For more than 50 years, scientists have puzzled over the genetic material contained in this “dark DNA.” But there’s a growing body of evidence showing that its proper functioning is critical for maintaining cells in a healthy state. Heterochromatin contains tens of thousands of units of dangerous DNA, known as “transposable elements” (or TEs). TEs remain silently “buried” in heterochromatin in normal cells — but under many pathological conditions they can “wake up” and occasionally even “jump” into our regular genetic code.

And if that change benefits a cell? How wonderful! Transposable elements have been co-opted for new purposes through evolutionary history — for instance the RAG genes in immune cells and the genes required for driving the development of the placenta and mammalian evolution have been derived from TEs.

But TEs may also wreak havoc on our health. In just the last few years, scientists have linked heterochromatin weakening to aging, premalignancy, cancer, and autoimmune disease.

“You can think of heterochromatin as a prison for transposable elements” says La Jolla Institute for Immunology (LJI) Professor Anjana Rao, Ph.D., the lead author of a new Nature Structural & Molecular Biology study, with key collaborators Professor Geoffrey J. Faulkner, Ph.D. of the University of Queensland, Robert Crawford, Ph.D., of biomodal (formerly Cambridge EpiGenetix), and Samuel Myers, Ph.D., Assistant Professor at LJI. “When heterochromatin loses its normal suppressive function, TEs escape and in parallel, the health of cells declines.”

The new study reveals a remarkable way that cells keep us safe from TEs gone wild. The researchers found that cells have taken advantage of an entire protein network to repress TE activity and keep themselves healthy.

“Reactivated transposable elements can create a lot of genomic instability,” says Hugo Sepulveda, Ph.D., a Pew Latin American Postdoctoral Fellow, former Instructor at LJI, and one of the two co-first authors of the new study with LJI Instructor Xiang Li, Ph.D.

“Even just increased expression of these elements can affect the expression of nearby genes, as we show in our new paper,” adds Sepulveda. “Abundant expression of transposable elements is a signature of many diseases, including cellular senescence, human aging, autoimmune disorders and many types of cancers.”

How do cells keep transposable elements under control?

Meet O-GlcNAc transferase (OGT), an enzyme at the heart of many essential cellular functions. According to the new study, OGT is also a lead choreographer when it comes to suppressing TEs and keeping gene expression running smoothly.

For the new project, the researchers followed up on the fact that OGT interacts with important proteins called TET enzymes, discovered by the Rao Lab in 2009. TET proteins are part of the complex machinery that makes sure our DNA is correctly modified in our cells and that our cells activate the right transcriptional programs.

TET proteins are involved in the critical cycle of DNA modifications, where they play a role in a process that results in the removal of molecular markers that attach to DNA (an event called DNA demethylation). The most abundant DNA markers, called 5mC and 5hmC, are normally associated with transcriptional silencing and activation, respectively. Researchers have shown that 5mC is associated with genes turned “off” while 5hmC, mediated by TET proteins, is associated with gene expression turned “on.”

This “on/off” epigenetic system gives our cells the flexibility to respond to environmental changes and health threats. DNA demethylation helps our immune cells spring into action if they detect a threat.

DNA demethylation is normal, but cells also need balance. You can’t have TET proteins activating every gene at the same time. In normal cells, TET protein activity is restricted to the genes that need to be expressed in that particular cell type.

In the new study, the scientists harnessed Oxford Nanopore sequencing technology and other cutting-edge sequencing techniques to discover where OGT comes in. One especially important and new technique that they used is called duet evoC. This multiomics solution enabling the 6-base genome, developed by biomodal, was essential to establish that both 5mC and 5hmC were simultaneously changing at the same sites in the genome.

The researchers found that OGT protects cells by restraining TET activity. This is extremely important for controlling TE expression because it prevents the silencing modification 5mC from being converted to the activating modification 5hmC in heterochromatin.

Without OGT at the helm, TET proteins ramp up DNA demethylation in the wrong places, turning on too many genes at once, including intact TEs normally “buried” in our genetic material.

Next steps for understanding cancers, autoimmune disease, and more

This finding shows how the non-coding regions of our genome can turn active when TET functions are altered. The new understanding of the OGT-TET partnership shows that these proteins, their mediated marks, and TE expression can affect our cells in a big way.

“We think of these elements as totally ‘silent,’ and therefore completely inert, but the reality is that cells have to make a huge — and constant — investment to keep TEs silent,” says Sepulveda.

This new research may also prove important for future drug development. Scientists have identified numerous genes linked to cancer, but controlling their expression remains a challenge. The new findings suggest we might stop cancer growth through interesting new avenues, such as by restraining TE activity in cancer cells.

“We want to control that activity, and we may now have an option through OGT and TETs,” says Sepulveda.

Rao emphasizes that further studies are needed to investigate how OGT controls DNA modifications and TE expression — and how the dysregulation of this mechanism contributes to autoimmune disorders, cancers, and other diseases.

This study was supported by the National Institutes of Health (grants R35 CA210043, NIGMS R35GM147554), an NHMRC Investigator Grant (GNT1173711), the Mater Foundation, the Pew Latin-American Fellows Program from The Pew Charitable Trusts, a fellowship from the California Institute for Regenerative Medicine, and the UCSD Graduate Training Program in Cellular and Molecular Pharmacology (through the institutional training grant NIH NIGMS T32 GM007752.)

A new study conducted at the Human and Environmental Physiology Research lab (HEPRU) at the University of Ottawa has unveiled significant findings on the effects of cold water acclimation on autophagic (the cells’ recycling system, which promotes cellular health) and apoptotic (the programmed cell death that gets rid of damaged cells) responses in young males. The research highlights the potential for cold exposure to enhance cellular resilience against stress.

The study, conducted by Kelli King, postdoctoral fellow, and Glen Kenny, Full Professor at uOttawa’s School of Human Kinetics and Director of HEPRU, involved ten healthy young males who underwent cold-water immersion at 14°C (57.2°F) for one hour across seven consecutive days. Blood samples were collected to analyze the participants’ cellular responses before and after the acclimation period.

“Our findings indicate that repeated cold exposure significantly improves autophagic function, a critical cellular protective mechanism,” says Professor Kenny. “This enhancement allows cells to better manage stress and could have important implications for health and longevity.”

The research revealed that while autophagy was initially dysfunctional after high-intensity cold stress, consistent exposure over a week led to increased autophagic activity and decreased cellular damage signals.

“By the end of the acclimation, we noted a marked improvement in the participants’ cellular cold tolerance,” explains King, the study’s first author. “This suggests that cold acclimation may help the body effectively cope with extreme environmental conditions.”

The implications of this study extend beyond athletic performance. Cold water immersion has gained popularity for its potential health benefits, and this research provides some scientific backing for its efficacy. The findings suggest that proper autophagic activity could not only extend cellular longevity but also prevent the onset of various diseases.

As the use of cold exposure becomes increasingly mainstream, understanding its effects on cellular mechanisms is vital. Professor Kenny emphasizes, “This work underscores the importance of acclimation protocols in enhancing human health, especially in contexts where individuals are exposed to extreme temperatures.”

“We were amazed to see how quickly the body adapted,” notes King. “Cold exposure might help prevent diseases and potentially even slow down aging at a cellular level. It’s like a tune-up for your body’s microscopic machinery.”

These results apply to young males and more research is needed to see if it would also apply to other cohorts.

Now Drexel researchers have developed a simple DNA PCR-based lab test — built on a more detailed genetic analysis of the main group of bacterial organisms that cause the infection — to help clinicians prescribe the right medicine for each patient. The results are published this week in the journal Genome Medicine.

“If this test becomes available to patients, they can avoid taking the wrong antibiotic, avoiding additional potential side effects and financial costs,” said lead author Katherine Innamorati, PhD, an instructor in Drexel University College of Medicine. “Faster treatment and better antibiotic stewardship is especially important for patients who may need to take multiple courses of antibiotics to fully eliminate the infection.”

The main bacterial pathogens associated with BV are a group of related bacterial species previously known as Gardnerella vaginalis. Earlier work by Garth Ehrlich, PhD, a professor of Microbiology and Immunology in the College of Medicine, and colleagues revealed that this group is actually composed of multiple species.

In the current paper, the authors built out this “family tree” much further. Using genome sequencing and genomic metrics on 129 Gardnerella spp. genomes, the team performed a detailed analysis revealing much greater diversity, including identifying 11 unique groups of organisms known as genospecies, which fall within several major clades, or groupings.

Using this data, the research team found that two of the clades are composed of five genospecies that are 100% resistant to metronidazole, but can be successfully treated with the antibiotic clindamycin. Both drugs are typically taken for a week and can be administered vaginally or by mouth. The team’s PCR test can distinguish among the strains, identifying ones that are highly resistant to metronidazole.

Symptomatic patients can experience vaginal itching, burning during urination, foul odor or gray, white or green discharge. BV is not considered a strictly sexually transmitted infection, but some sexual activities, including not using a condom, and other activities can increase the likelihood of developing BV.

An estimated half of BV cases show no noticeable symptoms, leading to many cases going untreated. Although about 30% of BV cases resolve without treatment, those with untreated cases may be at higher risk of sexually transmitted infections, greater likelihood of pregnancy complications and other negative impacts to quality of life resulting from inflammation of the mucosa in the reproductive tract.

“BV is a dysbiosis, meaning the whole microbiome of the lower reproductive tract is imbalanced,” said Ehrlich. “It’s possible that some patients may need both drugs — metronidazole might provide coverage for some microorganisms, particularly anerobic bacteria that grow in the absence of oxygen. So those with metronidazole resistant Gardnerella might benefit from treatment using both antibiotic drugs, but more research is needed to find out.”

The researchers have filed for a patent for the test. A commercial lab would be needed to offer this widely to patients. Demand from patients and patient support groups may help influence when such a test would become available. Right now, the test can help rule out metronidazole treatment based on highly resistant strains, and the team aims to expand its capabilities to also identify strains that have low resistance to metronidazole.

The team is also working on determining what gene(s) cause a resistant phenotype.

“It’s possible that expression of a gene could play a role in the resistance to an antibiotic, or help explain one aspect of how that resistance occurs, but our data suggests metronidazole resistance happens through multiple mechanisms, rather than one clear pattern,” said Ehrlich. “Much work remains to more fully understand the mechanisms by which different groups of genetic organisms become resistant to metronidazole.”

New randomized controlled trial data published this month in the New England Journal of Medicine suggested that women with BV who are in a monogamous relationship with a male partner may have a lower likelihood of BV coming back after 12 weeks if she takes the first line antibiotics while her male partner also takes the antibiotic and applies a topical antimicrobial clindamycin cream.

Additional authors on the study include Joshua P. Earl, Shirley C. Barrera, Rachel L. Ehrlich, Josephine Aiyeku, and Ari Gordon of Drexel, Evan Powell of University of Pittsburgh Medical Center, Adam C. Retchless of Allegheny Singer Research Institute, Azad Ahmed, Bhaswati Sen, Sergey Balashov, and Joshua Chang Mell of Drexel, and Sharon L. Hillier of the University of Pittsburgh.

“We’re a little worried about the weasels,” says Roland Kays, a research professor at North Carolina State University and scientist at the N.C. Museum of Natural Sciences. “We don’t see them very often, but it’s difficult to tell if they’re actually gone or if they’re just so sneaky that we can’t find them. We decided that we needed to better understand the best method to detect them. There wasn’t a great consensus on that.”

That problem is the focus of a new study by Kays and a host of collaborators, which examines what kind of bait is most effective at luring weasels out of hiding.

Between 2022 and 2023, researchers placed 486 camera traps in sites across the central and eastern United States where they knew weasels lived. They baited those traps with seven types of lures to see which ones attracted the most mustelids — a diverse family of carnivores that includes weasels, ferrets and martens.

Red meat outperformed all other baits, especially when supplemented with a bit of salmon oil. Weasels in the south also had a taste for chicken, Kays said. Because red meat is also attractive to most other predators, researchers used a new double-cage system to make it harder for larger animals to reach the bait.

“There is a huge variety of scent lures available, and trappers often make their own from all kinds of ingredients,” he said. “As it turns out, however, just having a chunk of meat works the best.”

Of all the weasel species to worry about, the “least weasel” is the most worrisome. As the world’s smallest carnivore, the least weasel is notoriously difficult to track down and has only been seen in a handful of camera trap surveys. Their range extends into the North Carolina mountains, and Kays hopes to use the findings from this study to survey least weasel populations there.

“Now that we have an understanding of the best ways to lure the weasels, we can be more confident in the findings of our surveys,” he said. “When we have sites where we don’t detect them, we can be much more assured that they aren’t just in hiding, they’re really just not there at all.”

A growing body of research has drawn connections between everyday discrimination — the routine and often subtle forms of mistreatment that people experience on a day-to-day basis — and poor mental health. A new study by Boston University School of Public Health (BUSPH) and Brown University suggests that higher exposure to discrimination increases a person’s chances of developing depression and/or anxiety, and that this outcome varies by race and ethnicity.

Published in JAMA Network Open, the study found that over half of US adults experienced some form of discrimination, and individuals with high exposure to discrimination have more than five times the chances of screening positive for depression, and five times the chances of screening positive for anxiety. Compared to adults who do not experience discrimination, adults who do experience this mistreatment have nearly nine times the odds of screening positive for both depression and anxiety.

These observations were similar for men and women, but more pronounced among multiracial, White, and Asian adults, populations that are often overlooked in research and discussions about the effect of discrimination on health.

The nationally representative findings provide valuable insight into the relationship between discrimination and mental health among multiple populations, building upon previous research on this subject that has been restricted by smaller study groups or limited comparisons between Black and White populations, or Hispanic or Latino and non-Hispanic or non-Latino populations. The researchers hope this data provides a deeper understanding of the mental health consequences of discrimination among a wider range of demographic groups, and encourages mental health screenings and support to mitigate these racial disparities.

“Our study expands our understanding beyond typical Black-White comparisons, showing that everyday discrimination is a widespread issue that negatively impacts mental health across all racial and ethnic groups,” says study lead and corresponding author Dr. Monica Wang, associate professor of community health sciences at BUSPH.

For the study, Dr. Wang and study senior author Dr. Marie-Rachelle Narcisse, assistant professor of psychiatry and human behavior at Brown, assessed 2023 national survey data to gauge experiences of discrimination, depression, and anxiety among nearly 30,000 adults ages 18 or older. This sample population was weighted to represent more than 258 million US adults. To measure discrimination, the researchers utilized standardized scales that capture the frequency of mistreatment, such as receiving poor service or being harassed. They also utilized standardized scales to quantify experiences with depression (such as feeling down or hopeless, or having little interest in doing things) and anxiety (such as feeling nervous or experiencing an inability to stop worrying).

Nearly 56 percent of adults experienced a form of discrimination, and 3.6 percent of this group reported experiencing high levels of discrimination, most prevalent among Black adults, followed by multiracial or other adults, Hispanic or Latino adults, White adults, and Asian adults. Discrimination was also more common among adults experiencing certain health disadvantages such as disabilities, obesity, and food insecurity, as well as immigrants and women.

The researchers theorize that a combination of social, cultural, and systemic factors may be driving discrimination-related depression or anxiety among specific racial and ethnic groups. Multiracial individuals may navigate unique experiences of mistreatment based on their multiple racial identities, while White individuals may experience mental health challenges that stem from mistreatment related to their income or educational levels. Asian adults may experience depression or anxiety stemming from language barriers or the “model minority” stereotype, which assumes all Asian individuals are high-achieving and successful.

These perceived experiences carry real psychological weight, says Dr. Narcisse.

“Studies have shown that discrimination shapes mental health most deeply when left unacknowledged,” she says. I hope this study creates more awareness. As in awareness, there is strength and the ability to seek healing more intentionally.”

Dr. Wang and Dr. Narcisse also caution that these findings do not suggest that discriminatory experiences and any related adverse mental health problems are less significant among Black, Hispanic, and Latino populations, as these groups continue to experience multiple health challenges driven by systemic racism and a long history of oppression.

“Our results are a powerful reminder that discrimination is everyone’s issue — and addressing it benefits society as a whole,” Dr. Wang says.

Dr. Wang is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases; Dr. Narcisse is supported by the National Institute of General Medical Sciences and the Bradley Hospital COBRE Center for Sleep and Circadian Rhythms in Child and Adolescent Mental Health. The funding sources had no role in the design or conduct of the study; collection, analysis, and interpretation of data; preparation, review, or approval of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.

The meniscus is a complex structure that serves as a critical shock absorber in the knee. and one-size-fits-all treatments aren’t always effective. Through creating a treatment adaptable to the different needs of patients, the researchers believe they may have unlocked a better fix no matter where the injury occurs in a meniscus.

“We developed a hydrogel that can be adjusted based on the patient’s age and the stiffness requirements of the injured tissue, which is important because the meniscus has different biochemical and biomechanical properties that vary depending upon the location in the tissue,” said the study’s senior author, Su Chin Heo, PhD, an assistant professor of Orthopaedic Surgery in the McKay Orthopaedic Research Lab at Penn. “Current treatments, including graft-base methods, do not fully recreate these complex differences, leading to poor healing.”

Hydrogels are flexible, water-absorbing materials commonly found in everyday products like contact lenses and baby diapers. The researchers developed a specialized hydrogel by first extracting proteins from donor cow meniscus tissue. Those proteins then directed new cells to become the right types of repair cells for the damaged meniscus and were used as the basis for the treatment’s structures.

To prevent rejection, the team removed cellular components from the cow tissue while preserving its structural framework. This “decellularization” process reduces the risk of immune reactions when implanted, making the treatment both safer and more effective.

To further customize the hydrogels, Heo and his fellow researchers used 3D-printing techniques to account for the variation in the meniscus tissue. That way, they could more closely match the tissue in the areas they were trying to repair. Mismatched tissues might not heal well.

“In our animal studies, we’ve seen the hydrogel integrate well with the surrounding tissue, potentially offering patients a more complete recovery,” said the study’s first author Se-Hwan Lee, PhD, a post-doctoral fellow in the McKay Lab. “It’s a more precise, biologically matched solution. We believe this could outperform current treatments.”

The team is now transitioning from small mammal studies to large animal models.

“Our first clinical goal will be to treat smaller, localized meniscus tears,” Heo said. “Once we have success there, I believe we could expand to more complex injuries in the meniscus.”

The study was supported by grants from the National Institutes of Health (K01 AR07787, R21 R077700, P30 AR069619, R01 AR056624, R01 HL163168), the National Science Foundation (CMMI 1548571), and Department of Veterans Affairs’ CReATE Motion Center (I50 RX004845) in the United States. It was also supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare (HI19C1095) and National R&D Program through the National Research Foundation of Korea (NRF), funded by Ministry of Science and ICT (RS-2024-00405574) in South Korea.