Reed-sternberg cells form by abscission failure in the presence of functional aurora B kinase

Large multinucleated Reed-Sternberg cells (RS) and large mononucleated Hodgkin cells (H) are traditionally considered to be the neoplastic population in classical Hodgkin lymphoma, (cHL) and postulated to promote the disease. However, the contribution of these larger cells to the progression of cHL remains debatable. We used established cHL cell lines and cHL cellular fractions composed of small mononucleated cells only or enriched in large RS/H cells to investigate RS/H cell origin and to characterize the cells which they derive from. We confirm that the small mononucleated cells give rise to RS/H cells, and we show that the latter proliferate significantly more slowly than the small cells. By using live-cell imaging, we demonstrate that binucleated RS cells are generated by failure of abscission when a few small cells attempt to divide. Finally, our results reveal that the small mononucleated cells are chromosomally unstable, but this is unlikely to be related to a malfunctioning chromosomal passenger protein complex. We propose that the small mononucleated cells, rather than the RS/H cells, are the main drivers of cHL

Neoplasias bidireccionais da tireoide Uma proposta de interpretacao histogenetica

Available from Fundacao para a Ciencia e a Tecnologia, Servico de Informacao e Documentacao, Av. D. Carlos I, 126, 1200 Lisboa / FCT - Fundação para o Ciência e a TecnologiaSIGLEPTPortuga

Survivin is required for stable checkpoint activation in taxol-treated HeLa cells

Survivin is an essential chromosomal passenger protein whose function remains unclear. Here, we have used RNA interference to specifically repress Survivin in cultured HeLa cells. Immunoblot analysis showed that Survivin was no longer detectable in cultures 60 hours after transfection with Survivin-specific siRNA. Live cell analysis showed that many Survivin-depleted cells were delayed in mitosis, and immunofluorescence analysis of fixed specimens revealed that Survivin-depleted cells accumulated in prometaphase with misaligned chromosomes. The chromosomal passenger proteins, INCENP and Aurora-B, which can interact directly with Survivin, were absent from the centromeres of Survivin-depleted cells. These data contribute to the emerging picture that Survivin operates together with INCENP and Aurora-B to perform its mitotic duties. Some Survivin-depleted cells eventually exited mitosis without completing cytokinesis. This resulted in a gradual increase in the percentage of multinucleated cells in the culture. Time-lapse imaging of synchronized cultures revealed that control and Survivin-depleted cells arrested in mitosis in the presence of nocodazole; however, the latter failed to arrest in mitosis when treated with taxol. Immunofluorescence studies revealed that Survivindepleted cells were unable to stably maintain BubR1 at the kinetochores in the presence of either taxol or nocodazole. Our data reveal that Survivin is not required for the spindle assembly checkpoint when it is activated by the loss of microtubules. However, Survivin is required for the maintenance of the checkpoint when it is activated by taxol, which is generally thought to cause a loss of spindle tension

Online testbench for LHCb High Level Trigger validation

The High Level Trigger (HLT) and Data Acquisition (DAQ) system selects about 2 kHz of events out of the 40 MHz of beam crossings. The selected events are consolidated into files on an onsite storage and then sent to permanent storage for subsequent analysis on the Grid. For local and full-chain tests a method to exercise the data-flow through the High Level Trigger when there are no actual data is needed. In order to test the system as much as possible under identical conditions as for data-taking the solution is to inject data at the input of the HLT at a minimum rate of 2 kHz. This is done via a software implementation of the trigger system which sends data to the HLT. The application has to simulate that the data it sends come from real LHCb readout-boards. Both simulation data and previously recorded real data can be re-played through the system in this manner. As the data rate is high (100 MB/s), care has been taken to optimise the emulator for throughput from the Storage Area Network (SAN). The emulator can be run in stand-alone mode or run as a pseudo-subdetector of LHCb, allowing for use of all the standard run-control tools. The architecture, implementation and performance of the emulator will be presente

Hístiocitose de Células de Langerhans: uma Doença - Várias Apresentações

A Histíocitose das células de Langerhans, anteriormente conhecida como Hístiocitose X, é uma doença rara, de etiologia desconhecida e que afecta 2 a 5 crianças por milhão, por ano. Esta doença consiste na proliferação e disseminação de células com característicasparticulares, entre as quais se destacam os grânulos de Birbeck intracitoplasmátícos, a expressão do antigénio de superfície CD la e a expressão citoplasmática e nuclear de proteína SlOO, próprias de células apresentadoras de antigénios no território cutâneo. A história natural varia entre uma doença benigna cora resolução espontânea e uma doença progressiva fatal. Os três casos de hístiocitose de células de Langerhans que descrevemos evidenciam a diversidade de apresentação e evolução desta doença.Palavras-Chave: Hístiocitose, Células de Langerhans; Diagnóstico; Prognóstico; Tratamento

High-speed data-injection for data-flow verification at LHCb

International audienceThe High Level Trigger (HLT) and Data Acquisition System select about 2 kHz of events out of the 40 MHz of beam crossings. The selected events are consolidated into files in onsite storage and then sent to permanent storage for subsequent analysis on the Grid. For local and full-chain tests a method to exercise the data-flow through the High Level Trigger is needed in the absence of real data. In order to test the system as much as possible under identical conditions as for data-taking, the solution would be to inject data at the input of the HLT at a minimum rate of 2 kHz. This is done via a software implementation of the trigger system which sends data to the HLT. The application has to simulate that the data it sends come from real LHCb readout-boards. Data can come from several input streams, which are selected according to probabilities or frequencies. Therefore the emulator offers runs which are not only identical data-flows coming from a sequence on tape, but physics-like pseudo-indeterministic data-flow, including lumi events and candidate b-quark events. Both simulation data and previously recorded real data can be re-played through the system in this manner. As the data rate is high (100 MB/s), care has been taken to optimize the emulator for throughput from the Storage Area Network. The emulator can be run in stand-alone mode, but even more interesting is that it can emulate any partition of LHCb in parallel with the real hardware partition. In this mode it is fully integrated into the standard run-control. The architecture, implementation, and performance results of the emulator and full tests will be presented. This emulator is a crucial part of the ongoing data-challenges in LHCb. Results from these Full System Integration Tests (FEST) will be presented, which helped to verify and benchmark the entire LHCb data-flow

Aurora B activity is normal in cHL small and large cells.

<p>A-F. Immunofluorescence images of small mononucleated cells (A-E) and large cell undergoing mitosis (F). A. Cell in prometaphase with Aurora B kinase properly localized at centromeres and phospho-Ser10-histone H3 on chromatin. B. One cell in telophase (left) and one cell in the last stages of cytokinesis (right). Aurora B localizes properly in the central spindle or in the thin intercellular bridge that connects the two sister cells, respectively. As expected, signal for phospho-Ser10-histone H3 is only observed in the cell on the left where nuclear envelope has not reformed yet. C. Cell in prometaphase with most of the chromosomes aligned at the metaphase plate and one mono-oriented chromosome on the spindle pole with the unattached kinetochore showing prominent accumulation of auto-phosphorylated Aurora B (white arrow). Asterisk indicates a spindle pole that is unspecifically labeled by the P-T232-Aurora B antibody. D. Cell in the last stages of cytokinesis with chromatin present in the intercellular bridge (white arrowhead). Auto-phosphorylated Aurora B accumulates on the intercellular bridge revealing that Aurora B has been properly activated at a time when abscission is taking place. E. Cell in telophase with chromatin bridges staining positive for phospho-Ser10-histone H3. F. Large cell with a double metaphase plate showing auto-phosphorylated Aurora B and therefore active kinase on centromeres. Asterisks are the spindle poles. Size bar is 5 μm.</p