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.

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.

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.

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Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 is also necessary for maintaining the cristae and thus essential for supporting cellular energetics. OPA1 exists as membrane-anchored long form (L-OPA1) and short form (S-OPA1) that lacks the transmembrane region and is generated by cleavage of L-OPA1. Mitochondrial dysfunction and cellular stresses activate the inner membrane–associated zinc metallopeptidase OMA1 that cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been that L-OPA1 is the functional form, whereas S-OPA1 is an inactive cleavage product in mammals, and that stress-induced OPA1 cleavage causes mitochondrial fragmentation and sensitizes cells to death. However, S-OPA1 contains all functional domains of dynamin proteins, suggesting that it has a physiological role. Indeed, we recently demonstrated that S-OPA1 can maintain cristae and energetics through its GTPase activity, despite lacking fusion activity. Here, applying oxidant insult that induces OPA1 cleavage, we show that cells unable to generate S-OPA1 are more sensitive to this stress under obligatory respiratory conditions, leading to necrotic death. These findings indicate that L-OPA1 and S-OPA1 differ in maintaining mitochondrial function. Mechanistically, we found that cells that exclusively express L-OPA1 generate more superoxide and are more sensitive to Ca2+-induced mitochondrial permeability transition, suggesting that S-OPA1, and not L-OPA1, protects against cellular stress. Importantly, silencing of OMA1 expression increased oxidant-induced cell death, indicating that stress-induced OPA1 cleavage supports cell survival. Our findings suggest that S-OPA1 generation by OPA1 cleavage is a survival mechanism in stressed cells.

pncRNA-D is an irradiation-induced 602-nt long noncoding RNA transcribed from the promoter region of the cyclin D1 (CCND1) gene. CCND1 expression is predicted to be inhibited through an interplay between pncRNA-D and RNA-binding protein TLS/FUS. Because the pncRNA-D–TLS interaction is essential for pncRNA-D–stimulated CCND1 inhibition, here we studied the possible role of RNA modification in this interaction in HeLa cells. We found that osmotic stress induces pncRNA-D by recruiting RNA polymerase II to its promoter. pncRNA-D was highly m6A-methylated in control cells, but osmotic stress reduced the methylation and also arginine methylation of TLS in the nucleus. Knockdown of the m6A modification enzyme methyltransferase-like 3 (METTL3) prolonged the half-life of pncRNA-D, and among the known m6A recognition proteins, YTH domain-containing 1 (YTHDC1) was responsible for binding m6A of pncRNA-D. Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS–pncRNA-D interaction. CRISPR/Cas9-mediated deletion of candidate m6A site decreased the m6A level in pncRNA-D and altered its interaction with the RNA-binding proteins. Of note, a reduction in the m6A modification arrested the cell cycle at the G0/G1 phase, and pncRNA-D knockdown partially reversed this arrest. Moreover, pncRNA-D induction in HeLa cells significantly suppressed cell growth. Collectively, these findings suggest that m6A modification of the long noncoding RNA pncRNA-D plays a role in the regulation of CCND1 gene expression and cell cycle progression.

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.

K. D. Cherednichenko, Yu. Yu. Ershova, A. V. Kiselev and S. N. Naboko
Trans. Moscow Math. Soc. 80 (2020), 251-294.
Abstract, references and article information

A. M. Savchuk and I. V. Sadovnichaya
Trans. Moscow Math. Soc. 80 (2020), 235-250.
Abstract, references and article information

V. A. Sadovnichii, Ya. T. Sultanaev and A. M. Akhtyamov
Trans. Moscow Math. Soc. 80 (2020), 123-131.
Abstract, references and article information

S. A. Kashchenko
Trans. Moscow Math. Soc. 80 (2020), 53-71.
Abstract, references and article information

S. A. Nazarov
Trans. Moscow Math. Soc. 80 (2020), 1-51.
Abstract, references and article information

Prótese auditiva ancorada em osso não emite um som como o aparelho convencional. Seu diferencial é vibrar o osso da cabeça.

The post SUS vai oferecer aparelho de última geração para tipo de perda auditiva até então sem tratamento appeared first on Saúde Próspera.

A. Knightly and C. Li
Memoirs of the AMS 224 (2012).
Abstract, references and article information

Publication Date: Apr 10 2020 On or before December 22, 2020, all ETFs that meet the definition of "Exchange Traded Fund" in Nasdaq Rule 5704(a)(1)(A) will need to be compliant with Rule 6c-11. If it is determined that an ETF no longer complies with Rule 6c-11 and therefore no longer complies Nasdaq Rule 5704, Nasdaq will generally issue a letter of deficiency. The ETF will generally be given 45 days to submit a plan to regain compliance. If the plan is accepted, Nasdaq Staff can grant an...

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6 November 2019 , Volume 95, Number 6

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

Invitation Only Research Event

23 January 2020

Invitation Only Research Event

Invitation Only Research Event

Event participants

Dr Kurt Campbell, Chairman, CEO and Co-Founder, The Asia Group; Assistant Secretary of State for East Asian and Pacific Affairs, 2009-13
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

8 April 2020

Research Event

Event participants

Antony Dapiran, Writer; Lawyer; Author of City on Fire: The Fight for Hong Kong
Chair: Jessie Lau, Journalist; Researcher; Artist; Board Member and Online Editor-in-Chief, NüVoices

15 April 2020

Research Event

Event participants

Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham House
Kerry Brown, Associate Fellow, Asia-Pacific Programme, Chatham House; Professor of Chinese Studies and Director of Lau China Institute, King’s College London

Detection and treatment of cancer have progressed, but neither is as precise as doctors would like. For example, tumors can change shape or location between pre-operative diagnosis and treatment so that radiation is aimed at a target which may have moved. Geometry, partial differential equations, and integer linear programming are three areas of mathematics used to process data in real-time, which allows doctors to inflict maximum damage to the tumor, with minimum damage to healthy tissue. One promising area of investigation is virotherapy: using viruses to destroy cancerous cells. Researchers are using mathematical models to discover how to use the viruses most beneficially.The models provide numerical outcomes for each of the many possibilities, thereby eliminating unsuccessful approaches and identifying candidates for further experimentation.Testing by simulation, which led to the development of anti-HIV cocktails, means good medicine is developed faster and cheaper than it can be by lab experiments and clinical trials alone. For More Information: Treatment Planning for Brachytherapy, Eva Lee, et al, Physics in Medicine and Biology, 1999.

Storm surge is often the most devastating part of a hurricane. Mathematical models used to predict surge must incorporate the effects of winds, atmospheric pressure, tides, waves and river flows, as well as the geometry and topography of the coastal ocean and the adjacent floodplain. Equations from fluid dynamics describe the movement of water, but most often such huge systems of equations need to be solved by numerical analysis in order to better forecast where potential flooding will occur. Much of the detailed geometry and topography on or near a coast require very fine precision to model, while other regions such as large open expanses of deep water can typically be solved with much coarser resolution. So using one scale throughout either has too much data to be feasible or is not very predictive in the area of greatest concern, the coastal floodplain. Researchers solve this problem by using an unstructured grid size that adapts to the relevant regions and allows for coupling of the information from the ocean to the coast and inland. The model was very accurate in tests of historical storms in southern Louisiana and is being used to design better and safer levees in the region and to evaluate the safety of all coastal regions. For More Information: A New Generation Hurricane Storm Surge Model for Southern Louisiana, by Joannes Westerink et al.

Archimedes was one of the most brilliant people ever, on a par with Einstein and Newton. Yet very little of what he wrote still exists because of the passage of time, and because many copies of his works were erased and the cleaned pages were used again. One of those written-over works (called a palimpsest) has resurfaced, and advanced digital imaging techniques using statistics and linear algebra have revealed his previously unknown discoveries in combinatorics and calculus. This leads to a question that would stump even Archimedes: How much further would mathematics and science have progressed had these discoveries not been erased? One of the most dramatic revelations of Archimedes. work was done using X-ray fluorescence. A painting, forged in the 1940s by one of the book.s former owners, obscured the original text, but X-rays penetrated the painting and highlighted the iron in the ancient ink, revealing a page of Archimedes. treatise The Method of Mechanical Theorems. The entire process of uncovering this and his other ideas is made possible by modern mathematics and physics, which are built on his discoveries and techniques. This completion of a circle of progress is entirely appropriate since one of Archimedes. accomplishments that wasn.t lost is his approximation of pi. For More Information: The Archimedes Codex, Reviel Netz and William Noel, 2007.

Archimedes was one of the most brilliant people ever, on a par with Einstein and Newton. Yet very little of what he wrote still exists because of the passage of time, and because many copies of his works were erased and the cleaned pages were used again. One of those written-over works (called a palimpsest) has resurfaced, and advanced digital imaging techniques using statistics and linear algebra have revealed his previously unknown discoveries in combinatorics and calculus. This leads to a question that would stump even Archimedes: How much further would mathematics and science have progressed had these discoveries not been erased? One of the most dramatic revelations of Archimedes. work was done using X-ray fluorescence. A painting, forged in the 1940s by one of the book.s former owners, obscured the original text, but X-rays penetrated the painting and highlighted the iron in the ancient ink, revealing a page of Archimedes. treatise The Method of Mechanical Theorems. The entire process of uncovering this and his other ideas is made possible by modern mathematics and physics, which are built on his discoveries and techniques. This completion of a circle of progress is entirely appropriate since one of Archimedes. accomplishments that wasn.t lost is his approximation of pi. For More Information: The Archimedes Codex, Reviel Netz and William Noel, 2007.

The collective motion of many groups of animals can be stunning. Flocks of birds and schools of fish are able to remain cohesive, find food, and avoid predators without leaders and without awareness of all but a few other members in their groups. Research using vector analysis and statistics has led to the discovery of simple principles, such as members maintaining a minimum distance between neighbors while still aligning with them, which help explain shapes such as the one below. Although collective motion by groups of animals is often beautiful, it can be costly as well: Destructive locusts affect ten percent of the world.s population. Many other animals exhibit group dynamics; some organisms involved are small while their groups are huge, so researchers. models have to account for distances on vastly different scales. The resulting equations then must be solved numerically, because of the incredible number of animals represented. Conclusions from this research will help manage destructive insects, such as locusts, as well as help speed the movement of people.ants rarely get stuck in traffic. Photo by Jose Luis Gomez de Francisco. For More Information: Swarm Theory, Peter Miller. National Geographic, July 2007.

Mathematics has helped investigators in several major cases of human rights abuses and election fraud. Among them: The 2009 election in Iran. A mathematical result known as Benford's Law states that the leading digits of truly random numbers aren't distributed uniformly, as might be expected. Instead, smaller digits, such as 1's, appear much more frequently than larger digits, such as 9's. Benford's Law and other statistical tests have been applied to the 2009 election and suggest strongly that the final totals are suspicious. Ethnic cleansing. When Slobodan Milosevic went on trial, it was his contention that the mass exodus of ethnic Albanians from Kosovo was due to NATO bombings and the activities of the Albanian Kosovo Liberation Army rather than anything he had ordered. A team collected data on the flow of refugees to test those hypotheses and was able to refute Milosevic's claim in its entirety. Guatemalan disappearances. Here, statistics is being used to extract information from over 80 million National Police archive pages related to about 200,000 deaths and disappearances. Sampling techniques give investigators an accurate representation of the records without them having to read every page. Families are getting long-sought after proof of what happened to their relatives, and investigators are uncovering patterns and motives behind the abductions and murders. Tragically, the people have disappeared. But because of this analysis, the facts won't. For More Information: Killings and Refugee Flow in Kosovo, March-June 1999, Ball et al., 2002.

Mathematics has helped investigators in several major cases of human rights abuses and election fraud. Among them: The 2009 election in Iran. A mathematical result known as Benford's Law states that the leading digits of truly random numbers aren't distributed uniformly, as might be expected. Instead, smaller digits, such as 1's, appear much more frequently than larger digits, such as 9's. Benford's Law and other statistical tests have been applied to the 2009 election and suggest strongly that the final totals are suspicious. Ethnic cleansing. When Slobodan Milosevic went on trial, it was his contention that the mass exodus of ethnic Albanians from Kosovo was due to NATO bombings and the activities of the Albanian Kosovo Liberation Army rather than anything he had ordered. A team collected data on the flow of refugees to test those hypotheses and was able to refute Milosevic's claim in its entirety. Guatemalan disappearances. Here, statistics is being used to extract information from over 80 million National Police archive pages related to about 200,000 deaths and disappearances. Sampling techniques give investigators an accurate representation of the records without them having to read every page. Families are getting long-sought after proof of what happened to their relatives, and investigators are uncovering patterns and motives behind the abductions and murders. Tragically, the people have disappeared. But because of this analysis, the facts won't. For More Information: Killings and Refugee Flow in Kosovo, March-June 1999, Ball et al., 2002.

Once a problem only in the developed world, obesity is now a worldwide epidemic. The overwhelming cause of the epidemic is a dramatic increase in the food supply and in food consumption not a surprise. Yet there are still many mysteries about weight change that can.t be answered either inside the lab, because of the impracticality of keeping people isolated for long periods of time, or outside, because of the unreliability of dietary diaries. Mathematical models based on differential equations can help overcome this roadblock and allow detailed analysis of the relationship between food intake, metabolism, and weight change. The models. predictions fit existing data and explain such things as why it is hard to keep weight off and why obese people are more susceptible to further weight gain. Researchers are also investigating why dieters often plateau after a few months and slowly regain weight. A possible explanation is that metabolism slows to match the drop in food consumed, but models representing food intake and energy expenditure as a dynamical system show that such a weight plateau doesn.t take effect until much later. The likely culprit is a combination of slower metabolism and a lack of adherence to the diet. Most people are in approximate steady state, so that long-term changes are necessary to gain or lose weight. The good news is that each (enduring) drop of 10 calories a day translates into one pound of weight loss over three years, with about half the loss occurring in the first year. For More Information: Quantification of the effect of energy imbalance on bodyweight, Hall et al. Lancet, Vol. 378 (2011), pp. 826-837.

Cutters of diamonds and other gemstones have a high-pressure job with conflicting demands: Flaws must be removed from rough stones to maximize brilliance but done so in a way that yields the greatest weight possible. Because diamonds are often cut to a standard shape, cutting them is far less complex than cutting other gemstones, such as rubies or sapphires, which can have hundreds of different shapes. By coupling geometry and multivariable calculus with optimization techniques, mathematicians have been able to devise algorithms that automatically generate precise cutting plans that maximize brilliance and yield. The goal is to find the final shape within a rough stone. There are an endless number of candidates, positions, and orientations, so finding the shape amounts to a maximization problem with a large number of variables subject to an infinite number of constraints, a technique called semi-infinite optimization. Experienced human cutters create finished gems that average about 1/3 of the weight of the original rough stone. Cutting with this automated algorithm improved the yield to well above 40%, which, given the value of the stones, is a tremendous improvement. Without a doubt, semi-infinite optimization is a girl.s (or boy.s) best friend.

Van Wedeen talks about the geometry of the brain's communication pathways.

Researcher: Michel C. Molinkovitch, University of Geneva Description: Michel C. Milinkovitch used math, physics, and biology for an amazing discovery about the patterns on a lizard's skin.

euromicron AG, a medium-sized technology group and expert on digital networking of business and production processes, held its Annual General Meeting 2019 in Frankfurt/Main on August 29, 2019. 42 percent of the share capital was represented. At the Annual General Meeting, the Executive Board reported on the operating performance in fiscal year 2018 and in the first half of 2019 and gave an outlook on the current fiscal year. One focus was on the implementation of the measures initiated to focus on and further develop the business model.