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Archive - Dec 24, 2018

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Cholesterol-Lowering Drugs Reduce Brown Fat

A certain proportion of the adult population has not only white adipose (or fatty) tissue (left), but also the brown kind (right). This brown adipose tissue helps to convert sugar and fat into heat. People with brown adipose tissue are better at regulating their body temperature in the winter, and are less likely to suffer from excess weight or diabetes. An international team of researchers led by Dr. Christian Wolfrum, Professor for Translational Nutritional Biology at ETH Zurich, has now discovered that the statin class of pharmaceuticals reduces the formation of brown adipose tissue. The article was published online on December 20,2018 in Cell Metabolism. It is titled “Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation.” Statins are prescribed as a way to reduce the risk of a heart attack because they reduce cholesterol levels in the blood. They are among the most commonly prescribed drugs worldwide. Dr. Wolfrum and his colleagues have been researching brown adipose tissue for many years. They looked into the question of how "bad" white fat cells, which form the layer of fat under our skin, become "good" brown fat cells. Having conducted cell culture experiments, they found out that the biochemical pathway responsible for producing cholesterol plays a central role in this transformation. They also discovered that the key molecule regulating the transformation is the metabolite geranylgeranyl pyrophosphate. Earlier studies showed that the cholesterol biochemical pathway is also central to the functioning of statins; one of their effects is to reduce the production of geranylgeranyl pyrophosphate. This is why the researchers wanted to know whether statins also impact the formation of brown adipose tissue.

Study Examines Primary Drivers of Increased Hospitalizations of Homeless Individuals

A homeless individual is one who lacks fixed and reliable housing, and approximately 553,000 people fit that description on any given night in the United States. A new retrospective cohort study led by investigators from Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital in Boston examines patterns, causes, and outcomes of acute hospitalizations between 2007 and 2013 for homeless individuals and non-homeless control groups in three populous and diverse U.S. states: Florida, California, and Massachusetts. Data suggest a rise in acute hospital use among homeless individuals for mental illness and substance use disorder. The results were published in the January 2019 issue of Medical Care. The article is titled “Trends, Causes, and Outcomes of Hospitalizations for Homeless Individuals--A Retrospective Cohort Study.” "The homeless population is aging, and the rate of hospitalizations for homeless individuals is increasing," said lead author Rishi Wadhera, MD, an investigator in the Smith Center for Outcomes Research in Cardiology at BIDMC. "Although there has been a recent push to establish better policy and public health measures to improve the health of homeless adults, few studies have examined the patterns and causes of hospitalizations in this population. We found that hospitalizations among homeless adults tend to be for a very different set of conditions than non-homeless adults, even after accounting for differences in demographics." To examine these trends, hospital discharge data was acquired from Massachusetts and Florida between 2001 and 2013 and from California between 2007 and 2011.

Phage Display Pioneer & Industry Leader Celebrates Success of Revolutionary Technology Together with 2018 Nobel Laureates in Chemistry

IONTAS Limited (IONTAS), a leader in the discovery and optimization of fully human antibodies, announced that its Founder and Chief Executive Officer, Dr. John McCafferty (photo), was invited to attend the Nobel Prize Award Ceremony in recognition of his pivotal contribution to the development of antibody phage display technology. The event, held in Stockholm, Sweden, on December 10, celebrated the 2018 Nobel Laureates and the success of phage display technology in modern drug discovery and development, which the Royal Swedish Academy of Sciences recognized in this year’s Nobel Prize in Chemistry (https://www.nobelprize.org/prizes/chemistry/2018/press-release/). Sir Gregory Winter (MRC Laboratory of Molecular Biology, Cambridge, UK) and Dr. George Smith (University of Missouri, Columbia, Missouri, USA) jointly received one half of the Nobel Prize in Chemistry 2018 “for the phage display of peptides and antibodies.” Dr. Frances Arnold (California Institute of Technology, Pasadena, California, USA) was awarded the other half “for the directed evolution of enzymes.” Dr. Smith published his breakthrough paper on display of peptides on filamentous bacteriophage in 1985. Inspired by this, Dr. Winter and Dr. McCafferty then applied the approach to antibody display, with the aim of producing new pharmaceuticals. While working in Dr. Winter’s group, Dr. McCafferty became the first to demonstrate the display of functional antibodies on the surface of phage (McCafferty et al., Nature, 1990) (https://www.nature.com/articles/348552a0). This landmark achievement, cited by the Nobel committee, made it possible to create “libraries” of phage particles containing billions of different human antibody genes from which antibodies to any target could be easily isolated.