ALBERT

Description: Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org . Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software.

Description: Stockwell, J. D., Weber, T. C., Baukus, A. J., and Jech, J. M. 2013. On the use of omnidirectional sonars and downwards-looking echosounders to assess pelagic fish distributions during and after midwater trawling. – ICES Journal of Marine Science, 70:196–203. Small pelagic fish can play an important role in the structure and function of ecosystems, and there is increasing interest in their non-market value. At the scale of fish aggregations, however, the impact of fishing has received relatively little attention, with most effort devoted to impacts of vessel and gear avoidance on stock size estimates. We used concurrent deployment of a downwards-looking echosounder (Simrad ES60 system) and an omnidirectional sonar (Simrad SP90 system) during commercial pairtrawling operations for Atlantic herring ( Clupea harengus ) in the Gulf of Maine to examine their potential for studying the impacts of fishing on herring aggregations. We compared a number of aggregation metrics to illustrate similarities and differences between the two systems, and then qualitatively examined their properties during and after pairtrawling events to illustrate potential applications. Our results suggest that using both downwards-looking and omnidirectional systems provides complementary information on fish aggregation metrics. Future applications of these systems in before–after–control-impact (BACI) designs may help inform management agencies when evaluating potential impacts of fishing at the time and space scales of pelagic fish aggregations.

Description: Microbial secondary metabolites are a potent source of antibiotics and other pharmaceuticals. Genome mining of their biosynthetic gene clusters has become a key method to accelerate their identification and characterization. In 2011, we developed antiSMASH, a web-based analysis platform that automates this process. Here, we present the highly improved antiSMASH 2.0 release, available at http://antismash.secondarymetabolites.org/ . For the new version, antiSMASH was entirely re-designed using a plug-and-play concept that allows easy integration of novel predictor or output modules. antiSMASH 2.0 now supports input of multiple related sequences simultaneously (multi-FASTA/GenBank/EMBL), which allows the analysis of draft genomes comprising multiple contigs. Moreover, direct analysis of protein sequences is now possible. antiSMASH 2.0 has also been equipped with the capacity to detect additional classes of secondary metabolites, including oligosaccharide antibiotics, phenazines, thiopeptides, homo-serine lactones, phosphonates and furans. The algorithm for predicting the core structure of the cluster end product is now also covering lantipeptides, in addition to polyketides and non-ribosomal peptides. The antiSMASH ClusterBlast functionality has been extended to identify sub-clusters involved in the biosynthesis of specific chemical building blocks. The new features currently make antiSMASH 2.0 the most comprehensive resource for identifying and analyzing novel secondary metabolite biosynthetic pathways in microorganisms.

Description: Active- and passive-acoustic methods are widely used tools for observing, monitoring, and understanding marine ecosystems. From 25 to 28 May 2015, 214 scientists from 31 nations gathered for an ICES symposium on Marine Ecosystem Acoustics (SoME Acoustics) to discuss three major themes related to acoustic observations of marine ecosystems: (i) recent developments in acoustic and platform technologies; (ii) acoustic characterisation of aquatic organisms, ecosystem structure, and ecosystem processes; and (iii) contribution of acoustics to integrated ecosystem assessments and management. The development of, and access to new instruments, such as broad bandwidth systems, enables insightful ecological studies and innovative management approaches. Unresolved ecological questions and the increasing move towards ecosystem based management pose further challenges to scientists and instrument developers. Considering the SoME Acoustics presentations in the context of three previous ICES symposia on fisheries acoustics, topics increasingly emphasize ecosystem studies and management. The continued expansion of work and progress in marine ecosystem acoustics is due to the cross-disciplinary work of fisheries acousticians, engineers, ecologists, modellers, and others. An analysis of the symposium co-authorship network reveals a highly connected acoustic science community collaborating around the globe.

Description: Secondary metabolites produced by microorganisms are the main source of bioactive compounds that are in use as antimicrobial and anticancer drugs, fungicides, herbicides and pesticides. In the last decade, the increasing availability of microbial genomes has established genome mining as a very important method for the identification of their biosynthetic gene clusters (BGCs). One of the most popular tools for this task is antiSMASH. However, so far, antiSMASH is limited to de novo computing results for user-submitted genomes and only partially connects these with BGCs from other organisms. Therefore, we developed the antiSMASH database, a simple but highly useful new resource to browse antiSMASH-annotated BGCs in the currently 3907 bacterial genomes in the database and perform advanced search queries combining multiple search criteria. antiSMASH-DB is available at http://antismash-db.secondarymetabolites.org/ .

Description: Recent evidence highlights an implication of B lymphocytes in the development and sustainment of chronic graft versus host disease (cGvH). The monoclonal anti-CD20-antibody rituximab has proven effective against steroid refractory cGvH. Data on the role of B lymphocytes in acute GvH (aGvH) is sparse. We report on a reduction of the incidence of aGvH in patients receiving rituximab as an element of conditioning as compared to patients conditioned without rituximab. All 6 patients receiving rituximab suffered from CD20 positive Non-Hodgkin-Lymphoma (NHL) and received cyclosporine and mycophenolate immunosuppression. Immunosuppression in the other 15 patients was achieved either with cyclosporine and mycophenolate (N=11) or cyclosporine and methotrexate (N=4). All patients except for one received dose reduced conditioning. Only patients beyond day 25 are included in the analysis; as of july 20th, 2006 median follow up is 151 days (range 27 to 322 days). Out of six patients receiving rituximab as an element of conditioning, one (16.7 %) developed moderate aGvH. Out of 15 patients who did not receive rituximab during conditioning, 10 (66.7 %) developed moderate to severe aGvH. Two patients developed severe acute GvH after early cessation of immunosuppression and/or donor lymphocyte infusion for progressive disease. If removed from this analysis, 8 out of 13 patients (61.5 %) developed aGvH after conditioning without rituximab. Taken together, these data present a trend that in patients conditioned with rituximab acute GvH occurs less frequently. These are amongst the first data indicating that rituximab might suppress the development of acute GvH. They are in accordance with work published before yet this is the first study systematically comparing two groups of patients. At present, no data exploring the influence of CD20 positive B lymphocytes or the effect of rituximab on graft-versus-tumor effects exist. It therefore remains to be investigated whether the suggested suppression of GvH by rituximab benefits overall survival by reducing transplantation related mortality or whether it is associated with a higher relapse rate due to an abrogated graft versus tumor effect. Furthermore, it remains to be elucidated whether the administration of rituximab before transplantation or during the restoration of the allogeneic immune system exerts prophylactic effects against cGvH and whether this influences both graft versus tumor effects and survival. Finally, we conclude that the addition of rituximab to the treatment of severe steroid refractory acute graft versus host reactions has to be tested in randomized trials.

Description: We tested the feasibility of a reduced-intensity conditioning regimen for hematopoietic stem cell transplantation (HSCT) perspectively allowing an adapted conditioning for performance and disease status. Treatment consisted of 2–4 Gy total body irradiation (TBI), 120mg/m2 fludarabine, 120mg/kg cyclophosphamide, 0–40 mg/kg anti-thymocyte globulin (ATG) and immunosuppression by ciclosporin-A and mycophenolate mofetil. Up to date, 10 patients (median age 59 years) ineligible for conventional conditioning due to age (〉50 years), concomitant disease or previous toxicities have been transplanted on an observational basis after obtaining written informed consent. 2 patients received grafts from related donors, 1 patient an unrelated graft with HLA-C mismatch in GvHD vector and all others unrelated matched grafts. 9 patients (90%) received 2 Gy TBI and ≥30mg/kg ATG. 1 patient received 4 Gy TBI and no ATG since presenting with progressiv disease at time of HSCT and receiving an related graft. Median pre-transplant adapted Charlson index was 2,5 (range 0–6), number of previous chemotherapy protocols 2 (range 1–5). No obvious graft rejection occurred. Of the patients evaluable beyond day +30 (N = 8) 8 patients (100%) achieved consistent neutrophil counts 〉500/μl and 6 (75%) consistent platelet counts of 〉25,000/μl. Median duration for neutropenia was 25 days (range 15 – 44 days) and for thrombocytopenia 23 days (range 7–55 days). 14 units (range 2–58) packed red cells and of 7 units (range 1–62) platelets had to be given. Median hospital stay was 49 days (range 34–66 days). Of 8 patients with a follow up beyond day +30, 6 (75%) showed a chimerism of 〉90% around day +30. 1 patient showed a chimerism of 50% due to parallel relapse while 1 patient was not evaluable due to sepsis. All patients evaluable for toxicity (N=8) had CTC grade 4 hematological toxicity. 6 patients (75%) experienced toxicities CTC ≥3, mainly infections. Two patients (25%) died of treatment-related infections. No gastrointestinal toxicity CTC ≥3° and no case of veno-occlusive disease was observed. Hemorrhagic cystitis CTC 2° was observed in 1 patient (10%). Of the patients with a Charlson index ≥3 (N=5), 2 (40%) died of infections and 3 (60%) experienced only toxicities of ≤3. Of the evaluable patients with neutrophil recovery (N=8), 1 (12,5%) presented with acute GvHD of the skin 2° and 2 (25%) respectively with acute GvHD 1° of the skin or gut. 4 patients (50%) showed no signs of acute GvHD. Of the 2 patients evaluable for day 〉+100, one has chronic limited GvHD. All cases of GvHD required no therapy. Of the three patients evaluable day +100, one suffered from relapse and two are alive in complete remission. Of the patients evaluable day +30 (N=8) two (25%) presented with relapse or progressive disease around day +30, 1 (12,5%) respectively showed stable disease or further remission and 4 patients (50%) showed persisting complete remission. We conclude that the presented regimen is applicable to patients not elegibile for conventional regimens due to its tolerable overall toxicity and particularly low gastrointestinal side effects. Moreover, due to the use of 3 cytotoxic agents and 3 immunosuppressive substances it offers the option for a conditioning adapted to commorbidity, disease status and graft characteristics. A respective stratification will be presented at the meeting.