Gene editing could render mosquitos infertile, reducing disease spread

Peer-Reviewed Publication

U.S. ARMY RESEARCH LABORATORY

 

IMAGE: NEW U.S. ARMY-FUNDED RESEARCH USES GENE EDITING TO RENDER CERTAIN MALE MOSQUITOES INFERTILE AND SLOW THE SPREAD OF DISEASES LIKE ZIKA AND YELLOW FEVER. view more 

CREDIT: UNIVERSITY OF CALIFORNIA SANTA BARBARA

RESEARCH TRIANGLE PARK, N.C. -- Mosquitos spread viruses that cause potentially deadly diseases such as Zika, dengue fever and yellow fever. New U.S. Army-funded research uses gene editing to render certain male mosquitoes infertile and slow the spread of these diseases.

Researchers at the Army’s Institute for Collaborative Biotechnologies and the University of California Santa Barbara used a gene editing tool known as CRISPR-Cas9 to target a specific gene tied to fertility in male mosquitoes. CRISPR-Cas9 is a genome editing tool that is creating a buzz in the science world, according to yourgenome.org. It is “faster, cheaper and more accurate than previous techniques of editing DNA and has a wide range of potential applications.”

Researchers experimented with the Aedes aegypti mosquitoes, which are found in tropical, subtropical and temperate regions throughout the world. The study, published in the Proceedings of the National Academy of Sciences, discerned how a mutation can suppress the fertility of female mosquitoes.

“This is yet one more important and exciting example of how synthetic biology tools are demonstrating unparalleled utility,” said Dr. James Burgess, ICB program manager for the U.S. Army Combat Capabilities Development Command, now known as DEVCOM, Army Research Laboratory. “In this case, it’s a precision increase from chainsaw to a scalpel leading to the correct biochemical outcome that could substantially reduce the population of a very infectious mosquito.”

To manage populations, scientists use a vector-control practice called the sterile insect technique in which they raise a lot of sterile male insects and they then release these males in numbers that overwhelm their wild counterparts. Females that mate with sterile males before finding a fertile one are themselves rendered infertile, thereby decreasing the size of the next generation.

Repeating this technique several times has the potential to crash the population because each generation is smaller than the last; releasing a similar number of sterile males has a stronger effect over time.

 

The sterile insect technique is effective in managing a number of agricultural pests, including the Mediterranean fruit fly, a crop pest in California. It has also been attempted with Aedes aegypti mosquitoes, but with limited success.

In the past, scientists used chemicals or radiation to sterilize male Aedes aegypti, but the chemicals or radiation impacted the mosquitos’ health to such an extent that they were less successful in mating with females, which undercuts the effectiveness of the sterile insect technique.

The research team wanted to identify a more targeted approach with less collateral damage, mutating a gene in mosquitoes that specifically caused male sterility without otherwise impacting the insects’ health.

“When CRISPR/Cas9 came out several years ago it just offered new opportunities to do things that you couldn’t do before,” said Dr. Craig Montell, distinguished professor at UC Santa Barbara. “So, the time seemed right to for us to start working on Aedes aegypti.”

Using gene editing in male Aedes aegypti, researchers found that the mutant male mosquitos produced no sperm, and unlike in previous efforts, the sterile studs were otherwise completely healthy; however, the team wasn’t sure whether sperm, albeit defective sperm from the sterile males, was needed to render female mosquitoes infertile, or whether the transfer of seminal fluid was all it took.

In one experiment, researchers introduced 15 mutant males into a group of 15 females for 24 hours. Then they swapped the males for 15 wild-type males, and left them there.

“Essentially, all of the females remained sterile,” Montell said. “This confirmed that males could suppress female fertility without producing sperm.”

Next the researchers set out to determine how timing played into the effect. They exposed the females to mutant males for different lengths of time. The scientists noticed little difference after 30 minutes, but female fertility quickly dropped after that. Montell noted that females copulated twice on average, even during the first 10 minutes. This indicated that females have to mate with many sterile males before being rendered infertile themselves.

Combining the females with the males for four hours cut female fertility to 20% of normal levels. After eight hours the numbers began leveling out around 10%.

According to Montell, Aedes aegypti populations could easily bounce back from an 80% drop in fertility. The success of sterile insect technique comes from subsequent, successive releases of sterile males, where each release will be more effective than the last as sterile males account for an ever-growing proportion of the population.

The team plans to continue investigating mosquito mating behaviors and fertility. They are devising a way to maintain stocks of males so they are only sterile in the wild and not in the lab. In addition, they are characterizing male mating behavior to uncover new ways to suppress mosquito populations.

“We’ve become very interested in studying many aspects of behavior in Aedes aegypti because these mosquitoes impact the health of so many people,” Montell said. “There is a pandemic every year from mosquito-borne diseases.”

The ICB is an Army-sponsored University Affiliated Research Center led by the University of California, Santa Barbara, in collaboration with the Massachusetts Institute of Technology, the California Institute of Technology and partners from the Army and industry. Interdisciplinary teams of biologists, chemists, physicists, psychologists, physicians and engineers develop biologically inspired, revolutionary technological innovations in systems and synthetic biology, bio-enabled materials and cognitive neuroscience.

Visit the laboratory's Media Center to discover more Army science and technology stories

 

As the Army’s national research laboratory, ARL is operationalizing science to achieve transformational overmatch. Through collaboration across the command’s core technical competencies, DEVCOM leads in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more successful at winning the nation’s wars and come home safely. DEVCOM Army Research Laboratory is an element of the U.S. Army Combat Capabilities Development Command. DEVCOM is a major subordinate command of the Army Futures Command.

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DOI

10.1073/pnas.2105075118 

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Suppression of female fertility in Aedes aegypti with a CRISPR-targeted male-sterile mutation

ARTICLE PUBLICATION DATE

1-Jun-2021

 

Best of both worlds: New organic–inorganic gas sensors for better air quality monitoring

Scientists develop novel gas sensors with improved detection sensitivity and durability by combining organic and inorganic materials

Peer-Reviewed Publication

INCHEON NATIONAL UNIVERSITY

 

IMAGE: IN A NEW STUDY, RESEARCHERS FROM KOREA HAVE DEVISED A HIGH-PERFORMANCE AND DURABLE GAS SENSOR USING A COMBINATION OF AN ORGANIC POLYMER AND INORGANIC GAS SENSING MATERIAL view more 

CREDIT: ALEXANDR PODVALNY ON PEXELS

With air pollution on the rise, especially in densely populated urban areas, testing for air quality and the presence of pollutant gases, such as carbon dioxide, nitrogen dioxide (NO2), and carbon monoxide, have become more important than ever. Sensitive gas sensing and monitoring technologies are, therefore, a pressing need. 

Of much recent research interest in this field are the novel organic field-effect transistor-based (OFET) sensors, which are highly sensitive, flexible, and lightweight, opening doors to portable gas sensors even on e-skins. However, OFETs are unstable, and therefore not durable, at room temperature. This limits their applicability and makes them inferior to existing inorganic sensors, which nonetheless, do not possess any of the flexibility and light weight of organic sensors.

Bridging the organic–inorganic gap, scientists from Incheon National University, Korea, led by Prof. Yeong Don Park, have created hybrid OFETs using a organic conjugated polymer and variations of an inorganic nanoporous material, zeolite. Their study was made available online on 6 April 2021 and will be published in Volume 420 Part 1 of Chemical Engineering Journal on 15 September 2021.

“The high degree of porosity in zeolite results in an exceptionally high specific surface area and, in turn, a strong adsorption response for small gas molecules. This also helps it adsorb the molecules in air that oxidize (react with) the gas sensor to destabilize it and reduce its durability.” explains Prof. Park. Their material boasts not only high durability, but also high sensitivity.

The team fabricated two OFET-based NO2 sensors using a combination of the conjugated polymer, poly(3-hexylthiophene) (P3HT) and one of two zeolite materials, PST-11 or Omega. They examined the sensing performances of both OFETs when exposed to NO2 gas. The hybridization provided the polymer with an orderly structure which in turn led to efficient interactions with the gas molecules and, consequently, high sensitivity. Among the two, the scientists observed that the PST-11–P3HT film was more sensitive to NO2 than the Omega–P3HT film due to a larger specific surface area.

Overall, Prof. Park explains: “Our approach represents a new way of conceptualizing the design and development of sensors. If our research is refined further, people can easily detect harmful gases in real time.” Speaking of his vision, he says: “Our devices can be integrated with wearable devices such as smart watches and e-skins to allow people to know about air pollution levels in areas other than industrial sites.”

While a pollution-free world is our end goal, it certainly wouldn’t hurt to stay safe while we get there.

 

***

 

Reference

Authors: Eun Hye Kwon (1), Hyejin An (2), Min Bum Park (1), Min Kim (2) and Yeong Don Park (1)

Title of original paper: Conjugated polymer–zeolite hybrids for robust gas sensors: Effect of zeolite surface area on NO2 sensing ability

Journal: Chemical Engineering Journal

DOI: 10.1016/j.cej.2021.129588

Affiliations:

(1) Incheon National University, Korea  

(2) Jeonbuk National University, Korea

 

About Incheon National University

Incheon National University (INU) is a comprehensive, student-focused university. It was founded in 1979 and given university status in 1988. One of the largest universities in South Korea, it houses nearly 14,000 students and 500 faculty members. In 2010, INU merged with Incheon City College to expand capacity and open more curricula. With its commitment to academic excellence and an unrelenting devotion to innovative research, INU offers its students real-world internship experiences. INU not only focuses on studying and learning but also strives to provide a supportive environment for students to follow their passion, grow, and, as their slogan says, be INspired.

Website: http://www.inu.ac.kr/mbshome/mbs/inuengl/index.html

 

About the authors

Professor Yeong Don Park focuses on research on the fabrication and characterization of conductive polymer-based devices, and Professor Minbum Park conducts research on zeolite’s gas adsorption. Together, they fuse two different research fields of organic and inorganic matter; this synergistic effect gives rise to excellent, high-quality, and innovative research!

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JOURNAL

Chemical Engineering Journal

DOI

10.1016/j.cej.2021.129588 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Conjugated polymer–zeolite hybrids for robust gas sensors: Effect of zeolite surface area on NO2 sensing ability

ARTICLE PUBLICATION DATE

14-Sep-2021

Study identifies possible antidote for club drug GHB overdose

Diclofenac blocks passage of GHB into the brain; other NSAIDs, including ibuprofen, may also limit toxicity of GHB, University at Buffalo researchers find

Peer-Reviewed Publication

UNIVERSITY AT BUFFALO

BUFFALO, N.Y. – Diclofenac and other non‐steroidal anti‐inflammatory drugs (NSAIDs) may limit the passage of gamma hydroxybutyric acid (a narcolepsy medication and illicit party drug commonly known as GHB) to the brain, decreasing the potential for fatal overdose, according to a University at Buffalo study.

The research found that treatment with diclofenac after taking GHB led to decreased concentrations of GHB in the brain and an improved respiration. The study, completed in animal models, was published in Biopharmaceutics & Drug Disposition. Previous studies completed by the UB researchers found that the NSAIDs ibuprofen and ketoprofen also affected the movement of GHB in the body.

GHB is approved for a number of clinical uses, including the treatment of narcolepsy, a chronic sleep disorder, and alcoholism. However, GHB prescriptions are limited due to its high potential for abuse as a club and date-rape drug. At high doses, the drug can cause amnesia, drowsiness and depressed breathing. There are currently no approved antidotes for GHB overdose. 

“The therapeutic utility of GHB in the treatment of narcolepsy [as Xyrem] has been overshadowed by its high prevalence of abuse. The abuse of GHB – known as Fantasy, Liquid Ecstasy and G – carries the risk of severe adverse effects including sedation, respiratory depression, hypothermia, coma and death,” says Marilyn Morris, PhD, SUNY Distinguished Professor and chair of the Department of Pharmaceutical Sciences in the UB School of Pharmacy and Pharmaceutical Sciences.

“Current treatment of GHB overdose is limited to supportive care. My laboratory has identified MCT1 inhibitors as a treatment strategy to prevent death after GHB overdoses. In this research, we identified the NSAID diclofenac as a MCT1 inhibitor and demonstrated its effectiveness as a potential antidote for GHB overdose. Also, our findings significantly suggest that diclofenac and other NSAIDs may decrease the effectiveness of Xyrem used in the treatment of narcolepsy.”  

Additional investigators include first author, UB alumna and former graduate student in Morris’ lab Vivian Rodriguez‐Cruz, PhD, research scientist at Eli Lilly and Company; and Tianjing Ren, PhD, postdoctoral researcher in the UB School of Pharmacy and Pharmaceutical Sciences.

Commonly sold under the brand name Voltaren, diclofenac is prescribed to treat pain and inflammation. Morris’ lab has found that some NSAIDs can block tissue uptake of drugs by monocarboxylate transporters (MCTs), a family of proteins that transport molecules across biological membranes, including the blood‐brain barrier, which protects the brain from toxins and pathogens circulating in the blood while allowing for the passage of nutrients.

GHB relies on MCTs for transport throughout the body, making the study of the inhibition of MCTs as an antidote a focus of Morris’ lab. 

The recent study sought to understand the impact diclofenac has on GHB toxicity by measuring the effect of their interaction on respiratory depression – the main cause of death following GHB overdose.

Diclofenac was found to inhibit the brain uptake of GHB by MCT1, the only monocarboxylate transporter present at the blood‐brain barrier, resulting in a reversal of respiratory depression after GHB overdose. 

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DOI

https://doi.org/10.1002/bdd.2296 

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Drug-drug interaction between diclofenac and gamma-hydroxybutyric acid

ARTICLE PUBLICATION DATE

30-Jun-2021

 

The Hobbit’s bite gets a stress test

Stone tools may have allowed Homo floresiensis to eat their meals with less chewing effort than earlier hominins.

Peer-Reviewed Publication

DUKE UNIVERSITY

 

IMAGE: A COMPUTER SIMULATION OF A HOMO FLORESIENSIS CRANIUM SHOWS THE PATTERN OF STRESS AND STRAIN IN THE BONES OF THE FACE DURING BITING. AREAS UNDER HIGH STRAIN ARE SHOWN IN WHITE, PINK AND RED. view more 

CREDIT: PLEASE CREDIT LEDOGAR LAB, DUKE UNIVERSITY

DURHAM, N.C. -- If you’ve ever suffered from a sore jaw that popped or clicked when you chewed gum or crunched hard foods, you may be able to blame it on your extinct ancestors.

That’s according to a Duke University-led study of the chewing mechanics of an ancient human relative called Homo floresiensis, which inhabited the Indonesian island of Flores before our species arrived there some 50,000 years ago.

Not much more than three feet tall, the hominin’s diminutive size earned it the nickname “the Hobbit,” after the characters in J.R.R. Tolkien’s “The Lord of the Rings.” For the new study, which was published Aug. 13 in the journal Interface Focus, the researchers wanted to understand how the Hobbit’s skull behaved while it ate its food.

However, thousands of years of fossilization had left its skull -- the only one that has been found so far -- damaged and misshapen. Before the researchers could test it out, they had to restore it as close to its original shape as possible. Collaborators at Italy’s University of Bologna created a 3D virtual model, built from X-ray CT scans, digitally filling in the missing pieces to reconstruct what the skull of Homo floresiensis might have looked like when it roamed the island some 100,000 to 60,000 years ago.

From that, they used computer simulations and a technique called finite element analysis to give the virtual skull characteristics that mimic the real thing, such as the stiffness of the bones and the pulling action of the muscles. Then they had the virtual skull chomp down with its back teeth -- premolars and molars -- and analyzed the forces at work with each bite, essentially subjecting it to a digital crash test.

The researchers mapped the strains within their digital model of the Hobbit’s facial bones during biting, comparing the results to similar simulations for earlier human relatives called australopiths that lived some two to three million years ago in Africa, along with chimpanzees and humans living today.

The team determined that the Hobbit’s bite could have exerted around 1300 Newtons of force, comparable to the chomping power of modern humans and several of our extinct cousins. But had it bitten down too vigorously on a hard nut or a tough hunk of meat, the findings suggest Homo floresiensis would have been at greater risk than our earlier human kin of straining its facial bones, or dislocating the joint where the lower and upper jaws meet.

“We don't really know what Homo floresiensis ate,” said first author Rebecca Cook, a doctoral student in evolutionary anthropology at Duke. Patterns of wear on the teeth, combined with pygmy elephant bones and other animal remains unearthed from the same cave where the Hobbit was found suggest that it ate at least some meat.

But the results suggest that exceedingly hard or tough foods, which would have been no problem for an australopith to gnaw on or crack open, might have given the Hobbit a TMJ headache.

“Similar patterns are observed in modern humans,” Cook said.

Millions of years of human evolution gave us smaller teeth and more lightweight skulls, because cooking our food and slicing and pounding it with stone tools, and probably also eating meat, made having overbuilt skulls unnecessary.

But years after the Hobbit’s discovery its facial features remain a puzzle. Its skull had a curious mix of traits, some of which -- like its heavyset lower jaw -- are similar to our earlier and more ape-like ancestors, while others -- like its small delicate face -- resemble humans today.

“This can make it confusing as to where this species falls on the family tree of hominin evolutionary relationships,” Cook said.

The new study suggests this shift to smaller faces, weaker bites and achey jaws evolved early, before the common ancestors of Homo floresiensis and modern humans went their separate ways.

Justin Ledogar, Duke researcher and senior author of the study, says the next step is to do similar analyses on earlier members of the genus Homo, including Homo erectus. The first known hominin to use fire and cook food, this species also had smaller teeth, jaws and faces than earlier hominins, and is thought by some to be the ancestor of Homo floresiensis.

The researchers say the work could help answer lingering questions about where Homo floresiensis came from, how it lived and how it fits into the human evolutionary tree.

“This study is just one small piece of a much larger puzzle,” Cook said.

This research was funded by the American Association of Physical Anthropology and Duke University, and by grants from the European Union’s Horizon 2020 Research and Innovation Programme (724046 SUCCESS) and the U.S. National Science Foundation (NSF-BCS-0725126).

CITATION: "The Cranial Biomechanics and Feeding Performance of Homo Floresiensis," Rebecca W. Cook, Antonino Vazzana, Rita Sorrentino, Stefano Benazzi, Amanda L. Smith, David S. Strait and Justin A. Ledogar. Interface Focus, Aug. 13, 2021. DOI: 10.1098/rsfs.2020.0083

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JOURNAL

Interface Focus

DOI

10.1098/rsfs.2020.0083 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

The Cranial Biomechanics and Feeding Performance of Homo Floresiensis

ARTICLE PUBLICATION DATE

13-Aug-2021

COI STATEMENT

This research was funded by the American Association of Physical Anthropology and Duke University, and by grants from the European Union’s Horizon 2020 Research and Innovation Programme (724046 SUCCESS) and the U.S. National Science Foundation (NSF-BCS-0725126).

 

Pusan National University researchers shed light on the early development of rice seeds

They discovered an enzyme essential for the correct growth of endosperm in rice, paving the way to higher yields

Peer-Reviewed Publication

PUSAN NATIONAL UNIVERSITY

 

IMAGE: CTP SYNTHASE IS ESSENTIAL FOR EARLY ENDOSPERM DEVELOPMENT BY REGULATING NUCLEI SPACING view more 

CREDIT: PUSAN NATIONAL UNIVERSITY

Agriculture, particularly that involving grains, has always been a steadfast pillar of civilization. Our current understanding of plant biology and genetics has helped us greatly improve the quality and yield of crops through various techniques, some of them focusing on the complex processes involved in seed development.

The seeds of most flowering plants have two distinct structures: the embryo and the endosperm. The embryo cells are created during fertilization, whereas the endosperm constitutes a structural and nutrient-rich body that protects and supports the embryo. The endosperm accounts for most of the nutritional value of the harvest in cereals like rice; many genetic studies focus on how to control the accumulation of starch during the final stages of endosperm development. On the other hand, not much is known about the genes that orchestrate early endosperm development in rice.

A team of scientists led by Assistant Professor Lae-Hyeon Cho (ORCID ID: 0000-0003-4514-4107) of Pusan National University, Korea, recently conducted a study to fill part of this knowledge gap. In their work, which was published in Plant Biotechnology Journal, the team analyzed the genome of a rice plant mutant whose seeds contained no endosperm and an abnormally enlarged embryo.

They identified a single mutation in the gene that codes for cytidine triphosphate synthase (CTPS), an enzyme that helps produce some of the building blocks of DNA and RNA. They also clarified the relationship between CTPS and the endosperm. It turns out CTPS forms macromolecular structures during the early stages of endosperm development, helping endosperm cells migrate within the seed. The mutant, having an altered form of CTPS, failed to produce this supporting structure, and thus its seeds ended up being endosperm-less.

Most notably, the scientists also showed that overexpression of CTPS in genetically modified rice plants results in a larger endosperm. This opens up an avenue for fine-tuning the size ratio between endosperm and embryo. “Controlling the embryo and endosperm size determines the quantity and quality of the seeds,” explains Dr. Cho, “It is important to increase the size of the embryo in moderation while also increasing that of the endosperm.”

Overall, the newfound insight provided by the research team could lead to more fruitful rice plantations. “Early seed development in rice ultimately determines the number of cells in the seed and is closely related to yield,” highlights Dr. Cho, “Our study may pioneer the field of research on the early development of the endosperm and contribute to improving the quality of food crops in the future.” Let us hope further progress in this field helps make food more accessible to the whole world!

 

***

 

Reference

Title of original paper: CTP synthase is essential for early endosperm development by regulating nuclei spacing

Journal: Plant Biotechnology Journal

DOI: https://doi.org/10.1111/pbi.13644

 

About Pusan National University

Pusan National University, located in Busan, South Korea, was founded in 1946, and is now the no. 1 national university of South Korea in research and educational competency. The multi-campus university also has other smaller campuses in Yangsan, Miryang, and Ami. The university prides itself on the principles of truth, freedom, and service, and has approximately 30,000 students, 1200 professors, and 750 faculty members. The university is composed of 14 colleges (schools) and one independent division, with 103 departments in all.      

Website: https://www.pusan.ac.kr/eng/Main.do

 

About the author

Lae-Hyeon Cho is an Assistant Professor at the Department of Plant Bioscience in Pusan National University, Korea. His group studies the various developmental processes of rice, a staple food crop throughout the world. They also aim to establish a molecular model system of rice for coping with recent climate changes by studying the regulation of the flowering time in rice in various external environments. Dr. Cho received a PhD in Plant Molecular Genetics from Pohang University of Science and Technology, Korea, in 2008.

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JOURNAL

Plant Biotechnology Journal

DOI

10.1111/pbi.13644 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

CTP synthase is essential for early endosperm development by regulating nuclei spacing

ARTICLE PUBLICATION DATE

30-May-2021

COI STATEMENT

The authors declare no conflict of interest.

Disclaimer: AAAS and EurekAlert! are not resp

Male Y chromosome facilitates the evolution of sex differences in body size

Peer-Reviewed Publication

UPPSALA UNIVERSITY

 

IMAGE: FEMALE AND A MALE (ILLUSTRATING THE SIZE CHANGE IN RESPONSE TO SELECTION) CALLOSOBRUCHUS MACULATUS BEETLE, AS WELL AS THEIR HOST PLANT VIGNA RADIATA. view more 

CREDIT: PAULA VASCONCELOS

Females and males differ in many ways and yet they share the same genome. The only exception is the male Y chromosome. Using beetles as a study system, new research from Uppsala University, now published in Nature Ecology & Evolution, shows that despite of the Y chromosome containing very few genes, it can dramatically change male body size and thus facilitate the evolution of sex differences.

Females and males typically differ in many ways in their morphology, physiology and behaviour. How such sex differences, known as sexual dimorphism, evolve is a puzzle because females and males share the same set of genes and an evolutionary change in one sex should cause a correlated change even in the other sex, thereby preventing sex differences from evolving. The new study shows that even small amounts of genetic differences between the sexes can facilitate the evolution of sexual dimorphism such that it can evolve in just a few generations.

 “Our experiments show that the autosomes as well as both sex chromosomes, the X and Y,  can harbor genetic variation important for sexual dimorphism, but the Y chromosome alone can alter the sex difference in size by as much as 30 percent. This is remarkable because in these beetles the Y chromosome contains just a handful of genes and represents a very small fraction of the genome, just like in humans. Many have thought that the Y only affects the most important reproductive processes in males, namely sperm production. Our findings suggest that the Y chromosome may have a broader role than previously appreciated,” says Philipp Kaufmann, a PhD student at the Uppsala University’s Department of Ecology and Genetics and the first author of the study.

CAPTION

Sexual size dimorphism under selection. Female seed beetle Callosobruchus maculatus (with darker colouration) and two males that differ in body size. In our study we used artificial selection to increase sexual size dimorphism, and the beetles in the photo show the variation in sex difference in size after selection.

CREDIT

Elina Immonen

The evolution of sexual dimorphism is however not only dependent on where in the genome genetic variation resides, but also on how natural and sexual selection can act on it. With the help of lab evolution, the research team showed that sexual size dimorphism could evolve when selecting on male size, but that when selection acted only on females, the shared part of the genome caused a correlated evolutionary response in males preventing dimorphism from evolving.

“The most drastic change in sexual dimorphism, an increase by 50 percent in only ten generations, occurred when we applied selection sexually antagonistically – favoring the opposite body size in the two sexes. This shows that under right kind of selection sex differences can clearly evolve rapidly, perhaps more easily than was previously thought,” says Elina Immonen, Assistant Professor at the Department of Ecology and Genetics, Uppsala University, and the principle investigator of the study.

“Combining information of what kind of genetic variation is available to selection with different forms of selection is a powerful way to test the determinants of evolution of sex differences. By isolating the effect of Y chromosome variation from the rest of the genome, we could directly demonstrate how large the effect of the Y chromosome is, something we didn’t expect to see when we started the work and this has helped understand how sexual dimorphism has evolved in this species. Future work will tell us more regarding how the Y chromosome can have such a large effect on males and how general its role is in the evolution of sex differences across taxa,” Immonen concludes.

CAPTION

Males with different Y chromosome haplotypes. The males differ in body size when they are otherwise genetically identical but differ in their Y chromosome.

CREDIT

Elina Immonen

More about the experiments

In their study, the researchers characterized the genetic architecture of body size in males and females by creating a large pedigree of over 8,000 beetles (the seed beetle Callosobruchus maculatus). This multi-generational family tree was used to quantify autosomal and sex chromosome linked genetic variation in body size. The use of artificial selection allowed testing how different forms of selection affect the evolution of size dimorphism and included selection acting only on males, only on females, or acting sexually antagonistically (in the opposite directions) in the two sexes. After ten generations of selection, the sexual size dimorphism was compared between the selection lines and the ancestral pedigree population. These two experiments clearly indicated that the Y chromosome play an important role in determining male response to selection. In order to test further the effect of the Y linked variation in isolation from variation in the rest of the genome, the research team carried out a third experiment. They isolated the effect of the Y chromosome on sexual size dimorphism in these beetles by introducing the different Y chromosomes into a genetically identical background. In other words, creating beetles that are identical twins to each other except for the Y chromosome.

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DOI

10.1038/s41559-021-01530-z 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Rapid evolution of sexual size dimorphism facilitated by Y-linked genetic variance

ARTICLE PUBLICATION DATE

18-Aug-2021

 HALT ANIMAL EXPERIMENTATION!

Prozac changes fat composition of the monkey brain

Peer-Reviewed Publication

SKOLKOVO INSTITUTE OF SCIENCE AND TECHNOLOGY (SKOLTECH)

 

IMAGE: HE STUDY LOOKED AT GENE EXPRESSION AND METABOLITE CONTENT CHANGES IN THE MACAQUE BRAIN FOLLOWING TWO-YEAR ADMINISTRATION OF THE COMMON ANTIDEPRESSANT FLUOXETINE, AKA. PROZAC. THE CONCENTRATIONS OF SOME PRODUCTS OF METABOLISM TURNED OUT TO BE DECREASED COMPARED TO THE CONTROL GROUP OF ANIMALS. SO-CALLED FREE POLYUNSATURATED FATTY ACIDS PROVED TO BE AFFECTED THE MOST. view more 

CREDIT: REWORKED BY NICOLAS POSUNKO/SKOLTECH FROM ANNA TKACHEV ET AL./INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Skoltech researchers and their colleagues from Russia, Germany, and the U.S. have found Prozac to reduce lipid concentrations in juvenile macaques who received the antidepressant for two years, compared to a control group of untreated animals. While none of the monkeys in the study were depressed, the findings still offer a plausible biochemical explanation for the drug’s side effects, particularly in young patients. The paper was published in the International Journal of Molecular Sciences.

Prozac is the most widely prescribed antidepressant in the world and is approved in the United States for treating children as young as 8 years old with major depressive disorder and 7 years old with obsessive-compulsive disorder. There is a certain amount of controversy surrounding this use, with some studies claiming the drug might actually increase the likelihood of suicidal thinking and behaviour and that this side effect could be more pronounced in young patients. This makes biochemical research into how fluoxetine — the active compound in Prozac — affects the brain, particularly in young age, highly relevant.

A series of earlier studies on the same group of animals carried out by the team’s collaborators investigated the effects of two-year fluoxetine administration to juvenile macaques on their impulsivity, sleep, social interaction, and the concentration of peripheral metabolites — the products of metabolism measured in the blood. This time, the researchers observed the drug’s effects on gene expression and brain metabolite content, primarily that of biomolecules called lipids.

“Lipids have long been known as the building blocks of cell membranes and as the molecules storing energy in the body’s fat tissue. More recently, their importance for proper brain functioning has become increasingly apparent. Lipids are abundant in the brain, where they are found not just in the cell membranes of neurons, whose properties they modulate, but also in the so-called myelin sheaths insulating axons — the brain’s ‘wiring.’ The brain is therefore a surprisingly ‘fat’ organ — in fact, it is nearly 60% fat,” the study’s first author, Anna Tkachev from Skoltech, said.

Biochemical brain research has tied lipid abnormalities to diseases, including schizophrenia, depression, and Alzheimer’s, making these molecules an important marker of brain health.

While the study only found slight variations in gene expression and insignificant changes in nonlipid metabolite content, decreased concentrations were observed for many of the over 300 lipids measured in the post-mortem brains of the macaques using a technique called mass spectrometry. The affected lipids were those that either incorporate what’s known as polyunsaturated fatty acids or are PUFAs occurring on their own, and not as part of larger lipid molecules. These so-called free PUFAs exhibited the most dramatic drop in their concentration. A familiar example of PUFAs are the omega-3 fatty acids, which humans ingest with sea fish and some other foods. They are important for health in general and for mental health in particular.

“One clue as to why the antidepressant might have more adverse effects when administered to young patients is that the younger a child’s age, the more rapid are the natural changes in the brain. Until the age of two, babies ramp up their brain PUFA content very rapidly, which explains one of the health benefits of breastfeeding: Breast milk is rich in fats and provides lipid building blocks for brain development. Although this lipid accumulation phase slows down progressively, it might not be 100% over in young teenagers, which is roughly the age equivalent of the juvenile macaques we studied,” Tkachev conjectured.

Examining the animals’ metabolite content in the blood, the researchers saw tentative indications of an overall PUFA drop in the body, though this was not nearly as pronounced as in the prelimbic cortex — the part of the brain analyzed in the paper.

“One important distinction between humans and macaques is that we have the alternative of ingesting PUFAs with fish, meat, and some other foods not typically consumed by macaques. They have to rely on their own livers to synthesize PUFAs. This means that if further research determines that the imbalances we observed have to do with disrupted lipid synthesis, this adverse effect could be alleviated in humans with a proper diet,” Tkachev explained.

“For this reason, it is necessary to measure metabolite content in human blood, and the traces of lipid imbalances left in macaque blood give reason to hope we might just find something similar in humans, without the need to actually dissect anyone’s brain,” the researcher went on. “If we don’t, it might be a sign of the imbalances stemming from factors other than synthesis disruptions, such as lipids having trouble entering the brain or possibly undergoing a redistribution toward other brain regions. New animal studies similar to ours but focusing on other brain parts could control for that.”

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The study reported in this story featured researchers from Skolkovo Institute of Science and Technology, Lomonosov Moscow State University, Max Planck Institute of Psychiatry, Ludwig-Maximilians University, and UC Davis.

Skoltech is a private international university located in Russia. Established in 2011 in collaboration with the Massachusetts Institute of Technology (MIT), Skoltech is cultivating a new generation of leaders in the fields of science, technology, and business, conducting research in breakthrough fields, and promoting technological innovation with the goal of solving critical problems that face Russia and the world. Skoltech is focusing on six priority areas: data science and artificial intelligence, life sciences, advanced materials and modern design methods, energy efficiency, photonics and quantum technologies, and advanced research. Website: https://www.skoltech.ru/.

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JOURNAL

International Journal of Molecular Sciences

DOI

10.3390/ijms22158089 

ARTICLE TITLE

Long-Term Fluoxetine Administration Causes Substantial Lipidome Alteration of the Juvenile Macaque Brain

ARTICLE PUBLICATION DATE

27-Jul-2021