Tag: science

750 Million Genetically Modified Mosquitoes Will Be Released in the Florida Keys

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There have been no reports of health or environmental harm in other locations where genetically modified mosquitoes have been introduced over the last decade.

By Lisa Winter

With the aim of reducing rates of the mosquito-borne illnesses yellow fever and dengue, a pilot program will release 750 million genetically modified mosquitoes into the Florida Keys in 2021, thanks to approval by the barrier islands’ Mosquito Control District Board of Commissioners at a meeting on Tuesday (August 18).

The strain of GM mosquitoes, known as OX513A, is an altered form of Aedes aegypti created by UK-based biotech firm Oxitec. Released mosquitoes will be all male, as male mosquitoes do not bite and generally only feed on nectar. Thanks to a conditionally lethal genetic variant, when OX513A mosquitoes mate with wild females, their offspring should die before they are old enough for females to begin biting.

Over the last 10 years, Oxitec deployed these GM mosquitoes in the Cayman Islands and Brazil. This will be the first release of any GM mosquitoes in the US. The Centers for Disease Control and Prevention (CDC) and scientists at the University of Florida will oversee program.

“It’s gone extremely well,” Oxitec scientist Kevin Gorman tells the AP. “We have released over a billion of our mosquitoes over the years. There is no potential for risk to the environment or humans.”

A September 2019 study published in Scientific Reports concluded that female progeny of Oxitec’s GM mosquitoes were not dying off as intended in Brazil. Less than a week after it was published, an editor’s note about criticisms was appended. In May 2020, the paper received a formal Editorial Expression of Concern about the study design and erroneous or misleading claims.

Oxitec’s journey to releasing the mosquitoes in the Florida Keys has been several years in the making. The company commissioned 25 studies to obtain approval from the CDC, the US Environmental Protection Agency (EPA), and seven state and local agencies in Florida, Oxitec reports. The pilot program will target the Florida Keys because A. aegypti mosquitoes are invasive there and are increasingly resistant to insecticides meant to control their numbers, according to reports.

“The science is there. This is something Monroe County needs,” Jill Cranny-Gage, a supporter of the program, said at the Mosquito Control District’s meeting, according to the AP. “We’re trying everything in our power, and we’re running out of options.”

Oxitec has also received federal approval to release the mosquitoes in Texas, BBC News reports, but will face a similar battle to get the go-ahead from state and local agencies.

https://www.the-scientist.com/news-opinion/750-million-gm-mosquitoes-will-be-released-in-the-florida-keys-67855?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_medium=email&_hsmi=93795084&_hsenc=p2ANqtz-9lmVxlNcCMOS833bxmZyvcCcSsJFmqsdVtUIQj7GO6I7635EymKxy49Mj9yuLx1fOyG5LdFBzN9kRQp3UU9BdiSubwVw&utm_content=93795084&utm_source=hs_email

Scientists Awaken Deep Sea Bacteria After 100 Million Years

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The microbes had survived on trace amounts of oxygen, and were able to feed and multiply once revived in the lab.


These bacteria, glowing green in this microscopy image, were revived from deep sea sediment more than 100 million years old.

by Amanda Heidt

Microbes extracted from deep sea sediments that settled during the age of the dinosaurs have been revived in the lab after eons spent in a dormant state. Despite needing oxygen to survive, the bacteria were able to make due with only trace amounts and almost no food for more than 100 million years. Once reanimated, most of the microbes were able to feed and multiply with seemingly no ill effects attributed to their long period of rest.

“The most exciting part of this study is that it basically shows that there is no limit to life in the old sediments of Earth’s oceans,” Steven D’Hondt, an oceanographer at the University of Rhode Island and a coauthor of the study, tells Reuters. “Maintaining full physiological capability for 100 million years in starving isolation is an impressive feat.”The endeavor, described Tuesday (July 28) in Nature Communications, shows just how little is known about the physiological limits of life on Earth, the authors report.

Researchers have long looked to the Earth’s most extreme corners to study the limits of life, including the deep sea, and lead author Yuki Morono, a geomicrobiologist at the Japan Agency for Marine-Earth Science and Technology, wanted to know just how high a tolerance bacteria have for conditions that would prove fatal for other organisms.

Morono collected sediment cores during a research cruise in 2010 aboard the JOIDES Resolution, a floating lab that operates 24 hours a day during scientific voyages. The team targeted the South Pacific Gyre off the east coast of Australia, often called an ocean desert because it lacks the nutrients needed to support even most plankton. As a result, very little organic matter falls to the seafloor more than three miles below.

Across the length of the roughly 250-foot cores, the team collected samples of clay spanning a deposition period between 13 million years ago and almost 102 million years ago. With the samples in the lab, they added nutrients such as nitrogen and carbon—food to jump start any life inside. For up to 557 days after, Morono would extract small chunks of sediment and dissolve them in water, searching for living cells. While a sample of sediment taken from a more oxygen-rich layer of the sea floor might contain more than 100,000 cells per cubic centimetre of mud, Science reports, these deep sea samples might initially only have 1,000 cells in that same volume.

Over time, the microbes began to multiply, a finding Morono initially attributed to “some mistake or a failure in the experiment,” he tells The Guardian. They ruled out contamination from other sources of seawater in the lab, ultimately confirming that what they were seeing was real. In many samples, as many as 99 percent of the microbes were revived. After 68 days, the total number of cells had increased by four orders of magnitude, up to 1 million cells per cubic centimetre.

A genetic analysis showed that the microbes were fairly diverse, representing 10 major groups of bacteria, some of which are widespread throughout other parts of the ocean. Kenneth Nealson, an environmental microbiologist retired from the University of Southern California who was not involved in the study, tells Science this finding “suggests that learning to survive under conditions of extreme energy limitation is a widespread ability,” a useful trick for microbes when food is scarce.

The relatively slow accumulation of sediments in the South Pacific Gyre ended up being key to the cells’ survival, The Guardian reports. When sediment builds up quickly, the pressure pushes out any oxygen that might otherwise linger between the grains to keep aerobic microbes alive. The authors report that if sediment accumulates at a rate of no more than three to six feet every 1 million years, it can remain oxygenated enough to support bacteria.

Some researchers are now pointing to what these findings might mean for the search for life on other planets, as they broaden what environments can be considered amenable to life. Speaking to Science, Andreas Teske, a microbiologist at the University of North Carolina, Chapel Hill, who was also not involved with the new study, says that even if a planet’s surface looks barren, “it may be holding out in the subsurface.”

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ADDF and Harrington Discovery Institute support novel research from Dr. Eugenia Trushina of Mayo Clinic Rochester to preserve aging neurons

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Eugenia Trushina, PhD: Mitochondria as a Therapeutic Target for Alzheimer

The Alzheimer’s Drug Discovery Foundation (ADDF) and Harrington Discovery Institute at University Hospitals have granted Eugenia Trushina, Ph.D., of Mayo Clinic Rochester, the ADDF-Harrington Scholar Award.

Dr. Trushina has been awarded $600,000 for her late stage preclinical research on new drug candidates that show promise in restoring mitochondrial function. In addition to funding, she will receive in-depth drug development support to help maximize her project’s potential for clinical success.

“The ADDF-Harrington partnership helps scientists move academic discoveries from their labs toward clinical studies, and eventually into the clinic to improve the lives of people living with and at risk of Alzheimer’s,” said Dr. Howard Fillit, the ADDF’s Founding Executive Director and Chief Science Officer. “The mitochondria, which are the powerhouses of the cell, are a promising new target in the fight to combat this devastating disease.”

Dr. Trushina has shown that restoring function in mitochondria may delay the onset or slow the progression of Alzheimer’s disease. The compounds she and her team have developed have shown a positive effect in both symptomatic and pre-symptomatic models of Alzheimer’s.

“Supporting this innovative therapeutic approach for patients with Alzheimer’s disease represents our dedication to developing new classes of medicines that are not otherwise traditionally pursued in the field,” said Dr. Andrew Pieper, Director of the Neurotherapeutics Center of the Harrington Discovery Institute and University Hospitals Morley-Mather Chair in Neuropsychiatry.

Dr. Trushina’s research was selected through a competitive process, based on its potential to advance towards the clinic as a novel approach to treat, prevent, or cure Alzheimer’s disease and related dementias. Collaboration between the ADDF and Harrington Discovery Institute for this award provides recipients with both research funding and expert guidance in order to efficiently bridge the gap between academia and pharma.

“We are in our seventh year of collaborating with the ADDF to address this major unmet medical need,” said Jonathan Stamler, MD, President, Harrington Discovery Institute and Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair of Cardiovascular Innovation and Professor of Medicine at University Hospitals and Case Western Reserve University. “This partnership leverages our combined expertise and resources to give the science the best chance of advancing towards a cure for Alzheimer’s disease.”

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About the Alzheimer’s Drug Discovery Foundation (ADDF)

The Alzheimer’s Drug Discovery Foundation is dedicated to rapidly accelerating the discovery of drugs to prevent, treat and cure Alzheimer’s disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer’s, employing a venture philanthropy model to support research in academia and the biotech industry. Through the generosity of its donors, the ADDF has awarded more than $150 million to fund over 626 Alzheimer’s drug discovery programs and clinical trials in 19 countries. To learn more, please visit: https://www.alzdiscovery.org/

About the Harrington Discovery Institute

The Harrington Discovery Institute at University Hospitals in Cleveland, Ohio–part of The Harrington Project for Discovery & Development–aims to advance medicine and society by enabling our nation’s most inventive scientists to turn their discoveries into medicines that improve human health. The institute was created in 2012 with a $50 million founding gift from the Harrington family and instantiates the commitment they share with University Hospitals to a Vision for a “Better World.”

About the Harrington Project for Discovery & Development

The Harrington Project for Discovery & Development (The Harrington Project), founded in late February 2012 by the Harrington Family and University Hospitals of Cleveland, is a $300 million national initiative built to bridge the translational valley of death. It includes the Harrington Discovery Institute and BioMotiv, a for-profit, mission-aligned drug development company that accelerates early discovery into pharma pipelines.

https://www.eurekalert.org/pub_releases/2020-07/addf-aah070720.php

Case Western Reserve University-led team develops new approach to treat certain neurological diseases

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Paul Tesar, professor of genetics and genome sciences, School of Medicine


Regeneration of myelin in the brain, shown in blue, after ASO drug treatment

A team led by Case Western Reserve University medical researchers has developed a potential treatment method for Pelizaeus-Merzbacher disease (PMD), a fatal neurological disorder that produces severe movement, motor and cognitive dysfunction in children. It results from genetic mutations that prevent the body from properly making myelin, the protective insulation around nerve cells.

Using mouse models, the researchers identified and validated a new treatment target—a toxic protein resulting from the genetic mutation. Next, they successfully used a family of drugs known as ASOs (antisense oligonucleotides) to target the ribonucleic acid (RNA) strands that created the abnormal protein to stop its production. This treatment reduced PMD’s hallmark symptoms and extended lifespan, establishing the clinical potential of this approach.

By demonstrating effective delivery of the ASOs to myelin-producing cells in the nervous system, researchers raised the prospect for using this method to treat other myelin disorders that result from dysfunction within these cells, including multiple sclerosis (MS).

Their research was published online July 1 in the journal Nature.

“The pre-clinical results were profound. PMD mouse models that typically die within a few weeks of birth were able to live a full lifespan after treatment,” said Paul Tesar, principal investigator on the research, a professor in the Department of Genetics and Genome Sciences at the School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics. “Our results open the door for the development of the first treatment for PMD as well as a new therapeutic approach for other myelin disorders.”

Study co-authors include an interdisciplinary team of researchers from the medical school, Ionis Pharmaceuticals Inc., a Carlsbad, California-based pioneer developer of RNA-targeted therapies, and Cleveland Clinic. First author Matthew Elitt worked in Tesar’s lab as a Case Western Reserve medical and graduate student.

PMD attacks the young

PMD is a rare, genetic condition involving the brain and spinal cord that primarily affects boys. Symptoms can appear in early infancy and begin with jerky eye movements and abnormal head movements. Over time, children develop severe muscle weakness and stiffness, cognitive dysfunction, difficulty walking and fail to reach developmental milestones such as speaking. The disease shortens life-expectancy, and people with the most severe cases die in childhood.

The disease results from errors in a gene called proteolipid protein 1 (PLP1). Normally, this gene produces proteolipid protein (PLP) a major component of myelin, which wraps and insulates nerve fibers to allow proper transmission of electrical signals in the nervous system. But a faulty PLP1 gene produces toxic proteins that kill myelin producing cells and prevent myelin from developing and functioning properly—resulting in the severe neurological dysfunction in PMD patients.

PMD impacts a few thousand people around the world. So far, no therapy has lessened symptoms or extended lifespans.

For nearly a decade, Tesar and his team have worked to better understand and develop new therapies for myelin disorders. They have had a series of successes, and their myelin-regenerating drugs for MS are now in commercial development.

Latest research

In the current laboratory work, the researchers found that suppressing mutant PLP1 and its toxic protein restored myelin-producing cells, produced functioning myelin, reduced disease symptoms and extended lifespans.

After validating that PLP1 was their therapeutic target, the researchers pursued pre-clinical treatment options. They knew mutations in the PLP1 gene produced faulty RNA strands that, in turn, created the toxic PLP protein.

So they teamed with Ionis Pharmaceuticals, a leader in RNA-targeted therapeutics and pioneer of ASOs. These short strings of chemically modified DNA can be designed to bind to a specific RNA target and block production of its protein product.

And that’s exactly what happened in their studies. The result was improved myelin and locomotion, and substantial extension of lifespan. “ASOs provided an opportunity to cut the disease-causing protein off at its source,” Elitt said.

The successful clinical use of ASOs is relatively new, yet recent developments seem promising. In 2016, the U.S. Food and Drug Administration approved the first ASO drug for a neurological disorder, spinal muscular atrophy. The drug, Spinraza, was developed by Ionis and commercialized by Biogen Inc. More ASO therapies are in development, and clinical trials and hold promise for addressing many neurological diseases that as of now have no effective treatment options.

Tesar said that ongoing and planned experiments in his laboratory will help guide future clinical development of ASO therapy for PMD. For example, researchers want to understand more about how well the treatment works after the onset of symptoms, how long it lasts, how often treatment needs to be given and whether it might be effective for all PMD patients, regardless of their specific form of the disease.

“While important research questions remain, I’m cautiously optimistic about the prospect for this method to move into clinical development and trials for PMD patients,” Tesar said. “I truly hope our work can make a difference for PMD patients and families.”

Case Western Reserve University-led team develops new approach to treat certain neurological diseases

After saving his own life with a repurposed drug, a Professor David Fajgenbaum reviews every drug being tried against Covid-19

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By Ryan Prior

Every morning, Dr. David Fajgenbaum takes three life-saving pills. He wakes up his 21-month-old daughter Amelia to help feed her. He usually grabs some Greek yogurt to eat quickly before sitting down in his home office.

Then he spends most of the next 14 hours leading dozens of fellow researchers and volunteers in a systematic review of all the drugs that physicians and researchers have used so far to treat Covid-19. His team has already pored over more than 8,000 papers on how to treat coronavirus patients.

The 35-year-old associate professor at the University of Pennsylvania Perelman School of Medicine leads the school’s Center for Cytokine Storm Treatment & Laboratory. For the last few years, he has dedicated his life to studying Castleman disease, a rare condition that nearly claimed his life.

Against epic odds, he found a drug that saved his own life six years ago, by creating a collaborative method for organizing medical research that could be applicable to thousands of human diseases.

But after seeing how the same types of flares of immune-signaling cells, called cytokine storms, kill both Castleman and Covid-19 patients alike, his lab has devoted nearly all of its resources to aiding doctors fighting the pandemic.

During a cytokine storm, the body’s overactive immune response begins to attack its own cells rather than just the virus. When that inflammatory response occurs in Covid-19 patients, cytokines are often the culprit for the severe lung damage, organ failure, blood clots or pneumonia that kills them.

Having personal experience tamping down his own cytokine responses gives him a unique insight.
“I’m alive because of a repurposed drug,” he said.

Now, repurposing old drugs to fight similar symptoms caused by a novel virus has become a global imperative.


Researchers from Fajgenbaum’s lab gather in a video call to discuss Covid-19 treatment data.

A global repository for Covid-19 treatment data

Researchers working with his lab have reviewed published data on more than 150 drugs doctors around the world have to treat nearly 50,000 patients diagnosed with Covid-19. They’ve made their analysis public in a database called the Covid-19 Registry of Off-label & New Agents (or CORONA for short).

It’s a central repository of all available data in scientific journals on all the therapies used so far to curb the pandemic. This information can help doctors treat patients and tell researchers how to build clinical trials.

The team’s process resembles that of the coordination Fajgenbaum used as a medical student to discover that he could repurpose Sirolimus, an immunosuppressant drug approved for kidney transplant patients, to prevent his body from producing deadly flares of immune-signaling cells called cytokines.

The 13 members of Fajgenbaum’s lab recruited dozens of other scientific colleagues to join their coronavirus effort. And what this group is finding has ramifications for scientists globally.

Based on their database, the team published the first systematic review of Covid-19 treatments in the journal Infectious Diseases and Therapy in May.

In that first analysis of the data, the team reviewed 2,706 journal articles published on the topic between December 1, 2019, and March 27, 2020. Just 155 studies met the team’s criteria for being included in the meta-review based on standards such as the size of the cohort, the nature of the study and the end points researchers chose for concluding their inquiries.

“It’s frustrating because we all want a drug that works for everyone,” he said. But that isn’t happening because the coronavirus affects people in ways that are much more complex.

They’re sorting through oceans of data

The first key thing to consider, Fajgenbaum said, was the huge variety of Covid-19 patient experiences. It’s hard to zero in on one particular therapy because there can be such significant differences in the timing of when the drug is administered, how severely Covid-19 strikes a given individual and the stage at which the disease has progressed.

Any change in one of those variables can render an otherwise effective drug impotent. But with massive amounts of patients, the clinical data was bearing out a few noticeable themes, he said.

First, the Covid-19 patients with more severe cytokine storms were more likely to need drugs targeted toward suppressing the immune system. Those with less severe cytokine storms were likely to benefit from an immune-boosting drug.

Outside of drugs designed to boost or suppress the immune system, another major category is antiviral therapies. Various antivirals hit the “viral cascade,” Fajgenbaum said. Some work by stopping the virus from infecting cells, others by halting replication within cells. Other antivirals act in between cells and the virus.

Keeping the database is a huge undertaking, given how stunning the pace of global scientific progress and collaboration has been in the face of the disease’s human toll.

“We set the really ambitious goal of just getting this started,” Fajgenbaum said.

In the three months since the cutoff date for their first paper, the team has reviewed more than 5,000 additional papers published by scientists around the world.

One of their biggest challenges has been fitting the puzzle pieces of the different studies. With each study designed differently, one data set can’t necessarily be grafted neatly onto another. That’s especially tricky when most people diagnosed with Covid-19 eventually get better anyway. It’s hard to parse out if a particular drug was effective and saved lives.

The goal of the CORONA database isn’t to find a wonder drug per se, but to help design better clinical trials that can establish a real cause-and-effect relationship between a drug agent and an individual’s survival.

In the war against the coronavirus, Fajgenbaum hopes CORONA aims to help light the way so the heavy artillery on the front lines can better know what to shoot at Covid-19.

“It’s hard to fight a war if you’re not keeping track of what weapons are being used against the enemy,” he said.


Shown here is one of the researchers’ computer screens as they review Covid-19 treatment data while on a video call. The left side shows a spreadsheet where they tabulate data from the studies. The right side shows the study they’re currently analyzing.

They’re collaborating with FDA analysts

Fajgenbaum’s CORONA database dovetails with ongoing work at the US Food and Drug Administration. For years, the agency has been developing an app called CURE ID, a platform designed to help health care providers capture novel uses of already approved drugs.

The app launched in December with two goals in mind: The first was to help advise physicians searching for new treatment ideas, prescription guidelines and emergency use advisories for drugs across hundreds of diseases. The agency’s second aim was to build a structure by which health providers in the trenches could quickly input anonymized information about their patients so that other doctors around the world could quickly see whether they had been successful using an off-label drug.

The app was ready just in time for the pandemic, and Fajgenbaum gave the keynote speech at its launch.

“It’s really been a terrific collaboration,” said a health policy analyst with the FDA. “His life follows very much the model we hope to use.”

Now that he and his team are working on the coronavirus, the urgency of their partnership has strengthened.

“Nobody wants to go to a database with no data in it,” the analyst said. “Rather than reinventing the wheel, he was kind enough to provide all his data.”

And while the CORONA database project is primarily intended to aid researchers, it’s tapping into major currents in health economics that explain weak points in the way the public and private sector develop therapies together.

“Covid-19 illustrates a market failure in how we build vaccines,” said Amitabh Chandra, a health economist with joint appointments as a professor at the Harvard Kennedy School and Harvard Business School. “We haven’t given firms the correct incentives to make vaccines before a pandemic. Vaccines are very hard to test before the pandemic hits.”

There aren’t old vaccines sitting on a shelf waiting to be dusted off to save the world from the coronavirus. But there are hundreds of FDA-approved drugs at your local pharmacy that can save lives immediately.

When teaching classes, Chandra uses a 2017 New York Times story profiling Fajgenbaum to illustrate the value of drug repurposing and motivate his students to think boldly about how to create economic incentives to cure diseases, particularly when a “invisible medicine” might be right under your nose.

“There’s no substitute for a good story to get people motivated,” he said.
Many drugs are beginning to stand out.

The combination of antivirals lopinavir and ritonavir is the Covid-19 treatment protocol with the most number of studies published so far. As of mid-June, the team had looked at papers on that drug pairing involving more than 4,500 patients.

Next, corticosteroids have shown particular promise, making appearances in studies with another 4,000 patients. At the cellular level, antivirals work for a variety of reasons, each with its own specialty in attacking the virus at different points in its life cycle. Corticosteroids are different, however.

“Steroids tend to act the same, with replicating cortisol,” Fajgenbaum said.

He feels particularly elated about a recent United Kingdom-based study on the steroid dexamethasone. The study garnered headlines for its result showing that a low-dose 10-day regimen of the drug could reduce the risk of death by a third among hospitalized patients requiring ventilation.

In their spreadsheets, the numbers around dexamethasone were like a beacon.
“We built CORONA to help uncover something like dexamethasone,” he said. “It’s a cheap repurposed drug that’s been around for 60 years. This is what it’s all about.”

Studies need rigor

Because Covid-19 is so new, many of the studies are observational or anecdotal. These types of studies obviously matter as scientists are building a foundation of knowledge.

But the best insights come from running double-blind placebo-controlled studies. One shortfall is that many of the published studies just don’t have the level of rigor to inform larger-scale scientific decision-making.

“There are a lot of biases in these observational studies,” Fajgenbaum said.
One drug, the anti-malarial drug hydroxychloroquine, has famously received a lot of boosterism from US President Donald Trump. But in the published studies available for Fajgenbaum’s team to review, the drug hasn’t outperformed others.

Two French studies on hydroxychloroquine drew red flags for the University of Pennsylvania-based team because of the clinical end point the researchers chose: the time when the coronavirus cleared the body. It can be problematic to base an argument for a drug’s success only on that particular metric, because it leaves out crucial details from a person’s longer-term experience following infection.

“‘Virally cured’ is a challenging term,” Fajgenbaum said. “We don’t know if they’re discharged how they fared after leaving the hospital.”

On top of that, the reviewers were skeptical because the virus took a long time to leave the patients’ bodies, which they refer to as “a high time to viral clearance.”

That indicator that could suggest the drug was slow to take effect, or that other factors, including the patient’s own immune system, played a larger role in expelling the pathogen.

Know how to sort through the data

With dozens of people working full time to sort through thousands of studies, it’s obviously impossible for a single frontline health provider to keep abreast of all there is to know about Covid-19 while also treating patients at the same time.

It’s even harder for the average person following the story in the news, especially if you’re not equipped with a graduate degree in statistical analysis.

“Covid threw the world in flux,” said Sheila Pierson, associate director for clinical research at the CSTL. A biostatistician originally hired to study Castleman disease, she’s accepted the new mission along with her colleagues.

“There’s a lot of great science being done,” she explained. With that pace of innovation, it’s incredibly difficult for the average person to stay up to date, so the CORONA database helps everyone with a little extra scientific literacy amid headlines about new treatments that induce a form of intellectual whiplash.

“You should rely on multiple news sources,” Pierson said, in order to sort through what may appear to be conflated messages about whether a certain drug works or not for a certain group of people.

“It’s difficult when you’re only looking at one person’s view of a drug,” she said. “Look for a different write-up and a different view.”

He’s repeating the same methods that saved his life

As of June 27, Fajgenbaum has lived free of Castleman’s cytokine storms for 77.72 months. His last Castleman relapse ended on January 5, 2014. He’s a living experiment, and in his personal accounting he won’t round up to the next full month. Each new day is a precious moment with a daughter he feared he’d never meet.

The doctor and researcher remains immune compromised and won’t take risks with the coronavirus.
He hasn’t set foot in a building other than his home since March 13. And his life still relies on siltuximab and chemotherapy infusions administered monthly through a chest port.

“I’m reminded every time I touch the port in my chest of the cytokine storms I had,” he said. “I want so badly to solve (Covid-19) the way I did with Castleman. I have the same sense of urgency.”

Castleman disease nearly killed Fajgenbaum five times in his 20s while he was working his way through University of Pennsylvania’s Perelman School of Medicine and then earning an MBA at the University of Pennsylvania’s Wharton School.

Each time, the deadly disease triggered cytokine storms that led to multiple organ failure.

But the young man created a global organization to rally doctors, scientists and patients toward finding a cure. With intense study and brilliant partners, he zeroed in on an already available immunosupressant that could be repurposed to save his life.

Last year he published his memoir, “Chasing My Cure,” detailing a journey in which at one point a priest was brought to his hospital room to give his last rites.

Fajgenbaum’s story reads likes the teaser for a hit Netflix series. But if it were a show, all of that is really just season one. Because, spoiler alert — then a global pandemic hit.

A year ago you might have thought what the writers threw at him in a second season might be a bit unrealistic. But this project is the obvious next step.

“I see myself bringing our experiences with Castleman now over to the global fight against corona,” he said.

https://www.cnn.com/2020/06/27/health/coronavirus-treatment-fajgenbaum-drug-review-scn-wellness/index.html

Researchers Make Mice Smell Odors that Aren’t Really There

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by Ruth Williams

By activating a particular pattern of nerve endings in the brain’s olfactory bulb, researchers can make mice smell a non-existent odor, according to a paper published June 18 in Science. Manipulating these activity patterns reveals which aspects are important for odor recognition.

“This study is a beautiful example of the use of synthetic stimuli . . . to probe the workings of the brain in a way that is just not possible currently with natural stimuli,” neuroscientist Venkatesh Murthy of Harvard University who was not involved with the study writes in an email to The Scientist.

A fundamental goal of neuroscience is to understand how a stimulus—a sight, sound, taste, touch, or smell—is interpreted, or perceived, by the brain. While a large number of studies have shown the various ways in which such stimuli activate brain cells, very little is understood about what these activations actually contribute to perception.

In the case of smell, for example, it is well-known that odorous molecules traveling up the nose bind to receptors on cells that then transmit signals along their axons to bundles of nerve endings—glomeruli—in a brain area called the olfactory bulb. A single molecule can cause a whole array of different glomeruli to fire in quick succession, explains neurobiologist Kevin Franks of Duke University who also did not participate in the research. And because these activity patterns “have many different spatial and temporal features,” he says, “it is difficult to know which of those features is actually most relevant [for perception].”

To find out, neuroscientist Dmitry Rinberg of New York University and colleagues bypassed the nose entirely. “The clever part of their approach is to gain direct control of these neurons with light, rather than by sending odors up the animal’s nose,” Caltech neurobiologist Markus Meister, who was not involved in the work, writes in an email to The Scientist.

The team used mice genetically engineered to produce light-sensitive ion channels in their olfactory bulb cells. They then used precisely focused lasers to activate a specific pattern of glomeruli in the region of the bulb closest to the top of the animal’s head, through a surgically implanted window in the skull. The mice were trained to associate this activation pattern with a reward—water, delivered via a lick-tube. The same mice did not associate random activation patterns with the reward, suggesting they had learned to distinguish the reward-associated pattern, or synthetic smell, from others.

Although the activation patterns were not based on any particular odors, they were designed to be as life-like as possible. For example, the glomeruli were activated one after the other within the space of 300 milliseconds from the time at which the mouse sniffed—detected by a sensor. “But, I’ll be honest with you, I have no idea if it stinks [or] it is pleasant” for the mouse, Rinberg says.

Once the mice were thoroughly trained, the team made methodical alterations to the activity pattern—changing the order in which the glomeruli were activated, switching out individual activation sites for alternatives, and changing the timing of the activation relative to the sniff. They tried “hundreds of different combinations,” Rinberg says. He likened it to altering the notes in a tune. “If you change the notes, or the timing of the notes, does the song remain the same?” he asks. That is, would the mice still be able to recognize the induced scent?

From these experiments, a general picture emerged: alterations to the earliest-activated regions caused the most significant impairment to the animal’s ability to recognize the scent. “What they showed is that, even though an odor will [induce] a very complex pattern of activity, really it is just the earliest inputs, the first few glomeruli that are activated that are really important for perception,” says Franks.

Rinberg says he thinks these early glomeruli most likely represent the receptors to which an odorant binds most strongly.

With these insights into the importance of glomeruli firing times for scent recognition, “the obvious next question,” says Franks, is to go deeper into the brain to where the olfactory bulb neurons project and ask, “ How does the cortex make sense of this?”

E. Chong et al., “Manipulating synthetic optogenetic odors reveals the coding logic of olfactory perception,” Science, 368:eaba2357, 2020.

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Electric current to the wrist triggers brain waves that help dampen tics in people with Tourette’s syndrome

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An unusual new treatment for Tourette’s syndrome involves applying an electrical current to the wrist, which travels up nerves to the brain and changes brainwaves. The approach, which moderately reduced the number of tics in volunteers with Tourette’s, suggests the condition is linked with an underactivity in brainwaves that normally keep us still.

People with Tourette’s syndrome make frequent involuntary jerks, facial twitches and noises. Tics usually arise around the age of 6, and while they often fade with time, for some they continue and can be debilitating. “Sometimes children literally break bones because they’re flinging themselves around so much,” says Stephen Jackson at the University of Nottingham in the UK.

In most people, when they are motionless, brainwaves cycle at about 12 times a second in part of the brain called the motor cortex, located at the top of the head. “It’s like the handbrake on a car – it maintains a stable posture,” says Jackson.

Previous research has shown that stimulating brainwaves in this area by using a strong oscillating magnetic field above the head can reduce tics in people with Tourette’s. Jackson wondered if there was a way to get this effect more easily.

His group placed an electrode on the wrist to deliver a mild current with a frequency of 12 times a second; the current was noticeable but not uncomfortable. The idea is that this current travels via nerves to the sensory cortex of the brain and induces oscillations at the same frequency in the neighbouring motor cortex.

When 19 people with Tourette’s tried out the electrode, it reduced the frequency of their tics by a third, compared with when the electrode was turned on for the same length of time but had no regular frequency. Voluntary movements were only slowed a little.

Normally people with Tourette’s feel an urge to tic slowly building until it becomes irresistable. Many of the volunteers reported that when the electrodes were at the right frequency, their urges reduced. Charlie, a 21-year-old with severe tics, said in a statement: “When the electrical pulses on the wrist started to increase, the tic urges decreased, which was a completely shocking experience for me, I was silent and still. I wanted to cry with happiness.”

Jackson’s group is developing a watch-like device that people can turn on to deliver the stimulation when it is needed.

Journal reference: Current Biology, DOI: 10.1016/j.cub.2020.04.044

Read more: https://www.newscientist.com/article/2245275-electric-current-helps-dampen-tics-in-people-with-tourettes-syndrome/#ixzz6OUvidHok

A new artificial eye mimics and may outperform human eyes

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A new design for an artificial eyeball (illustrated) could someday give keen eyesight to androids, or be used as a high-tech prosthetic.


The design for a new artificial eye (illustrated) is based on the structure of the human eye. At the back of the eyeball, a synthetic retina is embedded with nanoscale light sensors. Those sensors measure light that passes through the lens at the front of the eye. Wires attached to the back of the retina ferry signals from those sensors to external circuitry for processing, similar to the way nerve fibers connect the eyeball to the brain.

By Maria Temming

Scientists can’t yet rebuild someone with bionic body parts. They don’t have the technology. But a new artificial eye brings cyborgs one step closer to reality.

This device, which mimics the human eye’s structure, is about as sensitive to light and has a faster reaction time than a real eyeball. It may not come with the telescopic or night vision capabilities that Steve Austin had in The Six Million Dollar Man television show, but this electronic eyepiece does have the potential for sharper vision than human eyes, researchers report in the May 21 Nature.

“In the future, we can use this for better vision prostheses and humanoid robotics,” says engineer and materials scientist Zhiyong Fan of the Hong Kong University of Science and Technology.

The human eye owes its wide field of view and high-resolution eyesight to the dome-shaped retina — an area at the back of the eyeball covered in light-detecting cells. Fan and colleagues used a curved aluminum oxide membrane, studded with nanosize sensors made of a light-sensitive material called a perovskite (SN: 7/26/17), to mimic that architecture in their synthetic eyeball. Wires attached to the artificial retina send readouts from those sensors to external circuitry for processing, just as nerve fibers relay signals from a real eyeball to the brain.

The artificial eyeball registers changes in lighting faster than human eyes can — within about 30 to 40 milliseconds, rather than 40 to 150 milliseconds. The device can also see dim light about as well as the human eye. Although its 100-degree field of view isn’t as broad as the 150 degrees a human eye can take in, it’s better than the 70 degrees visible to ordinary flat imaging sensors.

In theory, this synthetic eye could perceive a much higher resolution than the human eye, because the artificial retina contains about 460 million light sensors per square centimeter. A real retina has about 10 million light-detecting cells per square centimeter. But that would require separate readings from each sensor. In the current setup, each wire plugged into the synthetic retina is about one millimeter thick, so big that it touches many sensors at once. Only 100 such wires fit across the back of the retina, creating images that have 100 pixels.

To show that thinner wires could be connected to the artificial eyeball for higher resolution, Fan’s team used a magnetic field to attach a small array of metal needles, each 20 to 100 micrometers thick, to nanosensors on the synthetic retina one by one. “It’s like a surgical operation,” Fan says.

The researchers’ current method of creating individual ultrasmall pixels is impractical, says Hongrui Jiang, an electrical engineer at the University of Wisconsin–Madison whose commentary on the study appears in the same issue of Nature. “For a few hundred nanowires, okay, fine, but how about millions?” Engineers will need a much more efficient way to manufacture vast arrays of tiny wires on the back of the artificial eyeball to give it superhuman sight, he says.

A new artificial eye mimics and may outperform human eyes

Chemists develop foolproof new test to track the fats we eat

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Philip Britz-McKibbin, Professor of Chemistry & Chemical Biology, McMaster University Credit: JD Howell, McMaster University

A team of researchers at McMaster University has developed a reliable and accurate blood test to track individual fat intake, a tool that could guide public health policy on healthy eating.

Establishing reliable guidelines has been a significant challenge for nutritional epidemiologists until now, because they have to rely on study participants faithfully recording their own consumption, creating results that are prone to human error and selective reporting, particularly when in the case of high-fat diets.

For the study, published in the Journal of Lipid Research, chemists developed a test, which detects specific non-esterified fatty acids (NEFAs), a type of circulating free fatty acid that can be measured using a small volume of blood sample.

“Epidemiologists need better ways to reliably assess dietary intake when developing nutritional recommendations,” says Philip Britz-McKibbin, professor in the Department of Chemistry & Chemical Biology at McMaster University and lead author of the study.

“The food we consume is highly complex and difficult to measure when relying on self-reporting or memory recall, particularly in the case of dietary fats. There are thousands of chemicals that we are exposed to in foods, both processed and natural,” he says.

The study was a combination of two research projects Britz-McKibbin conducted with Sonia Anand in the Department of Medicine and Stuart Phillips in the Department of Kinesiology.

Researchers first assessed the habitual diet of pregnant women in their second trimester, an important development stage for the fetus. The women, some of whom were taking omega-3 fish oil supplements, were asked to report on their average consumption of oily fish and full-fat dairy and were then tested with the new technology. Their study also monitored changes in omega-3 NEFAs in women following high-dose omega-3 fish oil supplementation as compared to a placebo.

Researchers were able to prove that certain blood NEFAs closely matched the diets and/or supplements the women had reported, suggesting the dietary biomarkers may serve as an objective tool for assessment of fat intake.

“Fat intake is among the most controversial aspects of nutritional public health policies given previously flawed low-fat diet recommendations, and the growing popularity of low-carb/high-fat ketogenic based diets” says Britz-McKibbin. “If we can measure it reliably, we can begin to study such questions as: Should pregnant women take fish oil? Are women deficient in certain dietary fats? Does a certain diet or supplement lead to better health outcomes for their babies?”

Researchers plan to study what impact NEFAs and other metabolites associated with dietary exposures during pregnancy, might have on childhood health outcomes in relation to the obesity, metabolic syndrome and chronic disease risk later in life.

https://medicalxpress.com/news/2020-05-chemists-foolproof-track-fats.html

The presence of receptors for SARS-CoV-2 on a wide variety of human cells supports the idea that COVID-19 is not just a respiratory disease but an illness across multiple organs.

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Human cell types within corresponding organs that express the genes for both ACE2 and CTSL (green dot) or both ACE2 and TMPRSS2 (orange dot).

by Chris Baraniuk

When the SARS-CoV-2 virus enters the human body, it breaks into cells with the help of two proteins that it finds there, ACE2 and TMPRSS2. While there has been much discussion of viral infection in gut and lung cells, researchers have dug into massive gene expression datasets to show that other potential target cells also producing ACE2 and TMPRSS2 are scattered throughout the body—including in the heart, bladder, pancreas, kidney, and nose. There are even some in the eye and brain.

The results, published in a preprint on bioRxiv April 21, show that such cells are strikingly abundant. Many are epithelial cells, which line the outer surface of organs. The new findings add to an emerging picture of SARS-CoV-2 as a virus that can target cells in many places in the human body, rather than being focused on a particular organ or part of the respiratory tract.

Cardiologist Frank Ruschitzka at the University Hospital of Zürich and colleagues separately published a letter in The Lancet April 17 in which they described how virus particles had been found in the vascular endothelium, a thin layer of cells lining blood vessels in various organs of the body, for instance.

“This is not just a virus pneumonia,” Ruschitzka, who was not involved in the latest study, tells The Scientist, referring to COVID-19. “This is a disease like we have never seen before—it is not an influenza, it hits the vessels all over, it hits the heart as well.”

To uncover the locations of cells bearing ACE2 and TMPRSS2, the preprint researchers turned to the Human Cell Atlas, a project that has allowed scientists to pool together data on human cells since 2016.

By scouring single-cell sequencing records of around 1.2 million individual cells from human tissue samples, the team was able to find out which of those cells produce both ACE2 and TMPRSS2, and note their locations in the body. The analysis used 16 unpublished datasets of lung and airway cells and 91 published datasets spanning a range of human organs.

Coauthor Christoph Muus, a graduate student at Harvard University and the Broad Institute, explains that while the data show cells in many locations in the body produce SARS-CoV-2 receptors, it’s not certain that the virus can infect all of those tissues.

“Expressing the receptor is a necessary condition but not necessarily a sufficient condition,” he says. For example, potential target cells were found in the testes, but scientists still don’t know if SARS-CoV-2 infects and replicates in that part of the body.

Jeremy Kamil, a virologist at Louisiana State University Health Shreveport, says the preprint provides important details about the human body that may help scientists understand how SARS-CoV-2 infects hosts. By finding viral protein fragments in tissue samples from patients who died because of COVID-19, scientists might be able to firm up which organs are genuine sites of infection, he adds.

“I’d say this paper gives people a roadmap at where you might want to look in the body to understand where this virus is going,” he says.

One limitation of the work is that relatively little metadata about the people who donated tissue samples were available for the various datasets, though information about age and gender were included in many. The researchers don’t know, for example, whether there was an ethnicity bias in the data, whether patients had pre-existing conditions, or whether they were taking any medications. All of these things could affect gene expression in particular cells.

Smoking status was available for a subset of the data, and the team used this to show that smoking is correlated with a greater expression of the ACE2 gene in the upper airway, but lower expression in certain lung cells. Further research is needed to understand whether this affects smokers’ susceptibility to COVID-19. Data from China suggest that smokers are 14 times more likely to develop a severe form of the disease.

Some researchers from the same group using similar data have also recently published papers in Cell and Nature. In those cases, the researchers focused on certain groups of cells. The study reported in Nature examined cells potentially involved in viral transmission and found that nasal epithelial cells, in particular, were associated with expression of ACE2 and TMPRSS2. The authors report that the virus might exploit cells that secrete fluids in the nasal passage, which might help it spread from one person to another in droplets released, say, when someone sneezes.

The Cell study, meanwhile, also found ACE2 and TMPRSS2 transcripts in nasal, gut, and lung cells but the researchers also found that the protein interferon activated ACE2 expression in vitro. The human body uses interferon to fight infections, so it is not clear whether the protein is of overall benefit or detriment to COVID-19 patients.

The use of so many different data sources backs up the validity of the preprint authors’ findings, says Marta Gaglia, a molecular biologist at Tufts University. She agrees with the researchers that discovering ACE2- and TMPRSS2-producing cells in various places around the body does not prove the virus can always infect such cells.

“I think the reality is that most of the problems come from the lung,” she adds. Plus, while doctors treating COVID-19 patients may detect problems in multiple organs, those issues might not necessarily be caused directly by SARS-CoV-2 infection, says Gaglia. A problematic immune system response, for instance, could damage certain tissues in the body as an indirect consequence of viral infection.

https://www.the-scientist.com/news-opinion/receptors-for-sars-cov-2-present-in-wide-variety-of-human-cells-67496?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_source=hs_email&utm_medium=email&utm_content=87213170&_hsenc=p2ANqtz-_vGzY0JSZbqON-CbrWnU2wp22vNPAa-zcPDPoSZR69MA0qXhi3ukYIXekJJKZ_A_GfMi8lV1cuO5y2DnnkhV-rdYFrPQ&_hsmi=87213170