Biology subjects

Cohen, J. M.

Publications and source records attributed to Cohen, J. M..

6 recordsLinked to original sources

bioRxiv2025

Macromolecular interactions dictate Polycomb-mediated epigenetic repression

The dynamic regulation of epigenetic states relies on complex macromolecular interactions. PRC2, the methyltransferase complex responsible for depositing H3K27me3, interacts with distinct accessory proteins to form the mutually exclusive subcomplexes PHF1-PRC2.1, MTF2-PRC2.1, PHF19-PRC2.1, and PRC2.2. The functions of these subcomplexes are unclear and thought to be highly redundant. Here we show that PRC2 subcomplexes have distinct roles in epigenetic repression of lineage-specific genes and stem cell differentiation. Using a human pluripotent stem cell model, we engineered a comprehensive set of separation-of-function mutants to dissect the roles of individual protein-protein and DNA-protein interactions. Our results show that PRC2.1 and PRC2.2 deposit H3K27me3 locus-specifically, resulting in opposing outcomes in cardiomyocyte differentiation. We find that MTF2 stimulates PRC2.1-mediated repression in stem cells and cardiac differentiation through its interaction with DNA and H3K36me3, while PHF19 antagonizes it. Furthermore, MTF2-PRC2.1 maintains normal cardiomyocyte function. Together, these results reveal the importance and specificity of individual macromolecular interactions in Polycomb-mediated epigenetic repression in human stem cells and differentiation. HighlightsO_LIThe PRC2.1 and PRC2.2 subcomplexes have distinct specificities for H3K27me3 deposition C_LIO_LIThe three PCL accessory proteins have distinct functions in regulating the PRC2 core complex, with MTF2 and PHF19 antagonizing each other C_LIO_LIInteractions between the PCL proteins and the PRC2 core, DNA, and H3K36me3 dictate PRC2 occupancy and activity at developmental genes C_LIO_LIPRC2.1 and PRC2.2 play opposing roles in stem cell cardiomyocyte differentiation C_LIO_LIMTF2 plays key functions in regulating differentiation timing and action potential rhythm in cardiomyocytes C_LI

molecular biology↗

bioRxiv2023

Non-Pyrogenicity and Biocompatibility of Parylene-Coated Magnetic Bead Implants

We verify the non-pyrogenicity of magnetic bead implants and submit them to a full chemical characterization and toxicological risk assessment. Further, we validate the cleaning efficacy, steam sterilization, and dry time of a magnetic bead insertion device. We believe these results to be valuable to further scientific progress in the use of magnetic bead implants for human-machine interfacing.

bioengineering↗

bioRxiv2022

Global change drivers and the risk of infectious disease

Anthropogenic change is contributing to the rise in emerging infectious diseases, but it remains unclear which global change drivers most increase disease and under what contexts. We amassed a dataset from the literature that includes 1,832 observations of infectious disease responses to global change drivers across 1,202 host-parasite combinations. We found that biodiversity loss, climate change, and introduced species were associated with increases in disease-related endpoints or harm (i.e., enemy release for introduced species), whereas urbanization was associated with decreases in disease endpoints. Natural biodiversity gradients, deforestation, forest fragmentation, and most classes of chemical contaminants had non-significant effects on these endpoints. Overall, these results were consistent across human and non-human diseases. Context-dependent effects of the global change drivers on disease were common and are discussed. These findings will help better target disease management and surveillance efforts towards global change drivers that increase disease. One-Sentence SummaryHere we quantify which global change drivers increase infectious diseases the most to better target global disease management and surveillance efforts.

ecology↗

bioRxiv2019

A meta-analysis reveals temperature, dose, life stage, and taxonomy influence host susceptibility to a fungal parasite

Complex ecological relationships, such as host-parasite interactions, are often modeled with laboratory experiments. However, some experimental laboratory conditions, such as temperature or infection dose, are regularly chosen based on convenience or convention and it is unclear how these decisions systematically affect experimental outcomes. Here, we conducted a meta-analysis of 58 laboratory studies that exposed amphibians to the pathogenic fungus Batrachochytrium dendrobatidis (Bd) to better understand how laboratory temperature, host life stage, infection dose, and host species affect host mortality. We found that host mortality was driven by thermal mismatches: hosts native to cooler environments experienced greater Bd-induced mortality at relatively warm experimental temperatures and vice versa. We also found that Bd dose positively predicted Bd-induced host mortality and that the superfamilies Bufonoidea and Hyloidea were especially susceptible to Bd. Finally, the effect of Bd on host mortality varied across host life stages, with larval amphibians experiencing lower risk of Bd-induced mortality than adults or metamorphs. Metamorphs were especially susceptible and experienced mortality when inoculated with much smaller Bd doses than the average dose used by researchers. Our results suggest that when designing experiments on species interactions, researchers should carefully consider the experimental temperature, and inoculum dose, and life stage and taxonomy of the host species.

ecology↗

bioRxiv2019

Transmission of West Nile virus and other temperate mosquito-borne viruses occurs at lower environmental temperatures than tropical diseases

The temperature-dependence of many important mosquito-borne diseases has never been quantified. These relationships are critical for understanding current distributions and predicting future shifts from climate change. We used trait-based models to characterize temperature-dependent transmission of 10 vector-pathogen pairs of mosquitoes (Culex pipiens, Cx. quinquefascsiatus, Cx. tarsalis, and others) and viruses (West Nile, Eastern and Western Equine Encephalitis, St. Louis Encephalitis, Sindbis, and Rift Valley Fever viruses), most with substantial transmission in temperate regions. Transmission is optimized at intermediate temperatures (23-26{degrees}C) and often has wider thermal breadths (due to cooler lower thermal limits) compared to pathogens with predominately tropical distributions (in previous studies). The incidence of human West Nile virus cases across US counties responded unimodally to average summer temperature and peaked at 24{degrees}C, matching model-predicted optima (24-25{degrees}C). Climate warming will likely shift transmission of these diseases, increasing it in cooler locations while decreasing it in warmer locations.

ecology↗

bioRxiv2017

Towards a Global Framework for Estimating Acclimation and Thermal Breadth that Predicts Risk from Climate Change

Thermal breadth, the range of body temperatures over which organisms perform well, and thermal acclimation, the ability to alter optimal performance temperature and critical thermal maximum or minimum with changing temperatures, reflect the capacity of organisms to respond to temperature variability and are thus crucial traits for coping with climate change. Although there are theoretical frameworks for predicting thermal breadths and acclimation, the predictions of these models have not been tested across taxa, latitudes, body sizes, traits, habitats, and methodological factors. Here, we address this knowledge gap using simulation modeling and empirical analyses of >2,000 acclimation strengths from >500 species using four datasets of ectotherms. After accounting for important statistical interactions, covariates, and experimental artifacts, we reveal that i) acclimation rate scales positively with body size contributing to a negative association between body size and thermal breadth across species and ii) acclimation capacity increases with body size, seasonality, and latitude (to mid-latitudinal regions) and is regularly underestimated for most organisms. Contrary to suggestions that plasticity theory and empirical work on thermal acclimation are incongruent, these findings are consistent with theory on phenotypic plasticity. We further validated our framework by demonstrating that it could predict global extinction risk to amphibian biodiversity from climate change.

ecology↗