68 research outputs found
Microbial communities and bioactive compounds in marine sponges of the family Irciniidae-a review
Marine sponges harbour complex microbial communities of ecological and biotechnological importance. Here, we propose the application of the widespread sponge family Irciniidae as an appropriate model in microbiology and biochemistry research. Half a gram of one Irciniidae specimen hosts hundreds of bacterial species-the vast majority of which are difficult to cultivate-and dozens of fungal and archaeal species. The structure of these symbiont assemblages is shaped by the sponge host and is highly stable over space and time. Two types of quorum-sensing molecules have been detected in these animals, hinting at microbe-microbe and host-microbe signalling being important processes governing the dynamics of the Irciniidae holobiont. Irciniids are vulnerable to disease outbreaks, and concerns have emerged about their conservation in a changing climate. They are nevertheless amenable to mariculture and laboratory maintenance, being attractive targets for metabolite harvesting and experimental biology endeavours. Several bioactive terpenoids and polyketides have been retrieved from Irciniidae sponges, but the actual producer (host or symbiont) of these compounds has rarely been clarified. To tackle this, and further pertinent questions concerning the functioning, resilience and physiology of these organisms, truly multi-layered approaches integrating cutting-edge microbiology, biochemistry, genetics and zoology research are needed.Portuguese Foundation [PTDC/MAR/101431/2008, PTDC/BIA-MIC/3865/2012]; European Regional Development Fund (ERDF) through the Operational Competitiveness Programme (COMPETE); national funds through FCT (Foundation for Science and Technology) [PEst-C/MAR/LA0015/2011]; FCT [SFRH/BD/60873/2009]info:eu-repo/semantics/publishedVersio
Differentiation between rebound thymic hyperplasia and thymic relapse after chemotherapy in pediatric Hodgkin lymphoma
Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum.
After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated.
After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth.
Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH
Hodgkin lymphoma:hypodense lesions in mediastinal masses
Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with mediastinal involvement from the EuroNet-PHL-C1 trial and explored correlations of HDV with patient characteristics, mediastinal tumor volume and progression-free survival. HDV occurred in 350 of 1178 patients (29.7%), typically in larger mediastinal volumes. There were different patterns in appearance with single lesions found in 243 patients (69.4%), multiple lesions in 107 patients (30.6%). Well delineated lesions were found in 248 cases (70.1%), diffuse lesions were seen in 102 cases (29.1%). Clinically, B symptoms occurred more often in patients with HDV (47.7% compared to 35.0% without HDV (p = 0.039)) and patients with HDV tended to be in higher risk groups. Inadequate overall early-18F-FDG-PET-response was strongly correlated with the occurrence of hypodense lesions (p < 0.001). Patients with total HDV > 40 ml (n = 80) had a 5 year PFS of 79.6% compared to 89.7% (p = 0.01) in patients with HDV < 40 ml or no HDV. This difference in PFS is not caused by treatment group alone. HDV is a common phenomenon in HL with mediastinal involvement.</p
Industry-Scale Orchestrated Federated Learning for Drug Discovery
To apply federated learning to drug discovery we developed a novel platform
in the context of European Innovative Medicines Initiative (IMI) project
MELLODDY (grant n{\deg}831472), which was comprised of 10 pharmaceutical
companies, academic research labs, large industrial companies and startups. The
MELLODDY platform was the first industry-scale platform to enable the creation
of a global federated model for drug discovery without sharing the confidential
data sets of the individual partners. The federated model was trained on the
platform by aggregating the gradients of all contributing partners in a
cryptographic, secure way following each training iteration. The platform was
deployed on an Amazon Web Services (AWS) multi-account architecture running
Kubernetes clusters in private subnets. Organisationally, the roles of the
different partners were codified as different rights and permissions on the
platform and administrated in a decentralized way. The MELLODDY platform
generated new scientific discoveries which are described in a companion paper.Comment: 9 pages, 4 figures, to appear in AAAI-23 ([IAAI-23 track] Deployed
Highly Innovative Applications of AI
Activation of the P2X7 ion channel by soluble and covalently bound ligands
The homotrimeric P2X7 purinergic receptor has sparked interest because of its capacity to sense adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD) released from cells and to induce calcium signaling and cell death. Here, we examine the response of arginine mutants of P2X7 to soluble and covalently bound ligands. High concentrations of ecto-ATP gate P2X7 by acting as a soluble ligand and low concentrations of ecto-NAD gate P2X7 following ADP-ribosylation at R125 catalyzed by toxin-related ecto-ADP-ribosyltransferase ART2.2. R125 lies on a prominent cysteine-rich finger at the interface of adjacent receptor subunits, and ADP-ribosylation at this site likely places the common adenine nucleotide moiety into the ligand-binding pocket of P2X7
Denkmalschutz und Stadtpolitik. Anmerkungen zum 25. Jahrestag des Förderprogramms Städtebaulicher Denkmalschutz
Drei Fälle, die zeigen, wohin es führt, wenn der städtebauliche Denkmalschutz – der der Ensembles und der der Bauwerke – von irregeleiteter politischer Übermacht außer Kraft gesetzt wird. Sie zeugen von der Schwierigkeit und der Bedeutung einer Arbeit, zu deren Durchsetzung es immer wieder nötig sein wird, Öffentlichkeit zu mobilisieren und sich der Unterstützung der Bürgerschaft zu versichern. Viel besser ist es natürlich, wenn alle Beteiligte – Fachleute, Eigentümer, kommunale und Landesinstanzen, die Öffentlichkeit – von vornherein an einem Strang ziehen. Eine solche Kooperation zu organisieren ist das Geheimnis vieler Erfolge; die Dokumentationen des Förderprogramms, das von seiten des Bundes in 25 Jahren mit über sechs Milliarden Euro unterstützt wurde, zeigen es an vielen Beispielen
Alte Werke auf neuen Instrumenten spielen. Zum Begriff der Wiederaufführung in Musik und Architektur
Wiederaufführungen sind in der musikalischen Praxis nicht nur gang und gäbe, sie bilden die Basis der gesamten Konzertpraxis; in der Architektur sind sie nicht selten umstritten. Einer der Gründe dafür ist, daß die über Jahrhunderte gewachsenen Städte, durch die die europäische Kultur sich auszeichnet, nicht als das architektonische Repertoire erkannt sind, das sie vorstellen. Der Einheimische ebenso wie der Reisende kann dessen Werkbestandteile sehend immer wieder wahrnehmen wie der hörende Rezipient Lieder, Sonaten, Sinfonien. Wo Bombenkrieg und Abrißwahn an wichtigen Stellen schmerzhafte Lücken in dieses Repertoire gerissen haben, spricht nichts gegen die Schließung der Lücke durch eine Wiederaufführung des verlorenen Werkes. Dessen Bedeutung auf seine materiale Identität zu beschränken ist ein ästhetischer Kurzschluß, der weder der theoretischen noch der praktischen Überprüfung standhält. Genau wie in der Konzertpraxis geht es dabei um die Qualität des Spiels und der Instrumente, und genau wie dort gründet sich beides auf die Dokumentation des Originals: hier Noten, dort Pläne, Bilder, Befunde. Der Unterschied zur Musik liegt in der Standortbezogenheit und der funktionellen Variabilität. Das erneuerte Seh-Werk der Architektur bedarf, anders als das bewegliche Hör-Werk der Musik, der Authentizität des originalen Standorts, um sich als erneuertes Repertoire-Element zu beglaubigen, die neue Nutzung aber, die ihm in der Regel aufgegeben ist, erzwingt ein Maß inwendiger Veränderung, dem immer wieder auch die alten Bauwerke unterlegen haben, ohne ihren ästhetischen Rang dadurch einzubüßen
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