Palladium uptake and its effect on behavioural and molecular markers in the freshwater shrimp Gammarus pulex

The expanded use of platinum group elements (PGEs), platinum (Pt), palladium (Pd), and rhodium (Rh), in automobile catalysts has led to increased levels of these metals in aquatic environments. However, data regarding acute toxicity and the sublethal effects of these metals on aquatic biota are limited. This study aimed to explore the response of the freshwater amphipod Gammarus pulex to PGEs. Investigations included the 96 LC50 test and several behavioural (vertical movement and feeding activity) and biochemical (acetylcholinesterase (AChE); osmoregulation; 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) reduction; reduced glutathione (GSH); glutathione-S-transferase (GST); thiobarbituric acid reactive substances (TBARS); heat shock proteins (HSPs) and protein phosphorylation) endpoints. Pd caused a significant reduction in the survival of G. pulex with a 96 h LC50 of 0.52 mg/L (4.89 μM). Pt or Rh increased the survival of G. pulex exposed to Pd. However, this was not associated with reduced Pd uptake. Exposure for 24 h to 0.5 mg/L Pd (4.69 μM) significantly decreased the vertical movement (64%) and feeding activity (95%) of G. pulex. However, lower Pd concentrations (≥0.25 mg/L (2.3 μM)) took 72 h to induce significant inhibition in feeding activity (50%). AChE activity was significantly increased (40%) following 72 h exposure to 0.5 mg/L Pd. GST activity was significantly inhibited (≥32%) following 72 h exposure to ≤0.25 mg/L Pd. The concentration of GSH was significantly increased (22 and 35%) following 72 h exposure 0.1 (0.94 μM) and 0.5 mg/L Pd2+, respectively. Exposure to ≤0.1 mg/L Pd caused a significant decrease (≤27%) in MTT reduction and significant increase (≤70%) in HSP60 content in mitochondrial extract (pellet) after 72 and 24 h exposure, respectively. The reactivity of anti-phosphoserine bodies with protein bands corresponding to 245 kDa in the pellet was significantly increased (38%) by exposure of gammarids to 0.5 mg/L Pd. Exposure to 0.1 mg/L Pd significantly increased (32%) the intensity of a 30 kDa anti-phosphothreonine reactive protein band in the post-mitochondrial extract, but higher Pd doses had no effect. In conclusion, this study provides original data suggesting the mitochondria as a main target of Pd toxicity. Further studies of Pd toxicity, under both laboratory and field conditions, are needed including the effect of long-term exposure to low Pd concentrations

Unveiling the Nexus: The interdependence of animal welfare, environment & sustainable development

On 2 March 2022, the UN Environment Assembly (UNEA) adopted the Animal Welfare - Environment - Sustainable Development Nexus Resolution. In this resolution, UNEA acknowledged that animal welfare can contribute to addressing environmental challenges . UNEA further acknowledged animal welfare\u27s contribution to promoting the One Health approach and achieving the Sustainable Development Goals. To understand these links, UNEA requested the UN Environment Programme (UNEP) to analyse and produce a report for the next convening of UNEA on the nexus between animal welfare, the environment, and sustainable development. Unveiling the Nexus: The interdependence of animal welfare, environment & sustainable development illuminates the value of an animal welfare perspective for addressing the drivers of environmental challenges and sustainable development. It highlights important links between animal welfare and biodiversity, climate change, pollution, health, food security, and livelihoods. This assessment, undertaken by the World Federation for Animals, aims to support those developing and contributing to the UNEP Nexus report. It aims to provide stakeholders with a basis to further explore why improving animal welfare is essential for the environmental and development community

Conservative treatment of CMC-1 osteoarthritis

Initially, osteoarthritis of the carpometacarpal joint of the thumb (CMC-1) should be conservatively treated. However, literature concerning this topic is absent. Therefore, 39 patients (71 hands) with conservatively treated osteoarthritis of the carpometacarpal joint of the thumb were reviewed. The minimum follow-up period was I year; the average follow-up period was 8.8 years. Thirty-two women had bilateral CMC-I osteoarthritis; the remaining seven patients had unilateral CMC-1 osteoarthritis. Although suggested by others, long-term pain relief was not observed in this study. Moreover, patient satisfaction, thumb strength, and mobility were not influenced by the duration of the CMC-1 osteoarthritis. In conservatively treated patients, worse results are achieved than in operated patients, especially concerning their subjective experiences. The authors therefore advise surgery, especially in the case of pain which hampers the activities of daily life

Genome characterization and taxonomy of <em>Actinomyces acetigenes</em> sp. nov., and <em>Actinomyces stomatis</em> sp. nov., previously isolated from the human oral cavity

\ua9 2023, The Author(s).Background: Actinomyces strains are commonly found as part of the normal microflora on human tissue surfaces, including the oropharynx, gastrointestinal tract, and female genital tract. Understanding the diversity and characterization of Actinomyces species is crucial for human health, as they play an important role in dental plaque formation and biofilm-related infections. Two Actinomyces strains ATCC 49340 T and ATCC 51655 T have been utilized in various studies, but their accurate species classification and description remain unresolved. Results: To investigate the genomic properties and taxonomic status of these strains, we employed both 16S rRNA Sanger sequencing and whole-genome sequencing using the Illumina HiSeq X Ten platform with PE151 (paired-end) sequencing. Our analyses revealed that the draft genome of Actinomyces acetigenes ATCC 49340 T was 3.27 Mbp with a 68.0% GC content, and Actinomyces stomatis ATCC 51655 T has a genome size of 3.08 Mbp with a 68.1% GC content. Multi-locus (atpA , rpoB, pgi , metG , gltA , gyrA, and core genome SNPs) sequence analysis supported the phylogenetic placement of strains ATCC 51655 T and ATCC 49340 T as independent lineages. Digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and average amino acid identity (AAI) analyses indicated that both strains represented novel Actinomyces species, with values below the threshold for species demarcation (70% dDDH, 95% ANI and AAI). Pangenome analysis identified 5,731 gene clusters with strains ATCC 49340 T and ATCC 51655 T possessing 1,515 and 1,518 unique gene clusters, respectively. Additionally, genomic islands (GIs) prediction uncovered 24 putative GIs in strain ATCC 49340 T and 16 in strain ATCC 51655 T, contributing to their genetic diversity and potential adaptive capabilities. Pathogenicity analysis highlighted the potential human pathogenicity risk associated with both strains, with several virulence-associated factors identified. CRISPR-Cas analysis exposed the presence of CRISPR and Cas genes in both strains, indicating these strains might evolve a robust defense mechanism against them. Conclusion: This study supports the classification of strains ATCC 49340 T and ATCC 51655 T as novel species within the Actinomyces, in which the name Actinomyces acetigenes sp. nov. (type strain ATCC 49340 T = VPI D163E-3 T = CCUG 34286 T = CCUG 35339 T) and Actinomyces stomatis sp. nov. (type strain ATCC 51655 T = PK606T = CCUG 33930 T) are proposed

Necrosis binding of Ac-Lys⁰(IRDye800CW)-Tyr³-octreotate: a consequence from cyanine-labeling of small molecules.

There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor uptake, especially when labeled to smaller targeting vectors such as peptides. Here we demonstrate the effect of cyanine-mediated dead cell-binding of Ac-Lys &lt;sup&gt;0&lt;/sup&gt; (IRDye800CW)-Tyr &lt;sup&gt;3&lt;/sup&gt; -octreotate (800CW-TATE) and how this can be used as an advantage for fluorescence-guided surgery. Binding of 800CW-TATE could be blocked with DOTA &lt;sup&gt;0&lt;/sup&gt; -Tyr &lt;sup&gt;3&lt;/sup&gt; -octreotate (DOTA-TATE) on cultured SSTR &lt;sub&gt;2&lt;/sub&gt; -positive U2OS cells and was absent in SSTR &lt;sub&gt;2&lt;/sub&gt; negative U2OS cells. However, strong binding was observed to dead cells, which could not be blocked with DOTA-TATE and was also present in dead SSTR &lt;sub&gt;2&lt;/sub&gt; negative cells. No SSTR &lt;sub&gt;2&lt;/sub&gt; -mediated binding was observed in frozen tumor sections, possibly due to disruption of the cells in the process of sectioning the tissue before exposure to the contrast agent. DOTA-TATE blocking resulted in an incomplete reduction of 61.5 ± 5.8% fluorescence uptake by NCI-H69-tumors in mice. Near-infrared imaging and dead cell staining on paraffin sections from resected tumors revealed that fluorescence uptake persisted in necrotic regions upon blocking with DOTA-TATE. This study shows that labeling peptides with cyanines can result in dead cell binding. This does not hamper the ultimate purpose of fluorescence-guided surgery, as necrotic tissue appears in most solid tumors. Hence, the necrosis binding can increase the overall tumor uptake. Moreover, necrotic tissue should be removed as much as possible: it cannot be salvaged, causes inflammation, and is tumorigenic. However, when performing binding experiments to cells with disrupted membrane integrity, which is routinely done with nuclear probes, this dead cell-binding can resemble non-specific binding. This study will benefit the development of fluorescent contrast agents

From mRNA expression of drug disposition genes to in vivo assessment of CYP-mediated biotransformation during zebrafish embryonic and larval development

This is the final version. Available on open access from MDPI via the DOI in this recordThe zebrafish (Danio rerio) embryo is currently explored as an alternative for developmental toxicity testing. As maternal metabolism is lacking in this model, knowledge of the disposition of xenobiotics during zebrafish organogenesis is pivotal in order to correctly interpret the outcome of teratogenicity assays. Therefore, the aim of this study was to assess cytochrome P450 (CYP) activity in zebrafish embryos and larvae until 14 d post-fertilization (dpf) by using a non-specific CYP substrate, i.e., benzyloxy-methyl-resorufin (BOMR) and a CYP1-specific substrate, i.e., 7-ethoxyresorufin (ER). Moreover, the constitutive mRNA expression of CYP1A, CYP1B1, CYP1C1, CYP1C2, CYP2K6, CYP3A65, CYP3C1, phase II enzymes uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and sulfotransferase 1st1 (SULT1ST1), and an ATP-binding cassette (ABC) drug transporter, i.e., abcb4, was assessed during zebrafish development until 32 dpf by means of quantitative PCR (qPCR). The present study showed that trancripts and/or the activity of these proteins involved in disposition of xenobiotics are generally low to undetectable before 72 h post-fertilization (hpf), which has to be taken into account in teratogenicity testing. Full capacity appears to be reached by the end of organogenesis (i.e., 120 hpf), although CYP1—except CYP1A— and SULT1ST1 were shown to be already mature in early embryonic development

Brain tumour diagnostics using a DNA methylation-based classifier as a diagnostic support tool

Aims: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. Methods: About 502 CNS tumour samples were analysed using (850 k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. Results: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score >= 0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect, the MP result predicted the right diagnosis for three of these cases. In six cases, the suggested class was interpreted as 'discrepant but noncontributory'. The remaining 33.7% of cases (169/502) had a calibrated score Conclusions: MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information.</div

Tracking of an electron beam through the solar corona with LOFAR

© ESO 2018. The Sun's activity leads to bursts of radio emission, among other phenomena. An example is type-III radio bursts. They occur frequently and appear as short-lived structures rapidly drifting from high to low frequencies in dynamic radio spectra. They are usually interpreted as signatures of beams of energetic electrons propagating along coronal magnetic field lines. Here we present novel interferometric LOFAR (LOw Frequency ARray) observations of three solar type-III radio bursts and their reverse bursts with high spectral, spatial, and temporal resolution. They are consistent with a propagation of the radio sources along the coronal magnetic field lines with nonuniform speed. Hence, the type-III radio bursts cannot be generated by a monoenergetic electron beam, but by an ensemble of energetic electrons with a spread distribution in velocity and energy. Additionally, the density profile along the propagation path is derived in the corona. It agrees well with three-fold coronal density model by (1961, ApJ, 133, 983)