Gem-induced cytoskeleton remodeling increases cellular migration of HTLV-1-infected cells, formation of infected-to-target T-cell conjugates and viral transmission

Efficient HTLV-1 viral transmission occurs through cell-to-cell contacts. The Tax viral transcriptional activator protein facilitates this process. Using a comparative transcriptomic analysis, we recently identified a series of genes up-regulated in HTLV-1 Tax expressing T-lymphocytes. We focused our attention towards genes that are important for cytoskeleton dynamic and thus may possibly modulate cell-to-cell contacts. We first demonstrate that Gem, a member of the small GTP-binding proteins within the Ras superfamily, is expressed both at the RNA and protein levels in Tax-expressing cells and in HTLV-1-infected cell lines. Using a series of ChIP assays, we show that Tax recruits CREB and CREB Binding Protein (CBP) onto a c-AMP Responsive Element (CRE) present in the gem promoter. This CRE sequence is required to drive Tax-activated gem transcription. Since Gem is involved in cytoskeleton remodeling, we investigated its role in infected cells motility. We show that Gem co-localizes with F-actin and is involved both in T-cell spontaneous cell migration as well as chemotaxis in the presence of SDF-1/CXCL12. Importantly, gem knock-down in HTLV-1-infected cells decreases cell migration and conjugate formation. Finally, we demonstrate that Gem plays an important role in cell-to-cell viral transmission

Neutrino-driven Explosions

The question why and how core-collapse supernovae (SNe) explode is one of the central and most long-standing riddles of stellar astrophysics. A solution is crucial for deciphering the SN phenomenon, for predicting observable signals such as light curves and spectra, nucleosynthesis, neutrinos, and gravitational waves, for defining the role of SNe in the evolution of galaxies, and for explaining the birth conditions and properties of neutron stars (NSs) and stellar-mass black holes. Since the formation of such compact remnants releases over hundred times more energy in neutrinos than the SN in the explosion, neutrinos can be the decisive agents for powering the SN outburst. According to the standard paradigm of the neutrino-driven mechanism, the energy transfer by the intense neutrino flux to the medium behind the stagnating core-bounce shock, assisted by violent hydrodynamic mass motions (sometimes subsumed by the term "turbulence"), revives the outward shock motion and thus initiates the SN blast. Because of the weak coupling of neutrinos in the region of this energy deposition, detailed, multidimensional hydrodynamic models including neutrino transport and a wide variety of physics are needed to assess the viability of the mechanism. Owing to advanced numerical codes and increasing supercomputer power, considerable progress has been achieved in our understanding of the physical processes that have to act in concert for the success of neutrino-driven explosions. First studies begin to reveal observational implications and avenues to test the theoretical picture by data from individual SNe and SN remnants but also from population-integrated observables. While models will be further refined, a real breakthrough is expected through the next Galactic core-collapse SN, when neutrinos and gravitational waves can be used to probe the conditions deep inside the dying star. (abridged)Comment: Author version of chapter for 'Handbook of Supernovae,' edited by A. Alsabti and P. Murdin, Springer. 54 pages, 13 figure

High-mass X-ray binaries and OB-runaway stars

High-mass X-ray binaries (HMXBs) represent an important phase in the evolution of massive binary systems. HMXBs provide unique diagnostics to test massive-star evolution, to probe the physics of radiation-driven winds, to study the process of mass accretion, and to measure fundamental parameters of compact objects. As a consequence of the supernova explosion that produced the neutron star (or black hole) in these systems, HMXBs have high space velocities and thus are runaways. Alternatively, OB-runaway stars can be ejected from a cluster through dynamical interactions. Observations obtained with the Hipparcos satellite indicate that both scenarios are at work. Only for a minority of the OB runaways (and HMXBs) a wind bow shock has been detected. This might be explained by the varying local conditions of the interstellar medium.Comment: 15 pages, latex (sty file included) with 5 embedded figures (one in jpg format), to appear in Proc. "Influence of binaries on stellar population studies", Eds. Vanbeveren, Van Rensberge

Modeling the Hubble Space Telescope ultraviolet and optical spectrum of spot 1 on the circumstellar ring of SN 1987A

We report and interpret Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph (STIS) long-slit observations of the optical and ultraviolet (1150-10270 Å) emission line spectra of the rapidly brightening spot 1 on the equatorial ring of SN 1987A between 1997 September and 1999 October (days 3869-4606 after outburst). The emission is caused by radiative shocks created where the supernova blast wave strikes dense gas protruding inward from the equatorial ring. We measure and tabulate line identifications, fluxes, and, in some cases, line widths and shifts. We compute flux correction factors to account for substantial interstellar line absorption of several emission lines. Nebular analysis shows that optical emission lines come from a region of cool (T e ≈ 10 4 K) and dense (n e ≈ 10 6 cm -3) gas in the compressed photoionized layer behind the radiative shock. The observed line widths indicate that only shocks with shock velocities V s < 250 km s -1 have become radiative, while line ratios indicate that much of the emission must have come from yet slower (V s ≲ 135 km s -1) shocks. Such slow shocks can be present only if the protrusion has atomic density n ≳ 3 × 10 4 cm -3, somewhat higher than that of the circumstellar ring. We are able to fit the UV fluxes with an idealized radiative shock model consisting of two shocks (V s = 135 and 250 km s -1). The observed UV flux increase with time can be explained by the increase in shock surface areas as the blast wave overtakes more of the protrusion. The observed flux ratios of optical to highly ionized UV lines are greater by a factor of ∼2-3 than predictions from the radiative shock models, and we discuss the possible causes. We also present models for the observed Ha line widths and profiles, which suggest that a chaotic flow exists in the photoionized regions of these shocks. We discuss what can be learned with future observations of all the spots present on the equatorial ring.published_or_final_versio

The plant WEE1 kinase is involved in checkpoint control activation in nematode-induced galls

Galls induced by plant‐parasitic nematodes involve a hyperactivation of the plant mitotic and endocycle machinery for their profit. Dedifferentiation of host root cells includes drastic cellular and molecular readjustments. In such background, potential DNA damage in the genome of gall cells is eminent. We questioned if DNA damage checkpoints activation followed by DNA repair occurred, or was eventually circumvented, in nematode‐induced galls. Galls display transcriptional activation of the DNA damage checkpoint kinase WEE1, correlated with its protein localization in the nuclei. The promoter of the stress marker gene SMR7 was evaluated under the WEE1‐knockout background. Drugs inducing DNA damage and a marker for DNA repair, PARP1 were used to understand mechanisms that might cope with DNA damage in galls. Our functional study revealed that gall cells lacking WEE1 conceivably entered mitosis prematurely disturbing the cell cycle despite the loss of genome integrity. The disrupted nuclei phenotype in giant cells hinted to the accumulation of mitotic defects. As well, WEE1‐knockout in Arabidopsis and downregulation in tomato repressed infection and reproduction of root‐knot nematodes. Together with data on DNA damaging drugs, we suggest a conserved function for WEE1 controlling a G1/S cell cycle arrest in response to replication defect in galls

Developing adaptive control:Age-related differences in task choices and awareness of proactive and reactive control demands

Developmental changes in executive function are often explained in terms of core cognitive processes and associated neural substrates. For example, younger children tend to engage control reactively in the moment as needed, whereas older children increasingly engage control proactively, in anticipation of needing it. Such developments may reflect increasing capacities for active maintenance dependent upon dorsolateral prefrontal cortex. However, younger children will engage proactive control when reactive control is made more difficult, suggesting that developmental changes may also reflect decisions about whether to engage control, and how. We tested awareness of temporal control demands and associated task choices in 5-year-olds and 10-year-olds and adults using a demand selection task. Participants chose between one task that enabled proactive control and another task that enabled reactive control. Adults reported awareness of these different control demands and preferentially played the proactive task option. Ten-year-olds reported awareness of control demands but selected task options at chance. Five-year-olds showed neither awareness nor task preference, but a subsample who exhibited awareness of control demands preferentially played the reactive task option, mirroring their typical control mode. Thus, developmental improvements in executive function may in part reflect better awareness of cognitive demands and adaptive behavior, which may in turn reflect changes in dorsal anterior cingulate in signaling task demands to lateral prefrontal cortex

Getting ready to use control:Advances in the measurement of young children's use of proactive control

A key developmental transition in executive function is in the temporal dynamics of its engagement: children shift from reactively calling to mind task-relevant information as needed, to being able to proactively maintain information across time in anticipation of upcoming demands. This transition is important for understanding individual differences and developmental changes in executive function; however, methods targeting its assessment are limited. We tested the possibility that Track-It, a paradigm developed to measure selective sustained attention, also indexes proactive control. In this task children must track a target shape as it moves unpredictably among moving distractors, and identify where it disappears, which may require proactively maintaining information about the target or goal. In two experiments (5-6 year-olds, Ns = 33, 64), children's performance on Track-It predicted proactive control across two established paradigms. These findings suggest Track-It measures proactive control in children. Theoretical possibilities regarding how proactive control and selective sustained attention may be related are also discussed

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

Hypernovae and Other Black-Hole-Forming Supernovae

During the last few years, a number of exceptional core-collapse supernovae (SNe) have been discovered. Their kinetic energy of the explosions are larger by more than an order of magnitude than the typical values for this type of SNe, so that these SNe have been called `Hypernovae'. We first describe how the basic properties of hypernovae can be derived from observations and modeling. These hypernovae seem to come from rather massive stars, thus forming black holes. On the other hand, there are some examples of massive SNe with only a small kinetic energy. We suggest that stars with non-rotating black holes are likely to collapse "quietly" ejecting a small amount of heavy elements (Faint supernovae). In contrast, stars with rotating black holes are likely to give rise to very energetic supernovae (Hypernovae). We present distinct nucleosynthesis features of these two types of "black-hole-forming" supernovae. Hypernova nucleosynthesis is characterized by larger abundance ratios (Zn,Co,V,Ti)/Fe and smaller (Mn,Cr)/Fe. Nucleosynthesis in Faint supernovae is characterized by a large amount of fall-back. We show that the abundance pattern of the most Fe deficient star, HE0107-5240, and other extremely metal-poor carbon-rich stars are in good accord with those of black-hole-forming supernovae, but not pair-instability supernovae. This suggests that black-hole-forming supernovae made important contributions to the early Galactic (and cosmic) chemical evolution.Comment: 49 pages, to be published in "Stellar Collapse" (Astrophysics and Space Science; Kluwer) ed. C. L. Fryer (2003

Effects of automated alerts on unnecessarily repeated serology tests in a cardiovascular surgery department: a time series analysis

<p>Abstract</p> <p>Background</p> <p>Laboratory testing is frequently unnecessary, particularly repetitive testing. Among the interventions proposed to reduce unnecessary testing, Computerized Decision Support Systems (CDSS) have been shown to be effective, but their impact depends on their technical characteristics. The objective of the study was to evaluate the impact of a Serology-CDSS providing point of care reminders of previous existing serology results, embedded in a Computerized Physician Order Entry at a university teaching hospital in Paris, France.</p> <p>Methods</p> <p>A CDSS was implemented in the Cardiovascular Surgery department of the hospital in order to decrease inappropriate repetitions of viral serology tests (HBV).</p> <p>A time series analysis was performed to assess the impact of the alert on physicians' practices. The study took place between January 2004 and December 2007. The primary outcome was the proportion of unnecessarily repeated HBs antigen tests over the periods of the study. A test was considered unnecessary when it was ordered within 90 days after a previous test for the same patient. A secondary outcome was the proportion of potentially unnecessary HBs antigen test orders cancelled after an alert display.</p> <p>Results</p> <p>In the pre-intervention period, 3,480 viral serology tests were ordered, of which 538 (15.5%) were unnecessarily repeated. During the intervention period, of the 2,095 HBs antigen tests performed, 330 unnecessary repetitions (15.8%) were observed. Before the intervention, the mean proportion of unnecessarily repeated HBs antigen tests increased by 0.4% per month (absolute increase, 95% CI 0.2% to 0.6%, <it>p </it>< 0.001). After the intervention, a significant trend change occurred, with a monthly difference estimated at -0.4% (95% CI -0.7% to -0.1%, <it>p </it>= 0.02) resulting in a stable proportion of unnecessarily repeated HBs antigen tests. A total of 380 unnecessary tests were ordered among 500 alerts displayed (compliance rate 24%).</p> <p>Conclusions</p> <p>The proportion of unnecessarily repeated tests immediately dropped after CDSS implementation and remained stable, contrasting with the significant continuous increase observed before. The compliance rate confirmed the effect of the alerts. It is necessary to continue experimentation with dedicated systems in order to improve understanding of the diversity of CDSS and their impact on clinical practice.</p