T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.

Corporate Members Event Nominees Breakfast Briefing Partners and Major Corporates

Event participants

Christophe Bellmann, Associate Fellow, Hoffmann Centre for Sustainable Resource Economy, Chatham House

Carolyn Deere Birkbeck, Associate Fellow, Global Economy and Finance Department and Hoffmann Centre for Sustainable Resource Economy, Chatham House

• 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

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

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.

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Researchers have poked another small hole in air gapped security by showing how the electronics inside computer power supply units (PSUs) can be turned into covert data transmission devices.

18 February 2020

Normally when creating a digital file, such as a picture, much more information is recorded than necessary-even before storing or sending. The image on the right was created with compressed (or compressive) sensing, a breakthrough technique based on probability and linear algebra. Rather than recording excess information and discarding what is not needed, sensors collect the most significant information at the time of creation, which saves power, time, and memory. The potential increase in efficiency has led researchers to investigate employing compressed sensing in applications ranging from missions in space, where minimizing power consumption is important, to MRIs, for which faster image creation would allow for better scans and happier patients. Just as a word has different representations in different languages, signals (such as images or audio) can be represented many different ways. Compressed sensing relies on using the representation for the given class of signals that requires the fewest bits. Linear programming applied to that representation finds the most likely candidate fitting the particular low-information signal. Mathematicians have proved that in all but the very rarest case that candidate-often constructed from less than a tiny fraction of the data traditionally collected-matches the original. The ability to locate and capture only the most important components without any loss of quality is so unexpected that even the mathematicians who discovered compressed sensing found it hard to believe. For More Information: "Compressed Sensing Makes Every Pixel Count," What's Happening in the Mathematical Sciences, Vol. 7, Dana Mackenzie.

As difficult as it is to do the census, the ensuing process of determining the number of congressional seats for each state can be even harder. The basic premise, that the proportion of each state's delegation in the House should match its proportion of the U.S. population, is simple enough. The difficulty arises when deciding what to do with the fractions that inevitably arise (e.g., New York can't have 28.7 seats). Over the past 200 years, several methods of apportioning seats have been used. Many sound good but can lead to paradoxes, such as an increase in the total number of House seats actually resulting in a reduction of a state's delegation. The method used since the 1940s, whose leading proponent was a mathematician, is one that avoids such paradoxes. A natural question is Why 435 seats? Nothing in the Constitution mandates this number, although there is a prohibition against having more than one seat per 30,000 people. One model, based on the need for legislators to communicate with their constituents and with each other, uses algebra and calculus to show that the ideal assembly size is the cube root of the population it represents. Remarkably, the size of the House mirrored this rule until the early 1900s. To obey the rule now would require an increase to 670, which would presumably both better represent the population and increase the chances that the audience in the seats for those late speeches would outnumber the speaker. For More Information: "E pluribus confusion", Barry Cipra, American Scientist, July-August 2010.

As difficult as it is to do the census, the ensuing process of determining the number of congressional seats for each state can be even harder. The basic premise, that the proportion of each state's delegation in the House should match its proportion of the U.S. population, is simple enough. The difficulty arises when deciding what to do with the fractions that inevitably arise (e.g., New York can't have 28.7 seats). Over the past 200 years, several methods of apportioning seats have been used. Many sound good but can lead to paradoxes, such as an increase in the total number of House seats actually resulting in a reduction of a state's delegation. The method used since the 1940s, whose leading proponent was a mathematician, is one that avoids such paradoxes. A natural question is Why 435 seats? Nothing in the Constitution mandates this number, although there is a prohibition against having more than one seat per 30,000 people. One model, based on the need for legislators to communicate with their constituents and with each other, uses algebra and calculus to show that the ideal assembly size is the cube root of the population it represents. Remarkably, the size of the House mirrored this rule until the early 1900s. To obey the rule now would require an increase to 670, which would presumably both better represent the population and increase the chances that the audience in the seats for those late speeches would outnumber the speaker. For More Information: "E pluribus confusion", Barry Cipra, American Scientist, July-August 2010.

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.

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.

And against the backdrop of threatened lives, crippled businesses and damaged economies, the UN chief warned the Petersberg Climate Dialogue in Berlin that the Sustainable Development Goals (SDGs) are also under threat.