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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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Phils’ Suárez K’s 10, continues historic run to 9-0

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Phils' Suárez K's 10, continues historic run to 9-0

PHILADELPHIA — Ranger Suárez stuck out 10 over seven innings and improved to 9-0 to lead the Philadelphia Phillies to their MLB-best 35th win, a 5-2 victory over the defending World Series champion Texas Rangers on Tuesday night.

Suárez’s season-opening run rivals Hall of Famers Grover Alexander and Juan Marichal among the best in baseball history.

Bryce Harper hit his 11th homer of the season to help the Phillies win for the ninth time in 11 games and continue one of the best starts in franchise history.

The Phillies have won 35 of their first 49 games for the second time in franchise history (1976). The Phillies are 27-6 in their last 33 games, marking the first time since at least 1901 they have won 27 games in a 33-game span.

This season, no pitcher in baseball has been better than Suárez.

“He knows what it takes to win games,” Harper said.

The 28-year-old lefty walked off to a standing ovation in the seventh after he caught Leody Taveras looking on a 91.6 mph sinker to end the inning. Suárez took a no-decision in his first start of the season before he reeled of wins in nine straight starts.

“I just try to throw and do the best work that I can,” Suárez said through an interpreter.

Suárez lowered his ERA to 1.36, the third-lowest ERA by a Phillies pitcher in his first 10 starts of a season. Suárez trails Alexander, who had a 1.24 ERA in first 10 starts of 1916 and a 1.31 ERA in his first 10 starts of 1915.

Suárez is the first pitcher to start 9-0 with a sub-1.50 ERA through 10 starts since Marichal did it for the San Francisco Giants in 1966. Oh, he’s also the first Phillies pitcher since Robin Roberts (1952) to win at least nine consecutive starts.

“It’s kind of mind-boggling, this historic run that he’s been on,” Phillies manager Rob Thomson said.

Jose Alvarado worked a scoreless ninth for his ninth save.

Ranger bested the Rangers, and continued his reign as Philadelphia’s top pitcher this season — no small feat for a rotation that already boasts Aaron Nola and Zack Wheeler. Suárez walked two and gave up a run before he yielded to Jeff Hoffman in the eighth inning.

Corey Seager hit a solo shot off Hoffman in the eighth to make it 3-2.

Hoffman got only two outs before Matt Strahm retired Nathaniel Lowe on a sharp line drive to left field with two runners on to end the inning.

This three-game series comes oh-so-close to serving as a World Series rematch. The Rangers needed only five games to beat Arizona and win the franchise’s first World Series — after Arizona won Games 6 and 7 in Philadelphia to rally and knock out the Phillies in the NL Championship Series.

Suárez fell into a rare early deficit after he gave up Marcus Semien‘s RBI single to left in the third.

The Phillies went ahead 2-1 off Jon Gray (2-2) on Kyle Schwarber‘s run-scoring single in the third and Alec Bohm‘s RBI single in the fourth. Harper connected off Rangers reliever Jacob Latz in the sixth for a 3-1 lead and help them snap a 12-game losing streak against the Rangers, that dates to 2014.

Bohm — who has 11 RBIs over his seven-game hitting streak — knocked in his NL-best 44th RBI on a double in the eighth, and Bryson Stott followed with a sacrifice fly for a 5-2 lead.

“They’re pitching well and they’re getting big hits,” Rangers manager Bruce Bochy said. “They’re a very good offensive club. They’re one of the best team in baseball, right now, that’s how well they’re playing.”

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Post Office inquiry: ‘Come clean’ victim demands of ex-boss Vennells

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Post Office inquiry: 'Come clean' victim demands of ex-boss Vennells

A victim of the Post Office Horizon scandal has told Sky News that ex-boss Paula Vennells must “come clean” in her evidence to the statutory inquiry.

Chirag Sidhpura, a former sub-postmaster who became one of the public champions for justice based on his own treatment at the hands of the Post Office, said he was expecting a “culture of denial” and “lies” over Ms Vennells’ three days of scheduled evidence.

She is due before the inquiry later this morning.

The 65-year-old, who was Post Office chief executive from 2012 to 2019, will be speaking publicly about what happened for the first time in almost a decade.

While she has since acknowledged that sub-postmasters were wrongly accused and prosecuted over faults in the Horizon accounting system under her watch, the inquiry will seek to uncover what she knew and when.

She told a committee of MPs in 2015: “We are a business that genuinely cares about the people who work for us. If there had been any miscarriages of justice, it would have been really important to me and the Post Office that we surfaced those. As the investigations have gone through, so far we have no evidence of that.”

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Chirag Sidhpura: ‘I have had breakdowns’

Victims at the heart of this scandal beg to differ.

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Post Office prosecutors were alerted to bugs with Horizon days before the trial and eventual conviction of sub-postmaster Seema Misra in 2010 – before Ms Vennells had taken over.

There is further evidence – in the form of recordings leaked to Sky News – to suggest Ms Vennells had been told by May 2013 that Horizon operator Fujitsu had remote access to the system.

On Tuesday, ITV News reported that she described potential wrongful convictions of sub-postmasters in an October 2013 email as “very disturbing”.

That was written more than a year before the company halted prosecutions.

Chirag Sidhpura’s experience

Chirag had written to Ms Vennells personally about his own case in 2017. A week later, his contract was terminated.

He chose to hand over more than £57,000 to avoid prosecution. He lost not only his business but also his house and mental health.

Chirag said of Ms Vennells’ evidence: “I think there is still going to be a culture of denial, lies, ‘I don’t remember, I don’t recall’.

“It is put to you in black and white you have done this, you made these decisions. Just come clean.”

ITV drama Mr Bates vs The Post Office ensured a spotlight was firmly placed on Ms Vennells, whose career has included stints at companies including L’Oreal and in the NHS.

She is also an Anglican priest.

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Read more:
Who is Paula Vennells?
The major questions for key Post Office boss to answer – and why her replies matter
The Post Office Horizon scandal explained

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Ex-Post Office exec accused of lying

A lawyer’s view

Paul Marshall, a lawyer for victims, told Sky News that the evidence from Ms Vennells was an opportunity to “make confession”, claiming she presided over a Post Office “cult” which had a corporate inability to accept flaws.

“In one sense, she was or became the leader of what was indistinguishable from a cult.

“It had a belief system in which everything that didn’t coincide with that cult and its set of beliefs had to be either destroyed or excluded and removed.”

Ms Vennells has pledged to co-operate fully with the inquiry and, like all witnesses, must give an oath to tell the truth ahead of her evidence.

A statement released by her earlier this year stated: “I continue to support and focus on co-operating with the inquiry and expect to be giving evidence in the coming months.

“I am truly sorry for the devastation caused to the sub-postmasters and their families, whose lives were torn apart by being wrongly accused and wrongly prosecuted as a result of the Horizon system.

“I now intend to continue to focus on assisting the Inquiry and will not make any further public comment until it has concluded.”

Follow the questioning of Paula Vennells at the inquiry live on Sky News on Wednesday. Watch Sky News live here, and on YouTube, or on TV on Freeview 233, Sky 501, Virgin 603, and BT 313. You can also follow the latest on the Sky News website and app.

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Government announce Anglesey as preferred site of new nuclear power station

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Government announce Anglesey as preferred site of new nuclear power station

Wylfa in North Wales is the preferred site for a major new nuclear power development, the government has announced.

Ministers are beginning talks with international energy firms to explore building the UK’s third mega-nuclear power station at the Anglesey site, according to the Department for Energy Security and Net Zero (DESNZ).

The department said the gigawatt nuclear power plant could provide enough clean power for six million homes for 60 years.

Britain has a target of generating a quarter of all electricity – around 24GW – from home-grown nuclear power by 2050.

The aim is part of the government’s plan to enhance energy security and deliver on net zero.

Currently, the UK generates about 15% of its electricity needs from nuclear capacity.

The Wylfa project could be similar in scale to Hinkley in Somerset and Sizewell in Suffolk, with hopes it would bring thousands of jobs and investment to the area.

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Labour has accused the government of “dither and delay” on new nuclear at Wylfa, after Japanese giant Hitachi pulled out of a previous project there in 2019 because of rising costs.

Wylfa’s twin reactor Magnox nuclear power station, which went online in 1971, stopped generating power at the end of 2015 and has been decommissioned.

Energy Security Secretary Claire Coutinho said: “Anglesey has a proud nuclear history and it is only right that, once again, it can play a central role in boosting the UK’s energy security.

“Wylfa would not only bring clean, reliable power to millions of homes – it could create thousands of well-paid jobs and bring investment to the whole of North Wales.”

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‘High-tech’ nuclear power for UK

The UK is working to expand nuclear power through traditional large-scale plants as well as small modular reactors (SMRs), which supporters hope will be quicker and cheaper to construct.

Great British Nuclear aims to announce winning bidders in the tendering process to build SMRs by the end of this year.

But this is later than the spring timetable the government set last October for announcing the successful companies.

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Tom Greatrex, chief executive of the Nuclear Industry Association, said the government is “absolutely right” to pursue more large-scale nuclear alongside the SMR programme.

He said: “Wylfa is the best site in Europe for a big nuclear project: It has an existing grid connection, the hard bedrock ideal for a nuclear power station, superior cooling water access, and some work to clear the site for large-scale construction was already done by the previous developer.”

Labour’s shadow energy minister Alan Whitehead said: “We welcome the government finally moving forward with a nuclear project identified by the last Labour government.

“But this should be the bare minimum – and celebrating a tentative step forward in 2024 on a project that should have been moving in 2010 tells you everything about this tired, snail’s-pace government.”

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