CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017-6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD2

The significance of hazardous chemicals in wastewater treatment works effluents

This is the post-print version of the final paper published in Science of The Total Environment. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.The advent of increasingly stringent and wider ranging European Union legislation relating to water and the environment has required regulators to assess compliance risk and to respond by formulating appropriate pollution control measures. To support this process the UK Water Industry has completed a national Chemicals Investigation Programme (CIP), to monitor over 160 wastewater treatment works (WwTWs) for 70 determinands. Final effluent concentrations of zinc, polynuclear aromatic hydrocarbons (fluoranthene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(g,h,i)perylene and indeno(1,2,3-cd)pyrene), “penta” congeners (BDEs) 47 and 99, tributyltin, triclosan, erythromycin, oxytetracycline, ibuprofen, propranolol, fluoxetine, diclofenac, 17β-estradiol and 17α-ethinyl estradiol exceeded existing or proposed Environmental Quality Standards (EQSs) in over 50% of WwTWs. Dilution by receiving water might ensure compliance with EQSs for these chemicals, apart from the BDEs. However, in some cases there will be insufficient dilution to ensure compliance and additional management options may be required

KCNK3 mutation causes altered immune function in pulmonary arterial hypertension patients and mouse models

Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we expose

Community-driven dispersal in an individual-based predator-prey model

We present a spatial, individual-based predator-prey model in which dispersal is dependent on the local community. We determine species suitability to the biotic conditions of their local environment through a time and space varying fitness measure. Dispersal of individuals to nearby communities occurs whenever their fitness falls below a predefined tolerance threshold. The spatiotemporal dynamics of the model is described in terms of this threshold. We compare this dynamics with the one obtained through density-independent dispersal and find marked differences. In the community-driven scenario, the spatial correlations in the population density do not vary in a linear fashion as we increase the tolerance threshold. Instead we find the system to cross different dynamical regimes as the threshold is raised. Spatial patterns evolve from disordered, to scale-free complex patterns, to finally becoming well-organized domains. This model therefore predicts that natural populations, the dispersal strategies of which are likely to be influenced by their local environment, might be subject to complex spatiotemporal dynamics.Comment: 43 pages, 7 figures, vocabulary modifications, discussion expanded, references added, Ecological Complexity accepte

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients

BACKGROUND: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination. METHODS: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. RESULTS: After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4 CONCLUSION: Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals

The Effect of Pyridoxamine on Large Artery Stiffening and Brain Oxidative Stress and Inflammation with Age

39 pagesAs people age, large elastic arteries become stiffer and cerebral arteries become dysfunctional. This research sought to determine whether treatment with pyridoxamine, a form of vitamin B6, prevents age-related arterial stiffening by limiting the increases in advanced glycation end products (AGEs), and thereby ameliorates the downstream consequences in cerebral arteries and cerebral cortex by limiting increases in oxidative stress and inflammation. 20 old mice were treated with pyridoxamine for 4 months and pulse wave velocity (PWV), a measure of aortic stiffness, was performed at baseline and every other month. Tissue samples from old control, young control, and old pyridoxamine treated mice were analyzed for gene expression of pro- and antioxidant enzymes and inflammatory cytokines. Aorta samples from each group were analyzed for AGEs by immunofluorescence and for thickness of the arterial wall by Verhoeff Van Gieson staining. Aortic PWV was greater in old control versus young control arteries (306 ± 12 cm/s vs. 273 ± 16 cm/s, p=0.005) however, aortic PWV in pyridoxamine-treated mice did not increase over time (p>0.05). Pyridoxamine did not change AGEs (0.05 ± 0.02 AU) versus old and young control arteries (0.01 ± 0.003 AU vs 0.1 ± 0.05 AU, p=0.10). There was no change to arterial wall structure between groups. In the cerebral cortex, SOD1 trended toward elevation in old pyridoxamine arteries as compared to old controls. IL-1 was significantly increased in old pyridoxamine versus young control (1.0 0.29 AU vs. 3.2 0.60 AU, p=0.03), the same was true in the MCA (1.0 0.29 AU vs. 3.2 0.60 AU, p=0.03). These results suggest that pyridoxamine may reduce arterial stiffening. While previous studies have indicated a reduction in AGEs with pyridoxamine treatment, this was not evident in the present study. Pyridoxamine may increase SOD1 expression, while increases in IL-1 is likely a result of the aging process and not modified by pyridoxamine treatment. Further studies are needed to identify the mechanism by which pyridoxamine prevents age-related arterial stiffening