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Levantine Crested Rat And Early Human Dispersals (Paleontology)

Crested rat fossils suggest that ecological corridors once connected Africa to the Levant, according to a study.

Early humans and other hominins dispersed out of Africa through the Levant multiple times, but whether these journeys relied on technology to cross the Saharo-Arabian deserts or followed ecological corridors created by climate change is unclear.

Ignacio Lazagabaster and colleagues analyzed rodent fossils discovered in the Cave of the Skulls in the southern Judean Desert as a proxy for the paleoenvironment of the Dead Sea region during the Late Pleistocene.

Phylogenetic analyses of a sequenced mitochondrial genome and morphological comparisons suggest that the fossils, which were dated to between 42,000 and more than 103,000 years ago, belong to a now-extinct subspecies, Lophiomys imhausi maremortum subsp. nov., of the eastern African crested rat, an enigmatic large rodent equipped with a poisonous pelt and a helmet-like skull. Because extant crested rats live in habitats with relatively dense vegetation, the authors used species distribution models to estimate the timing and location of previously suitable habitats in the region.

View of the Dead Sea and the southern Judean Desert from the Cave of the Skulls. Ignacio A. Lazagabaster

The results* suggest a brief period during the Last Interglacial when green habitat corridors connected eastern Africa to the Levant across the present-day Judean Desert, facilitating the dispersal of crested rats and humans out of Africa, according to the authors.

“Rare crested rat subfossils unveil Afro-Eurasian ecological corridors synchronous with early human dispersals,” by Ignacio A. Lazagabaster et al.

Featured image: A skull of the Dead Sea crested rat subspecies found in situ in the Cave of the Skulls in the southern Judean Desert. Ignacio A. Lazagabaster.


Thomas Cromwell’s Tudor London Mansion Revealed in Unprecedented Detail (Archeology)

New insights come on anniversary of Cromwell’s death and ahead of the final part of the ‘Wolf Hall’ trilogy which hits West End later this year.

The magnificent London mansion of Thomas Cromwell has been revealed for the first time in an artist’s impression, following a new study which examines the building in unprecedented detail.

Dr Nick Holder, a historian and research fellow at English Heritage and the University of Exeter, has scrutinized an exceptionally rich source of information, including letters, leases, surveys and inventories, to present the most thorough insight to-date on “one of the most spectacular private houses” in 1530s London.

Published in the peer-reviewed Journal of the British Archaeological Association, his findings* – which have informed the artist’s impression created by illustrator Peter Urmston – include floor plans for the mansion, which had 58 rooms plus servants’ garrets, and a large garden.

The plans have been released before but the evidence behind them hasn’t been presented until now.

Together with an accompanying room-by-room analysis of another of Cromwell’s London homes, it provides a fascinating new insight into the life and personality of a man who was one of the architects of the English Reformation and helped engineer the annulment of Henry VIII’s marriage to Catherine of Aragon, allowing him to marry Anne Boleyn.

Cromwell, who as Henry VIII’s henchman was the most powerful man in England, still captures the public imagination – and inspires novels, including Hilary Mantel’s award-winning Wolf Hall series, plays and TV series – today, almost 500 years after his death.

The mansion, next to the Austin Friars monastery in the City of London, cost Cromwell at least £1,600 to build, including around £550 on the land.

Cromwell had lived in Italy and spoke Italian and it is “very likely” the architecture contained fashionable new Italian Renaissance features, says Dr Holder.

Construction began in July 1535 and, like many building projects, there were hitches, including a delay in October the following year when the 80-strong team of workmen was sent to Yorkshire to fight the rebels of the Pilgrimage of Grace uprising.

Cromwell also seems to have undertaken a “land grab”, confiscating a 22-foot strip of land to enlarge his garden, which may have had a bowling alley and tennis court.

The mansion, which boasted bedding made cloth of gold, damask and velvet, acted as a family home, an administrative base and a venue for entertainment. It may even have been designed in the anticipation, or perhaps fear, of a visit from the king.

Prestigious visitors would have been guided up the large stair tower to one of the sumptuous first-floor halls, the parlor or the ladies’ parlor. The heated halls were decorated with tapestry hangings and one had three distinctive oriel (bay) windows.

The mansion was also a store for Cromwell’s personal armouy – in reality enough for a small army. This included several hundred sets of “almayne revettes” (German plate armor for infantry), nearly 100 sallets and bascinets (head-pieces and helmets) and weaponry including 759 bows, complete with hundreds of sheaves of arrows.

Cromwell would, however, have had little time to enjoy his spectacular new home before he was executed for treason in 1540.

He had moved to the mansion from a 14-room neighboring townhouse, for which he probably paid £4 a year in rent. Documents, including two inventories from Cromwell’s tenancy, provide a room-by-room description of this home and its contents, which included 28 rings, three of which Cromwell was wearing at the time of the inventory. They also give an intriguing glimpse into his religious outlook.

Dr Holder says: “We think of Cromwell as Henry VIII’s henchman, carrying out his policy, including closing down the monasteries, and we know that by about 1530 Cromwell became one of the new Evangelical Protestants.

“But when you look at the inventory of his house in the 1520s, he doesn’t seem such a religious radical, he seems more of a traditional English Catholic.

“He’s got various religious paintings on the wall, he’s got his own holy relic, which is very much associated with traditional Catholics, not with the new Evangelicals, and he’s even got a home altar. In the 1520s he seems like much more of a conventional early Tudor Catholic gentleman.”

The coats of arms of his patron Cardinal Wolsey and former patron, Thomas Grey, which were on display in the townhouse, meanwhile, reveal a sense of loyalty beneath Cromwell’s ruthless exterior, says Dr Holder.

The exceptionally detailed analysis was made possible thanks to a “treasure trove” of documents held in the archives of the Drapers’ Company, the trade group that bought Cromwell’s mansion after his death.

Dr Holder adds: “These two houses were the homes of this great man, they were the places where he lived with his wife and two daughters, where his son grew up. It was also the place he went back to at night after being with Henry VIII at court and just got on with the hard graft of running the country.

“No one else has looked at these two houses in quite as much detail comparing all the available evidence. This is about as close as you are going to get to walking down these 16th-century corridors.”


Featured image: Artist conception of the Cromwell home. Peter Urmston

Provided by Taylor & Francis Group 

Scientists Designed World’s Most Sophisticated COVID-19 Sequencing System – Here’s How They Did It? (Biology)

New bioinformatics software and cloud computing approaches developed at the University of Birmingham, have enabled the UK’s COVID-19 genome sequencing effort to be the most sophisticated in the world.

The system, called CLIMB-COVID was designed for the COVID-19 Genomics UK (COG-UK) consortium, set up in March 2020 to tackle the huge challenge of rapidly sequencing SARS-CoV-2 genomes. In a new paper, published this month in Genome Biology, the research team discussed the approach they took.

The first version of CLIMB-COVID was designed and built by researchers at the University of Birmingham and Cardiff University in under a month and has been instrumental in processing the sequencing data of more than 675,000 coronavirus genomes, including identifying and tracking the Alpha and Delta variants that became dominant in the UK. CLIMB-COVID also integrates new software from collaborators at the University of Edinburgh and the Centre for Genomic Pathogen Surveillance.

CLIMB-COVID enables a distributed sequencing system, harnessing sequencing capability from universities, academic institutes and the UK’s four public health agencies. The CLIMB-COVID software and database infrastructure was able to receive all this data, process it and help analyse it into interpretable outputs for public health analysts.

All the data from the project has been integrated and shared in real-time. Not only has this enabled the UK’s public health agencies to work together more easily, but enabling seamless access and collaboration with academics, also enabled the early detection and evaluation of new variants of the virus.

Understanding viral evolution is important for understanding how the virus is spreading in local, national and international settings. It provides valuable epidemiological information revealing the chains of transmission that must be stopped in order to stop outbreaks.

Dr Samuel Nicholls, lead author on the paper, says: “Building this kind of decentralised sequencing system has not been possible before now, because the software infrastructure has not been available. By designing that system, we have shown how genetic sequencing can be used as a vital tool in any public health response.”

The COG-UK consortium benefited particularly from cloud computing resources established as part of the CLIMB-BIG-DATA project in which the University of Birmingham and Cardiff University has played a pivotal role, as well as the University of Birmingham’s BEAR high performance computing infrastructure which provided additional capacity. This cloud infrastructure provides the computing and storage capacity required to analyse the large genome datasets produced by the consortium, as well as facilitating national and international research capabilities.

Dr Nicholls adds: “The CLIMB-COVID system is open source. That means anyone in the world can access our computer code and all genomic data, and can see how we work. We have never seen such a co-ordinated, sustained effort to generate real-time genomic surveillance data at this scale and pace and this is why the UK is world-leading in the genomic sequencing of SARS-CoV-2.”

Notes to editor:

Nicholls et al (2021). ‘CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance’. Genome Biology.

Provided by University of Birmingham

SwRI Team Zeroes In On Source Of the Impactor That Wiped Out the Dinosaurs (Planetary Science)

The impactor believed to have wiped out the dinosaurs and other life forms on Earth some 66 million years ago likely came from the outer half of the main asteroid belt, a region previously thought to produce few impactors. Researchers from Southwest Research Institute have shown that the processes that deliver large asteroids to Earth from that region occur at least 10 times more frequently than previously thought and that the composition of these bodies match what we know of the dinosaur-killing impactor. 

The SwRI team — including Dr. David Nesvorný, Dr. William Bottke and Dr. Simone Marchi — combined computer models of asteroid evolution with observations of known asteroids to investigate the frequency of so-called Chicxulub events. Over 66 million years ago, a body estimated to be 6 miles across hit in what is now Mexico’s Yucatan peninsula and formed Chicxulub crater, which is over 90 miles across. This massive blast triggered a mass extinction event that ended the reign of the dinosaurs. Over the last several decades, much has been learned about the Chicxulub event, but every advance has led to new questions.

“Two critical ones still unanswered are: ‘What was the source of the impactor?’ and ‘How often did such impact events occur on Earth in the past?’” Bottke said.

To probe the Chicxulub impact, geologists have previously examined 66-million-year-old rock samples found on land and within drill cores. The results indicate the impactor was similar to the carbonaceous chondrite class of meteorites, some of the most pristine materials in the solar system. Curiously, while carbonaceous chondrites are common among the many mile-wide bodies that approach the Earth, none today are close to the sizes needed to produce the Chicxulub impact with any kind of reasonable probability.

“We decided to look for where the siblings of the Chicxulub impactor might be hiding,” said Nesvorný, lead author of a paper describing the research.

“To explain their absence, several past groups have simulated large asteroid and comet breakups in the inner solar system, looking at surges of impacts on Earth with the largest one producing Chicxulub crater,” said Bottke, one of the paper’s co-authors. “While many of these models had interesting properties, none provided a satisfying match to what we know about asteroids and comets. It seemed like we were still missing something important.” 

To solve this problem, the team used computer models that track how objects escape the main asteroid belt, a zone of small bodies located between the orbits of Mars and Jupiter. Over eons, thermal forces allow these objects to drift into dynamical “escape hatches” where the gravitational kicks of the planets can push them into orbits nearing Earth. Using NASA’s Pleaides Supercomputer, the team followed 130,000 model asteroids evolving in this slow, steady manner for hundreds of millions of years. Particular attention was given to asteroids located in the outer half of the asteroid belt, the part that is furthest from the Sun. To their surprise, they found that 6-mile-wide asteroids from this region strike the Earth at least 10 times more often than previously calculated.

“This result is intriguing not only because the outer half of the asteroid belt is home to large numbers of carbonaceous chondrite impactors, but also because the team’s simulations can, for the first time, reproduce the orbits of large asteroids on the verge of approaching Earth,” said co-author Marchi. “Our explanation for the source of the Chicxulub impactor fits in beautifully with what we already know about how asteroids evolve.”

Overall, the team found that 6-mile-wide asteroids hit the Earth once every 250 million years on average, a timescale that yields reasonable odds that the Chicxulub crater occurred 66 million years ago. Moreover, nearly half of impacts were from carbonaceous chondrites, a good match with what is known about the Chicxulub impactor.

“This work will help us better understand the nature of the Chicxulub impact, while also telling us where other large impactors from Earth’s deep past might have originated,” Nesvorný said.

The journal Icarus is publishing a paper about this research, “Dark Primitive Asteroids Account for a Large Share of K/Pg-Scale Impacts on the Earth” (Volume 368, 1 November 2021, 114621, Elsevier publications).

A link to the published paper can be found here: , while a preprint is available here:

Featured image: An SwRI team modeled evolutionary processes in the main asteroid belt and discovered that impactors such as the one that ended the reign of the dinosaurs are most likely from the outer half of the main asteroid belt. The team also discovered that delivery processes from that region occur 10 times more often than previously thought. © Courtesy of SwRI/Don Davis

Provided by Southwest Research Institute

The Thinnest CD-RW: Atomic-scale Data Storage Possible (Nanotechnology)

Using a focused laser beam, scientists can manipulate properties of nanomaterials, thus ‘writing’ information onto monolayer materials. By this means, the thinnest light disk at atomic level was demonstrated.

The bottleneck in atomic-scale data storage area may be broken by a simple technique, thanks to recent innovative studies conducted by scientists from Nanjing Normal University (NJNU) and Southeast University (SEU).

Through a simple, efficient and low-cost technique involving the focused laser beam and ozone treatment, the NJNU and SEU research teams, leading by Prof. Hongwei Liu, Prof. Junpeng Lu and Prof. Zhenhua Ni demonstrated that the photoluminescence (PL) emission of WS2 monolayers can be controlled and modified, and consequently, it works as the thinnest light disk with rewritable data storage and encryption capability.

“In our childhood, most of us are likely to have experience of focusing sunlight onto a piece of paper by magnifying glass and trying to ignite the paper. The scorched spot on paper is a sort of data recording at the moment. Instead of focusing sunlight, we focus laser beam on modified atomic level materials and study effects of the focused laser beam on PL emissions of the materials,” said Prof. Lu.

Data storage and encryption: information ‘drawn’ on ozone treated WS2 films

Owing to its advantage of direct visibility, PL is usually considered as an ideal technology in terms of encryption and decryption data storage. For a straightforward and effective encryption data storage method, the following aspects are desired: (i) direct writing (fast writing-in speed); (ii) high security level; (iii) large data storage capacity; (iv) visual decryption reading; (v) erasing capability.

To address these technological challenges, researchers demonstrate the thinnest light disk with encryption functionality.

The write-through and erasable encryption are realized on WS2 monolayers. The writing-in and reading-out of information are enabled by the directly controlling of fluorescence contrast of WS2 monolayers. Ozone and focused laser beam scanning are employed to on-demand manipulate PL emission and realize encryption.

With this simple and low cost approach, the scientists were able to use the focused laser beam to selectively ‘write’ information onto any region of the film to storage encrypted data. In addition, the written data are erasable, making the monolayer light disk reusable.

Interestingly, the evolution of PL emission with different writing laser powers could be used to assign different gray levels. The 16 gray levels assignment indicates a typical triangle WS2 monolayer with the side length of 60 μm can storage ~1 KB data. Owing the high spatial resolution and power sensitivity, the storage capacity within 1 nm thickness could be up to ~62.5 MB/cm2 and the writing speed can reach ~6.25 MB/s. This technology will be beneficial to extend the optical encryption into low dimensional regime, offering an unexpected information-secure solution to exchange data.

This innovation was first published online in the journal Advanced Functional Materials on 24 June 2021.

The fast-growing information field demands higher security and larger storage capability. To develop light disk that cater to the industry standard, The research teams from NJNU and SEU will extend the versatile focused laser beam technique to wafer-scale monolayer material. In addition, they will look into further improving the storge capability of light disk via normal direction stacking.

Featured image: Design of The Thinnest Light Disk: Direct-Writing, Erasable Data Storage and Encryption on WS2 Monolayers. The writing-in and reading-out of information are enabled by the directly controlling of fluorescence contrast of WS2 monolayers. (Image: Prof. Zhenhua Ni’s Lab)

Reference: Weiwei Zhao et al, The Thinnest Light Disk: Rewritable Data Storage and Encryption on WS2 Monolayers, Advanced Functional Materials (2021). DOI: 10.1002/adfm.202103140

Provided by Nanjing Normal University

Penn Medicine Discovery Clarifies the Problem of T-Cell “Exhaustion” (Biology)

Findings provide lessons for immune-based therapy research

Researchers in the Perelman School of Medicine at the University of Pennsylvania have illuminated an important limitation of the immune system in prolonged battles against cancers or viruses: T cells, which are among the most powerful weapons in the immune systems of humans and other vertebrates, remain substantially programmed to stay exhausted even many weeks after exposure to a virus ended. The findings were published today in Nature Immunology.

Scientists have known that T cells can lose their ability to fight viruses and tumors when they have prolonged exposure to these enemies. They have hoped that this “T cell exhaustion” phenomenon could be reversed relatively easily, for example when the T cells are no longer exposed to the virus or tumor in question. Scientists now will need to take into account this limitation, including when devising immune-based therapies against chronic viral infections and cancers.

“Our findings suggest that once T cells become exhausted, they remain fundamentally ‘wired’ to be exhausted—thus it may be hard to get them to become effective virus- and cancer-fighters again,” said study senior author E. John Wherry, PhDchair of the department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania.

The recognition of the T cell exhaustion problem emerged about two decades ago from studies of long-term viral infections, including studies by Wherry and his laboratory. Scientists eventually concluded that long-term exposure not only to viruses but also to cancerous tumors could exhaust T cells. Exhausted T cells start producing much lower amounts of immune response-stimulating proteins, and generally become less able to kill virus-infected cells or tumor cells.

Researchers have hoped that by blocking certain activity-inhibiting receptors on exhausted T cells, they could reinvigorate the T cells in cancer patients and in patients infected long-term with viruses such as HIV or Hepatitis C virus. However, there is evidence now that such reinvigoration, for example with cancer drugs called PD-1 inhibitors, tends to be incomplete and temporary.

One question that hasn’t been resolved is whether, and to what extent, exhausted T cells can recover normal functions if they no longer have exposure to the virus or tumor that exhausted them. In other words, if a person goes into long-term remission from cancer, will his or her anti-tumor T cells become un-exhausted, providing some measure of immunity against future cancer recurrence?

Nature Immunology02
Although exhausted T cells recovered from chronic infection (REC-TEX) regain some function and features of memory T cells (TMEM), they retain epigenetic scars indicating the control of gene expression is “locked in” to their exhaustion history. © Penn Medicine

Wherry and colleagues, including first author Mohamed Abdel-Hakeem, PhD, a postdoctoral research associate in the Wherry Laboratory, addressed this question in the new study. They examined mouse T cells that had been exhausted by chronic exposure to a mouse virus called LCMV—long used as a standard model of T cell-exhausting infection.

The researchers found that most of the exhausted T cells died when they were no longer exposed to LCMV. The small proportion that survived recovered some of the gene expression patterns that would be expected in normal, memory-type T cells that help sustain a long-term immune defense following infection. But for the most part, the T cells remained programmed to stay in the exhausted, ineffective state, especially when called into action again upon reinfection.

A cell is programmed to be in a certain state or identity by an “epigenetic” system of molecules that control which genes are active or inactive in the cell. These molecules often work by altering the structure of coiled DNA in the nucleus of the cell, making some genes more accessible to gene-copying enzymes, and others less accessible. In the study, the researchers observed that the epigenetic, DNA-structure changes that are characteristic of exhausted T cells mostly remained stable in these cells after LCMV exposure ended.

“Exhaustion apparently leaves durable ‘epigenetic scars’ in T cells that constrain their ability to support an immune response. These findings point to a need to discover how to reverse that epigenetic scarring,” Wherry said.

In principle, future treatments that reverse those epigenetic changes could turn exhausted T cells in patients into normal memory T cells again. Epigenetic drugs have long been a hope of cancer therapy because tumor cells also undergo epigenetic dysregulation. These drugs, however, remain somewhat unwieldly or imprecise in their effects. However, if the right epigenetic drugs can be found to modulate immune cells that could help patients fight ongoing cancers or viral infections, and could also provide patients with stronger long-term immunity following the eradication of tumors or chronic viral infections. Studies at Penn Medicine are ongoing to manipulate the epigenetics of exhausted T cells in combination with immunotherapy.

Support for the research was provided by the National Institutes of Health (AI155577, AI105343, AI115712, AI117950, AI108545, AI082630, and CA210944), the Parker Institute for Cancer Immunotherapy, the Cancer Research Institute, Fonds de Recherche Québec—Santé, and the Canadian Network on Hepatitis C.

Featured image: Profiling of differentiation state of Exhausted T cells (TEX), Memory T cells (TMEM) and exhausted T cells that have recovered from chronic infection (REC-TEX). The purple shading for REC-TEX indicates only partial overlap with each of the other two cell types. In other words, REC-TEX do not fully recover from exhaustion © Penn Medicine

Reference: Abdel-Hakeem, M.S., Manne, S., Beltra, JC. et al. Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation. Nat Immunol 22, 1008–1019 (2021).

Provided by Penn Medicine

Scientists Use Tiny Bubbles To Help Treat Common Childhood Cancer (Medicine)

Researchers at UCL have developed a new way to deliver drugs that can shut down cancer-promoting mutations in neuroblastoma. The findings in mice, show the method, which uses tiny bubbles to deliver therapies directly to tumour cells, reduced tumour growth and improved survival.

Neuroblastoma is the most common solid tumour found in children and accounts for about 15% of all cancer-related deaths in children. Tumours develop from certain types of nerve cells and are most commonly found in the abdomen. Children who are diagnosed above the age of one often fail to respond to treatment or relapse at a later time, meaning that there is an urgent need for new treatment options. 

The research, published in Advanced Functional Materials and funded by Worldwide Cancer Research, now offers a new potential treatment approach. MYCN is a gene that is associated with poor prognosis and is found to be mutated or overactive in about 20% of neuroblastoma cases. The gene is usually expressed during foetal development and is involved in cell growth and development. Neuroblastoma cells continue to express too much MYCN, leading to uncontrolled cell growth and division and preventing cancer cells from dying.

Researchers at UCL Great Ormond Street Institute of Child Health have now found a way to silence MYCN by delivering a certain type of genetic material called siRNA, directly to the tumour cells. They developed nanoparticles – or tiny bubbles – that use the leaky blood vessels around the tumour and certain features that are only present on tumour cells to home in on the tumours.

The vast majority of nanoparticles, which were delivered via injection, located to the tumour and successfully shut down the MYCN gene causing the cancer. The treatment caused the tumours to grow at a slower pace and prolonged the time that the mice survived the cancer.

Senior author, Professor Stephen Hart, UCL GOS ICH, said: “These findings show that this approach with MYCN siRNA delivered by a nanoparticle is a new potential therapy for neuroblastoma. The next steps would be to develop methods of scaling up production to clinical grade, and to show that the treatment is safe. Current therapies such as surgery, radio and chemotherapy are effective at removing the primary tumour but, unfortunately, in many cases the tumour will return at other sites in the body, which is much harder to treat. We hope that this therapy might augment conventional therapies and provide a way of targeting the therapy to these new tumour sites.”

Dr Helen Rippon, Chief Executive at Worldwide Cancer Research said: “Each year about 100 families in the UK receive the devastating news that their child has developed neuroblastoma. Unfortunately, the cancer is often detected at a relatively late stage and intense treatment is needed.

“We are funding researchers, like Professor Hart, to start new cancer cures and this innovative research shows just how important investment in early-stage discovery research is. Using new methods, such as nanoparticles, to deliver treatment straight to the heart of cancer is an incredibly exciting area of research. These new results now offer hope to patients and their families by paving the way for effective new treatment options.”



  • UCL Great Ormond Street Institute of Child Health

Provided by UCL

New Insights Into the Relationship Between How We Feel And Our Views On Aging (Psychology)

A new study finds that the disconnect between how old we feel and how old we want to be can offer insights into the relationship between our views on aging and our health.

Subjective age discordance (SAD) – the difference between how old you feel and how old you would like to be—is a fairly new concept in the psychology of aging. However, the work to this point has used SAD to look at longitudinal data and how people’s views on aging evolve over months or years.

“We wanted to see whether SAD could help us assess day-to-day changes in our views on aging, and how that may relate to our physical health and well-being,” says Shevaun Neupert, co-author of the study and a professor of psychology at North Carolina State University.

SAD is determined by taking how old you feel, subtracting how old you would like to be and then dividing it by your actual age. The higher the score, the more you feel older than you want to be.

For this study, researchers enrolled 116 adults aged 60-90 and 107 adults aged 18-36. Study participants filled out an online survey every day for eight days. The survey was designed to assess how old participants felt each day, their ideal age, their positive and negative mood over the course of the day, any stresses they experienced, and any physical complaints, such as backaches or cold symptoms.

“We found that both older adults and younger adults experienced SAD,” Neupert says. “It was more pronounced in older adults, which makes sense. However, it fluctuated more from day to day in younger adults, which was interesting.”

“We think younger adults are getting pushed and pulled more,” says Jennifer Bellingtier, first author of the paper, and a researcher at Friedrich Schiller University Jena. “Younger adults are concerned about negative stereotypes associated with aging, but may also be dealing with negative stereotypes associated with younger generations and wishing they had some of the privileges and status associated with being older.”

Two additional findings stood out.

“On days when the age you feel is closer to your ideal age, people tend to have a more positive mood,” Bellingtier says. “And, on average, people who have more health complaints also had higher SAD scores.”

Neither finding was surprising, but both show the value of the SAD concept as a tool for understanding people’s views on age and aging. It may also offer a new approach for the way we think about aging and its impacts on health.

“Previous research has found that how old you feel can affect your physical and mental well-being, and interventions to address that have focused on trying to make people feel younger,” Neupert says.

“That approach is problematic, in that it effectively encourages ageism,” says Bellingtier. “Our findings in this study suggest that another approach to improving well-being would be to find ways to reduce this subjective age discordance. In other words, instead of telling people to feel young, we could help people by encouraging them to raise their ‘ideal’ age.”

The paper, “Daily Experiences of Subjective Age Discordance and Well-Being,” is published in the journal Psychology and Aging.

Reference: Jennifer A. Bellingtier et al, Daily experiences of subjective age discordance and well-being., Psychology and Aging (2021). DOI: 10.1037/pag0000621

Provided by North Carolina State University

Turning the Molecular Clock Back On Halts Neuroblastoma Tumor Growth (Medicine)

Researchers at Baylor College of Medicine and Texas Children’s Cancer Center have found that the molecular clock may be key to treating neuroblastoma. The researchers studied patients with high expression of MYCN, known to be the major oncogenic driver of neuroblastoma. In those patients, two main components of the molecular clock were repressed—BMAL1, which oscillates to drive the clock cycle, and RORa, which activates BMAL1. This repression correlated with poor clinical outcome.

“We were very interested in how MYCN can reprogram tumor metabolism,” said Dr. Eveline Barbieri, assistant professor of pediatrics—hematology and oncology at Baylor. “We found that MYCN amplification inhibits BMAL1 expression and oscillation, leading to metabolic reprograming and oncogenesis.”

Because BMAL1 and RORa suppression allowed the tumor cells to grow, the researchers wanted to know if restoring these components of the molecular clock would stop growth in neuroblastoma cells. They tested two approaches in the lab—genetic overexpression of RORa and a pharmaceutical approach using a synthetic ligand that reactivates RORa. Both techniques successfully restored BMAL1 expression and oscillation.

Restoring the clock blocked tumor growth

“Our strategy to restore BMAL1 expression also blocked tumor growth, suggesting that repression of the molecular clock is indeed oncogenic,” Barbieri said. “We showed that restoration of the molecular clock suppresses neuroblastoma growth and also makes neuroblastoma tumors more sensitive to conventional chemotherapy treatments, offering a potential future therapeutic approach.”

“Our cells follow a molecular clock that controls cell metabolism, much like the body’s circadian rhythm controls sleep cycles. We know that metabolic processes are really important in how tumors develop resistance to chemotherapy,” Barbieri said. “In the future, if we can develop therapeutics that restore the molecular clock in a clinical setting, we may be able to use them in combination with standard chemotherapy to avoid treatment resistance.”

Featured image: A microscopic view of a typical neuroblastoma. Credit: National Cancer Institute

Reference: Myrthala Moreno-Smith et al, Restoration of the molecular clock is tumor suppressive in neuroblastoma, Nature Communications (2021). DOI: 10.1038/s41467-021-24196-4

Provided by Baylor College of Medicine