The study’s researchers had previously developed the 28-item San Diego Wisdom Scale (SD-WISE-28), which has been used in large national and international studies, biological research and clinical trials to evaluate wisdom.

But in a study publishing in International Psychogeriatrics, researchers found that a shortened seven-item version (SD-WISE-7 or Jeste-Thomas Wisdom Index), was comparable and reliable.

“Wisdom measures are increasingly being used to study factors that impact mental health and optimal aging. We wanted to test if a list of only seven items could provide valuable information to test wisdom,” said senior author Dilip V. Jeste, MD, senior associate dean for the Center of Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine.

Past studies have shown that wisdom is comprised of seven components: self-reflection, pro-social behaviors (such as empathy, compassion and altruism), emotional regulation, acceptance of diverse perspectives, decisiveness, social advising (such as giving rational and helpful advice to others) and spirituality.

The latest study surveyed 2,093 participants, ages 20 to 82, through the online crowdsourcing platform Amazon Mechanical Turk.

The seven statements, selected from SD-WISE-28, relate to the seven components of wisdom and are rated on a 1 to 5 scale, from strongly disagree to strongly agree. Examples of the statements include “I remain calm under pressure” and “I avoid situations where I know my help will be needed.”

“Shorter doesn’t mean less valid,” said Jeste. “We selected the right type of questions to get important information that not only contributes to the advancement of science but also supports our previous data that wisdom correlates with health and longevity.”

Additionally, the SD-WISE-7 was found to strongly and positively correlate with resilience, happiness and mental well-being and strongly and negatively correlate with loneliness, depression and anxiety.

“There are evidence-based interventions to increase levels of specific components of wisdom, which would help reduce loneliness and promote overall well-being,” said Jeste.

“Like the COVID-19 vaccine protects us from the novel coronavirus, wisdom can aid in protecting us from loneliness. Thus, we can potentially help end a behavioral pandemic of loneliness, suicides and opioid abuse that has been going on for the last 20 years.”

Next steps include genetic, biological, psychosocial and cultural studies of large numbers of diverse populations to assess wisdom, as well as various factors related to mental, physical and cognitive health in people across the lifespan.

“We need wisdom for surviving and thriving in life. Now, we have a list of questions that take less than a couple of minutes to answer that can be put into clinical practice to try to help individuals,” said Jeste.

Co-authors include: Michael Thomas with Colorado State University; and Barton Palmer, Ellen Lee, Jinyuan Liu, Rebecca Daly and Xin Tu, all with UC San Diego.

This proof of principle study, published in Nature Communications today (Friday 3^rd December), demonstrates how the technology could be used to improve animal welfare in scientific research and perhaps also agriculture.

In scientific research and also farming, there is often a need for either male or female animals. For example, laboratory research into male or female reproduction requires only animals of the sex being studied. And in farming, only female animals are required for egg production and in dairy herds. This means it is common practice for animals of the unrequired sex to be culled after birth.

The researchers’ new method uses a two-part genetic system to inactivate embryos shortly after fertilisation, allowing only the desired sex to develop. Such a genetically-based method to control the sex of offspring could drastically reduce culling in both industries.

The embryo selection is based on the fact that there are two elements of CRISPR-Cas9 — the Cas9 enzyme that cuts the DNA, allowing scientists to alter specific regions, and the guide RNA which carries the Cas9 to the right location on the genome. The team placed one element of the system on the father’s X or Y chromosome, meaning that it will only be inherited by female or male embryos respectively. The other element is contributed by the mother, and is inherited by all embryos.

They targeted the Top1 gene, which is essential to DNA replication and repair. When an embryo formed from a sperm and egg, each containing one half of CRISPR-Cas9, the gene-editing was triggered in the embryo and it was not able to develop beyond a very early stage of around 16 to 32 cells.

Using this method, the researchers were able to control, with 100% effect, the sex of a litter. To produce a male-only litter, the researchers edited the father’s X chromosome, meaning only females inherited the deleterious mutation, and for a female-only litter, they edited the Y chromosome.

Surprisingly, the method did not lead to a 50% decrease in the number of offspring produced, rather the litter sizes were between 61% — 72% of the control litters. The researchers suggest this is because animals such as mice produce more eggs than required during each ovarian cycle, allowing for a proportion of them to be lost during early development without reducing litter size. This means that in situations where one sex is needed, fewer breeding animals will be required in order to produce the same number of the desired sex of offspring.

As the Top1 gene is well conserved across mammals, these results may also be applicable to other animals.

Charlotte Douglas, first author and former PhD student and postdoctoral scientist at the Crick, says: “This method works as we split the genome editing process in half, between a male and female, and it is only when the two halves meet in an embryo through breeding, that it is activated. Embryos with both halves cannot develop beyond very early cell stages.

“We’ve also shown this process works successfully in different combinations — introducing either the Cas9 or the guide RNA elements on to the mother’s or father’s chromosomes.”

As the offspring which survive only contain half of the CRISPR-Cas9 elements within their genome, this acts as a control preventing the sex-selection being passed down to further generations, unless they are selectively bred with an individual of the opposite sex containing the other half. This is different to genetic engineering through ‘gene-drive’ methods, which seek to spread a genetic mutation widely amongst a population.

There are also no harmful effects of the gene edit in the surviving offspring.

James Turner, author and group leader of the Sex Chromosome Biology Laboratory at the Crick says: “This work could have immediate and valuable impact in scientific laboratories, as we’ve shown how it is safe and effective in mice, a common mammal used in medical and scientific research. While a lot of research needs both sexes, there are areas of study where only one is needed. For example, when studying the reproductive system, sex-specific diseases, or certain hormones.”

Peter Ellis, author and senior lecturer in molecular genetics and reproduction at University of Kent, says: “The implications of this work are potentially far-reaching when it comes to improving animal welfare, but should be considered at ethical and regulatory levels.

“In particular, before any potential use in agriculture, there would need to be extensive public conversation and debate, as well as changes to legislation. On the scientific side, there is also much work to be done over a number of years. Further research is needed, first to develop the particular gene editing toolkits for different species, and then to check they are safe and effective.”

Most people fall into one of three ‘information-seeking types’: those that mostly consider the impact of information on their feelings when deciding whether to get informed, those that mostly consider how useful information will be for making decisions, and those that mostly seek information about issues they think about often, according to the findings published in Nature Communications.

Co-lead author Professor Tali Sharot (UCL Psychology & Language Sciences and Max Planck UCL Centre for Computational Psychiatry and Ageing Research) said: “Vast amounts of information are now available to individuals. This includes everything from information about your genetic make-up to information about social issues and the economy. We wanted to find out: how do people decide what they want to know? And why do some people actively seek out information, for example about COVID vaccines, financial inequality and climate change, and others don’t?

“The information people decide to expose themselves to has important consequences for their health, finance and relationships. By better understanding why people choose to get informed, we could develop ways to convince people to educate themselves.”

The researchers conducted five experiments with 543 research participants, to gauge what factors influence information-seeking.

In one of the experiments, participants were asked how much they would like to know about health information, such as whether they had an Alzheimer’s risk gene or a gene conferring a strong immune system. In another experiment, they were asked whether they wanted to see financial information, such as exchange rates or what income percentile they fall into, and in another one, whether they would have liked to learn how their family and friends rated them on traits such as intelligence and laziness.

Later, participants were asked how useful they thought the information would be, how they expected it would make them feel, and how often they thought about each subject matter in question.

The researchers found that people choose to seek information based on these three factors: expected utility, emotional impact, and whether it was relevant to things they thought of often. This three-factor model best explained decisions to seek or avoid information compared to a range of other alternative models tested.

Some participants repeated the experiments a couple of times, months apart. The researchers found that most people prioritise one of the three motives (feelings, usefulness, frequency of thought) over the others, and their specific tendency remained relatively stable across time and domains, suggesting that what drives each person to seek information is ‘trait-like’.

In two experiments, participants also filled out a questionnaire to gauge their general mental health. The researchers found that when people sought information about their own traits, participants who mostly wanted to know about traits they thought about often, reported better mental health.

Co-lead author, PhD student Christopher Kelly (UCL Psychology & Language Sciences and Max Planck UCL Centre for Computational Psychiatry and Ageing Research) said: “By understanding people’s motivations to seek information, policy makers may be able to increase the likelihood that people will engage with and benefit from vital information. For example, if policy makers highlight the potential usefulness of their message and the positive feelings that it may elicit, they may improve the effectiveness of their message.

“The research can also help policy makers decide whether information, for instance on food labels, needs to be disclosed, by describing how to fully assess the impact of information on welfare. At the moment policy-makers overlook the impact of information on people’s emotions or ability to understand the world around them, and focus only on whether information can guide decisions.”

The study was funded by Wellcome.

The researchers, who reported their finding Dec. 1 in Nature, were studying a set of immune cells called group 3 innate lymphoid cells (ILC3s), which help the immune system tolerate beneficial microbes and suppress inflammation in the intestines and other organs throughout the body. They discovered a unique subset of these ILC3s that circulate in the bloodstream and can infiltrate the brain — and, to their surprise, do not quench inflammation but instead ignite it.

The scientists called this subset inflammatory ILC3s, and found them in the central nervous system of mice with a condition modeling MS. Instead of constraining the immune response, this subset of ILC3s spurred another group of immune cells called T cells to attack myelinated nerve fibers, leading to MS-like disease symptoms. The researchers detected similar inflammatory ILC3s in the peripheral blood and cerebrospinal fluid of MS patients.

“This work has the potential to inform our understanding of, and potential treatments for, a broad variety of conditions involving T-cell infiltration of the brain,” said senior author Dr. Gregory Sonnenberg, associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

MS affects more than two million people worldwide. Other conditions that feature chronic brain inflammation afflict tens of millions more and include Alzheimer’s and Parkinson’s diseases. There is also evidence that neuroinflammation develops naturally with aging and is a major factor in age-related cognitive decline, and more recently inflammatory T-cell responses in the brain have been linked to neurological symptoms associated with SARS-CoV-2 infection.

The researchers have shown in recent work that ILC3s residing in the gut act as sentinels and immune regulators, suppressing inflammation — including inflammatory T-cell activity — and warding off cancer. In the new study, they examined the roles of ILC3s in the brain, and found, contrary to their expectation, that ILC3s are not normally present in the brain under healthy conditions but can infiltrate the brain from the bloodstream during inflammation. When they do infiltrate the central nervous system, they have pro-inflammatory rather than anti-inflammatory effects.

The researchers showed with a mouse model of MS that these inflammatory ILC3s in the brain function as antigen-presenting cells: They display bits of myelin protein, the main ingredient in the insulating layer around nerve fibers, to T cells — prompting them to attack myelin, causing the nerve damage that gives rise to disease signs. They found the inflammatory ILC3s in close association with T cells in regions of active inflammation and nerve damage in the mouse brains.

“The infiltration of these inflammatory ILC3s to the brains and spinal cords of mice coincides with the onset and peak of disease,” said first author John Benji Grigg, a Weill Cornell Graduate School of Medical Sciences doctoral candidate in the Sonnenberg laboratory. “Further, our experimental data in mice demonstrate these immune cells play a key role in driving the pathogenesis of neuro-inflammation.”

The researchers discovered that they could prevent MS-like disease in the animals by removing from the ILC3s a key molecule called MHCII, which normally is used in the antigen-presenting process — the removal essentially blocks the cells’ ability to activate myelin-attacking T cells.

“Despite our very best disease-modifying therapies for MS, patients continue to progress, and since disease onset is early in life, they face the prospect of permanent physical and cognitive disability,” said co-author Dr. Tim Vartanian, professor of neuroscience in the Feil Family Brain and Mind Institute at Weill Cornell Medicine, chief of the division of multiple sclerosis and neuro-immunology and a professor of neurology in the Department of Neurology at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center. “Identification of inflammatory ILC3s with antigen presentation capabilities in the central nervous system of people with MS offers a new strategic target to prevent nervous system injury.”

Finally, the researchers discovered that ILC3s that reside in other tissues in the body can be programmed, in effect, to counter the activity of brain-infiltrating T cells, preventing the MS-like condition disease in mice.

This work was completed in close collaboration with Dr. Ari Waisman, director of the Institute for Molecular Medicine at the University Medical Center of Johannes Gutenberg University Mainz, where the researchers built on prior research demonstrating that there are gut-resident ILC3s that display antigens to T cells in a slightly different way to promote T-cell inactivity, or “tolerance.” The researchers demonstrated that by experimentally exposing these tolerance-inducing intestinal ILC3s to myelin, they could block neuroinflammatory T-cell activity and the development of MS-like disease in the mice.

The work therefore points to the possibility that MS and potentially many other inflammatory conditions could someday be treated either by directly inhibiting the activity of inflammatory ILC3s that infiltrate the brain, or by targeting self-antigens to the intestinal ILC3s that promote tolerance in other tissues, Dr. Sonnenberg said.