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42 previously unknown genes discovered for Alzheimer’s disease

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42 previously unknown genes discovered for Alzheimer’s disease

“Life-style components akin to smoking, train and weight loss program affect our growth of Alzheimer’s, and appearing to deal with these now’s a optimistic approach of decreasing danger ourselves,” she added. “Nonetheless, 60-80% of illness danger relies on our genetics and due to this fact we should proceed to hunt out the organic causes and develop much-needed remedies for the hundreds of thousands of individuals affected worldwide.”

The beforehand unknown genes level to further pathways for illness development moreover the well-known APOE e4 gene or the event of amyloid beta and tau, two hallmark proteins that construct up within the mind with devastating outcomes as Alzheimer’s progresses.

“Creating an intensive listing of Alzheimer’s illness danger genes is like having the sting items of a puzzle put collectively, and whereas this work would not give us the complete image, it supplies a precious framework for future developments,” stated Susan Kohlhaas, director of analysis at Alzheimer’s Analysis UK, who was not concerned within the analysis.

Quite a few the newly found genes give attention to very detailed reactions between proteins within the physique that govern how irritation and the immune system may harm mind cells, the research discovered.

“The brand new danger variants recognized within the current research are considerably related to development” to Alzheimer’s illness, says the research, revealed Monday within the journal Nature Genetics.

The invention will present scientists with potential new targets for remedies, drugs and life-style modifications which may cut back the chance of the lethal mind illness, consultants say.

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“The way forward for Alzheimer’s illness is precision drugs and prevention,” stated Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic within the Middle for Mind Well being at Florida Atlantic College’s Schmidt School of Drugs.

“This paper provides us so many extra instruments in our toolbox to, finally, extra exactly goal Alzheimer’s illness,” stated Isaacson, who was not concerned within the research.

New illness pathways

The worldwide research analyzed the genomes of 111,326 individuals with clinically identified Alzheimer’s and in contrast these with genes from 677,663 cognitively wholesome individuals. The genomes had been provided by clinics in over 15 members of the European Union, Argentina, Australia, Brazil, Canada, Iceland, Nigeria, New Zealand, the UK and the US.

The research recognized 75 genes which might be linked to an elevated danger of Alzheimer’s, 33 of which had been already recognized. It additionally confirmed years of analysis into the roles of amyloid beta and tau.

Of the 42 new genes discovered to be linked to Alzheimer’s, many clustered into a number of suspected however unconfirmed pathways for illness growth. One such pathway is the physique’s immune system, designed to guard us from germ invaders.

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Quite a few genes had been related to an immune regulator known as LUBAC, which the physique must activate genes and stop cell loss of life. The research additionally discovered that microglia, immune cells within the mind which might be tasked with “taking out the trash” — clearing away broken neurons — play a key position in individuals with identified Alzheimer’s illness.

A few of the newly found genes could trigger microglia to be much less environment friendly, “which may speed up the illness,” Williams stated.

One other key pathway, in line with the research, entails genes related to irritation. The physique makes use of irritation as a protection mechanism to kill off pathogens, but it surely additionally performs a task in eradicating broken cells.

Just one drink per day can shrink your brain, study says

One protein that stood out within the research was tumor necrosis issue alpha, which is made by the immune system to manage irritation. The research discovered a cluster of genes related to TNF, as it’s known as. Although the chemical’s true position is to assemble the physique’s defenses for a struggle, additionally it is a perpetrator in lots of autoimmune illnesses by which the physique turns upon itself, akin to rheumatoid and psoriatic arthritis, Crohn’s illness and sort 1 diabetes.

Further sophisticated gene interactions had been discovered by the research, all of which illustrate that “Alzheimer’s illness is a multifactorial illness, made up of various pathologies, and every individual has their very own highway,” Isaacson stated.

“Clinicians at all times say, ‘as soon as you have seen one individual with Alzheimer’s, you have seen one individual with Alzheimer’s.’ The illness presents in another way and progresses in another way in several individuals,” he stated.

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A standard trigger?

One other key perception of the research was that mind issues akin to Parkinson’s, frontotemporal dementia, Lewy physique illness and amyotrophic lateral sclerosis could have the identical underlying genetic foundation: “Taken as a complete, these knowledge could thus emphasize a possible continuum between neurodegenerative illnesses,” the research stated.

“The scientific and medical neighborhood view neurodegenerative illness processes as very totally different and distinct, and that is how we have been learning them for a very long time,” stated Dr. Kellyann Niotis, a neurologist specializing in Alzheimer’s and Parkinson’s illness prevention at Weill Cornell Drugs and NewYork-Presbyterian.

“This emphasizes that there could also be a bigger continuum between these illness processes than we actually understood earlier than,” stated Niotis, who was not concerned within the research.

“Younger individuals could have related underlying genetic dangers, and so they may result in Parkinson’s in a single individual and Alzheimer’s within the different,” she stated. “In actuality, it’s much less related. What issues is knowing that that is what goes mistaken of their physique, so let’s begin early and goal this pathway.”

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Exercise may protect your brain even if you have signs of dementia, study finds

By producing this extra full image of genetic danger — which must be fleshed out and outlined in future research — the research authors additionally developed “a brand new scoring system to foretell the chance of Alzheimer’s illness,” Tara Spires-Jones, deputy director of the Centre for Discovery Mind Sciences on the College of Edinburgh, stated in a press release.

“This device shall be helpful for researchers however is not going to seemingly be used any time quickly for people who find themselves not collaborating in medical trials,” stated Spires-Jones, who was not concerned within the research.

Clinician researchers like Isaacson and Niotis know {that a} device like that’s exactly what sufferers need who’re frightened about their mind well being.

“Individuals wish to know, ‘what are my possibilities?’ after which ‘what can I do about it?’ ” Isaacson stated. “Not immediately, however within the close to future, we’ll have the ability to calculate an individual’s chance of creating Alzheimer’s or one other mind dysfunction in a extra exact approach, and that may assist with precision medical and life-style administration.”

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Russia launches Christmas Day attack on Ukraine’s energy system

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Russia launches Christmas Day attack on Ukraine’s energy system

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Russia has carried out a Christmas Day attack on Ukraine’s energy system, leaving more than half a million people without heating, water and electricity. 

Ukrainian President Volodymyr Zelenskyy said the attack, the 13th large-scale assault of 2024 on the country’s grid, was “deliberate” and not a coincidence. “What could be more inhuman?” he wrote on X.

About 50 of the 70 missiles fired in the attack were intercepted, along with a “significant” portion of the more than 100 attack drones deployed, he added.

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This year Ukrainians marked Christmas Day on December 25 for the second time, after switching to the western Gregorian calendar last year. The decision to stop celebrating Christmas on January 7 in line with the Orthodox calendar was made by Kyiv to break with Russian influence.

Oleh Syniehubov, governor of Ukraine’s eastern Kharkiv region, told Ukraine’s national television news that the attack had left more than 500,000 people without heating, water and electricity.

Temperatures across Ukraine are around freezing point.

Heating supplies were also cut in some areas of Ukraine’s Ivano-Frankivsk and Dnipropetrovsk regions, in the west and south of the country. 

Ukraine’s energy grid operator, Ukrenergo, urged consumers to limit consumption by not switching on multiple appliances at once, adding that the system was still recovering from the previous Russian attack on December 13.

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Ukraine’s largest private energy company, DTEK, said that its power stations had been damaged and one of its long-term employees killed.

Ukraine’s foreign minister, Andriy Sybiha, said on X that the attack reflects Russian President Vladimir Putin’s response to “those who spoke about illusionary ‘Christmas ceasefire’”.

Hungarian Prime Minister Viktor Orbán said last week that Zelenskyy had rejected his proposal for a ceasefire and prisoner exchange on the January 7 Orthodox Christmas.

Ukraine denied that such a proposal was ever on the table, asking Hungary to “refrain from manipulations” regarding the war. On Friday, Heorhii Tykhyi, spokesperson for Ukraine’s foreign ministry, described it as “PR, a move” by Orbán.

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American Airlines lifts ground stop that froze Christmas Eve travelers

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American Airlines lifts ground stop that froze Christmas Eve travelers

An American Airlines agent talks to a customer at O’Hare International Airport in Chicago, Ill., last week. On Tuesday, the airline issued a national halt to flights.

Kamil Krzacznski/AFP via Getty Images


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Kamil Krzacznski/AFP via Getty Images

American Airlines passengers across the U.S. endured a sudden disruption of service on Christmas Eve, as a “technical issue” forced the airline to request a nationwide ground stop of its operations.

“The ground stop has now been lifted,” the Federal Aviation Administration told NPR shortly after 8 a.m. ET.

On Facebook and X, passengers shared stories of boarding planes early on Christmas Eve — only to be left waiting on the tarmac. In some cases, they described being told the flight would return to its gate so everyone onboard could deplane.

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The ground stop lasted for about one hour, according to the airline.

 “We sincerely apologize to our customers for the inconvenience this morning,” the airline said.

In a statement sent to NPR, American says the widespread delays were caused by a “vendor technology issue” affecting systems that are needed for a flight to be “released” — one of the final key steps before a plane takes off from an airport.

Early circumstances around Tuesday’s outage seemed ominous, reminding travelers of a nightmare scenario that played out two years ago when computer problems fueled a meltdown for Southwest Airlines as it tried to cope with bad weather during the holidays.

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Southwest stranded millions of travelers — and was later ordered to pay a $140 million civil penalty.

Aviation industry veterans like George Hamlin, a consultant, notes that Southwest took the brunt of the blame for the meltdown — but, he adds, “now we’re finding out that it’s a larger, more endemic problem than that.”

Delayed American Airlines passengers who posted to social media Tuesday said pilots blamed the slowdown on a computer system that aims to ensure an optimal center of gravity by balancing planes’ cargo weight and other factors.

Winter weather also threatens to snarl Christmas Eve travel, including storms along the East and West Coasts of the U.S.

The FAA’s operations page shows nearly a dozen airports were deicing planes Tuesday morning, including at Philadelphia International, and Dulles International and Reagan National outside Washington, D.C.

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If you’re flying, the FAA recommends checking your airline’s flight status updates for potential delays. As of 9 a.m. ET, the FlightAware website’s “Misery Map” showed some 544 flights had been delayed and five canceled since 6 a.m. Nearly 120 of those delays were at Charlotte, N.C.’s, airport.

Nearly 12.7 million passengers are expected to fly on American Airlines this winter holiday season, comprising more than 118,000 flights, according to the airline. The most-traveled days in that span are both Fridays, ahead of and just after Christmas.

NPR’s Joel Rose contributed reporting.

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Private equity payouts fell 50% short in 2024

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Private equity payouts fell 50% short in 2024

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Private equity funds cashed out just half the value of investments they typically sell in 2024, the third consecutive year payouts to investors have fallen short because of a deal drought.

Buyout houses typically sell down 20 per cent of their investments in any given year, but industry executives forecast that cash payouts for the year would be about half that figure.

Cambridge Associates, a leading adviser to large institutions on their private equity investments, estimated that funds had fallen about $400bn short in payments to their investors over the past three years compared with historical averages.

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The data underline the increasing pressure on firms to find ways to return cash to investors, including by exiting more investments in the year ahead.

Firms have struggled to strike deals at attractive prices since early 2022, when rising interest rates caused financing costs to soar and corporate valuations to fall.

Dealmakers and their advisers expect that merger and acquisition activity will accelerate in 2025, potentially helping the industry work through what consultancy Bain & Co. has called a “towering backlog” of $3tn in ageing deals that must be sold in the years ahead.

Several large public offerings this year including food transport giant Lineage Logistics, aviation equipment specialist Standard Aero and dermatology group Galderma have provided private equity executives with confidence to take companies public, while Donald Trump’s election has added to Wall Street exuberance.

But Andrea Auerbach, global head of private investments at Cambridge Associates, cautioned that the industry’s issues could take years to work through.

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“There is an expectation that the wheels of the exit market will start to turn. But it doesn’t end in one year, it will take a couple of years,” Auerbach said.

Private equity firms have used novel tactics to return cash to investors while holdings have proved difficult to sell.

They have made increasing use of so-called continuation funds — where one fund sells a stake in one or more portfolio companies to another fund to another fund the firm manages — to engineer exits.

Jefferies forecasts that there will be $58bn of continuation fund deals in 2024, representing a record 14 per cent of all private equity exits. Such funds made up just 5 per cent of all exits in the boom year of 2021, Jefferies found.

But some private equity investors are sceptical that the industry will be able to sell assets at prices close to funds’ current valuations.

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“You have a huge amount of capital that has been invested on assumptions that are no longer valid,” a large industry investor told the Financial Times.

They warned that a record $1tn-plus in buyouts were struck in 2021, just before interest rates rose, and many deals are carried on firms’ books at overly optimistic valuations.

Goldman Sachs recently noted in a report that private equity asset sales, which had historically been done at a premium of at least 10 per cent to funds’ internal valuations, have in recent years been made at discounts of 10-15 per cent.

“[Private] equity in general is still over-marked, which is leading to this situation where assets are still stuck,” said Michael Brandmeyer of Goldman Sachs Asset Management in the report.

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