Episodic records of jellyfish ingestion of plastic items reveal a novel pathway for trophic transference of marine litter

Invertebrates represent the most plentiful component of marine biodiversity. To date, only few species have been documented for marine litter intake. Here, we report for the first time the presence of macroplastic debris in a jellyfish species. Such novel target to plastic pollution highlights an under studied vector of marine litter along marine trophic web, raising further concern over the impact on marine wildlife

Benchmarking whole exome sequencing in the German Network for Personalized Medicine

Introduction Whole Exome Sequencing (WES) has emerged as an efficient tool in clinical cancer diagnostics to broaden the scope from panel-based diagnostics to screening of all genes and enabling robust determination of complex biomarkers in a single analysis. Methods To assess concordance, six formalin-fixed paraffin-embedded (FFPE) tissue specimens and four commercial reference standards were analyzed by WES as matched tumor-normal DNA at 21 NGS centers in Germany, each employing local wet-lab and bioinformatics investigating somatic and germline variants, copy-number alteration (CNA), and different complex biomarkers. Somatic variant calling was performed in 494 diagnostically relevant cancer genes. In addition, all raw data were re-analyzed with a central bioinformatic pipeline to separate wet- and dry-lab variability. Results The mean positive percentage agreement (PPA) of somatic variant calling was 76% and positive predictive value (PPV) 89% compared a consensus list of variants found by at least five centers. Variant filtering was identified as the main cause for divergent variant calls. Adjusting filter criteria and re-analysis increased the PPA to 88% for all and 97% for clinically relevant variants. CNA calls were concordant for 82% of genomic regions. Calls of homologous recombination deficiency (HRD), tumor mutational burden (TMB), and microsatellite instability (MSI) status were concordant for 94%, 93%, and 93% respectively. Variability of CNAs and complex biomarkers did not increase considerably using the central pipeline and was hence attributed to wet-lab differences. Conclusion Continuous optimization of bioinformatic workflows and participating in round robin tests are recommend

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Protein engineering studies of myoglobin

The goals of the work described in this thesis were to gain further insight into structure-function relationships in the oxygen binding protein myoglobin, alter the structure of this protein to enhance a low level latent peroxidase function, and to add a new functionality in the form of a manganese binding site. An initial step in these studies was the elucidation of the high resolution structure of recombinant horse heart myoglobin to confirm that this protein is properly expressed and folded in a manner comparable to horse heart myoglobin obtained from natural sources. The additional variant myoglobins that were studied were organized into three groups. The first was constructed to probe aspects of the role of the distal heme pocket residue His64. Replacement of this histidine with threonine generated a five coordinate heme iron atom in the ferric state, whereas substitution with tyrosine yielded a six coordinate heme iron atom. The lack of peroxidase activity in the His64Thr variant protein appears to be a direct result of an inability to participate effectively in proton transfer during peroxide heterolysis. For the His64Tyr variant protein, the difficulty of dissociating the distal tyrosine ligand from the heme iron center appears to prevent hydrogen peroxide binding to the heme and thus limit peroxidase activity. Additional experiments were designed to facilitate the interpretation and understanding of the structural consequences of ligand binding to myoglobin. In particular, structural characterizations were completed of azide - heme ligation complexes with wild-type recombinant horse heart myoglobin and the His64Thr variant protein. These studies established that there are no large structural rearrangements required for the formation of an azide complex with either protein. However, substitution of His64 with threonine did show two unexpected effects in terms of azide complex formation. These included the observation of two bound azide conformations and on the proximal side of the heme pocket, the presence of a shorter hydrogen bond between Ser92 and the proximal heme iron ligand His93. The second group of variant proteins studied was prepared to probe the influence of amino acid substitutions in the heme binding pocket. These included replacements at the distal heme pocket residues Leu29 and Val67, and at Leu 104 which is located on the proximal side of the heme. These studies showed that substitution of Leu29 for a tyrosine or a lysine can be accommodated in the heme pocket of myoglobin. The peroxidase activity of both variant proteins is higher than that of wild-type myoglobin. This increase in activity appears to be correlated primarily with an increase in the polarity of the distal heme pocket. Surprisingly, the observed increase in heme reduction potential for the Val67Arg variant protein was also accompanied by an increase in peroxidase activity to approximately 8 times that of wild-type myoglobin. The Leul04Asn variant protein also showed an approximate 3-fold increase in activity towards hydrogen peroxide. A third group of variant proteins was designed to build a functional manganese binding site into horse heart myoglobin. Structural studies of the Lys45Glu and Lys45Glu/Lys63Glu variant proteins were conducted and indicate manganese binding occurs at the solvent exposed edge of the heme with ligands being formed by Glu45 and the heme D-propionate group. These residues constitute a site that is comparable to the one found later in structural studies of a manganese peroxidase by other workers. These myoglobin variants show ~ 3-fold enhancement in the rate of oxidation of Mn(II) to Mn(III) in the presence of hydrogen peroxide. Additional structural studies using Cd(II) ions were also conducted, and in this case two binding sites were located. Overall, the present work demonstrates that amino acid substitutions can influence the latent peroxidase activity of myoglobin and that it is possible to construct a Mn(II) ion binding site at an appropriate position on the surface of myoglobin to promote detectable manganese peroxidase activity.Medicine, Faculty ofBiochemistry and Molecular Biology, Department ofGraduat

Bewegungsanweisungen - Hilfe oder Hindernis beim Erlernen sportlicher Bewegungen?

Gröben B, Maurus P. Bewegungsanweisungen - Hilfe oder Hindernis beim Erlernen sportlicher Bewegungen? In: Prohl R, Laging R, eds. Bewegungskompetenz als Bildungsdimension. Hamburg: Czwalina; In Press: 137-152

Hepatoblastoma in an Infant after Contraceptive Intake during Pregnancy

To the Editor: In recent studies, an association between the use of contraceptive steroids and the development of benign liver adenomas has been suggested.1 To our knowledge, nothing has been reported about a possible tumorigenic effect to the fetus if the mother inadvertently continues to use oral contraceptives into pregnancy. We observed a seven-month-old male infant with an inoperable hepatoblastoma of the mixed type. Parents and grandparents were in good health. Among the great-grandparents, three had died of cancer: of a hypernephroma, of a tumor of the colon and of a liver cancer (possibly a hepatoma). At the time. No extract is available for articles shorter than 400 words. © 1977, Massachusetts Medical Society. All rights reserved.SCOPUS: le.jinfo:eu-repo/semantics/publishe

Apomorphine pump in advanced Parkinson's disease: Effects on motor and nonmotor symptoms with brain metabolism correlations

International audienc