BTG interacts with retinoblastoma to control cell fate in Dictyostelium.

In the genesis of many tissues, a phase of cell proliferation is followed by cell cycle exit and terminal differentiation. The latter two processes overlap: genes involved in the cessation of growth may also be important in triggering differentiation. Though conceptually distinct, they are often causally related and functional interactions between the cell cycle machinery and cell fate control networks are fundamental to coordinate growth and differentiation. A switch from proliferation to differentiation may also be important in the life cycle of single-celled organisms, and genes which arose as regulators of microbial differentiation may be conserved in higher organisms. Studies in microorganisms may thus contribute to understanding the molecular links between cell cycle machinery and the determination of cell fate choice networks. Here we show that in the amoebozoan D. discoideum, an ortholog of the metazoan antiproliferative gene btg controls cell fate, and that this function is dependent on the presence of a second tumor suppressor ortholog, the retinoblastoma-like gene product. Specifically, we find that btg-overexpressing cells preferentially adopt a stalk cell (and, more particularly, an Anterior-Like Cell) fate. No btg-dependent preference for ALC fate is observed in cells in which the retinoblastoma-like gene has been genetically inactivated. Dictyostelium btg is the only example of non-metazoan member of the BTG family characterized so far, suggesting that a genetic interaction between btg and Rb predated the divergence between dictyostelids and metazoa. While the requirement for retinoblastoma function for BTG antiproliferative activity in metazoans is known, an interaction of these genes in the control of cell fate has not been previously documented. Involvement of a single pathway in the control of mutually exclusive processes may have relevant implication in the evolution of multicellularity

Invasive salmonellosis by the very rare salmonella choleraesuis in a returning traveler on a tumor necrosis factor-α inhibitor

Salmonella choleraesuis is one of the least commonly reported nontyphoidal salmonellae in the United States, accounting for only 0.08% and ranking lower than 20th place among all human source salmonellosis reported to the CDC in 2009. In the state of Connecticut, only 12 cases have been reported since 1998 and our case is the only case since 2008. We report a case of invasive Salmonellosis caused by Salmonella choleraesuis in a patient on an antitumor necrosis factor-α agent (adalimumab) who recently returned from a trip to the Dominican Republic

Pan-european assessment, monitoring, and mitigation of stressors on the health of bees

Inter-individual differences in pesticide sensitivity may trigger variability in the risk posed by pesticides. Therefore, to better inform pesticide risk assessment for bees, we studied the variability of responses to several pesticides based on endogenous (developmental stage, genetic background, caste) and exogenous factors (pesticide co-exposure). We mainly investigated the toxicity of the insecticide sulfoxaflor, the fungicide azoxystrobin and the herbicide glyphosate. We first used LD50 tests to determine the acute oral and contact toxicity of these pesticides across the different bee species, developmental stages (larva vs adult in honey bees), castes (honey bee and bumble bee workers, queens and drones), and genetic backgrounds (honey bee subspecies). We then considered the risks posed by chronic and sublethal exposures to pesticides by implementing behavioural and reproductive endpoints in the screening of pesticide toxicity. Data showed that azoxystrobin and glyphosate under the test conditions were mildly toxic to bees. However, a large variability in bee sensitivity to sulfoxaflor was found, especially across species and individuals of different castes or sex. This variability is therefore important to consider for increasing the safety margin of the risk posed by insecticides in bees. Several effects induced by sublethal concentrations or doses of pesticides are also described, such as the occurrence of a Non-Monotonic Dose-Response (NMDR) and delayed effects in honey bees, impairment of reproductive performances in bumble bees, and a decreased longevity of Osmia adult females (although no effects were found on larval development). Finally, an interaction between pesticides was found when exposure was by contact, but not under oral exposure. In conclusion, the range of effects described here provides very useful insights for better understanding the toxicity of pesticides and therefore the risks they might pose to bees.Prepared under contract from the European Commission; Grant agreement No. 773921; EU Horizon 2020 Research and Innovation action.Prepared under contract from the European Commission; Grant agreement No. 773921; EU Horizon 2020 Research and Innovation action

Pan-european assessment, monitoring, and mitigation of stressors on the health of bees

Within the PoshBee Project we have tested three bee species – honey bees Apis mellifera, bumble bees Bombus terrestris and solitary bees Osmia bicornis – for their sensitivity to pesticides and analysed the clearance of pesticides from bees. For each species, all castes and sexes were studied. We synthesised the mortality data (LD50 or results of limit tests) with the toxicokinetic patterns and analysed this against the background of inter- and intraspecific variation in life-histories of the tested bees. The clearance of sulfoxaflor is relatively similar across all bee species tested and in females after contact treatment it tends to be retained. The toxicity increases over time independently of the clearance from the body. The clearance of azoxystrobin was rapid in Osmia and bumble bees, as well as in honey bee queens, but in honey bee workers there was very little clearance. Similar to sulfoxaflor the toxicity increased over time, although the residues were detected at very low levels. Glyphosate tended to be retained in bumble bees after contact treatment but cleared rapidly after oral treatment. For Osmia bees only in males after contact treatment was the glyphosate almost lost. The toxicity of a pesticide is dependent on the exact dosage, but also the exposure route and time, as well as the speed of detoxification and clearance from a body. The assessment for the hazard that a less toxic pesticide might pose, can be largely dependent on the exposure route. The effects of pesticide toxicity can increase even after the molecules have been cleared out of the body.Prepared under contract from the European Commission; Grant agreement No. 773921; EU Horizon 2020 Research and Innovation action.Prepared under contract from the European Commission; Grant agreement No. 773921; EU Horizon 2020 Research and Innovation action

Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: impact of the 79A>C cytidine deaminase polymorphism

To study the impact of the 79A > C polymorphism in the cytidine deaminase (CDA) gene on the pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in non-small-cell lung cancer (NSCLC) patients. Patients (n = 20) received gemcitabine 1,125 mg/m(2) as a 30 min i.v. infusion as part of treatment for NSCLC. Plasma samples were collected during 0-6 h after gemcitabine administration. Gemcitabine and dFdU were quantified by high performance liquid chromatography with ultraviolet detection. The CDA 79A > C genotype was determined with PCR and DNA sequencing. Gemcitabine was rapidly cleared from plasma and undetectable after 3 h. The allele frequency of the 79A > C polymorphism was 0.40. Diplotypes were distributed as A/A n = 8, A/C n = 8 ,and C/C n = 4. No significant differences were found between the different CDA genotypes and gemcitabine or dFdU AUC, clearance, or half-life. The 79A > C polymorphism in the CDA gene does not have a major consistent and signficant impact on gemcitabine pharmacokinetics

First LIGO search for gravitational wave bursts from cosmic (super)strings

We report on a matched-filter search for gravitational wave bursts from cosmic string cusps using LIGO data from the fourth science run (S4) which took place in February and March 2005. No gravitational waves were detected in 14.9 days of data from times when all three LIGO detectors were operating. We interpret the result in terms of a frequentist upper limit on the rate of gravitational wave bursts and use the limits on the rate to constrain the parameter space (string tension, reconnection probability, and loop sizes) of cosmic string models.Comment: 11 pages, 3 figures. Replaced with version submitted to PR

Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts

Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec 17 2009 to Jan 8 2010 and Sep 2 to Oct 20 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with ~50% or better probability with a few pointings of wide-field telescopes.Comment: 17 pages. This version (v2) includes two tables and 1 section not included in v1. Accepted for publication in Astronomy & Astrophysic

Stacked Search for Gravitational Waves from the 2006 SGR 1900+14 Storm

We present the results of a LIGO search for short-duration gravitational waves (GWs) associated with the 2006 March 29 SGR 1900+14 storm. A new search method is used, "stacking'' the GW data around the times of individual soft-gamma bursts in the storm to enhance sensitivity for models in which multiple bursts are accompanied by GW emission. We assume that variation in the time difference between burst electromagnetic emission and potential burst GW emission is small relative to the GW signal duration, and we time-align GW excess power time-frequency tilings containing individual burst triggers to their corresponding electromagnetic emissions. We use two GW emission models in our search: a fluence-weighted model and a flat (unweighted) model for the most electromagnetically energetic bursts. We find no evidence of GWs associated with either model. Model-dependent GW strain, isotropic GW emission energy E_GW, and \gamma = E_GW / E_EM upper limits are estimated using a variety of assumed waveforms. The stacking method allows us to set the most stringent model-dependent limits on transient GW strain published to date. We find E_GW upper limit estimates (at a nominal distance of 10 kpc) of between 2x10^45 erg and 6x10^50 erg depending on waveform type. These limits are an order of magnitude lower than upper limits published previously for this storm and overlap with the range of electromagnetic energies emitted in SGR giant flares.Comment: 7 pages, 3 figure

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

All-sky search for periodic gravitational waves in LIGO S4 data

We report on an all-sky search with the LIGO detectors for periodic gravitational waves in the frequency range 50-1000 Hz and with the frequency's time derivative in the range -1.0E-8 Hz/s to zero. Data from the fourth LIGO science run (S4) have been used in this search. Three different semi-coherent methods of transforming and summing strain power from Short Fourier Transforms (SFTs) of the calibrated data have been used. The first, known as "StackSlide", averages normalized power from each SFT. A "weighted Hough" scheme is also developed and used, and which also allows for a multi-interferometer search. The third method, known as "PowerFlux", is a variant of the StackSlide method in which the power is weighted before summing. In both the weighted Hough and PowerFlux methods, the weights are chosen according to the noise and detector antenna-pattern to maximize the signal-to-noise ratio. The respective advantages and disadvantages of these methods are discussed. Observing no evidence of periodic gravitational radiation, we report upper limits; we interpret these as limits on this radiation from isolated rotating neutron stars. The best population-based upper limit with 95% confidence on the gravitational-wave strain amplitude, found for simulated sources distributed isotropically across the sky and with isotropically distributed spin-axes, is 4.28E-24 (near 140 Hz). Strict upper limits are also obtained for small patches on the sky for best-case and worst-case inclinations of the spin axes.Comment: 39 pages, 41 figures An error was found in the computation of the C parameter defined in equation 44 which led to its overestimate by 2^(1/4). The correct values for the multi-interferometer, H1 and L1 analyses are 9.2, 9.7, and 9.3, respectively. Figure 32 has been updated accordingly. None of the upper limits presented in the paper were affecte