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.
A parade marking the US Army’s 250th anniversary – and President Trump’s 79th birthday – is under way.
You can watch the event in the livestream above.
President Trump said it was going to be a “big day” and admitted: “We want to show off a little bit.”
Today is the first time in more than 30 years that tanks have rolled through the US capital.
Officials have estimated around 200,000 people could turn out, including protesters, plus 6,600 soldiers, 150 vehicles and 50 aircraft.
However, it appears far fewer have turned out – possibly due to the poor weather – and the president has warned any protesters who interfere “will be met with very big force”.
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Mr Trump is watching alongside the first lady and defence secretary as troops and military hardware file past – accompanied at times by up tempo rock music.
The event started half an hour early due to forecasted heavy rain, with cloud forcing the cancellation of a flypast by fighter jets.
Helicopters such as Apaches, Chinooks and Black Hawks are still taking part however.
Image: Pic: Reuters
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Military parachutists from the Golden Knights began the parade by swooping in, and some of the soldiers are parading in historic uniforms, complete with horses and wagons.
Vehicles from the Second World War era are also taking part.
President Trump stood and saluted many of the passing soldiers. He is said to have got the idea for the parade after being impressed with France’s Bastille Day celebrations during a visit in 2017.
Metal plates have been put down on some of Washington’s streets to protect the tarmac against the heaviest tanks – the 60-ton M1 Abrams.
Even so, the US Army has set aside several million dollars in case of any damage.
The last time such a major display took place in the US was 1991 when tanks and troops paraded to celebrate the ousting of Saddam Hussein’s army from Kuwait.
Image: Pic: Reuters
Image: Pic: Reuters
Image: Pic: Reuters
The event has been criticised by some for being something more associated with a dictatorial regime such as Russia or North Korea.
An estimated cost as high as $45m (£33.33m) has also raised eyebrows given the administration’s efforts to slash the budget of many federal departments.
Among the critics is California governor Gavin Newsom, who has been trading barbs with Mr Trump since the outbreak of riots in LA.
“And we all know, this Saturday, he’s ordering our American heroes – the United States military – forcing them to put on a vulgar display to celebrate his birthday, just as other failed dictators have done in the past,” he said.
Image: Pic: AP
Image: Pic: Reuters
Image: Pic: Reuters
The show of military might also comes as more than 1,500 protests against the Trump administration, organised under the slogan ‘No Kings’, have been planned across the US on Saturday.
Los Angeles is the scene of one demonstration, with police firing tear gas to disperse people and US Marines stationed outside the city’s federal building.
Unless Bitcoin upgrades its core cryptography in the next five years, the trust it has built over 16 years could be wiped out by a single quantum attack. Urgent upgrades are needed to protect the world’s leading cryptocurrency.
The son of an Air India plane crash victim, who was sitting one row behind the man who survived, has told Sky News he will relive “her last moments” until the day he dies.
Manju Mahesh Patel, 79, was on the London Gatwick-bound plane when it crashed in Ahmedabad shortly after take-off on Thursday.
In an interview with Sky News, Chirag Mahesh Patel, Manju’s son, said he hopes his mother’s death was “instant” and “painless”.
“To the day I die I will think, ‘what were her last moments?’,” he said.
Pointing to a framed family photograph of Ms Patel at the family home, he added: “I want to remember mum like this.
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“I don’t want to have to go and identify a burnt corpse, your own parent. How does someone, how do you ever get over that? That will be with me, that’s with me for life.”
Ms Patel had been staying in Ahmedabad for the past few months doing charity work at a temple. She was due to be picked up by her son at Gatwick on Thursday night.
Image: A family photo of Chirag Mahesh Patel with his mother
In tears, Mr Patel described his mother as “very strong” and a woman “who really loved her family”.
“The thing about my mum,” he said, “is her bond with her faith. It’s unbreakable.
“She had ultimate faith… and in times of stress she would always say God’s name… So, I know that upon take-off, I know that she was saying his name.”
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1:57
What could have caused the India plane crash?
Mr Patel said that when he realised his mother was on the flight it was just “a normal day” and “it didn’t seem real”.
He said the last time he had spoken to her he had reminded her to take her diabetes medicine and had then missed a call from her at 4am to say she had arrived at the airport.
He described “the most heartbreaking thing” was how much Ms Patel was looking forward to seeing her grandchildren, saying “it was everything to her”.
She had told him she packed her suitcase with lollipops for her six-year-old grandson, and special crisps for her 15-year-old older grandchild.
Image: Ms Patel with her six-year-old grandson
“It’s unimaginable even in my worst nightmare,” he said. “And the thing that kills me… is she was so looking forward to seeing us… she kept saying I bought this for you, I bought that, I bought the things for the kids.”
Mr Patel and his wife are due to fly to India on Saturday night to provide a DNA sample to help identify his mother’s remains.
He expressed his anger at what he called a “disgusting” and “appalling” lack of communication from Air India – which he said passed his details to a hospital but never contacted him personally.
He described feeling “neglected” by the airline, which he said would only offer him an Air India flight – and no help organising accommodation.
Mr Patel said he refused to get on the Gatwick flight back to Ahmedabad and has booked with another provider to travel to India instead.
Image: Ms Patel with her elder grandchild
“I said [to the airline] all of this happened on Thursday, you’re telling me on Friday afternoon, do you want that flight this evening? That one crashed? The one coming back where 172 goes out? They asked do you want Air India 172? I said how can you ask me that. My mum just died on Air India.”
Mr Patel said he wanted “answers” and transparency in any air accident investigation.
Air India said in a statement: “Air India stands in solidarity with the families of the passengers who tragically lost their lives in the recent accident. Our teams on the ground are doing everything possible to extend care and support during this incredibly difficult time.
“As part of our continued efforts, Air India will be providing an interim payment of ₹25 lakh or approximately £21,000 each to the families of the deceased and to the survivor, to help address immediate financial needs. This is in addition to the ₹1 crore or approximately £85,000 support already announced by Tata Sons.
“All of us at Air India are deeply saddened by this loss. We mourn with the families, loved ones, and everyone affected.”
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3:24
Families in India wait for bodies of relatives
The company’s chief executive and managing director Campbell Wilson said in a video message posted on social media that over 200 “trained caregivers” were now in place to offer dedicated assistance to families, along with counselling and other services.
He said Air India was in the process of completing precautionary safety checks on Boeing 787 aircraft as directed by regulator the Directorate General of Civil Aviation (DGCA), which would “be completed within the timelines prescribed by the regulator”.
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Mr Wilson said he had also visited the crash site and said other members of the management team would remain present “for as long as it takes”.
The aircraft’s data recorder, often referred to as a black box, has been recovered and will form part of the investigation into the worst aviation crash in a decade.
‘He was too young’: Families grieve those lost in Air India crash
It was an emotional service at Derby’s Geeta Bhawan Hindu temple, as dozens of friends, colleagues and neighbours gathered to remember Dr Prateek Joshi, his wife Komi, their daughter Miraya, and twin sons Nakul and Pradyut.
Some wiped tears from their eyes, as a colleague was asked spontaneously to pay tribute to Dr Joshi, who had been bringing his family to live in the city, when the Air India flight they were on crashed seconds after take-off.
“He was too young, too much still to give, too much still to be done, too much to offer,” his friend told worshippers.
“He was taken from us in a very cruel and abrupt way, and his family as well, and we all think about his family back in India who is missing a son, missing a daughter-in-law and missing all their grandchildren who they’ll never see growing up.”
Derby South MP Catherine Atkinson said Dr Joshi, who was a radiologist at the Royal Derby hospital, had been “contributing to our NHS and the health of so many in our city and beyond”.
She said his wife was a pathologist who had resigned from her job in India.
“I won’t forget the photograph of them on the plane, full of optimism about their new adventure,” she said, as her voice broke.
“The losses make us all hug our families and loved ones a little closer and remind us how precious our time together is.”
Dr Joshi was described as a “warm, smiling man, full of joy” who enjoyed walking in the Peak District and who had discovered “a love of fish and chips”.
His neighbour and colleague Manoj Ramtohal told Sky News Dr Joshi always had time for people.
“He was very caring and very polite, very friendly, you couldn’t meet a better man than Prateek,” he said.