Microbial community day-to-day dynamics during a spring algal bloom event in a tributary of Three Gorges Reservoir.

The microbial food-loop is critical to energy flow in aquatic food webs. We tested the hypothesis that species composition and relative abundance in a microbial community would be modified by the development of toxic algal blooms either by enhanced carbon production or toxicity. This study tracked the response of the microbial community with respect to composition and relative abundance during a 7-day algal bloom event in the Three Gorges Reservoir in May 2018. Chlorophyll a biomass, microscopic identification and cell counting of algae and algal abundance (ind. L-1) and carbon, nutrient concentrations (total phosphorus and nitrogen, dissolved total phosphorus and nitrogen), and DNA high throughput sequencing were measured daily. Algal density (1.2 × 109 ind. L-1) and Chlorophyll a (219 µg L-1) peaked on May 20th-21st, when the phytoplankton community was dominated by Chlorella spp. and Microcystis spp. The concentrations of both dissolved total nitrogen and phosphorus declined during the bloom period. Based on DNA high throughput sequencing data, the relative abundance of eukaryotic phytoplankton, microzooplankton (20-200 µm), mesozooplankton (>200 µm), and fungal communities varied day by day while the prokaryotic community revealed a more consistent structure. Enhanced carbon production during the bloom was closely associated with increased heterotrophic microbial composition in both the prokaryotic and eukaryotic communities. A storm event, however, that caused surface cooling and deep mixing of the water column greatly modified the composition and relative abundance of species in the microbial loop. The high temporal variability and dynamics observed in this study suggest that many factors, and not just algal blooms, were interacting to determine the composition and relative abundance of species of the microbial loop.

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.

BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma.

The BCL6 gene codes for a zinc-finger transcription factor and is involved in chromosomal rearrangements in 30-40% of diffuse large-cell lymphoma (DLCL). These rearrangements cluster within the 5' regulatory region of BCL6 spanning its first non-coding exon. To determine the functional consequences of these alterations, we have analyzed the structure of the rearranged BCL6 alleles and their corresponding RNA and protein species in two DLCL biopsies and one tumor cell line which carried the t(3;14)(q27;q32) translocation involving the BCL6 and immunoglobulin heavy-chain (IgH) loci. In all three cases, the breakpoints were mapped within the IgH switch region and the BCL6 first intron, leading to the juxtaposition of part of the IgH locus upstream and in the same transcriptional orientation to the BCL6 coding exons. An analysis of cDNA clones showed that these recombinations generate chimeric IgH-BCL6 transcripts which initiated from IgH germline transcript promoters (I mu or I gamma 3), but retain a normal BCL6 coding domain. In the tumor cell line, the chimeric I gamma 3-BCL6 allele, but not the germline BCL6 gene, was transcriptionally active and produced a normal BCL6 protein. These findings indicate that t(3;14) translocations alter BCL6 expression by promoter substitution and imply that the consequence of these alterations is the deregulated expression of a normal BCL6 protein.