Could this spell the end for mosquitos?
Researchers have used CRISPR/Cas9 gene editing to target a specific gene tied to fertility in male mosquitoes.
The researchers were then able to discern how this mutation can suppress the fertility of female mosquitoes.
Mosquitoes are one of humanity's greatest nemeses, estimated to spread infections to nearly 700 million people per year and cause more than one million deaths.
As reported in the Proceedings of the National Academy of Sciences, the discovery represents a breakthrough in one technique for controlling populations of Aedes aegypti, a mosquito that transmits dengue, yellow fever, Zika, and other viruses.
Craig Montell, professor of molecular, cellular, and developmental biology at the University of California, Santa Barbara, and coauthors were working to improve a vector-control practice called the sterile insect technique (SIT). To manage populations, scientists raise a lot of sterile male insects. They then release these males in numbers that overwhelm their wild counterparts.
The idea is that 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. What's more, because each generation is smaller than the last, releasing a similar number of sterile males has a stronger effect over time.
CRISPR IS A BETTER ALTERNATIVE TO CHEMICALS
SIT has proven effective in managing a number of agricultural pests, including the medfly (Mediterranean fruit fly), a major pest in California. It has also been attempted with A. aegypti mosquitoes, which originated in Africa, but have since become invasive across many parts of the world, due in no small part to climate change and global travel.
In the past, scientists used chemicals or radiation to sterilize male A. aegypti.
"There are enough genes that affect fertility that just a random approach of blasting a large number of genes will cause the males to be infertile," says Montell. However, the chemicals or radiation affected the animals' health to such an extent that they were less successful in mating with females, which undercuts the effectiveness of the sterile insect technique.
Montell figured there had to be a more targeted approach with less collateral damage. He and his colleagues, including co-first authors Jieyan Chen and Junjie Luo, set out to mutate a gene in mosquitoes that specifically caused male sterility without otherwise affecting the insects' health. The best candidate they found was b2-tubulin (B2t); mutation of the related B2t gene in fruit flies is known to cause male sterility.
Using CRISPR/Cas9, the researchers knocked out B2t in male A. aegypti. They found that the mutant males produced no sperm, but unlike in previous efforts, the sterile studs were otherwise completely healthy. There was some debate over whether sperm—albeit defective sperm from the sterile males—was needed to render female mosquitoes infertile, or whether transfer of seminal fluid was all it took.
In one experiment, the researchers introduced 15 mutant males into a group of 15 females for 24 hours. Then they swapped the B2t males for 15 wild-type males, and left them there. "Essentially, all of the females remained sterile," Montell says. This confirmed that B2t males could suppress female fertility without producing sperm.
"THERE IS A PANDEMIC EVERY YEAR FROM MOSQUITO-BORNE DISEASES."
Next the team 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 notes that females copulated twice on average even during the first 10 minutes. This indicated to him that females have to mate with many sterile males before being rendered infertile themselves.
Combining the females with the B2t males for four hours cut female fertility to 20% of normal levels. After eight hours the numbers began leveling out around 10%.
MOSQUITO MATING BEHAVIORS
With the insights from the time trials, the team sought to approximate SIT under more natural conditions. They added different ratios of B2t and wild-type males at the same time to a population of 15 females for one week, and recorded female fertility. A ratio of about 5 or 6 sterile males to one wild-type male reduced female fertility by half. A ratio of 15 to 1 suppressed fertility to about 20%, where it leveled off.
Now, Aedes aegypti populations could easily bounce back from an 80% drop in fertility, Montell says. The success of SIT 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.
Montell plans to continue investigating mosquito mating behaviors and fertility. They are devising a way to maintain stocks of B2t 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," says Montell, who has conducted a lot of research using fruit flies in the past. "There is a pandemic every year from mosquito-borne diseases."
"When CRISPR/Cas9 came out several years ago it just offered new opportunities to do things that you couldn't do before. So, the time seemed right to for us to start working on Aedes aegypti."
A newly discovered coronavirus — but not the one that causes COVID-19 — has made some dogs very sick.
- A different coronavirus outbreak in late 2019 made many dogs in the UK very ill.
- The strangeness of the disease led veterinarians to send questionnaires to their peers and pet owners.
- The findings point toward the need for better systems to identify disease outbreaks in animals.
A recent study suggests that a mysterious disease plaguing dogs in the UK is caused by a novel coronavirus. This virus, which coincidentally appeared in late 2019 and began to concern veterinarians in early 2020, is not related to the virus which causes COVID-19, but can make your four-legged friend feel quite ill.
Novel coronavirus in dogs
The term "coronavirus" doesn't refer to a single disease, but a family of viruses (more formally, Coronaviridae) that share a shape similar to a crown (hence the name, "corona"). They infect many different kinds of animals and cause various diseases from COVID-19 and SARS to the common cold.
This new coronavirus, a variant of canine enteric coronavirus, was first noticed in January 2020 when a veterinarian in the United Kingdom treated "an unusually high number" of dogs with severe vomiting and other gastrointestinal issues at his office. Concerned about this spike in doggy indigestion, they reached out to other veterinarians to see if they were reporting a similar outbreak.
Online questionnaires were sent out to more than a thousand vets and pet owners to map the outbreak and collect information on which animals were being affected. Analysis of this data showed that nearly all of the cases involved vomiting and a loss of appetite, and half of them also involved diarrhea. Most of the cases took place in south and northwest England, though a large outbreak also occurred in and around the Scottish city of Edinburgh.
The data also suggested that male dogs in contact with other dogs were most likely to be infected, hinting at "either transmission between dogs or a common environmental source." The dogs recovered in more than 99 percent of cases.
Hoping to move beyond the questionnaire, the authors also turned to records to piece together what happened.
While public health data for animals is less frequently gathered than it is for humans, electronic records of pet admissions to veterinarian offices and pet insurance payouts do exist. The researchers accessed these records and found that the number of dogs recorded with stomach problems rose between December 2019 and March 2020, with nearly double the number of expected cases occurring during that time. There was also a concomitant rise in prescriptions for drugs to treat those conditions.
A later comparison of samples from dogs that were sick and healthy control dogs confirmed the presence of the novel coronavirus in the ill dogs. All of this was later compiled into a study that was recently published in Emerging Infectious Diseases, which is produced by the CDC.
Should I be concerned?
This coronavirus only affects dogs, and the researchers didn't find anything to suggest that humans could become infected.
However, the scale of the outbreak and the lack of tools immediately available to determine what was happening led the researchers to suggest that better organization is needed. Many of the authors are involved in creating a disease surveillance system for dogs, known as SAVSNet-Agile.
The authors also mention that "previous CeCoV [canine enteric coronavirus] seasonality suggests further outbreaks may occur." Thanks to this study, your local vet might be a little more prepared for it next time.
Scientists are using bioelectronic medicine to treat inflammatory diseases, an approach that capitalizes on the ancient "hardwiring" of the nervous system.
- Bioelectronic medicine is an emerging field that focuses on manipulating the nervous system to treat diseases.
- Clinical studies show that using electronic devices to stimulate the vagus nerve is effective at treating inflammatory diseases like rheumatoid arthritis.
- Although it's not yet approved by the US Food and Drug Administration, vagus nerve stimulation may also prove effective at treating other diseases like cancer, diabetes and depression.
Could a tiny electronic device treat some diseases more safely and effectively than pharmaceutical medicines?
For Kelly Owens, the answer was clear. She spent more than a decade suffering from Crohn's disease, a chronic inflammatory bowel disease that left her with severe arthritis in her joints. The pain forced her to use a cane, sometimes a wheelchair. She tried more than 20 medications and racked up more than $1 million in medical bills, but her condition didn't improve.
A physician told Owens and her husband that they shouldn't have children, and that she'd have to take steroids for life.
Then Owens turned to bioelectronic medicine. She reached out to Dr. Kevin Tracey, a pioneer in the field and president and CEO of the Feinstein Institutes for Medical Research in New York. Soon after, Owens and her husband moved to Amsterdam to participate in a clinical trial involving a relatively new bioelectronic approach to treat inflammation.
Doctors implanted a small electronic device in her chest that stimulated her vagus nerve, the body's longest cranial nerve. After two weeks, Owens didn't need the cane or wheelchair. Soon she was jogging on a treadmill.
A growing body of research within bioelectronic medicine shows it's possible to treat diseases by manipulating the nervous system. The field is essentially a fusion of neuroscience, molecular biology and neurotechnology. Dr. Tracey and his colleagues think the field may someday replace or supplement many pharmaceutical drugs used to treat major diseases, including cancer and Alzheimer's.
But how? The answer centers on how the nervous system controls molecular processes in the body.
...the most revolutionary aspect of bioelectronic medicine, according to Dr. Tracey, is that approaches like vagus nerve stimulation wouldn't come with harmful and potentially deadly side effects, as many pharmaceutical drugs currently do.
The nervous system’s ancient reflexes
You accidentally place your hand on a hot stove. Almost instantaneously, your hand withdraws.
What triggered your hand to move? The answer is not that you consciously decided the stove was hot and you should move your hand. Rather, it was a reflex: Skin receptors on your hand sent nerve impulses to the spinal cord, which ultimately sent back motor neurons that caused your hand to move away. This all occurred before your "conscious brain" realized what happened.
Similarly, the nervous system has reflexes that protect individual cells in the body.
"The nervous system evolved because we need to respond to stimuli in the environment," said Dr. Tracey. "Neural signals don't come from the brain down first. Instead, when something happens in the environment, our peripheral nervous system senses it and sends a signal to the central nervous system, which comprises the brain and spinal cord. And then the nervous system responds to correct the problem."
So, what if scientists could "hack" into the nervous system, manipulating the electrical activity in the nervous system to control molecular processes and produce desirable outcomes? That's the chief goal of bioelectronic medicine.
"There are billions of neurons in the body that interact with almost every cell in the body, and at each of those nerve endings, molecular signals control molecular mechanisms that can be defined and mapped, and potentially put under control," Dr. Tracey said in a TED Talk.
"Many of these mechanisms are also involved in important diseases, like cancer, Alzheimer's, diabetes, hypertension and shock. It's very plausible that finding neural signals to control those mechanisms will hold promises for devices replacing some of today's medication for those diseases."
How can scientists hack the nervous system? For years, researchers in the field of bioelectronic medicine have zeroed in on the longest cranial nerve in the body: the vagus nerve.
What's more, clinical trials show that vagus nerve stimulation not only "shuts off" inflammation, but also triggers the production of cells that promote healing.
The vagus nerve
Electrical signals, seen here in a synapse, travel along the vagus nerve to trigger an inflammatory response.
Credit: Adobe Stock via solvod
The vagus nerve ("vagus" meaning "wandering" in Latin) comprises two nerve branches that stretch from the brainstem down to the chest and abdomen, where nerve fibers connect to organs. Electrical signals constantly travel up and down the vagus nerve, facilitating communication between the brain and other parts of the body.
One aspect of this back-and-forth communication is inflammation. When the immune system detects injury or attack, it automatically triggers an inflammatory response, which helps heal injuries and fend off invaders. But when not deployed properly, inflammation can become excessive, exacerbating the original problem and potentially contributing to diseases.
In 2002, Dr. Tracey and his colleagues discovered that the nervous system plays a key role in monitoring and modifying inflammation. This occurs through a process called the inflammatory reflex. In simple terms, it works like this: When the nervous system detects inflammatory stimuli, it reflexively (and subconsciously) deploys electrical signals through the vagus nerve that trigger anti-inflammatory molecular processes.
In rodent experiments, Dr. Tracey and his colleagues observed that electrical signals traveling through the vagus nerve control TNF, a protein that, in excess, causes inflammation. These electrical signals travel through the vagus nerve to the spleen. There, electrical signals are converted to chemical signals, triggering a molecular process that ultimately makes TNF, which exacerbates conditions like rheumatoid arthritis.
The incredible chain reaction of the inflammatory reflex was observed by Dr. Tracey and his colleagues in greater detail through rodent experiments. When inflammatory stimuli are detected, the nervous system sends electrical signals that travel through the vagus nerve to the spleen. There, the electrical signals are converted to chemical signals, which trigger the spleen to create a white blood cell called a T cell, which then creates a neurotransmitter called acetylcholine. The acetylcholine interacts with macrophages, which are a specific type of white blood cell that creates TNF, a protein that, in excess, causes inflammation. At that point, the acetylcholine triggers the macrophages to stop overproducing TNF – or inflammation.
Experiments showed that when a specific part of the body is inflamed, specific fibers within the vagus nerve start firing. Dr. Tracey and his colleagues were able to map these relationships. More importantly, they were able to stimulate specific parts of the vagus nerve to "shut off" inflammation.
What's more, clinical trials show that vagus nerve stimulation not only "shuts off" inflammation, but also triggers the production of cells that promote healing.
"In animal experiments, we understand how this works," Dr. Tracey said. "And now we have clinical trials showing that the human response is what's predicted by the lab experiments. Many scientific thresholds have been crossed in the clinic and the lab. We're literally at the point of regulatory steps and stages, and then marketing and distribution before this idea takes off."
The future of bioelectronic medicine
Vagus nerve stimulation can already treat Crohn's disease and other inflammatory diseases. In the future, it may also be used to treat cancer, diabetes, and depression.
Credit: Adobe Stock via Maridav
Vagus nerve stimulation is currently awaiting approval by the US Food and Drug Administration, but so far, it's proven safe and effective in clinical trials on humans. Dr. Tracey said vagus nerve stimulation could become a common treatment for a wide range of diseases, including cancer, Alzheimer's, diabetes, hypertension, shock, depression and diabetes.
"To the extent that inflammation is the problem in the disease, then stopping inflammation or suppressing the inflammation with vagus nerve stimulation or bioelectronic approaches will be beneficial and therapeutic," he said.
Receiving vagus nerve stimulation would require having an electronic device, about the size of lima bean, surgically implanted in your neck during a 30-minute procedure. A couple of weeks later, you'd visit, say, your rheumatologist, who would activate the device and determine the right dosage. The stimulation would take a few minutes each day, and it'd likely be unnoticeable.
But the most revolutionary aspect of bioelectronic medicine, according to Dr. Tracey, is that approaches like vagus nerve stimulation wouldn't come with harmful and potentially deadly side effects, as many pharmaceutical drugs currently do.
"A device on a nerve is not going to have systemic side effects on the body like taking a steroid does," Dr. Tracey said. "It's a powerful concept that, frankly, scientists are quite accepting of—it's actually quite amazing. But the idea of adopting this into practice is going to take another 10 or 20 years, because it's hard for physicians, who've spent their lives writing prescriptions for pills or injections, that a computer chip can replace the drug."
But patients could also play a role in advancing bioelectronic medicine.
"There's a huge demand in this patient cohort for something better than they're taking now," Dr. Tracey said. "Patients don't want to take a drug with a black-box warning, costs $100,000 a year and works half the time."
Michael Dowling, president and CEO of Northwell Health, elaborated:
"Why would patients pursue a drug regimen when they could opt for a few electronic pulses? Is it possible that treatments like this, pulses through electronic devices, could replace some drugs in the coming years as preferred treatments? Tracey believes it is, and that is perhaps why the pharmaceutical industry closely follows his work."
Over the long term, bioelectronic approaches are unlikely to completely replace pharmaceutical drugs, but they could replace many, or at least be used as supplemental treatments.
Dr. Tracey is optimistic about the future of the field.
"It's going to spawn a huge new industry that will rival the pharmaceutical industry in the next 50 years," he said. "This is no longer just a startup industry. [...] It's going to be very interesting to see the explosive growth that's going to occur."
From baboon hierarchies to the mind-gut connection, the path to defeating depression starts with understanding its causes.
- According to the World Health Organization, more than 264 million people suffer from depression. It is the leading cause of disability and, at its worst, can lead to suicide. Unfortunately, depression is often misunderstood or ignored until it is too late.
- Psychologist Daniel Goleman, comedian Pete Holmes, neuroscientist Emeran Mayer, psychiatrist Drew Ramsey, and more outline several of the social, chemical, and neurological factors that may contribute to the complex disorder and explain why there is not a singular solution or universal "cure" that can alleviate the symptoms.
- From gaining insight into how the brain-gut connection works and adopting a more Mediterranean diet, to seeking help from medical or spiritual practitioners, depression is a personal battle that requires a personalized strategy to keep it at bay, as well as more research and understanding.
Could we have predicted COVID-19 through social media trends?
- The first human cases of COVID-19 (subsequently named SARS-Cov-2) were first reported by officials in Wuhan City, China, in December 2019. The first cases of the virus in Europe were discovered at the end of January 2020.
- Although there were really no preventative measures that could have completely stopped the pandemic, a new study takes a retrospective look at the months preceding the rapid spread of this virus.
- Researchers suggest that, in a successive phase of the pandemic (or any pandemic), monitoring social media could help public health authorities mitigate the risks of a contagion resurgence.
Although there were really no preventative measures that could have completely stopped the pandemic, a new study takes a retrospective look at the months preceding the rapid spread of this virus. Specifically, this study focused on Twitter to decide if there were 'warning signs' of the upcoming pandemic on social media.
Could social media have predicted the pandemic?
Geo-localization of pneumonia-related tweets posted across Europe since December 2019.
(A) Number of users discussing pneumonia between 15 December 2019 and 21 January 2020, after filtering out press releases and news accounts. (B) Relative variation in number of users discussing pneumonia between winter seasons 2019 and 2020.
Since January 2020, when the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) began to spread from China to Europe and the United States, criticism has intensified over the ways public health authorities across the globe could have better managed the threat.
Throughout this pandemic, different surveillance strategies have been used to monitor the spread of the virus, including sentinel surveillance systems, household surveys, lab-based surveys, community-based surveys, and the Integrated Disease Surveillance and Response (IDSR) framework. More recently, social media outlets have been used for monitoring epidemics and informing the judgments and decisions of public health officials and experts.
A new study conducted by researchers at IMT School for Advanced Studies Lucca analyzed data from Twitter to uncover early warning signs of COVID-19 outbreaks in Europe during the winter season of 2019-2020. On December 31, 2019, WHO (World Health Organization) was informed of the first "cases of pneumonia of unknown etiology." Tracking spikes in pneumonia trends was a big part of this study.
Why focus on pneumonia?
Pneumonia is the most severe condition induced by COVID-19. Additionally, the flu season in 2020 was milder than in previous years, which means there were fewer cases of flu-induced pneumonia.
The study used "pneumonia" as a keyword to track potential COVID-19 induced cases.
The study created a unique database including all public messages posted on Twitter between December 1, 2014 and March 1, 2020. This search included the seven most commonly spoken languages: English, Germany, French, Italian, Spanish, Polish, and Dutch.
There were several adjustments made to avoid overestimations on the number of tweets mentioning cases of pneumonia during this time. Most notably, the study removed the effects on posting activity of COVID-19 related news that appeared up to January 21, 2020 (the day this virus was recognized as a serious transmissible disease), due to the fact that most tweets after this date mentioning pneumonia would be related to the COVID-19 outbreak even if they did not use the word COVID in the tweet.
The analysis shows an increase in tweets mentioning the keyword "pneumonia" in most of the European countries included in the study as early as January 2020.
In Italy, for example, where the first lock-down measures to contain the spread of COVID-19 were introduced on February 22, 2020 - the increase rate in mentions of the keyword during the first weeks of 2020 differs substantially from the rate observed in the same weeks of the previous years.
This could indicate that potentially hidden infection hotspots were identifiable several weeks before the announcement of the first local source of the virus in Italy (which happened on February 20, 2020, in Codogno, Italy.) France exhibited a similar pattern, whereas Spain, Poland, and the U.K. witnessed a delay of two weeks.
The analysis of tweets was then correlated to the regions where the first cases of infections were later reported.
The authors discovered through geo-localization that over 13,000 tweets in this same period came from the regions where the first cases of COVID-19 were later reported.
"Our study adds on to the existing evidence that social media can be a useful tool of epidemiological surveillance. They can help intercept the first signs of a new disease, before it proliferates undetected, and also track its spread," explains Massimo Riccaboni, full professor of Economics at the IMT School, to Eurekalert. Massimo coordinated the large-scale research effort.
How could this help in the future?
Researchers suggest that, in a successive phase of the pandemic (or any pandemic), monitoring social media could help public health authorities mitigate the risks of a contagion resurgence. For example, by adopting stricter measures of social distancing where the infections appear to be increasing. The researchers of the study suggest that these tools could also be a way forward to an integrated epidemiological surveillance system that is globally managed by international health organizations.