B cell-specific conditional expression of Myd88(p.L252P) leads to the development of diffuse large B cell lymphoma in mice

The adaptor protein MYD88 is critical to relay activation of Toll-like receptor signaling to NF-{kappa}B activation.MYD88 mutations, particularly the p.L265P mutation, have been described in numerous distinct B cell malignancies, including diffuse large B cell lymphoma (DLBCL). 29% of activated B cell (ABC)-type DLBCL, which is characterized by constitutive activation of the NF-{kappa}B pathway, carry the p.L265P mutation. In addition, ABC-DLBCL frequently displays focal copy number gains affecting BCL2. Here, we generated a novel mouse model, in which Cre-mediated recombination, specifically in B cells, leads to the conditional expression of Myd88(p.L252P)(the orthologous position of the human MYD88(p.L265P) mutation) from the endogenous locus. These animals develop a lympho-proliferative disease, and occasional transformation into clonal lymphomas. The clonal disease displays morphological and immunophenotypical characteristics of ABC-DLBCL. Lymphomagenesis can be accelerated by crossing in a further novel allele, which mediates conditional overexpression ofBCL2 Cross-validation experiments in human DLBCL samples revealed that bothMYD88andCD79Bmutations are substantially enriched in ABC-DLBCL, compared to germinal center B cell DLBCL. Furthermore, analyses of human DLBCL genome sequencing data confirmed that BCL2 amplifications frequently co-occur with MYD88 mutations, further validating our approach. Lastly,in silicoexperiments revealed that particularly MYD88-mutant ABC-DLBCL cells display an actionable addiction to BCL2. Altogether, we generated a novel autochthonous mouse model of ABC-DLBCL, which could be used as a preclinical platform for the development and validation of novel therapeutic approaches for the treatment of ABC-DLBCL

Incised valley paleoenvironments interpreted by seismic stratigraphic approach in Patos Lagoon, Southern Brazil

<div><p>ABSTRACT: The Rio Grande do Sul (RS) coastal plain area (33,000 km 2 ) had its physiography modified several times through the Quaternary, responding to allogenic and autogenic forcings. The Patos Lagoon covers a significant area of RS coastal plain (10,000 km 2 ), where incised valleys were identified in previous works. About 1,000 km of high resolution (3.5 kHz) seismic profiles, radiocarbon datings, Standard Penetration Test (SPT) and gravity cores were analyzed to interpret the paleoenvironmental evolution as preserved in incised valley infills. Seismic facies were recognized by seismic parameters. The sediment cores were used to ground-truth the seismic interpretations and help in the paleoenvironmental identification. Key surfaces were established to detail the stratigraphical framework, and seismic facies were grouped into four seismic units, which one classified in respective system tracts within three depositional sequences. The oldest preserved deposits are predominantly fluvial and estuarine facies, representing the falling stage and lowstand system tracts. The Holocene transgressive records are dominated by muddy material, mainly represented by estuarine facies with local variations. The transgression culminated in Late Holocene deposits of Patos Lagoon, representing the highstand system tract. The depositional pattern of the vertical succession was controlled by eustatic variations, while the autogenic forcing (paleogeography and sediment supply) modulated the local facies variation.</p></div

Loricate Choanoflagellates from the South Atlantic coastal zone (~32 S) including the description of diplotheca tricyclica sp. nov.

The biodiversity of marine heterotrophic protists is poorly known in the South Atlantic coastal zone (~32 °S) especially regarding the nanoflagellates. The presence of loricate choanoflagellates was reported for the first time in the Patos Lagoon estuary and the adjacent coastal zone. Seventeen species of eleven genera of loricate choanoflagellates were observed between October 1998 and May 2000 in fixed water samples (lugol's solution + glutaraldehyde) in a JEM 100-SX transmission electron microscope. Most species were recorded in euhaline and mixopolyhaline waters during the spring and summer, none in autumn and a few (four) in winter. The absence of choanoflagellates at the more sheltered inshore stations is due freshwater influence, and at the beach station,probably due the strong wave action. The probably cosmopolitan species Pleurasiga minima, Cosmoeca norvegica, C. ventricosa and Parvicorbicula circularis were present in spring or summer in the estuary channel and coastal area while Stephanoeca diplocostata which apparently prefers lower temperature, was recorded in winter. Calotheca alata and Campyloacantha spinifera are mainly temperate species and were present in spring. The new species Diplotheca tricyclica was recorded at the estuary channel in the summer 1999, in high salinity water.A biodiversidade de protistas heterotróficos é pouco conhecida na zona costeira do Atlântico Sul (~32 °S), especialmente dos nanoflagelados. No presente estudo, foi registrada pela primeira vez a presença de coanoflagelados loricados no estuário da Lagoa dos Patos e na zona costeira adjacente. Dezessete espécies de onze gêneros de coanoflagelados loricados foram observadas em amostras de água fixadas (solução de lugol + glutaraldeido) coletadas entre outubro de 1998 e maio de 2000, e analisadas em microscópio de transmissão JEM 100-SX. A maior parte das espécies foi registrada em águas euhalinas e mixopolihalinas durante a primavera e o verão, nenhuma no outono e poucas (quatro) no inverno. A ausência de coanoflagelados nas estações mais protegidas deve-se a influência da água doce, e na estação da praia deve-se, provavelmente, a forte ação das ondas. As espécies, provavelmente cosmopolitas, Pleurasiga minima, Cosmoeca norvegica, C. ventricosa and Parvicorbicula circularis ocorreram na primavera ou no verão no canal principal do estuário e na área costeira, enquanto Stephanoeca diplocostata, que aparentemente prefere baixas temperaturas, foi registrada no inverno. Calotheca alata e Campyloacantha spinifera são principalmente de ambientes temperados e estiveram presentes na primavera. Uma espécie nova, Diplotheca tricyclica, foi registrada na área do canal principal do estuário, no verão de 1999, em águas de alta salinidade

Habitat selection of the pink shrimp farfantepenaeus paulensis and the blue crab callinectes sapidus in an estuary in southern Brazil: influence of salinity and submerged seagrass meadows

This study was conducted in two estuarine inlets (Saco da Mangueira and Saco do Arraial) at the Patos Lagoon estuary, southern Brazil. The changes in relative abundance and size of post-larvae and juvenile shrimp Farfantepenaeus paulensis and juvenile blue crab Callinectes sapidus were compared, considering the influence of salinity and the presence of submerged seagrass meadows. The analyses were performed using generalized linear models (GLM) for abundance variations and ANOVA for variations on the size of individuals. The pink shrimp was more abundant at Saco da Mangueira, in seagrass meadows and areas of higher salinity. The blue crab was more abundant at Saco do Arraial and in lower levels of salinity. The importance of submerged vegetation for the blue crab lies in a preference of smaller crabs of the species for the seagrass meadows. It has been shown that these species choose different habitats in the estuary, and both the salinity and the presence of submerged seagrass meadows influence the selection of habitat