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Dec 28 2023 Johns Hopkins Medicine

Scientists at the Johns Hopkins University School of Medicine and the National Institutes of Health have identified a protein in the visual system of mice that appears to be key for stabilizing the body's circadian rhythms by buffering the brain's response to light. The finding, published Dec. 5 in PLoS Biology, advances efforts to better treat sleep disorders and jet lag, the study authors say. If circadian rhythms adjusted to every rapid change in illumination, say an eclipse or a very dark and rainy day, they would not be very effective in regulating such periodic behaviors as sleep and hunger. The protein we identified helps wire the brain during neural development to allow for stable responses to circadian rhythm challenges from day to day."

Alex Kolodkin, Ph.D., professor in the Johns Hopkins Department of Neuroscience and deputy director for the Institute for Basic Biomedical Sciences

Kolodkin co-led the study with Samer Hattar, Ph.D., chief of the Section on Light and Circadian Rhythms at the National Institute of Mental Health.

Scientists have long known that most living things have a circadian "clock," a set of biological rhythms that operate on about a 24-hour cycle and that affect alertness, sleepiness, appetite and body temperature, among other cyclic behaviors. Upsetting this system -; through shift work or long-distance travel over multiple time and light zones in humans, for example -; can have severe consequences. Previous studies link persistent upsets in circadian rhythm to increased risk of cancer, depression and a host of other medical problems.

Circadian systems are essentially "trained" by exposure to light. Although researchers have made significant headway over the last few decades in outlining the mechanisms responsible for circadian rhythms, it has remained unclear how the brain becomes wired for them.

To learn more, Kolodkin and Hattar, along with study first authors John Hunyara and Kat Daly and their colleagues, searched a database for biological molecules present during development in the mouse brain's control center for circadian rhythms -; the suprachiasmatic nucleus (SCN).

Located deep within both the mouse and human brain in the hypothalamus, the SCN sits near areas that control vision and makes connections with brain cells that lead to the retina, the light-sensing part of the eye.

The research team quickly zeroed in on a cell surface protein called teneurin-3 (Tenm3), part of a larger family of proteins that play key roles in the visual system circuit assembly and more generally in other central nervous system circuits.

When the researchers genetically altered mice to prevent Tenm3 production, the animals developed fewer connections between the retina and the SCN, compared with animals with intact Tenm3. However, the mice lacking Tenm3 developed far more connectivity between cells in the core and shell of the SCN, where Tenm3 tends to localize. Related StoriesBreakthrough in Parkinson's research: Scientists identify protein synthesis pathway as culpritHemoglobin-like protein plays an important role in the development of the heart, study findsStudy reveals hidden inactive form of p38a protein

To see how Tenm3 might stabilize circadian rhythms or subject them to disruption by even a tiny bit of light, the scientists designed a set of experiments.

First, they trained mice lacking Tenm3 on a 12-hour light/dark cycle, then shifted the dark period ahead by six hours. Mice with intact Tenm3 took about four days to readjust their circadian rhythms to the shift, as measured by activity patterns diagnostic of normal sleep cycles. The animals without Tenm3, however, adjusted far more rapidly, in about half the time.

When the researchers performed a similar experiment with light twice as dim as in the earlier test, it took the Tenm3-intact mice about eight days to adjust their circadian cycles, but only about four days for the mice without Tenm3. Even just a 15-minute pulse of dim light triggered the Tenm3-lacking mice – but not the mice with normal Tenm3 protein -; to produce a brain chemical that serves as a proxy for light exposure, suggesting a heightened sensitivity to light cues necessary for setting or resetting the circadian clock.

These findings suggest to the authors that Tenm3 helps wire the brain to maintain stable circadian rhythms even when light exposure is variable. By learning more about this system and Tenm3's role, says Hattar, researchers may eventually be able to diagnose and treat glitches that lead to insomnia and other sleep disorders in people, or possibly develop treatments for jet lag.

"There are very clear implications for human health," he says.

Other Johns Hopkins researchers who contributed to this study include Katherine Torres.

This study was funded by grants from the NIH (R01EY032095) and the Intramural Research Program at the NIMH (ZIAMH002964). Source:

Johns Hopkins MedicineJournal reference:

Hunyara, J. L., et al. (2023). Teneurin-3 regulates the generation of nonimage-forming visual circuitry and responsiveness to light in the suprachiasmatic nucleus. PLOS Biology. doi.org/10.1371/journal.pbio.3002412.

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Migrants locked up in notorious El Salvador jail released in Venezuela-US prisoner swap

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Migrants locked up in notorious El Salvador jail released in Venezuela-US prisoner swap

On Friday, Paola Paiva waited in a hotel near Caracas airport, nervous but giddy with excitement to be reunited with her brother, finally.

For five months, Arturo Suarez has been detained in a notorious prison in El Salvador.

“I am going to wait for my brother to call me,” she told Sky News, “and after giving him a hug, I want to just listen to him, listen to his voice. Let him talk and tell us his story.”

Suarez was one of the more than 250 Venezuelan migrants who had been living in America but were arrested in immigration raids by the Trump administration and sent to El Salvador, a showpiece act in the president’s promise to deport millions of migrants.

Paola Paiva holds a vigil for brother Arturo Suarez. Pic: Reuters
Image:
Paola Paiva holds a vigil for brother Arturo Suarez. Pic: Reuters

Most of the men had never even been to El Salvador before. Their detention has been controversial because the White House claims the men are all part of the dangerous Tren de Aragua gang but has provided little evidence to support this assertion.

The only evidence Paola had that Suarez was still alive was a picture of him published on a news website showing the inside of the maximum security CECOT jail.

He is one of dozens of men with their hands and feet cuffed, heads shaved and bodies shackled together.

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Now he is returning to his home country, one of the bargaining chips in a deal that saw the release of ten Americans and US permanent residents who had been seized by the Venezuelan authorities.

Venezuelans arrive back in home country after being detained in El Salvador
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Venezuelans arrive back in home country after being detained in El Salvador

Paola had tried to go to the airport to greet her brother as he disembarked a charter plane bringing the men back from El Salvador but authorities told her to wait at a nearby hotel.

“They told us they are taking them all to a hotel to rest,” she said.

“But I managed to get someone to give my phone number on a piece of paper to my brother, so I am expecting his call tomorrow, as soon as he can access a phone.

“We heard they are going to perform some medical exams on them and check their criminal records,” she added. “I’m not afraid; I’m not worried since my brother has a clean record.

“I am so happy. I knew this day would happen, and that it would be unexpected, that no one was going to notify us. I knew it was going to be a total surprise.”

US citizens released from Venezuela. Pic: Reuters
Image:
US citizens released from Venezuela. Pic: Reuters

The Trump administration had paid the El Salvador government, led by President Nayib Bukele, millions of dollars to imprison the men.

Homeland security secretary Kristi Noem visited CECOT last month, posing in front of prisoners for a photo opportunity.

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But Cristosal, an international human rights group based in El Salvador, says it has “documented systematic physical beatings, torture, intentional denial of access to food, water, clothing, health care,” inside the prison.

A video which was seemingly filmed aboard the charter flight bringing the Venezuelan migrants back to Caracas shows Arturo briefly talking about his experience inside.

He looks physically well but speaks into the camera and says: “We were four months with no communication, no phone calls, kidnapped, we didn’t know what (the) day was, not even the time.

“We were beat up at breakfast, lunch and dinner,” he continues.

Sky News interviewed Arturo Suarez‘s brother Nelson near his home in the US in April, weeks after Arturo – an aspiring singer – had been arrested by immigration and customs enforcement (ICE) agents while filming a music video inside a house.

Nelson said he believed Arturo’s only crime was “being Venezuelan and having tattoos.” He showed me documents that indicate Arturo has no criminal record in Venezuela, Chile, Colombia or the United States, the four countries he has lived in.

Now Nelson is delighted Arturo is being released – but worries for his future.

“The only thing that casts a shadow in such a moment of joy is that bit of anger when I think that all the governments involved are going to use my brother’s story, and the others on that flight, as political gain,” he said.

“Each of them will tell a different story, making themselves the heroes, when the reality is that many innocent people suffered unfairly and unnecessarily, and many families will remain separated after this incident due to politics, immigration and fear.”

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Ha Long Bay: At least 34 dead after tourist boat capsizes in Vietnam

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Ha Long Bay: At least 34 dead after tourist boat capsizes in Vietnam

At least 34 people have died after a tourist boat capsized in Vietnam, according to state media reports.

The Wonder Sea boat was reportedly carrying 53 people, including five crew members, when it capsized due to strong winds in Ha Long Bay on Saturday.

It happened at roughly 2pm local time (7am GMT). Rescue teams have found 11 survivors and recovered 34 bodies, eight of them children, the state-run Vietnam News Agency said, citing local authorities.

People on a capsized tourist boat being rescued in Ha Long Bay, Vietnam. Pic: QDND via AP
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Rescuer in Ha Long Bay are searching for survivors. Pic: QDND via AP

The People’s Army Newspaper, which cited local border guards, said authorities have not yet confirmed details about the tourists, including their nationalities, as the rescue operation continues.

Most of the passengers were tourists, including about 20 children, from the country’s capital city, Hanoi, the newspaper said.

The incident comes shortly after the arrival of Storm Wipha in the South China Sea, bringing strong winds, heavy rain and lightning to the area.

A body being carried on stretcher after a tourist boat capsized in Ha Long Bay, Vietnam. Pic: QDND via AP
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A body being carried on stretcher after a tourist boat capsized in Ha Long Bay, Vietnam. Pic: QDND via AP

The named storm is the third typhoon to hit the South China Sea this year, and is expected to make landfall along the northern coast of Vietnam early next week.

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Disruptions linked to the storm have also had an impact on air travel, according to Noi Bai Airport.

The airport reported that nine incoming flights were diverted to other airports, while three outgoing flights were temporarily grounded due to adverse weather conditions.

Tourist boats cruise in Halong Bay. File pic: Reuters
Image:
Tourist boats cruise in Halong Bay. File pic: Reuters

The winds brought by Storm Wipha reached up to 63mph (101kmph) and gusts of up to 68mph (126kmph) as it passed south of Taiwan on Saturday, according to the island’s Central News Agency.

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Ha Long Bay is around 125mi (200km) north east of Hanoi and attracts tens of thousands of visitors each year.

Of those who visit Ha Long Bay, many choose to take overnight boat tours to further explore the area.

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Gaza: More than 30 people killed ‘as Israeli troops open fire towards Palestinians waiting for aid’

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Gaza: More than 30 people killed 'as Israeli troops open fire towards Palestinians waiting for aid'

More than 30 people have been killed after Israeli troops opened fire towards crowds of Palestinians waiting for aid, according to witnesses and hospital officials.

The deaths occurred near distribution hubs operated by the US-Israeli-backed Gaza Humanitarian Foundation (GHF), which began distributing food packages in Gaza at the end of May, after Israel eased its 11-week blockade of aid into the territory.

At least 32 people were killed on Saturday, according to the Hamas-run Gaza health ministry, while a further 100 people were injured, according to local reports.

Most of the deaths came as Palestinians massed in the Teina area, around 3km (2 miles) away from a GHF aid distribution centre east of the city of Khan Younis.

More than 3o killed near aid distribution centres. Pic:Mariam Dagga/AP
Image:
More than 30 people killed near aid distribution centres. Pic: Mariam Dagga/AP

Mahmoud Mokeimar said he was walking with crowds of people – mostly young men – towards the food hub when troops fired warning shots as the crowd advanced, before opening fire towards the marching people.

“It was a massacre… the occupation opened fire at us indiscriminately,” he said.

Injured Palestinians are brought to Nasser Hospital in Khan Younis. Pic: Mariam Dagga/AP
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Injured Palestinians are brought to Nasser Hospital in Khan Younis. Pic: Mariam Dagga/AP

Akram Aker said troops fired machine guns mounted on tanks and drones.

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“They encircled us and started firing directly at us,” he said.

The Nasser Hospital in Khan Younis said it received 25 bodies, along with dozens of wounded.

Seven other people, including one woman, were killed in the Shakoush area, hundreds of yards north of another GHF hub in Gaza’s southernmost city of Rafah, the hospital said.

The army and GHF did not immediately comment on Saturday’s violence.

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The GFH, which has four distribution centres, three of which are in the southern Gaza Strip, says it has distributed millions of meals to hungry Palestinians.

But local health officials and witnesses say hundreds of people have been killed by Israeli army fire as they try to reach the distribution hubs.

The GHF, which employs private armed guards, says there have been no deadly shootings at its sites, though this week, 20 people were killed at one of its locations, most of them in a stampede.

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The group accused Hamas agitators of causing a panic, but gave no evidence to back the claim.

The army, which is not at the sites but secures them from a distance, says it only fires warning shots if crowds get too close to its forces.

The 21-month war in Gaza was triggered when Hamas militants stormed into southern Israel on 7 October 2023, killing 1,200 people and taking 250 others hostage.

An Israeli military offensive has killed more than 58,000 Palestinians, according to the Gaza health ministry, while Gaza’s more than two million Palestinians are living through a catastrophic humanitarian crisis.

Israel and Hamas have been holding ceasefire talks in Qatar in recent weeks, but international mediators say there have been no breakthroughs.

US President Donald Trump said another 10 hostages will be released from Gaza shortly, without providing details.

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