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Female mosquito fate in absence of food

Female mosquito fate in absence of food


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What happens to female mosquitoes which want to lay egg but couldn't find mammal host for blood, will that mosquito simply die, if no mammals in area would mosquitoes will be absent too?


Mosquitoes are drawn to flowers as much as people -- and now scientists know why

Without their keen sense of smell, mosquitoes wouldn't get very far. They rely on this sense to find a host to bite and spots to lay eggs.

And without that sense of smell, mosquitoes could not locate their dominant source of food: nectar from flowers.

"Nectar is an important source of food for all mosquitoes," said Jeffrey Riffell, a professor of biology at the University of Washington. "For male mosquitoes, nectar is their only food source, and female mosquitoes feed on nectar for all but a few days of their lives."

Yet scientists know little about the scents that draw mosquitoes toward certain flowers, or repel them from others. This information could help develop less toxic and better repellents, more effective traps and understand how the mosquito brain responds to sensory information -- including the cues that, on occasion, lead a female mosquito to bite one of us.

Riffell's team, which includes researchers at the UW, Virginia Tech and UC San Diego, has discovered the chemical cues that lead mosquitoes to pollinate a particularly irresistible species of orchid. As they report in a paper published online Dec. 23 in the Proceedings of the National Academy of Sciences, the orchid produces a finely balanced bouquet of chemical compounds that stimulate mosquitoes' sense of smell. On their own, some of these chemicals have either attractive or repressive effects on the mosquito brain. When combined in the same ratio as they're found in the orchid, they draw in mosquitoes as effectively as a real flower. Riffell's team also showed that one of the scent chemicals that repels mosquitoes lights up the same region of the mosquito brain as DEET, a common and controversial mosquito repellant.

Their findings show how environmental cues from flowers can stimulate the mosquito brain as much as a warm-blooded host -- and can draw the mosquito toward a target or send it flying the other direction, said Riffell, who is the senior author of the study.

The blunt-leaf orchid, or Platanthera obtusata, grows in cool, high-latitude climates across the Northern Hemisphere. From field stations in the Okanogan-Wenatchee National Forest in Washington state, Riffell's team verified past research showing that local mosquitoes pollinate this species, but not its close relatives that grow in the same habitat. When researchers covered the flowers with bags -- depriving the mosquitoes of a visual cue for the flower -- the mosquitoes would still land on the bagged flowers and attempt to feed through the canvas. Orchid scent obviously attracted the mosquitoes. To find out why, Riffell's team turned to the individual chemicals that make up the blunt-leaf orchid's scent.

"We often describe 'scent' as if it's one thing -- like the scent of a flower, or the scent of a person," said Riffell. "Scent is actually a complex combination of chemicals -- the scent of a rose consists of more than 300 -- and mosquitoes can detect the individual types of chemicals that make up a scent."

Riffell describes the blunt-leaf orchid's scent as a grassy or musky odor, while its close relatives have a sweeter fragrance. The team used gas chromatography and mass spectroscopy to identify dozens of chemicals in the scents of the Platanthera species. Compared to its relatives, the blunt-leaf orchid's scent contained high amounts of a compound called nonanal, and smaller amounts of another chemical, lilac aldehyde.

Riffell's team also recorded the electrical activity in mosquito antennae, which detect scents. Both nonanal and lilac aldehyde stimulated antennae of mosquitoes that are native to the blunt-leaf orchid's habitat. But these compounds also stimulated the antennae of mosquitoes from other regions, including Anopheles stephensi, which spreads malaria, and Aedes aegypti, which spreads dengue, yellow fever, Zika and other diseases.

Experiments of mosquito behavior showed that both native and non-native mosquitoes preferred a solution of nonanal and lilac aldehyde mixed in the same ratio as found in blunt-leaf flowers. If the researchers omitted lilac aldehyde from the recipe, mosquitoes lost interest. If they added more lilac aldehyde -- at levels found in the blunt-leaf orchid's close relatives -- mosquitoes were indifferent or repelled by the scent.

Using techniques developed in Riffell's lab, they also peered directly into the brains of Aedes increpitus mosquitoes, which overlap with blunt-leaf orchids, and a genetically modified strain of Aedes aegypti previously developed by Riffell and co-author Omar Akbari, an associate professor at UC San Diego. They imaged calcium ions -- signatures of actively firing neurons -- in the antenna lobe, the region of the mosquito brain that processes signals from the antennae.

These brain imaging experiments revealed that nonanal and lilac aldehyde stimulate different parts of the antenna lobe -- and even compete with one another when stimulated: The region that responds to nonanal can suppress activity in the region that responds to lilac aldehyde, and vice versa. Whether this "cross talk" makes a flower attractive or repelling to the mosquito likely depends on the amounts of nonanal and lilac aldehyde in the original scent. Blunt-leaf orchids have a ratio that attracts mosquitoes, while closely related species do not, according to Riffell.

"Mosquitoes are processing the ratio of chemicals, not just the presence or absence of them," said Riffell. "This isn't just important for flower discrimination -- it's also important for how mosquitoes discern between you and I. Human scent is very complex, and what is probably important for attracting or repelling mosquitoes is the ratio of particular chemicals. We know that some people get bit more than others, and maybe a difference in ratio explains why."

The team also discovered that lilac aldehyde stimulates the same region of the antenna lobe as DEET. That region may process "repressive" scents, though further research would need to verify this, said Riffell. It's too soon to tell if lilac aldehyde may someday be an effective mosquito repellant. But if it is, there is an added bonus.

"It smells wonderful," said Riffell.

Lead author is Chloé Lahondère, who conducted the research as a UW postdoctoral fellow and is now a research assistant professor at Virginia Tech. Additional co-authors are Clément Vinauger, a former UW postdoctoral researcher and current assistant professor at Virginia Tech UW biology graduate students Ryo Okubo and Jeremy Chan and UW postdoctoral researcher Gabriella Wolff. The research was funded by the National Institutes of Health, the Air Force Office of Scientific Research and the University of Washington.

For more information, contact Riffell at 206-685-2573 or [email protected]

Grant numbers: RO1-DC013693, R21-AI137947, FA9550-14-1-0398, FA9550-16-1-0167

James Urton
University of Washington
206-543-2580
[email protected]

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.


Scientists describe how mosquitoes are attracted to humans

Mosquitoes are drawn to human skin and breath. Credit: Genevieve M. Tauxe, Ray Lab, UC Riverside.

Female mosquitoes, which can transmit deadly diseases like malaria, dengue fever, West Nile virus and filariasis, are attracted to us by smelling the carbon dioxide we exhale, being capable of tracking us down even from a distance. But once they get close to us, they often steer away toward exposed areas such as ankles and feet, being drawn there by skin odors.

Why does the mosquito change its track and fly towards skin? How does it detect our skin? What are the odors from skin that it detects? And can we block the mosquito skin odor sensors and reduce attractiveness?

Recent research done by scientists at the University of California, Riverside can now help address these questions. They report on Dec. 5 in the journal Cell that the very receptors in the mosquito's maxillary palp that detect carbon dioxide are ones that detect skin odors as well, thus explaining why mosquitoes are attracted to skin odor – smelly socks, worn clothes, bedding – even in the absence of CO2.

"It was a real surprise when we found that the mosquito's CO2 receptor neuron, designated cpA, is an extremely sensitive detector of several skin odorants as well, and is, in fact, far more sensitive to some of these odor molecules as compared to CO2," said Anandasankar Ray, an associate professor in the Department of Entomology and the project's principal investigator. "For many years we had primarily focused on the complex antennae of mosquitoes for our search for human-skin odor receptors, and ignored the simpler maxillary palp organs."

Until now, which mosquito olfactory neurons were required for attraction to skin odor remained a mystery. The new finding – that the CO2-sensitive olfactory neuron is also a sensitive detector of human skin – is critical not only for understanding the basis of the mosquito's host attraction and host preference, but also because it identifies this dual receptor of CO2 and skin-odorants as a key target that could be useful to disrupt host-seeking behavior and thus aid in the control of disease transmission.

To test whether cpA activation by human odor is important for attraction, the researchers devised a novel chemical-based strategy to shut down the activity of cpA in Aedes aegypti, the dengue-spreading mosquito. They then tested the mosquito's behavior on human foot odor – specifically, on a dish of foot odor-laden beads placed in an experimental wind tunnel – and found the mosquito's attraction to the odor was greatly reduced.

Next, using a chemical computational method they developed, the researchers screened nearly half a million compounds and identified thousands of predicted ligands. They then short-listed 138 compounds based on desirable characteristics such as smell, safety, cost and whether these occurred naturally. Several compounds either inhibited or activated cpA neurons of which nearly 85 percent were already approved for use as flavor, fragrance or cosmetic agents. Better still, several were pleasant-smelling, such as minty, raspberry, chocolate, etc., increasing their value for practical use in mosquito control.

Confident that they were on the right track, the researchers then zeroed in on two compounds: ethyl pyruvate, a fruity-scented cpA inhibitor approved as a flavor agent in food and cyclopentanone, a minty-smelling cpA activator approved as a flavor and fragrance agent. By inhibiting the cpA neuron, ethyl pyruvate was found in their experiments to substantially reduce the mosquito's attraction towards a human arm. By activating the cpA neuron, cyclopentanone served as a powerful lure, like CO2, attracting mosquitoes to a trap.

"Such compounds can play a significant role in the control of mosquito-borne diseases and open up very realistic possibilities of developing ways to use simple, natural, affordable and pleasant odors to prevent mosquitoes from finding humans," Ray said. "Odors that block this dual-receptor for CO2 and skin odor can be used as a way to mask us from mosquitoes. On the other hand, odors that can act as attractants can be used to lure mosquitoes away from us into traps. These potentially affordable 'mask' and 'pull' strategies could be used in a complementary manner, offering an ideal solution and much needed relief to people in Africa, Asia and South America – indeed wherever mosquito-borne diseases are endemic. Further, these compounds could be developed into products that protect not just one individual at a time but larger areas, and need not have to be directly applied on the skin."

Currently, CO2 is the primary lure in mosquito traps. Generating CO2 requires burning fuel, evaporating dry ice, releasing compressed gas or fermentation of sugar – all of which is expensive, cumbersome, and impractical for use in developing countries. Compounds identified in this study, like cyclopentanone, offer a safe, affordable and convenient alternative that can finally work with surveillance and control traps.

Ray was joined in the study by the three UCR co-first authors Genevieve M. Tauxe, Dyan MacWilliam and Sean Michael Boyle and Tom Guda. Boyle is now a postdoctoral researcher at Stanford University.

The team tested the efficacy of ethyl pyruvate in the lab on Aedes aegypti using an arm-in-cage set-up (the experimenter's hand was gloved and not exposed to mosquito bites or the test chemicals). The researchers tested the efficacy of cyclopentanone as a lure on C. quinquefasciatus, the mosquito that spreads West Nile virus and filariasis, using traps in a modified greenhouse at UC Riverside.


Mosquitoes are not naturally infected with disease agents. They must be acquired by feeding on infected individuals before they can pass them to healthy ones. For example, a person bitten by Anopheles quadrimaculatus, a potential vector of malaria, does not mean that he or she will contract malaria unless the mosquito had first fed on an individual suffering from the parasite. This is unlikely to occur in Kentucky.

West Nile virus (WNV) is one of the most common arthropod-borne viruses (arboviruses) in the U.S. It is maintained and transmitted among birds, primarily by Culex mosquitoes. A person can become ill if they are bitten by an infected mosquito. Infected individuals may experience an abrupt onset of fever, nausea, vomiting, and severe headaches. These symptoms usually develop within 5 to 7 days after someone is bitten. People of any age may contract the disease. However, disease incidence is greater and symptoms more severe in people 60 years or older. Mortality rates range from 2 to 20 percent, with the highest mortality occurring in the oldest age groups.


WNV normally cycles between house mosquitoes and birds.
Mosquitoes can pass the virus to people, horses and other mammals. (www.cdc.gov)

Humans become infected with West Nile virus only after being bitten by a mosquito that had formerly contracted the pathogen from an infected bird. There is no person-to-person transmission via mosquitoes, because the virus concentration in human blood never reaches a sufficient level to infect biting mosquitoes. Humans and horses are considered to be “accidental” or “dead end” hosts for this disease. This means that the amount of virus in their blood is too low for mosquitoes that feed on them to become infected. Disease outbreaks are most likely to occur from mid-summer through early fall when Culex populations are at their peak.

Dog heartworm is caused by a filarial worm, Dirofilaria immitis. It is a serious disease for most dog breeds. Several mosquito species can transmit this parasite. A mosquito can ingest immature stages of the worms, called microfilariae. After several days, the infected larvae are transmitted via the mosquito's mouthparts to a healthy dog when the mosquito feeds again. The larvae grow and eventually migrate to the right ventricle of the dog's heart where they mature and reproduce. The adult female worm can grow to approximately 11 inches and the male 6 inches.


Large numbers of adult dog heartworms can develop in the host dog.


Ecology: A world without mosquitoes

Eradicating any organism would have serious consequences for ecosystems — wouldn't it? Not when it comes to mosquitoes, finds Janet Fang.

Every day, Jittawadee Murphy unlocks a hot, padlocked room at the Walter Reed Army Institute of Research in Silver Spring, Maryland, to a swarm of malaria-carrying mosquitoes (Anopheles stephensi). She gives millions of larvae a diet of ground-up fish food, and offers the gravid females blood to suck from the bellies of unconscious mice — they drain 24 of the rodents a month. Murphy has been studying mosquitoes for 20 years, working on ways to limit the spread of the parasites they carry. Still, she says, she would rather they were wiped off the Earth.

That sentiment is widely shared. Malaria infects some 247 million people worldwide each year, and kills nearly one million. Mosquitoes cause a huge further medical and financial burden by spreading yellow fever, dengue fever, Japanese encephalitis, Rift Valley fever, Chikungunya virus and West Nile virus. Then there's the pest factor: they form swarms thick enough to asphyxiate caribou in Alaska and now, as their numbers reach a seasonal peak, their proboscises are plunged into human flesh across the Northern Hemisphere.

So what would happen if there were none? Would anyone or anything miss them? Nature put this question to scientists who explore aspects of mosquito biology and ecology, and unearthed some surprising answers.

There are 3,500 named species of mosquito, of which only a couple of hundred bite or bother humans. They live on almost every continent and habitat, and serve important functions in numerous ecosystems. "Mosquitoes have been on Earth for more than 100 million years," says Murphy, "and they have co-evolved with so many species along the way." Wiping out a species of mosquito could leave a predator without prey, or a plant without a pollinator. And exploring a world without mosquitoes is more than an exercise in imagination: intense efforts are under way to develop methods that might rid the world of the most pernicious, disease-carrying species (see 'War against the winged').

Yet in many cases, scientists acknowledge that the ecological scar left by a missing mosquito would heal quickly as the niche was filled by other organisms. Life would continue as before — or even better. When it comes to the major disease vectors, "it's difficult to see what the downside would be to removal, except for collateral damage", says insect ecologist Steven Juliano, of Illinois State University in Normal. A world without mosquitoes would be "more secure for us", says medical entomologist Carlos Brisola Marcondes from the Federal University of Santa Catarina in Brazil. "The elimination of Anopheles would be very significant for mankind."

Elimination of mosquitoes might make the biggest ecological difference in the Arctic tundra, home to mosquito species including Aedes impiger and Aedes nigripes. Eggs laid by the insects hatch the next year after the snow melts, and development to adults takes only 3–4 weeks. From northern Canada to Russia, there is a brief period in which they are extraordinarily abundant, in some areas forming thick clouds. "That's an exceptionally rare situation worldwide," says entomologist Daniel Strickman, programme leader for medical and urban entomology at the US Department of Agriculture in Beltsville, Maryland. "There is no other place in the world where they are that much biomass."

“If there was a benefit to having them around, we would have found a way to exploit them. We haven't wanted anything from mosquitoes except for them to go away. , ”

Views differ on what would happen if that biomass vanished. Bruce Harrison, an entomologist at the North Carolina Department of Environment and Natural Resources in Winston-Salem estimates that the number of migratory birds that nest in the tundra could drop by more than 50% without mosquitoes to eat. Other researchers disagree. Cathy Curby, a wildlife biologist at the US Fish and Wildlife Service in Fairbanks, Alaska, says that Arctic mosquitoes don't show up in bird stomach samples in high numbers, and that midges are a more important source of food. "We (as humans) may overestimate the number of mosquitoes in the Arctic because they are selectively attracted to us," she says.

Mosquitoes consume up to 300 millilitres of blood a day from each animal in a caribou herd, which are thought to select paths facing into the wind to escape the swarm. A small change in path can have major consequences in an Arctic valley through which thousands of caribou migrate, trampling the ground, eating lichens, transporting nutrients, feeding wolves, and generally altering the ecology. Taken all together, then, mosquitoes would be missed in the Arctic — but is the same true elsewhere?

"Mosquitoes are delectable things to eat and they're easy to catch," says aquatic entomologist Richard Merritt, at Michigan State University in East Lansing. In the absence of their larvae, hundreds of species of fish would have to change their diet to survive. "This may sound simple, but traits such as feeding behaviour are deeply imprinted, genetically, in those fish," says Harrison. The mosquitofish (Gambusia affinis), for example, is a specialized predator — so effective at killing mosquitoes that it is stocked in rice fields and swimming pools as pest control — that could go extinct. And the loss of these or other fish could have major effects up and down the food chain.

Many species of insect, spider, salamander, lizard and frog would also lose a primary food source. In one study published last month, researchers tracked insect-eating house martins at a park in Camargue, France, after the area was sprayed with a microbial mosquito-control agent 1 . They found that the birds produced on average two chicks per nest after spraying, compared with three for birds at control sites.

Most mosquito-eating birds would probably switch to other insects that, post-mosquitoes, might emerge in large numbers to take their place. Other insectivores might not miss them at all: bats feed mostly on moths, and less than 2% of their gut content is mosquitoes. "If you're expending energy," says medical entomologist Janet McAllister of the Centers for Disease Control and Prevention in Fort Collins, Colorado, "are you going to eat the 22-ounce filet-mignon moth or the 6-ounce hamburger mosquito?"

With many options on the menu, it seems that most insect-eaters would not go hungry in a mosquito-free world. There is not enough evidence of ecosystem disruption here to give the eradicators pause for thought.

As larvae, mosquitoes make up substantial biomass in aquatic ecosystems globally. They abound in bodies of water ranging from ephemeral ponds to tree holes 2 to old tyres, and the density of larvae on flooded plains can be so high that their writhing sends out ripples across the surface. They feed on decaying leaves, organic detritus and microorganisms. The question is whether, without mosquitoes, other filter feeders would step in. "Lots of organisms process detritus. Mosquitoes aren't the only ones involved or the most important," says Juliano. "If you pop one rivet out of an airplane's wing, it's unlikely that the plane will cease to fly."

The effects might depend on the body of water in question. Mosquito larvae are important members of the tight-knit communities in the 25–100-millilitre pools inside pitcher plants 3 , 4 (Sarracenia purpurea) on the east coast of North America. Species of mosquito (Wyeomyia smithii) and midge (Metriocnemus knabi) are the only insects that live there, along with microorganisms such as rotifers, bacteria and protozoa. When other insects drown in the water, the midges chew up their carcasses and the mosquito larvae feed on the waste products, making nutrients such as nitrogen available for the plant. In this case, eliminating mosquitoes might affect plant growth.

In 1974, ecologist John Addicott, now at the University of Calgary in Alberta, Canada, published findings on the predator and prey structure within pitcher plants, noting more protozoan diversity in the presence of mosquito larvae 5 . He proposed that as the larvae feed, they keep down the numbers of the dominant species of protozoa, letting others persist. The broader consequences for the plant are not known.

A stronger argument for keeping mosquitoes might be found if they provide 'ecosystem services' — the benefits that humans derive from nature. Evolutionary ecologist Dina Fonseca at Rutgers University in New Brunswick, New Jersey, points as a comparison to the biting midges of the family Ceratopogonidae, sometimes known as no-see-ums. "People being bitten by no-see-ums or being infected through them with viruses, protozoa and filarial worms would love to eradicate them," she says. But because some ceratopogonids are pollinators of tropical crops such as cacao, "that would result in a world without chocolate".

Without mosquitoes, thousands of plant species would lose a group of pollinators. Adults depend on nectar for energy (only females of some species need a meal of blood to get the proteins necessary to lay eggs). Yet McAllister says that their pollination isn't crucial for crops on which humans depend. "If there was a benefit to having them around, we would have found a way to exploit them," she says. "We haven't wanted anything from mosquitoes except for them to go away."

Ultimately, there seem to be few things that mosquitoes do that other organisms can't do just as well — except perhaps for one. They are lethally efficient at sucking blood from one individual and mainlining it into another, providing an ideal route for the spread of pathogenic microbes.

"The ecological effect of eliminating harmful mosquitoes is that you have more people. That's the consequence," says Strickman. Many lives would be saved many more would no longer be sapped by disease. Countries freed of their high malaria burden, for example in sub-Saharan Africa, might recover the 1.3% of growth in gross domestic product that the World Health Organization estimates they are cost by the disease each year, potentially accelerating their development. There would be "less burden on the health system and hospitals, redirection of public-health expenditure for vector-borne diseases control to other priority health issues, less absenteeism from schools", says Jeffrey Hii, malaria scientist for the World Health Organization in Manila.

Phil Lounibos, an ecologist at the Florida Medical Entomology Laboratory in Vero Beach says that "eliminating mosquitoes would temporarily relieve human suffering". His work suggests that efforts to eradicate one vector species would be futile, as its niche would quickly be filled by another. His team collected female yellow-fever mosquitoes (Aedes aegypti) from scrap yards in Florida, and found that some had been inseminated by Asian tiger mosquitoes (Aedes albopictus), which carry multiple human diseases. The insemination sterilizes the female yellow-fever mosquitoes — showing how one insect can overtake another.

Given the huge humanitarian and economic consequences of mosquito-spread disease, few scientists would suggest that the costs of an increased human population would outweigh the benefits of a healthier one. And the 'collateral damage' felt elsewhere in ecosystems doesn't buy much sympathy either. The romantic notion of every creature having a vital place in nature may not be enough to plead the mosquito's case. It is the limitations of mosquito-killing methods, not the limitations of intent, that make a world without mosquitoes unlikely.

And so, while humans inadvertently drive beneficial species, from tuna to corals, to the edge of extinction, their best efforts can't seriously threaten an insect with few redeeming features. "They don't occupy an unassailable niche in the environment," says entomologist Joe Conlon, of the American Mosquito Control Association in Jacksonville, Florida. "If we eradicated them tomorrow, the ecosystems where they are active will hiccup and then get on with life. Something better or worse would take over."


Mosquitoes that can carry malaria eliminated in lab experiments

Mosquito that causes malaria, Anopheles gambiae . Credit: NIAID, CC BY

The team from Imperial College London were able to crash caged populations of the malaria vector mosquito Anopheles gambiae in only 7-11 generations.

This is the first time experiments have been able to completely block the reproductive capacity of a complex organism in the laboratory using a designer molecular approach.

The technique, called gene drive, was used to selectively target the specific mosquito species An. gambiae that is responsible for malaria transmission in sub-Saharan Africa. There are around 3500 species of mosquito worldwide, of which only 40 related species can carry malaria.

The hope is that mosquitoes carrying a gene drive would be released in the future, spreading female infertility within local malaria-carrying mosquito populations and causing them to collapse.

In 2016, there were around 216 million malaria cases and an estimated 445,000 deaths worldwide, mostly of children under five years old.

Lead researcher Professor Andrea Crisanti, from the Department of Life Sciences at Imperial, said: "2016 marked the first time in over two decades that malaria cases did not fall year-on-year despite huge efforts and resources, suggesting we need more tools in the fight."

The team's results, published today in Nature Biotechnology, represent the first time gene drive has been able to completely suppress a population, overcoming resistance issues previous approaches have faced.

Professor Crisanti added: "This breakthrough shows that gene drive can work, providing hope in the fight against a disease that has plagued mankind for centuries. There is still more work to be done, both in terms of testing the technology in larger lab-based studies and working with affected countries to assess the feasibility of such an intervention.

"It will still be at least 5-10 years before we consider testing any mosquitoes with gene drive in the wild, but now we have some encouraging proof that we're on the right path. Gene drive solutions have the potential one day to expedite malaria eradication by overcoming the barriers of logistics in resource-poor countries."

The team targeted a gene in An. gambiae called doublesex, which determines whether an individual mosquito develops as a male or as a female.

The team engineered a gene drive solution designed to selectively alter a region of the doublesex gene that is responsible for female development. Males who carried this modified gene showed no changes, and neither did females with only one copy of the modified gene. However, females with two copies of the modified gene showed both male and female characteristics, failed to bite and did not lay eggs.

Their experiments showed that the gene drive transmitted the genetic modification nearly 100% of the time. After eight generations no females were produced and the populations collapsed because of lack of offspring.

Previous attempts to develop gene drive for population suppression have encountered 'resistance', where targeted genes developed mutations that allowed the gene to carry out its function, but that that were resistant to the drive. These changes would then be passed down to the offspring, halting the gene drive in its tracks.

One of the reasons doublesex was picked for the gene drive target was that it was thought not to tolerate any mutations, overcoming this potential source of resistance. Indeed, in the study no functional mutated copy of the doublesex gene arose and spread in the population.

While this is the first time resistance has been overcome, the team say additional experiments are needed to investigate the efficacy and the stability of the gene drive under confined laboratory settings that mimic tropical environments.

This involves testing the technology on larger populations of mosquitoes confined in more realistic settings, where competition for food and other ecological factors may change the fate of the gene drive.

The doublesex gene targeted in the study is similar across the insect world, although different insects have different exact genetic sequences. This suggests the technology could be used in the future to specifically target other disease-carrying insects.

Recent work from Imperial showed that suppressing An. gambiae populations in local areas is unlikely to affect the local ecosystem.


Mosquitoes Are Drawn to Flowers As Much as People — Now Scientists Finally Know Why

Without their keen sense of smell, mosquitoes wouldn’t get very far. They rely on this sense to find a host to bite and spots to lay eggs.

And without that sense of smell, mosquitoes could not locate their dominant source of food: nectar from flowers.

“Nectar is an important source of food for all mosquitoes,” said Jeffrey Riffell, a professor of biology at the University of Washington. “For male mosquitoes, nectar is their only food source, and female mosquitoes feed on nectar for all but a few days of their lives.”

Aedes mosquitoes feeding from Platanthera flowers. Credit: Kiley Riffell

Yet scientists know little about the scents that draw mosquitoes toward certain flowers, or repel them from others. This information could help develop less toxic and better repellents, more effective traps and understand how the mosquito brain responds to sensory information — including the cues that, on occasion, lead a female mosquito to bite one of us.

Riffell’s team, which includes researchers at the UW, Virginia Tech and UC San Diego, has discovered the chemical cues that lead mosquitoes to pollinate a particularly irresistible species of orchid. As they report in a paper published online on December 23, 2019, in the Proceedings of the National Academy of Sciences, the orchid produces a finely balanced bouquet of chemical compounds that stimulate mosquitoes’ sense of smell. On their own, some of these chemicals have either attractive or repressive effects on the mosquito brain. When combined in the same ratio as they’re found in the orchid, they draw in mosquitoes as effectively as a real flower. Riffell’s team also showed that one of the scent chemicals that repels mosquitoes lights up the same region of the mosquito brain as DEET, a common and controversial mosquito repellant.

Their findings show how environmental cues from flowers can stimulate the mosquito brain as much as a warm-blooded host — and can draw the mosquito toward a target or send it flying the other direction, said Riffell, who is the senior author of the study.

The researchers used bags placed over the orchids to collect samples of their scents in the field. Credit: Kiley Riffell

The blunt-leaf orchid, or Platanthera obtusata, grows in cool, high-latitude climates across the Northern Hemisphere. From field stations in the Okanogan-Wenatchee National Forest in Washington state, Riffell’s team verified past research showing that local mosquitoes pollinate this species, but not its close relatives that grow in the same habitat. When researchers covered the flowers with bags — depriving the mosquitoes of a visual cue for the flower — the mosquitoes would still land on the bagged flowers and attempt to feed through the canvas.

Orchid scent obviously attracted the mosquitoes. To find out why, Riffell’s team turned to the individual chemicals that make up the blunt-leaf orchid’s scent.

“We often describe ‘scent’ as if it’s one thing — like the scent of a flower, or the scent of a person,” said Riffell. “Scent is actually a complex combination of chemicals — the scent of a rose consists of more than 300 — and mosquitoes can detect the individual types of chemicals that make up a scent.”

Riffell describes the blunt-leaf orchid’s scent as a grassy or musky odor, while its close relatives have a sweeter fragrance. The team used gas chromatography and mass spectroscopy to identify dozens of chemicals in the scents of the Platanthera species. Compared to its relatives, the blunt-leaf orchid’s scent contained high amounts of a compound called nonanal, and smaller amounts of another chemical, lilac aldehyde.

Using a gas chromatogram to separate the individual chemicals that make up a flower’s scent while simultaneously recording electrical activity from a mosquito’s antenna to see which chemicals stimulate the mosquito’s antenna. Credit: Kiley Riffell

Riffell’s team also recorded the electrical activity in mosquito antennae, which detect scents. Both nonanal and lilac aldehyde stimulated antennae of mosquitoes that are native to the blunt-leaf orchid’s habitat. But these compounds also stimulated the antennae of mosquitoes from other regions, including Anopheles stephensi, which spreads malaria, and Aedes aegypti, which spreads dengue, yellow fever, Zika and other diseases.

Experiments of mosquito behavior showed that both native and non-native mosquitoes preferred a solution of nonanal and lilac aldehyde mixed in the same ratio as found in blunt-leaf flowers. If the researchers omitted lilac aldehyde from the recipe, mosquitoes lost interest. If they added more lilac aldehyde — at levels found in the blunt-leaf orchid’s close relatives — mosquitoes were indifferent or repelled by the scent.

Using techniques developed in Riffell’s lab, they also peered directly into the brains of Aedes increpitus mosquitoes, which overlap with blunt-leaf orchids, and a genetically modified strain of Aedes aegypti previously developed by Riffell and co-author Omar Akbari, an associate professor at UC San Diego. They imaged calcium ions — signatures of actively firing neurons — in the antenna lobe, the region of the mosquito brain that processes signals from the antennae.

A mosquito tethered to the underside of a microscope stage for calcium imaging of its antenna lobe. Credit: Kiley Riffell

These brain imaging experiments revealed that nonanal and lilac aldehyde stimulate different parts of the antenna lobe — and even compete with one another when stimulated: The region that responds to nonanal can suppress activity in the region that responds to lilac aldehyde, and vice versa. Whether this “cross talk” makes a flower attractive or repelling to the mosquito likely depends on the amounts of nonanal and lilac aldehyde in the original scent. Blunt-leaf orchids have a ratio that attracts mosquitoes, while closely related species do not, according to Riffell.

“Mosquitoes are processing the ratio of chemicals, not just the presence or absence of them,” said Riffell. “This isn’t just important for flower discrimination — it’s also important for how mosquitoes discern between you and I. Human scent is very complex, and what is probably important for attracting or repelling mosquitoes is the ratio of particular chemicals. We know that some people get bit more than others, and maybe a difference in ratio explains why.”

The team also discovered that lilac aldehyde stimulates the same region of the antenna lobe as DEET. That region may process “repressive” scents, though further research would need to verify this, said Riffell. It’s too soon to tell if lilac aldehyde may someday be an effective mosquito repellant. But if it is, there is an added bonus.

“It smells wonderful,” said Riffell.

Reference: “The olfactory basis of orchid pollination by mosquitoes” by Chloé Lahondère, Clément Vinauger, Ryo P. Okubo, Gabriella H. Wolff, Jeremy K. Chan, Omar S. Akbari and Jeffrey A. Riffell, 23 December 2019, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.1910589117

Lead author is Chloé Lahondère, who conducted the research as a UW postdoctoral fellow and is now a research assistant professor at Virginia Tech. Additional co-authors are Clément Vinauger, a former UW postdoctoral researcher and current assistant professor at Virginia Tech UW biology graduate students Ryo Okubo and Jeremy Chan and UW postdoctoral researcher Gabriella Wolff. The research was funded by the National Institutes of Health, the Air Force Office of Scientific Research and the University of Washington.


HOUSE MOUSE

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Identification and Range
: The house mouse (Mus musculus) is a small, slender rodent that has a slightly pointed nose small, black, somewhat protruding eyes large, scantily haired ears, and a nearly hairless tail with obvious scale rings. The adult mouse weighs about 2/5 to 4/5 ounces. They are generally grayish-brown with a gray or buff belly. Similar mice include the white-footed mice and jumping mice( which have a white belly), and harvest mice (which have grooved upper incisor teeth.) Native to central Asia, this species arrived in North America along with settlers from Europe and other points of origin. A very adaptable species, the house mouse often lives in close association with humans and therefore is termed one of the "commensal" rodents along with Norway and roof rats. Following their arrival on colonists’ ships, house mice spread across North America and now are found in every state including coastal areas of Alaska, and in the southern parts of Canada.
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Habitat: House mice live in and around homes, farms, commercial establishments, as well as in open fields and agricultural lands. The onset of cold weather each fall in temperate regions is said to cause mice to move into structures in search of shelter and food.
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Food Habits: House mice eat many types of food but prefer seeds and grain. They are not hesitant to sample new foods and are considered "nibblers," sampling many kinds of items that may exist in their environment. Foods high in fat, protein, or sugar may be preferred even when grain and seed also are present. Such items include bacon, chocolate candies, butter and nutmeats. A single mouse eats only about 3 grams of food per day (8 pounds per year) but because of their habit of nibbling on many foods and discarding partially eaten items, mice destroy considerably more food than they consume. Unlike Norway and roof rats, they can get by with little or no free water, although they readily drink water when it is available. They obtain their water needs from the food they eat. An absence of liquid water or food of adequate moisture content in their environment may reduce their breeding potential.
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General Biology, Reproduction, and Behavior: House mice are mainly nocturnal, although at some locations considerable daytime activity may be seen. Seeing mice during daylight hours does not necessarily mean there is a high population present, although this usually is true for rats Mice have poor eyesight, relying more on their hearing and their excellent senses of smell, taste and touch. They are considered essentially colorblind.

House mice can dig and may burrow into the ground in fields or around structures when other shelter is not readily available. Nesting may occur here or in any sheltered location. Nests are constructed of fibrous materials and generally have the appearance of a "ball" of material loosely woven together. These nests are usually 4 to 6 inches in diameter. Litters of 5 or 6 young are born 19 to 21 days after mating, although females that conceive while still nursing may have a slightly longer gestation period. Newborn mice are naked and their eyes are closed. They grow rapidly and after 2 w3eeks they are covered with hair and their eyes and ears are open. They begin to make short excursions from the nest and eat solid food at 3 weeks. Weaning soon follows, and mice are sexually mature as early as 6 to 10 weeks old.

Mice may breed year-round and a female may have 5 to 10 litters per year. Mouse populations can therefore grow rapidly under good conditions, although breeding and survival of young slow markedly when population densities become high.

During its daily activities, a mouse normally travels an area averaging 10 to 30 feet in diameter, seldom traveling further than this to obtain food or water. Mice constantly explore and learn about their environment, memorizing the locations of pathways, obstacles, food and water, shelter and other elements in their domain. They quickly detect new objects in their environment, but they do not fear novel objects as do rats. This behavior should be remembered if faced with a large population of mice in a residential, industrial or agricultural setting. Proper placements of mouse bait is a must if you are to have a successful baiting program.
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Acknowledgements

We would like to acknowledge the use of the University of Oxford Advanced Research Computing (ARC) facility in carrying out this work (http://dx.doi.org/10.5281/zenodo.22558).

Funding

The authors are supported by a grant from the Bill & Melinda Gates Foundation.

Availability of data and materials

Settlement data collected by the United Nations Office for the Coordination of Human Affairs (OCHA [57]), inland water data extracted from the digital chart of the world (DCW [58]), and rainfall data from the “ERA-interim reanalysis” (available from the European Centre for Medium-Range Weather Forecasts [59]).


Lipid availability determines fate of skeletal progenitor cells via SOX9

The avascular nature of cartilage makes it a unique tissue 1-4 , but whether and how the absence of nutrient supply regulates chondrogenesis remain unknown. Here we show that obstruction of vascular invasion during bone healing favours chondrogenic over osteogenic differentiation of skeletal progenitor cells. Unexpectedly, this process is driven by a decreased availability of extracellular lipids. When lipids are scarce, skeletal progenitors activate forkhead box O (FOXO) transcription factors, which bind to the Sox9 promoter and increase its expression. Besides initiating chondrogenesis, SOX9 acts as a regulator of cellular metabolism by suppressing oxidation of fatty acids, and thus adapts the cells to an avascular life. Our results define lipid scarcity as an important determinant of chondrogenic commitment, reveal a role for FOXO transcription factors during lipid starvation, and identify SOX9 as a critical metabolic mediator. These data highlight the importance of the nutritional microenvironment in the specification of skeletal cell fate.

Conflict of interest statement

The authors declare no competing interests.

Figures

Extended Data Figure 1. Removal of periosteum…

Extended Data Figure 1. Removal of periosteum reduces bone formation and callus vascularization

Extended Data Figure 2. Reducing vascularization alters…

Extended Data Figure 2. Reducing vascularization alters but does not prevent bone healing

Extended Data Figure 3. In silico modelling…

Extended Data Figure 3. In silico modelling supports a role for nutritional stress in chondrogenic…

Extended Data Figure 4. Skeletal progenitors resist…

Extended Data Figure 4. Skeletal progenitors resist nutritional stress via induction of SOX9

Extended Data Figure 5. Reduced lipid availability…

Extended Data Figure 5. Reduced lipid availability favours chondrogenesis over osteogenesis

Extended Data Figure 6. Chondrocytes do not…

Extended Data Figure 6. Chondrocytes do not depend on FAO

( a ) Quantification of…

Extended Data Figure 7. Changes in FAO…

Extended Data Figure 7. Changes in FAO and autophagy after lipid deprivation

Extended Data Figure 8. Lipids regulate SOX9…

Extended Data Figure 8. Lipids regulate SOX9 through FoxO signalling

Extended Data Figure 9. Flow cytometry gating…

Extended Data Figure 9. Flow cytometry gating for cell sorting

Figure 1. Preventing vascular ingrowth during bone…

Figure 1. Preventing vascular ingrowth during bone healing induces chondrogenesis


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