This study documented the levels of microplastics in three commercially important small pelagic fish species in South African waters, namely European anchovy (Engraulis encrasicolus), West Coast ...round herring (Etrumeus whiteheadi) and South African sardine (Sardinops sagax). Data suggested variation between species with a higher concentration of microplastics for S. sagax (mean of 1.58 items individual-1) compared to Et. whiteheadi (1.38 items individual-1) and En. encrasicolus (1.13 items individual-1). The occurrence of microplastics was also higher for S. sagax (72%) and Et. whiteheadi (72%) compared to En. encrasicolus (57%). Microfibres accounted for 80% of ingested microplastics (the remainder were plastic fragments) with the main ingested polymers being poly(ethylene:propylene:diene) (33% occurrence), polyethylene (20%), polyamide (20%), polyester (20%) and polypropylene (7%). The abundance of ingested items was not significantly correlated with fish caudal length or body weight, and spatial investigation indicated an increase in the abundance of ingested items from the West to the South coast. Etrumeus whiteheadi is proposed as a bio-indicator for microplastics for South Africa.
Seafloor sediments have been defined as sinks for microplastics in the marine environment and could therefore represent suitable matrices for their long-term monitoring. On a regional aspect, the ...adoption of a common indicator for microplastics in seafloor sediments would allow regional monitoring and assessments through international frameworks such as OSPAR. This study presents the findings of a research and development project monitoring the occurrence and abundance of microplastics in UK seafloor sediments for the period 2013-2021, supporting the development of a national monitoring programme for microplastics in seafloor sediments for the UK (England and Wales). A fast-screening technique based on Nile Red staining of polymers coupled with µ-FTIR was applied and validated using µ-FTIR-FPA. Microplastic particles were detected in all 189 sediment samples from 15 stations selected around the UK for each investigated year (2013 - 2021). Microplastic concentrations (20 – 5000 µm) ranged from 133 – 6,933 particles kg
-1
dry weight sediment for 2020-2021. Microplastics mainly consisted of fragments (73%), fibres (19%) and spheres (8%). Plastic fragments ranged from 46 to 3276 µm and plastic fibres from 300 to 1731 µm in length with a mean diameter of 16 µm. Single particle analysis using µ-FTIR indicated a prevalence of Rayon, PP, Rayon/Nylon/Polyester blends, Rubber, PS, PE, PA, PVC, Acrylic, EMAA and PET. Fragments were mainly white in colour (46%) followed by brown (38%), black (1%), blue (1%) and orange (1%). Fibres were mainly white in colour (57%) followed by black (14%), orange (14%) and red (14%). A trend assessment at the UK regional seas levels indicated little visual evidence of any trends in the abundance of microplastics over time in any of the regional seas – with the possible exception of the Northern North Sea with a reduction in abundance over time for the time-period 2013-2021.
The UK Marine Management Organisation (MMO) tasked the Centre for Environment, Fisheries & Aquaculture Science (Cefas) with reviewing the current UK dispersant efficacy testing procedures. The aim ...was to identify possibilities to increase standardisation, improve health and safety performance and explore harmonisation possibilities with international dispersant efficacy testing procedures. The US EPA ‘Baffled Flask Test’ (BFT) was adopted, implemented and validated as a new standard method in the UK. The outputs from this study suggest that dispersant efficacy results from the adopted BFT test and the currently used protocol are in a similar range and results presented by the US EPA.
As a result, the transition to the adopted BFT test will require minimal changes in the assessment of the results or reporting and increase harmonisation between tests used in the UK and North America.
•The US EPA BFT method was adopted as new standard for dispersant testing in the UK.•The new method provides comparable results to the LR448 protocol.•The new BFT method facilitates global harmonisation for dispersant efficacy testing.•The new robust and sensitive method reduces the use of hazardous solvents.
Major histocompatibility complex-II (MHC-II)-Associated Peptide Proteomics (MAPPs) is a mass spectrometry-based approach to identify and relatively quantitate naturally processed and presented ...MHC-II-associated peptides that can potentially activate T cells and contribute to the immunogenicity of a drug. Acceptance of the MAPPs technology as an appropriate preclinical (and potentially clinical) immunogenicity risk assessment tool depends not only on its technical stability and robustness but also on the ability to compare results across experiments and donors. To this end, we developed a specialized MAPPs data processing pipeline, dataMAPPs, which presents complex mass spectrometric data sets in the form of heat maps (heatMAPPs), enabling rapid and convenient comparison between conditions and donors. A customized normalization procedure based on identified endogenous peptides standardizes signal intensities within and between donors and enables cross-experimental comparison. We evaluated the technical reproducibility of the MAPPs platform using tool compounds with respect to the most prominent experimental factors and found that the systematic biological differences across donors by far outweighed any technical source of variation. We illustrate the capability of the MAPPs platform to generate data that may be used for preclinical risk assessment of drug-induced immunogenicity and discuss its applicability in the clinics.
IL-17A is purported to help drive early pathogenesis in acute respiratory distress syndrome (ARDS) by enhancing neutrophil recruitment. Although IL-17A is the archetypal cytokine of T-helper 17 ...cells, it is produced by a number of lymphocytes, the source during ARDS being unknown.
To identify the cellular source and the role of IL-17A in the early phase of lung injury.
Lung injury was induced in wild-type (C57BL/6) and IL-17 knockout (KO) mice with aerosolized LPS (100 μg) or Pseudomonas aeruginosa infection. Detailed phenotyping of the cells expressing RORγt, the transcriptional regulator of IL-17 production, in the mouse lung at 24 hours was performed by flow cytometry.
A 100-fold reduction in neutrophil infiltration was observed in the lungs of the IL-17A KO compared with wild-type mice. The majority of RORγt(+) cells in the mouse lung were the recently identified group 3 innate lymphoid cells (ILC3s). Detailed characterization revealed these pulmonary ILC3s (pILC3s) to be discrete from those described in the gut. The critical role of these cells was verified by inducing injury in recombinase-activating gene 2 KO mice, which lack T cells but retain innate lymphoid cells. No amelioration of pathology was observed in the recombinase-activating gene 2 KO mice.
IL-17 is rapidly produced during lung injury and significantly contributes to early immunopathogenesis. This is orchestrated largely by a distinct population of pILC3s. Modulation of the activity of pILC3s may potentiate early control of the inflammatory dysregulation seen in ARDS, opening up new therapeutic targets.
The forebrain cholinergic system promotes higher brain function in part by signaling through the M₁ muscarinic acetylcholine receptor (mAChR). During Alzheimer's disease (AD), these cholinergic ...neurons degenerate, therefore selectively activating M₁ receptors could improve cognitive function in these patients while avoiding unwanted peripheral responses associated with non-selective muscarinic agonists. We describe here benzyl quinolone carboxylic acid (BQCA), a highly selective allosteric potentiator of the M₁ mAChR. BQCA reduces the concentration of ACh required to activate M₁ up to 129-fold with an inflection point value of 845 nM. No potentiation, agonism, or antagonism activity on other mAChRs is observed up to 100 μM. Furthermore studies in M₁⁻/⁻ mice demonstrates that BQCA requires M₁ to promote inositol phosphate turnover in primary neurons and to increase c-fos and arc RNA expression and ERK phosphorylation in the brain. Radioligand-binding assays, molecular modeling, and site-directed mutagenesis experiments indicate that BQCA acts at an allosteric site involving residues Y179 and W400. BQCA reverses scopolamine-induced memory deficits in contextual fear conditioning, increases blood flow to the cerebral cortex, and increases wakefulness while reducing delta sleep. In contrast to M₁ allosteric agonists, which do not improve memory in scopolamine-challenged mice in contextual fear conditioning, BQCA induces β-arrestin recruitment to M₁, suggesting a role for this signal transduction mechanism in the cholinergic modulation of memory. In summary, BQCA exploits an allosteric potentiation mechanism to provide selectivity for the M₁ receptor and represents a promising therapeutic strategy for cognitive disorders.
Planetary Instrument for X-ray Lithochemistry (PIXL) is a micro-focus X-ray fluorescence spectrometer mounted on the robotic arm of NASA’s
Perseverance
rover. PIXL will acquire high spatial ...resolution observations of rock and soil chemistry, rapidly analyzing the elemental chemistry of a target surface. In 10 seconds, PIXL can use its powerful 120 μm-diameter X-ray beam to analyze a single, sand-sized grain with enough sensitivity to detect major and minor rock-forming elements, as well as many trace elements. Over a period of several hours, PIXL can autonomously raster-scan an area of the rock surface and acquire a hyperspectral map comprised of several thousand individual measured points. When correlated to a visual image acquired by PIXL’s camera, these maps reveal the distribution and abundance variations of chemical elements making up the rock, tied accurately to the physical texture and structure of the rock, at a scale comparable to a 10X magnifying geological hand lens. The many thousands of spectra in these postage stamp-sized elemental maps may be analyzed individually or summed together to create a bulk rock analysis, or subsets of spectra may be summed, quantified, analyzed, and compared using PIXLISE data analysis software. This hand lens-scale view of the petrology and geochemistry of materials at the
Perseverance
landing site will provide a valuable link between the larger, centimeter- to meter-scale observations by Mastcam-Z, RIMFAX and Supercam, and the much smaller (micron-scale) measurements that would be made on returned samples in terrestrial laboratories.
Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have ...contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment.
In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed.
These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR.
The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis.
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