Novel cargo-binding site in the β and δ subunits of coatomer

Arginine (R)-based ER localization signals are sorting motifs that confer transient ER localization to unassembled subunits of multimeric membrane proteins. The COPI vesicle coat binds R-based signals but the molecular details remain unknown. Here, we use reporter membrane proteins based on the proteolipid Pmp2 fused to GFP and allele swapping of COPI subunits to map the recognition site for R-based signals. We show that two highly conserved stretches—in the β- and δ-COPI subunits—are required to maintain Pmp2GFP reporters exposing R-based signals in the ER. Combining a deletion of 21 residues in δ-COP together with the mutation of three residues in β-COP gave rise to a COPI coat that had lost its ability to recognize R-based signals, whilst the recognition of C-terminal di-lysine signals remained unimpaired. A homology model of the COPI trunk domain illustrates the recognition of R-based signals by COPI

High-resolution monitoring of toxic dinoflagellate species and their biogeographic distribution in the North Atlantic and Polar Seas

Dinoflagellate species of the genus Dinophysis have become target organisms for surveillance and monitoring of microalgae as they may produce potent diarrhetic shellfish toxins and therefore have negative socio-economic impacts. The formation of Dinophysis blooms as well as toxin composition and cellular toxin content depends on several multifactorial climate and environmental drivers and it might be expected that the occurrence of toxic events becomes more intense, widespread, frequent and unexpected in future decades due to climate variability. Conventional methods for the identification of microalgae e.g. microscopy, still have some deficiencies as they are very time-consuming and need special knowledge and experience, especially in case of difficult morphological species distinction. Standard quantification methods also might fail to detect and determine Dinophysis species due to their typically low cell densities and their spatial heterogeneity (=patchiness). Therefore innovative technologies for environmental monitoring of toxic microalgae are needed to prevent humans and aquatic environments from toxic threats and damage. We analysed the occurrence, abundance and dispersal of toxic dinoflagellate species in Nordic seas and the Arctic Ocean. Genetic analyses included a modular composed autonomous rRNA biosensor approach that allows rapid, precise and economically efficient high-resolution quantification and identification of microalgae in aquatic environments. Next generation sequencing (Illumina) was used to get additional information on distributional patterns of the most common dinoflagellate species in the observation area

Experiences with Glofitamab Administration following CAR T Therapy in Patients with Relapsed Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is a rare type of B-cell Non-Hodgkin lymphoma (NHL) affecting predominantly male patients. While complete remissions following first-line treatment are frequent, most patients ultimately relapse, with a usually aggressive further disease course. The use of cytarabine-comprising induction chemotherapy and autologous stem cell transplantation, Rituximab maintenance, Bruton's tyrosine kinase (BTK) inhibitors and CAR T therapy has substantially improved survival. Still, options for patients relapsing after CAR T therapy are limited and recommendations for the treatment of these patients are lacking. We report two cases of patients with mantle cell lymphoma who relapsed after CAR T therapy and were treated with the bispecific CD20/CD3 T cell engaging antibody glofitamab. Both patients showed marked increases of circulating CAR T cells and objective responses after glofitamab administration. Therapy was tolerated without relevant side effects in both patients. One patient completed all 12 planned cycles of glofitamab therapy and was alive and without clinical progression at the last follow-up. The second patient declined further treatment after the first cycle and succumbed to disease progression. We review the literature and investigate possible mechanisms involved in the observed responses after administration of glofitamab, such as proliferation of CAR T cells, anti-tumor effects of the bispecific antibody and the role of other possibly contributing factors. Therapy with bispecific antibodies might offer an effective and well-tolerated option for patients with mantle cell lymphoma relapsing after CAR T therapy

Plankton Multiproxy Analyses in the Northern Patagonian Shelf, Argentina: Community Structure, Phycotoxins, and Characterization of Toxic Alexandrium Strains

The extensive Argentine continental shelf supports high plankton productivity and fish catches. In particular, El Rincón coastal area and the adjacent shelf fronts (38.5-42°S, 58.5-62°W) comprise diverse habitats and hold species of economic and ecological value. So far, studies of the microbial community present at the base of the food web remain scarce. Here, we describe the late winter plankton (5-200 μm) structure in terms of abundance, biomass, species composition, functional groups, and phycotoxin profiles in surface waters of El Rincón in September 2015. Diatoms are the most abundant and the largest contributors to carbon biomass at most stations. They dominated the coastal and inner-shelf (depths 20 μm) heterotrophic protists such as various ciliates and dinoflagellates species were more abundant offshore. Scanning of phycotoxins disclosed that paralytic shellfish poisoning (PSP) toxins were dominated by gonyautoxins-1/4 (GTX1/4), whereas lipophilic toxins were detected in low abundance, for example, domoic acid (DA). However, a bloom of Pseudo-nitzschia spp. (up to 3.6 × 105 cells L-1) was detected at inner-shelf stations. Pectenotoxin-2 (PTX-2) and 13-desmethyl spirolide C (SPX-1) were the most abundant in the field. The PTX-2 co-occurred with Dinophysis spp., mainly D. tripos, while SPX-1 dominated at middle-shelf stations, where cells of Alexandrium catenella (1 strain) and A. ostenfeldii (3 strains) were isolated. The quantitative PSP profiles of the Alexandrium strains differed significantly from the in situ profiles. Moreover, the three A. ostenfeldii strains produced PSP and additionally, five novel spirolides. Phylogenetic analyses of these newly isolated strains from the South Atlantic revealed a new ribotype group, suggesting a biogeographical distinction in the population. The plankton survey presented here contributes baseline knowledge to evaluate potential ecosystem changes and track the global distribution of toxigenic species.Fil: Guinder, Valeria Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Tillmann, Urban. Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung; AlemaniaFil: Krock, Bernd. Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung; AlemaniaFil: Delgado, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Krohn, Torben. Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung; AlemaniaFil: Garzon Cardona, John Edison. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Metfies, Katja. Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung; Alemania. Helmholtz Institute for Functional Marine Biodiversity; AlemaniaFil: López Abbate, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Silva, Ricardo. Instituto Nacional de Investigación y Desarrollo Pesquero; ArgentinaFil: Lara, Ruben Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

Rebound Thrombocytosis after Induction Chemotherapy is a Strong Biomarker for Favorable Outcome in AML Patients

https://scholarlycommons.pacific.edu/pacifican/1478/thumbnail.jp

Impact of a long-lived anticyclonic mesoscale eddy on seawater anomalies in the northeastern tropical Pacific Ocean: a composite analysis from hydrographic measurements, sea level altimetry data, and reanalysis model products

Using observational data, satellite altimeters, and reanalysis model products, we have investigated eddy-induced seawater anomalies and heat and salt transport in the northeastern tropical Pacific Ocean. An eddy detection algorithm (EDA) was used to identify eddy formation at the Mexican Tehuantepec Gulf (TT) in July 2018 during an unusually strong summer wind event. The eddy separated from the coast with a mean translation velocity of 11 cm s−1 and a mean radius of 115 km and traveled 2050–2400 km westwards off the Central American coast, where it was followed at approx 114∘ W and 11∘ N for oceanographic observation between April and May 2019. The in situ observations show that the major eddy impacts are restricted to the upper 300 m of the water column and are traceable down to 1500 m water depth. In the eddy core at 92 m water depth an extreme positive temperature anomaly of 8.2 ∘C, a negative salinity anomaly of −0.78 psu, a positive fluorescence anomaly of +0.8 mg m−3, and a positive dissolved oxygen concentration anomaly of 137 µmol kg−1 are observed. Compared with annual climatological averages in 2018, the water trapped within the eddy is estimated to transport an average positive westward zonal heat anomaly of 85×1012 W and an average westward negative salt anomaly of  kg s−1. The heat transport is the equivalent of 1 % of the total annual zonal eddy-induced heat transport at this latitude in the Pacific Ocean. Understanding the dynamics of long-lived mesoscale eddies that may reach the seafloor in this region of the Pacific Ocean is especially important in light of potential deep-sea mining activities that are being targeted on this area

Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years.

The outcome of AML patients ≥65 years remains disappointing. Current post-induction strategies for elderly AML patients fit for intensive treatment involve additional cycles of chemotherapy or allogeneic transplantation. Consolidation with autologous transplantation (ASCT) is poorly studied in these patients. In this single-center retrospective analysis, we determined survival rates of AML patients ≥65 years undergoing busulfan/cyclophosphamide conditioning before ASCT in first remission between 2007 and 2015. We found elderly AML patients with ASCT to have longer progression-free survival (PFS; 16.3 vs. 5.1 months, P=0.0166) and overall survival (OS; n.r. vs. 8.2 months; P=0.0255) than elderly AML patients without ASCT consolidation. In addition, elderly AML patients undergoing ASCT had comparable PFS (P=0.9462) and OS (P=0.7867) as AML patients below 65 years receiving ASCT consolidation in CR1. Our data suggest that ASCT is an option in elderly fit AML patients who appear to benefit from autologous consolidation similarly to younger AML patients

Plankton Multiproxy Analyses in the Northern Patagonian Shelf, Argentina: Community Structure, Phycotoxins, and Characterization of Toxic Alexandrium Strains

The extensive Argentine continental shelf supports high plankton productivity and fish catches. In particular, El Rincón coastal area and the adjacent shelf fronts (38.5–42°S, 58.5–62°W) comprise diverse habitats and hold species of economic and ecological value. So far, studies of the microbial community present at the base of the food web remain scarce. Here, we describe the late winter plankton (5–200 μm) structure in terms of abundance, biomass, species composition, functional groups, and phycotoxin profiles in surface waters of El Rincón in September 2015. Diatoms are the most abundant and the largest contributors to carbon biomass at most stations. They dominated the coastal and inner-shelf (depths <50 m), while dinoflagellates and small flagellates (<15 μm) dominated offshore at the middle-shelf waters (depth ∼100 m). In addition, large (>20 μm) heterotrophic protists such as various ciliates and dinoflagellates species were more abundant offshore. Scanning of phycotoxins disclosed that paralytic shellfish poisoning (PSP) toxins were dominated by gonyautoxins-1/4 (GTX1/4), whereas lipophilic toxins were detected in low abundance, for example, domoic acid (DA). However, a bloom of Pseudo-nitzschia spp. (up to 3.6 × 105 cells L-1) was detected at inner-shelf stations. Pectenotoxin-2 (PTX-2) and 13-desmethyl spirolide C (SPX-1) were the most abundant in the field. The PTX-2 co-occurred with Dinophysis spp., mainly D. tripos, while SPX-1 dominated at middle-shelf stations, where cells of Alexandrium catenella (1 strain) and A. ostenfeldii (3 strains) were isolated. The quantitative PSP profiles of the Alexandrium strains differed significantly from the in situ profiles. Moreover, the three A. ostenfeldii strains produced PSP and additionally, five novel spirolides. Phylogenetic analyses of these newly isolated strains from the South Atlantic revealed a new ribotype group, suggesting a biogeographical distinction in the population. The plankton survey presented here contributes baseline knowledge to evaluate potential ecosystem changes and track the global distribution of toxigenic species