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Published3 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, iSABEL HOLDSWORTHBy Beth RoseBBC Access AllIn early January a shortage of available guide dogs was reported. For some visually impaired people the wait is too long and they decide to train their own guide dogs.Isabel Holdsworth had been making the daily commute across London from Dagenham to Kings Cross for years. Being visually impaired she had worked with five different guide dogs, until it came to a sad and abrupt end.”My dog died suddenly and I had to go to work and college the next day – two tubes, a 40 minute walk – with no dog,” she told BBC Access All.She used her white cane instead, knowing it could be a long time before she was matched with another dog. But it wasn’t easy. “I was on Liverpool Street Station and almost fell in front of the Tube,” she says. “I thought ‘I can’t do this anymore’.”She had an idea – could she train her own dog?It’s not a common way to go about it, but for years people have been doing this. The big question for guide dog owners is, if a dog is self-trained and not accredited by a big organisation, will they be allowed to take it to places dogs can’t usually go, like restaurants, shops and in taxis? The answer is yes, the law doesn’t make a distinction. Isabel started researching the possibility of training her own dog and spoke to others who had done so.She felt confident she could also do this and began searching rescue centres until she found Lucy, a one-year-old Labrador. Lucy hadn’t had the best start in life with little socialisation and family life but Isabel felt she had found the right dog. Having taken Lucy home, Isabel invested in a training clicker and food to reward Lucy and then booked a weeks leave from work to get started. Image source, iSABEL HOLDSWORTHAbigail Hughes understands Isabel’s drive to do this. She co-founded PAWtected, an organisation that works with about 80 people every year to train their own assistance dogs. She says she started offering online and in-person courses when she realised dogs weren’t always available for people who needed support, including autistic adults. “You’ve got lesser-known dogs like allergen detection dogs, so that you don’t come into contact with something you’re severely allergic to,” she says. “There are dogs who can help with PTSD and other traumatic circumstances.”Back in London, Isabel ventured out with Lucy. She had bought a harness and, armed with her trusty cane which she used at the same time, they started walking the street they lived on. One of the first tasks was to teach Lucy to avoid obstacles. Isabel knew there was a lamppost on her road so she braced herself then “smacked into it and jumped back” yelping in pain. LISTEN: You can hear more from Isabel and Abigail on the BBC Access All podcast.Radio 1Xtra’s Reece Parkinson also chats about his recent diagnosis of Type 1 diabetes and how he manages his blood sugar while DJ-ing in Ibiza. Isabel made a huge deal about the pain hoping Lucy would take note. Then they tried the approach again.”Lucy did a great big wide circuit around it. I didn’t really have any problem with obstacles after that.”This isn’t a standard way to train assistance dogs. It’s usually pain-free and involves lots of repetition and positive reinforcement with treats. Crossing roads was another essential and involved Lucy trying to learn that she mustn’t always follow the commands her owner gives her because it might be dangerous – something called “intelligent disobedience”. That means if Isabel instructs Lucy to cross the road but there’s a car coming, Lucy must refuse. Being a trainer who is blind, Isabel had to ensure she knew the layout of the road and where cars might appear before practising.She says it took about four months until she had “absolute trust” in her dog. But it paid off. When Isabel hadn’t heard a quiet electric car approaching, Lucy stopped Isabel from getting hit. Isabel’s aim had always been to get back to commuting with a dog and after just seven days of training she felt Lucy had learned enough to set them on their way. But returning to the office wasn’t all plain sailing.”The first day Lucy went into the office, she pulled down the soft walls between the offices. She ate through the boss’s phone cable and network cable.”Happily the company was understanding. Isabel says it took about two years to fully train Lucy. It’s a similar length of time that Guide Dogs, the UKs biggest provider of assistance dogs, takes to train its puppies before they are matched with a partner. Image source, PAWtectedGuide Dogs is currently struggling to meet demand. The Covid pandemic paused breeding, training and socialising for five months. As well as fewer dogs, the number of those making it through the process dropped from 65% to less than 50% – the lowest in decades – and the average waiting time for a guide dog increased to 18 months.The organisation said it was “devastated” by this, in its annual report. “In all our 90 years, we have never had two years as tumultuous and challenging as 2020 and 2021.”One way it is trying to mitigate this, and to diversify its gene pools, is by working with international partners. In 2022 it received dogs from America, Japan and Finland.Tim Stafford, its director of canine affairs, says dogs bring “incredible benefits” to a person’s life” but he believes guide dogs should be independently assessed rather than owner-trained to “provide clarity, reassure the public and service providers”.Although receivers of many guide dogs are used to getting dogs from a big charity, many other assistance dog charities are not so big and so the onus is on disabled people to obtain and train their own dogs.Abigail says PAWtected has helped hundreds of people and on a practical level it can be quite “simple” to start training a dog for tasks such as taking your socks off.”You start off by playing a game of tug with the sock,” she says. “Then you put the sock on your foot, leaving a tail at the end, and encourage them to play tug at the end of your foot so that they can pull it off. It builds up really slowly through fun games.”For Isabel the hundreds of hours of training paid off. “Lucy was the best guide dog I ever had,” she says, but adds that time and expense, such as vet bills and public liability insurance, need to be factored in before anyone attempts it. “It’s not an easy thing to do but it’s not impossible for a blind person to train their own dog. It’s the buzziest feeling ever.” You can listen to the podcast and find information and support on the Access All pageMore on this storyWhat does it take to raise a guide dog puppy?4 days agoRelated Internet LinksPAWtectedGuide DogsThe BBC is not responsible for the content of external sites.

Published1 day agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy George WrightBBC NewsChina has taken down more than 1,000 social media accounts – some with millions of followers – that criticised the government’s Covid policies.Social media platform Weibo said it had suspended or banned accounts for what it described as personal attacks against Chinese Covid specialists.Weibo did not specify which posts had prompted the action.China scrapped its strict zero-Covid policy in December and has seen a rapid surge of infections and deaths.Online criticism has until recently largely focused on the strict enforcement of Covid regulations, including lockdowns that required people to stay at home in isolation for weeks. But recent posts have taken aim at experts who have defended the sudden decision to drop restrictions, despite supporting them just weeks ago. Weibo said it had spotted almost 13,000 violations, including attacks on experts, scholars and medical workers. Temporary or permanent bans have been handed to 1,120 accounts.”It is not acceptable to hurl insults at people who hold a different point of view, or publish personal attacks and views that incite conflicts,” Weibo said in a statement. Any kind of move that is destructive to the [Weibo] community would be handled in a serious manner.”How is China trying to beat its latest Covid surge?Young Chinese self-infect amid Covid fears for elderlyChina criticises ‘political’ Covid tourist rulesSince China abandoned key parts of zero-Covid following historic protests against the policy, there have been reports of hospitals and crematoriums being overwhelmed.But China has stopped publishing daily cases data and has announced only 22 Covid deaths since December, using its own strict criteria.On Saturday, China marked the first day of the 40-day period of Lunar New Year, known as the world’s largest annual migration of people. The Ministry of Transport said it expects more than two billion passengers to travel over the next 40 days, an increase of 99.5% year-on-year and reaching 70% of trip numbers in 2019.This has led to widespread concerns that the festival may see another wave of infections, especially in rural areas that are less well-equipped with ICU beds and ventilators.From Sunday, China will drop a requirement for travellers coming from abroad to quarantine, meaning many Chinese will be able to travel abroad for the first time in almost three years.More on this storyYoung Chinese self-infect amid Covid fears for elderly3 days agoHow is China trying to beat its latest Covid surge?3 days agoCelebrity deaths spark fears over China Covid toll3 days agoChina under-representing Covid deaths, WHO warns4 days ago

PHILADELPHIA — Over a matter of weeks, Tracey McCann watched in horror as the bruises she was accustomed to getting from injecting fentanyl began hardening into an armor of crusty, blackened tissue. Something must have gotten into the supply.Switching corner dealers didn’t help. People were saying that everyone’s dope was being cut with something that was causing gruesome, painful wounds.“I’d wake up in the morning crying because my arms were dying,” Ms. McCann, 39, said.In her shattered Philadelphia neighborhood, and increasingly in drug hot zones around the country, an animal tranquilizer called xylazine — known by street names like “tranq,” “tranq dope” and “zombie drug” — is being used to bulk up illicit fentanyl, making its impact even more devastating.Xylazine causes wounds that erupt with a scaly dead tissue called eschar; untreated, they can lead to amputation. It induces a blackout stupor for hours, rendering users vulnerable to rape and robbery. When people come to, the high from the fentanyl has long since faded and they immediately crave more. Because xylazine is a sedative and not an opioid, it resists standard opioid overdose reversal treatments.More than 90 percent of Philadelphia’s lab-tested dope samples were positive for xylazine, according to the most recent data.“It’s too late for Philly,” said Shawn Westfahl, an outreach worker with Prevention Point Philadelphia, a 30-year-old health services center in Kensington, the neighborhood at the epicenter of the city’s drug trade. “Philly’s supply is saturated. If other places around the country have a choice to avoid it, they need to hear our story.”A study published in June detected xylazine in the drug supply in 36 states and the District of Columbia. In New York City, xylazine has been found in 25 percent of drug samples, though health officials say the actual saturation is certainly greater. In November, the Food and Drug Administration issued a nationwide four-page xylazine alert to clinicians.Shawn Westfahl, center left, attended to a man who Mr. Westfahl believed had just injected tranq dope, in the Kensington section of Philadelphia.Hilary Swift for The New York TimesTracey McCann is in recovery from tranq dope at a treatment center near St. Louis. “I’d wake up in the morning crying because my arms were dying,” she said.Neeta Satam for The New York TimesIn December, the Office of National Drug Control Policy said it was tracking the spread closely, and the journal Pediatrics published an analysis of three cases of xylazine ingestion by toddlers.But xylazine’s true prevalence is unknown. Hospitals don’t test for it. Some state medical examiners don’t routinely do so, either.The drug exists in a legal gray zone. Approved 50 years ago by the F.D.A. as a veterinarian-prescribed analgesic, it is not listed as a controlled substance for animals or humans and so is not subject to strict monitoring. Thus, it has not been on the radar of federal law enforcement for diversion or abuse.As with many trapped by tranq, Ms. McCann’s hellish descent began with prescription opioids. In 2009, when she was 27, she developed a dependence on painkillers prescribed after a severe car crash. A boyfriend she met at one of her six stays in rehab introduced her to heroin. Cheaper and more potent fentanyl elbowed heroin off the streets. Then, as the Covid-19 pandemic descended in 2020, tranq stormed Philadelphia.Fentanyl Overdoses: What to KnowCard 1 of 5Devastating losses.

PHILADELPHIA — Over a matter of weeks, Tracey McCann watched in horror as the bruises she was accustomed to getting from injecting fentanyl began hardening into an armor of crusty, blackened tissue. Something must have gotten into the supply.Switching corner dealers didn’t help. People were saying that everyone’s dope was being cut with something that was causing gruesome, painful wounds.“I’d wake up in the morning crying because my arms were dying,” Ms. McCann, 39, said.In her shattered Philadelphia neighborhood, and increasingly in drug hot zones around the country, an animal tranquilizer called xylazine — known by street names like “tranq,” “tranq dope” and “zombie drug” — is being used to bulk up illicit fentanyl, making its impact even more devastating.Xylazine causes wounds that erupt with a scaly dead tissue called eschar; untreated, they can lead to amputation. It induces a blackout stupor for hours, rendering users vulnerable to rape and robbery. When people come to, the high from the fentanyl has long since faded and they immediately crave more. Because xylazine is a sedative and not an opioid, it resists standard opioid overdose reversal treatments.More than 90 percent of Philadelphia’s lab-tested dope samples were positive for xylazine, according to the most recent data.“It’s too late for Philly,” said Shawn Westfahl, an outreach worker with Prevention Point Philadelphia, a 30-year-old health services center in Kensington, the neighborhood at the epicenter of the city’s drug trade. “Philly’s supply is saturated. If other places around the country have a choice to avoid it, they need to hear our story.”A study published in June detected xylazine in the drug supply in 36 states and the District of Columbia. In New York City, xylazine has been found in 25 percent of drug samples, though health officials say the actual saturation is certainly greater. In November, the Food and Drug Administration issued a nationwide four-page xylazine alert to clinicians.Shawn Westfahl, center left, attended to a man who Mr. Westfahl believed had overdosed on tranq dope, in the Kensington section of Philadelphia.Hilary Swift for The New York TimesTracey McCann is in recovery from tranq dope at a treatment center near St. Louis. “I’d wake up in the morning crying because my arms were dying,” she said.Neeta Satam for The New York TimesIn December, the Office of National Drug Control Policy said it was tracking the spread closely, and the journal Pediatrics published an analysis of three cases of xylazine ingestion by toddlers.But xylazine’s true prevalence is unknown. Hospitals don’t test for it. Some state medical examiners don’t routinely do so, either.The drug exists in a legal gray zone. Approved 50 years ago by the F.D.A. as a veterinarian-prescribed analgesic, it is not listed as a controlled substance for animals or humans and so is not subject to strict monitoring. Thus, it has not been on the radar of federal law enforcement for diversion or abuse.As with many trapped by tranq, Ms. McCann’s hellish descent began with prescription opioids. In 2009, when she was 27, she developed a dependence on painkillers prescribed after a severe car crash. A boyfriend she met at one of her six stays in rehab introduced her to heroin. Cheaper and more potent fentanyl elbowed heroin off the streets. Then, as the Covid-19 pandemic descended in 2020, tranq stormed Philadelphia.Fentanyl Overdoses: What to KnowCard 1 of 5Devastating losses.

A young version of the coronavirus makes up one-quarter of Covid cases across the United States and over 70 percent of new cases in the Northeast.Three years into the pandemic, the coronavirus continues to impress virologists with its swift evolution.A young version, known as XBB.1.5, has quickly been spreading in the United States over the past few weeks. As of Friday, the Centers for Disease Control estimated that it made up 72 percent of new cases in the Northeast and 27.6 percent of cases across the country.The new subvariant, first sampled in the fall in New York State, has a potent array of mutations that appear to help it evade immune defenses and improve its ability to invade cells.“It is the most transmissible variant that has been detected yet,” Maria Van Kerkhove, the Covid-19 technical lead at the World Health Organization, said at a news conference on Wednesday.XBB.1.5 remains rare in much of the world. But Tom Wenseleers, an evolutionary biologist at KU Leuven in Belgium, expects it to spread quickly and globally. “We’ll have another infection wave, most likely,” he said.Advisers at W.H.O. are assessing the risk that XBB.1.5 poses. Jacob Lemieux, an infectious disease doctor at Massachusetts General Hospital, said that the surge in cases would not match the first Omicron spike that Americans experienced a year ago. “Is it a Category Five hurricane?” he said. “No.”Still, he warned that XBB.1.5 could worsen what is already shaping up to be a rough Covid winter, as people gather indoors and don’t receive boosters that can ward off severe disease.Dr. Ashish K. Jha, the White House Covid-19 response coordinator, said that the Biden administration was monitoring the emergence of XBB.1.5 and urging people to take advantage of existing countermeasures. Preliminary studies suggest that bivalent vaccines should provide decent protection against XBB and its descendants. Paxlovid will also remain effective at fighting infections.“We feel pretty comfortable that our countermeasures are going to continue to work,” Dr. Jha said. “But we’ve got to make sure people are using them.”One thing Dr. Lemieux and other experts are confident about is that XBB.1.5 is not the last chapter in the coronavirus’s evolution. In fact, they expect that a descendant of XBB.1.5 may soon gain mutations that make it even better at spreading.More on the Coronavirus PandemicNew Subvariant: A highly contagious version of the Omicron variant — known officially as XBB.1.5 or by its subvariant nickname, Kraken — is quickly spreading in the United States.Pfizer’s Boosters: Federal officials said that fears that the Covid booster shots made by Pfizer may increase the risk of strokes in people aged 65 and older were not borne out by an intensive scientific investigation.Travel: The European Union advised its 27 member nations to require negative Covid-19 tests for travelers boarding flights from China to the region, amid a surge in coronavirus cases in the country.Misinformation: As Covid cases and deaths rise in parts of the United States, misleading claims continue to spread, exasperating overburdened doctors and evading content moderators.That descendant may already exist, infecting people without raising notice yet. But sequencing efforts have declined so much worldwide that the discovery of the next generation of XBB.1.5 may be delayed. “As sequencing becomes less and less available at a global level, it’s difficult for us to track each of the subvariants of Omicron,” Dr. Van Kerkhove said.Scientists have reconstructed the evolution of XBB.1.5 (which some have nicknamed Kraken) by poring over new sequences of coronaviruses in online databases. The first major step came last year when two earlier forms of Omicron infected the same person. As the viruses replicated, their genetic material was shuffled together. A new hybrid form emerged, with genetic material from both viral parents. Virus-watchers named it XBB.This mixing, called recombination, happens fairly often among coronaviruses. Over the course of the pandemic, scientists have found a number of recombinant forms of SARS-CoV-2, the cause of Covid-19.Most recombinant SARS-CoV-2 viruses have dwindled away in a matter of weeks or months, unable to outcompete other lineages. XBB, on the other hand, got a winning ticket in the genetic lottery. From one parent, it gained a set of mutations that helped it evade antibodies from previous infections and vaccinations. From the other parent, it gained a separate set of mutations that made it even more evasive.“XBB literally picked up the most possible mutations that it could possibly pick up from those two parents,” said Thomas Peacock, a virologist at Imperial College London. The new combination made XBB one of the most evasive Omicron subvariants in existence last summer.Recent experiments suggest that XBB paid a steep price for its power to evade immunity. The mutations allow it to escape antibodies by altering the shape of the protein, called spike, that covers its surface. But some of those mutations also make it harder for XBB spike proteins to grab tightly to cells — the first step required for an infection.That loose grip may have lessened XBB’s advantage against other forms of the virus. In late 2022, it jostled alongside a number of other Omicron subvariants. In Singapore, XBB caused a surge in October, for example, while remaining rare in many other parts of the world.As XBB multiplied, it continued to mutate into new forms. The earliest samples of XBB.1.5 were isolated in October in New York. The new subvariant gained one crucial mutation, known as F486P.The entrance to a busy fever clinic in Beijing last month. XBB.1.5 is present in China, but for now in only a small percentage of recent sequences.Gilles Sabrié for The New York TimesYunlong Cao of Peking University and his colleagues tested out XBB.1.5 in dishes of cells, comparing how it fared against earlier forms of XBB. The researchers found that the F486P mutation allowed XBB.1.5 to grab tightly to cells again. But the new subvariant could still evade antibodies as well as earlier forms of XBB.Dr. Cao and his colleagues posted their results online on Thursday. The data has not yet been published in a scientific journal.XBB.1.5 most likely evolved somewhere in the northeastern United States, where early samples were first identified and where it remains most common. Once scientists could recognize it, they could track its growth.In Connecticut, for example, Nathan Grubaugh at Yale University and his colleagues found that by mid-December, other Omicron subvariants were falling. Only XBB.1.5 cases were growing. Dr. Grubaugh estimates that it is about 20 percent more transmissible than BQ.1, which had been the dominant form.“It doesn’t have those signs of a really big wave like we saw before,” he said. “It’s not going to come close to what it was last year.”How severe XBB.1.5 infections are compared with other forms of the coronavirus is not yet clear. “It’s serious,” Dr. Grubaugh said. “I just don’t necessarily know if it’s really more serious than some of the other Omicron lineages in terms of the overall impact.”XBB.1.5 has already spread to other countries, and is growing rapidly in Germany, Denmark and elsewhere in Europe. But its impact is likely to differ from place to place. In India, for instance, it will encounter many people who were infected with its parental strains last year, so it may face stronger immunity, Dr. Peacock said.In China, which experienced a large surge of cases in late 2022, its prospects are even harder to predict. For most of the pandemic, China almost never shared virus sequences with international databases. Cooperation has increased in the past few weeks, but the databases may still not reflect the state of play in the country.Much of XBB.1.5’s advantage in the United States comes from its ability to evade existing immunity, including that which is against other Omicron subvariants. In China, where there is less immunity, it may not have that edge. Dr. Peacock speculated that after other variants spread through China, it may then be XBB.1.5’s turn to rise.Dr. Wenseleers said that the spread of XBB.1.5 outside China made him skeptical that restrictions on Chinese travelers would keep cases down. “It’s kind of pointless,” he said. “It would be better to make sure the elderly are well-vaccinated.”As XBB.1.5 spreads, it continues to mutate, and experts believe that it can become even better at evading antibodies.Scientists are already scanning new sequences being uploaded to an international database called GISAID in the hopes of spotting an upgraded version of XBB.1.5. But their job is getting harder because governments are pulling back on sequencing efforts. “Worldwide, sequencing has taken a real hit,” Dr. Peacock said.The United States, which once lagged behind other nations, has managed to maintain a fairly strong sequencing effort. Without it, Dr. Peacock said, XBB.1.5 might have stayed below the radar for much longer. If XBB.1.5’s next generation is evolving somewhere with little sequencing, it may go undetected for some time to come.Dr. Lemieux said that paring back on sequencing was a mistake, given how many infections and deaths the virus is still causing. “This is a part of public health,” he said.And Dr. Peacock said that XBB.1.5 demonstrated that the evolution of the coronavirus would not slow down anytime soon. “Give it another two years, and maybe we can reassess where we think this is,” he said.

Scientists from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) today reported that an inflammatory trigger like one present during viral infections is elevated in Alzheimer’s disease and progressive supranuclear palsy, a rare brain disorder.
“We have identified a new trigger of brain inflammation in these disorders,” said Elizabeth Ochoa, PhD, study author from UT Health San Antonio. The finding published in Science Advances is novel for this reason, she said.
Ochoa, a recent doctoral graduate, and her mentor, Bess Frost, PhD, study senior author, are investigators with the Sam and Ann Barshop Institute for Longevity and Aging Studies, the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, and the Department of Cell Systems and Anatomy at UT Health San Antonio. Frost is the Bartell Zachry Distinguished Professor for Research in Neurodegenerative Disorders.
Alzheimer’s disease and progressive supranuclear palsy are marked by toxic deposits of a protein called tau. Their research found that tau-induced “jumping genes” — which can relocate or copy themselves to other locations in the genome — form double-stranded RNA. This abnormal RNA mimics the inflammatory trigger that is also present in viral infections.
“Transposable elements — the so-called jumping genes — are a new area of interest in understanding Alzheimer’s disease. Our study provides new insights into how they can drive the disease process in addition to their ability to jump,” Ochoa said. “These double-stranded RNAs look like a virus to the immune system even though the jumping genes are a part of our normal genome.”
The researchers detected accumulation of double-stranded RNA in postmortem brain tissue from patients with Alzheimer’s disease and progressive supranuclear palsy and in brains of mouse and fruit fly models of tauopathy.

“We found substantial deposits of double-stranded RNA in astrocytes, which are cells that provide metabolic support for neurons, regulate neurotransmitters and maintain blood-brain barrier integrity,” Frost said. “In aging and disease, astrocytes respond to injury and disruption of the neuronal environment. Our findings open new doors for understanding astrocyte biology and their role in transposable element control.”
Loss of neurons, which are cells of the central nervous system, is progressive in Alzheimer’s and other neurodegenerative diseases.
The researchers conducted experiments in fruit flies to quickly test their questions about double-stranded RNA and inflammation in the brain. “To ensure that what we found in our fruit fly experiments is relevant to mammalian disease, we also studied brain tissue from mouse models and from postmortem human brains affected by tauopathy,” Ochoa said.
“As we are currently targeting jumping gene activation in a local Phase II clinical trial for patients with Alzheimer’s disease, it’s important to understand the full repertoire of toxic molecules, including double-stranded RNAs, that jumping genes produce,” Frost said.
Ochoa recently earned her PhD from the Cell Biology, Genetics and Molecular Medicine Discipline of the Integrated Biomedical Sciences program at UT Health San Antonio. She earned her undergraduate degree from Seattle University.
Frost, associate professor of cell systems and anatomy in the Barshop and Biggs institutes at UT Health San Antonio, received the highly competitive Edith and Peter O’Donnell Award in Medicine in 2020 from TAMEST, the Texas Academy of Medicine, Engineering, Science and Technology. She was also a Gold Medalist in 2022 for the Oskar Fischer Prize.
Acknowledgments
This study was supported by the National Institute of Neurological Diseases and Stroke, the Rainwater Foundation and the National Institute of General Medical Sciences. Coauthor Kevin Bieniek, PhD, is the director of the UT Health San Antonio Glenn Biggs Institute Brain Bank, which is supported by the National Institute on Aging, the Texas Alzheimer’s Research and Care Consortium, the Bill and Rebecca Reed Precision Medicine Center and the Bartell and Mollie Zachry Endowment for Alzheimer’s Research and Patient Care.
The Mayo Clinic Brain Bank provided human brain tissue. Coauthor William Ray, PhD, of the Neurodegeneration Consortium, Therapeutics Discovery Division at The University of Texas MD Anderson Cancer Center provided mouse brain tissue for analyses.

Eukaryotic cells — the ones that make up most life as we know it, including all animals, plants and fungi — are highly structured objects.
These cells assemble and maintain their own smaller, internal bits: the membrane-bound organelles like nuclei, which store genetic information, or mitochondria, which produce chemical energy. But much remains to be learned about how they organize themselves into these spatial compartments.
Physicists at Washington University in St. Louis conducted new experiments that show that eukaryotic cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey a universal scaling relationship that the scientists predict theoretically, their new framework suggests that organelles grow in random bursts from a limiting pool of building blocks.
The study was published Jan. 6 in Physical Review Letters.
“In our work, we suggest that the steps by which organelles are grown — far from being an orderly ‘brick-by-brick’ assembly — occur in stochastic bursts,” said Shankar Mukherji, assistant professor of physics in Arts & Sciences.
“Such bursts fundamentally limit the precision with which organelle size is controlled but also maintain noise in organelle size within a narrow window,” Mukherji said. “Burstlike growth provides a general biophysical mechanism by which cells can maintain, on average, reliable yet plastic organelle sizes.”
Organelles must be flexible enough to allow cells to grow or shrink them as environments demand. Still, the size of organelles must be maintained within certain limits. Biologists have previously identified certain molecular factors that regulate organelle sizes, but this study provides new insights into the quantitative principles underlying organelle size control.
While this study used budding yeast as a model organism, the team is excited to explore how these assembly mechanisms are utilized across different species and cell types. Mukherji said that they plan to examine what these patterns of robustness can teach us about how to harness organelle assembly for bioengineering applications and how to spot defects in organelle biogenesis in the context of disease.
“The pattern of organelle size robustness is shared between budding yeast and human iPS cells,” Mukherji said. “The underlying molecular mechanisms producing these bursts are yet to be fully elucidated and are likely to be organelle-specific and potentially species-specific.”
Funding: This research was supported by the National Institutes of Health (NIH R35GM142704).
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Materials provided by Washington University in St. Louis. Original written by Talia Ogliore. Note: Content may be edited for style and length.

A new USC Leonard Davis School of Gerontology study challenges existing ideas of how buildup of a protein called amyloid beta (Aβ) in the brain is related to Alzheimer’s disease.
While buildup of amyloid protein has been associated with Alzheimer’s-related neurodegeneration, little is known about how the protein relates to normal brain aging, said University Professor Caleb Finch, the study’s senior author and holder of the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School.
To explore the levels of Aβ in human brains, the researchers analyzed tissue samples from both healthy brains and brains of patients with dementia. More severe Alzheimer’s cases were indicated by higher Braak staging scores, a measurement of how widely signs of Alzheimer’s pathology are found within the brain.
The analysis revealed that older, cognitively healthy brains showed similar amounts of dissolvable, non-fibrillar amyloid protein as brains of Alzheimer’s patients. But, as the researchers expected, the brains of Alzheimer’s patients had higher amounts of insoluble Aβ fibrils, the form of amyloid protein that aggregates to form the telltale “plaques” seen in the disease, said Max Thorwald, the study’s first author and a postdoctoral researcher at the USC Leonard Davis School.
The findings challenge the idea that simply having higher amounts of amyloid protein in general is an underlying cause of Alzheimer’s, say Finch and Thorwald. Instead, the increase in soluble Aβ may be a general aging-related change in the brain not specific to Alzheimer’s, while higher levels of fibrillary amyloid appear to be a better indicator of poorer brain health.
Rather than Alzheimer’s simply involving increased production of Aβ protein, the more important issue may be a reduced ability to effectively clear the protein and stave off the creation of plaque-contributing fibrillary amyloid, Thorwald said.
“These findings further support the use of aggregated, or fibrillary, amyloid as a biomarker for Alzheimer’s treatments,” Thorwald said. “The site in which amyloid processing occurs has less precursor and enzyme available for processing, which may suggest the removal of amyloid as a key issue during Alzheimer’s.”
Increases in amyloid levels happen during early adulthood and differ by brain region. Further studies, including those investigating drugs to possibly break down amyloid, should incorporate positron emission tomography (PET) imaging in both healthy individuals and Alzheimer’s patients of a wide range of ages to determine how and where amyloid processing and removal changes in the brain over time, he added.
“The brain’s frontal cortex has more amyloid production compared to the cerebellum during the aging process in human brains, which coincides with their Alzheimer’s-correlated pathologies in late life,” Thorwald said. “Future projects should examine amyloid over the life course in both cognitively normal and Alzheimer’s patients with both modulation of amyloid processing or removal of amyloid through monoclonal antibodies currently used in clinical trials for Alzheimer’s treatment.”
Monoclonal antibody treatment lemanecab has been observed to reduce Aβ plaques in clinical trials and recently received FDA approval for its potential to slow cognitive decline in Alzheimer’s patients, but the results warrant further careful research regarding long-term impact, Finch said.
“Lecanemab clearly works to diminish fibrillar amyloid,” he said. “However, we are concerned with major side effects, including brain swelling and bleeding, that were 100% more than in controls, with unknown delayed or latent impact.”
Learning more about how the brain processes and removes proteins such as Aβ could provide important insights into Alzheimer’s disease and its causes. Finch noted that very few cases of dementia occur with amyloid plaques, or masses of aggregated Aβ protein, as the only pathology present in affected patients’ brains. Instead, most cases present with more complicated tissue abnormalities, from buildup of additional types of protein to small bleeds in the brain: “The aging brain is a jungle.”
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Materials provided by University of Southern California. Original written by Beth Newcomb. Note: Content may be edited for style and length.

The length of a specific generation can tell us a lot about the biology and social organization of humans. Now, researchers at Indiana University can determine the average age that women and men had children throughout human evolutionary history with a new method they developed using DNA mutations.
The researchers said this work can help us understand the environmental challenges experienced by our ancestors and may also help us in predicting the effects of future environmental change on human societies.
“Through our research on modern humans, we noticed that we could predict the age at which people had children from the types of DNA mutations they left to their children,” said study co-author Matthew Hahn, Distinguished Professor of biology in the College of Arts and Sciences and of computer science in the Luddy School of Informatics, Computing and Engineering at IU Bloomington. “We then applied this model to our human ancestors to determine what age our ancestors procreated.”
According to the study, published today in Science Advances and co-authored by IU post-doctoral researcher Richard Wang, the average age that humans had children throughout the past 250,000 years is 26.9. Furthermore, fathers were consistently older, at 30.7 years on average, than mothers, at 23.2 years on average, but the age gap has shrunk in the past 5,000 years, with the study’s most recent estimates of maternal age averaging 26.4 years. The shrinking gap seems to largely be due to mothers having children at older ages.
Other than the recent uptick in maternal age at childbirth, the researchers found that parental age has not increased steadily from the past and may have dipped around 10,000 years ago because of population growth coinciding with the rise of civilization.
“These mutations from the past accumulate with every generation and exist in humans today,” Wang said. “We can now identify these mutations, see how they differ between male and female parents, and how they change as a function of parental age.”
Children’s DNA inherited from their parents contains roughly 25 to 75 new mutations, which allows scientists to compare the parents and offspring, and then to classify the kind of mutation that occurred. When looking at mutations in thousands of children, IU researchers noticed a pattern: The kinds of mutations that children get depend on the ages of the mother and the father.
Previous genetic approaches to determining historical generation times relied on the compounding effects of either recombination or mutation of modern human DNA sequence divergence from ancient samples. But the results were averaged across both males and females and across the past 40,000 to 45,000 years.
Hahn, Wang and their co-authors built a model that uses de novo mutations — a genetic alteration that is present for the first time in one family member as a result of a variant or mutation in a germ cell of one of the parents or that arises in the fertilized egg during early embryogenesis — to separately estimate the male and female generation times at many different points throughout the past 250,000 years.
The researchers were not originally seeking to understand the relationship of gender and age at conception over time; they were conducting a broader investigation about the number of mutations passed from parents to children. They only noticed the age-based mutation patterns while seeking to understand differences and similarities between these pattens in humans versus other mammals, such as cats, bears and macaques.
“The story of human history is pieced together from a diverse set of sources: written records, archaeological findings, fossils, etc.,” Wang said. “Our genomes, the DNA found in every one of our cells, offer a kind of manuscript of human evolutionary history. The findings from our genetic analysis confirm some things we knew from other sources (such as the recent rise in parental age), but also offer a richer understanding of the demography of ancient humans. These findings contribute to a better understanding of our shared history.”
Additional contributors to this research were Samer I. Al-Saffar, a graduate student at IU at the time of the study, and Jeffrey Rogers of the Baylor College of Medicine.

The ancient Romans were masters of engineering, constructing vast networks of roads, aqueducts, ports, and massive buildings, whose remains have survived for two millennia. Many of these structures were built with concrete: Rome’s famed Pantheon, which has the world’s largest unreinforced concrete dome and was dedicated in A.D. 128, is still intact, and some ancient Roman aqueducts still deliver water to Rome today. Meanwhile, many modern concrete structures have crumbled after a few decades.
Researchers have spent decades trying to figure out the secret of this ultradurable ancient construction material, particularly in structures that endured especially harsh conditions, such as docks, sewers, and seawalls, or those constructed in seismically active locations.
Now, a team of investigators from MIT, Harvard University, and laboratories in Italy and Switzerland, has made progress in this field, discovering ancient concrete-manufacturing strategies that incorporated several key self-healing functionalities. The findings are published in the journal Science Advances, in a paper by MIT professor of civil and environmental engineering Admir Masic, former doctoral student Linda Seymour, and four others.
For many years, researchers have assumed that the key to the ancient concrete’s durability was based on one ingredient: pozzolanic material such as volcanic ash from the area of Pozzuoli, on the Bay of Naples. This specific kind of ash was even shipped all across the vast Roman empire to be used in construction, and was described as a key ingredient for concrete in accounts by architects and historians at the time.
Under closer examination, these ancient samples also contain small, distinctive, millimeter-scale bright white mineral features, which have been long recognized as a ubiquitous component of Roman concretes. These white chunks, often referred to as “lime clasts,” originate from lime, another key component of the ancient concrete mix. “Ever since I first began working with ancient Roman concrete, I’ve always been fascinated by these features,” says Masic. “These are not found in modern concrete formulations, so why are they present in these ancient materials?”
Previously disregarded as merely evidence of sloppy mixing practices, or poor-quality raw materials, the new study suggests that these tiny lime clasts gave the concrete a previously unrecognized self-healing capability. “The idea that the presence of these lime clasts was simply attributed to low quality control always bothered me,” says Masic. “If the Romans put so much effort into making an outstanding construction material, following all of the detailed recipes that had been optimized over the course of many centuries, why would they put so little effort into ensuring the production of a well-mixed final product? There has to be more to this story.”
Upon further characterization of these lime clasts, using high-resolution multiscale imaging and chemical mapping techniques pioneered in Masic’s research lab, the researchers gained new insights into the potential functionality of these lime clasts.

Historically, it had been assumed that when lime was incorporated into Roman concrete, it was first combined with water to form a highly reactive paste-like material, in a process known as slaking. But this process alone could not account for the presence of the lime clasts. Masic wondered: “Was it possible that the Romans might have actually directly used lime in its more reactive form, known as quicklime?”
Studying samples of this ancient concrete, he and his team determined that the white inclusions were, indeed, made out of various forms of calcium carbonate. And spectroscopic examination provided clues that these had been formed at extreme temperatures, as would be expected from the exothermic reaction produced by using quicklime instead of, or in addition to, the slaked lime in the mixture. Hot mixing, the team has now concluded, was actually the key to the super-durable nature.
“The benefits of hot mixing are twofold,” Masic says. “First, when the overall concrete is heated to high temperatures, it allows chemistries that are not possible if you only used slaked lime, producing high-temperature-associated compounds that would not otherwise form. Second, this increased temperature significantly reduces curing and setting times since all the reactions are accelerated, allowing for much faster construction.”
During the hot mixing process, the lime clasts develop a characteristically brittle nanoparticulate architecture, creating an easily fractured and reactive calcium source, which, as the team proposed, could provide a critical self-healing functionality. As soon as tiny cracks start to form within the concrete, they can preferentially travel through the high-surface-area lime clasts. This material can then react with water, creating a calcium-saturated solution, which can recrystallize as calcium carbonate and quickly fill the crack, or react with pozzolanic materials to further strengthen the composite material. These reactions take place spontaneously and therefore automatically heal the cracks before they spread. Previous support for this hypothesis was found through the examination of other Roman concrete samples that exhibited calcite-filled cracks.
To prove that this was indeed the mechanism responsible for the durability of the Roman concrete, the team produced samples of hot-mixed concrete that incorporated both ancient and modern formulations, deliberately cracked them, and then ran water through the cracks. Sure enough: Within two weeks the cracks had completely healed and the water could no longer flow. An identical chunk of concrete made without quicklime never healed, and the water just kept flowing through the sample. As a result of these successful tests, the team is working to commercialize this modified cement material.
“It’s exciting to think about how these more durable concrete formulations could expand not only the service life of these materials, but also how it could improve the durability of 3D-printed concrete formulations,” says Masic.
Through the extended functional lifespan and the development of lighter-weight concrete forms, he hopes that these efforts could help reduce the environmental impact of cement production, which currently accounts for about 8 percent of global greenhouse gas emissions. Along with other new formulations, such as concrete that can actually absorb carbon dioxide from the air, another current research focus of the Masic lab, these improvements could help to reduce concrete’s global climate impact.
The research team included Janille Maragh at MIT, Paolo Sabatini at DMAT in Italy, Michel Di Tommaso at the Instituto Meccanica dei Materiali, in Switzerland, and James Weaver at the Wyss Institute for Biologically Inspired Engineering at Harvard University. The work was carried out with the assistance of the archeological museum of Priverno, Italy.