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In the United States, citizens and policymakers heavily rely upon Environmental Protection Agency mandated regulatory networks to monitor air pollution; increasingly they also depend on low-cost sensor networks to supplement spatial gaps in regulatory monitor networks coverage. Although these regulatory and low-cost networks in tandem provide enhanced spatiotemporal coverage in urban areas, low-cost sensors are located often in higher income, predominantly White areas. Such disparity in coverage may exacerbate existing inequalities and impact the ability of different communities to respond to the threat of air pollution. Here we present a study using cost-constrained multiresolution dynamic mode decomposition (mrDMDcc) to identify the optimal and equitable placement of fine particulate matter (PM2.5) sensors in four U.S. cities with histories of racial or income segregation: St. Louis, Houston, Boston, and Buffalo. This novel approach incorporates the variation of PM2.5 on timescales ranging from 1 day to over a decade to capture air pollution variability. We also introduce a cost function into the sensor placement optimization that represents the balance between our objectives of capturing PM2.5 extremes and increasing pollution monitoring in low-income and nonwhite areas. We find that the mrDMDcc algorithm places a greater number of sensors in historically low-income and nonwhite neighborhoods with known environmental pollution problems compared to networks using PM2.5 information alone. Our work provides a roadmap for the creation of equitable sensor networks in U.S. cities and offers a guide for democratizing air pollution data through increasing spatial coverage of low-cost sensors in less privileged communities.

BackgroundH2A.X is an H2A variant histone in eukaryotes, unique for its ability to respond to DNA damage, initiating the DNA repair pathway. H2A.X replacement within the histone octamer is mediated by the FAcilitates Chromatin Transactions (FACT) complex, a key chromatin remodeler. FACT is required for DEMETER (DME)-mediated DNA demethylation at certain loci in Arabidopsis thaliana female gametophytes during reproduction. Here, we sought to investigate whether H2A.X is involved in DME- and FACT-mediated DNA demethylation during reproduction.ResultsH2A.X is encoded by two genes in Arabidopsis genome, HTA3 and HTA5. We generated h2a.x double mutants, which displayed a normal growth profile, whereby flowering time, seed development, and root tip organization, S-phase progression and proliferation were all normal. However, h2a.x mutants were more sensitive to genotoxic stress, consistent with previous reports. H2A.X fused to Green Fluorescent Protein (GFP) under the H2A.X promoter was highly expressed especially in newly developing Arabidopsis tissues, including in male and female gametophytes, where DME is also expressed. We examined DNA methylation in h2a.x developing seeds and seedlings using whole genome bisulfite sequencing, and found that CG DNA methylation is decreased genome-wide in h2a.x mutant endosperm. Hypomethylation was most striking in transposon bodies, and occurred on both parental alleles in the developing endosperm, but not the embryo or seedling. h2a.x-mediated hypomethylated sites overlapped DME targets, but also included other loci, predominately located in heterochromatic transposons and intergenic DNA.ConclusionsOur genome-wide methylation analyses suggest that H2A.X could function in preventing access of the DME demethylase to non-canonical sites. Overall, our data suggest that H2A.X is required to maintain DNA methylation homeostasis in the unique chromatin environment of the Arabidopsis endosperm.

Fungal infections, widespread throughout the world, affect a broad range of life forms, including agriculturally relevant plants, humans, and insects. In defending against fungal infections, the fruit fly Drosophila melanogaster employs the Toll pathway to induce a large number of immune peptides. Some have been investigated, such as the antimicrobial peptides (AMPs) and Bomanins (Boms); many, however, remain uncharacterized. Here, we examine the role in innate immunity of two related peptides, Daisho1 and Daisho2 (formerly IM4 and IM14, respectively), found in hemolymph following Toll pathway activation. By generating a CRISPR/Cas9 knockout of both genes, Δdaisho, we find that the Daisho peptides are required for defense against a subset of filamentous fungi, including Fusarium oxysporum, but not other Toll-inducible pathogens, such as Enterococcus faecalis and Candida glabrata. Analysis of null alleles and transgenes revealed that the two daisho genes are each required for defense, although their functions partially overlap. Generating and assaying a genomic epitope-tagged Daisho2 construct, we detected interaction in vitro of Daisho2 peptide in hemolymph with the hyphae of F. oxysporum. Together, these results identify the Daisho peptides as a new class of innate immune effectors with humoral activity against a select set of filamentous fungi.

Fungal infections, widespread throughout the world, affect a broad range of life forms, including agriculturally relevant plants, humans, and insects. In defending against fungal infections, the fruit fly Drosophila melanogaster employs the Toll pathway to induce a large number of immune peptides. Some have been investigated, such as the antimicrobial peptides (AMPs) and Bomanins (Boms); many, however, remain uncharacterized. Here, we examine the role in innate immunity of two related peptides, Daisho1 and Daisho2 (formerly IM4 and IM14, respectively), found in hemolymph following Toll pathway activation. By generating a CRISPR/Cas9 knockout of both genes, Δdaisho, we find that the Daisho peptides are required for defense against a subset of filamentous fungi, including Fusarium oxysporum, but not other Toll-inducible pathogens, such as Enterococcus faecalis and Candida glabrata. Analysis of null alleles and transgenes revealed that the two daisho genes are each required for defense, although their functions partially overlap. Generating and assaying a genomic epitope-tagged Daisho2 construct, we detected interaction in vitro of Daisho2 peptide in hemolymph with the hyphae of F. oxysporum. Together, these results identify the Daisho peptides as a new class of innate immune effectors with humoral activity against a select set of filamentous fungi.

Toll mediates a robust and effective innate immune response across vertebrates and invertebrates. In Drosophila melanogaster, activation of Toll by systemic infection drives the accumulation of a rich repertoire of immune effectors in hemolymph, including the recently characterized Bomanins, as well as the classical antimicrobial peptides (AMPs). Here we report the functional characterization of a Toll-induced hemolymph protein encoded by the bombardier (CG18067) gene. Using the CRISPR/Cas9 system to generate a precise deletion of the bombardier transcriptional unit, we found that Bombardier is required for Toll-mediated defense against fungi and Gram-positive bacteria. Assaying cell-free hemolymph, we found that the Bomanin-dependent candidacidal activity is also dependent on Bombardier, but is independent of the antifungal AMPs Drosomycin and Metchnikowin. Using mass spectrometry, we demonstrated that deletion of bombardier results in the specific absence of short-form Bomanins from hemolymph. In addition, flies lacking Bombardier exhibited a defect in pathogen tolerance that we trace to an aberrant condition triggered by Toll activation. These results lead us to a model in which the presence of Bombardier in wild-type flies enables the proper folding, secretion, or intermolecular associations of short-form Bomanins, and the absence of Bombardier disrupts one or more of these steps, resulting in defects in both immune resistance and tolerance.

Toll mediates a robust and effective innate immune response across vertebrates and invertebrates. In Drosophila melanogaster, activation of Toll by systemic infection drives the accumulation of a rich repertoire of immune effectors in hemolymph, including the recently characterized Bomanins, as well as the classical antimicrobial peptides (AMPs). Here we report the functional characterization of a Toll-induced hemolymph protein encoded by the bombardier (CG18067) gene. Using the CRISPR/Cas9 system to generate a precise deletion of the bombardier transcriptional unit, we found that Bombardier is required for Toll-mediated defense against fungi and Gram-positive bacteria. Assaying cell-free hemolymph, we found that the Bomanin-dependent candidacidal activity is also dependent on Bombardier, but is independent of the antifungal AMPs Drosomycin and Metchnikowin. Using mass spectrometry, we demonstrated that deletion of bombardier results in the specific absence of short-form Bomanins from hemolymph. In addition, flies lacking Bombardier exhibited a defect in pathogen tolerance that we trace to an aberrant condition triggered by Toll activation. These results lead us to a model in which the presence of Bombardier in wild-type flies enables the proper folding, secretion, or intermolecular associations of short-form Bomanins, and the absence of Bombardier disrupts one or more of these steps, resulting in defects in both immune resistance and tolerance.

The DEMETER (DME) DNA glycosylase catalyzes genome-wide DNA demethylation and is required for endosperm genomic imprinting and embryo viability. Targets of DME-mediated DNA demethylation reside in small, euchromatic, AT-rich transposons and at the boundaries of large transposons, but how DME interacts with these diverse chromatin states is unknown. The STRUCTURE SPECIFIC RECOGNITION PROTEIN 1 (SSRP1) subunit of the chromatin remodeler FACT (facilitates chromatin transactions), was previously shown to be involved in the DME-dependent regulation of genomic imprinting in Arabidopsis endosperm. Therefore, to investigate the interaction between DME and chromatin, we focused on the activity of the two FACT subunits, SSRP1 and SUPPRESSOR of TY16 (SPT16), during reproduction in Arabidopsis We found that FACT colocalizes with nuclear DME in vivo, and that DME has two classes of target sites, the first being euchromatic and accessible to DME, but the second, representing over half of DME targets, requiring the action of FACT for DME-mediated DNA demethylation genome-wide. Our results show that the FACT-dependent DME targets are GC-rich heterochromatin domains with high nucleosome occupancy enriched with H3K9me2 and H3K27me1. Further, we demonstrate that heterochromatin-associated linker histone H1 specifically mediates the requirement for FACT at a subset of DME-target loci. Overall, our results demonstrate that FACT is required for DME targeting by facilitating its access to heterochromatin.

The Bomanins (Boms) are a family of a dozen secreted peptides that mediate the innate immune response governed by the Drosophila Toll receptor. We recently showed that deleting a cluster of 10 Bom genes blocks Toll-mediated defenses against a range of fungi and gram-positive bacteria. Here, we characterize the activity of individual Bom family members. We provide evidence that the Boms overlap in function and that a single Bom gene encoding a mature peptide of just 16 amino acids can act largely or entirely independent of other family members to provide phenotypic rescue in vivo. We further demonstrate that the Boms function in Drosophila humoral immunity, mediating the killing of the fungal pathogen Candida glabrata in an in vitro assay of cell-free hemolymph. In addition, we find that the level of antifungal activity both in vivo and in vitro is linked to the level of Bom gene expression. Although Toll dictates expression of the antimicrobial peptides (AMPs) drosomycin and metchnikowin, we find no evidence that Boms act by modifying the expression of the mature forms of these antifungal AMPs.

Simple Summary: This research explores how the increase in telemedicine during the COVID-19 pandemic has impacted the accessibility of breast reconstruction for breast cancer patients. This study compares patient data from before and during the widespread adoption of telehealth, focusing on how far patients traveled for surgery and their follow-up care. The findings indicate that while the rate of breast reconstruction surgeries remained consistent, telehealth significantly enhanced follow-up care, suggesting it plays a crucial role in improving healthcare access and continuity for breast cancer patients. This underscores the potential of telemedicine to bridge gaps in healthcare delivery, particularly for post-mastectomy care. Objective: To examine how the recent sharp rise in telemedicine has impacted trends in accessibility of breast reconstruction (BR). Patients and Methods: A retrospective study reviewed patients who underwent a total mastectomy at our institution from 1 August 2016 to 31 January 2022. By comparing cohorts before and during the widespread implementation of telemedicine, we assessed telehealth's impact on healthcare accessibility, measured by distance from patients' residences to our institution. Results: A total of 359 patients were included in this study. Of those, 176 received total mastectomy prior to the availability of telemedicine, and 183 in the subsequent period. There were similar baseline characteristics among patients undergoing mastectomy, including distance from place of residence to hospital (p = 0.67). The same proportion elected to receive BR between groups (p = 0.22). Those declining BR traveled similar distances as those electing the procedure, both before the era of widespread telemedicine adoption (40.3 and 35.6 miles, p = 0.56) and during the height of telemedicine use (22.3 and 61.3 miles, p = 0.26). When tracking follow-up care, significantly more patients during the pandemic pursued at least one follow-up visit with their original surgical team, indicative of the increased utilization of telehealth services. Conclusions: While the rate of BR remained unchanged during the pandemic, our findings reveal significant shifts in healthcare utilization, highly attributed to the surge in telehealth adoption. This suggests a transformative impact on breast cancer care, emphasizing the need for continued exploration of telemedicine's role in enhancing accessibility and patient follow-up in the post-pandemic era. [ABSTRACT FROM AUTHOR]

Background Gluteal augmentation with autologous fat grafting, colloquially referred to as Brazilian butt lift (BBL), is an increasingly common procedure with a highly reported complication profile. Objectives In this study we aimed to analyze the prevalence and characteristics of complications that accompanied these surgeries at ambulatory surgery facilities. Methods Adults patients who experienced fat grafting complications from 2019 to 2021 were identified in QUAD A, formerly known as the American Association for Accreditation of Ambulatory Surgery Facilities (AAAASF, Highland Park, IL, USA), database. Patients and complications were analyzed based on sociodemographic, surgery-, and facility-specific variables with descriptive statistics and logistic regression. Results Overall, 436 fat grafting procedures with complications were reported to QUAD A, with an overall complication rate of 0.94%. Of these complications, 164 (37.6%) were confirmed to be from gluteal augmentation procedures. Notably, the number of gluteal augmentation with fat grafting complications decreased from the year 2019 (48) to 2020 (36), then nearly doubled from 2020 to 2021 (69). The majority of patients were female (96.7%), with a mean age of 42.0 years and a mean BMI of 28.3 kg/m2. Wound infection was the most commonly documented complication (22.3%). Of the patients who experienced complications, 35.9% presented to a hospital for their complications and 12.6% required reoperation. Four deaths were described. There was no association between sociodemographic or surgical variables and increased odds of readmission or reoperation (P >.05), except for increasing surgeon number and reoperation (P =.02). Conclusions Gluteal augmentation accounts for a large proportion of complications from fat grafting procedures. Increased reporting requirements may aid in future determination of incidences of complications and improve patient safety. Level of Evidence: 3 [ABSTRACT FROM AUTHOR]