• Review of Mama
• What We Watched: The Last Stand, Tangled, Silent Hill: Revelations, Bob's Burgers, South Park, Arrested Development and The Hole. 

• Warm Bodies review
• The History of Zombie Movies That Rudy Likes
• What We Watched: Bob's Burgers, Some Bob Marley documentary, Movie 43 and The Innkeepers

• Review of Chan Wook Park's Stoker.
• What We Watched: Dredd, The Artist is Present, Side by Side, Silver Lining's Playbook, Arrested Development, All-Star Celebrity Apprentice, Bob's Burgers.

• Review of Oz: The Great and Powerful
• Movie Homework: Network/Closer
• What We Watched: Dredd, Undefeated, Sassy Pants, Game of Thrones, Gummo, This is 40

• Review of Harmony Korine's Spring Breakers
• Movie Homework: The Seven Year Itch/Bronson/Kirikou and the Sorceress

• Evil Dead Review
• The Walking Dead Season 3 Discussion
• Other banter

• The Place Beyond the Pines Review
• From Up On Poppy Hill Review
• Movie Homework: Beasts of the Southern Wild/Shame
• What We Watched: Evil Dead, Game of Thrones, The Staircase & A Dangerous Method

• Oblivion Review
• Jason's thoughts on Rob Zombie's The Lords of Salem
• Robert's thoughts on Trance
• Movie Homework: Slapshot/Do Deca Pentathlon/Session 9
• What We Watched: Game of Thrones, Sex and Lucia, Jack Reacher, Which Way is the Front Lime From Here, Loose Change 9/11

• Iron Man 3 Review
• Star Trek: Into Darkness Review
• The Great Gatsby Review
• What We Watched

• Man Of Steel Review
• This Is The End Review
• What We Watched

• Pacific Rim Review
• World War Z mini-review
• What We Watched: The Lone Ranger, Breaking Bad, Mad Men, Celeste and Jesse Forever, Despicable Me 2, Ruby Sparks, Melancholia, Do The Right Thing, ESPN 30 for 30: Broke, etc.

• Upstream Color review
• The Kings of Summer review
• Blackfish review
• What We Watched: Fruitvale Station, At World's End, The Spectacular Now, Elysium, Only God Forgives, and The ABCs of Death
• Grand Theft Auto 5 talk

• Gravity Review
• What We Watched: Room 237, The American Scream, Bless Me Ultima, Ernest Scared Stupid, The Conjuring, V/H/S 2, H. H. Holmes: America's First Serial Killer & Attack on Titan.
• Gravity Spoiler Discussion (after the outro music). 

• 12 Years A Slave Review
• What We Watched: Seduced and Abandoned, Bad Granpda, Grave Encounters, Carrie, Oliver Stone's Untold History of the United States, Adventure Time, Chopping Mall, Frenzy, The Halloween Tree, Sisters, Altered States, Sleepaway Camp, American Mary, Friday the 13th IV: The Final Chapter, Cannibal Holocaust, Prince of Darkness & The Fog. 

• Thor: The Dark World Review
• Frances Ha Review
• What We Watched

• The Hunger Games: Catching Fire review
• The Wolverine Reviews
• What We Watched: jOBS, Steve Jobs: The Lost Interview, WWE For All Mankind: Life and Career of Mick Foley and The Lakota 38

• Oldboy Review
• Frozen Review
• What We Watched: Fargo, Homefront, Gravity
• The Walking Dead Mid-Season Spoiler Discussion
• Oldboy Spoiler Discussion
• Thor: The Dark World Acid-Indused Hypothesizing 

• American Hustle
• The Hobbit: The Desolation of Smaug
• Anchorman 2: The Legend Continues
• Out of the Furnace
• 2014 Bucket List Films
• What We Watched: Bully, Prisoners, Powwow Highway, Miss Representation, The Spectacular Now, Knuckle, Shut Up And Play The Hits, Mike Birbiglia: My Girlfriend's Boyfriend and The Act of Killing. 

23 April 2020

The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains.

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.

Expert

A. G. Sergeev and Kh. A. Khachatryan
Trans. Moscow Math. Soc. 80 (2020), 95-111.
Abstract, references and article information

Tratamento genético foi testado em Layla Richards que estava desenganada pelos médicos. Especialistas ressaltam que os resultados são iniciais e podem não ocorrer em outros pacientes.

The post Terapia inédita reverte leucemia incurável em bebê de 1 ano appeared first on Saúde Próspera.

Aos primeiros sinais de visão embaçada, as hipóteses mais frequentes sempre são miopia, astigmatismo, hipermetropia. Mas esses sintomas podem indicar outra doença ocular chamada ceratocone - uma deformidade progressiva da córnea, que assume o formato...

The post Visão embaçada e distorcida nem sempre é miopia: fique atento aos sinais do ceratocone appeared first on Saúde Próspera.

6 November 2019 , Volume 95, Number 6

8 January 2020 , Volume 96, Number 1

Mathematics is not just numbers and brute force calculation there is considerable art and elegance to the subject. So it is natural that mathematics is now being used to analyze artists. styles and to help determine the identities of the creators of disputed works. Attempts at measuring style began with literature based on statistics of word use and have successfully identified disputed works such as some of The Federalist Papers. But drawings and paintings resisted quantification until very recently. In the case of Jackson Pollock, his paintings have a demonstrated complexity to them (corresponding to a fractal dimension between 1 and 2) that distinguishes them from simple random drips. A team examining digital photos of drawings used modern mathematical transforms known as wavelets to quantify attributes of a collection of 16th century master.s drawings. The analysis revealed measurable differences between authentic drawings and imitations, clustering the former away from the latter. This is an impressive feat for the non-experts and their model, yet the team agrees that its work, like mathematics itself, is not designed to replace humans, but to assist them. For More Information: The Style of Numbers Behind a Number of Styles, Dan Rockmore, The Chronicle of Higher Education, June 9, 2006.

Invisibility is no longer confined to fiction. In a recent experiment, microwaves were bent around a cylinder and returned to their original trajectories, rendering the cylinder almost invisible at those wavelengths. This doesn't mean that we're ready for invisible humans (or spaceships), but by using Maxwell's equations, which are partial differential equations fundamental to electromagnetics, mathematicians have demonstrated that in some simple cases not seeing is believing, too. Part of this successful demonstration of invisibility is due to metamaterials electromagnetic materials that can be made to have highly unusual properties. Another ingredient is a mathematical transformation that stretches a point into a ball, "cloaking" whatever is inside. This transformation was discovered while researchers were pondering how a tumor could escape detection. Their attempts to improve visibility eventually led to the development of equations for invisibility. A more recent transformation creates an optical "wormhole," which tricks electromagnetic waves into behaving as if the topology of space has changed. We'll finish with this: For More Information: Metamaterial Electromagnetic Cloak at Microwave Frequencies, D. Schurig et al, Science, November 10, 2006.

The heart.s function of pumping blood may seem fairly simple but the underlying mechanisms and electrical impulses that maintain a healthy rhythm are extremely complex. Many areas of mathematics, including differential equations, dynamical systems, and topology help model the electrical behavior of cardiac cells, the connections between those cells and the heart.s overall geometry. Researchers aim to gain a better understanding of the normal operation of the heart, as well as learn how to diagnose the onset of abnormalities and correct them. Of the many things that can go wrong with a heart.s rhythm, some measure of unpredictability is (surprisingly) not one of them. A healthy heartbeat is actually quite chaotic not regular at all. Furthermore, beat patterns become less chaotic as people age and heart function diminishes. In fact, one researcher recommends that patients presented with a new medication should ask their doctors, "What is this drug going to do to my fractal dimensionality?" For More Information: Taking Mathematics to Heart: Mathematical Challenges in Cardiac Electrophysiology, John W. Cain, Notices of the AMS, April 2011, pp. 542-549.

Some of the simplest and most well-known curves parabolas and ellipses, which can be traced back to ancient Greece are also among the most useful. Parabolas have a reflective property that is employed in many of today.s solar power technologies. Mirrors with a parabolic shape reflect all entering light to a single point called the focus, where the solar power is converted into usable energy. Ellipses, which have two foci, have a similar reflecting property that is exploited in a medical procedure called lithotripsy. Patients with kidney stones and gallstones are positioned in a tank shaped like half an ellipse so that the stones are at one focus. Acoustic waves sent from the other focus concentrate all their energy on the stones, pulverizing them without surgery. Math can sometimes throw you a curve, but that.s not necessarily a bad thing. Parabolas and ellipses are curves called conic sections. Another curve in this category is the hyperbola, which may have the most profound application of all the nature of the universe. In plane geometry, points that are a given distance from a fixed point form a circle. In space, points that are a given spacetime distance from a fixed point form one branch of a hyperbola. This is not an arbitrary mandate but instead a natural conclusion from the equations that result when the principle of relativity is reconciled with our notions of distance and causality. And although a great deal of time has elapsed since the discovery of conic sections, they continue to reap benefits today. For More Information: Practical Conic Sections: The Geometric Properties of Ellipses, Parabolas and Hyperbolas, J. W. Downs, 2010.

Researcher: Christopher Butson, Scientific Computing and Imaging Institute, University of Utah. Christopher Butson talks about work he's done to help treat Parkinson's disease.

Researcher: Wesley Pegden, Carnegie Mellon University
Moment Title: Piling On and on and on!
Description: Wesley Pegden talks about simulating sandpiles

Researcher: Stefan Siegmund, TU-Dresden Moment: http://www.ams.org/samplings/mathmoments/mm137-hurricane.pdf Description: Stefan Siegmund talks about his an invention to protect homes during hurricanes.

Steven Strogatz and Mary Bushman talk about math's role in controlling HIV and understanding malaria, respectively. Mary Bushman says, "It's really cool to try and use math to nail down some questions that have gone unanswered for a really long time."

Fumie Tazaki talks about creating the first image of a black hole and its shadow, which relied on Fourier transforms. About the work to make the image, she says, "Our collaboration has 200 members and we did it with all of our efforts."

euromicron AG, a medium-sized technology group and expert on the digital networking of business and production processes, has now fully placed the capital increase it resolved on July 10, 2019.

In-form American sprinter, Michael Rodgers, ran a world-leading 9.94 seconds and there were no Caribbean