Tuesday, July 18, 2023

MUTUAL AID

Bioluminescent bacteria coordinate signaling to colonize squid’s light organ


Peer-Reviewed Publication

PENN STATE

Hawaiian bobtail squid 

IMAGE: NEW STUDY SHEDS LIGHT ON HOW BIOLUMINESCENT BACTERIA COORDINATE CELLULAR SIGNALING TO COLONIZE THE LIGHT ORGAN OF THE HAWAIIAN BOBTAIL SQUID IN A MUTUALLY BENEFICIAL RELATIONSHIP. view more 

CREDIT: MICHELLE BIXBY / PENN STATE




Bioluminescent bacteria and the Hawaiian bobtail squid have formed a longstanding mutually beneficial relationship. How the bacteria coordinate their behavior to colonize the squid—through cellular signaling and cues from the environment—is detailed in new study led by Penn State researchers.

A paper describing the study is available online in the journal eLife. The researchers also show that the mechanism that they describe is likely to be widespread in a broad array of bacteria and that understanding this coordination of cellular signaling will be important for understanding how bacteria colonize their hosts more generally.

“The bacteria we study, known as Vibrio fischeri, is associated with many different marine hosts, but its association with the Hawaiian bobtail squid is the best characterized,” said Tim Miyashiro, associate professor of biochemistry and molecular biology in the Penn State Eberly College of Science and the leader of the research team.

The squid have a specialized light organ tucked within the underside of their mantle that is occupied by the bacteria. The bacteria’s glow is believed to help camouflage the squid when viewed by potential predators from below. The bacteria, in turn, get nutrients from the squid to support their growth. The squid, however, are not born with the bacteria in their light organs. Bacteria from the environment must make their way into the light organ after the squid hatch.

“Aspects of bacterial behavior in the light organ have been characterized,” said Miyashiro, “but the cellular mechanisms that allow the bacteria to colonize the squid in the first place are still poorly understood, so we set out to investigate how the bacteria initiates colonization.”

Inside the light organ, bacterial behavior is coordinated through “quorum sensing.” The bacteria release signaling molecules that increase in concentration as the bacterial population grows and becomes denser. When enough bacteria are present—when a quorum is reached—a signaling pathway is activated such that the bacteria will begin to produce bioluminescence and their ability to move is suppressed. Prior to colonizing the light organ, the bacteria form large aggregates of cells as well, but if the quorum sensing pathway were activated they might not be motile enough to move into the light organ.

“So, the question is ‘how do the bacteria avoid the quorum sensing pathway when they form these large aggregates outside of the squid and instead initiate behavior that promotes colonization?’” said Miyashiro. “What we saw was that the aggregation pathway activates the production of a small RNA molecule that is normally repressed by quorum sensing. Therefore, when the signaling pathway that leads to aggregation is activated outside the squid, the RNA molecule is expressed, which enables the cells to bypass quorum sensing to remain motile and dark.”

The small RNA--called Qrr1—is part of the quorum sensing pathway that represses the ability of the bacteria to produce bioluminescence and promotes motility until a quorum is reached. When a quorum is reached, expression of Qrr1 is subsequently shut down.

“Qrr1 has also been shown to be important for promoting colonization,” said Miyashiro. “You might expect that Qrr1 would be repressed during aggregation like it is during quorum sensing, but that is not what happens. So, we performed a number of experiments aimed at characterizing the molecular control of Qrr1 expression during aggregation.”

The researchers showed that Qrr1 can be activated by a transcription factor—a protein that controls when and where genes are turned on in a cell--that also controls genes involved in aggregation. The transcription factor—a protein called SypG—is similar to the one used to regulate Qrr1 by the quorum sensing pathway This similarity enables SypG to promote expression of Qrr1 in the aggregates during colonization and ensures Qrr1 is not expressed once inside the light organ to allow bioluminescence.

“This complex regulatory architecture that controls Qrr1 expression allows it to play these two important roles and helps coordinate the shift in behavior from colonization to bioluminescence,” said Miyashiro. “When we look across the bacterial family that includes V. fischeri, we see very similar structures that suggest to us that this type of coordination is likely to be important for many symbiotic bacteria.”

In addition to Miyashiro, the research team at Penn State includes Ericka D. Surrett, graduate student in the biochemistry, microbiology, and molecular biology (BMMB) program; Kirsten R. Guckes, postdoctoral scholar in Miyashiro’s lab; Shyan Cousins, and undergraduate student; Terry B. Ruskoski, BMMB graduate student; Andrew G. Cecere, research technologist in Miyashiro’s lab; and C. Denise Okafor, assistant professor of biochemistry and molecular biology and of chemistry. The research team also includes Denise A. Ludvik and Mark J. Mandel at the University of Wisconsin-Madison.

This work was supported by the U.S. National Institute of General Medical Sciences, the Howard Hughes Medical Institute Gilliam Fellowship, and National Institute of Allergy and Infectious Diseases Fellowship. Miyashiro is a member of the One Heath Microbiome Center at Penn State and the Penn State Huck Institutes for the Life Sciences.

 

Why are mosquitos so obsessed with me? (video)


Business Announcement

AMERICAN CHEMICAL SOCIETY

Why are mosquitos so obsessed with me? (video) 

IMAGE: SOME PEOPLE ARE MORE ATTRACTIVE TO MOSQUITOS THAN OTHERS, AND NEW RESEARCH IS STARTING TO SHOW WHY. THIS REACTIONS EPISODE DIVES INTO THE CHEMISTRY OF THE MOLECULES ON OUR SKIN THAT MAKE SOME OF US SO MUCH MORE APPEALING TO THESE PESKY INSECTS. IT ALSO REVEALS WHICH PRODUCTS WE CAN USE TO TRY TO DETER THEM. HTTPS://YOUTU.BE/VYUUG72GWB0 view more 

CREDIT: THE AMERICAN CHEMICAL SOCIETY



WASHINGTON, July 17, 2023 — Some people are more attractive to mosquitos than others, and new research is starting to show why. This Reactions episode dives into the chemistry of the molecules on our skin that make some of us so much more appealing to these pesky insects. It also reveals which products we can use to try to deter them. https://youtu.be/VYUug72GWB0

Reactions is a video series produced by the American Chemical Society and PBS Digital Studios. Subscribe to Reactions at http://bit.ly/ACSReactions and follow us on Twitter @ACSReactions.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

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STILL NO REASON TO DROP THEM ON THEIR HEADS

Children’s IQs not diminished by concussion


UCalgary led study published in Pediatrics can reduce parental fears

Peer-Reviewed Publication

UNIVERSITY OF CALGARY

Keith Yeates 

IMAGE: PRINCIPAL INVESTIGATOR KEITH YEATES SAYS THE STUDY MAY BRING SOME RELIEF TO PARENTS CONCERNED ABOUT THEIR CHILD'S RECOVERY FROM CONCUSSION. view more 

CREDIT: RILEY BRANDT, UNIVERSITY OF CALGARY




The angst parents feel when their children sustain injuries is surely one of the universal conditions of parenthood. That anxiety is heightened greatly when those injuries involve concussions. But a new study led out of the University of Calgary, published today in the medical journal Pediatrics, may set worried parental minds slightly at ease.

The findings – taken from emergency room visits in children’s hospitals in Canada and the United States – show that IQ and intelligence is not affected in a clinically meaningful way by pediatric concussions.

The study compares 566 children diagnosed with concussion to 300 with orthopedic injuries. The children range in age from eight to 16 and they were recruited from two cohort studies. The Canadian cohort encompasses data collected from five children’s hospital emergency rooms, including Alberta Children’s Hospital in Calgary, along with those in Vancouver, Edmonton, Ottawa, and Montreal (CHU Sainte-Justine). In the Canadian hospitals, patients completed IQ tests three months postinjury.

The U.S. cohort was conducted at two children’s hospitals in Ohio, wherein patients completed IQ tests three to 18 days, postinjury.

“Obviously there’s been a lot of concern about the effects of concussion on children, and one of the biggest questions has been whether or not it affects a child’s overall intellectual functioning,” says Dr. Keith Yeates, PhD, a professor in UCalgary’s Department of Psychology and senior author of the Pediatrics paper. Yeates is a renowned expert on the outcomes of childhood brain disorders, including concussion and traumatic brain injuries.

“The data on this has been mixed and opinions have varied within the medical community,” says Yeates.  “It’s hard to collect big enough samples to confirm a negative finding. The absence of a difference in IQ after concussion is harder to prove than the presence of a difference.”

Combining the Canadian and U.S. cohorts gave the Pediatrics study an abundant sample and it allowed Yeates and his co-authors – from universities in Edmonton, Montreal, Vancouver, Ottawa, Atlanta, Utah, and Ohio, along with Calgary’s Mount Royal University – to test patients with a wide range of demographics and clinical characteristics.

“We looked at socioeconomic status, patient sex, severity of injuries, concussion history, and whether there was a loss of consciousness at the time of injury,” says Yeates. “None of these factors made a difference. Across the board, concussion was not associated with lower IQ.”

The children with concussion were compared to children with orthopedic injuries other than concussion to control for other factors that that might affect IQ, such as demographic background and the experience of trauma and pain. This allowed the researchers to determine whether the children’s IQs were different than what would be expected minus the concussion.

The findings of the study are important to share with parents, says Dr. Ashley Ware, PhD, a professor at Georgia State University and lead author of the paper. While the Pediatrics research was underway, Ware was a Killam Postdoctoral Fellow at UCalgary, where Yeates was her supervisor.

“Understandably, there’s been a lot of fear among parents when dealing with their children’s concussions,” Ware says. “These new findings provide really good news, and we need to get the message to parents.”

Dr. Stephen Freedman, PhD, co-author of the paper, a professor of pediatrics and emergency medicine at the Cumming School of Medicine, agrees. “It’s something doctors can tell children who have sustained a concussion, and their parents, to help reduce their fears and concerns,” says Freedman. “It is certainly reassuring to know that concussions do not lead to alterations in IQ or intelligence.”

Another strength of the Pediatrics research is that incorporates the two cohort studies, one testing patients within days of their concussions and the other after three months.

“That makes our claim even stronger,” says Ware. “We can demonstrate that even in those first days and weeks after concussion, when children do show symptoms such as a pain and slow processing speed, there’s no hit to their IQs. Then it’s the same story three months out, when most children have recovered from their concussion symptoms. Thanks to this study we can say that, consistently, we would not expect IQ to be diminished from when children are symptomatic to when they’ve recovered.” 

She adds: “It’s a nice ‘rest easy’ message for the parents.”

 

SCI-FI-TEK

New study shows multiple advantages of capturing carbon where it is produced


EPFL engineers propose a system-wide integration solution for carbon capturing in the cement production, steel manufacturing, and waste incineration sectors.

Peer-Reviewed Publication

ECOLE POLYTECHNIQUE FÉDÉRALE DE LAUSANNE




EPFL engineers in Sion, Switzerland have demonstrated the potential for achieving net-zero and net-negative emissions in essential industrial sectors through the integration of carbon capture and mineralization directly in the industries themselves. The research focuses on the strategic sectors of cement production, steel manufacture, and waste incineration. It offers a cost-effective and energy-efficient approach to mitigate CO2emissions, thereby contributing significantly to reaching global climate targets.

With the urgent need to address carbon emissions from factories and industrial facilities, the research from the Laboratory of Industrial Process and Energy Systems Engineering (IPESE) introduces a solution to integrate CO2 capture and mineralization within the production process. The carbonates formed through mineralization provide a safe and long-term storage solution for CO2, effectively removing it from the atmosphere. As a further ecological benefit, the mineralized carbon can be used as a building material. This, in turn, preventing the extraction of new materials and contributes to reduced emissions and a circular economy.

According to Professor François Marechal, head of IPESE, these key industrial sectors need CO2 capturing to reach carbon neutrality. “Reaching net-zero cannot be done by replacing fossil fuels with renewable energy alone. In this study we demonstrate the importance of adopting a process integration to reduce the cost of the capture and of the sequestration,” says Marechal. According to the research, mineralization, or achieving the ultimate oxidation state for carbon, guarantees a safe and long-term sequestration and solves the problem of finding deep geological locations for sequestration.

Reusing materials found nearby and on site

EPFL’s research by PhD student Rafael Castro-Amoedo applies a systems engineering approach that integrates capture and mineralization directly within the industrial sectors themselves, taking advantage of their large amounts of waste heat, alkaline solid residues, and process emissions. These sectors currently represent approximately 12% of all EU emissions, and the carbon could be sequestrated at a cost of 62 and 85 EUR per ton of CO2. The costs detailed in the study offering economic benefits of up to 50% over deploying capture and storage separately and highlight the importance of applying a process system integration. Environmentally, applying this methodology would amount to a reduction of 860 million tons of CO2 and represents savings of 535 billion EUR when compared to the overall social costs of inaction. Put into context, these savings would total around 130 EUR per year for each European citizen.

The successful implementation of this transformative solution would require a significant retrofitting effort across industries. The research shows that a six-year timeline is necessary to retrofit existing facilities and fully integrate the proposed carbon capture and mineralization technology. This timeframe would allow for the gradual transition of industries towards a more sustainable and climate-friendly future.

The research is published in the journal Energy and Environmental Science and represents a significant step towards achieving net-zero and net-negative emissions in industrial sectors. By capturing CO2 directly from factories, utilizing waste residues, and integrating external minerals, this innovative approach offers a cost-effective, energy-efficient, and environmentally sound solution. The economic benefits and potential cost savings associated with Amoedo’s integrated solution make a compelling case for increased policy measuresand carbon pricing reform. With continued support and collaboration, this research holds the potential to revolutionize industrial practices, mitigate climate change, and pave the way for a sustainable future.

EV

Argonne to use J.D. Power data sets to better understand electric vehicle market and charging infrastructure


Through analysis of new data sets, Argonne researchers will explore electric vehicle adoption patterns

Business Announcement

DOE/ARGONNE NATIONAL LABORATORY



Collaboration will advance understanding of electric vehicle landscape.

Through a new collaboration formed by a contract between the U.S. Department of Energy’s (DOE) Argonne National Laboratory and J.D. Power, a company focused on data analytics and consumer insights, Argonne researchers will use J.D. Power’s EV IndexSM, to access new electric vehicle (EV) data sets. These data sets that will enable valuable insights into the rapidly growing market for EVs and an understanding of consumers’ experience with EV charging infrastructure (charging stations).

Through the analysis of J.D. Power’s data sets, Argonne researchers will be able to better understand drivers’ interest in EVs, patterns of EV adoption and EV owners’ experience with charging stations; including their preferences, usage patterns and the challenges they may face.

“Combined with Argonne’s technical data and analysis, J.D. Power’s data on EV-related consumer behavior will help Argonne and DOE advance the understanding of the current EV user and charging landscape,” said Claus Daniel, Argonne’s associate laboratory director for advanced energy technologies. “This understanding will support decision-making that moves the nation closer to its clean transportation and climate goals.”

As the demand for EVs continues to rise, researchers and policymakers face the critical task of understanding consumer preferences, barriers to adoption and charging experiences. This knowledge will help inform the development of more accessible and reliable charging networks, ultimately driving the widespread adoption of EVs.

Argonne is a leader in tracking and assessing trends and barriers to vehicle electrification in the U.S. and supply chains that support electrification. Argonne provides key EV data and analysis on a broad range of topics — from EV manufacturing to reductions in gasoline consumption and carbon emissions — to the DOE.

 

Study finds tracking brain waves could reduce post-op complications


Distinctive EEG patterns indicate when a patient’s state of unconsciousness under general anesthesia is more profound than necessary

Peer-Reviewed Publication

MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Amplitude of alpha waves 

IMAGE: AS PATIENTS RECEIVE INCREASING DOSES OF PROPOFOL (PANELS A THROUGH D), THE AMPLITUDE OF ALPHA WAVES GRADUALLY FLATTENS UNTIL PATIENTS ENTER THE STATE KNOWN AS BURST SUPPRESSION (D). AS THE DOSE IS DECREASED (PANELS E-G), THE AMPLITUDE RETURNS TO NORMAL. view more 

CREDIT: MIT RESEARCHERS



CAMBRIDGE, MA -- When patients undergo general anesthesia, their brain activity often slows down as they sink into unconsciousness. Higher doses of anesthetic drugs can induce an even deeper state of unconsciousness known as burst suppression, which is associated with cognitive impairments after the patient wakes up.

A new study from MIT, in which the researchers analyzed the EEG patterns of patients under anesthesia, has revealed brain wave signatures that could help anesthesiologists determine when patients are transitioning into that deeper state of unconsciousness. This could enable them to prevent patients from falling into that state, reducing the risk of postoperative brain dysfunction.

One of these distinctive patterns emerged in the brain’s alpha waves (which have a frequency of eight to 14 cycles per second). Once patients became unconscious, these waves started to wax and wane in amplitude. As patients went deeper into unconsciousness, the pattern of this waxing and waning in amplitude, or amplitude modulation, continually changed.

“If you track this modulation as it gets deeper or shallower, you have a very principled way to track level of unconsciousness under anesthesia,” says Emery Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience and a member of MIT’s Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science.

Brown is the senior author of the new study, which appears this week in the Proceedings of the National Academy of Sciences. The lead authors of the paper are Picower Institute research scientist Elie Adam, Ohyoon Kwon ’20, and graduate student Karla Montejo.

Measuring brain waves

Brain waves, which are generated by synchronized neuronal activity, oscillate at different frequencies depending on what kind of task the brain is performing. When the brain is strongly engaged in mental activity, it produces higher-frequency beta (15-30 hertz) and gamma (greater than 30 hertz) oscillations, which are believed to help organize information and enhance communication between different brain regions.

Commonly used anesthesia drugs such as propofol have a significant effect on these oscillations. During anesthesia induced by propofol or other anesthetics that increase the effectiveness of GABAergic inhibitory receptors in the brain, the brain enters a state of unconsciousness known as slow-delta-alpha (SDA). This state is characterized by slow (0.1-1 hertz), delta (1-4 hertz) and alpha (8-14 hertz) oscillations.

With higher doses of these anesthetic drugs, the brain can fall into an even deeper state of unconsciousness. When in this state, known as burst suppression, EEG recordings from the brain show long periods of inactivity, punctuated by brief bursts of low-amplitude oscillations. When patients enter this state, they are more likely to experience postoperative confusion, delirium, and memory loss. These effects, which can last for hours, days, weeks, or months, are more common in elderly patients.

SDA and burst suppression produce distinctive EEG patterns that have been well-studied. However, they have been studied as separate brain states; what happens during the transition between the two states is less clear. That transition is what the MIT team set out to analyze in this study.

To do that, the researchers studied 10 healthy volunteers and 30 patients who were undergoing surgery. Most of the patients received propofol intravenously, and the rest received sevoflurane, a commonly used anesthetic gas. Both of these drugs act on GABA receptors in the brain, which reduce neuron excitability.

As the dosage of propofol was increased, patients showed two distinctive patterns of change in their EEGs. The first pattern was seen in the alpha waves, which started to wax and wane. As the dose increased, waxing was shortened and waning was prolonged, until the patient reached the state of burst suppression.

“You can see a very strong modulation, which is always there. As the modulation gets to be more profound, it eventually flattens out, and that's when the brain reaches the deeper state,” Brown says.

When the amount of drug was reduced, the amplitude of the alpha waves began to increase again.

The researchers also found a distinctive pattern in the slow and delta waves seen in the patients’ EEG readings. Slow and delta oscillations are the slowest brain waves, and as the amount of drug was increased, the frequency of these waves became slower and slower, reflecting a decrease in brain activity.

Metabolic disruption

The researchers hypothesize that propofol exerts these effects through its influence on neuron metabolism. The drug is postulated to disrupt the production of ATP, the molecules that cells use to store energy. As ATP production declines, neurons eventually become unable to fire, leading to burst suppression.

“This is consistent with the observation that burst suppression is very frequent in older patients, because their metabolic state may be less well-regulated than that of younger patients,” Brown says.

The findings could offer anesthesiologists more refined control over a patient’s state of unconsciousness during surgery, says Brown. He now hopes to develop an algorithm that could generate a warning that a patient is approaching burst suppression, which could be displayed on a monitor in the operating room. He says that anesthesiologists could also learn to make that determination by looking for these patterns in a patient’s EEG.

“One of the reasons we're excited about this is that it’s something you can actually see in the raw EEG,” Brown says. “Now that we have pointed out these patterns, they’re very easy to see.”

The researchers now plan to further explore what is happening to the brain’s metabolism during the transition to burst suppression, using animal models.

###

The research was funded in part by the Picower Institute Innovation Fund and the National Institutes of Health.

 

Bacterial protein found in the urogenital tract may contribute to reduced fertility, birth defects


Study underscores significant implications for cancer and obstetrics medicine, as well as diagnostics, and preventative therapy

Peer-Reviewed Publication

UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE

Bacterial Protein Found in the Urogenital Tract May Contribute to Reduced Fertility, Birth Defects 

IMAGE: THE BACTERIAL PROTEIN DNAK (GREEN) IS TAKEN UP INTO HUMAN CANCER CELLS AND MOVES TO THE CELL’S NUCLEUS (BLUE), WHERE THE DNA IS LOCATED. view more 

CREDIT: PNAS 2018 DEC 18; 115(51): E12005–E12014.



A team of researchers from the University of Maryland School of Maryland’s (UMSOM) Institute of Human Virology (IHV), a Center of Excellence of the Global Virus Network (GVN), published new findings that emphasize the crucial role of the urinary and genital tract microbiota in adverse pregnancy outcomes and genomic instability that originate in the womb during fetal development.

The study, published on July 17 in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), established a new link between genomic instability and a protein from Mycoplasma fermentans, a kind of bacterium that commonly colonizes the urogenital tract. This bacterial protein also reduced fertility in mother mice and resulted in more birth defects in their newborn pups.

This research was spearheaded by Davide Zella, PhD, Assistant Professor of Biochemistry and Molecular Biology at UMSOM’s IHV and Robert Gallo, MD, The Homer & Martha Gudelsky Distinguished Professor in Medicine, Co-Founder and Emeritus Director of UMSOM’s IHV, and Co-Founder and Chair of the Scientific Leadership Board of the Global Virus Network.

"Our results not only broaden our understanding of the interplay between the urogenital tract microbiota and human reproductive health, but also shed light on the previously unidentified contribution of the human microbiota to genetic abnormalities," said lead author on the study Francesca Benedetti, PhD, Research Associate of Biochemistry and Molecular Biology in UMSOM’s IHV.

“We aim to further explore the mechanisms underlying these findings and their potential implications for preventing and treating chromosomal abnormalities and genetic diseases,” said co-lead author Giovannino Silvestri, PhD, former Research Associate of Medicine in UMSOM’s IHV.

The human microbiota is known to affect metabolism, susceptibility to infectious diseases, immune system regulation, and more. One of these bacterial components, Mycoplasmas, have been linked to various cancers.

The research team has been studying one Mycoplasma protein, DnaK, which belongs to a family of proteins that safeguards other bacterial proteins against damage and aids in their folding when they are newly made, acting as a so-called ‘chaperone.’ However, while this protein is advantageous for bacteria, its effects on animal cells are less favorable. To this regard, the team had previously demonstrated that this DnaK is taken up by the body’s cells and it interferes with key proteins involved in preserving DNA integrity and in cancer prevention, such as the tumor suppressor protein p53.

For this latest study, researchers created mice that make the DnaK protein normally produced by the bacterium Mycoplasma fermentans. These mice with exposure to DnaK accrued genomic instability in which entire sections of the genome were duplicated or deleted, resulting in mice with varying numbers of copies of certain genes.

The team noticed that some of these mice from 3-5 weeks of age had problems with movement and coordination. They found that these mice have a deletion in the Grid2 gene, which in humans leads to the rare genetic disease known as spinocerebellar ataxia-18 (SCAR18) that causes delayed development of skilled movements and intellectual disabilities.

“Remarkably, this instance marks the first time a mouse model successfully recapitulated a human genetic disease de novo, showcasing this model's potential for further cancer biology research,” said Dr. Zella.

More than a third of the female mice that made the DnaK protein were unable to get pregnant. Additionally, more than 20 percent of the pups born from moms with the DnaK protein had some sort of birth defect/deformity.

“The occurrences of genomic instability, in the form of increased number of copy number variations, could explain the decreased fertility and the increased instances of abnormally developed fetuses we observed upon DnaK exposure,” said Dr. Gallo. “These data build upon our initial work which discovered the disruptive role of DnaK on key proteins involved in the proper repair of damaged DNA, which are also known to play a role in the onset of copy number variations. Our ongoing commitment is to better understand the potential implications of these findings in cellular transformation and cancer.”

UMSOM Dean Mark T. Gladwin, MD, who is also Vice President for Medical Affairs, University of Maryland, Baltimore and the John Z. and Akiko K. Bowers Distinguished Professor, commended the work. “The researchers raise a significant question regarding whether DnaK can interfere with fetal development in humans. An important next step would be to investigate whether neutralizing either the bacteria or this protein could preserve fertility and prevent certain birth defects,” he said.

About the Institute of Human Virology

Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland, and the University of Maryland Medical System, the IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. The IHV combines the disciplines of basic research, epidemiology, and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders, most notably HIV, the virus that causes AIDS. For more information, visit ihv.org and follow us on Twitter @IHVmaryland.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world — with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

Researchers discover group of genes that influence pain and brain communication can also influence alcohol use disorder risk

Peer-Reviewed Publication

INDIANA UNIVERSITY SCHOOL OF MEDICINE




INDIANAPOLIS—An estimated 16 million people in the United States have alcohol use disorders (AUDs), according to the National Institutes on Alcohol Abuse and Alcoholism (NIAAA). Now, Indiana University researchers have made a substantial discovery in the role genes play in the development of AUDs, finding that alteration of a group of genes known to influence neuronal plasticity and pain perceptions, rather than single gene defect, is linked to AUDs.

“We know inherited genes are a major contributor to this disease, because past studies have shown family genetics to be directly associated with alcohol dependence within a family,  such as identical twins raised in different environments,” said Feng Zhou, PhD, professor emeritus of anatomy, cell biology and physiology at IU School of Medicine.

Zhou is the lead author, along with William Muir, PhD, professor emeritus of genetics at the Purdue Department of Animal Sciences, of a new publication in Alcohol: Clinical and Experimental Research which details their new findings.

Researchers used three different animal models created in the IU Alcohol Research Center to study how the genes impact desire for alcohol. The study involved statistically sorting through about 3 billion DNA base pairs containing nearly 30,000 genes, in 70 individual animals to identify the handful that were responsible for drinking behaviors. Thanks to their experimental design, the researchers could identify population differences based on drinking behaviors rather than chance genetic differences or other environmental influences.

“These rat models are all uniquely qualified as criteria for human outcomes,” said Zhou.

The genes that mediate pain sensation act in concert with two other groups of neural channel and neural excitation genes which perform neural communication functions, the team found.

“The function of these three groups of genes is important for neuroadaptation and neuroplasticity, meaning that they can change brain communications,” Zhou said.

They also discovered a key cohort of genes impacted alcohol use, with some of the genes having silent mutations, meaning they did not alter the amino acid sequence translated, but influenced the rate and conformation of gene transcription, causing changes in the other genes that had an impact on alcoholism.

“This is the first time these multiple models have ever been used for this pursuit,” Muir said. “In the past, research has focused on a single gene and how it can contribute to alcohol use, but now, we can see that these large groups of genes make a difference, which can help guide future research and clinical care for those suffering from AUDs.”

“The brain must be modified over the drinking period. That kind of modification is similar to drug abuse,” Zhou said. “It is genetically prone neural plasticity or neural adaptation to a certain level that makes drinking more pleasurable and more tolerable, or pain relief.”

“The alleviation of pain appears to be one motivation to drink and continue to drink,” Muir said. “Knowing that, it’s possible that early counseling can produce drinking avoidance.”

The new findings raise the possibility of genetic testing for alcoholism. People who get tested and know that they have a high genetic tendency to become an alcoholic might take extra care to moderate their drinking.

“One future direction is how these animal findings would translate to humans,” Zhou said. “If verified, then treatment or prevention can be more focused.”

Other study authors include Chiao-Ling Lo, PhD and Richard Bell, PhD of IU School of Medicine and the Indiana Alcohol Research Center at IU School of Medicine.

About IU School of Medicine

IU School of Medicine is the largest medical school in the United States and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.