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Eyes wide shut: How newborn mammals dream the world they’re entering
As a newborn mammal opens its eyes for the first time, it can already make visual sense of the world around it. But how does this happen before they have experienced sight?
Writing in the July 23 issue of Science, a team led by Michael Crair, the William Ziegler III Professor of Neuroscience and professor of ophthalmology and visual science, describes waves of activity that emanate from the neonatal retina in mice before their eyes ever open.
This activity disappears soon after birth and is replaced by a more mature network of neural transmissions of visual stimuli to the brain, where information is further encoded and stored.
“At eye opening, mammals are capable of pretty sophisticated behavior,” said Crair, senior author of the study, who is also vice provost for research at Yale.” But how do the circuits form that allow us to perceive motion and navigate the world? It turns out we are born capable of many of these behaviors, at least in rudimentary form.”
In the study, Crair’s team, led by Yale graduate students Xinxin Ge and Kathy Zhang, explored the origins of these waves of activity. Imaging the brains of mice soon after birth but before their eyes opened, the Yale team found that these retinal waves flow in a pattern that mimics the activity that would occur if the animal were moving forward through the environment.
“This early dream-like activity makes evolutionary sense because it allows a mouse to anticipate what it will experience after opening its eyes, and be prepared to respond immediately to environmental threats,” Crair noted.
Going further, the Yale team also investigated the cells and circuits responsible for propagating the retinal waves that mimic forward motion in neonatal mice. They found that blocking the function of starburst amacrine cells, which are cells in the retina that release neurotransmitters, prevents the waves from flowing in the direction that mimics forward motion. This in turn impairs the development of the mouse’s ability to respond to visual motion after birth.
Intriguingly, within the adult retina of the mouse these same cells play a crucial role in a more sophisticated motion detection circuit that allows them to respond to environmental cues.
Mice, of course, differ from humans in their ability to quickly navigate their environment soon after birth. However, human babies are also able to immediately detect objects and identify motion, such as a finger moving across their field of vision, suggesting that their visual system was also primed before birth.
“These brain circuits are self-organized at birth and some of the early teaching is already done,” Crair said. “It’s like dreaming about what you are going to see before you even open your eyes.”
Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.
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Global life expectancy to increase by nearly 5 years by 2050 despite geopolitical, metabolic, and environmental threats
The latest findings from the Global Burden of Disease Study (GBD) 2021, published today in The Lancet, forecast that global life expectancy will increase by 4.9 years in males and 4.2 years in females between 2022 and 2050.
This study indicates that the ongoing shift in disease burden to non-communicable diseases (NCDs) — like cardiovascular diseases, cancer, chronic obstructive pulmonary disease, and diabetes — and exposure to NCD-associated risk factors — such as obesity, high blood pressure, non-optimal diet, and smoking — will have the greatest impact on disease burden of the next generation.
As the disease burden continues to shift from CMNNs to NCDs and from years of life lost (YLLs) to years lived with disability (YLDs), more people are expected to live longer, but with more years spent in poor health. Global life expectancy is forecasted to increase from 73.6 years of age in 2022 to 78.1 years of age in 2050 (a 4.5-year increase). Global healthy life expectancy (HALE) — the average number of years a person can expect to live in good health — will increase from 64.8 years in 2022 to 67.4 years in 2050 (a 2.6-year increase).
To come to these conclusions, the study forecasts cause-specific mortality; YLLs; YLDs; disability-adjusted life years (DALYs, or lost years of healthy life due to poor health and early death); life expectancy; and HALE from 2022 through 2050 for 204 countries and territories.
“In addition to an increase in life expectancy overall, we have found that the disparity in life expectancy across geographies will lessen,” said Dr. Chris Murray, Chair of Health Metrics Sciences at the University of Washington and Director of the Institute for Health Metrics and Evaluation (IHME). “This is an indicator that while health inequalities between the highest- and lowest-income regions will remain, the gaps are shrinking, with the biggest increases anticipated in sub-Saharan Africa.”
Dr. Murray added that the biggest opportunity to speed up reductions in the global disease burden is through policy interventions aimed to prevent and mitigate behavioral and metabolic risk factors.
These findings build upon the results of the GBD 2021 risk factors study, also released today in The Lancet. This accompanying study found that the total number of years lost due to poor health and early death (measured in DALYs) attributable to metabolic risk factors has increased by 50% since 2000. Read more on the risk factors report at https://bit.ly/GBDRisks2021.
The study also puts forth various alternative scenarios to compare the potential health outcomes if different public health interventions could eliminate exposure to several key risk factor groups by 2050.
“We forecast large differences in global DALY burden between different alternative scenarios to see what is the most impactful on our overall life expectancy data and DALY forecasts,” said Dr. Stein Emil Vollset, first author of the study who leads the GBD Collaborating Unit at the Norwegian Institute of Public Health. “Globally, the forecasted effects are strongest for the ‘Improved Behavioral and Metabolic Risks’ scenario, with a 13.3% reduction in disease burden (number of DALYs) in 2050 compared with the ‘Reference’ (most likely) scenario.”
The authors also ran two more scenarios: one focused on safer environments and another on improved childhood nutrition and vaccination.
“Though the largest effects in global DALY burden were seen from the ‘Improved Behavioral and Metabolic Risk’ scenario, we also forecasted reductions in disease burden from the ‘Safer Environment’ and ‘Improved Childhood Nutrition and Vaccination’ scenarios beyond our reference forecast, said Amanda E. Smith, Assistant Director of Forecasting at IHME. “This demonstrates the need for continued progress and resources in these areas and the potential to accelerate progress through 2050.”
“There is immense opportunity ahead for us to influence the future of global health by getting ahead of these rising metabolic and dietary risk factors, particularly those related to behavioral and lifestyle factors like high blood sugar, high body mass index, and high blood pressure,” continued Dr. Murray.
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A trial HIV vaccine triggered elusive and essential antibodies in humans
An HIV vaccine candidate developed at the Duke Human Vaccine Institute triggered low levels of an elusive type of broadly neutralizing HIV antibodies among a small group of people enrolled in a 2019 clinical trial.
The vaccine candidate targets an area on the HIV-1 outer envelope called the membrane proximal external region (MPER), which remains stable even as the virus mutates. Antibodies against this stable region in the HIV outer coat can block infection by many different circulating strains of HIV.
“This work is a major step forward as it shows the feasibility of inducing antibodies with immunizations that neutralize the most difficult strains of HIV,” said senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute (DHVI). “Our next steps are to induce more potent neutralizing antibodies against other sites on HIV to prevent virus escape. We are not there yet, but the way forward is now much clearer.”
The research team analyzed data from a phase 1 clinical trial of a vaccine candidate developed by Haynes and S. Munir Alam, Ph.D., at DHVI.
Twenty healthy, HIV-negative people enrolled in the trial. Fifteen participants received two of four planned doses of the investigational vaccine, and five received three doses.
After just two immunizations, the vaccine had a 95% serum response rate and a 100% blood CD4+ T-cell response rate — two key measurements that demonstrated strong immune activation. Most of the serum responses mapped to the portion of the virus targeted by the vaccine.
Importantly, broadly neutralizing antibodies were induced after just two doses.
The trial was halted when one participant experienced a non-life-threatening allergic reaction, similar to rare incidents reported with COVID-19 vaccinations. The team investigated the cause of the event, which was likely from an additive.
“To get a broadly neutralizing antibody, a series of events needs to happen, and it typically takes several years post-infection,” said lead author Wilton Williams, Ph.D., associate professor in Duke’s Department of Surgery and member of DHVI. “The challenge has always been to recreate the necessary events in a shorter space of time using a vaccine. It was very exciting to see that, with this vaccine molecule, we could actually get neutralizing antibodies to emerge within weeks.”
Other features of the vaccine were also promising, most notably how the crucial immune cells remained in a state of development that allowed them to continue acquiring mutations, so they could evolve along with the ever-changing virus.
The researchers said there is more work to be done to create a more robust response, and to target more regions of the virus envelope. A successful HIV vaccine will likely have at least three components, all aimed at distinct regions of the virus.
“Ultimately, we will need to hit all the sites on the envelope that are vulnerable so that the virus cannot escape,” Haynes said. “But this study demonstrates that broadly neutralizing antibodies can indeed be induced in humans by vaccination. Now that we know that induction is possible, we can replicate what we have done here with immunogens that target the other vulnerable sites on the virus envelope.”
In addition to Haynes and Williams, study authors include S. Munir Alam, Gilad Ofek, Nathaniel Erdmann, David Montefiori, Michael S. Seaman, Kshitij Wagh, Bette Korber, Robert J. Edwards, Katayoun Mansouri, Amanda Eaton, Derek W. Cain, Mitchell Martin, Robert Parks, Maggie Barr, Andrew Foulger, Kara Anasti, Parth Patel, Salam Sammour, Ruth J. Parsons, Xiao Huang, Jared Lindenberger, Susan Fetics, Katarzyna Janowska, Aurelie Niyongabo, Benjamin M. Janus, Anagh Astavans, Christopher B. Fox, Ipsita Mohanty, Tyler Evangelous, Yue Chen, Madison Berry, Helene Kirshner, Elizabeth Van Itallie, Kevin Saunders, Kevin Wiehe, Kristen W. Cohen, M. Juliana McElrath, Lawrence Corey, Priyamvada Acharya, Stephen R. Walsh, and Lindsey R. Baden.
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A powerful tool speeds success in achieving highly efficient thermoelectric materials
Thermoelectric materials could play an important role in the clean energy transition, as they can produce electricity from sources of heat that would otherwise go to waste without generating additional greenhouse gases or requiring large up-front investment. But their promise has been slowed by the fact that most current thermoelectric materials don’t efficiently produce enough power to be useful for many practical applications.
Zhifeng Ren, director of the Texas Center for Superconductivity at UH (TcSUH) and corresponding author for the paper, said the materials’ performance remained stable for more than two years.
While a variety of approaches have been used to improve efficiency, a concept known as electronic band convergence has gained attention for its potential to improve thermoelectric performance. “It is normally difficult to get high performance from thermoelectric materials because not all of the electronic bands in a material contribute,” Ren said. “It’s even more difficult to make a complex material where all of the bands work at the same time in order to get the best performance.”
For this work, he said, the scientists first focused on devising a calculation to determine how to build a material in which all the different energy bands can contribute to the overall performance. They then demonstrated that the calculation worked in practice as well as in theory, building a module to further verify the obtained high performance at the device level.
Band convergence is considered a good approach for improving thermoelectric materials because it increases the thermoelectric power factor, which is related to the actual output power of the thermoelectric module. But until now, discovering new materials with strong band convergence was time-consuming and resulted in many false starts. “The standard approach is trial and error,” said Ren, who is also the Paul C.W. Chu and May P. Chern Endowed Chair in Condensed Matter Physics at UH. “Instead of doing a lot of experiments, this method allows us to eliminate unnecessary possibilities that won’t give better results.”
To efficiently predict how to create the most effective material, the researchers used a high-entropy Zintl alloy, YbxCa1-xMgyZn2-ySb2, as a case study, designing a series of compositions through which band convergence was achieved simultaneously in all of the compositions.
Ren described how it works like this: If a team of 10 people try to lift an object, the taller members will carry most of the load while the shorter members do not contribute as much. In band convergence, the goal is to make all the band team members more similar — tall band members would be shorter, in this example, and short members taller — so all can contribute to carrying the overall load.
Here, the researchers started with four parent compounds containing five elements in total — ytterbium, calcium, magnesium, zinc and antimony — running calculations to determine which combinations of the parent compounds could reach band convergence. Once that was determined, they chose the best among these high-performance compositions to construct the thermoelectric device.
“Without this method, you would have to experiment and try all possibilities,” said Xin Shi, a UH graduate student in Ren’s group and lead author on the paper. “There’s no other way you can do that. Now, we do a calculation first, we design a material, and then make it and test it.”
The calculation method could be used for other multi-compound materials, too, allowing researchers to use this approach to create new thermoelectric materials. Once the proper parent compounds are identified, the calculation determines what ratio of each should be used in the final alloy.
In addition to Ren and Shi, the paper’s authors include Dr. Shaowei Song, a researcher at the Texas Center for Superconductivity, and Dr. Guanhui Gao from the Department of Materials Science and Nanoengineering at Rice. Gao is now at UH.
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