What Role for Angiogenesis in Childhood Acute Lymphoblastic Leukaemia?

The role of angiogenesis in acute leukaemia has been discussed since the cloning of the gene of vascular endothelial growth factor (VEGF) from the acute myelogenous leukemia cell line (HL60) and, thereafter, when the first studies reported increased bone marrow vascularity and elevation of angiogenic cytokines in acute lymphoblastic leukaemia (ALL). VEGF and basic fibroblast growth factor (bFGF) are the major proangiogenic cytokines that have been studied, and evaluation of their prognostic impact in childhood ALL has been reported in several studies, though with controversial results. The antiangiogenic response, contributing to the angiogenic balance, has scarcely been reported. The origin of the factors, their prognostic value, and their relevance as good markers of what really happens in the bone marrow are discussed in this paper. The place of antiangiogenic drugs in ALL has to be defined in the global treatment strategy

User-friendly imaging algorithms for interferometry

OPTICON currently supports a Joint Research Activity (JRA) dedicated to providing easy to use image reconstruction algorithms for optical/IR interferometric data. This JRA aims to provide state-of-the-art image reconstruction methods with a common interface and comprehensive documentation to the community. These tools will provide the capability to compare the results of using different settings and algorithms in a consistent and unified way. The JRA is also providing tutorials and sample datasets to introduce the principles of image reconstruction and illustrate how to use the software products. We describe the design of the imaging tools, in particular the interface between the graphical user interface and the image reconstruction algorithms, and summarise the current status of their implementation.European Community’s Seventh Framework Programme (FP7/2013–2016) (Grant ID: 312430 (OPTICON))This is the author accepted manuscript. The final version is available from SPIE via http://dx.doi.org/10.1117/12.223338

Hypoxia promotes chemoresistance in acute lymphoblastic leukemia cell lines by modulating death signaling pathways

International audienceBackground: Several studies show that bone marrow (BM) microenvironment and hypoxia condition can promote the survival of leukemic cells and induce resistance to anti-leukemic drugs. However, the molecular mechanism for chemoresistance by hypoxia is not fully understood.Methods: In the present study, we investigated the effect of hypoxia on resistance to two therapies, methotrexate (MTX) and prednisolone (PRD), in two cell models for acute lymphoblastic leukemia (ALL). To look for an implication of hypoxia in chemoresistance, cell viability, total cell density and cell proliferation were analyzed. Survival and death signaling pathways were also screened by "reverse phase protein array" (RPPA) and western blotting experiments conducted on selected proteins to confirm the results.Results: We found that hypoxia promotes chemoresistance in both ALL cell lines. The induction of drug-resistance by hypoxia was not associated with an increase in total cell density nor an increase in cell proliferation. Using RPPA, we show that chemoresistance induced by hypoxia was mediated through an alteration of cell death signaling pathways. This protective effect of hypoxia seems to occur via a decrease in pro-apoptotic proteins and an increase in anti-apoptotic proteins. The results were confirmed by immunoblotting. Indeed, hypoxia is able to modulate the expression of anti-apoptotic proteins independently of chemotherapy while a pro-apoptotic signal induced by a chemotherapy is not modulated by hypoxia.Conclusions: Hypoxia is a factor in leukemia cell resistance and for two conventional chemotherapies modulates cell death signaling pathways without affecting total cell density or cell proliferation

Digestive and appendicular soft-parts, with behavioural implications, in a large Ordovician trilobite from the Fezouata Lagerstätte, Morocco

Trilobites were one of the most successful groups of marine arthropods during the Palaeozoic era, yet their soft-part anatomy is only known from a few exceptionally-preserved specimens found in a handful of localities from the Cambrian to the Devonian. This is because, even if the sclerotized appendages were not destroyed during early taphonomic stages, they are often overprinted by the three-dimensional, mineralised exoskeleton. Inferences about the ventral anatomy and behavioural activities of trilobites can also be derived from the ichnological record, which suggests that most Cruziana and Rusophycus trace fossils were possibly produced by the actions of trilobites. Three specimens of the asaphid trilobite Megistaspis (Ekeraspis) hammondi, have been discovered in the Lower Ordovician Fezouata Konservat-Lagerstätte of southern Morocco, preserving appendages and digestive tract. The digestive structures include a crop with digestive caeca, while the appendages display exopodal setae and slight heteropody (cephalic endopods larger and more spinose than thoracic and pygidial ones). The combination of these digestive structures and the heteropody has never been described together among trilobites, and the latter could assist in the understanding of the production of certain comb-like traces of the Cruziana rugosa group, which are extraordinarily abundant on the shallow marine shelves around Gondwana.This work has been supported by the Spanish Ministry of Economy and Competitiveness, project number CGL2012- 39471/BTE.Peer reviewe

Cytochemical techniques and energy-filtering transmission electron microscopy applied to the study of parasitic protozoa

The study of parasitic protozoa plays a major role in cell biology, biochemistry and molecular biology. Numerous cytochemical techniques have been developed in order to unequivocally identify the nature of subcellular compartments. Enzyme and immuno-cytochemistry allow the detection of, respectively, enzymatic activity products and antigens in particular sites within the cell. Energy-filtering transmission electron microscopy permits the detection of specific elements within such compartments. These approaches are particularly useful for studies employing antimicrobial agents where cellular compartments may be destroyed or remarkably altered and thus hardly identified by standard methods of observation. In this regard cytochemical and spectroscopic techniques provide valuable data allowing the determination of the mechanisms of action of such compounds

Estimating the phase in ground-based interferometry: performance comparison between single-mode and multimode schemes

In this paper we compare the performance of multi and single-mode interferometry for the estimation of the phase of the complex visibility. We provide a theoretical description of the interferometric signal which enables to derive the phase error in presence of detector, photon and atmospheric noises, for both multi and single-mode cases. We show that, despite the loss of flux occurring when injecting the light in the single-mode component (i.e. single-mode fibers, integrated optics), the spatial filtering properties of such single-mode devices often enable higher performance than multimode concepts. In the high flux regime speckle noise dominated, single-mode interferometry is always more efficient, and its performance is significantly better when the correction provided by adaptive optics becomes poor, by a factor of 2 and more when the Strehl ratio is lower than 10%. In low light level cases (detector noise regime), multimode interferometry reaches better performance, yet the gain never exceeds 20%, which corresponds to the percentage of photon loss due to the injection in the guides. Besides, we demonstrate that single-mode interferometry is also more robust to the turbulence in both cases of fringe tracking and phase referencing, at the exception of narrow field of views (<1 arcsec).Comment: 9 pages (+ 11 online material appendices) -- 8 Figures. Accepted in A&

Possible detection of phase changes from the non-transiting planet HD 46375b by CoRoT

The present work deals with the detection of phase changes in an exoplanetary system. HD 46375 is a solar analog known to host a non-transiting Saturn-mass exoplanet with a 3.0236 day period. It was observed by the CoRoT satellite for 34 days during the fall of 2008. We attempt to identify at optical wavelengths, the changing phases of the planet as it orbits its star. We then try to improve the star model by means of a seismic analysis of the same light curve and the use of ground-based spectropolarimetric observations. The data analysis relies on the Fourier spectrum and the folding of the time series. We find evidence of a sinusoidal signal compatible in terms of both amplitude and phase with light reflected by the planet. Its relative amplitude is Delta Fp/F* = [13.0, 26.8] ppm, implying an albedo A=[0.16, 0.33] or a dayside visible brightness temperature Tb ~ [1880,2030] K by assuming a radius R=1.1 R_Jup and an inclination i=45 deg. Its orbital phase differs from that of the radial-velocity signal by at most 2 sigma_RV. However, the tiny planetary signal is strongly blended by another signal, which we attribute to a telluric signal with a 1 day period. We show that this signal is suppressed, but not eliminated, when using the time series for HD 46179 from the same CoRoT run as a reference. This detection of reflected light from a non-transiting planet should be confirmable with a longer CoRoT observation of the same field. In any case, it demonstrates that non-transiting planets can be characterized using ultra-precise photometric lightcurves with present-day observations by CoRoT and Kepler. The combined detection of solar-type oscillations on the same targets (Gaulme et al. 2010a) highlights the overlap between exoplanetary science and asteroseismology and shows the high potential of a mission such as Plato.Comment: 4 pages, 6 figure

Oxygen as a Driver of Early Arthropod Micro-Benthos Evolution

BACKGROUND: We examine the physiological and lifestyle adaptations which facilitated the emergence of ostracods as the numerically dominant Phanerozoic bivalve arthropod micro-benthos. METHODOLOGY/PRINCIPAL FINDINGS: The PO(2) of modern normoxic seawater is 21 kPa (air-equilibrated water), a level that would cause cellular damage if found in the tissues of ostracods and much other marine fauna. The PO(2) of most aquatic breathers at the cellular level is much lower, between 1 and 3 kPa. Ostracods avoid oxygen toxicity by migrating to waters which are hypoxic, or by developing metabolisms which generate high consumption of O(2). Interrogation of the Cambrian record of bivalve arthropod micro-benthos suggests a strong control on ecosystem evolution exerted by changing seawater O(2) levels. The PO(2) of air-equilibrated Cambrian-seawater is predicted to have varied between 10 and 30 kPa. Three groups of marine shelf-dwelling bivalve arthropods adopted different responses to Cambrian seawater O(2). Bradoriida evolved cardiovascular systems that favoured colonization of oxygenated marine waters. Their biodiversity declined during intervals associated with black shale deposition and marine shelf anoxia and their diversity may also have been curtailed by elevated late Cambrian (Furongian) oxygen-levels that increased the PO(2) gradient between seawater and bradoriid tissues. Phosphatocopida responded to Cambrian anoxia differently, reaching their peak during widespread seabed dysoxia of the SPICE event. They lacked a cardiovascular system and appear to have been adapted to seawater hypoxia. As latest Cambrian marine shelf waters became well oxygenated, phosphatocopids went extinct. Changing seawater oxygen-levels and the demise of much of the seabed bradoriid micro-benthos favoured a third group of arthropod micro-benthos, the ostracods. These animals adopted lifestyles that made them tolerant of changes in seawater O(2). Ostracods became the numerically dominant arthropod micro-benthos of the Phanerozoic. CONCLUSIONS/SIGNIFICANCE: Our work has implications from an evolutionary context for understanding how oxygen-level in marine ecosystems drives behaviour

Strong near-infrared emission in the sub-AU disk of the Herbig Ae star HD 163296: evidence of refractory dust?

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.We present new long-baseline spectro-interferometric observations of the Herbig Ae star HD 163296 (MWC 275) obtained in the H and K bands with the AMBER instrument at the VLTI. The observations cover a range of spatial resolutions between ∼3 and ∼12 milliarcseconds, with a spectral resolution of ∼30. With a total of 1481 visibilities and 432 closure phases, they represent the most comprehensive (u, v) coverage achieved so far for a young star. The circumstellar material is resolved at the sub-AU spatial scale and closure phase measurements indicate a small but significant deviation from point-symmetry. We discuss the results assuming that the near-infrared excess in HD 163296 is dominated by the emission of a circumstellar disk. A successful fit to the spectral energy distribution, near-infrared visibilities and closure phases is found with a model in which a dominant contribution to the H and K band emission originates in an optically thin, smooth and point-symmetric region extending from about 0.1 to 0.45 AU. At a distance of 0.45 AU from the star, silicates condense, the disk becomes optically thick and develops a puffed-up rim, whose skewed emission can account for the non-zero closure phases. We discuss the source of the inner disk emission and tentatively exclude dense molecular gas as well as optically thin atomic or ionized gas as its possible origin. We propose instead that the smooth inner emission is produced by very refractory grains in a partially cleared region, extending to at least ∼0.5 AU. If so, we may be observing the disk of HD 163296 just before it reaches the transition disk phase. However, we note that the nature of the refractory grains or, in fact, even the possibility of any grain surviving at the very high temperatures we require (∼2100−2300 K at 0.1 AU from the star) is unclear and should be investigated further.We acknowledge fundings from CNRS and INAF (grant ASI-INAF I/016/07/0). This work was in part performed under contract with the Jet Propulsion Laboratory (JPL) funded by NASA through the Michelson Fellowship Progra