Inhibition of oncogenic transcription factor REL by the natural product derivative calafianin monomer 101 induces proliferation arrest and apoptosis in human B-lymphoma cell lines

Increased activity of transcription factor NF-κB has been implicated in many B-cell lymphomas. We investigated effects of synthetic compound calafianin monomer (CM101) on biochemical and biological properties of NF-κB. In human 293 cells, CM101 selectively inhibited DNA binding by overexpressed NF-κB subunits REL (human c-Rel) and p65 as compared to NF-κB p50, and inhibition of REL and p65 DNA binding by CM101 required a conserved cysteine residue. CM101 also inhibited DNA binding by REL in human B-lymphoma cell lines, and the sensitivity of several B-lymphoma cell lines to CM101-induced proliferation arrest and apoptosis correlated with levels of cellular and nuclear REL. CM101 treatment induced both phosphorylation and decreased expression of anti-apoptotic protein Bcl-XL, a REL target gene product, in sensitive B-lymphoma cell lines. Ectopic expression of Bcl-XL protected SUDHL-2 B-lymphoma cells against CM101-induced apoptosis, and overexpression of a transforming mutant of REL decreased the sensitivity of BJAB B-lymphoma cells to CM101-induced apoptosis. Lipopolysaccharide-induced activation of NF-κB signaling upstream components occurred in RAW264.7 macrophages at CM101 concentrations that blocked NF-κB DNA binding. Direct inhibitors of REL may be useful for treating B-cell lymphomas in which REL is active, and may inhibit B-lymphoma cell growth at doses that do not affect some immune-related responses in normal cells.R01 GM094551 - NIGMS NIH HHS; P50 GM067041 - NIGMS NIH HHS; GM094551 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; GM067041 - NIGMS NIH HH

Cuticular Compounds Bring New Insight in the Post-Glacial Recolonization of a Pyrenean Area: Deutonura deficiens Deharveng, 1979 Complex, a Case Study

Background: In most Arthropod groups, the study of systematics and evolution rely mostly on neutral characters, in this context cuticular compounds, as non-neutral characters, represent an underexplored but potentially informative type of characters at the infraspecific level as they have been routinely proven to be involved in sexual attraction. Methods and Findings: The collembolan species complex Deutonura deficiens was chosen as a model in order to test the utility of these characters for delineating four infraspecific entities of this group. Specimens were collected for three subspecies (D. d. deficiens, D. d. meridionalis, D. d. sylvatica) and two morphotypes (D. d. sylvatica morphoype A and B) of the complex; an additional species D. monticola was added. Cuticular compounds were extracted and separated by gas chromatography for each individual. Our results demonstrate that cuticular compounds succeeded in separating the different elements of this complex. Those data allowed also the reconstruction of the phylogenetic relationships among them. Conclusions: The discriminating power of cuticular compounds is directly related to their involvement in sexual attraction and mate recognition. These findings allowed a discussion on the potential involvement of intrinsic and paleoclimatic factors in the origin and the diversification of this complex in the Pyrenean zone. This character type brings the first advanc

Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018.

As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration

First imaging results from the Iapetus B/C flyby of the Cassini spacecraft

Cassini had a relatively close flyby at Iapetus on New Year's Eve 2005. The 288 ISS images set various constraints on the origin theories of the dark/bright dichotomy, as revealed multiple surface structures at up to 740 m/pxl size

Observational detection of eclipses of J5 Amalthea by the Galilean satellites

We carried out observations of the small jovian satellite Amalthea (J5) as it was being eclipsed by the Galilean satellites near the 2009 equinox of Jupiter in order to apply the technique of mutual event photometry to the astrometric determination of this satellite's position. The observations were carried out during the period 06/2009-09/2009 from the island of Maui, Hawaii and Siding Spring, Australia with the 2m Faulkes Telescopes North and South respectively. We observed in the near-infrared part of the spectrum using a PanStarrs-Z filter with Jupiter near the edge of the field in order to mitigate against the glare from the planet. Frames were acquired at rates >1/min during eclipse times predicted using recent JPL ephemerides for the satellites. Following subtraction of the sky background from these frames, differential aperture photometry was carried out on Amalthea and a nearby field star. We have obtained three lightcurves which show a clear drop in the flux from Amalthea, indicating that an eclipse took place as predicted. These were model-fitted to yield best estimates of the time of maximum flux drop and the impact parameter. These are consistent with Amalthea's ephemeris but indicate that Amalthea is slightly ahead of, and closer to Jupiter than, its predicted position by approximately half the ephemeris uncertainty in these directions. We argue that a ground-based campaign of higher-cadence photometry accurate at the 5% level or better during the next season of eclipses in 2014-15 should yield positions to within 0".5 and affect a corresponding improvement in Amalthea's ephemeris.Comment: Published in A&A in 2010; 6 pages, 2 figures, 3 table

The Effect of Expanded Antiretroviral Treatment Strategies on the HIV Epidemic among Men Who Have Sex with Men in San Francisco

Modeling of expanding antiretroviral treatment to all HIV infected adults already in care in San Francisco predicts reductions in new HIV infections at 5 years of 59% among men who have sex with men (MSM). Addition of annual HIV testing for MSM to universal treatment decreases new infections by 76%

The roles of charge exchange and dissociation in spreading Saturn's neutral clouds

Neutrals sourced directly from Enceladus's plumes are initially confined to a dense neutral torus in Enceladus's orbit around Saturn. This neutral torus is redistributed by charge exchange, impact/photodissociation, and neutral-neutral collisions to produce Saturn's neutral clouds. Here we consider the former processes in greater detail than in previous studies. In the case of dissociation, models have assumed that OH is produced with a single speed of 1 km/s, whereas laboratory measurements suggest a range of speeds between 1 and 1.6 km/s. We show that the high-speed case increases dissociation's range of influence from 9 to 15 Rs. For charge exchange, we present a new modeling approach, where the ions are followed within a neutral background, whereas neutral cloud models are conventionally constructed from the neutrals' point of view. This approach allows us to comment on the significance of the ions' gyrophase at the moment charge exchange occurs. Accounting for gyrophase: (1) has no consequence on the H2O cloud; (2) doubles the local density of OH at the orbit of Enceladus; and (3) decreases the oxygen densities at Enceladus's orbit by less than 10%. Finally, we consider velocity-dependent, as well as species-dependent cross sections and find that the oxygen cloud produced from charge exchange is spread out more than H2O, whereas the OH cloud is the most confined.Comment: Accepted to the Journal of Geophysical Research, 49 pages, 10 figure

Effects of compressibility on driving zonal flow in gas giants

The banded structures observed on the surfaces of the gas giants are associated with strong zonal winds alternating in direction with latitude. We use three-dimensional numerical simulations of compressible convection in the anelastic approximation to explore the properties of zonal winds in rapidly rotating spherical shells. Since the model is restricted to the electrically insulating outer envelope, we therefore neglect magnetic effects. A systematic parametric study for various density scaleheights and Rayleigh numbers allows to explore the dependence of convection and zonal jets on these parameters and to derive scaling laws. While the density stratification affects the local flow amplitude and the convective scales, global quantities and zonal jets properties remain fairly independent of the density stratification. The zonal jets are maintained by Reynolds stresses, which rely on the correlation between zonal and cylindrically radial flow components. The gradual loss of this correlation with increasing supercriticality hampers all our simulations and explains why the additional compressional source of vorticity hardly affects zonal flows. All these common features may explain why previous Boussinesq models were already successful in reproducing the morphology of zonal jets in gas giants.Comment: 17 pages, 15 figures, 2 tables, accepted for publication in Icaru