The new study, which the researchers noted is the first to demonstrate the beneficial effect of this type of meal timing intervention in humans, appears online in the journal Science Advances. It was funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.

“This is a rigorous and highly controlled laboratory study that demonstrates a potential intervention for the adverse metabolic effects associated with shift work, which is a known public health concern,” said Marishka Brown, Ph.D., director of the NHLBI’s National Center on Sleep Disorders Research. “We look forward to additional studies that confirm the results and begin to untangle the biological underpinnings of these findings.”

For the study, the researchers enrolled 19 healthy young participants (seven women and 12 men). After a preconditioning routine, the participants were randomly assigned to a 14-day controlled laboratory protocol involving simulated night work conditions with one of two meal schedules. One group ate during the nighttime to mimic a meal schedule typical among night workers, and one group ate during the daytime.

The researchers then evaluated the effects of these meal schedules on their internal circadian rhythms. That’s the internal process that regulates not just the sleep-wake cycle, but also the 24-hour cycle of virtually all aspects of your bodily functions, including metabolism.

The researchers found that nighttime eating boosted glucose levels — a risk factor for diabetes — while restricting meals to the daytime prevented this effect. Specifically, average glucose levels for those who ate at night increased by 6.4% during the simulated night work, while those who ate during the daytime showed no significant increases.

“This is the first study in humans to demonstrate the use of meal timing as a countermeasure against the combined negative effects of impaired glucose tolerance and disrupted alignment of circadian rhythms resulting from simulated night work,” said study leader Frank A.J.L. Scheer, Ph.D., professor of medicine at Harvard Medical School and director of the Medical Chronobiology Program at Brigham & Women’s Hospital in Boston.

The researchers said that the mechanisms behind the observed effects are complex. They believe that the nighttime eating effects on glucose levels during simulated night work are caused by circadian misalignment. That corresponds to the mistiming between the central circadian “clock” (located in the brain’s hypothalamus) and behavioral sleep/wake, light/dark, and fasting/eating cycles, which can influence peripheral “clocks” throughout the body. The current study shows that, in particular, mistiming of the central circadian clock with the fasting/eating cycles plays a key role in boosting glucose levels. The work further suggests the beneficial effects of daytime eating on glucose levels during simulated night work may be driven by better alignment between these central and peripheral “clocks.”

“This study reinforces the notion that when you eat matters for determining health outcomes such as blood sugar levels, which are relevant for night workers as they typically eat at night while on shift,” said the study co-leader Sarah L. Chellappa, M.D., Ph.D., a researcher in the nuclear medicine department at the University of Cologne, Germany. Chellappa formerly worked with Scheer in Brigham & Women’s Medical Chronobiology Program.

To translate these findings into practical and effective meal timing interventions, the researchers said more study is needed, including with real-life shift workers in their typical work environment.

Researchers from MIT, the La Jolla Institute for Immunology, and other institutions have now designed a new nanoparticle adjuvant that may be more potent than others now in use. Studies in mice showed that it significantly improved antibody production following vaccination against HIV, diphtheria, and influenza.

“We started looking at this particular formulation and found that it was incredibly potent, better than almost anything else we had tried,” says Darrell Irvine, the Underwood-Prescott Professor with appointments in MIT’s departments of Biological Engineering and Materials Science and Engineering; an associate director of MIT’s Koch Institute for Integrative Cancer Research; and a member of the Ragon Institute of MGH, MIT, and Harvard.

The researchers now hope to incorporate the adjuvant into an HIV vaccine that is currently being tested in clinical trials, in hopes of improving its performance.

Irvine and Shane Crotty, a professor at the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology, are the senior authors of the study, which appears today in Science Immunology. The lead authors of the paper are Murillo Silva, a former MIT postdoc, and Yu Kato, a staff scientist at the La Jolla Institute.

More powerful vaccines

Although the idea of using adjuvants to boost vaccine effectiveness has been around for decades, there are only a handful of FDA-approved vaccine adjuvants. One is aluminum hydroxide, an aluminum salt that induces inflammation, and another is an oil and water emulsion that is used in flu vaccines. A few years ago, the FDA approved an adjuvant based on saponin, a compound derived from the bark of the Chilean soapbark tree.

Saponin formulated in liposomes is now used as an adjuvant in the shingles vaccine, and saponins are also being used in a cage-like nanoparticle called an immunostimulatory complex (ISCOM) in a Covid-19 vaccine that is currently in clinical trials.

Researchers have shown that saponins promote inflammatory immune responses and stimulate antibody production, but how they do that is unclear. In the new study, the MIT and La Jolla team wanted to figure out how the adjuvant exerts its effects, and to see if they could make it more potent.

They designed a new type of adjuvant that is similar to the ISCOM adjuvant but also incorporates a molecule called MPLA, which is a toll-like receptor agonist. When these molecules bind to toll-like receptors on immune cells, they promote inflammation. The researchers call their new adjuvant SMNP (saponin/MPLA nanoparticles).

“We expected that this could be interesting because saponin and toll-like receptor agonists are both adjuvants that have been studied separately and shown to be very effective,” Irvine says.

The researchers tested the adjuvant by injecting it into mice along with a few different antigens, or fragments of viral proteins. These included two HIV antigens, as well as diphtheria and influenza antigens. They compared the adjuvant to several other approved adjuvants and found that the new saponin-based nanoparticle elicited a stronger antibody response than any of the others.

One of the HIV antigens that they used is an HIV envelope protein nanoparticle, which presents many copies of the gp120 antigen that is present on the HIV viral surface. This antigen recently completed initial testing in phase 1 clinical trials. Irvine and Crotty are part of the Consortium for HIV/AIDS Vaccine Development at the Scripps Research Institute, which ran that trial. The researchers now hope to develop a way to manufacture the new adjuvant at large scale so it can be tested along with an HIV envelope trimer in another clinical trial beginning next year. Clinical trials that combine envelope trimers with the traditional vaccine adjuvant aluminum hydroxide are also underway.

“Aluminum hydroxide is safe but not particularly potent, so we hope that (the new adjuvant) would be an interesting alternative to elicit neutralizing antibody responses in people,” Irvine says.

Rapid flow

When vaccines are injected into the arm, they travel through lymph vessels to the lymph nodes, where they encounter and activate B cells. The research team found that the new adjuvant speeds up the flow of lymph to the nodes, helping the antigen to get there before it starts to break down. It does this in part by stimulating immune cells called mast cells, which previously were not known to be involved in vaccine responses.

“Getting to the lymph nodes quickly is useful because once you inject the antigen, it starts slowly breaking down. The sooner a B cell can see that antigen, the more likely it’s fully intact, so that B cells are targeting the structure as it will be present on the native virus,” Irvine says.

Additionally, once the vaccine reaches the lymph nodes, the adjuvant causes a layer of cells called macrophages, which act as a barrier, to die off quickly, making it easier for the antigen to get into the nodes.

Another way that the adjuvant helps boost immune responses is by activating inflammatory cytokines that drive a stronger response. The TLR agonist that the researchers included in the adjuvant is believed to amplify that cytokine response, but the exact mechanism for that is not known yet.

This kind of adjuvant could also be useful for any other kind of subunit vaccine, which consists of fragments of viral proteins or other molecules. In addition to their work on HIV vaccines, the researchers are also working on a potential Covid-19 vaccine, along with J. Christopher Love’s lab at the Koch Institute. The new adjuvant also appears to help stimulate T cell activity, which could make it useful as a component of cancer vaccines, which aim to stimulate the body’s own T cells to attack tumors.

The research was funded by the National Institute of Allergy and Infectious Diseases, the Koch Institute’s Marble Center for Cancer Nanomedicine, the U.S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT, the Koch Institute Support (core) Grant from the National Cancer Institute, the International AIDS Vaccine Initiative, and the Ragon Institute.

Moreover, Wraparound may hold the potential for reducing disparities in outcomes for youth of color, which has long been found in mental health services.

A team of researchers, led by Jonathan Olson, PhD, at the University of Washington Department of Psychiatry and Behavioral Sciences, Seattle, WA, USA, conducted a meta-analysis of 17 controlled studies, and their results, published between 1996 and 2019 in order to compare the effects of Wraparound to regular services in youth with SED (serious emotional disorders).

“For many years, public systems have used Wraparound because it makes sense and provides families with the kind of compassionate approach, something that all families say they want and need,” said Dr. Eric Bruns, Professor of Psychiatry and senior author on the research team. “Now we have clear results that support what many have seen in their own local systems of care: that Wraparound is more effective and cost-effective than traditional services.”

Significant effects in favor of Wraparound across a range of important youth outcomes were found — including reduced out-of-home placements and improved mental health functioning and school outcomes. The study also found significantly lower overall care costs for youth in Wraparound care, due to less spending on costly out-of-home placements. Across the 17 studies, Wraparound effects were more positive for samples with higher proportions of youth of color.

“Wraparound lives up to principles we want to uphold — for example, being youth- and family-driven, strengths-based and using a team of people with a blank checkbook to ‘do whatever it takes’ to meet the needs of the youth and family,” added Dr. Bruns. “While many states have taken Wraparound to scale, others have been more hesitant, saying it wasn’t ‘evidence-based.’ This study should help address those concerns.”

Wraparound was established in the 1980s as an alternative to service delivery strategies that kept youth and family services in fragmented siloes, driven by professionals and often relying on costly institution-based care rather than investing in community supports. Instead, Wraparound invests in a care coordinator with a low caseload who convenes a team that includes the family, friends and members of the wider community, as well as service and support providers.

Dr. Olson also points out, however, that the study additionally reinforced how important it is to implement high-quality Wraparound services that are true to the model: “Unfortunately, many studies were conducted before there were measures of fidelity, or measures of ‘doing Wraparound right,'” he said. “However, for studies that did measure fidelity, we saw more positive outcomes for youth and families who received care that was of high-quality and closely adhered to Wraparound principles.”

The potential for Wraparound to better meet the needs of youth of color was an unexpected finding, concluded Dr. Bruns, but perhaps not surprising: “We need to remember that in all these studies, Wraparound was compared to more traditional services delivered in mental health, child welfare and juvenile justice.

“There is a long history of research showing disparities in access and outcomes for youth of color and their families. It may be that by allowing for more youth and family voice and choice, and teams that include family, friends, and community members, Wraparound helps reduce those disparities. However, such questions were not the explicit focus of these studies. We need to investigate the issue of what may address disparities with greater rigor.”

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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.