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Interstitial meiofauna, organisms smaller than 500 μm that live between sediment grains, are the most abundant animals on Earth. They play crucial roles in biogeochemical cycles, but their responses to microplastics (MPs) remain understudied. Due to their size, meiofauna may be particularly vulnerable to MPs. We quantified how realistic levels of MP contamination affect bioturbation, oxygen penetration depth (OPD), and diffusive oxygen uptake (DOU) in sediment mesocosms over thirteen days. Bioturbation depth and OPD increased, while DOU decreased across all treatments. However, sediments containing MPs had lower bioturbation depth and slightly higher OPD compared to controls. The reduction in bioturbation was likely due to meiofauna stress, while the highest MP contamination caused increased bioturbation depth, likely due to evasion responses. Increased OPD over time was likely due to reduced labile organic matter. This study highlights how bioturbation, OPD, and DOU shift with MP pollution, confirming MPs' impacts on ecosystem functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Oral immune tolerance (OT) is a complex process with unknown genetic regulation. Our aim is to explore possible genetic control of OT in patients with rheumatoid arthritis (RA)., Methods: RA patients with increased interferon γ production invitro when their isolated peripheral blood mononuclear cells (PBMC) were cultured with type II bovine collagen α1 chain [α1 (II)] were enrolled in this study and were randomly assigned to the "Low dose" type II collagen (CII) group (30 µg/day for 10 weeks, followed by 50 µg/day for 10 weeks, followed by 70 µg/day for 10 weeks) or "High dose" CII group (90 µg/day for 10 weeks, followed by 110 µg/day for 10 weeks, followed by 130 µg/day for 10 weeks). Heparinized blood was obtained at baseline and after each of the 10 weeks treatment for analysis of the invitro production of IFNγ by their PBMC stimulated by α1(II) . Single nucleotide polymorphism (SNP) analysis of the responders and non-responders to oral CII was conducted using GeneChip Mapping 10 K 2.0 Array., Results: The SNP A-15,737 was found to associate with the ability of CII to suppress IFNγ production by α1(CII)-stimulated RA PBMC. The potential for SNP A-15,737 to associate with the OT response for patients with another autoimmune disease [OT induced by oral type I bovine collagen (CI) in patients with diffuse cutaneous systemic sclersodid (dsSSc)] was also explored., Conclusions: The ROT1 region plays a role in the control of IFNγ production after oral dosing of auto-antigens, thereby determining if oral tolerance to that antigen will develop., Competing Interests: Declaration of competing interests Drs. Arnold E. Postlethwaite and Weikuan Gu are listed on a US Patent #10,450,610B2 owned by University of Tennessee Research Foundation. This work was supported by grant AR45252 (AEP) and AR9–2242 (AEP from NIAMS/NIH and grants from Department of Veterans Affairs (AEP, WG). The authors thank Ms. Angela Cody for excellent help in drafting this manuscript. This publication is dedicated to honoring Dr. Arnold E. Postlethwaite for his more 50 years of dedicated research and contribution on the immune disease and the field of biomedical sciences., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Microplastic (MP) pollution is an ongoing problem in coastal systems, where wastewater treatment plants (WWTPs) deposit particles daily. This study examined MP characteristics at WWTP outflow and control sites in St. Andrew Bay in Northwestern Florida, USA. WWTP sites contained mostly polypropylene fragments (180.1 μm avg. size), while reference sites contained polypropylene fragments, and polyethylene and polyester fibers (315.3 μm avg. size). MP sizes were strongly linked to distance from the nearest WWTP, while shape and polymer compositions were more closely related to dissolved oxygen concentrations and distance to the nearest water input source. The prevalence of polypropylene fragments at WWTP sites suggests that extreme weather events during the study flushed land-based debris into the system, where it was buried in the sediments. Increased abundances of polyester and polyethylene terephthalate in the winter at WWTP sites are indicative of the role that laundering synthetic textiles plays in coastal MP pollution., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aaron Ridall reports financial support was provided by PADI Foundation. Aaron Ridall reports financial support was provided by Friends of Gumbo Limbo. Aaron Ridall reports financial support was provided by Southern Association of Marine Laboratories., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Wastewater treatment plants (WWTPs) cause approximately 25 % of microplastics (MPs) in the marine environment. While research on MPs in WWTP effluent has demonstrated that an abundance of particles enter the marine environment, little effort has gone to assessing MP abundances in coastal sediments to determine their seasonal and spatial variability. Here, we assessed MP abundances in sediments at sites of WWTP outflow and at non-polluted sites over six consecutive seasons within the St. Andrew Bay system in Northwestern Florida. We showed that MP abundances were highest at one of the WWTP sites, where they increased with increasing distance away from the input source (3.16 ± 1.59 MP/kg to 34.03 ± 11.69 MP/kg sediment dry weight). We also found that mean MP abundances were highest in the winter (12.41 ± 3.56 MPs/kg sediment dry weight) and lowest in the spring (2.17 ± 0.63 MPs/kg sediment dry weight). Therefore, while WWTPs differentially retain MPs in their removal processes, MP pollution in the St. Andrew Bay system shows seasonal dynamics like other studies. Although average MP abundance in surface sediments (0-5 cm) was higher than in subsurface sediments (5-10 cm) at all sites, this difference was not as substantial as has been found in other studies. Based on mean MP abundance in surface sediments, we estimate that there are 30 billion MPs within the surface layer of sediment in the St. Andrew Bay system, and that the particles export to the Gulf of Mexico because of seasonal flushing between the winter and spring. The distributions of MPs in the system were also likely driven by extreme weather events that occurred in the bay system during 2018 and 2020, which acts as a cautionary tale for coastal urban ecosystems in the face of sea level rise and climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: In the United States, physical activity (PA) among adolescents is declining; 75% of high school students do not meet daily PA guidelines. Low rates of PA are more prevalent among high school girls. Schools provide an optimal environment to target and promote PA. However, school climate has not yet been studied for its importance in promoting PA among high school students, particularly girls., Methods: A cross-sectional analysis was conducted using the Georgia Student Health Survey (GSHS) 2.0 data on perceptions of different school climate measures and self-reported weekly PA levels to study gender differences in the association of PA with school climate., Results: Data from a total of 362,926 students (48% males and 52% females) were analyzed. For both genders, the odds of being physically active increased with a more positive report of supportive school environments, school connectedness, peer social support, school physical environments, cultural acceptance, school safety, and adult social support. Peer victimization was associated with increased odds of PA among females but lower odds for males., Conclusion: Results suggest that improving school climate can increase PA among adolescents. As new or existing school-based interventions and policies are considered by states and local governments, improving the school climate should be part of the overall strategy. Future research is needed on peer victimization among physically active females., Implications and Contributions: This study evaluated gender differences in the association between measures of school climate and PA among high school students. School climate or policies fostering positive environments including feelings of safety, connectedness, and peer support may increase adolescent PA; addressing peer victimization and fights may reduce gender disparities in PA., (© 2022 The Foundation for Professionals in Services for Adolescents.)

Messenger RNA (mRNA) has become a promising tool in therapeutic cancer vaccine strategies. Owing to its flexible design and rapid production, mRNA is an attractive antigen delivery format for cancer vaccines targeting mutated peptides expressed in a tumor-the so-called neoantigens. These neoantigens are rarely shared between patients, and inclusion of these antigens in a vaccine requires the production of individual batches of patient-tailored mRNA. The authors have developed MIDRIX NEO , a personalized mRNA-loaded dendritic cell vaccine targeting tumor neoantigens, which is currently being evaluated in a phase 1 clinical study in lung cancer patients. To facilitate this study, the authors set up a Good Manufacturing Practice (GMP)-compliant production process for the manufacture of small batches of personalized neoantigen-encoding mRNA. In this article, the authors describe the complete mRNA production process and the extensive quality assessment to which the mRNA is subjected. Validation runs have shown that the process delivers mRNA of reproducible, high quality. This process is now successfully applied for the production of neoantigen-encoding mRNA for the clinical evaluation of MIDRIX NEO . To the authors' knowledge, this is the first time that a GMP-based production process of patient-tailored neoantigen mRNA has been described., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Many efforts have been devoted to improve the performance of dendritic cell (DC)-based cancer vaccines. Ideally, a DC vaccine should induce robust type 1-polarized T-cell responses and efficiently expand antigen (Ag)-specific cytotoxic T-cells, while being applicable regardless of patient human leukocyte antigen (HLA) type. Production time should be short, while maximally being good manufacturing practice (GMP)-compliant. We developed a method that caters to all of these demands and demonstrated the superiority of the resulting product compared with DCs generated using a well-established "classical" protocol., Methods: Immunomagnetically purified monocytes were cultured in a closed system for 3 days in GMP-compliant serum-free medium and cytokines, and matured for 24 h using monophosphoryl lipid A (MPLA)+ interferon-gamma (IFN-γ). Mature DCs were electroporated with messenger RNA (mRNA) encoding full-length antigen and cryopreserved. "Classical" DCs were cultured for 8 days in flasks, with one round of medium and cytokine supplementation, and matured with tumor necrosis factor alpha (TNF-α) + prostaglandin E2 (PGE2) during the last 2 days., Results: Four-day MPLA/IFN-γ-matured DCs were superior to 8-day TNF-α/PGE2-matured DCs in terms of yield, co-stimulatory/co-inhibitory molecule expression, resilience to electroporation and cryopreservation and type 1-polarizing cytokine and chemokine release after cell thawing. Electroporated and cryopreserved DCs according to our protocol efficiently present epitopes from tumor antigen-encoding mRNA, inducing a strong expansion of antigen-specific CD8+ T-cells with full cytolytic capacity., Conclusion: We demonstrate using a GMP-compliant culture protocol the feasibility of generating high yields of mature DCs in a short time, with a superior immunogenic profile compared with 8-day TNF-α/PGE2-matured DCs, and capable of inducing vigorous cytotoxic T-cell responses to antigen from electroporated mRNA. This method is now being applied in our clinical trial program., (Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)