By Laura Sanders

Exercise’s power to boost the brain might require a little help from the liver.

A chemical signal from the liver, triggered by exercise, helps elderly mice keep their brains sharp, suggests a study published in the July 10 Science. Understanding this liver-to-brain signal may help scientists develop a drug that benefits the brain the way exercise does.

Lots of studies have shown that exercise helps the brain, buffering the memory declines that come with old age, for instance. Scientists have long sought an “exercise pill” that could be useful for elderly people too frail to work out or for whom exercise is otherwise risky. “Can we somehow get people who can’t exercise to have the same benefits?” asks Saul Villeda, a neuroscientist at the University of California, San Francisco.

Villeda and colleagues took an approach similar to experiments that revealed the rejuvenating effects of blood from young mice (SN: 5/5/14). But instead of youthfulness, the researchers focused on fitness. The researchers injected sedentary elderly mice with plasma from elderly mice that had voluntarily run on wheels over the course of six weeks. After eight injections over 24 days, the sedentary elderly mice performed better on memory tasks, such as remembering where a hidden platform was in a pool of water, than elderly mice that received injections from sedentary mice.

Comparing the plasma of exercised mice with that of sedentary mice showed an abundance of proteins produced by the liver in mice that ran on wheels.

The researchers closely studied one of these liver proteins produced in response to exercise, called GPLD1. GPLD1 is an enzyme, a type of molecular scissors. It snips other proteins off the outsides of cells, releasing those proteins to go do other jobs. Targeting these biological jobs with a molecule that behaves like GPLD1 might be a way to mimic the brain benefits of exercise, the researchers suspect.

Old mice that were genetically engineered to make more GPLD1 in their livers performed better on the memory tasks than other old sedentary mice, the researchers found. The genetically engineered sedentary mice did about as well in the pool of water as the mice that exercised. “Getting the liver to produce this one enzyme can actually recapitulate all these beneficial effects we see in the brain with exercise,” Villeda says.

Blood samples from elderly people also hint that exercise raises GPLD1 levels. Elderly people who were physically active (defined as walking more than 7,100 steps a day) had more of the protein than elderly people who were more sedentary, data on step-counters showed.

GPLD1 seems to exert its effects from outside of the brain, perhaps by changing the composition of the blood in some way, the researchers suspect.

But the role of GPLD1 is far from settled, cautions Irina Conboy, a researcher at the University of California, Berkeley who studies aging. There’s evidence that GPLD1 levels are higher in people with diabetes, she points out, hinting that the protein may have negative effects. And different experiments suggest that GPLD1 levels might actually fall in response to certain kinds of exercise in rats with markers of diabetes.

“We know for sure that exercise is good for you,” Conboy says. “And we know that this protein is present in the blood.” But whether GPLD1 is good or bad, or whether it goes up or down with exercise, she says, “we don’t know yet.”

CITATIONS
A. M. Horowitz et al. Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain. Science. Vol. 369, July 10, 2020, p. 167. doi: 10.1126/science.aaw2622.

Boosting a liver protein may mimic the brain benefits of exercise

By Vanessa Bates Ramirez

Four years ago, three big tech companies had plans in the works to beam internet down to Earth from the sky, and each scenario sounded wilder than the next. SpaceX requested permission to launch 4,425 satellites into orbit to create a global internet hotspot. Facebook wanted to use solar-powered drones and laser-based tech to shoot wifi to antennas. And Google’s Loon was building giant balloons to house solar-powered electronics that would transmit connectivity down from the stratosphere.

As incredible as it all sounds, two of these schemes have started to come to fruition. Loon balloons made their (non-emergency) debut in Kenya this week, with 35 balloons transmitting a 4G signal to 31,000 square miles of central and western Kenya. And SpaceX is in the process of signing up beta testers for its internet-via-satellite, with over 500 satellites currently in orbit. Facebook, however, stopped work on its internet drones in mid-2018.

Here’s a quick refresher on how the Loon and SpaceX systems work.

Big White Internet Balloons

Loon balloons are made of polyethylene, one of the most common plastics around (it’s in grocery bags, plastic bottles, kids’ toys, etc.). They’re 15 meters (49 feet) wide, and designed to hover in the stratosphere 20 kilometers (12 miles) above Earth. They’re launched by a custom-built crane that’s pointed downwind.

Specially-developed software uses predictive modeling of stratospheric winds and decision-making algorithms to shift the balloons as needed for a more reliable connection down below (balloons need to be within 40 kilometers of users for the service to work). The software constantly learns to improve the balloons’ choreography and thus the network’s quality, and the system can function autonomously.

The electronics inside the balloons get a wifi signal from a local telecoms partner at a ground station. In Kenya, Loon partnered with Telkom Kenya, the country’s third-largest carrier. The signal gets relayed across multiple nearby balloons that transmit it back down to peoples’ phones and other devices. Each balloon can cover an area of 5,000 square kilometers (a little under 2,000 square miles, or about the size of the state of Delaware).

A field testing session in Kenya in late June registered an upload speed of 4.74 Mpbs, a download speed of 18.9Mbps, and latency of 19 milliseconds. For comparison’s sake, the average speed in the US is 52 Mpbs upload and 135 Mbps download; so service will be a bit slower in Kenya. One other small problem: since the electronics in the balloons are solar-powered, they only send down a signal during daylight hours; service is currently available from 6am to 9pm.

Signals from Starlink

Just this past week, SpaceX launched 57 more of its Starlink satellites, bringing the total in orbit to over 500. It’s a fraction of the planned total of 4,425, but a pretty solid start. The satellites are orbiting 715 to 790 miles above Earth’s surface. Each one weighs 260 kilograms, about as much as a small car, and can reach an area 1,300 miles in diameter on the ground at a speed of one gigabit per second.

SpaceX plans for the first 1,600 satellites to be at one orbital altitude, followed by 2,825 more to be placed at four different altitudes. Each satellite is estimated to last five to seven years.

In late June SpaceX announced it was looking for beta testers for its internet service. You can sign up on Starlink’s website, and you’ll be notified if testing is going to take place in the area where you live. The company plans to start at higher latitudes (like Seattle, according to a May 7 tweet from Elon Musk), then move progressively southward.

Internet for All

According to the Alliance for Affordable Internet, over half of the world’s population now has internet access—but a large percentage of that is low-quality, meaning they can’t use features like online learning, video streaming, and telehealth. A 2019 report by the organization found that only 28 percent of the African population has internet access through a computer, while 34 percent have access through a mobile phone.

Though expanding internet to the whole of the world’s population will come with some drawbacks (such as more channels for misinformation or hate speech, and not being able to go anywhere to truly “unplug”), the broader consensus is that the internet will serve as a greatly empowering and liberating force, giving people instant access to information and enabling countless business and learning opportunities that otherwise wouldn’t exist.

We probably didn’t think this would happen via giant balloons and thousands of satellites, but it won’t be the first time the developing world leapfrogs right over cumbersome, outdated technologies. If SpaceX and Loon continue on their current trajectories, it will only be a matter of time—and not all that much of it—before we’re living in a planet-wide internet bubble.

Google Loon Is Now Beaming WiFi Down to Earth From Giant Balloons

September 1988, Shreveport, Louisiana: 20-year-old William David McKinney had been fatally shot by a white teenager. Racial tensions, already simmering, boiled over. In the aftermath, anger, frustration and pleas for change.

The city was described as a “powder keg.” Thirty-two years later, that powder keg is exploding with yards signs that say, simply, “We Care.” They are everywhere.

“Everybody around here is like family, and that’s what neighborhoods is for – is to help one another,” said one resident, Johnnie.

Through the streets (back before COVID made it impossible), White and Black join together to walk the neighborhood, and pray for it – and this was before the killing of George Floyd. And while Shreveport has been changed like just about every city by his death, what hasn’t changed is the belief of a Shreveport pastor that communities torn down by bigotry, segregation and poverty can be built back up simply by neighbors caring for neighbors.

“We can email people all over the world, and we don’t know who’s living and dying four houses away from us,” said Mack McCarter, who invited “Sunday Morning” correspondent Lee Cowan to Shreveport back in February. He’s a proud native of this city. He left to go to seminary, and didn’t return for years, but when he did, he set up shop in Allendale – the “Bottoms,” as some used to call it – a neighborhood long plagued by crime and drugs.

Cowan asked, “What did people think when they saw you walking down these streets?”


Mack McCarter

“Well, so, I drove down and I thought, ‘Good heavens, I’m going to die.’ But I pulled over and stopped, and then went up to their shotgun row house, knocked on the door, and said, ‘There’s a group of us that believe if we’ll get to be friends then we can change this city.’ And not many doors opened.”

Not at first, but he kept knocking, and he started attending church in the area, too, mingling with the congregation just like any neighbor might. And over time, something started to happen. “I saw friendship overcome our racial divide,” McCarter said. “I saw it overcome our socioeconomic divide. I saw it overcome the fact that we had been strangers. And for sure, I saw it overcome fear.”

The experience was so impactful that he set up a non-profit called Community Renewal International, a faith-based organization that’s been making friends out of strangers for more than 25 years.

He hired those who believed as strongly as he did that an outstretched hand could work wonders.

“If we don’t do something to restore those relationships and restore that love from person to person, then America’s gonna collapse. We are going to fail,” said Sharpel Welch.

Welch (a civil society fellow with the Manhattan Institute) and Emmitt Welch live in what’s called a Friendship House, one of ten built in communities all around Shreveport – it’s part residence, part community center. The goal there is to mentor – to solve problems internally, street by street.

“Government is not gonna come down and model loving your neighbor to stressed and blighted neighborhoods,” Sharpel said. “They can’t do that. We have to do it.”

The Welches have taken in seven children from the neighborhood, raising them as their own. That’s what’s happening on one side of the Friendship House.

The other side is open to anyone in the neighborhood who needs it – and those who show up the most are teens. Emmitt and Sharpel Welch run a youth club, but it’s hardly your average after-school program.


Sharpel Welch leads a meeting of her Friendship House’s youth club.

“We spent time going to the local judicial system, getting kids out of handcuffs,” said Emmitt. “We’re going to parent meetings. We’re going to see the principal, to put ’em back in school after suspension. We were just doing a lot of work.”

That kind of help is often rejected, but not when it comes from inside the community. That’s what made the difference for Lakyra Burks, who said, “We care about our community, we care about our neighbors. And if we didn’t have those things, who would we lean on?”

Tierney Turner, whose father was killed when she was two, has watched the stability the Welches have brought become infectious. “The whole inside of my life got changed,” Turner said. “Introduced me to the world and what I can do better, to not have that situation happen to me, or my future husband or my family.”

Since Community Renewal moved in, crime has moved out – it’s dropped by more than half in Allendale. Graduation rates are up, and so is home ownership.

Skeptical? So is everybody.

Cowan said, “Some people watching this are gonna say, ‘It’s just too simple.'”

“Just another ‘fluffy program,’ yeah,” Sharpel said.

“Not even fluffy. It’s gotta be more …”

“Be more to it, yeah!” she laughed.

Emmitt said, “And to those people, I dare them to try it.”

“I get the cynical people,” Sharpel said. “I will challenge them, and I have done it. Get to know everybody on your street. First name, last name, something about them that you didn’t know before.”

McCarter has expanded the program into some of Shreveport’s wealthiest neighborhoods. “Human beings have faults and problems and heartaches, whether you’re rich or poor,” he said.

Paige Hoffpauir lives in a community where stately homes line a private golf course. “It might look good, but that doesn’t mean it is good,” she said.

She’s not comparing her problems with anyone’s, but she did realize that sometimes the only thing residents in this gated community had in common was the gate. “It’s painful to live on a street, and not know your neighbor,” she said.

Isolation can be a real thing, even in a crowded sub-division. Her block parties look a little different than the one in Allendale, but many of the same people were there, and were there for the same reason.

“‘Random acts of kindness,’ that’s a great bumper sticker; it will not stop the disintegration of community,” Mack McCarter said. “It has to be intentional acts of connected caring.”

McCarter is no pushover; he gets the idea is pretty hard to grasp. But he believes to his core that caring can not only be cathartic, it might just change the world.

He said, “Lee, I am living for the hope that one day, one day in the human race, some child is gonna say, ‘What’s hate?’ And I’m living for that day.”

Story produced by Dustin Stephens. Editor: Carol Ross.

https://www.cbsnews.com/news/rebuilding-caring-communities-block-by-block/

by Dyani Lewis

General view as customers return to the Regal Moon JD Wetherspoons pub in Rochdale, England.
As restrictions are lifted, many researchers worry that the risk of catching COVID-19 will go up in crowded indoor spaces.Credit: Anthony Devlin/Getty

In Lidia Morawska’s home city of Brisbane on Australia’s east coast, roadside signs broadcast a simple message: ‘Wash hands, save lives.’ She has no problem with that: “Hand washing is always a good measure,” says the aerosol scientist, who works at the Queensland University of Technology. But the sign might be outdated.

Converging lines of evidence indicate that SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, can pass from person to person in tiny droplets called aerosols that waft through the air and accumulate over time. After months of debate about whether people can transmit the virus through exhaled air, there is growing concern among scientists about this transmission route.

This week, Morawska and aerosol scientist Donald Milton at the University of Maryland, College Park, supported by an international group of 237 other clinicians, infectious-disease physicians, epidemiologists, engineers and aerosol scientists, published a commentary (1) in the journal Clinical Infectious Diseases that urges the medical community and public-health authorities to acknowledge the potential for airborne transmission. They also call for preventive measures to reduce this type of risk.

The researchers are frustrated that key agencies, such as the World Health Organization (WHO), haven’t been heeding their advice in their public messages.

In response to the commentary, the WHO has softened its position, saying in a press conference on 7 July that it will issue new guidelines about transmission in settings with close contact and poor ventilation. “We have to be open to this evidence and understand its implications regarding the modes of transmission, and also regarding the precautions that need to be taken,” said Benedetta Allegranzi, technical leader of the WHO task force on infection control.

Morawska is “really pleased, relieved, and amazed”, by the WHO’s statement.

For months, the WHO has steadfastly pushed back against the idea that there is a significant threat of the coronavirus being transmitted by aerosols that can accumulate in poorly ventilated venues and be carried on air currents. The agency has maintained that the virus is spread mainly by contaminated surfaces and by droplets bigger than aerosols that are generated by coughing, sneezing and talking. These are thought to travel relatively short distances and drop quickly from the air.

This type of guidance has hampered efforts that could prevent airborne transmission, such as measures that improve ventilation of indoor spaces and limits on indoor gatherings, say the researchers in the commentary: “We are concerned that the lack of recognition of the risk of airborne transmission of COVID-19 and the lack of clear recommendations on the control measures against the airborne virus will have significant consequences: people may think that they are fully protected by adhering to the current recommendations, but in fact, additional airborne interventions are needed for further reduction of infection risk.”

This is particularly important now, as government-mandated lockdowns ease and businesses reopen. “To control [the pandemic], we need to control all the means of infection,” says Morawska, who first contacted the WHO with her concerns and published a summary of the evidence (2) in early April.

But this conclusion is not popular with some experts because it goes against decades of thinking about respiratory infections. Since the 1930s, public-health researchers and officials have generally discounted the importance of aerosols — droplets less than 5 micrometres in diameter — in respiratory diseases such as influenza. Instead, the dominant view is that respiratory viruses are transmitted by the larger droplets or through contact with droplets that fall on surfaces or are transferred by people’s hands. When SARS-CoV-2 emerged at the end of 2019, the assumption was that it spread in the same way as other respiratory viruses and that airborne transmission was not important.

The WHO is following the available evidence, and has moderated its earlier opposition to the idea that the virus might spread through aerosols, according to Allegranzi. She says that although the WHO acknowledges that airborne transmission is plausible, current evidence falls short of proving the case. She adds that recommendations for physical distancing, quarantine and wearing masks in the community are likely go some way towards controlling aerosol transmission if it is occurring.

Age-old debate

The debate over transmission routes has big implications for efforts to stop the virus from spreading. Smaller, lighter aerosols can linger and accumulate in the air and travel long distances on air currents. But studies going back to those of engineer William Wells in the 1930s have suggested that large droplets fall out of the air within about 2 metres.

When SARS-CoV-2 emerged, health officials recommended frequent hand washing and maintaining a physical distance to break droplet and contact transmission routes. And some researchers and clinicians say these approaches are enough. Contact-tracing data support those measures, says Kate Grabowski, an infectious-disease epidemiologist at Johns Hopkins University in Baltimore, Maryland. “The highest-risk contacts are those that are individuals you share a home with or that you’ve been in a confined space with for a substantial period of time, which would lead me to believe it’s probably driven mostly by droplet transmission,” she says, although she says that aerosol transmission might occur on rare occasions.

But other researchers say that case studies of large-scale clusters have shown the importance of airborne transmission. When the news media reported large numbers of people falling ill following indoor gatherings, that caused Kim Prather, an aerosol scientist at the University of California, San Diego, to begin questioning the adequacy of the social-distancing recommendations from the US Centers for Disease Control and Prevention (CDC), which call for people to stay 6 feet (1.8 metres) apart. The indoor spread suggested the virus was being transmitted in a different way from how health authorities had assumed. “For an atmospheric chemist, which I am, the only way you get there is you put it in the air and everybody breathes that air,” says Prather, who joined the commentary. “That is the smoking gun.”

Many researchers concerned about airborne transmission point to the example of a fateful choir rehearsal that took place an hour’s drive from Seattle, Washington, on 10 March. Sixty-one members of the Skagit Valley Chorale gathered for a practice that lasted two-and-a-half hours. Despite there being hand sanitizer at the door, and choir members refraining from hugs and handshakes, at least 33 choristers contracted SARS-CoV-2, and two eventually died. Investigators concluded that the virus could have spread in aerosols produced by singing, and a ‘super-emitter’ who produced more aerosol particles than is typical, although they couldn’t rule out transmission through objects or large droplets (3).

But Morawska has modelled the conditions in the rehearsal hall and says there is no need to invoke the idea of a superspreader (4). Inadequate ventilation, the long exposure time and the singing were sufficient to explain the number of people who became infected. And no amount of ventilation could have reduced the risk to an acceptable level for the two-and-a-half-hour rehearsal, she says.

In another case, researchers used a tracer gas to show that aerosols carried on currents from an air-conditioning unit in a restaurant in Guangzhou, China, were to blame for an outbreak affecting ten diners from three separate families. None of the staff or patrons seated near other air-conditioning units were infected (5).

Meanwhile, a tour-bus passenger in Hunan province in China infected 8 of the 49 people on the bus. One of those sat 4.5 metres away from the infected person and entered and exited the bus through a different door. “That excludes the possibility of contacting each other or [being] in very close contact,” says Yang Yang, an epidemiologist at the University of Florida in Gainsville who is co-authoring a report on the case. “I think there is enough evidence for us to be very concerned in indoor environments, especially in confined spaces,” he says.

Dangerous droplets

Case studies can provide circumstantial evidence that aerosols are carrying the virus, but researchers want to nail down how and when that happens. The problem is catching aerosols in the act.

Laboratory studies going back to the 1930s and 1940s concluded that droplets expelled through talking or coughing are larger than aerosols. These bigger droplets, more than 5 micrometres in diameter, drop out of the air quickly because they are too heavy to ride on light air currents.

But more-sensitive experiments are now painting a more complex picture that points to the importance of aerosols as a transmission route. A study published in May used laser-light scattering to detect droplets emitted by healthy volunteers when speaking. The authors calculated (6) that for SARS-CoV-2, one minute of loud speaking generates upwards of 1,000 small, virus-laden aerosols 4 micrometres in diameter that remain airborne for at least 8 minutes. They conclude that “there is a substantial probability that normal speaking causes airborne virus transmission in confined environments”.

Another study (7) published by Morawska and her colleagues as a preprint, which has not yet been peer reviewed, found that people infected with SARS-CoV-2 exhaled 1,000–100,000 copies per minute of viral RNA, a marker of the pathogen’s presence. Because the volunteers simply breathed out, the viral RNA was likely to be carried in aerosols rather than in the large droplets produced during coughing, sneezing or speaking.

Other laboratory studies suggest that aerosols of SARS-CoV-2 remain infectious for longer than do aerosols of some related respiratory viruses. When researchers created aerosols of the new coronavirus, they remained infectious for at least 16 hours, and had greater infectivity than aerosols of the coronaviruses SARS-CoV and MERS-CoV, which cause severe acute respiratory syndrome and Middle East respiratory syndrome, respectively (8).

Outside the lab, it is much more of a challenge to detect aerosols and show that they can transmit the virus. In one study, researchers in Wuhan, China, detected SARS-CoV-2 RNA in aerosol samples collected in a hospital (9). But the WHO and others have criticized studies such as this because they detect only viral RNA, not infectious virus. “All these researchers are struggling to find the viable virus” in clinical settings, says Allegranzi. “Whenever this is found, it will be really very relevant.”

One of the problems researchers face in studying virus viability in aerosols is the way that samples are collected. Typical devices that suck in air samples damage a virus’s delicate lipid envelope, says Julian Tang, a virologist at the University of Leicester, UK. “The lipid envelope will shear, and then we try and culture those viruses and get very, very low recovery,” he says.

A few studies, however, have successfully measured the viability of aerosol-borne virus particles. A team at the US Department of Homeland Security Science & Technology Directorate in Washington DC found that environmental conditions play a big part in how long virus particles in aerosols remain viable. SARS-CoV-2 in mock saliva aerosols lost 90% of its viability in 6 minutes of exposure to summer sunlight, compared with 125 minutes in darkness (10). This study suggests that indoor environments might be especially risky, because they lack ultraviolet light and because the virus can become more concentrated than it would in outdoor spaces.

Researchers say that one big unknown remains: how many virus particles are needed to trigger an infection? That’s one reason that Allegranzi would like to see randomized trials that demonstrate that interventions aimed at controlling aerosols actually work. One example, she says, would be a trial showing that tight-fitting respirator masks offer better protection than looser-fitting medical masks in a health-care setting.

Tang, who contributed to the commentary, says the bar of proof is too high regarding airborne transmission. “[The WHO] ask for proof to show it’s airborne, knowing that it’s very hard to get proof that it’s airborne,” he says. “In fact, the airborne-transmission evidence is so good now, it’s much better than contact or droplet evidence for which they’re saying wash [your] hands to everybody.”

Policy evolution

Ultimately, says Morawska, strong action from the top is crucial. “Once the WHO says it’s airborne, then all the national bodies will follow,” she says.

In the commentary in Clinical Infectious Diseases, she and the other researchers argue that studies on SARS-CoV-2 and other viruses strongly suggest that airborne transmission of SARS-CoV-2 is an important pathway (1). The commentary urges public-health organizations, including the WHO, and the medical community to take into account the possibility of the airborne route.

The WHO says it is paying attention to such concerns. It will “continue to examine everything that is emerging”, says Allegranzi. But last week, she questioned the qualifications of those driving the debate. “There is this movement, which made their voice very loud by publishing various position papers or opinion papers,” she says. “Why don’t we ask ourselves … why are these theories coming mainly from engineers, aerobiologists, and so on, whereas the majority of the clinical, infectious-diseases, epidemiology, public health, and infection-prevention and control people do not think exactly the same? Or they appreciate this evidence, but they don’t think that the role is so prominent?”

Is the coronavirus airborne? Experts can’t agree

Morawska disputes this characterization. And the list of people who joined the commentary reveals 40 physicians, virologists and infectious-disease epidemiologists, along with at least 20 aerosol scientists who work directly on transmission of infectious agents.

During the 7 July press conference, Maria Van Kerkhove, the WHO’s technical lead for COVID-19, said about the commentary; “Many of the signatories are engineers, which is a wonderful area of expertise, which adds to growing knowledge about the importance of ventilation.”

Governments have started to move on their own to combat airborne transmission. In May, the guidance from the German department of health changed to state explicitly that “Studies indicate that the novel coronavirus can also be transmitted through aerosols … These droplet nuclei can remain suspended in the air over longer periods of time and may potentially transmit viruses. Rooms containing several people should therefore be ventilated regularly.” The CDC doesn’t mention aerosols or airborne transmission, but it updated its website on 16 June to say that the closeness of contact and the duration of exposure is important.

A spokesperson for the UK’s Scientific Advisory Group for Emergencies says there is weak evidence for aerosol transmission in some situations, but the group nonetheless recommends “that measures to control transmission include those that target aerosol routes”. When the United Kingdom reviewed its social-distancing guidelines, it advised people to take extra precautions in situations where it isn’t possible to stay 2 metres apart. The advice includes recommendations to wear a face mask and to avoid face-to-face interactions, poor ventilation and loud talking or singing.

Allegranzi says that the WHO’s panel of 35 experts that vets emerging evidence has discussed airborne transmission on at least four occasions, and that the WHO is working with aerobiologists and engineers to discuss emerging evidence and develop better ventilation guidelines.

This is not the first time during the pandemic that clinicians and researchers have criticized the WHO for being slow to update guidelines. Many had called on the agency early on to acknowledge that face masks can help to protect the general public. But the WHO did not make an announcement on this until 5 June, when it changed its stance and recommended the wearing of cloth masks when social distancing wasn’t possible, such as on public transport and in shops. Many countries were already recommending or mandating their use. On 3 April, the CDC issued recommendations to use masks in areas where transmission rates are high. And evidence backs up those actions: a systematic review found ten studies of COVID-19 and related coronaviruses — predominantly in health-care settings — that together show that face masks do reduce the risk of infection (11).

Allegranzi acknowledges that regarding the WHO’s position on masks, “the previous [advice] maybe was less clear or more cautious”. She says that emerging evidence that a person with SARS-CoV-2 is able to pass it on before symptoms have started (pre-symptomatic) or without ever showing symptoms (asymptomatic), factored into the decision to change the guidance. Additional research — commissioned by the WHO — showing that cloth face masks are an effective barrier, was also an important factor.

Researchers who argue for the importance of aerosols say that governments and businesses should take specific steps to reduce this potential route of transmission. Morawska would like to see recommendations against air recirculation in buildings and against overcrowding; and she calls for standards that stipulate effective levels of ventilation, and possibly ones that require air systems to filter out particles or use ultraviolet light to kill airborne viruses (12).

Allegranzi maintains that current WHO recommendations are sound. “It’s a bundle of precautions, including hand hygiene, including masks, including the distancing, which are all important,” she says. “Some of these measures will have an impact also on aerosol transmission, if it’s a reality.

doi: 10.1038/d41586-020-02058-1

References
1. Morawska, L. & Milton, D. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciaa939 (2020).

2. Morawska, L. & Coa, J. Environ. Int. 139, 105730 (2020).

3. Hamner, L. et al. Morb. Mortal. Wkly Rep. 69, 606–610 (2020).

4. Buonanno, G., Morawska, L. & Stabile, L. Preprint at medrXiv https://doi.org/10.1101/2020.06.01.20118984 (2020).

5. Li, Y. et al. Preprint at medrXiv https://doi.org/10.1101/2020.04.16.20067728v1 (2020).

6. Stadnytskyi, V., Bax, C. E., Bax, A. & Anfinrud, P. Proc. Natl Acad. Sci. USA 117, 11875–11877 (2020).

7. Ma, J. et al. Preprint at medrXiv https://doi.org/10.1101/2020.05.31.20115154 (2020).

8. Fears, A. C. et al. Emerg. Infect. Dis. https://doi.org/10.3201/eid2609.201806 (2020).

9. Liu, Y. et al. Nature 582, 557–560 (2020).

10. Shuit, M. et al. J. Infect. Dis. https://doi.org/10.1093/infdis/jiaa334 (2020).

11. Chu, D. K. et al. Lancet 395, 1973–1987 (2020).

12. Morawska, L. et al. Environ. Int. 142, 105832 (2020).


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

By Lauren Mascarenhas and Sandee LaMotte

If you were one of the Americans who decided to self-isolate before you were required to by state or local mandate, good for you.

You saved lives.

That’s the finding of a study published Monday in the journal “The Lancet: Infectious Diseases,” which used mobile phone data to track how people behaved between January 1 and April 20, a time before widespread calls by state and local officials to stay at home.

The study found that individual decisions to stay put in homes, except for necessary outings for food and medical supplies, likely helped slow the spread of coronavirus before state or local stay-at-home orders were implemented by government officials.

Fast spread slowed by individual behavior

Within four months of Covid-19 first being reported in the US, the disease had spread to every state and to more than 90% of all counties.

The study found that social distancing measures and the slowdown of coronavirus were primarily driven by changes in individual behavior and local regulations, noting that state and federal regulations were implemented either too late or not at all.

In all 25 counties evaluated in the study, individuals moved around less six to 29 days before statewide stay-at-home orders were implemented.

In 21 counties, cell phone data found mobility slowed on an individual level even before local stay-at-home orders were in place, according to study author Lauren Gardner, an associate professor in the department of civil and systems engineering at the Johns Hopkins Whiting School of Engineering.

Is using cell phone data a good way to track behavior?

They are a “pretty good indicator of travel patterns because phones are often carried around by the person in question,” Flavio Toxvaerd, a lecturer in economics at the Interdisciplinary Research Centre at the University of Cambridge, said in an email.

“In any case, the results chime with those found using other data, such as transaction data from credit cards,” said Toxvaerd, who was not involved in the study.

From late January to mid-April, the study found people reduced their daily movements by varying amounts: In New York City, people reduced their normal activity by 35%; while people in Houston’s Harris County reduced their activity by 63% of what was typical.

The study found it took about nine to 12 days, on average, for the effects to begin showing in infection rates, which is somewhat consistent with the 5 to 14 day incubation period of the virus.

Gardner’s team said the strong connection between social distancing and decreased transmission rates means that a return to normal mobility around the country creates a significant risk of increased infections — one that will likely not be apparent for up to three weeks after people begin resuming their normal activity.

“Indeed, information here is key,” Toxvaerd said. “You cannot react to changes in infection risks if you don’t know what they are.

“There are those for which information may not change behavior,” he added. “For those people, we may have to provide incentives for desirable social distancing behavior, for example through fines and inducements to stay at home.”

Some limitations

The study did not differentiate among low-risk trips, like going to the park, and higher-risk trips, like going to the grocery store. Because the data did not include sociodemographic information, the researchers could not isolate information about older adults, those with medical disorders and underserved communities, for whom social distancing can be more difficult.

“If individual-level and local actions were not taken, and social distancing behavior was delayed until the state-level directives were implemented, COVID-19 would have been able to circulate unmitigated for additional weeks in most locations, inevitably resulting in more infections and deaths,” Gardner said in a statement.

“It is within the power of each US resident, even without government mandates, to help slow the spread of COVID-19,” she added.

https://www.cnn.com/2020/07/01/health/covid-19-staying-home-saved-lives-wellness/index.html


Writer and educator James Weldon Johnson (1871-1938) who wrote “Lift Every Voice and Sing.”

By Saeed Ahmed

“Lift Every Voice and Sing” is not so much a song as a hymn — a call to action that honors African Americans’ long, painful struggle for freedom and affirms their rightful place in our national identity.

Sing a song full of faith that the dark past has taught us.

Sing a song full of the hope that the present has brought us.

Like “America the Beautiful,” it’s about the promise this nation holds for all its citizens. And like the resilience it celebrates, it’s now a deeply rooted part of African American culture — some 120 years after it was written.

As America continues its reckoning with systemic racism, the NFL has announced it will play the song before every game in Week 1 of the 2020 NFL season.

How the song came about: The song was written in 1899 by James Weldon Johnson, who had been tasked with delivering an address to celebrate President Abraham Lincoln’s birthday the following year. He began prepping for it, but as he writes in his autobiography, “I wanted something else also.”

He took his words to his younger brother, a classically trained composer named J. Rosamond Johnson, and “Lift Ev’ry Voice and Sing” (as it is accurately titled) was born.

For Johnson, writing the lyrics was an emotional experience. “I could not keep back the tears, and made no effort to do so,” he wrote.

Where it was first performed: At the time, Johnson was the principal of the segregated Stanton School in Jacksonville, Florida. That’s where the hymn debuted the following year, sung by 500 children at an event celebrating Black history.

It caught on immediately and was performed at churches and school assemblies.
“Recently I spoke for the summer labor school at Bryn Mawr College,” Johnson wrote in his autobiography, “and was surprised to hear it fervently sung by the white students there and to see it in their mimeographed folio of songs.”
Later, the National Association for the Advancement of Colored People adopted it as its official song.

“During the Jazz Age, the Swing Era, World War II and the early Cold War years, dynamic new styles of African American popular song emerged, but ‘Lift Ev’ry Voice and Sing’ continued to be both a sentimental and a dignified favorite of black communities,” wrote Burton Peretti in his book, “Lift Every Voice: The History of African American Music.”

It was sung to celebrate Nelson Mandela’s release from prison in 1990, and at President Barack Obama’s inauguration in 2009. Beyonce sang a 90-second snippet when she became the first black woman to headline Coachella.
Why it still resonates so deeply: Scholar Rudolph P. Byrd put it best in a piece for CNN.

“While there is no specific reference to African-Americans in the hymn,” he wrote, “the genesis and context make it impossible to ignore the centrality of the history of African-Americans and their heroic movement from slavery to freedom in a democratic republic that for centuries countenanced the contradiction of slavery, and later, segregation, to the hymn’s inspiration and composition.”

Here are the full lyrics:

Lift ev’ry voice and sing
‘Til earth and heaven ring
Ring with the harmonies of Liberty.
Let our rejoicing rise
High as the list’ning skies
Let it resound loud as the rolling sea.
Sing a song full of the faith that the dark past has taught us
Sing a song full of the hope that the present has brought us.
Facing the rising sun of our new day begun
Let us march on ’til victory is won.
Stony the road we trod
Bitter the chastening rod
Felt in the days when hope unborn had died.
Yet with a steady beat
Have not our weary feet
Come to the place for which our fathers sighed?
We have come over a way that with tears has been watered
We have come, treading our path through the blood of the slaughtered.
Out from the gloomy past
‘Til now we stand at last
Where the white gleam of our bright star is cast.
God of our weary years
God of our silent tears
Thou who has brought us thus far on the way.
Thou who has by Thy might
Led us into the light
Keep us forever in the path, we pray.
Lest our feet stray from the places, our God, where we met Thee
Lest, our hearts drunk with the wine of the world, we forget Thee.
Shadowed beneath Thy hand
May we forever stand
True to our God
True to our native land.

https://www.cnn.com/2020/07/03/us/lift-every-voice-and-sing-history-trnd/index.html?utm_term=159386411622837ae55b67943&utm_source=The+Good+Stuff+07%2F04%2F20+NEW&utm_medium=email&utm_campaign=222675_1593864116229&bt_ee=ldoYz%2FneoXDeJJXjVfcDAAZ%2FAvgI%2BmVs0Z%2BK5PWCcqY1C2%2BUY3IZEtU75EBEGPMX&bt_ts=1593864116229


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

by DAVID NIELD

We already know that our brains have a waste disposal system that keeps dead and toxic neurons from clogging up our biological pathways. Now, scientists have managed to capture a video of the process for the first time, in laboratory tests on mice.

There’s still a lot we don’t know about how dead neurons are cleared out, and how the brain reacts to them, so the new research could be a significant step forward in figuring some of that out – even if we’ve not yet confirmed that human brains work in the exact same way.

“This is the first time the process has ever been seen in a live mammalian brain,” says neurologist Jaime Grutzendler from the Yale School of Medicine in Connecticut.

Further down the line, these findings might even inform treatments for age-related brain decline and neurological disorders – once we know more about how brain clean-up is supposed to work, scientists can better diagnose what happens when something goes wrong.

The team focussed in on the glial cells responsible for doing the clean-up work in the brain; they used a technique called 2Phatal to target a single brain cell for apoptosis (cell death) in a mouse and then followed the route of glial cells using fluorescent markers.

“Rather than hitting the brain with a hammer and causing thousands of deaths, inducing a single cell to die allows us to study what is happening right after the cells start to die and watch the many other cells involved,” says Grutzendler.

“This was not possible before. We are able to show with great clarity what exactly is going on and understand the process.”

Three types of glial cells – microglia, astrocytes, and NG2 cells – were shown to be involved in a highly coordinated cell removal process, which removed both the dead neuron and any connecting pathways to the rest of the brain. The researchers observed one microglia engulf the neuron body and its main branches (dendrites), while astrocytes targeted smaller connecting dendrites for removal. They suspect NG2 may help prevent the dead cell debris from spreading.

The researchers also demonstrated that if one type of glial cell missed the dead neuron for whatever reason, other types of cells would take over their role in the waste removal process – suggesting some sort of communication is occurring between the glial cells.

Another interesting finding from the research was that older mouse brains were less efficient at clearing out dead neural cells, even though the garbage removal cells seemed to be just as aware that a dying cell was there.

This is a good opportunity for future research, and could give experts insight into how older brains start to fail in various ways, as the garbage disposal service starts to slow down or even breaks.

New treatments might one day be developed that can take over this clearing process on the brain’s behalf – not just in elderly people, but also those who have suffered trauma to the head, for example.

“Cell death is very common in diseases of the brain,” says neurologist Eyiyemisi Damisah, from the Yale School of Medicine.

“Understanding the process might yield insights on how to address cell death in an injured brain from head trauma to stroke and other conditions.”

The research has been published in Science Advances.

https://www.sciencealert.com/for-the-first-time-scientists-capture-video-of-brains-clearing-out-dead-neurons

Cleveland Bachs!

Posted: July 1, 2020 in Uncategorized
Tags: ,

For the past few weeks, I’ve been traveling around my adopted home of Cleveland playing the Prelude to Bach’s First Cello Suite. Music may not be able to solve the world’s problems, but I believe it can, as Lincoln said, “bind up the nation’s wounds.”

“With malice toward none; with charity for all; with firmness in the right, as God gives us to see the right, let us strive on to finish the work we are in; to bind up the nation’s wounds…to do all which may achieve and cherish a just and a lasting peace among ourselves, and with all nations.”

Abraham Lincoln, Second Inaugural Address

Special thanks to Katarina Davies for her help with this project. Also, thanks to Grace Gill and Jennifer Woloschyn Harrell.