Bowdoin Science Journal

Biology

Carcinization: Is it Happening to Everybody?

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If evolution had a favorite body plan, it might just be the crab.

This idea lies at the heart of carcinization, which is the repeated, independent evolution of crab-like body forms across diverse crustacean lineages. The term, first coined by zoologist Lancelot Borradaile in 1916 as “one of the many attempts of Nature to evolve a crab,” carcinization has since become one of evolutionary biology’s most fascinating examples of convergent evolution. However, as McLaughlin and Lemaitre argue in their 1997 review, Carcinization in the Anomura – fact or fiction?, the phenomenon is more complex than a linear march towards “true crabs.” More recent research, in Wolfe et al. (2021), How to Become a Crab: Phenotypic Constraints on a Recurring Body Plan, reframes carcinization as a repeated evolutionary outcome shaped not only by natural selection, but by deep developmental and structural constraints.

Across decapod crustaceans, crab-like forms have evolved multiple times. Within the Anomura alone (Figure 1), a group that includes hermit crabs, king crabs, squat lobsters, porcelain crabs, and coconut crabs, independent lineages have converged on broadly similar morphologies: a widened, flattened carapace, reduced and folded abdomen (pleon), and a compact body plan adapted for seafloor life. Porcelain crabs (Porcellanidae), king crabs (Lithodidae), and the terrestrial coconut crab (Birgus latro) all appear, at first glance, to have independently become crabs (McLaughlin & Lemaitre 1997).

Figure 1. Convergent evolution of crab-like body forms (carcinization) across major decapod crustacean groups, including true crabs (Brachyura), porcelain crabs (Porcellanidae), hairy stone crabs (Lomisidae), and king crabs (Lithodoidea) (Wolfe et al. 2021).

McLaughlin and Lemaitre emphasize that these similarities reflect multiple independent origins rather than a single evolutionary trajectory. Crucially, they challenge older, linear interpretations of crab evolution, such as the idea that king crabs evolved directly from hermit crabs through a gradual transformation. Instead, they argue that “carcinized” forms evolve through a variety of anatomical routes and should not be interpreted as stages in a single progression toward a crab “ideal state.”

Wolfe et al. extends this argument by reframing carcinization as part of a broader pattern of phenotypic constraint and integration. Rather than viewing crab-like forms as independently assembled traits, they propose that key features, such as carapace widening, abdominal folding, skeletal reinforcement, and locomotor reorganization, are developmentally and functionally linked. This phenotypic integration means that once certain traits evolve, they bias the evolution of others, channeling morphology toward a crab-like configuration. In this sense, carcinization is not simply selection acting on isolated traits, but the coordinated evolution of an interconnected body system (Wolfe et al. 2021).

This perspective also helps to explain why crab-like forms are so recurring. A compact, flattened body provides clear ecological advantages, including protection through a reduced exposed surface area, improved maneuverability in complex habitats, and enhanced stability for seafloor locomotion. However, neither paper supports the idea that these advantages alone guarantee convergence. Instead, Wolfe et al. emphasizes that carcinization emerges from the interaction between ecological pressures and developmental architecture that constrains how bodies can be reorganized.

Importantly, carcinization is not a one-way evolutionary trend. Both McLaughlin and Lemaitre and Wolfe et al. highlight the existence of  “decarcinization”, which is the evolutionary loss of crab-like features. For example, frog crabs (Raninoidea) evolved more elongated, less compact body forms despite belonging to the true crabs, while the fossil crab Callichimaera perplexa displayed several unusual non-crab-like traits (Wolfe et al. 2021). Some lineages become more crab-like over time, while others revert toward more elongated or exposed body forms. This bidirectional pattern undermines any notion of evolutionary inevitability and suggests a changing landscape of morphological possibilities shaped by trade-offs between protection, mobility, and ecological specialization.

Fossil evidence further complicates the picture (Figure 2). Early crab-like fossils often display mosaic combinations of traits, involving partial abdominal folding, intermediate carapace shapes, or ambiguous limb structures, making it difficult to reconstruct a single pathway toward modern crabs. Wolfe et al. argue that these fossils support a stepwise and potentially repeated assembly of crab-like forms rather than a single origin of the “crab body plan.”

Figure 2. Fossil examples of crab evolution showing uncarcinized, carcinized, and decarcinized body forms across major decapod lineages. Uncarcinized forms include the more elongated, lobster-like body plans shown in A, C, and D. Carcinized forms, characterized by broadened carapaces and reduced abdomens, are shown in B and H-J. Decarcinized forms, which exhibit partial reversals away from the classic crab-like body plan, are shown in E-G. Together, these fossils illustrate how crab-like morphologies evolved repeatedly through time, while some lineages also lost or reversed key crab-like traits (Wolfe et al., 2021).

At the center of Wolfe et al. is a shift in how carcinization is interpreted. Earlier accounts sometimes framed it as evolution repeatedly “trying to make a crab,” implying a directional or goal-like process. Both McLaughlin and Lemaitre and Wolfe et al. reject this framing. Instead, they argue that crab-like morphologies repeatedly evolve because they can arise through relatively simple modifications of existing crustacean body plans, given how crustacean body plans are developmentally organized. Evolution does not aim toward crabs; rather, crab-like forms repeatedly arise because they are among the structurally available solutions to similar ecological challenges.

This has broader implications for evolution. Wolfe et al. suggests that carcinization is best understood as a case study in how constraints and integration can shape the predictability of evolution. In some contexts, evolution may appear highly repeatable, not because outcomes are predetermined, but because developmental systems channel variation along restricted and recurrent pathways. At the same time, the existence of multiple independent origins and reversals shows that these pathways are not exclusive or deterministic (Wolfe et al. 2021).

So, is carcinization happening to everybody?

Not exactly. Yes, in the sense that crab-like body plans have evolved repeatedly across independent lineages, suggesting strong functional and developmental biases toward this form. But no, because carcinization is neither universal nor inevitable. Many crustaceans never approach a crab-like form, and even within carcinized groups, evolution frequently reverses direction or produces only partial convergence (Wolfe et al. 2021, McLaughlin & Lemaitre 1997). Similar patterns of convergent evolution occur throughout nature, including the repeated evolution of streamlined, torpedo-shaped swimming bodies in sharks, dolphins, and ichthyosaurs in response to the limitations of moving through water (Futuyma & Kirkpatrick, 2017), illustrating how comparable environmental pressures can produce similar morphologies in distantly related lineages.

Ultimately, carcinization reveals something more subtle than a march toward a single optimal design. It highlights how evolution operates within a landscape shaped by ecological opportunity, developmental constraint, and historical contingency. The crab body plan is not evolution’s endpoint; it is a repeatedly accessible solution that emerges when different evolutionary paths converge on similar structural answers to similar problems.

Literature Cited

  1. Futuyma, D. J., & Kirkpatrick, M. (2017). Evolution (4th ed.). Sinauer Associates.
  2. McLaughlin, P. A., & Lemaitre, R. (1997). Carcinization in the Anomura—Fact or fiction? I. Evidence from adult morphology. Contributions to Zoology, 67(2), 79–123.
  3. Wolfe, J. M., Luque, J., & Bracken-Grissom, H. D. (2021). How to become a crab: Phenotypic constraints on a recurring body plan. BioEssays, 43(5), Article 2100020. https://doi.org/10.1002/bies.202100020

Efficacy of Neoantigen Vaccines against Triple Negative Breast Cancer

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Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer because of its high risk of recurrence and limited treatment options. Unlike other breast cancer types, TNBC lacks three key molecular markers—estrogen receptor (ER), progesterone receptor (PR), and HER2—which are commonly targeted in standard therapies. As a result, patients are largely limited to chemotherapy, the current standard of care. Even then, outcomes remain poor: only about 20% of patients achieve a complete response, and those who do not face a significantly higher risk of recurrence and mortality (Nedeljković & Damjanović, 2019). 

A promising new approach aims to overcome this limitation by turning the patient’s own tumor into a therapeutic target. While the concept of neoantigen mutation vaccines has existed for roughly 10-15 years and has been tested on cancers such as melanoma, vaccine efficacy against breast cancer is understudied. The paper “Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC” by Ugur Sahin et. al, aims to understand whether personalized neoantigen mRNA vaccines could generate strong and lasting immune responses specifically in patients with TNBC. These vaccines are designed using the unique genetic mutations found in an individual’s tumor, offering a highly tailored form of immunotherapy.

The concept hinges on neoantigens—mutated protein fragments that arise from cancer-specific DNA changes. Because these mutations are not found in normal cells, neoantigens are recognized as foreign by the immune system, making them ideal targets for immune attack. However, identifying which mutations will actually provoke a strong immune response is a major challenge, requiring sophisticated computational tools to predict which neoantigens are most likely to be effective.

In this study, 14 patients with TNBC who had already completed standard treatments—but remained at high risk of recurrence—were enrolled. For each patient, both tumor tissue and normal tissue were collected. Researchers then sequenced the tissue using Next Generation Sequencing (NGS). Next Generation Sequencing uses imaging to track fluorescently labeled nucleotides. The raw data is then processed by high powered computing software to align sequences to a reference genome. This process is much more cost and time efficient than alternative methods such as Sanger sequencing which can only handle smaller reading frames. The exact software was not specified by the study but some popular platforms are Integrative Genomics Viewer (IGV), used for the visualization and Illumina Connected Analytics, used to identify nucleotide discrepancies.

Figure 1. Stages of Illumina Next Generation Sequencing Technology. https://www.mdpi.com/2076-2607/10/9/1815

By highlighting genome misalignments, NGS aided researchers in identifying mutations unique to each patient’s tumor. From these mutations a  select subset were chosen as vaccine targets based on their predicted ability to generate strong immune responses. Selected mutations were encoded into a personalized mRNA vaccine, with each vaccine containing instructions for up to 20 different neoantigens.

Figure 2. Workflow of individual vaccine development. Includes above mentioned NGS in Step 2. https://doi.org/10.1038/s41573-021-00387-y.

The mRNA design itself was carefully optimized. Structural features such as the 5′ cap, 3′ tail, and poly(A) sequence were modified to improve stability and enhance protein translation within immune cells. Once administered, the mRNA is taken up by dendritic cells, specialized immune cells that act as messengers. These cells translate the mRNA into protein fragments and present them to T cells, effectively “teaching” the immune system what to attack.

Figure 3. Activation of CD8+ T cells through binding with antigen presented on MHC I. https://www.mdpi.com/1422-0067/26/22/10988.

Importantly, the vaccine platform does more than simply deliver antigens, it also stimulates the immune system directly. The RNA–lipoplex (RNA–LPX) technology uses uridine-containing mRNA that activates Toll-like receptors (TLRs), proteins that normally detect viral infections. This triggers a type I interferon response, an early antiviral defense mechanism. By mimicking a viral infection, the vaccine creates a strong activation signal alongside antigen presentation, leading to a powerful expansion of antigen-specific T cells, particularly CD8⁺ T cells, which are responsible for killing cancer cells.

Figure 4. Type 1 interferon response through the use of RNA lipoplex technology. https://www.sciencedirect.com/science/article/pii/S1525001623006019#fig1.

Patients received their personalized vaccines approximately one year after completing chemotherapy and the average time to develop a vaccine was sixty-nine days. The full treatment consisted of eight doses. Doses were given weekly for the first six weeks and the last two were administered biweekly. The entire treatment period lasted 64 days. Researchers monitored immune responses by measuring CD4⁺ and CD8⁺ T-cell activity before vaccination and starting 7-14 days after the final dose. Specifically, T-cell activation was measured using assays such as IFNγ ELISpot and flow cytometry, which together show whether immune cells respond to tumor neoantigens. The IFNγ ELISpot assay works by detecting individual T cells that release interferon gamma (IFNγ) when exposed to vaccine-matched peptides; each signal corresponds to a single activated T cell, so the number of “spots” reflects the strength of the immune response. Flow cytometry complements this by labeling cells with fluorescent markers and passing them through a laser-based detector, allowing researchers to identify which T-cell populations (such as CD4⁺ or CD8⁺ T cells) are activated and whether they are producing cytokines after stimulation. Patient immune system responses were tracked all the way until six years following their treatment. 

The results were striking. All 14 patients developed immune responses against at least one of their tumor-specific neoantigens. More than half of these responses were de novo, meaning they were newly generated by the vaccine rather than expansions of pre-existing immune cells. This finding is especially important, as it demonstrates that the vaccine can actively overcome the immune system’s natural tolerance to cancer by eliminating cancer completely. 

In addition to generating new responses, the vaccines produced broad and multi-targeted immunity. Because each vaccine encoded multiple neoantigens, the immune system was trained to recognize several tumor-specific targets simultaneously. This reduces the likelihood that cancer cells can evade detection by mutating a single antigen. Even more encouraging, these T-cell responses were shown to be durable, persisting for months to years after vaccination. Such long-term immune activity raises the possibility of sustained protection against cancer recurrence.

The treatment was also well tolerated. The most commonly reported side effects—headache, fatigue, nausea, and chills—occurred within one to three days after vaccination and were generally mild. No severe adverse effects were reported, suggesting that the therapy is not only effective at stimulating the immune system but also safe for patients.

Overall, these findings suggest that personalized neoantigen mRNA vaccines can transform tumors that are typically “invisible” to the immune system into clear targets for attack. By inducing strong, multi-target, and long-lasting T-cell responses, this approach addresses several key challenges in cancer immunotherapy. It also highlights the evolving role of computational biology in medicine, as predicting effective neoantigens is essential to the success of these vaccines.

While the results are promising, important limitations remain. The study involved a small cohort of just 14 patients and did not include a large randomized control group. Additionally, while immune responses were robust, longer-term clinical outcomes such as recurrence rates and overall survival require further investigation. The process of designing and manufacturing personalized vaccines is also time-intensive and costly, though advances in technology may help streamline these steps in the future.

Nevertheless, this study represents a significant step forward. It demonstrates that individualized mRNA vaccines are not only feasible but also capable of generating meaningful immune responses in patients with difficult-to-treat cancers like TNBC. As larger clinical trials are conducted and the technology continues to improve, personalized cancer vaccines may become a powerful new tool—one that turns each patient’s unique tumor biology into a blueprint for their own cure.

 

References:

Illumina. 2022. Sequencing Technology | Sequencing by synthesis. www.illuminacom. https://www.illumina.com/science/technology/next-generation-sequencing/sequencing-technology.html.

Malla R, Srilatha Mundla, Farran B, Ganji Purnachandra Nagaraju. 2024. mRNA vaccines and their delivery strategies: A journey from infectious diseases to cancer. Molecular therapy. 32(1):13–31. doi:https://doi.org/10.1016/j.ymthe.2023.10.024.

Nedeljković M, Damjanović A. 2019. Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge. Cells. 8(9):957. doi:https://doi.org/10.3390/cells8090957.

Sahin, U., Schmidt, M., Derhovanessian, E. et al. Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC. Nature 651, 1088–1096 (2026). https://doi.org/10.1038/s41586-025-10004-2

New developments in understanding plankton transport

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By definition, plankton are small organisms that predominantly drift along with ocean currents. They typically swim slowly in relation to ocean currents. Plankton have been shown to exhibit gyrotaxis, which is directed locomotion to balance gravity and viscous torques, to passively alter their movements (Kessler, 1985). When performing this response, plankton experience net flow even in turbulence with no net flow by preferentially sampling turbulence fluctuations. In contrast to this original method of transport, Dibenedetto et al. theorized that plankton “surf” ocean currents by sensing and reorienting in response to the velocity gradient, doubling their net speed in turbulence (2025). 

In their experiment, Dibenedetto et al. studied Crepidula fornicata, which are slipper snails with approximately spherical planktonic larvae that use cilia for movement. They tend to swim upwards to prevent sinking because their bottom-heaviness makes them negatively buoyant. Both early-stage (2 day-old) and late-stage (12 day-old) larvae were observed in a jet-stirred turbulence tank in a random order of low, medium, and high turbulence. They found that C. fornicata actively rotate to oppose local vorticity, or fluid rotation, contrasting with the typical passive response that is assumed (Vorticity – an Overview | ScienceDirect Topics, n.d.). They then compared these results to simulations of passive gyrotaxis, which is characterized by a reduction in upward swimming, and active surfing, which is characterized by an increased rate in upward swimming, because these methods cannot be isolated experimentally. They again found that C. fornicata behavior more closely aligns with surfing (DiBenedetto et al., 2025).

Figure 1: Larval response to instantaneous vorticity in early-stage larvae (A), late-stage larvae (B), and simulation (C) at various turbulence levels.

Dibenedetto et al. found a strong anti-correlation between plankton horizontal relative velocity and fluid vorticity in both age stages at all levels of turbulence (Figure 1). This is consistent with active surfing behavior because the flow’s vorticity and gravitational torque would tilt larvae counterclockwise due to their bottom-heaviness, but they actively resisted these forces and instead tilted clockwise. This behavior was more consistent in late-stage larvae. Furthermore, their velocity more closely resembles that of surfing rather than gyrotaxis in the simulation.

Figure 2: Velocity sampling of early-stage and late-stage larvae at various dissipation rates.

Additionally, they found that late-stage larvae preferentially sampled upwelling vertical velocities relative to mean fluid velocity (Figure 2). This was especially prevalent in higher turbulence levels. Early-stage larvae did not exhibit this behavior, indicating that they are not as skilled at surfing as late-stage larvae. Overall, this study found that passive reorientation models to describe plankton response to turbulence are often insufficient, as active surfing was exhibited in C. fornicata to increase the speed of their upward transport. Further research on the interplay between passive and active responses to turbulence is necessary to fully understand plankton transport. Plankton transport is valuable in allowing for the dispersal of planktonic larvae and supporting global marine food webs, as many organisms rely on consuming plankton for energy.

References

DiBenedetto, M. H., Monthiller, R., Eloy, C., & Mullineaux, L. S. (2025). Plankton active response to turbulence enables efficient transport. Journal of Experimental Biology, 228(24), jeb251123. https://doi.org/10.1242/jeb.251123 

Kessler, J. O. (1985). Hydrodynamic focusing of motile algal cells. Nature, 313(5999), 218–220. https://doi.org/10.1038/313218a0 

Vorticity—An overview | ScienceDirect Topics. (n.d.). Retrieved February 22, 2026, from https://www.sciencedirect.com/topics/physics-and-astronomy/vorticity 

From Pack to Patient: Improvising Stability in the Backcountry

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In remote and wilderness environments, injuries that are manageable in hospitals can quickly become life-threatening due to delayed access to medical care. Femur fractures are particularly dangerous because they cause severe pain and often substantial internal blood loss. Without rapid stabilization, patients may experience shock before reaching definitive treatment (Broken Femur). Considering that evacuation from remote areas may take hours or even days, effective field stabilization is critical.

In modern emergency medicine, traction splints are commonly used to stabilize femoral fractures during transport. These devices apply longitudinal traction to the injured leg, helping align bone fragments. By maintaining proper alignment, traction splints can reduce pain and limit additional bleeding, making them part of the pre-hospital care toolkit.

In wilderness settings, however, rescuers and outdoor travelers often lack access to specialized medical equipment. As a result, wilderness medicine training frequently teaches practitioners how to construct improvised traction splints using available materials, such as sticks or clothing. 

wilderness traction splint showing the lower leg
Stick to It: Mastering the Art of Improvised Splint Techniques. Retrieved May 3, 2026, from https://www.sixptsurvival.com/post/stick-to-it-mastering-the-art-of-improvised-splint-techniques

Despite their widespread use in training, surprisingly little empirical research has evaluated the effectiveness of traction splints in prehospital care. Even fewer studies have examined whether improvised traction splints can generate adequate traction or provide stability comparable to commercially manufactured devices (Weichenthal et al., 2012). This lack of evidence raises an important question for wilderness medicine practitioners: can improvised traction splints function as reliable alternatives when commercial equipment is unavailable?

To address this question, Weichenthal and colleagues conducted a pilot study comparing an improvised traction splint with three commercially available devices. The researchers designed a prospective randomized crossover study involving 10 healthy volunteers. Each participant tested all four splints, allowing the researchers to directly compare device performance.

Participants were placed in four traction splints in randomized order: the Hare traction splint, the Sager splint, the Faretech CT-EMS splint, and an improvised traction splint constructed using standard wilderness first aid techniques. Each device remained in place for 30 minutes before measurements were taken.

Three types of femur traction splints
Three types of traction splints were used as comparisons for the improvised traction splint. Illustration by Martina Toganto Guaqueta

The primary outcome measured in the study was the amount of traction force generated after 30 minutes. Traction force was measured in pounds to determine whether each splint produced clinically appropriate levels of traction. Researchers also assessed outcomes related to patient experience. After each trial, participants rated the comfort and stability of the splint on a scale from 1 to 10 and reported any side effects, such as pain or numbness.

The results showed that all four devices generated similar traction forces, ranging from 10.4 to 13.3 pounds. These values fall within the commonly recommended guideline of approximately 10 percent of a patient’s body weight, indicating that each device produced clinically adequate traction (Davis et al., 2026). Importantly, the improvised traction splint performed comparably to the three commercial splints in this primary measure.

Participants’ subjective ratings also showed minimal differences among the devices. Comfort and stability scores were similar across all four splints, suggesting that the improvised splint did not compromise the user experience. Side effects, including mild discomfort and occasional numbness, were reported with every splint tested. However, these effects were not unique to the improvised device; in fact, the improvised splint produced fewer reported side effects than some commercial splints.

Although these findings suggest that improvised traction splints may be effective, several limitations must be considered. First, the study included only 10 participants, limiting the statistical power and generalizability of the results. Larger studies would be needed to confirm these findings. Additionally, the participants were healthy volunteers rather than patients with actual femur fractures. In real injuries, pain, swelling, and muscle spasms could influence both splint performance and patient comfort. The study was also conducted in a controlled environment, not during an actual wilderness scenario. In practice, splints may remain in place for extended periods while patients are transported across uneven terrain or exposed to harsh environmental conditions. These factors could affect how effective the improvised devices are.

Despite these limitations, the study provides preliminary evidence that improvised traction splints can generate traction comparable to commercial devices while maintaining similar levels of comfort and stability. In the back country, where access to specialized equipment may be limited, the ability to improvise effective stabilization methods is an essential skill. Further research involving patients with actual femur fractures, larger participant groups, and real evacuation scenarios would help clarify the clinical effectiveness of improvised traction splints. Nevertheless, this pilot study suggests that when commercial devices are unavailable, improvised traction splints may serve as a practical and potentially effective tool for stabilizing femur fractures in wilderness settings.

 

This article is based on Lori Weichenthal’s Improvised Traction Splints: A Wilderness Medicine Tool or Hindrance?. 

 

References:

Broken Femur: Causes, Symptoms, and Treatment. (n.d.). Cleveland Clinic. Retrieved May 3, 2026, from https://my.clevelandclinic.org/health/diseases/22299-broken-femur

Davis, D. D., Ginglen, J. G., Kwon, Y. H., & Kahwaji, C. I. (2026). EMS Traction Splint. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK507842/

Stick to It: Mastering the Art of Improvised Splint Techniques. (n.d.). Retrieved May 3, 2026, from https://www.sixptsurvival.com/post/stick-to-it-mastering-the-art-of-improvised-splint-techniques

Weichenthal, L., Spano, S., Horan, B., & Miss, J. (2012). Improvised Traction Splints: A Wilderness Medicine Tool or Hindrance? Wilderness & Environmental Medicine, 23(1), 61–64. https://doi.org/10.1016/j.wem.2011.12.005

 

An Eight-Week Shot at Equality: Advancing Male Hormonal Contraceptives

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For decades, contraceptive responsibility has largely fallen on women. While multiple hormonal birth control methods exist for females, options for men remain limited to condoms or vasectomy. With vasectomy being considered a more permanent choice, the tubes are charged with moving the sperm from the testes to the head of the penis.  This imbalance has prompted researchers to explore hormonal contraceptives for men that temporarily suppress sperm production without permanently affecting fertility. One promising approach involves injectable hormone combinations that can reduce sperm counts while maintaining normal hormone levels in the body.

Male hormonal contraceptives work by disrupting the hormonal signals that regulate sperm production. Under normal conditions, the hypothalamus and pituitary release luteinizing hormone (LH)(What Is Luteinizing Hormone?) and follicle-stimulating hormone (FSH) (Follicle-Stimulating Hormone (FSH): What It Is & Function), which stimulate the testes to produce testosterone and sperm. Introducing external hormones interferes with this process through negative feedback. The higher levels of hormones inhibit further production.  Gu et al. , used testosterone undecanoate (TU), a long-acting form of testosterone, together with depot medroxyprogesterone acetate (DMPA), a progestin that further suppresses gonadotropin production. The DMPA is the same hormone found in the commonly used female contraceptive known as the depot shot (Depot Medroxyprogesterone Acetate and Bone Effects). This dual-hormone strategy reduces sperm production while maintaining circulating testosterone levels necessary for normal male physiology. 

Gu et al. investigated whether combining TU and DMPA could provide an effective injectable contraceptive. Their Phase I open-label clinical trial included 30 healthy Chinese men, divided into three treatment groups: TU alone, TU with a low dose of DMPA, and TU with a higher dose of DMPA. The study took place over an eight-week baseline period, followed by 24 weeks of hormone treatment, and finally a 24-week recovery phase after treatment ended. During this time, researchers monitored sperm counts and hormone levels to assess both effectiveness and safety. 

To evaluate whether the treatment could function as a contraceptive, researchers monitored sperm concentration for slightly over a year. Azoospermia refers to the complete absence of sperm in semen, while severe oligozoospermia describes extremely low sperm counts. Both conditions significantly reduce the likelihood of fertilization and are commonly used as indicators of contraceptive effectiveness. 

The results showed that the combination of TU and DMPA suppressed sperm production more effectively than testosterone alone. Nearly all participants receiving the dual-hormone regimen reached azoospermia or severe oligozoospermia, while two individuals in the TU-only group experienced a rebound in sperm concentration. Importantly, sperm production returned to normal levels during the recovery phase, suggesting that the contraceptive effect was reversible. 

These findings support the growing interest in dual-hormone male contraceptive strategies, mirroring the already existing female contraceptives. By combining an androgen with a progestin, researchers were able to suppress sperm production more consistently than with testosterone alone. The eight-week injection interval may also make this approach practical, as longer dosing intervals are generally easier for patients to maintain.

However, several limitations remain. The small sample size restricts the ability to generalize the results, and the relatively short duration prevents researchers from fully evaluating long-term safety. The study also did not track pregnancy outcomes directly, and instead relied on sperm counts as a proxy for contraceptive effectiveness. Additionally, because the participants were drawn from a single demographic group, hormonal responses may differ in more diverse populations. 

Despite these limitations, the study represents an important step toward expanding male contraceptive options. A reliable injectable contraceptive lasting several weeks could help shift contraceptive responsibility toward a more equitable model of family planning. Consequent research will likely focus on larger clinical trials, optimizing hormone dosages, and testing alternative progestins to further improve effectiveness and acceptability.

Ultimately, advances in male hormonal contraception could transform how couples approach birth control. By providing men with a safe and reversible contraceptive option, these approaches may move reproductive decision-making toward a more shared responsibility.

 

This article is based on Yi-qun Gu’s Male Hormonal Contraception: Effects of Injections of Testosterone Undecanoate and Depot Medroxyprogesterone Acetate at Eight-Week Intervals in Chinese Men. 

 

References:

BuzzRx. (2022, November 28). How Would Male Birth Control Work? [Post]. buzzrx.com. (How Would Male Birth Control Work?). BuzzRx. https://www.buzzrx.com/blog/how-would-male-birth-control-work

Depot Medroxyprogesterone Acetate and Bone Effects. (n.d.). Retrieved May 3, 2026, from https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/06/depot-medroxyprogesterone-acetate-and-bone-effects

Follicle-Stimulating Hormone (FSH): What It Is & Function. (n.d.). Retrieved May 3, 2026, from https://my.clevelandclinic.org/health/articles/24638-follicle-stimulating-hormone-fsh

Gu, Y., Tong, J., Ma, D., Wang, X., Yuan, D., Tang, W., & Bremner, W. J. (2004). Male Hormonal Contraception: Effects of Injections of Testosterone Undecanoate and Depot Medroxyprogesterone Acetate at Eight-Week Intervals in Chinese Men. The Journal of Clinical Endocrinology & Metabolism, 89(5), 2254–2262. https://doi.org/10.1210/jc.2003-031307

What Is Luteinizing Hormone? (n.d.). Cleveland Clinic. Retrieved May 3, 2026, from https://my.clevelandclinic.org/health/body/22255-luteinizing-hormone

Rethinking Fluids in Pediatric Septic Shock: Early Adrenaline Instead of More Fluid

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Septic shock is a severe complication of infection in which the body’s immune response becomes dysregulated. Those in septic shock experience impaired circulation, poor tissue perfusion, and ultimately organ dysfunction (What Is Septic Shock?). In pediatric patients, septic shock remains a major cause of critical illness, with mortality rates estimated between 17–32%. Pediatric cases often present differently from adult cases, most notably, children decompensate very fast and have a “cold shock” presentation. This means that rather than the vasodilation characteristic of “warm shock,” they experience low cardiac output and high vascular resistance. Essentially, children will appear stable, then quickly nosedive (Condition Topics). 

To improve oxygen delivery to tissues and restore circulating blood volume, current treatment guidelines advocate rapid fluid resuscitation with 40–60 mL/kg of intravenous fluids in the first hour of sepsis and treatment. Interestingly, there is little evidence to support this guideline, and growing observational data indicate that excessive fluid administration may worsen outcomes, including increased mortality and the need for respiratory assistance. The guideline itself is based on an adult model; however, it does not translate to a pediatric situation. Alternative resuscitation techniques are becoming more popular as a result of these worries, especially if starting vasoactive drugs earlier could lessen the requirement for large fluid quantities while preserving hemodynamic stability. Hemodynamic stability refers to stable blood pressure, flow, and adequate oxygen delivery. 

To investigate whether earlier initiation of vasoactive support could reduce fluid exposure in pediatric septic shock, Harley et al. conducted the Resuscitation in Pediatric Sepsis Randomized Controlled Pilot Platform Study in the Emergency Department  (RESPOND ED). This was an open-label, randomized controlled study in four pediatric emergency departments throughout Australia. The trial was made up of  40 children with septic shock, ranging from 28 days to 18 years. 

Children in the early-adrenaline group received an initial 20 mL/kg fluid bolus followed by early initiation of adrenaline. On the other hand, the standard-care group received 40–60 mL/kg of fluid resuscitation before administering medications that force the heart to contract (inotropes), consistent with current guidelines. A fluid bolus is the rapid administration of intravenous fluids. The primary aim of the study was to evaluate the feasibility of future related studies, while an exploratory outcome measured 28-day survival free of organ dysfunction.

This study demonstrated that the protocol was feasible. Adrenaline was given significantly earlier in the intervention group (~16 minutes) compared with the standard-care group (~49 minutes), which resulted in reduced fluid exposure. The early-adrenaline group received no additional fluid beyond the initial amount administered, while the standard-care group received around 20 mL/kg more fluid within the first 24 hours. 

Clinical outcomes were similar between groups, with no mortality observed, comparable organ dysfunction–free days, and similar pediatric intensive care unit (PICU) admission rates and length of stay. Importantly, the intervention appeared safe, with no serious adverse events, such as extravasation injuries or limb ischemia associated. These circulation-based conditions are common side effects of peripheral adrenaline administration.

The RESPOND ED pilot trial demonstrates that an early-adrenaline, fluid-sparing resuscitation strategy is feasible and safe in pediatric emergency departments. While the study was not made to detect differences in mortality or major clinical outcomes, it showed that clinicians can successfully initiate vasoactive support earlier and reduce overall fluid exposure without increasing adverse events. These findings challenge the long-standing fluid-first treatment approach and suggest that earlier hemodynamic support may be a viable alternative approach. Future research will need to build on these results through larger trials, optimized dosing strategies, and broader patient populations to better determine whether early vasoactive therapy can improve outcomes and better define treatment guidelines for pediatric septic shock.

 

This article was based on Amanda Harley’s Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED): Study Protocol and Analysis Plan. 

 

References 

Condition Topics. (n.d.). Yale Medicine. Retrieved May 3, 2026, from https://www.yalemedicine.org/conditions

Harley, A., George, S., King, M., Phillips, N., Keijzers, G., Long, D., Gibbons, K., Bellomo, R., & Schlapbach, L. J. (2021). Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED): Study Protocol and Analysis Plan. Frontiers in Pediatrics, 9, 663028. https://doi.org/10.3389/fped.2021.663028

What Is Septic Shock? (n.d.). Cleveland Clinic. Retrieved May 3, 2026, from https://my.clevelandclinic.org/health/diseases/23255-septic-shock

LiNx: A Dual-Pronged Approach to Cancer Immunotherapy

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mRNA vaccines have emerged from the COVID-19 pandemic as a promising approach to fighting infectious diseases (Kutikuppala et al. 2024). Different from traditional vaccines, which use a weakened version of a virus, mRNA vaccines deliver an mRNA corresponding to a protein on the surface of the virus. This mRNA allows our immune system to recognize and make small parts of the virus so that it can create antibodies to combat it (Cleveland Clinic 2024). However, mRNA is an unstable and negatively charged molecule, so it must be encased with some type of transport protection to prevent its degradation during delivery (Kutikuppala et al. 2024).

Lipid nanoparticles, or LNPs, have gained popularity in recent years as an effective delivery platform for mRNA vaccines due to their highly tunable composition and their ability to prevent nucleic acid degradation (Xu et al., 2025). One popular example is the utilization of LNPs in the Moderna mRNA-1273 COVID vaccine, where mRNA encoding the protein on the outside of the virus that is recognized by the immune system was encapsulated in an LNP. Vaccination with this LNP-encapsulated mRNA resulted in 90% lower risk of contracting COVID within 21 days for those over the age of 16, demonstrating the power and possibility of this technology (Noor, 2021).

LNPs are extremely small particles composed of: 1) ionizable lipids, which act as a case for the nucleic acid being delivered; 2) phospholipids regulating cell membrane fusion; 3) PEG-lipids and 4) cholesterol which both affect its size and stability (Figure 1) (Xu et al., 2025). An LNP’s formulation can have substantial effects on its ability to avoid cellular barriers for vaccine mRNA entry to a targeted area. For example, degradation of LNPs by enzymes and/or other immune cells after entering the body can affect a vaccine’s ability to reach the targeted tissue (Hou et al., 2021). This is especially critical for scientists working on immunotherapies, as a variation in lipid composition can determine whether the LNP will be taken up by immune cells like dendritic cells or other antigen-presenting cells, which present the LNP to other immune cells and start the immune response (Hou et al., 2021). 

 

Figure showing the composition of LNPs. Phospholipid bilayer with cholesterol surrounds the LNP, which contains nucleic acid encapsulated within ionizable lipids
Figure 1. Composition of lipid nanoparticles. Adapted from 2025 Xu et al.

Hydrogels have also been utilized by scientists as vaccine carriers that can also augment immune responses. Hydrogels are natural or synthetic materials containing a 3D network of cross-linked polymer chains that allow them to absorb large amounts of a target substance (Ho et al. 2022). Depending on the composition of the hydrogel, scientists have found evidence of greatly increased immune cell recruitment and prolonged immune memory in mouse models of melanoma after a hydrogel-based vaccine was delivered (Kerr et al., 2023; Pal et al., 2024). In other words, the immune response was stronger and also more effective upon encountering a pathogen a second time. Therefore, if a hydrogel were to be used to deliver an LNP, finding the right composition is extremely important, as it can greatly impact its efficacy.

In their paper, Zhu et al. report the effectiveness of LiNx, a nanofiber-hydrogel composite (NHC) mRNA LNP matrix, in tumor and melanoma mouse models. Essentially, they embedded their LNPs within the 3D network of extremely small and cross-linked fibers in a hydrogel to significantly boost the immune response to cancer. 

LiNx works as a subcutaneous injection combining the potent immune activation capability of LNPs with the immunostimulatory microenvironment provided by the NHC. While the NHC recruits immune cells to the injection site and promotes immune cell signaling, the LNPs introduce nearby cells to the encapsulated mRNA, resulting in a coordinated adaptive immune response (Figure 2).

Diagram showing LiNx mechanism. It's delivered into the body, transfects non-APCs, enters an APC and is processed and presented through MHC1 or MHC2 pathways
Figure 2. Diagram of LiNx mechanism. (1) LiNx is delivered into the body and (2) transfects non-antigen-presenting cells. (3) The LNP enters an antigen-presenting cell, and the mRNA within is processed and presented through (4) two different pathways. Adapted from 2025 Zhu et al.

The lipid composition of LNPs can affect not only their size and stability, but also their transfection and delivery efficacy, or their ability to deliver the vaccine mRNA into host cells like dendritic cells (which start the immune response). To identify the top-performing LNP formulations, the researchers screened over one thousand different lipid compositions. Three top-performing LNP formulations were identified based on their transfection efficiency in bone marrow-derived dendritic cells: C10, D6, and F5. All of these formulations also separately activated powerful Th1 responses, a type of immune response meant to eliminate bacteria, viruses, and cancer cells, after three doses of subcutaneous injections.  

To simply quantify the host cell recruitment and transfection profile of the three different formulations, the researchers injected LiNx containing C10, D6, or F5 LNP into mice and measured the present immune cells 3 and 7 days post-injection. At both 3 and 7 days post-injection, a considerable amount of host cells were found in the NHC scaffold for all three formulations. The D6 formulation showed the greatest host cell recruitment, having a 12.6-fold increase compared to the control.

The researchers then performed a similar experiment, injecting mice with LiNx loaded with a test mRNA to get a better idea of the performance of each formulation compared to each other. They found that 10 days after injection, the D6 formulation contained over one-hundred-fold more transfected cells than C10 and F5-mRNA LiNx. Fourteen days post-injection, the D6-mRNA LiNx was also found to have recruited a more diverse range of immune cells associated with robust and specific immune responses like T cells and B cells. On the other hand, the C10 and F5-mRNA LiNx recruited more immune cells associated with general immune responses, like neutrophils. This shows that the D6-mRNA LiNx induces a stronger and more customized immune response. Additionally, three months post-vaccination, there were 10x more central memory T cells present in the spleens of D6-mRNA mice compared to the control and other formulations, indicating a stronger long-term memory response. These results suggest that the D6 LiNx is the most efficient LiNx formulation. 

Having characterized the immune activation induced by D6-mRNA LiNx, the researchers then tested its effectiveness in cancer mouse models. Mice were inoculated with colorectal cancer cells and received vaccinations of one of the LiNx formulations four days later. These mice were administered the vaccines in a single dose, while a separate control group received three doses of only D6 LNPs. The negative control group received only the NHC and protein without the LNP. The median survival time of the single-dose D6 LiNx mice was 75 days compared to 31 days for the negative control group and 37.5 days for the three-dose group, underscoring a heightened tumor suppression response. Fifty percent of these mice remained tumor-free after 100 days. This experiment demonstrated LiNx’s anti-cancer potential in vivo. 

In their paper, Zhu et al. demonstrated the effectiveness of a dual-modal approach to cancer immunotherapy. Through the combination of lipid nanoparticle mRNA delivery and a hydrogel microenvironment, they were able to induce a substantially stronger immune response characterized by tumor suppression and long-term immune memory in mouse models. The superior performance of a singular dose of D6 LiNx compared to three LNP doses illustrates the promise found in combining delivery methods with immune-boosting materials for the future development of stronger and longer-lasting cancer immunotherapies.

 

References:

Ho T-C et al. 2022. Hydrogels: Properties and Applications in Biomedicine. Molecules. 27(9):2902. 

Hou X, Zaks T, Langer R, Dong Y. 2021. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 6(12):1078–1094. 

Kerr MD et al. 2023. Biodegradable scaffolds for enhancing vaccine delivery. Bioeng Transl Med. 8(6):e10591. 

Kutikuppala LVS et al. 2024. Prospects and Challenges in Developing mRNA Vaccines for Infectious Diseases and Oncogenic Viruses. Med Sci (Basel). 12(2):28. 

mRNA Vaccines: What They Are & How They Work. 2024. Cleveland Clinic; [accessed 2026 May 2]. https://my.clevelandclinic.org/health/treatments/21898-mrna-vaccines

Noor R. 2021. Developmental Status of the Potential Vaccines for the Mitigation of the COVID-19 Pandemic and a Focus on the Effectiveness of the Pfizer-BioNTech and Moderna mRNA Vaccines. Curr Clin Microbiol Rep. 8(3):178–185. 

Pal S et al. 2024. Extracellular Matrix Scaffold-Assisted Tumor Vaccines Induce Tumor Regression and Long-Term Immune Memory. Adv Mater. 36(15):e2309843. 

Xu S et al. 2025. Lipid nanoparticles: Composition, formulation, and application. Mol Ther Methods Clin Dev. 33(2):101463. 

Zhu Y et al. 2025. An mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy. Nat Commun. 16(1):5707. 






Epigenetic Signatures of Intergenerational Trauma in Three Generations of Syrian Refugees

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The effects of traumatic experiences are known to have various consequences on a person’s life. However, what is less commonly studied is the impact of maternal traumatic experiences or maternal stress on future generations. A recent 2025 study “Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees” conducted by Connie J. Mulligan et al. looks at maternal trauma, stress, and exposure to violence in three generations of Syrian mothers to study the epigenetic impact of violence on future offspring. Mothers exposed to traumatic violence while pregnant have the potential to genetically impact offspring through epigenetic modification. This type of genetic modification causes changes to cellular gene expression through the mechanism of DNA methylation (DNAm), which refers to the addition of a methyl group to a DNA sequence. For instance, DNAm plays a role in cellular differentiation and development, so that the function of cells is determined. This means that even though all your cells have the same genes, different expression in each cell means that you can have muscle cells and nerve cells (Centers for Disease Control and Prevention 2025). Relating to pregnancy, when a pregnant mother is lacking in nutrients, their baby could have different levels of DNAm, which could explain why they had an increased likelihood for certain diseases (Centers for Disease Control and Prevention 2025). Epigenetic modification can lead to increases or decreases in gene expression, which suggests that DNAm plays a role in controlling the impact of maternal trauma in offspring health outcomes.

In this study, maternal trauma is considered to be violent experiences that include being beaten, seeing someone else be beaten, shot, or killed. Additionally, maternal stressors include nutritional deficiencies, exposure to toxins, and psychosocial stressors like anxiety or trauma. These stressors can be transmitted from mother to offspring through cellular changes in the maternal and fetal stress response system, known as the HPA axes, and glucocorticoid metabolism, which allows the body to maintain and regulate stress hormones. The transmission of these stressors are associated with changes in newborn gene expression and epigenetic age acceleration or worse health outcomes. A developing fetus is characterized by high phenotypic plasticity, meaning that their genes are likely to produce different phenotypes, or physical characteristics determined by genetics, as a result of environmental factors. This allows a fetus to use environmental cues to determine an optimal phenotype to survive the postnatal environment, particularly if the mother is experiencing trauma or stressors.

This study specifically used the Developmental Origins of Health and Disease (DOHaD) hypothesis as a framework to look at epigenetic variation as a method of mediating the impact of psychosocial trauma on future generations. The DOHaD hypothesis states that early life adversity has an impact on later health outcomes; for instance, there are strong associations with low birthweight and adverse living conditions with an increased risk of cardiovascular disease in adulthood. This study looked at DNAm signatures of war-related violence across three generations of Syrian refugees by comparing germline, prenatal, and direct exposures to violence. The researchers proposed that there is a presence of differentially methylated positions (DMPs) in DNA that are sensitive to a psychosocial, and therefore violent, environment that are transmissible to future generations. In this study, the researchers propose the hypothesis that exposures to violence can lead to intergenerational epigenetic marks.

This study samples three groups of three-generation Syrian families with varying exposures to violence (Fig. 1). This study defined the exposure groups by using the regional conflicts of the Hama city massacre in 1980 and the Syrian uprising and armed conflicts beginning in 2011. The participants in this study were recruited in Jordan by snowball sampling, which is a method where research participants help researchers in finding other subjects (Oregon State University 2010). The Syrian women who participated had experienced violence and were pregnant during the 1980 or 2011 conflicts before fleeing to Jordan. Syrian families who moved to Jordan before 1980 and had not experienced exposure to violence were used as the control group.

Figure 1. Three groups of three-generation Syrian families with direct, prenatal, and germline exposure to violence. The control group is unexposed to violence. The direct exposure group refers to pregnant mothers who directly experienced the traumatic violence. In the 1980 group, the grandmothers were directly exposed to violence. In the 2011 group, the mothers and older children directly experienced violence. The prenatal exposure group refers to the fetus that was exposed to maternal stress in the womb as a result of the direct exposure to violence that their mother experienced. In the 1980 group, the prenatally exposed fetus in the F1 generation grew up to become a mother in the F2 generation. In the 2011 group, the prenatally exposed fetus in the F2 generation grew up to be a child in the F3 generation. The germline exposure group refers to a fetus whose mother prenatally experienced the violence, so the affected DNA in their reproductive egg cells were inherited by the fetus. In the 1980 group, the germline exposed fetus in the F2 generation grew up to be a child in the F3 generation.

Survey data and buccal swab samples were collected from the mothers and children for 10 families in the 1980 exposure group, 22 families in the 2011 exposure group and 16 families in the control group. A buccal swab is a method to non-invasively collect DNA from the cells inside of a person’s cheek. The buccal samples were collected using Transport swabs or DNA Buccal Swabs. The survey data consisted of an interview with the mothers and screening for traumatic events experienced by using the Traumatic Events Checklist. The researchers then calculated a trauma events score by counting the number of affirmative answers to the Traumatic Events Checklist. DNA methylation data was collected using a hybridizing technique to measure the genetic similarities between DNA sequences. Sensitivity analyses were used to test the robustness of their results to the distribution of age. Enrichment analysis was used to identify if any biological themes appeared more often than expected by chance, which would indicate what the modified genes would do. In addition, epigenetic age estimation was collected by analyzing DNAm patterns to determine biological age. To determine whether there was a linear relationship between DNAm and the amount of trauma events, DNAm was plotted against the cumulative number of violence trauma events.

This study had a three generation study design, which allowed for the DNAm signatures of various exposures to violence to be compared. The first exposure group was the 1980 group, which consisted of maternal grandmothers who were pregnant daughters (F2 generation) were prenatally exposed to violence and their grandchildren (F3 generation) were germline exposed to war violence. The 2011 exposure group included mothers (F2 generation) who were pregnant before fleeing Syria, so the fetus was prenatally exposed in utero and older children in the family (F3 generation) were directly exposed to violent conflict. The control group included Syrian mothers and grandmothers that lived in Jordan before 1980. 

To generate DNAm data, an epigenome-wide association study (EWAS) was conducted to identify differentially methylated positions (DMPs) that were associated with each exposure to violence. The researchers identified that the final set of 35 DMPs had 14 sites that were associated with germline exposure to violence and 21 sites that were associated with direct exposure to violence. No DMPs were associated with prenatal exposure to violence. Additionally, 32 DMPs had the same directionality (Fig. 2).

 

Forest plots and box plots depicting genome-wide significant differences in site-specific DNAm when comparing violence exposure groups and controls.
Figure 2. Genomic differences in site-specific DNAm when comparing direct exposure groups vs. control, prenatal exposure groups vs. control, and germline exposure groups vs. control. The control group experienced no exposure to violence.

The largest difference in DNAm compared to the control group was at a germline DMP at a site that produces keratin and has a potential role in some cancers. The highest DNAm was observed at the germline DNA and two directly associated DMPs, at a site with proteins that play a role in cell death. The germline-associated DMP showed a statistically significant reduction in DNAm in germline, direct, and prenatally exposed individuals. When the relationship between DNAm and the amount of violent trauma events was looked at, the plot suggested that most DMPs showed a dose-response relationship between DNAm and the amount of trauma events (Fig. 3).

Plots illustrating DNAm levels for individual Trauma Event scores for 14 gremlin exposure DMPs and 21 direct exposure DMPs.
Figure 3. DNAm levels of direct and germline exposure to violence groups compared to control group. This suggests that the number of trauma effects experienced causes shifts in DNAm.

After testing for epigenetic aging, there was a high correlation between epigenetic and chronological age in the study sample. Compared to children, the mothers had a higher variation in epigenetic age compared to chronological age. When analyzing the mothers, there was no significant association between epigenetic age acceleration and trauma exposure. However, when analyzing only the children, prenatal exposure to violence trauma was associated with epigenetic age acceleration.

This study suggests that the impacts of maternal stress and trauma can have effects on future generations through epigenetic mechanisms. The epigenetic marks on the DNA of mothers exposed to traumatic violent experiences, in the form of DNAm and DMPs, found in this study reveal that trauma has an effect on DNA expression. Thirty-two of all DMPs found showed a similar directionality of change in DNAm, which suggests that there is a common epigenetic signature of violence across germline, prenatal, and direct exposures to violence. The epigenetic marks found in this study may contribute to enhanced responses to future stressful experiences, which is also known as epigenetic “priming.” This means that genes are prepared to activate and quickly respond to future environmental cues.

Furthermore, the epigenetic marks could be used as biomarkers to identify individuals who could benefit from intervention programs. This study also identified that there is an association between epigenetic age acceleration and prenatal exposure to violence, which could be correlated with accelerated biological aging and with future health outcomes. For instance, environmental toxins may affect future generations more than those directly exposed (Korolenko et al. 2023).

To further investigate the effects of violence of intergenerational genetic marks, there needs to be research conducted on larger and more diverse population groups. There should also be studies that collect other types of body tissues or blood, since there can be tissue-dependent differences in DNAm. Additionally, it’s important to study other forms of epigenetic modifications, such as histone modifications or non-coding RNAs. This type of research is important because it allows refugees to be better understood and helps address the traumatic issues they face. Understanding the genetic mechanisms underlying trauma can encourage policymakers and humanitarian organizations to provide better resources to refugee populations.

 

 

 

Citations:

Centers for Disease Control and Prevention. 2025. Epigenetics, Health, and Disease. Genomics and Your Health. https://www.cdc.gov/genomics-and-health/epigenetics/index.html.

Korolenko AA, Noll SE, Skinner MK. 2023. Epigenetic Inheritance and Transgenerational Environmental Justice. The Yale Journal of Biology and Medicine. 96(2):241–250. doi:https://doi.org/10.59249/FKWS5176. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303257/.

Mulligan, C.J., Quinn, E.B., Hamadmad, D. et al. Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees. Sci Rep 15, 5945 (2025). https://doi.org/10.1038/s41598-025-89818-z

Oregon State University. 2010. Snowball Sampling | Division of Research and Innovation. Division of Research and Innovation. https://research.oregonstate.edu/ori/irb/policies-and-guidance-investigators/guidance/snowball-sampling.



Infant Development and The Social Sharing of Microbes

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The human digestive tract, which includes the mouth, esophagus, stomach, intestines, anus, and rectum, contains a highly diverse and complex community of microorganisms, known collectively as the gut microbiome. The gut microbiome forms during birth and rapidly evolves throughout infancy. This phase of development is absolutely crucial for the health of the immune system, metabolism, and long-term health outcomes, as it plays a large role in reducing the risk of allergies, diabetes, and many bowel and cardiovascular diseases (Borrego-Ruiz and Borrego, 2025). While it may be tempting to think that the sharing of microbes among infants is a bad thing, this is largely not the case. The microbes that are transmitted in a nursery and other similar environments are mainly non-pathogenic, meaning that they do not cause disease. Many of these microbes are actually beneficial for health, aiding in digestion, immune system development, and more. Typically, the development of the gut microbiome has been thought to be through vertical transmission, where microbes are passed from the mother or other close, immediate family contact, to infants. However, a recent study from Ricci et al. (2026) published in Nature suggests that gut microbiome development through simple vertical transmission serves as an incomplete model. Instead, they suggest that another key process is at play: horizontal transmission. This kind of transmission is the sharing of microbes between unrelated people. In infants, this often occurs in communal environments like nurseries.

Researchers Ricci and colleagues sought to investigate if infants obtained microbes just from their families, or if they acquired them from their peers, especially in a daycare setting. In the study, Ricci et al. analyzed how social interactions influence the human gut microbiome in infants by studying 43 infants in the UK between the ages of four and fifteen months, as well as their parents, siblings, caregivers, and even household pets. These authors analyzed DNA sequences obtained from samples of the stool of these infants over time to gather data about which microbes were present in their gut microbiomes. They analyzed several timepoints, including before and after nursery attendance began. This study design allowed the researchers to effectively track the transmission of microbes between individuals. The DNA sequencing approach taken by this group offered the advantages of more accurate, strain-level identification of microbes and allowed tracking of where certain microbes originated, because they analyzed entire DNA sequences. The alternative to this approach is culturing stool samples, which offers opportunity for additional testing but a severe limitation in that most microbes can not be cultured in a lab (Ricci et al., 2026).

Looking specifically in a daycare setting, the researchers discovered that infants experienced a significant increase in sharing of microbes, indicating that a nursery setting can play an important role in shaping the gut microbiome. This increase in transmission was seen at a much higher rate compared to settings within family-only units, where sharing was relatively stable. These findings indicate that horizontal transmission can be just as important as vertical transmission when it comes to developing and increasing biodiversity of the infant gut microbiome.

But how are microbes transmitted between infants in a nursery environment? It all comes down to proximity and activities. Researchers found increased microbial transmission between infants who spent more time together or had frequent physical contact compared to those that didn’t. Additionally, activities such as playing with the same toys and touching the same surfaces further facilitated microbe exchange. These findings show that exchange of microbes between infants in a nursery is not random, but rather a process that follows a pattern of behavior exhibited by the infants.

On top of understanding that microbial transmission occurs, the study highlighted the individual differences between infants and how they were affected by the conditions in the nursery. The researchers found that infants with siblings had more diverse microbiomes from the start of the study compared to those without, likely due to more microbe exposure at home from siblings. In turn, these infants acquired less new microbe strains, suggesting that previous microbe exposure can influence later development of the microbiome. This highlights the importance of being exposed to a diverse range of microbes as an infant, tying into the hygiene hypothesis, which states that without an early, diverse exposure to microbes, children are more likely to develop allergies and autoimmune diseases (Sironi and Clerici, 2010). Infants who had previously taken antibiotics, and therefore had a lack of diversity in their gut microbiome, experienced a recovery from being in a nursery environment. While the infants did recover fully, they recovered with a different composition of microbes. Through exposure to new strains around them, infants regained microbial diversity, highlighting the adaptability of the infant gut microbiome in the face of disruption. The findings of the study illustrate how the social environments of infants can be crucial in developing a gut microbiome that supports a healthy body.

This study also has its limitations. The number of nurseries was quite small, three to be exact, and researchers did not address the long-term presence of these microbes and their impact on health in the future. As such, because the infants were from a similar region, these findings may not be applicable to other populations who have different environmental and socioeconomic differences. Additionally, possible confounding variables such as diet and broader environmental conditions were not studied. Future research is needed to account for these limitations and progress the body of knowledge on infant horizontal transmission, as well as the microbial composition of infants who do not get placed in daycare or other social settings.

Overall, Ricci et al. (2026) challenge our current understanding of how the human gut microbiome develops. By looking beyond the process of vertical transmission, we learn that the microbiome is also influenced by social interaction, behaviors, and shared environments. Specifically, nursery settings are centers of important microbial exchanges, where infants are constantly exposed to new microbes. The results of this study emphasize that infant social interactions can biologically shape long-term health through development of the gut microbiome.

 

Works Cited

Borrego-Ruiz A, Borrego JJ. 2025. Early-life gut microbiome development and its potential long-term impact on health outcomes. Microbiome Res Rep. 4(2). doi:10.20517/mrr.2024.78. [accessed 2026 May 3]. https://www.oaepublish.com/articles/mrr.2024.78.

Ricci L, Heidrich V, Punčochář M, Armanini F, Ciciani M, Nabinejad A, Fazaeli F, Piperni E, Servais C, Pinto F, et al. 2026. Baby-to-baby strain transmission shapes the developing gut microbiome. Nature. 651(8104):191–200. doi:10.1038/s41586-025-09983-z. [accessed 2026 May 3]. https://www.nature.com/articles/s41586-025-09983-z.

Sironi M, Clerici M. 2010. The hygiene hypothesis: an evolutionary perspective. Microbes and Infection. 12(6):421–427. doi:10.1016/j.micinf.2010.02.002. [accessed 2026 May 3]. https://linkinghub.elsevier.com/retrieve/pii/S128645791000050X.



How Epigenetics Dictates the Birth of New Neurons

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One of the most contentious debates in neuroscience has revolved around the question of whether the adult human brain can produce new neurons. Though there is evidence that rodents maintain a population of immature neurons throughout their lives, confirming this phenomenon in humans is troublesome, namely due to post-mortem tissue degradation and the lack of specific molecular markers. A new study by Disouky et al. (2026), published in Nature, carries out a deep dive into this process. Disouky et al. reveal that the “birth” of new neurons not only occurs in the adult human hippocampus but that its decline in Alzheimer’s disease is dictated by changes in the cell’s epigenetic landscape. In other words, while the sequence of the DNA remains the same, the chemical tags and structural packing of the genome changes, effectively deciding which genes are turned on or off.

To settle the debate, researchers analyzed over 355,000 individual cell nuclei from the hippocampi of young adults, healthy seniors, and people with Alzheimer’s. They discovered a clear assembly line in the brain where starter cells, known as neural stem cells, begin a transformation into neuroblasts. These cells then become Immature Neurons before finally graduating into mature granule neurons that are fully integrated into memory circuits. The team used a predictive calculation called RNA velocity to prove that these cells actually move through these stages, confirming that the adult human brain maintains a pool of neural stem cells. RNA velocity, by taking into account the concentration of various RNA populations, can project the dynamics within the cell (La Manno et al., 2018). In other words, a cell’s stage in development can be determined by what types of RNA it is producing.

The study’s most important discovery involves epigenetics, which dictates how the brain’s internal switches are managed. If DNA is like a massive library of books (genes), then epigenetics determines which books are actually open and readable. The researchers found that in Alzheimer’s disease, the problem isn’t just that cells are dying, but that the books for making new neurons are being slammed shut. This is known as a change in chromatin accessibility (Klemm et al., 2019). In Alzheimer’s patients, the number of immature neurons is slashed significantly compared to healthy individuals. Interestingly, in people with preclinical Alzheimer’s—those with early symptoms of Alzheimer’s—these DNA locks are beginning to appear. So, while the DNA itself remains the same, its expression differs.

A diagram depicting chromatin accessibility from various stages, to closed, permissive, and open domains.
Chromatic accessibility allows for differences in DNA expression without directly altering its genetic sequence. Figure from Klemm et al., 2019

When the authors looked at a third population group known as SuperAgers (SA)—people over 80 years old with the memory capacity of someone in their fifties—they found a distinct profile of neurogenesis, new neuron formation. The brains of SuperAgers contained a significantly greater number of immature neurons compared to those with Alzheimer’s. Even after excluding potential outliers, the researchers observed a 2.5-fold increase in immature neurons in the SuperAger group compared to other cohorts. This suggests there is a “resilience signature” of neurogenesis that may play a role in maintaining exceptional memory capacity despite advanced age. This signature is primarily characterized by maintained chromatin accessibility in regions that are typically “locked” or downregulated in the Alzheimer’s brain.

Ultimately, this research shifts the focus of Alzheimer’s study from simple cell death to the underlying gene regulatory networks that govern how cells function and grow. By identifying the specific “activator” and “repressor” switches (transcription factors) that are active in SuperAgers versus those that are shut down in Alzheimer’s, the study provides a roadmap for future medical interventions. For example, targeting the specific chromatin regions that govern synaptic plasticity could potentially prevent or mitigate the deterioration of neurogenesis seen in dementia. While the study notes limitations due to the high variability of human brain samples and limited sample sizes, the findings highlight the critical role of epigenetics as a more definitive indicator of cognitive health than traditional gene expression alone. This suggests that the future of treating cognitive decline may lie in opening up the brain’s internal library in order to restore its natural ability to regenerate and remember.

 

References

Disouky, A., Sanborn, M. A., Sabitha, K. R., Mostafa, M. M., Ayala, I. A., Bennett, D. A., Lu, Y., Zhou, Y., Keene, C. D., Weintraub, S., Gefen, T., Mesulam, M., Geula, C., Maienschein-Cline, M., Rehman, J., & Lazarov, O. (2026). Human hippocampal neurogenesis in adulthood, ageing and Alzheimer’s disease. Nature, 652(8112), 1264–1273. https://doi.org/10.1038/s41586-026-10169-4

Klemm, S. L., Shipony, Z., & Greenleaf, W. J. (2019). Chromatin accessibility and the regulatory epigenome. Nature Reviews Genetics, 20(4), 207–220. https://doi.org/10.1038/s41576-018-0089-8

La Manno, G., Soldatov, R., Zeisel, A., Braun, E., Hochgerner, H., Petukhov, V., Lidschreiber, K., Kastriti, M. E., Lönnerberg, P., Furlan, A., Fan, J., Borm, L. E., Liu, Z., Van Bruggen, D., Guo, J., He, X., Barker, R., Sundström, E., Castelo-Branco, G., . . . Kharchenko, P. V. (2018). RNA velocity of single cells. Nature, 560(7719), 494–498. https://doi.org/10.1038/s41586-018-0414-6