Gene Therapy Applications to Cancer Treatment

Over the past ten years significant advances have been made in the fields of gene therapy and tumour immunology, such that there now exists a considerable body of evidence validating the proof in the principle of gene therapy based cancer vaccines. While clinical benefit has so far been marginal, data from preclinical and early clinical trials of gene therapy combined with standard therapies are strongly suggestive of additional benefit. Many reasons have been proposed to explain the paucity of clinical responses to single agent vaccination strategies including the poor antigenicity of tumour cells and the development of tolerance through down-regulation of MHC, costimulatory, signal transduction, and other molecules essential for the generation of strong immune responses. In addition, there is now evidence from animal models that the growing tumour may actively inhibit the host immune response. Removal of the primary tumour prior to T cell transfer from the spleen of cancer bearing animals, led to effective tumour cell line specific immunity in the recipient mouse suggesting that there is an ongoing tumour-host interaction. This model also illustrates the potential difficulties of clinical vaccine trials in patients with advanced stage disease

Beschluss und Wissenschaftliche Begründung der Ständigen Impfkommission (STIKO) für die Aktualisierung der Influenza-Impfempfehlung für Personen im Alter von ≥ 60 Jahren

Die STIKO empfiehlt allen Personen im Alter von ≥60 Jahren im Herbst eine jährliche Impfung gegen die saisonale Influenza mit einem inaktivierten, quadrivalenten Influenza-Hochdosis-Impfstoff mit aktueller von der WHO empfohlener Antigenkombination. Solange Hochdosis-Impfstoffe für die Altersgruppe 60-64 Jahre nicht zugelassen sind, werden für die Influenza-Impfung von Personen in diesem Alter weiterhin inaktivierte, quadrivalente Influenza-Impfstoffe (unabhängig vom Impfstofftyp) empfohlen. Eine Empfehlung für die Anwendung eines Influenza-Hochdosis-Impfstoffs ist in gleichem Maße bei der Impfempfehlung für Reisende zu berücksichtigen. Die Veröffentlichung dieser Empfehlung zu diesem Zeitpunkt, ohne Berücksichtigung der aktuellen Verfügbarkeit von Influenza-Hochdosis-Impfstoffen, soll gewährleisten, dass der entsprechende Impfstoffbedarf bei der Planung, Produktion und Beschaffung von Influenza-Impfstoffen ab der Saison 2021/2022 berücksichtigt werden kann

Dissociation of Cohesin from Chromosome Arms and Loss of Arm Cohesion during Early Mitosis Depends on Phosphorylation of SA2

Cohesin is a protein complex that is required to hold sister chromatids together. Cleavage of the Scc1 subunit of cohesin by the protease separase releases the complex from chromosomes and thereby enables the separation of sister chromatids in anaphase. In vertebrate cells, the bulk of cohesin dissociates from chromosome arms already during prophase and prometaphase without cleavage of Scc1. Polo-like kinase 1 (Plk1) and Aurora-B are required for this dissociation process, and Plk1 can phosphorylate the cohesin subunits Scc1 and SA2 in vitro, consistent with the possibility that cohesin phosphorylation by Plk1 triggers the dissociation of cohesin from chromosome arms. However, this hypothesis has not been tested yet, and in budding yeast it has been found that phosphorylation of Scc1 by the Polo-like kinase Cdc5 enhances the cleavability of cohesin, but does not lead to separase-independent dissociation of cohesin from chromosomes. To address the functional significance of cohesin phosphorylation in human cells, we have searched for phosphorylation sites on all four subunits of cohesin by mass spectrometry. We have identified numerous mitosis-specific sites on Scc1 and SA2, mutated them, and expressed nonphosphorylatable forms of both proteins stably at physiological levels in human cells. The analysis of these cells lines, in conjunction with biochemical experiments in vitro, indicate that Scc1 phosphorylation is dispensable for cohesin dissociation from chromosomes in early mitosis but enhances the cleavability of Scc1 by separase. In contrast, our data reveal that phosphorylation of SA2 is essential for cohesin dissociation during prophase and prometaphase, but is not required for cohesin cleavage by separase. The similarity of the phenotype obtained after expression of nonphosphorylatable SA2 in human cells to that seen after the depletion of Plk1 suggests that SA2 is the critical target of Plk1 in the cohesin dissociation pathway

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Macroparasite community in molluscs of a tidal basin in the Wadden Sea

We provide a quantitative inventory of macroparasites in intertidal molluscs from a tidal basin in the Wadden Sea (eastern North Sea). Gastropods and bivalves contained a species rich macroparasite community consisting of trematodes (26 species), turbellarians (1), nematodes (1), copepods (2) and polychaetes (1) in 3,800 host individuals from 10 host species. Highest parasite burdens were observed in the gastropods Hydrobia ulvae and Littorina littorea and in the bivalves Cerastoderma edule and Mytilus edulis. In contrast, only one parasite species and no trematodes were found in Crepidula fornicata. The parasite community in the molluscs was similar to other Western European localities but some parasite species showed obvious differences, related to the large-scale distribution of intermediate and final hosts. Parasitism seems to be a common phenomenon in molluscs of the Wadden Sea and hence the detrimental effects observed in experiments can be expected to frequently happen in the field.Keywords: Trematodes - Nematodes - Copepods - Polydora ciliata - Parasitism - Intertidal - Wadden Sea - Gastropods - Bivalve

Overview: Quasi-Lagrangian observations of Arctic air mass transformations -Introduction and initial results of the HALO-(AC) 3 aircraft campaign

International audienceThe global warming is amplified in the Arctic. To collect data that help to constrain weather and climate models, which often do not realistically represent the enhanced Arctic warming, the HALO-(AC)³ aircraft campaign was conducted in March and April 2022 over the Norwegian and Greenland Seas, the Fram Strait, and the central Arctic Ocean. Observations were made over areas of open ocean, the marginal sea ice zone, and the central Arctic sea ice. Two low-flying and one long-range, high-altitude research aircraft have been employed. Whenever possible, the three aircraft were flown in collocated formation. The campaign focused on one specific challenge posed by the models: The reasonable representation of transformations of air masses during their meridional transport into (northward by moist and warm air intrusions, WAIs) and out of (southward via marine cold air outbreaks, CAOs) the Arctic. To observe the air mass transformations, a quasi-Lagrangian flight strategy using trajectory calculations was realized enabling to sample the moving air mass parcels twice along their trajectories. Eight distinct WAI and 12 CAO cases were probed extensively. From the quasi-Lagrangian measurements, we have derived the diabatic heating and moistening of the moving air masses during CAOs and WAIs, the development of cloud macrophysical and microphysical properties along the southward pathways of the air masses during CAOs, and the moisture budget of WAIs. As an example result, we have obtained typical values of the surface-driven diabatic heating between 1–3 K h-1 and of the near-surface moistening between 0.05–0.3 g kg-1 h-1 within the lowest about 0.5 km. From the observations of WAIs, a weak diabatic cooling of up to 0.4 K h-1 and a moisture loss of up to 0.1 g kg-1 h-1 from the ground to about 5 km altitude were derived. In addition, we discuss the frequency of occurrence of the different thermodynamic phases of Arctic low-level clouds, the interaction of Arctic cirrus with sea ice, water vapor, and aerosol particles, and the characteristic microphysical and chemical properties of Arctic aerosol particles. Finally, we provide proof of a concept to measure mesoscale divergence and subsidence in the Arctic using data from dropsondes released during circular flight patterns