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Abstract The habitat quality of urban forest patches is determined by the composition and structure of vegetation which in turn affects the quality of trophic resources and shelter provided for wildlife species. In addition, urban development in the landscape surrounding forest patches can affect species' movement between patches, further influencing habitat quality. Understanding how species respond to variation in habitat quality among urban forest patches is especially important for species that contribute to ecosystem services and disservices for urban residents. Here, we assessed habitat quality provided by urban forest patches for white‐footed mice (Peromyscus leucopus) because they are one of the key reservoir species for Lyme disease and they influence disease dilution ecosystem services provided by mammal communities. We examined variation in vegetation composition and structure in forest patches across a gradient of landscape‐scale urban development in and around Philadelphia, PA, USA. In particular, we focused on shifts in vegetation composition and structure associated with invasive understory shrubs given their prevalence in our study system. We then quantified the numerical (index of relative abundance) and morphological responses of white‐footed mice to variation in habitat quality. While we observed no significant effects of environmental variables on our index of mouse relative abundance in forest patches, environmental variables associated with vegetation structure and composition were associated with shifts in mouse morphology. Most notably, mice were larger at sites with more invasive shrub species. This indicates that invasive understory shrubs may be creating higher‐quality habitat for white‐footed mice. Because larger‐bodied mice are likely to feed more ticks, this result has significant implications for Lyme disease dynamics in urban areas, such as amplified transmission.

Many tissue-specific stem cells maintain the ability to produce multiple cell types during long periods of non-division, or quiescence. FOXO transcription factors promote quiescence and stem cell maintenance, but the mechanisms by which FOXO proteins promote multipotency during quiescence are still emerging. The single FOXO ortholog in C. elegans, daf-16, promotes entry into a quiescent and stress-resistant larval stage called dauer in response to adverse environmental cues. During dauer, stem and progenitor cells maintain or re-establish multipotency to allow normal development to resume after dauer. We find that during dauer, daf-16/FOXO prevents epidermal stem cells (seam cells) from prematurely adopting differentiated, adult characteristics. In particular, dauer larvae that lack daf-16 misexpress collagens that are normally adult-enriched. Using col-19p::gfp as an adult cell fate marker, we find that all major daf-16 isoforms contribute to opposing col-19p::gfp expression during dauer. By contrast, daf-16(0) larvae that undergo non-dauer development do not misexpress col-19p::gfp. Adult cell fate and the timing of col-19p::gfp expression are regulated by the heterochronic gene network, including lin-41 and lin-29. lin-41 encodes an RNA-binding protein orthologous to LIN41/TRIM71 in mammals, and lin-29 encodes a conserved zinc finger transcription factor. In non-dauer development, lin-41 opposes adult cell fate by inhibiting the translation of lin-29, which directly activates col-19 transcription and promotes adult cell fate. We find that during dauer, lin-41 blocks col-19p::gfp expression, but surprisingly, lin-29 is not required in this context. Additionally, daf-16 promotes the expression of lin-41 in dauer larvae. The col-19p::gfp misexpression phenotype observed in dauer larvae with reduced daf-16 requires the downregulation of lin-41, but does not require lin-29. Taken together, this work demonstrates a novel role for daf-16/FOXO as a heterochronic gene that promotes expression of lin-41/TRIM71 to contribute to multipotent cell fate in a quiescent stem cell model.

The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct changes in molecular and cellular phenotype that are generally context-independent. Posterior polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional studies support the hypothesis that CEnC undergo a MET-like transition in PPCD, termed endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be considered a corollary to the classic EMT/MET paradigm.

The advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.

The coordinate regulation of metabolism and epigenetics to establish cell state-specific gene expression patterns during lineage progression is a central aspect of cell differentiation, but the factors that regulate this elaborate interplay are not well-defined. The imprinted Dlk1-Dio3 noncoding RNA (ncRNA) cluster has been associated with metabolism in various progenitor cells, suggesting it functions as a regulator of metabolism and cell state. Here, we directly demonstrate that the Dlk1-Dio3 ncRNA cluster coordinates mitochondrial respiration and chromatin structure to maintain proper cell state. Stable mouse muscle cell lines were generated harboring two distinct deletions in the proximal promoter region, resulting in either greatly upregulated or downregulated expression of the entire Dlk1-Dio3 ncRNA cluster. Both mutant lines displayed impaired muscle differentiation along with dysregulated structural gene expression and abnormalities in mitochondrial respiration. Genomewide chromatin accessibility and histone methylation patterns were also severely affected in these mutants. Our results strongly suggest that muscle cells are sensitive to Dlk1-Dio3 ncRNA dosage, and that the cluster coordinately regulates metabolic activity and the epigenome to maintain proper cell state in the myogenic lineage. [ABSTRACT FROM AUTHOR]

The habitat quality of urban forest patches is determined by the composition and structure of vegetation which in turn affects the quality of trophic resources and shelter provided for wildlife species. In addition, urban development in the landscape surrounding forest patches can affect species' movement between patches, further influencing habitat quality. Understanding how species respond to variation in habitat quality among urban forest patches is especially important for species that contribute to ecosystem services and disservices for urban residents. Here, we assessed habitat quality provided by urban forest patches for white‐footed mice (Peromyscus leucopus) because they are one of the key reservoir species for Lyme disease and they influence disease dilution ecosystem services provided by mammal communities. We examined variation in vegetation composition and structure in forest patches across a gradient of landscape‐scale urban development in and around Philadelphia, PA, USA. In particular, we focused on shifts in vegetation composition and structure associated with invasive understory shrubs given their prevalence in our study system. We then quantified the numerical (index of relative abundance) and morphological responses of white‐footed mice to variation in habitat quality. While we observed no significant effects of environmental variables on our index of mouse relative abundance in forest patches, environmental variables associated with vegetation structure and composition were associated with shifts in mouse morphology. Most notably, mice were larger at sites with more invasive shrub species. This indicates that invasive understory shrubs may be creating higher‐quality habitat for white‐footed mice. Because larger‐bodied mice are likely to feed more ticks, this result has significant implications for Lyme disease dynamics in urban areas, such as amplified transmission. [ABSTRACT FROM AUTHOR]

Many women experience depressive symptoms after birth, and rates among African Americans are as high as 40 percent. Spirituality and religiosity are valued in African American communities, but their relevance to new mothers has not been empirically tested. We examined effects of religiosity and spirituality on trajectories of depressive symptoms during the year following childbirth. Data were collected by the Eunice Kennedy Shriver NICHD Community and Child Health Network (CCHN) focused on maternal-child health disparities. The sample consisted of 702 low SES African American predominantly Christian women. Participants were interviewed in their homes throughout the year following a birth. Spirituality and religiosity each independently predicted changes in depressive symptoms with low levels predicting increases over time. Effects of religiosity were mediated by a woman's spirituality. Religiosity and spirituality functioned as significant, interrelated protective factors in this study which provides novel insight about lower income African American women following birth.

Hydrogen sulfide (H2S) is an important reactive sulfur species that is involved in many biological functions, and H2S imbalances have been indicated as a potential biomarker for various diseases. Different H2S donors have been developed to deliver H2S directly to biological systems, but few reports include donors with optical responses that allow for tracking of H2S release. Moreover, donor systems that use the same chemistry to deliver H2S across a palette of fluorescent responses remain lacking. Here we report five thiol‐activated fluorescence turn‐on COS/H2S donors that utilize blue, yellow, orange, red, and near infrared‐emitting dyes functionalized with an H2S‐releasing sulfenyl thiocarbonate scaffold. Upon treatment with thiols, each donor provides a fluorescence turn‐on response (3–310‐fold) and high H2S release efficiencies (>60 %). Using combined electrode and fluorescence experiments, we directly correlate the measured H2S release with the fluorescence response. All donors are biocompatible and release H2S in live cell environments. In addition, we demonstrate that the NIR donor allows for imaging H2S release in live rats via subcutaneous injection of the donor loaded into an alginate gel, which to the best of our knowledge is the first in vivo tracking of H2S release from a fluorogenic donor in non‐transparent organisms. [ABSTRACT FROM AUTHOR]