Urban Re-Greening: A Case Study in Multi-Trophic Biodiversity and Ecosystem Functioning in a Post-Industrial Landscape

The biodiversity of urban and post-industrial ecosystems is a highly relevant and growing new frontier in ecological research. Even so, the functionality of these ecosystems may not always be successfully predicted based on prior biodiversity and ecosystem functioning theory. Indeed, evidence suggests that the general biological impoverishment within the urban context envisioned thirty years ago was overstated. Many of the world’s urban centers support some degree of biodiversity that is indigenous, as well as a complex array of non-native species, resulting in highly functional, and often, novel communities. For over two decades, a multi-disciplinary team has examined the sub-lethal impact of soil metal contamination on the multi-trophic biodiversity and ecosystem functioning of a post-industrial brownfield in the New York City metropolitan area. We do this through examinations of photosynthesis, carbon allocation, and soil enzyme activity as well as multi-trophic metal translocation via the plant and rhizosphere. In this paper, we synthesize the findings of our research network and apply the results to a framework of functional diversity. Due to the unique constraints many post-industrial lands impose on communities, functional diversity may be more meaningful to ecosystem health than species richness

Environmental Forensic Characterization of Former Rail Yard Soils Located Adjacent to the Statue of Liberty in the New York/New Jersey Harbor

Identifying inorganic and organic soil contaminants in urban brownfields can give insights into the adverse effects of industrial activities on soil function, ecological health, and environmental quality. Liberty State Park in Jersey City (N.J., USA) once supported a major rail yard that had dock facilities for both cargo and passenger service; a portion remains closed to the public, and a forest developed and spread in this area. The objectives of this study were to: 1) characterize the organic and inorganic compounds in Liberty State Park soils and compare the findings to an uncontaminated reference site (Hutcheson Memorial Forest); and 2) identify differences between the barren low-functioning areas and the forested high-functioning areas of the brownfield. Soil samples were solvent-extracted, fractionated, and analyzed by gas chromatography–mass spectrometry and subjected to loss-on-ignition, pyrolysis-gas chromatography–mass spectrometry, inductively-coupled-plasma mass spectrometry, and optical microscopy analyses. Compared to soil from the reference site, the forested soils in Liberty State Park contained elevated percentages of organic matter (30–45%) and more contaminants, such as fossil-fuel-derived hydrocarbons and coal particles. Microscopy revealed bituminous and anthracite coal, coke, tar/pitch, and ash particles. Barren and low-functioning site 25R had a similar organic contaminant profile but contained a higher metal load than other Liberty State Park sites and also lacked higher plant indicators. These can obscure the signatures of contaminants, and data from adjacent barren and vegetated sites are valuable references for soils studies. A deeper understanding of the chemistry, biochemistry, and ecology of barren soils can be leveraged to prevent land degradation and to restore dysfunctional and phytotoxic soils

MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate metabolism in pancreatic cancer

Aberrant glucose metabolism is one of the hallmarks of cancer that facilitates cancer cell survival and proliferation. Here, we demonstrate that MUC1, a large, type I transmembrane protein that is overexpressed in several carcinomas including pancreatic adenocarcinoma, modulates cancer cell metabolism to facilitate growth properties of cancer cells. MUC1 occupies the promoter elements of multiple genes directly involved in glucose metabolism and regulates their expression. Furthermore, MUC1 expression enhances glycolytic activity in pancreatic cancer cells. We also demonstrate that MUC1 expression enhances in vivo glucose uptake and expression of genes involved in glucose uptake and metabolism in orthotopic implantation models of pancreatic cancer. The MUC1 cytoplasmic tail is known to activate multiple signaling pathways through its interactions with several transcription factors/coregulators at the promoter elements of various genes. Our results indicate that MUC1 acts as a modulator of the hypoxic response in pancreatic cancer cells by regulating the expression/stability and activity of hypoxia-inducible factor-1α (HIF-1α). MUC1 physically interacts with HIF-1α and p300 and stabilizes the former at the protein level. By using a ChIP assay, we demonstrate that MUC1 facilitates recruitment of HIF-1α and p300 on glycolytic gene promoters in a hypoxia-dependent manner. Also, by metabolomic studies, we demonstrate that MUC1 regulates multiple metabolite intermediates in the glucose and amino acid metabolic pathways. Thus, our studies indicate that MUC1 acts as a master regulator of the metabolic program and facilitates metabolic alterations in the hypoxic environments that help tumor cells survive and proliferate under such conditions

Non-leaching, highly biocompatible nanocellulose surfaces that efficiently resist fouling by bacteria in an artificial dermis model

Peer reviewe

Non-leaching, Highly Biocompatible Nanocellulose Surfaces That Efficiently Resist Fouling by Bacteria in an Artificial Dermis Model

Bacterial biofilm infections incur massive costs on healthcare systems worldwide. Particularly worrisome are the infections associated with pressure ulcers and prosthetic, plastic, and reconstructive surgeries, where staphylococci are the major biofilm-forming pathogens. Non-leaching antimicrobial surfaces offer great promise for the design of bioactive coatings to be used in medical devices. However, the vast majority are cationic, which brings about undesirable toxicity. To circumvent this issue, we have developed antimicrobial nanocellulose films by direct functionalization of the surface with dehydroabietic acid derivatives. Our conceptually unique design generates non-leaching anionic surfaces that reduce the number of viable staphylococci in suspension, including drug-resistant Staphylococcus aureus, by an impressive 4-5 log units, upon contact. Moreover, the films clearly prevent bacterial colonization of the surface in a model mimicking the physiological environment in chronic wounds. Their activity is not hampered by high protein content, and they nurture fibroblast growth at the surface without causing significant hemolysis. In this work, we have generated nanocellulose films with indisputable antimicrobial activity demonstrated using state-of-the-art models that best depict an "in vivo scenario". Our approach is to use fully renewable polymers and find suitable alternatives to silver and cationic antimicrobials. © 2020 American Chemical Society

Meningococcal disease surveillance in the Asia-Pacific region (2020): The global meningococcal initiative.

The degree of surveillance data and control strategies for invasive meningococcal disease (IMD) varies across the Asia-Pacific region. IMD cases are often reported throughout the region, but the disease is not notifiable in some countries, including Myanmar, Bangladesh and Malaysia. Although there remains a paucity of data from many countries, specific nations have introduced additional surveillance measures. The incidence of IMD is low and similar across the represented countries (<0.2 cases per 100,000 persons per year), with the predominant serogroups of Neisseria meningitidis being B, W and Y, although serogroups A and X are present in some areas. Resistance to ciprofloxacin is also of concern, with the close monitoring of antibiotic-resistant clonal complexes (e.g., cc4821) being a priority. Meningococcal vaccination is only included in a few National Immunization Programs, but is recommended for high-risk groups, including travellers (such as pilgrims) and people with complement deficiencies or human immunodeficiency virus (HIV). Both polysaccharide and conjugate vaccines form part of recommendations. However, cost and misconceptions remain limiting factors in vaccine uptake, despite conjugate vaccines preventing the acquisition of carriage.S

MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate metabolism in pancreatic cancer

Aberrant glucose metabolism is one of the hallmarks of cancer that facilitates cancer cell survival and proliferation. Here, we demonstrate that MUC1, a large, type I transmembrane protein that is overexpressed in several carcinomas including pancreatic adenocarcinoma, modulates cancer cell metabolism to facilitate growth properties of cancer cells. MUC1 occupies the promoter elements of multiple genes directly involved in glucose metabolism and regulates their expression. Furthermore, MUC1 expression enhances glycolytic activity in pancreatic cancer cells. We also demonstrate that MUC1 expression enhances in vivo glucose uptake and expression of genes involved in glucose uptake and metabolism in orthotopic implantation models of pancreatic cancer. The MUC1 cytoplasmic tail is known to activate multiple signaling pathways through its interactions with several transcription factors/coregulators at the promoter elements of various genes. Our results indicate that MUC1 acts as a modulator of the hypoxic response in pancreatic cancer cells by regulating the expression/stability and activity of hypoxia-inducible factor-1α (HIF-1α). MUC1 physically interacts with HIF-1α and p300 and stabilizes the former at the protein level. By using a ChIP assay, we demonstrate that MUC1 facilitates recruitment of HIF-1α and p300 on glycolytic gene promoters in a hypoxia-dependent manner. Also, by metabolomic studies, we demonstrate that MUC1 regulates multiple metabolite intermediates in the glucose and amino acid metabolic pathways. Thus, our studies indicate that MUC1 acts as a master regulator of the metabolic program and facilitates metabolic alterations in the hypoxic environments that help tumor cells survive and proliferate under such conditions

Collaborative development of predictive toxicology applications

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals

Single-cell analysis implicates Th17-to-Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis

Background Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder, characterised by eruptions of painful, neutrophil-filled pustules on the palms and soles. While PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat. Objective We sought to investigate the immune pathways that underlie the pathogenesis of PPP. Methods We applied bulk- and single-cell RNA-sequencing methods to the analysis of skin biopsies and peripheral blood mononuclear cells. We validated our results by flow cytometry and immune fluorescence microscopy Results Bulk RNA-sequencing of patient skin detected an unexpected signature of T-cell activation, with a significant overexpression of several Th2 genes typically upregulated in atopic dermatitis. To further explore these findings, we carried out single-cell RNA-sequencing in peripheral blood mononuclear cells of healthy and affected individuals. We found that the memory CD4+T-cells of PPP patients were skewed towards a Th17 phenotype, a phenomenon that was particularly significant among CLA+ skin-homing cells. We also identified a subset of memory CD4+ T-cells which expressed both Th17 (KLRB1/CD161) and Th2 (GATA3) markers, with pseudo-time analysis suggesting that the population was the result of Th17 to Th2 plasticity. Interestingly, the GATA3+/CD161+ cells were over-represented among the PBMCs of affected individuals, both in the scRNA-seq dataset and in independent flow-cytometry experiments. Dual positive cells were also detected in patient skin by means of immune fluorescence microscopy. Conclusions These observations demonstrate that PPP is associated with complex T-cell activation patterns and may explain why biologics that target individual T-helper populations have shown limited therapeutic efficacy. Clinical implications The simultaneous activation of Th17 and Th2 responses in PPP supports the therapeutic use of agents that inhibit multiple T-cell pathways

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course