Saturday, February 10, 2024

Harnessing human evolution to advance precision medicine

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SAN DIEGO

Andes 1 

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PEOPLE WHO VISIT THE ANDES MOUNTAIN RANGE IN SOUTH AMERICA CAN FEEL THE PHYSICAL EFFECTS OF LOWER OXYGEN LEVELS AT HIGHER ALTITUDES. HOWEVER, SOME PEOPLE WHO LIVE THERE HAVE EVOLVED OVER HUNDREDS OF GENERATIONS TO TOLERATE THESE LOW-OXYGEN CONDITIONS.

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CREDIT: ELYSIA COOK MCDERMOTT




Humans are still evolving, and Tatum Simonson, PhD, founder and co-director of the Center for Physiological Genomics of Low Oxygen at University of California School of Medicine, plans to use evolution to improve healthcare for all.

Her latest research, which was published February 9, 2024 in Science Advances, reveals that a gene variant in some Andean people is associated with reduced red blood cell count at high altitude, enabling them to safely live high in the mountains in low-oxygen conditions. Simonson’s UC San Diego lab is applying those findings toward understanding whether there may be a genetic component to why some people with sleep apnea or pulmonary diseases such as chronic obstructive pulmonary disease (COPD) fare better than others.

Explained Simonson, “There are people with COPD who breathe a lot and maintain a higher oxygen saturation. Others with the same disease don't breathe as much, and their oxygen saturation is low. Researchers suspect there may be genetic differences underlying this variation, similar to the variation we find in pathways important for oxygen sensing and responses underlying natural selection at high altitude.” 

Our cells need oxygen to survive. When there isn’t enough in the environment, our bodies produce extra red blood cells, which transport oxygen throughout the body. Too many red blood cells, however, create a dangerous condition called excessive erythrocytosis (EE), which makes the blood viscous, which could lead to stroke or heart failure. 

Her previous research showed that many mountain-dwelling Tibetans exposed to low-oxygen situations are born with innate mechanisms that protect them from poor outcomes at high altitude, including the overproduction of red blood cells.  Part of this is due to changes in the regulation of the EPAS1 gene, which lowers hemoglobin concentrations by regulating the pathway that responds to changing oxygen levels. Advances in genetics have shown that modern Tibetans received this genetic advantage from their ancestors who mixed with archaic humans living in Asia tens of thousands of years ago—a unique evolutionary history confined to this population.

For her latest research, Dr. Simonson, who is also the John B. West Endowed Chair in Respiratory Physiology and associate professor in the Division of Pulmonary, Critical Care, Sleep Medicine & Physiology at UC San Diego School of Medicine, zoomed in on the EPAS1 region of the genome. She and her team focused on a mutation in the gene that is present in some people living in the Andes but is absent in all other human populations. When they scanned whole Andean genomes, they found a pattern surrounding this variant suggesting that the genetic change, which alters only a single amino acid in the protein product, happened by chance, relatively recently (from 9,000 to 13,000 years ago), and spread very quickly through hundreds of generations within the Andean population.  

Similar to Tibetans, the EPAS1 gene is associated with lower red blood cell count in Andeans who possess it. However, the researchers were surprised to find that the variant works in a completely different way from the Tibetan version of the gene; rather than regulating its levels, the Andean variant changes the genetic makeup of the protein, altering the DNA in every single cell. 

“Tibetans have, in general, an average lower hemoglobin concentration, and their physiology deals with low oxygen in a way that doesn’t increase their red blood cells to excessively high levels. Now we have the first signs of evidence that Andeans are also going down that path, involving the same gene, but with a protein-coding change. Evolution has worked in these two populations, on the same gene, but in different ways,” said Simonson. 

This study exemplifies a current approach in research that connects genetic targets of natural selection with complex disease genes—understanding, for example, how natural genetic variation contributes to adaptive and maladaptive responses to low oxygen, as this study reveals.

In Simonson’s lab, that means figuring out what downstream target genes are being turned on in response to low oxygen, among other things. Said Simonson, “This paper shows one gene associated with one particular phenotype, but we think there are many different genes and components of oxygen transport involved. It’s just one piece of that puzzle, and could provide researchers with information relevant to other populations.” 

Simonson and her team are working with Latino populations in San Diego and El Centro, California, as well as Tijuana and Ensenada, Mexico, taking them to high altitudes and recording their breathing while awake and asleep. They’re cross-referencing their findings with publicly available databases to determine whether the findings they’ve made in Andeans are also found in local Latinos who may share some genetic variants with the Andeans.

“In precision medicine, it’s important to recognize variation in genetic backgrounds, specifically in historically understudied populations,” Simonson said. “If we can find some shared genetic factors in populations in an extreme environment, that may help us understand aspects of health and disease in that group and groups more locally. In that way, this study aims to push research forward, and towards comprehensive personalized medicine approaches in clinics here in San Diego.”

Co-authors of the study include: Elijah S. Lawrence, Wanjun Gu, James J. Yu, Erica C. Heinrich, Katie A. O’Brien, Carlos A. Vasquez, Quinn T. Cowan , Patrick T. Bruck , Kysha Mercader, Mona Alotaibi, Tao Long, James E. Hall, Esteban A. Moya, Marco A. Bauk, Jennifer J. Reeves, Mitchell C. Kong, Rany M. Salem, Keolu P. Fox, Atul Malhotra, Frank L. Powel, Mohit Jain and Alexis C. Komor at UC San Diego, Ryan J. Bohlender, Hao Hu and Chad D. Huff at University of Texas MD Anderson Cancer Center, Cecilia Anza-Ramirez, Gustavo Vizcardo-Galindo , Jose-Luis Macarlupu , Rómulo Figueroa-Mujíca, Daniela Bermudez, Noemi Corante and Francisco C. Villafuerte at Universidad Peruana Cayetano Heredia, Eduardo Gaio at Universidad de Brasília, Veikko Salomaa and Aki S. Havulinna at Finnish Institute for Health and Welfare and Andrew J. Murray at Cambridge University and Gianpiero L. Cavalleri at Royal College of Surgeons in Ireland.

This study was funded, in part, by the National Institutes of Health (Grants R01HL145470 [TSS] and T32HL134632 [JEH]), Geographic  Society  Explorer  Award,  and  John  B  West  Endowment  in  Respiratory Physiology (TSS), Wellcome Trust Award 107544/Z/15/Z (FCV), Marie Skłodowska-Curie grant agreement No 890768 (KAO), National Academies of Sciences, Engineering, and Medicine Ford Foundation Fellowship (CAV), National Science Foundation Grant No DGE-2038238 (PTB), Research Corporation for Science Advancement through Cottrell Scholar Award 27502 (ACK), Science Foundation Ireland 12/IP/1727 (GLC), Finnish Foundation for Cardiovascular Research and Juho Vainio Foundation (VS), and Academy of Finland (ASH).

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UC San Diego Researchers found that a gene variant in some Andean people is associated with reduced red blood cell count at high altitude, enabling them to safely live high in the mountains in low-oxygen conditions. The results could help scientists improve precision medicine for sleep apnea and pulmonary diseases, such as chronic obstructive pulmonary disease (COPD).

CREDIT

Elysia Cook McDermott


 

Uncovering the green miracle of urbanization


To reveal the significant changes in vegetation cover in 328 cities in China between 1990 and 2022 and the impact factors


Peer-Reviewed Publication

SCIENCE CHINA PRESS

Figure 1. Summary of fractional vegetation cover (FVC) changes in cities of different sizes. 

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MEC, MEGACITIES; LC, LARGE CITIES; MC, MEDIUM CITIES; SMC, SMALL-MEDIUM CITIES; SM, SMALL CITIES. LETTERS (A, B, C, ETC.) REPRESENT SIGNIFICANT DIFFERENCES AT THE 0.05 LEVEL FOR CITIES OF DIFFERENT SIZES IN EACH YEAR. THE DASHED LINE DENOTES THE MEAN FVC OF CITIES OF ALL SIZES IN EACH YEAR.

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CREDIT: ©SCIENCE CHINA PRESS




Between 1990 and 2005, the national average urban FVC decreased from 0.38 to 0.35 due to the increase of floor area ratio and impervious surface in urban areas. The decline is particularly pronounced in megacities, small, medium and small cities. However, since 2005, this trend has significantly reversed, and all cities in the country have shown an increasing trend of FVC, with an average increase of 27.31% (Figure 1). Especially in megacities, the increase of FVC is particularly significant, which is closely related to the expansion of urban scale and the implementation of ecological construction policies.

Change characteristics of FVC in new and old urban areas. The FVC of new urban areas is generally higher than that of old urban areas, and this phenomenon is particularly obvious in megacities and large cities. This shows that in the process of urban expansion, the planning and construction of new urban areas pay more attention to ecological balance, while the old urban areas are facing the pressure of reducing the green area. Using case studies of Beijing, Yichun, Yulin, Lishui, and Hailaer (Figure 2), the researchers show the changing trend of FVC from the old urban areas to the new urban areas. The data of these cities show that over time, the FVC of new urban areas gradually shifts to high FVC, a trend that is common in cities of different sizes, although the degree of migration to high FVC decreases with the decrease of city size.

The study also found that the average vegetation coverage of all cities in China was positively correlated with urban GDP (R=0.86), temperature (R=0.81), wind speed (R=0.68) and urban construction land area (R=0.70), but negatively correlated with urban precipitation (R=-0.24) (Figure 3). For large and medium-sized cities, the top three factors affecting FVC are GDP, urban population and temperature. However, for cities in arid/semi-arid regions, FVC changes are more sensitive to climatic factors (such as precipitation), indicating that the influence of climatic conditions on urban greening in these regions cannot be ignored.

This study shows the spatial and temporal evolution of urban greening in China, and also reveals the compound effects of economic development, population growth, climate change, and policy orientation on urban vegetation coverage. This is of great significance for guiding future urban planning and promoting urban greening and ecological construction. With the deepening of urbanization process, how to balance urban development and ecological protection to achieve green and sustainable development will become an important issue for city managers and planners.

Publication information

Feng F, Yang X, Jia B, Li X, Li X, Xu C, Wang K. 2024. Variability of urban green space and its driving factors in 328 cities in China. Science China Earth Sciences, 67(02): 466-482, https://doi.org/10.1007/s11430-022-1219-2

Figure 2. Statistical distribution of vegetation coverage in new and old urban areas in different years 

 

Walking on the move: New insights into the neurology of locomotion


Peer-Reviewed Publication

UNIVERSITY OF COLOGNE




In a new study, scientists from the University of Cologne gained new insights into the mechanism of the rhythmic activation of nerve cells (neurons) in stick insects that control the leg muscles during walking. The researchers showed that the neurons that activate the depressor muscle in the leg are rhythmically excited, unlike those of the other leg muscles. So far, it has been assumed that all of these so-called motor neurons are activated in the same way by central neural networks. The study was published under the title ‘The synaptic drive of central pattern-generating networks to leg motor neurons of a walking insect is motor neuron pool specific’ in the journal Current Biology.

The UoC research team investigates the neural foundations of motion generation in animals, in particular those underlying locomotor activities such as walking. For this purpose, the team led by Professor Dr Ansgar Büschges analyses insects, among other arguments, as the requirements for the nervous system regarding the generation and control of walking movements are very similar across animal kingdom. In many animals, for example, there are networks in the central nervous system that form the basis for the generation of rhythmic activity patterns for many forms of movements, whether for rhythmic locomotor activity such as running, swimming, crawling and flying or for vegetative functions such as breathing.

These highly specialized networks are referred to as central pattern generators (CPGs). They generate the rhythmic motor activity of the muscles for movement in interaction with information from sensory organs, neurons called proprioceptors; proprioceptors report movements and inform the central nervous system. In the case of walking, they are located on and in the insect’s legs. The networks do this by activating the so-called motor neurons that innervate the muscles. So far, it was assumed that such CPGs have the same influence on all motor neurons they target. In their new study, Angelina Ruthe, Dr Charalampos Mantziaris and Professor Büschges disproved this assumption about the locomotor activity of insects.

In their experiments, the scientists pharmacologically activated the CPGs in the central nervous system of the stick insect Carausius morosus and investigated their influence on the motor neurons that innervate its leg muscles. They found that all motor neuron groups of the leg muscles, except one, receive identical drive from the networks: rhythmic inhibitory signals from the CPGs. Only the motor neurons, which innervate the depressor muscle of the leg, are controlled by phasic excitatory drive. Interestingly, the leg depressor muscle is precisely the muscle of the insect which is responsible for generating leg stance during any walking situation – regardless of whether the animal runs up or down horizontally, on the ceiling or on a branch. “The rhythmic excitation and thus the specific activation of this motor neuron pool by the CPGs could serve to ensure the exact timing of the contraction of the depressor muscle and thus the start of the stance phase and its stabilization," explained Professor Büschges.

The study was funded by the German Research Foundation (DFG).

 

Study visually captures a hard truth: Walking home at night is not the same for women


Heat maps show men look straight ahead; women scan periphery

Peer-Reviewed Publication

BRIGHAM YOUNG UNIVERSITY

Gender-based heat map images of walking at night 

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GENDER-BASED HEAT MAP IMAGES SHOW WHERE MEN TEND TO LOOK AND WHERE WOMEN TEND TO LOOK ON A PATH AT NIGHT. WOMEN FOCUSED SIGNIFICANTLY MORE ON POTENTIAL SAFETY HAZARDS — THE PERIPHERY OF THE IMAGES — WHILE MEN LOOKED DIRECTLY AT FOCAL POINTS OR THEIR INTENDED DESTINATION

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CREDIT: IMAGES COURTESY OF THE JOURNAL OF VIOLENCE AND GENDER.



An eye-catching new study shows just how different the experience of walking home at night is for women versus men.

The study, led by Brigham Young University public health professor Robbie Chaney, provides clear visual evidence of the constant environmental scanning women conduct as they walk in the dark, a safety consideration the study shows is unique to their experience.

Chaney and co-authors Alyssa Baer and Ida Tovar showed pictures of campus areas at four Utah universities — Utah Valley University, Westminster, Brigham Young University and University of Utah — to participants and asked them to click on areas in the photos that caught their attention. Women focused significantly more on potential safety hazards — the periphery of the images — while men looked directly at focal points or their intended destination.

“The resulting heat maps represent perhaps what people are thinking or feeling or doing as they are moving through these spaces,” Chaney said. “Before we started the study, we expected to see some differences, but we didn’t expect to see them so contrasting. It’s really visually striking.”

Nearly 600 individuals took part in the study, published recently in the journal Violence and Gender, with 56% of participants being female and 44% being male. Each participant looked at 16 images and were told to imagine themselves walking through those areas. They used a Qualtrics heat map tool to click on the areas of the image that stood out the most to them.

While men tended to focus on the path or a fixed object (like a light, the walking path or a garbage can), the women's visual pattern represented a scanning of the perimeter (bushes, dark areas next to a path).

Chaney, along with Baer and Tovar — both BYU undergrads at the time of the study’s inception — say the findings provide some insight into what it is like to walk home as a woman, which could be multiplied through years or a lifetime of experiences.

“This project has been a fantastic conversation starter to bring awareness to lived experiences, particularly of women in this case,” said Baer, who recently finished graduate school at George Washington University and now works in Washington, D.C. “My hope is that in having concrete data we are able to start conversations that lead to meaningful action.”

Authors said the data suggests that because environment is perceived and experienced differently by women and men, decision makers in building campus and community environments should consider the varied experiences, perceptions and safety of both.

“Why can’t we live in a world where women don’t have to think about these things? It’s heartbreaking to hear of things women close to me have dealt with,” Chaney said. “It would be nice to work towards a world where there is no difference between the heat maps in these sets of images. That is the hope of the public health discipline.”

Friday, February 09, 2024

ALLITERATION

Foul fumes pose pollinator problems



UNIVERSITY OF WASHINGTON

Pale Evening Primrose in field 

IMAGE: 

IMAGE OF A FIELD SITE IN EASTERN WASHINGTON SHOWING PALE EVENING PRIMROSE FLOWERS.

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CREDIT: JEREMY CHAN/UNIVERSITY OF WASHINGTON




Link to Google Drive folder containing images and videos with caption and credit information: https://drive.google.com/drive/folders/1KMo7RucC9LCg90iQH3obxutfmA79jNQv?usp=sharing

 

Post-embargo link to release: https://www.washington.edu/news/2024/02/08/pollinator-pollution/

 

FROM: James Urton

University of Washington

206-543-2580

jurton@uw.edu 

(Note: researcher contact information at the end)

 

 

Embargoed by Science

For public release at 2 p.m. U.S. Eastern Time (11 a.m. U.S. Pacific Time) on Thursday, Feb. 8, 2024

 

 

Foul fumes pose pollinator problems

 

A team led by researchers at the University of Washington has discovered a major cause for a drop in nighttime pollinator activity — and people are largely to blame.

The researchers found that nitrate radicals (NO3) in the air degrade the scent chemicals released by a common wildflower, drastically reducing the scent-based cues that nighttime pollinators rely on to locate the flower. In the atmosphere, NO3 is produced by chemical reactions among other nitrogen oxides, which are themselves released by the combustion of gas and coal from cars, power plants and other sources. The findings, published Feb. 9 in the journal Science, are the first to show how nighttime pollution creates a chain of chemical reactions that degrades scent cues, leaving flowers undetectable by smell. The researchers also determined that pollution likely has worldwide impacts on pollination.

The team — co-led by Jeff Riffell, a UW professor of biology, and Joel Thornton, a UW professor of atmospheric sciences — studied the pale evening primrose (Oenothera pallida). This wildflower grows in arid environments across the western U.S. They chose this species because its white flowers emit a scent that attracts a diverse group of pollinators, including nocturnal moths, which are one of its most important pollinators. 

At field sites in eastern Washington, the researchers collected scent samples from pale evening primrose flowers. Back in the laboratory, they used chemical analysis techniques to identify the dozens of individual chemicals that make up the wildflower’s scent. 

“When you smell a rose, you’re smelling a diverse bouquet composed of different types of chemicals,” said Riffell. “The same is true for almost any flower. Each has its own scent made up of a specific chemical recipe.”

Once they had identified the individual chemicals that make up the wildflower’s scent, the team used a more advanced technique called mass spectrometry to observe how each chemical within the scent reacted to NO3. They found that reacting with NO3 nearly eliminated certain scent chemicals. In particular, the pollutant decimated levels of monoterpene scent compounds, which in separate experiments moths found most attractive.

Moths, which smell through their antennae, have a scent-detection ability that is roughly equivalent to dogs — and several thousand times more sensitive than the human sense of smell. Research suggests that several moth species can detect scents from miles away, according to Riffell. 

Using a wind tunnel and computer-controlled odor-stimulus system, the team investigated how well two moth species — the white-lined sphinx (Hyles lineata) and the tobacco hawkmoth (Manduca sexta) — could locate and fly toward scents. When the researchers introduced the pale evening primrose’s normal scent, both species would readily fly toward the scent source. But when the researchers introduced the scent and NO3 at levels typical for a nighttime urban setting, Manduca’s accuracy dropped by 50% and Hyles — one of the chief nocturnal pollinators of this flower — could not locate the source at all. 

Experiments in a natural setting backed up these findings. In field experiments, the team showed that moths visited a fake flower emitting unaltered scent as often as they visited a real one. But, if they treated the scent first with NO3, moth visitation levels dropped by as much as 70%.

 “The NO3 is really reducing a flower’s ‘reach’ — how far its scent can travel and attract a pollinator before it gets broken down and is undetectable,” said Riffell. 

The team also compared how daytime and nighttime pollution conditions impacted the wildflower’s scent chemicals. Nighttime pollution had a much more destructive effect on the scent’s chemical makeup than daytime pollution. The researchers believe this is largely due to sunlight degrading NO3.

The team used a computer model that simulates both global weather patterns and atmospheric chemistry to locate areas most likely to have significant problems with plant-pollinator communication. The areas identified include western North America, much of Europe, the Middle East, Central and South Asia, and southern Africa. 

“Outside of human activity, some regions accumulate more NO3 because of natural sources, geography and atmospheric circulation,” said Thornton, who added that natural sources of NO3 include wildfires and lightning. “But human activity is producing more NO3 everywhere. We wanted to understand how those two sources — natural and human — combine and where levels could be so high that they could interfere with the ability of pollinators to find flowers.”

The researchers hope their study is just the first of many to help uncover the full scope of pollinator failure.

“Our approach could serve as a roadmap for others to investigate how pollutants impact plant-pollinator interactions, and to really get at the underlying mechanisms,” said Thornton. “You need this kind of holistic approach, especially if you want to understand how widespread the breakdown in plant-pollinator interactions is and what the consequences will be.”

The study highlights the dangers of human-fueled pollution and its implications for all pollinators as well as the future of agriculture.

“Pollution from human activity is altering the chemical composition of critical scent cues, and altering it to such an extent that the pollinators can no longer recognize it and respond to it,” said Riffell.

Approximately three-quarters of the more than 240,000 species of flowering plants rely on pollinators, Riffell said. And more than 70 species of pollinators are endangered or threatened. 

Lead author on the paper is Jeremy Chan, a postdoctoral researcher at the University of Copenhagen who conducted this study as a UW doctoral student in biology. Co-authors are Sriram Parasurama in the UW Department of Biology; Rachel Atlas, a postdoctoral researcher at the Pierre Simon Laplace Institute in France who participated in this study as a UW doctoral student in atmospheric sciences; Ursula Jongebloed, a UW doctoral students in atmospheric sciences; Ruochong Xu, a doctoral student at Tsinghua University in China; Becky Alexander, a UW professor of atmospheric sciences; and Joseph Langenhan, a professor of chemistry at Seattle University. The research was funded by the Air Force Office of Scientific Research, the National Science Foundation, the National Institutes of Health, the Human Frontiers in Science Program, and the University of Washington.

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For more information, contact Riffell at 206-348-0789 or jriffell@uw.edu and Thornton at 206-543-4010 or joelt@uw.edu.

Reference: Chan JK, Parasurama S, Atlas R, Xu R, Jongeblood UA, Alexander B, Langenhan JM, Thornton JA, Riffell JA. “Olfaction in the Anthropocene: NO3 negatively affects floral scent and nocturnal pollination.” Science 2024. DOI: 10.1126/science.adi0858

A note from Science for journalists: “Advance copies of embargoed papers may be obtained by registered reporters from our press package, SciPak, at https://www.eurekalert.org/press/scipak/. For reporters having difficulties accessing the paper from the press package, please have them contact scipak@aaas.org.”  

Grant numbers:

  • Air Force Office of Scientific Research: FA9550-21-1-0101 and FA9550-20-1-0422
  • National Science Foundation: 2121935
  • National Institutes of Health: R01AI148300
  • Human Frontiers in Science Program: RGP0044/2021

Name pronunciation guide:

  • Jeff Riffell: Jef RIF-el
  • Joel Thornton: Jol THORN-tun

Link to Google Drive folder containing images and videos with caption and credit information: https://drive.google.com/drive/folders/1KMo7RucC9LCg90iQH3obxutfmA79jNQv?usp=sharing