Thursday, August 03, 2023

 

Associations of military-related traumatic brain injury with new-onset mental health conditions and suicide risk

JAMA Network Open

Peer-Reviewed Publication

JAMA NETWORK




About The Study: In this study including 860,000 soldiers, rates of new-onset mental health conditions were higher among individuals with a history of military-related traumatic brain injury (TBI) compared with those without. Moreover, risk for suicide was both directly and indirectly associated with history of TBI.  

Authors: Lisa A. Brenner, Ph.D., of the VHA Rocky Mountain Mental Illness Research Education and Clinical Center in Aurora, Colorado, is the corresponding author. 

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamanetworkopen.2023.26296)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

 http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2023.26296?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=073123

About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication. 

NEUROLINGUISTIC PROGRAMING (NLP)

Analysis of court transcripts reveals biased jury selection


Peer-Reviewed Publication

CORNELL UNIVERSITY




ITHACA, NY - Cornell researchers have shown that data science and artificial intelligence tools can successfully identify when prosecutors question potential jurors differently, in an effort to prevent women and Black people from serving on juries.

In a first-of-its-kind study, researchers used natural language processing (NLP) tools to analyze transcripts of the jury selection process. They found multiple quantifiable differences in how prosecutors questioned Black and white members of the jury pool. Once validated, this technology could provide evidence for appeals cases and be used in real time during jury selection to ensure more diverse juries.

The study, “Quantifying Disparate Questioning of Black and White Jurors in Capital Jury Selection,” published July 14 in the Journal of Empirical Legal Studies. First author is Anna Effenberger ’22, now a global markets analyst at Goldman Sachs.

Striking jurors on the basis of race or gender has been illegal since the Supreme Court’s landmark Batson vs. Kentucky case in 1986, but this type of discrimination still occurs, said study co-author John Blume, the Samuel F. Leibowitz Professor of Trial Techniques at Cornell Law School and director of the Cornell Death Penalty Project.

“One of the things the courts have looked at is whether the prosecutor questions Black and white jurors differently,” Blume said. “NLP software allows you to do that on a much more sophisticated level, looking at not just at the number, but the way in which the questions are put together.”

Under the assumption that Black and female jurors will be more sympathetic to a defendant – especially a Black one – prosecutors will sometimes press them to reveal disqualifying information. A common tactic in capital cases is to provide an especially gruesome description of the execution process and then ask if the person would be willing to sentence the defendant to death. If the answer is no, that person is struck from the jury pool.

To see if NLP software could identify this and other signs of disparate questioning, Blume collaborated with Martin Wells, the Charles A. Alexander Professor of Statistical Sciences in the Cornell Ann. S Bowers College of Computing and Information Science, and Effenberger to analyze transcripts from 17 capital cases in South Carolina. Their dataset included more than 26,000 questions that judges, defense attorneys and the prosecution asked potential jurors.

The researchers looked not only at the number of questions asked of Black, white, male and female potential jurors, but also the topics covered, each question’s complexity and the parts of speech used.

“We consistently found racial differences in a number of these measures,” Wells said. “When we do job interviews, we usually have a list of questions, and we want to ask everyone the same question, and here that’s not the case.”

The analysis showed significant differences in the length, complexity and sentiment of the questions prosecutors asked of Black potential jurors compared to white ones, indicating they were likely attempting to shape their responses. The questions asked by judges and the defense showed no such racial differences.

The study also found evidence that prosecutors had attempted to disqualify Black individuals by using their views on the death penalty. Prosecutors asked Black potential jurors – especially those who were ultimately excused from serving – more explicit and graphic questions about execution methods compared to white potential jurors.

In six of the 17 cases analyzed in the study, a judge had later ruled that the prosecutor illegally removed potential jurors on the basis of race. By looking at the combined NLP analyses for each case, the researchers could successfully distinguish between cases that violated Batson vs. Kentucky, and ones that hadn’t.

The researchers said the findings prove that NLP tools can successfully identify biased jury selection. Now, they hope to see similar studies performed on larger datasets with more diverse types of cases.

Once the validity of this method is established, “this could be done during jury selection almost in real time,” Wells said.

Whether used to monitor jury selection or to provide evidence for an appeal, this software could be a powerful tool to diversify juries – especially for defendants who are potentially facing the death penalty.

Support for this research came from the Cornell Death Penalty Project and the Theodore Eisenberg Research Fellows program.

WHITE SUPREMACIST MEDICINE

Association of racial and ethnic identity with attrition from M.D.-Ph.D. Training programs


JAMA Internal Medicine

Peer-Reviewed Publication

JAMA NETWORK



About The Study: This study found significant racial and ethnic disparities in attrition from M.D.-Ph.D. training, where Black students had greater than 50% higher odds of leaving M.D.-Ph.D. training than their peers. Notably, compared with 17% of white students, 29% of Black M.D.-Ph.D. students did not complete their training. 

Authors: Mytien Nguyen, M.S., of the Yale School of Medicine in New Haven, Connecticut, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2023.2822)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2023.2822?guestAccessKey=b66d1e14-3470-454e-91d8-53ca76b8f47c&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=073123

IRONY; THE MOST WOKE ACADEMY

Urban resilience champion to lead University of Miami’s Climate Resilience Academy


Michael Berkowitz, who built the 100 Resilient Cities initiative, and later Resilient Cities Catalyst, from ideas into global movements, will serve as the executive director of the fledgling academy.

Business Announcement

UNIVERSITY OF MIAMI

Michael Berkowitz 

IMAGE: MICHAEL BERKOWITZ HAS BEEN NAMED EXECUTIVE DIRECTOR OF THE UNIVERSITY OF MIAMI'S CLIMATE RESILIENCE ACADEMY. view more 

CREDIT: COURTESY MICHAEL BERKOWITZ




Flood waters that turned many of Mumbai’s streets into rivers during the heavy monsoon rains of 2007 taught Michael Berkowitz a lesson in resilience he would long remember. 

He was living in Mumbai, heading up corporate security and business continuity efforts for Deutsche Bank, when floods inundated India’s financial capital. 

“The water was waist deep in parts of the city, and there was a lot of finger-pointing about how the city was not prepared and how its infrastructure had failed,” Berkowitz recalled. “But what I noticed were people wading through water to get to work, people helping each other in truly remarkable ways. I was impressed with the spirit of the Mumbaikars. I didn’t know it then, but such an ethos is a hallmark of resilience thinking—it’s not just how infrastructure performs, but how society more generally responds to climate shocks.” 

Berkowitz took that lesson to heart, assimilating it with others he learned during a brilliant career in risk and resilience that has seen him spearhead initiatives at a multitude of levels. 

Now, he has embarked on a new challenge. 

Berkowitz, who founded and built the Rockefeller Foundation’s 100 Resilient Cities (100RC) from an idea into an influential global city network, working across 48 countries to help cities around the world become more resilient to physical, social, and economic shocks and stresses, has been named the founding executive director of the University of Miami’s Climate Resilience Academy

Launched on Earth Day (April 22) in 2022, the academy supports the University’s 12 schools and colleges in their efforts to conduct interdisciplinary research, train the next generation of climate scientists and practitioners, and solve the most pressing problems caused by climate change—all while partnering with industry, government, universities, and other stakeholders. 

A $5 million commitment from Eric T. Levin, a former University trustee and the former president of the University’s Citizens Board, which represents business leaders throughout South Florida, made the academy possible. 

Berkowitz, who also becomes the Eric T. Levin Endowed Chair in Climate Resilience, begins his new post on Aug. 21. 

“A thought leader in resilience” is how Guillermo “Willy” Prado, interim executive vice president for academic affairs and provost, described Berkowitz. “South Florida is often called ground zero for sea level rise. And with the extreme weather our region—indeed, our nation—is now experiencing, Michael’s appointment couldn’t be timelier,” he pointed out. 

“A key goal of our new academy is to foster partnership outside the University, to get business, government, nonprofits, and other academic institutions involved in this endeavor,” Prado continued. “Michael is the linchpin in our plans to make that happen. His global network, partnerships with private and public sectors, and experience developing and executing a vision for resilient communities will benefit South Florida, the nation, and beyond.” 

Champion of urban resilience 

In 2019, with the senior management team of 100RC, Berkowitz helped create Resilient Cities Catalyst (RCC), a global nonprofit that helps cities and their partners change the way they plan and act in the face of climate change. RCC’s on-the-ground efforts range from helping communities in California unlock millions of dollars of climate funding to partnering with Australia’s Minderoo Foundation to design a vision for more resilience in the aftermath of wildfires and floods. Led by RCC’s co-founders, that work will continue. 

Fittingly, 100RC supported Greater Miami to unify its resilience work through the creation of Resilient 305, a plan to help local municipalities better prepare for and respond to hurricanes, sunny day flooding, and sea level rise as well as social and economic inequities. “When you think about the worldwide effort to build resilience, there are fewer places where that is more evident and more critical than in South Florida,” Berkowitz said. “It’s not just South Florida’s exposure to climate risks, but it’s the region as a central point of immigration and migration across Latin and North America. It’s this incredible opportunity with a booming economy and a burgeoning tech sector,” he added. “Gentrification, displacement, and vulnerability have occurred in the face of all of that. These are issues that speak to the resilience of a city, of a region, and of a community. And being able to tap into what is a world-class research and teaching institution that is clearly committed to addressing these issues made the University of Miami an attractive place to continue my work in resilience.” 

His appointment comes at a time when climatologists and others the world over are warning that the planet is reaching a tipping point in the climate crisis. Earth’s average surface temperature for 2022 tied with 2015 as the fifth warmest on record, and the past nine years have been the warmest since 1880, when modern recordkeeping began, according to a NASA analysis. 

The warming climate is leaving its calling card in the form of stronger hurricanes, more intense droughts, more severe wildfires, and ever-rising sea levels. And with the El Niño climate phenomenon, which has a heating effect, in full force this year, 2023 could become the hottest year on record by the time it ends, a group of Berkeley Earth scientists have warned.

The Climate Resilience Academy, Berkowitz said, is the University’s “moon shot” against climate change, with more than 85 institution-wide research projects already underway to address the climate crisis and related resilience issues—from protecting and restoring coral reefs to mitigating the warming climate’s impact on vulnerable populations. 

“It’s the academy’s role to connect the amazing work being done by our researchers more effectively to practitioners so that they can, in turn, use and ultimately scale the innovations that are coming out of the University,” Berkowitz said. “And it is our goal to connect those practitioners back into the University so that we can understand the demand signal and what new innovations are needed to tackle problems. If we can create that virtuous cycle of demand informing research and research having an impact in communities, that will be a mark of success for this new academy.” 

Pivotal role of students 

Students, both at the undergraduate and graduate level, will be an integral part of that cycle, Berkowitz noted. 

“Urban resilience as a profession is relatively new,” he explained. “A multitude of people from different disciplines and who are trained in different ways are currently the practitioners of resilience. But we’re hoping that the practitioners of tomorrow—the students—bring a new level of sophistication to it. That they approach it in more interdisciplinary and inclusive ways, thinking not just about the past science but also new possibilities for the future. All of these are hallmarks of resilience thinking. We need to train the future generations of practitioners and leaders, and using Miami and South Florida as a living laboratory to do that is the perfect strategy.” 

Berkowitz’s accomplishments while serving as president of 100 Resilient Cities from 2013 to 2019 run the gamut. The 4,000 actions the organization helped spearhead in its partnership with cities resulted in more than 150 collaborations between the private and public sectors, including $230 million of pledged support from platform partners and more than $25 billion leveraged from national, philanthropic, and private sources to implement resilience projects. RCC has built on that legacy, working closely with communities, project owners, and regional stakeholders across the United States and around the world. 

Under his leadership, 100RC co-led City Xchange, an effort to connect tech and innovation with cities to solve resilience challenges. And with UN Habitat, the organization led the creation of the Medellin Collaboration on Urban Resilience to align international urban resilience efforts. 

100RC, Berkowitz noted, spearheaded the creation of the chief resilience officer, using as a guide a white paper from the Zürich, Switzerland-based, reinsurance company Swiss Re that suggested countries hire chief risk officers. “We amended it to think more about building capacities rather than just understanding the risks that were on the books—that is, we took it a step further, advancing the idea of the interdisciplinary nature of building capacities that could help a city survive and thrive in the face of disaster. And that was the original job description of the chief resilience officer.” 

Those positions were originally grant funded by 100RC. Now, as the climate crisis worsens, municipal and county governments across the United States are hiring full-time chief resilience officers to address the impacts of climate change. 

But among all of 100RC’s accomplishments, “I’m most proud of the community we built,” said Berkowitz, noting that some who have served as chief resilience officers for major cities have moved on to key positions at federal agencies such as FEMA and the National Oceanic and Atmospheric Administration. 

“Of course, Jim Murley, [chief resiliency officer for Miami-Dade County], and Jane Gilbert, [chief heat officer for Miami-Dade], are still doing really important work in Miami through Resilient 305,” said Berkowitz, referring to a plan to help local municipalities better prepare for and respond to hurricanes, sunny day flooding, and sea level rise as well as social and economic inequities. 

“It’s not only the community of chief resilience officers we built but also folks in business, in nonprofits, in civil society, and at universities across sectors and silos,” he explained. “There’s this real legacy of a community that is thinking about our risks and opportunities in new and important ways. And part of that is this understanding that resilience is not just about how our infrastructure withstands the initial disaster. If a hurricane hits Miami, it’s important that the infrastructure withstand that, that buildings not collapse, that roads not wash away,” he added. 

“But the resilience of South Florida is so much more than that. It’s all these other aspects of how neighbors check on neighbors, how different economic sectors can rebound more quickly and carry the region while recovery happens across the economy. It’s how well the poorest and most vulnerable of our fellow community members can get back on their feet,” he continued. “All these things are the hallmarks of a more resilient community. That wasn’t always understood. It’s much better understood in 2023 than it was in 2013, when we started 100 Resilient Cities. So, that’s the legacy I’m most proud of.” 

Storied career 

Berkowitz’s career in the field of resiliency is an unlikely one. Following undergraduate study in political science at the University of Delaware, he traveled to Washington, D.C., in hopes of landing a job in politics. “I had no connections in the field of politics, so I just applied for internships wherever I could get them,” he recalled. 

He got a job as a reporter for a major newsletter that covered emergency preparedness, reporting and writing stories on emergency management-related topics that affected local and national businesses. 

New York City Emergency Management recruited him. And during a seven-year stint that began in 1998 with that office, he worked in various roles. He wrote contingency plans for biological terrorism, extreme heat, and coastal storms. He oversaw the city’s emergency mapping and data center during the response to the 9/11 terrorist attacks, and he responded to other incidents such as the Northeast blackout of 2003 and the West Nile virus outbreak in the New York City area in 1999. 

From there, it was on to Deutsche Bank, where for eight years he worked in several key positions for the multinational investment bank and financial services company. 

Then came his storied stints as president of 100RC and founding principal of RCC. 

Now, the University of Miami gets the founding executive director for its fledgling Climate Resilience Academy. 

“Michael brings experience outside of academia,” Levin said. “He’s done great work with 100 Resilient Cities, and he’s had to work with a variety of leaders under different circumstances. He’s built up a lot of resilience himself. So, the experience he brings in building an organization from just the concept to a full-fledged, very effective, very influential organization is valuable for us.”

Levin praised Rodolphe el-Khoury, dean of the School of Architecture, and Sharan Majumdar, a professor of atmospheric sciences at the Rosenstiel School of Marine, Atmospheric, and Earth Science, for serving as the academy’s interim directors and for leading the planning process and defining the mission that established the foundations of the academy. 

“They did a masterful job and all of the heavy lifting as far as corralling the faculty and administrators and fleshing out the academy’s ideas, making it possible for us to attract someone of Michael’s stature,” Levin said. 

“It has been an honor to co-lead the development of the academy during its fledgling stages,” Majumdar said. “The most fulfilling part has been the integration of ideas generated by students, staff, and faculty, which were supported by our leadership and Eric.” 

Berkowitz, added Majumdar, “is poised to nurture the collective enthusiasm and the diverse array of talent across our schools and colleges in collaboration with external partners and stakeholders. As a long-standing leader and founder of organizations in the climate resilience arena, Michael brings a wealth of experience to lead the academy’s vision and its execution. His breadth and depth of connections across multiple sectors will help bolster the University’s reputation through meaningful partnerships, while making a direct contribution to the well-being of society.” 

“One of the most exciting aspects of building the Climate Resilience Academy was framing and channeling the University’s enormous capacity in the climate change space. We designed the academy as an instrument for aligning the wealth of talent and resources in tackling big challenges. With years spent in the field, leading a trailblazing resilience program, Michael is perfectly poised for putting this prodigious instrument to good use,” said el-Khoury.

Diving deep: Unveiling the secrets of microalgae to cope with environmental challenges.

A groundbreaking study led by Giulia Ghedini, principal investigator at Gulbenkian, has shed new light on the intricate relationship between competition, evolution, and ecological communities.


Peer-Reviewed Publication

INSTITUTO GULBENKIAN DE CIENCIA

Dunaliella tertiolecta 

IMAGE: DUNALIELLA TERTIOLECTA © MORITZ KLAASSEN, IGC 2023 view more 

CREDIT: © MORITZ KLAASSEN, IGC 2023




Environmental change, such as ocean warming, alters resource competition and biodiversity. Thus, it is essential to understand how organisms respond to increased competition because changes in their size and metabolism affect the productivity of ecosystems.

Competition has long been recognized as a driving force behind rapid evolution. Still, until now, a mechanistic framework for identifying the specific traits that evolve and their trajectories has yet to be developed. Researchers at Gulbenkian and Monash University turned to metabolic theory, which explicitly predicts how competition shapes the evolution of metabolism and size. However, these predictions were not extensively tested, especially in communities where organisms must compete with multiple species. What is the best strategy to deal with interspecific competition?

With that unanswered question in mind, the researchers based their study on the experimental evolution of marine phytoplankton, which are unicellular microalgae that produce 50% of Earth’s oxygen. They used a green microalgae species called Dunaliella tertiolecta, which they evolved for ten weeks (~70 generations) in one of three environments: alone, competing with a population of this same species, or with a community of three other phytoplankton species. 

Interestingly, researchers observed that the organisms evolved to be smaller and more energy efficient under competition. The unexpected findings arose from the rapid evolution of metabolic plasticity. Researchers discovered that the organisms that evolved with competitors showed greater metabolic plasticity, so they use resources faster when abundant but reduce their metabolism to be more energy efficient when resources are scarce. These changes mean they can sustain larger population sizes than organisms that evolved alone without compromising their population growth rate – they got the best of both worlds.

To Giulia Ghedini, the study's first author, “This result made sense, but it was initially difficult to explain because the current (metabolic) theory does not predict improvements in both traits. Through several reiterations, we were able to piece it all together.” Researchers were able to predict the evolution of body size and population trajectories based on the metabolic theory “for the most part and also show that the evolution of metabolic plasticity can lead to some unexpected results,” added Giulia, joyful for such a discovery, that sheds some light on how organisms might respond to changing resource regimes driven by global change.

In the future, the research team wants to extend this work to determine if other competitors follow similar (or different) evolutionary trajectories and the overall consequences of such evolutionary responses for the community. Understanding how metabolic plasticity evolves is essential to forecast changes in the diversity and productivity of ecosystems.

The study was developed in collaboration with Prof. Dustin Marshall, Monash University, and funded by the Australian Research Council and la Caixa Foundation.

 QUANTUM BIOLOGY

Nuclear spin's impact on biological processes uncovered


Peer-Reviewed Publication

THE HEBREW UNIVERSITY OF JERUSALEM

Rapid Passage of Magnetic Water Molecules into Cells 

IMAGE: RAPID PASSAGE OF MAGNETIC WATER MOLECULES INTO CELLS view more 

CREDIT: PNAS




A research team led by Prof. Yossi Paltiel at the Hebrew University of Jerusalem with groups from HUJI, Weizmann and IST Austria new study reveals the influence of nuclear spin on biological processes. This discovery challenges long-held assumptions and opens up exciting possibilities for advancements in biotechnology and quantum biology.

Scientists have long believed that nuclear spin had no impact on biological processes. However, recent research has shown that certain isotopes behave differently due to their nuclear spin. The team focused on stable oxygen isotopes (16O, 17O, 18O) and found that nuclear spin significantly affects oxygen dynamics in chiral environments, particularly in its transport.

The findings, published in the prestigious Proceedings of the National Academy of Sciences (PNAS), have potential implications for controlled isotope separation and could revolutionize nuclear magnetic resonance (NMR) technology.

Prof. Yossi Paltiel, the lead researcher, expressed excitement about the significance of these findings. He stated, "Our research demonstrates that nuclear spin plays a crucial role in biological processes, suggesting that its manipulation could lead to groundbreaking applications in biotechnology and quantum biology. This could potentially revolutionize isotopic fractionation processes and unlock new possibilities in fields such as NMR."

The story in detail

Researchers have been studying the “strange” behavior of tiny particles in living things, funding some places where quantum effects change biological processes. For example studying bird navigation quantum effects may help some birds find their way in long journeys. In plants efficiently using sunlight for energy is affected by quantum effects.

This connection between the tiny world of particles and living beings likely goes back billions of years when life began and molecules with a special shape called chirality appeared. Chirality is important because only molecules with the right shape can do the jobs they need to in living things.

The link between chirality quantum mechanics was found in "spin," which is like a tiny magnetic property. Chiral molecules can interact differently with particles based on their spin, creating something called Chiral Induced Spin Selectivity (CISS).

Scientists have found that spin affects tiny particles, like electrons, in living processes involving chiral molecules. They wanted to see if spin also affects larger particles, like ions and molecules which supply the base for biological transport.  So, they did experiments with water particles that have different spins. The results showed that spin influences how water behaves in cells, entering at different speeds and reacting in a unique way when chiral molecules are involved.

This study highlights the importance of spin in the processes of life. Understanding and controlling spin could have a big impact on how living things work. It might also help improve medical imaging and create new ways to treat illnesses.

The research was a collaborative effort among scientists from various institutions, including the Institute of Earth Sciences and Life Sciences in Hebrew and the Weizmann Institute, with the study led by the Department of Applied Physics at Hebrew University.

Funding: NMS acknowledges the support of the Ministry of Energy, Israel, as part of the scholarship program for graduate students in the fields of energy. ML acknowledges support by the European Research Council (ERC) Starting Grant No. 801770 (ANGULON).

The team includes: Yossi Paltiel, Ofek Vardi, Yuval Kolodny, Stav Ferrera, Naama Maroudas-Sklare, Nir Yuran, Shira Yochelis. Department of Applied Physics, Hebrew University of Jerusalem; Nir Keren, Silberman Institute of Life Sciences, Hebrew University of Jerusalem; Artem Volosniev, Areg Ghazarya, Mikhail Lemeshko, IST Austria (Institute of Science and Technology Austria; Amijai Saragovi, The Hebrew University Medical School; Nir Galili, Itay Halevye ,Weizmann Institute of Science; Hagit P. Affek, Boaz Luz, Yonaton Goldsmith, Institute of Earth Sciences, Hebrew University of Jerusalem

The Hebrew University of Jerusalem is Israel's premier academic and research institution. With over 25,000 students from 90 countries, it is a hub for advancing scientific knowledge and holds a significant role in Israel's civilian scientific research output, accounting for nearly 40% of it and has received over 11,000 patents. The university's faculty and alumni have earned eight Nobel Prizes and a Fields Medal, underscoring their contributions to ground-breaking discoveries. In the global arena, the Hebrew University ranks 77th according to the Shanghai Ranking, making it the top-ranked Israeli institution. To learn more about the university's academic programs, research initiatives, and achievements, visit the official website at http://new.huji.ac.il/en

Disclaimer: AA

 

Modifications to amino acids in sperm could be behind infertility


Researchers dive into the molecular-level details of sperm formation


Peer-Reviewed Publication

MICHIGAN MEDICINE - UNIVERSITY OF MICHIGAN




Sperm play a critical role in the creation of new life, delivering essentially half of the genetic material required.

The success of this process relies on the generation of a developmentally competent sperm cell, which is often determined by shape. Indeed, during in vitro fertilization, the “best-looking” sperm is selected to fertilize an egg.

However, how this optimal shape translates to proper sperm function is difficult to assess because of many confounding factors.

Researchers at the University of Michigan are now delving into the molecular-level details of sperm formation, with a particular focus on how abnormalities in this process might lead to male-factor infertility.

Unlike other cells in the body, sperm possess a unique characteristic—their genetic material is packed with proteins called protamines.

Protamines have been found in various living organisms such as plants, fish, and mammals, spanning hundreds of millions of years of evolution.

The significance of this protamine-based packaging system of sperm cells raises an intriguing question: why do sperm use protamines to package DNA instead of histones, which are employed by all other cell types?

To uncover the significance of protamines in reproduction, Saher Sue Hammoud, Ph.D., Sy Redding, Ph.D., Lindsay Moritz, Ph.D., Samantha Schon, M.D., and their team conducted an in-depth study of the molecular sequence composition of protamines to understand how variations in the protein effect function.

“We started looking at protamines because they are in many animal species and are also rapidly evolving, so there’s a lot of sequence variation,” said Hammoud, an associate professor of human genetics, obstetrics and gynecology and urology.

Most mammals have multiple types of protamines and these need to be maintained in well-defined ratio, and deviations in this ratio have been associated with infertility.

Conventional wisdom has it that protamines are particularly efficient at tightly packaging DNA into dense structures called chromatin because they are rich in arginine, a positively charged amino acid that strongly binds to the negatively charged DNA.

However, recent studies have shown that protamines also have non-arginine amino acids that are species specific and have unexpected post-translational modifications, that chemically change proteins after they are made.

This study, published in the journal Nature Structural & Molecular Biology, explores previously unrecognized features of protamines.

“The molecules that interact and package DNA are known to have positively charged features. What’s really beautiful about this work is it reveals other logic embedded in these proteins that we never really considered, other amino acids that are doing very important jobs as well,” said Redding, assistant professor of biochemistry and molecular biotechnology at the University of Massachusetts Chan Medical School.

Furthermore, what was intriguing was the presence of post-translational modifications on protamines, despite the fact that sperm are not transcriptionally active. 

“The fact that protamines have all of these different modifications on them suggests that these modifications must have some function in chromatin packaging,” said Moritz, a postdoctoral fellow in the Hammoud Lab and co-first author on the paper.

Using mice, they analyzed a modified lysine residue specific to a mouse protamine and present in mature mouse sperm. Substituting lysine with an alanine amino acid (which cannot be modified) resulted in abnormally shaped sperm, impaired embryonic development, and reduced fertility.

What’s more surprising was replacing the lysine with a positively charged arginine did not correct the defective sperm packaging, meaning the interactions go beyond the charge of the molecule.

Male-factor infertility often lacks a clear cause, which highlights the importance of studying these modifications.

Noted Schon, assistant professor in the U-M Department of Obstetrics and Gynecology and co-first author on the paper, "I think these modifications are interesting as another avenue of research and identifying the cause of infertility, and the fact that it might play a role in the early embryo has huge significance as a potential diagnostic tool and post-fertilization for IVF."

The team hopes to next examine the mechanisms of sperm cell packaging in greater detail in the hopes of recreating the process completely in vitro.

Additional authors: Mashiat Rabbani, Yi Sheng, Ritvija Agrawal, Juniper Glass-Klaiber, Caleb Sultan, Jeannie M Camarillo, Jourdan Clements, Michael R Baldwin, Adam G Diehl, Alan P Boyle, Patrick J O'Brien, Kaushik Ragunathan, Yueh-Chiang Hu, Neil L Kelleher, Jayakrishnan Nandakumar, Jun Z Li, Kyle E Orwig

Paper cited: “Sperm chromatin structure and reproductive fitness are altered by substitution of a single amino acid in mouse protamine 1”, Nature Structural & Molecular BiologyDOI: 10.1038/s41594-023-01033-4

 

New UArizona study links brain waves directly to memory


The findings could lay foundations for cognitive impairment therapy and help improve memory.


Peer-Reviewed Publication

UNIVERSITY OF ARIZONA




Neurons produce rhythmic patterns of electrical activity in the brain. One of the unsettled questions in the field of neuroscience is what primarily drives these rhythmic signals, called oscillations. University of Arizona researchers have found that simply remembering events can trigger them, even more so than when people are experiencing the actual event.

The researchers, whose findings are published in the journal Neuron, specifically focused on what are known as theta oscillations, which emerge in the brain's hippocampus region during activities like exploration, navigation and sleep. The hippocampus plays a crucial role in the brain's ability to remember the past.

Prior to this study, it was believed that the external environment played a more important role in driving theta oscillations, said Arne Ekstrom, professor of cognition and neural systems in the UArizona Department of Psychology and senior author of the study. But Ekstrom and his collaborators found that memory generated in the brain is the main driver of theta activity.

"Surprisingly, we found that theta oscillations in humans are more prevalent when someone is just remembering things, compared to experiencing events directly," said lead study author Sarah Seger, a graduate student in the Department of Neuroscience.

The results of the study could have implications for treating patients with brain damage and cognitive impairments, including patients who have experienced seizures, stroke and Parkinson's disease, Ekstrom said. Memory could be used to create stimulations from within the brain and drive theta oscillations, which could potentially lead to improvements in memory over time, he said.

UArizona researchers collaborated on the study with researchers from the University of Texas Southwestern Medical Center in Dallas, including neurosurgeon Dr. Brad Lega and research technician Jennifer Kriegel. The researchers recruited 13 patients who were being monitored at the center in preparation for epilepsy surgery. As part of the monitoring, electrodes were implanted in the patients' brains for detecting occasional seizures. The researchers recorded the theta oscillations in the hippocampus of the brain.

The patients participated in a virtual reality experiment, in which they were given a joystick to navigate to shops in a virtual city on a computer. When they arrived at the correct destination, the virtual reality experiment was paused. The researchers asked the participants to imagine the location at which they started their navigation and instructed them to mentally navigate the route they just passed through. The researchers then compared theta oscillations during initial navigation to participants' subsequent recollection of the route.

During the actual navigation process using the joystick, the oscillations were less frequent and shorter in duration compared to oscillations that occurred when participants were just imagining the route. So, the researchers conclude that memory is a strong driver of theta oscillations in humans.

One way to compensate for impaired cognitive function is by using cognitive training and rehabilitation, Ekstrom said.

"Basically, you take a patient who has memory impairments, and you try to teach them to be better at memory," he said.

In the future, Ekstrom is planning to conduct this research in freely walking patients as opposed to patients in beds and find how freely navigating compares to memory with regard to brain oscillations.

"Being able to directly compare the oscillations that were present during the original experience, and during a later retrieval of that is a huge step forward in the field in terms of designing new experiments and understanding the neural basis of memory," Seger said.