pandemic crisis. But the word reform is like gift wrap – a handy cover for any offering, thought-through or otherwise.

Perhaps we should ditch the word entirely, and with it the forest of feelpinions about what governments “must” do to advance an author’s previously-held ideological positioning in the post-corona world.

As the pachyderms increasingly clash with farmers and villagers over disappearing land, scientists study the way the animals' minds work

Some plants, like soybean, are known to possess an innate defense machinery that helps them develop resistance against insects trying to feed on them. However, exactly how these plants recognize signals from insects has been unknown until now. Scientists have now uncovered the cellular pathway that helps these plants to sense danger signals and elicit a response, opening doors to a myriad of agricultural applications.

Catering companies are having to get creative to stay in business during COVID-19.

Follow our live Covid-19 update HERE Coronavirus: The symptoms

Coronavirus: the symptoms Read our LIVE updates on coronavirus here

Follow our live Covid-19 updates HERE Coronavirus: The symptoms

Follow our live coronavirus updates here Coronavirus: the symptoms

A paramedic was left unable to go to work after a brick was thrown through their car window.

Pair in Leicestershire reprimanded for illicit weekend venture which prompted police helicopter search

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All essential workers are to be able to get coronavirus tests if they need them due to increased screening capacity, health secretary Matt Hancock announced today.

The Government's new portal for arranging coronavirus tests has sparked confusion today, following a message suggesting home tests had run out by 9am.

Mr White also took issue with the duchess's allegation that the publisher "acted dishonestly" when deciding which parts of her letter to her father to publish.

This is the moment a firefighter's star-spangled tribute entertained health workers outside a Manhattan hospital.

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Cancer patients are being kept awake during operations to protect them from coronavirus, the Evening Standard can reveal.

Data can be retrieved even after owners perform a factory reset, researcher says.

https://www.ebay.com/itm/Microsoft-Xbox-One-X-1TB-Black-Console-as-is-for-repair-or-parts-only/264227168298

YMMV obviously--I ordered two of these a month ago and they have been running fine for me.  All I had to do was reinstall the newest system update and they have both been fine with no issues.  One system's issue noted was "freezes" and the other was "no video". 

It says he has only 2 in stock, but I bought two a while back and the listing has remained active for the entire time with stock available, so he probably leaves the number low to keep demand going. This is probably a bulk buyer who doesn't extensively troubleshoot the systems.  I am not affiliated with the seller.  Cosmetically, the systems are nice enough to trade in without taking a refurb fee when stores re-open for business.

Bill & Ted fans now have a chance to appear in the franchise’s next instalment.A new contest unveiled on Tuesday urges people to film themselves playing music and/or dancing to a pre-recorded demo track.

Visual challenges remain before autonomous cars are ready for the masses.

Chris Labelle has a hard time getting through his latest song, Frontliners, without becoming emotional.  The Ottawa country singer wrote the tune — an unabashedly sentimental anthem of gratitude for front-line workers — during one of the sleepless nights leading up to the birth of his first child with wife Julie. Their baby boy, Grayson, […]

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Character's fate was famously left ambiguous at the end of the seminal gangster drama