The LPL/ADAM29 expression ratio is a novel prognosis indicator in chronic lymphocytic leukemia

Although the zeta-associated protein of 70 kDa (ZAP-70) is overexpressed in patients with chronic lymphocytic leukemia (CLL) displaying unmutated IGVH genes and poor prognosis, a previous microarray study from our group identified overexpression of LPL and ADAM29 genes among unmutated and mutated CLL, respectively. To assess the prognostic value of these genes, we quantified their expression by real-time quantitative polymerase chain reaction (PCR) in a cohort of 127 patients with CLL and correlated this with clinical outcome, IGVH mutational status, and ZAP-70 protein expression. IGVH mutational status, ZAP-70, and the LPL and ADAM29 mRNA ratios (L/A ratio) were predictive of event-free survival for the whole cohort and for patients with stage A disease. in patients in stage B and C, the L/A ratio was an independent prognostic factor, whereas ZAP-70 did not predict survival. Simultaneous usage of the L/A ratio and ZAP-70 expression allowed an almost perfect (99%) assessment of the IGVH status in the 80% of patients with concordant results (L/A(+), ZAP-70(+) or L/A(-), ZAP-70(-)). LPL and ADAM29 gene expression could also be determined by a simple competitive multiplex reverse transcription PCR assay. Overall, quantification of LPL and ADAM29 gene expression is a strong prognostic indicator in CLL, providing better prognostic assessment than ZAP-70 in advanced stages of the disease.Hop La Pitie Salpetriere, Serv Hematol Biol, F-75013 Paris, FranceInst Pasteur, Unite Immunohematol & Immunopathol, F-75724 Paris, FranceUniversidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, São Paulo, BrazilInst Pasteur, Dept Ecosyst & Epidemiol Malad Infect, Paris, FranceHop La Pitie Salpetriere, Serv Immunol, Paris, FranceInst Pasteur, Ctr Rech Vaccinale & Biomed, Paris, FranceUniversidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, São Paulo, BrazilWeb of Scienc

The UV surface habitability of Proxima <i>b</i>: first experiments revealing probable life survival to stellar flares

Abstract We use a new interdisciplinary approach to study the UV surface habitability of Proxima b under quiescent and flaring stellar conditions. We assumed planetary atmospheric compositions based on CO2 and N2 and surface pressures from 100 to 5000 mbar. Our results show that the combination of these atmospheric compositions and pressures provide enough shielding from the most damaging UV wavelengths, expanding the ”UV-protective” planetary atmospheric compositions beyond ozone. Additionally, we show that the UV radiation reaching the surface of Proxima b during quiescent conditions would be negligible from the biological point of view, even without an atmosphere. Given that high UV fluxes could challenge the existence of life, then, we experimentally tested the effect that flares would have on microorganisms in a ”worst case scenario” (no UV-shielding). Our results show the impact that a typical flare and a superflare would have on life: when microorganisms receive very high fluences of UVC, such as those expected to reach the surface of Proxima b after a typical flare or a superflare, a fraction of the population is able to survive. Our study suggests that life could cope with highly UV irradiated environments in exoplanets under conditions that cannot be found on Earth

An experimental study of the biological impact of a superflare on the TRAPPIST-1 planets

In the present study, we conducted experiments to assess the biological effects of high fluences of UV radiation (UVR) on the TRAPPIST-1 planetary system (planets e, f, g within the habitable zone), unlike previous estimates made by other authors which used theoretical approaches. To this end, we first calculated the UV fluxes at the orbits of the planets of the TRAPPIST-1 system during quiescent conditions and during a superflare. We then studied the effects of UVR on microbial life by exposing UV-tolerant (Deinococcus radiodurans) and UV-susceptible bacteria (Escherichia coli) to fluences equivalent to a superflare on the unshielded surface of these planets. Based on the results of our laboratory experiments, we have found a survival fraction of 6.31 × 10−8 for D. radiodurans and a survival fraction below the limit of detection for E. coli at the surface of the planet e, which would receive the highest UVR flux. These survival fractions were higher for the planets f and g. In contrast to the results obtained by other authors which used theoretical estimates, we show that a fraction of the population of microorganisms could tolerate the high UVR fluences of a superflare on the surface of TRAPPIST-1 planets, even without any shielding such as that provided by an atmosphere or an ocean. Our study evidences the existence of methodological problems in theoretical approaches. It also emphasizes the importance of performing specifically designed biological experiments to predict microbial survival in extraterrestrial contexts

Lipoprotein lipase is frequently overexpressed or translocated in cervical squamous cell carcinoma and promotes invasiveness through the non-catalytic C terminus.

BACKGROUND: We studied the biological significance of genes involved in a novel t(8;12)(p21.3;p13.31) reciprocal translocation identified in cervical squamous cell carcinoma (SCC) cells. METHODS: The rearranged genes were identified by breakpoint mapping, long-range PCR and sequencing. We investigated gene expression in vivo using reverse-transcription PCR and tissue microarrays, and studied the phenotypic consequences of forced gene overexpression. RESULTS: The rearrangement involved lipoprotein lipase (LPL) and peroxisome biogenesis factor-5 (PEX5). Whereas LPL-PEX5 was expressed at low levels and contained a premature stop codon, PEX5-LPL was highly expressed and encoded a full-length chimeric protein (including the majority of the LPL coding region). Consistent with these findings, PEX5 was constitutively expressed in normal cervical squamous cells, whereas LPL expression was negligible. The LPL gene was rearranged in 1 out of 151 cervical SCCs, whereas wild-type LPL overexpression was common, being detected in 10 out of 28 tissue samples and 4 out of 10 cell lines. Forced overexpression of wild-type LPL and PEX5-LPL fusion transcripts resulted in increased invasiveness in cervical SCC cells, attributable to the C-terminal non-catalytic domain of LPL, which was retained in the fusion transcripts. CONCLUSION: This is the first demonstration of an expressed fusion gene in cervical SCC. Overexpressed wild-type or translocated LPL is a candidate for targeted therapy

Protective effects of halite to vacuum and vacuum-ultraviolet radiation: A potential scenario during a young sun superflare

Halite (NaCl mineral) has exhibited the potential to preserve microorganisms for millions of years on Earth. This mineral was also identified on Mars and in meteorites. In this study, we investigated the potential of halite crystals to protect microbial life-forms on the surface of an airless body (e.g., meteorite), for instance, during a lithopanspermia process (interplanetary travel step) in the early Solar System. To investigate the effect of the radiation of the young Sun on microorganisms, we performed extensive simulation experiments by employing a synchrotron facility. We focused on two exposure conditions: vacuum (low Earth orbit, 10-4 Pa) and vacuum-ultraviolet (VUV) radiation (range 57.6-124 nm, flux 7.14 W/m2), with the latter representing an extreme scenario with high VUV fluxes comparable to the amount of radiation of a stellar superflare from the young Sun. The stellar VUV parameters were estimated by using the very well-studied solar analog of the young Sun, κ1 Cet. To evaluate the protective effects of halite, we entrapped a halophilic archaeon (Haloferax volcanii) and a non-halophilic bacterium (Deinococcus radiodurans) in laboratory-grown halite. Control groups were cells entrapped in salt crystals (mixtures of different salts and NaCl) and non-trapped (naked) cells, respectively. All groups were exposed either to vacuum alone or to vacuum plus VUV. Our results demonstrate that halite can serve as protection against vacuum and VUV radiation, regardless of the type of microorganism. In addition, we found that the protection is higher than provided by crystals obtained from mixtures of salts. This extends the protective effects of halite documented in previous studies and reinforces the possibility to consider the crystals of this mineral as potential preservation structures in airless bodies or as vehicles for the interplanetary transfer of microorganisms.X.C.A. acknowledges CNPEM for the beamtime grantedto the proposal TGM—16126 (LNLS), FAPESP postdoc-toral fellowship (years 2013–2014) (Processo nro: 2012/20106-5), Brazil, and funding from PIP—CONICET 0754,Argentina. M.L. and P.O. acknowledge the Austrian ScienceFund (FWF): P30949-N36, I5711-N for supporting thisproject. J.E.H. acknowledges the financial support of FAPESP (Sao Paulo State) and CNPQ (Brazil) financingagencies. G.F.P.M. acknowledges grant 474972/2009-7from CNPq/Brazil.Peer reviewe