The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXR^MyeLDLR^–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXR^MyeLDLR^–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXR^MyeLDLR^–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.

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.

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.

The music of most hit songs is pretty well known, but sometimes there are mysteries. One question that remained unanswered for over forty years is: What instrumentation and notes make up the opening chord of the Beatles. "A Hard Day.s Night"? Mathematician Jason Brown - a big Beatles fan - recently solved the puzzle using his musical knowledge and discrete Fourier transforms, mathematical transformations that help decompose signals into their basic parts. These transformations simplify applications ranging from signal processing to multiplying large numbers, so that a researcher doesn.t have to be "working like a dog" to get an answer. Brown is also using mathematics, specifically graph theory, to discover who wrote "In My Life," which both Lennon and McCartney claimed to have written. In his graphs, chords are represented by points that are connected when one chord immediately follows another. When all songs with known authorship are diagrammed, Brown will see which collection of graphs - McCartney.s or Lennon.s - is a better fit for "In My Life." Although it may seem a bit counterintuitive to use mathematics to learn more about a revolutionary band, these analytical methods identify and uncover compositional principles inherent in some of the best Beatles. music. Thus it.s completely natural and rewarding to apply mathematics to the Fab 4 For More Information: Professor Uses Mathematics to Decode Beatles Tunes, "The Wall Street Journal", January 30, 2009..

James Sethian and Frank Morgan talk about their research investigating bubbles.

Muthu Alagappan explains how topology and analytics are bringing a new look to basketball.

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

Rob Schneiderman talks about the metaphorical connections between math and music

Secretary for Justice Teresa Cheng today refuted suggestions that the law prohibiting group gatherings to combat the COVID-19 epidemic was being misused to crack down on protests and people's freedoms.

During a media session, Ms Cheng responded to criticisms from some legislators that Police were abusing the measure to clamp down on protests.

She said: “The Government respects and protects the freedoms that are set out in our laws, Basic Law and the Hong Kong Bill of Rights Ordinance. However, these freedoms are not absolute. Insofar as they violate the laws, then of course appropriate actions will have to be taken.”

The Government had earlier introduced the Prevention & Control of Disease (Prohibition on Group Gathering) Regulation (Cap. 599G) to prohibit group gatherings with more than four people in public places with a view to combating COVID-19.

The regulation was made in accordance with the Prevention & Control of Disease Ordinance (Cap. 599).

“Cap. 599G is enforced under Cap. 599 as a matter of the public health emergency situation that is facing Hong Kong at the moment. It is promulgated to encourage social distancing. It is not with any other motive except for the safety and health of the people in Hong Kong.

“I hope that you will all comply with it in spirit and in form, so that you will not gather and thereby extend Hong Kong's position in this public health emergency situation. That is the only way by which we can get back to normal life as soon as possible.”

In response to a reporter's question on the relevant provisions in the Basic Law that pertain to the Liaison Office of the Central People's Government in the Hong Kong Special Administrative Region, Ms Cheng remarked that the liaison office must also comply with Hong Kong laws.

“The Central People's Government as defined in the Constitution Law is actually the State Council, and therefore when one looks at the whole thing about the Constitution Law, Article 5 of the Constitution Law states unequivocally that every body that is set up will have to comply with the relevant laws and the Constitution Law.

“In other words, the liaison office will have to obey and comply with the laws in Hong Kong.”

More than 30 local music and dance groups will perform in the Youth Music & Dance Marathon on January 5.

The free event presented by the Leisure & Cultural Services Department will be held from 1pm to 6pm that day at the Cultural Centre Piazza.

Event highlights will include performances by singers and groups from the Renaissance Foundation and My Main Stage as well as other local bands such as Chonotenki and Gainorva.

The Hong Kong Academy for Performing Arts’ School of Dance, the Hong Kong Schools Dance Association and other groups will also give a variety of dance performances such as Chinese, street, jazz, modern, cha-cha-cha, jive and J-pop.

Click here for details.

The city's annual Jazz Marathon will be held on April 25.

The all-day music event will see artists from France, India, Italy, Japan, the Mainland, Russia and the US collaborate with local musicians to create a borderless jazz soundscape.

The Day Marathon Concert will be held from 2.30pm to 6pm while the Night Marathon Concert will be held from 7.15pm to 10.45pm.

 
Ahead of the concerts, jazz workshops with the artists will be held on April 24.

Presented by the Leisure & Cultural Services Department, the events will be held at Queen Elizabeth Stadium in Wan Chai.

Tickets are available at URBTIX.

Click here for details.

We as mathematicians seem practically hell-bent on removing the phrase “I’m just not a math person” from students’ vocabularies. Maybe that’s why they scream it so loudly and defiantly? Math has so many tactical advantages over sports and the arts. … Continue reading →

Sarah Tomasello
Jan 1, 2008; 21:19-25
Articles

W. Guyton Hornsby
Apr 1, 2005; 18:102-107
Articles

Sue McLaughlin
Oct 1, 2010; 23:272-277
Special Report

Betsy B. Dokken
Jul 1, 2008; 21:160-165
From Research to Practice/Cardiovascular Disease and Diabetes

updated April 1, 2020

In response to current challenges that colleges and universities face as a result of the spread of COVID-19, the American Mathematical Society is offering libraries and institutions additional support, in line with recommendations in the ICOLC Statement on the Global COVID-19 Pandemic and Its Impact on Library Services and Resources.

The AMS is also participating in the Copyright Clearance Center Education Continuity License program, providing access to our content for distance learning and other educational uses at no cost to the user.

We are extending grace access for content hosted on our platforms (including MathSciNet) through the end of May for our existing customers. We will re-evaluate this timing as needed.

As courses transition to online, we can provide instructors with complimentary electronic “reserve” copies of our textbooks for cases in which students do not have access to their print copies.

E-books purchased through the perpetual access model on the AMS platform are always available DRM-free with unlimited simultaneous use. In addition, we are partnering with ProQuest to allow multi-user access through mid-June to all e-books purchased on their platforms. Read ProQuest’s statement.

We are providing remote access to all our content, including MathSciNet. In normal circumstances, this remote access can be set up while on campus or while connected via institution VPN (in order to validate IP-based access). We realize many students, faculty, and researchers did not have an opportunity to initiate this access before leaving campus, so we have given instructions to our library partners on how patrons can connect to our content. Please contact your librarian for assistance.

Libraries: if you have not received instructions to share with your patrons, please email us at cust-serv@ams.org or be in touch about any other of your library’s needs.

Review all AMS Resources & Updates.

(Dartmouth College) Annual award supports the research and teaching careers of talented young faculty in the chemical sciences.

"In his new book--The Math of Life & Death: 7 Mathematical Principles that Shape Our Lives--mathematician Kit Yates makes complex mathematical concepts easily accessible to anyone, and which can improve decision making in an increasingly quantitative society. In this Q&A, Yates discusses why math is relevant to everyday life." See "Mathematician Kit Yates on Anti Vaxxer Movement, Air Travel Germs and Samoa's Measles Outbreak," by Meredith Wold Schizer, Newsweek, December 23, 2019.