This month, Insights & Outcomes is enjoying that last bit of summer with some recent research into pharmacy ‘deserts’, nuclear pores, the way skin cells find their true purpose – and news of an early career award for some innovative planetary research.
As always, you can find more science and medicine news on the Science & Technology and Health & Medicine pages of Yale News.
Customization of nuclear pores
The nucleus in a cell is a fortress that protects precious genetic information stored in it and its size is usually proportional to the size of the cell it houses. In cancer cells, however, the nucleus becomes so distorted that clinicians can diagnose the disease based on size alone.
But how does the cell regulate the size of the nucleus in the first place? The answer lies in the many membranes that surround the nucleus and help carry genetic information to the right destinations in the cell, Yale University researchers discovered.
In a new study, a team led by dr. Shirin Bahmanyarassociate professor of molecular, cellular, and developmental biology, and former Yale graduate student Michael Mauronow at Columbia University, used high-resolution quantitative fluorescence microscopy to study the process in life C. elegans worms. They found that a protein called Ndc1 regulates the attachment of membranes that encapsulate the nucleus and the density of openings called nuclear pores and also helps speed up the expansion rate of the nucleus.
“It’s like inflating a balloon, with air coming through the pores of the core and the membranes expanding like the latex allowing the core to grow,” Mauro said.
To the researchers’ surprise, they also found that increased membrane production could only make the nuclei bigger, even if Ndc1 isn’t there to insert new pores. In cases where nuclei grow abnormally large, the tasks of increasing nuclear pores and increasing membranes are uncoupled, leaving no control over the size limitation of nuclei.
The research is important not only for our understanding of how cancer can hijack the nucleus, but also helps answer fundamental biological questions, such as how nucleus size controls the transition, in embryos, from maternal to individual control of genome activation and affects the timing. of the cell cycle. The work was published in the journal eLife.
Defining Pharmacy Deserts
Pharmacy deserts, areas where people don’t have access to pharmacies, are a major cause of health care inequalities in the United States. While the location of these deserts is often determined by the distance to the nearest pharmacy, access issues aren’t fully captured, Yale researchers argue.
“Especially in urban environments, distance may not be the right measure,” said Peter Kahn, a pulmonary and intensive care fellow in the Yale School of Medicine’s Department of Internal Medicine. “In these areas, short distances can sometimes take a long time to travel.”
In a new study, Kahn, Walter Mathis, assistant professor of psychiatry, and a group of colleagues calculated the number of pharmacy deserts based on travel time in the four largest U.S. cities — New York, Los Angeles, Chicago and Houston — and considered walking, car travel and public transportation. They reported their findings in the Journal of the American Pharmacists Association.
By defining pharmacy deserts as areas where a pharmacy cannot be reached within 15 minutes, they found that the number of pharmacy deserts in each city differed depending on the mode of transportation. For example, New York City and Chicago, which have more robust public transportation systems, had fewer pharmacy deserts when traveling by public transportation than by car or foot. But Los Angeles and Houston, neither of which have comparable public transportation options, had more pharmacy deserts when traveling by public transportation. And whether determined by distance or travel time, pharmacy deserts were more commonly found in predominantly Black and Latinx neighborhoods, they said.
Ultimately, this more nuanced understanding will help address the problem, the researchers say. “Knowing more about the barriers to entry to pharmacies and where they persist will help us reduce the number of pharmacists abandoned,” Mathis says.
Eyes on the Planetary Research Prize
The American Astronomical Society’s Division of Planetary Sciences has awarded the Harold C. Urey Prize 2022 for outstanding achievement in planetary research by an early scientist at Juan Loraan assistant professor in Yale’s Division of Earth and Planetary Sciences.
Lora earned the award for his development of a new global circulation model (GCM) of Saturn’s moon Titan, which Lora has used to successfully explain Titan’s precipitation patterns and surface fluid distribution. The model takes into account the effects of atmospheric nebulae and the impact of Titan’s subsurface hydrology.
Lora’s model is important to the success of NASA’s Dragonfly drone mission to Titan’s surface. Lora is one of the mission’s principal investigators.
Lora has applied similar techniques to Earth’s hydroclimate to understand changes in atmospheric rivers, which are an important part of the water cycle affected by climate change.
The award organizers also praised Lora for his mentorship of students and early scientists.
Managing an Enzyme Inflammation
The human immune system is primed to fend off microbial invaders, but sometimes it can fail, causing an inflammatory disease. For example, an enzyme that plays an important regulatory role in the function of immune system cells called macrophages has been linked to inflammatory bowel disease, arthritis and an inability to clear infections.
A team of Yale chemists and immunobiologists set out to investigate the biochemistry of the enzyme, laccase domain-containing 1 (LACC1), and found that one of its products — a common supplement used by bodybuilders — could be a potential nutraceutical. to fight those inflammatory diseases. Yale’s Zheng Weiswho has joint agreements in the laboratories of Jason Crawford and Richard Flavelset out to describe the biochemical steps involved in how LACC1 contributes to proinflammatory macrophage function in mice and humans.
For their study, the team infected mice without LACC1 with a strain of the Salmonella bacteria and then treated them with LACC1’s product – the amino acid L-ornithine, which is often used as an athletic supplement and sleep aid. The treated mice showed a newfound ability to fight infection, leading researchers to speculate that L-ornithine may also help treat other inflammatory diseases.
Co-corresponding authors of the paper, which is published in the journal Nature, are Crawford, associate professor of chemistry and microbial pathogenesis and director of the Institute of Biomolecular Design and Discovery at Yale West Campus, and Flavell, Sterling Professor of Immunobiology and researcher of the Howard Hughes Medical Institute.
Navigating phase mazes
Some of the most important systems in medicine, energy and industry depend on the interplay between phases of matter – such as vapors, liquids and solids – when they come into contact.
There are mixtures, such as oil and water, that are relatively easy to understand, partly because they have a minimal number of components. But what if, as with cell membranes, there are thousands of components? How can scientists understand phase behavior in such an environment?
In a new study published in the journal Physical Review Research, lead author Isabella Grafa postdoctoral associate in the Yale Department of Physics, and Benjamin Machtaassistant professor of physics and member of the Quantitative Biology Institute, offer a way out of the phase maze.
Graf and Machta have developed a theoretical framework to systematically reduce the complexity of mixtures with as many as one million components. Rather than investigating components in the high-dimensional space of possible mixtures, the new framework focuses on ranking the primary physical features of the components themselves — and how those physical features determine phase behavior.
“We believe that our work is especially useful for systems with a large number of components and will allow us to find principles underlying phase separation in such systems,” Graf said.
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