Learning about human cancer from fruit flies

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Loss of Parafibromin/Hyrax results in loss of neural stem cell (NSC) polarity, leading to a switch from asymmetric to symmetric division. Upper panels: Dividing NSCs from control (left) and Hyrax knockdown (right) were labeled with a cell polarity protein aPKC (grey) and DNA (cyan). The asymmetric localization of aPKC is lost in the knockdown. Lower panels: Telophase NSCs from the brain were labeled with a mitotic marker phospho-Histone H3 (PH3 in magenta) and a membrane marker GFP (green) marking the cell outline. Blue lines and red lines indicate the diameter of two daughter cells of NSCs. Control NSC (left) divides asymmetrically to produce two daughter cells with distinct sizes, while Hyrax knockdown NSC (right) divides symmetrically to generate two daughter cells of similar sizes. Scale bars: 5 mm. Credit: Duke-NUS

Scientists in Singapore and Spain have gained new insights into the activity of a tumor-suppressor protein in fruit flies that could aid the understanding of some human cancers. The study, published in PLOS Biology, might eventually lead researchers toward new cancer treatments and prevention.

Duke-NUS Medical School scientists collaborated with colleagues from the Institute for Research in Biomedicine from the Barcelona Institute of Science and Technology, the Genome Institute of Singapore and NUS to investigate a human tumor-suppressor protein called Parafibromin. The normal activities of Parafibromin prevent tumors from developing, but deficiencies in these activities have been linked to several cancers, including hyperparathyroidism-jaw tumor syndrome and breast, gastric, colorectal and lung cancers. Until now, the exact role of the protein in health and disease in the nervous system has remained unknown.

Although fruit flies and humans may seem very different, researchers often find that crucial molecular pathways, signaling and control systems are shared across many species, having originated early in the evolution of a diverse variety of organisms.

“As Hyrax—an evolutionarily-related protein—is the analog of Parafibromin, we examined it in brain cell development in Drosophila fruit flies as a first step towards better understanding,” said Dr. Deng Qiannan, first author of the study and Research Fellow with the Neuroscience and Behavioral Disorders (NBD) program at Duke-NUS.

“We discovered that the Hyrax protein plays an essential role during the development of the Drosophila central , and so we believe that Parafibromin may also perform a similar function in humans,” said Dr. Cayetano Gonzalez, a co-author of the study and Head of the Cell Division Laboratory at the Institute for Research in Biomedicine, Barcelona.

The results revealed previously undiscovered functions for the in controlling cell polarity—the asymmetric organization of proteins—in the stem cells that generate mature nerve cells. Loss of Hyrax function was found to lead to the overgrowth of neural in the Drosophila brain. This was linked to influences on cell structures called centrosomes, which coordinate cell division, and to the regulation of two other known tumor-suppressor proteins, Polo and Aurora-A kinases.

“Loss of and centrosomal abnormalities are hallmarks of human cancers,” said Professor Wang Hongyan, the corresponding senior author of the study and Deputy Director of the NBD program at Duke-NUS. “These surprising new findings may be very relevant for understanding the role of Parafibromin in human cancers, perhaps especially in the brain.”

More research will be needed to explore whether these findings in can be applied to Parafibromin in humans and the research team has already begun new investigations towards this goal.

“Translating basic scientific research into discoveries of clinical significance is a primary goal of medical research. Professor Wang and her colleagues have taken a very interesting first step that could one day have an impact on treatment and prevention,” said Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS.

More information:
Qiannan Deng et al, Parafibromin governs cell polarity and centrosome assembly in Drosophila neural stem cells, PLOS Biology (2022). DOI: 10.1371/journal.pbio.3001834

Learning about human cancer from fruit flies (2022, October 19)
retrieved 21 October 2022
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Alligators exposed to PFAS show autoimmune effects

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Credit: Pixabay/CC0 Public Domain

A recent study of alligators in the Cape Fear River found the animals had elevated levels of 14 different per- and polyfluoroalkyl (PFAS) chemicals in their blood serum, as well as clinical and genetic indicators of immune system effects. The work adds to the body of evidence connecting PFAS exposure with adverse immune system effects.

The research team, led by Scott Belcher, associate professor of biology at North Carolina State University, took blood samples and did health evaluations on 49 alligators living along the Cape Fear River between 2018 and 2019. They compared these results to a reference population of 26 alligators from Lake Waccamaw, located in the adjoining Lumber River basin.

“We looked at 23 different PFAS and saw clear differences between both types and levels of PFAS in the two populations,” Belcher says. “We detected an average of 10 different PFAS in the Cape Fear River samples, compared to an average of five different PFAS in the Lake Waccamaw population.

“Additionally, blood concentrations of fluoroethers such as Nafion byproduct 2 were present at higher concentrations in alligators from the Cape Fear River basin, whereas these levels were much lower—or not detected—in alligators from Lake Waccamaw. Our data showed that as we moved downstream from Wilmington to Bald Head Island, overall PFAS concentrations decreased.”

But the most unusual observation the team made was that alligators in the Cape Fear River had a number of unhealed or infected lesions.

“Alligators rarely suffer from infections,” Belcher says. “They do get wounds, but they normally heal quickly. Seeing infected lesions that weren’t healing properly was concerning and led us to look more closely at the connections between PFAS exposure and changes in the immune systems of the alligators.”

A qRT-PCR genetic analysis revealed significantly elevated levels of interferon-alpha (INF-α) responsive genes in the Cape Fear River alligators: their levels were 400 times higher than those of the Lake Waccamaw alligators, which had much lower PFAS blood concentrations.

“INF-α is a secreted immune protein involved in stimulating ,” Belcher says. “The set of INF-α responsive genes we analyzed are normally involved with viral infections. In humans, chronic (or long-term) high expression of this set of genes is an important indicator of autoimmune diseases, especially lupus. Additionally, some PFAS exposures in humans are linked with chronic autoimmune disorders like and thyroid disease.

“When we see elevated expression of INF-α in these alligators, then, it tells us that something in these alligators’ immune responses is being disrupted.”

With five years’ worth of sampling data, much of it taken from the same alligators on an annual basis, the researchers are in a good position to continue following PFAS exposure and health changes in both individuals and the larger populations within both habitats.

“Alligators are a sentinel species—harbingers of dangers to human health,” Belcher says. “Seeing these associations between PFAS exposure and disrupted immune function in the Cape Fear River alligators supports connections between adverse human and animal health effects and PFAS exposure.”

The work appears in Frontiers in Toxicology and was supported by the National Institute of Environmental Health Sciences (award numbers P42ES031009, P30 ES025128 and T32ES007046), North Carolina Sea Grant, and the North Carolina Policy Collaboratory. Belcher is corresponding author of the work, which is part of a collaboration with the PFAS testing network and Cape Fear River Watch.

More information:
Blood Concentrations of Per- and Polyfluoroalkyl Substances are Associated with Autoimmune-like Effects in American Alligators from Wilmington, North Carolina, Frontiers in Toxicology (2022). DOI: 10.3389/ftox.2022.1010185

Alligators exposed to PFA

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Bright colors in the animal kingdom: Why some use them to impress and others to intimidate

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Poison dart frogs are found in wet tropical forests throughout Central and South America. They are known to exhibit a wide array of bright colors beginning from birth. These vibrant warning colors allude to a deadly toxin found inside their skin. Individuals of some species carry enough toxin to kill—in theory—up to 10 adult people. Credit: Da Vinci Science Center

High up in a tree sits a bright red vermilion flycatcher. The males of this songbird species use their red feathers to attract females. Meanwhile, an Arizona mountain kingsnake slithers among the rocks below. Its vivid red, yellow and black coloring mimics that of the venomous coral snake to keep predators away. But why did these two species evolve similar colors to send completely different messages?

Researchers at the University of Arizona set out to better understand how vibrant color patterns evolved in . They found a strong and consistent link between the function of animals’ and the activity patterns of their ancestors. Species that use their bright colors as a sexual signal were found to be descended from ancestors that were active during the day. Conversely, that use aposematism—bright coloring that warns predators that species are toxic—were found to have had ancestors that were active at night.

The research, published in the journal Evolution, was done by Zachary Emberts and John J. Wiens, both in the UArizona Department of Ecology and Evolutionary Biology. Their findings open a doorway to understanding the evolutionary differences between many of today’s colorful species.

“This pattern generally seems to hold across land vertebrates, a group with about 40,000 species that evolved over 350 million years,” said Wiens, a professor of ecology and and senior author of the paper. “It doesn’t matter how a species produces the colors. The way that a bird makes red is different from how a lizard makes red, but this general pattern of day-night activity still works.”

According to the researchers, vividly colored lizards and birds typically use their coloring as a sexual signal for mates. In contrast, colorful amphibians and snakes generally wear them as a warning signal for predators. Many of these amphibians and snakes are diurnal, meaning they are active during the day, yet their ancestors were nocturnal, or active during the night.

The results showed no clear connection between warning colors and present-day diurnal or nocturnal activity. However, when the scientists used evolutionary relationships and statistics to estimate the day-night activity patterns in the ancestors of these species, a pattern emerged: sexual coloration was associated with ancestors that were active during daylight, whereas warning coloration was associated with ancestors that had a nocturnal lifestyle.

Early in their evolution, most ancestors of the studied species started out drab and dully colored. Over time, vivid coloration evolved separately across many different lineages. Because they helped animals survive and reproduce, bright color patterns became established and passed on to , said Emberts, a postdoctoral research associate in EEB and the paper’s first author.

“Traits that we see today in species can be a result of their evolutionary history,” he said. “We were looking for evolutionary patterns, so we did two separate analyses, one that used their current day-night activity and one that used their ancestral day-night activity.”

The ancestors of amphibians and snakes spent time mating and interacting with members of their own species in darkness. Having bright colors offered no sexual advantage for them because the colors couldn’t be seen by potential mates. According to the researchers, this absence of visual sexual signaling at night may have opened the possibility for intense colors to evolve for a very different purpose: a warning signal to predators.

“Warning colors have evolved even in species with no eyes,” Wiens said. “It’s questionable whether most snakes or amphibians can see colors, so their bright colors are generally used for signaling to predators rather than to members of the same species.”

Arizona mountain kingsnakes are found in the southwestern U.S. and northern Mexico. Non-venomous, they have similar coloring to that of the venomous coral snakes. This coloration evolved as a mechanism for protection from predators. Credit: John J. Wiens

The researchers have another idea that could help explain the results.

“The most straightforward potential explanation for this trend is situations where an animal is disturbed at times of inactivity,” Emberts said. “When they’re sleeping during the day and a predator disturbs them, that bright coloration becomes important.”

Wiens pointed to the example of the red-eyed tree frog, a mostly green frog found in tropical rainforests in Central America. While snoozing, its uniform green coloring blends in with the surrounding foliage. When startled by a predator, the frog can expose its red eyes, bright orange hands and feet, and vibrant blue and yellow flanks. The unexpected display of brilliant colors may buy the frog just enough time to escape.

The researchers analyzed data from 1,824 land vertebrate species, looking for correlations between being diurnal versus nocturnal and the function of animals’ bright coloring.

They categorized colors as warning signals if a species qualified as poisonous or unpalatable, or mimicked another species with these deterring characteristics. Colors were categorized as sexual signals if one sex—commonly the males—developed vibrant coloring at sexual maturity, while the other sex did not.

“Animals generally use these colors either as a sexual signal or as a warning signal—rarely both,” Wiens said.

The researchers analyzed whether a species was diurnal or nocturnal, whether it had conspicuous colors or not, and whether those colors were used as warning or sexual signals. “Conspicuous” colors included red, orange, yellow, blue and purple. Few species reside in colorful environments, so the animals’ striking colors stand out from the natural background. The results indicated that this color palette was used for the two different purposes to roughly equal extent, with blue being somewhat of an exception.

“It’s interesting to see that for some colors like red, orange and yellow, they’re used with similar frequency as both a way to avoid predators and as a way for mate attraction,” said Emberts. “On the flip side, blue coloration was more frequently associated with mating as opposed to predator avoidance.”

The researchers’ analyses included all the major groups of land-living vertebrates—amphibians, mammals, birds, crocodilians, turtles, lizards and snakes.

Wiens and Emberts plan to further study the evolution of color across other animals, insects and plants. Additionally, they hope to determine when conspicuous colors first evolved and how their functions have changed over time.

More information:
Zachary Emberts et al, Why are animals conspicuously colored? Evolution of sexual versus warning signals in land vertebrates, Evolution (2022). DOI: 10.1111/evo.14636

Bright colors in the animal kingdom: Why some use them to impress and others to intimidate (2022, October 18)
retrieved 19 October 2022
from https://phys.org/news/2022-10-bright-animal-kingdom-intimidate.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced witho

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