Macrophage transactivation for chemokine production identified as a negative regulator of granulomatous inflammation using agent-based modeling

Cellular activation in trans by interferons, cytokines and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and / or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation

Soluble glycoprotein VI is a predictor of major bleeding in patients with suspected heparin-induced thrombocytopenia

We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day of sample collection because of the high levels of sGPVI in platelet concentrates. We assessed the association of sGPVI (high vs low) with International Society on Thrombosis and Haemostasis major bleeding events by multivariable logistic regression, adjusting for other known risk factors for bleeding. Fifty-four patients were excluded due to recent platelet transfusion, leaving 256 patients for analysis. Eighty-nine (34.8%) patients had a major bleeding event. Median sGPVI levels were significantly elevated in patients with major bleeding events compared with those without major bleeding events (49.09 vs 31.93 ng/mL; P \u3c .001). An sGPVI level \u3e43 ng/mL was independently associated with major bleeding after adjustment for critical illness, sepsis, cardiopulmonary bypass surgery, and degree of thrombocytopenia (adjusted odds ratio, 2.81; 95% confidence interval, 1.51-5.23). Our findings suggest that sGPVI is associated with major bleeding in hospitalized patients with suspected HIT. sGPVI may be a novel biomarker to predict bleeding risk in patients with suspected HIT

Range and primary habitats of Hawaiian insular false killer whales: informing determination of critical habitat

The article of record as published may be found at https://dx.doi.org/10.3354/esr00435For species listed under the US Endangered Species Act, federal agencies must designate 'critical habitat', areas containing features essential to conservation and/or that may require special management considerations. In November 2010, the National Marine Fisheries Service proposed listing a small demographically isolated population of false killer whales Pseudorca crassidens in Hawai'i as endangered but has not yet proposed designating critical habitat. We assessed the population's range and heavily used habitat areas using data from 27 satellite tag deployments. Assessment of independence of individuals with temporally overlapping data indicated that data were from 22 'groups'. Further analyses were restricted to 1 individual per group. Tag data were available for periods of between 13 and 105 d (median = 40.5 d), with 8513 locations (93.4% from July-January). Analyses of photo-identification data indicated that the population is divided into 3 large associations of individuals (social clusters), with tag data from 2 of these clusters. Ranges for these 2 clusters were similar, although one used significantly deeper waters, and their high-use areas differed. A minimum convex polygon range encompassing all locations was ~82800 km2, with individuals ranging from Ni'ihau to Hawai'i Island and up to 122 km offshore. Three high-use areas were identified: (1) off the north half of Hawai'i Island, (2) north of Maui and Moloka'i and (3) southwest of Lana'i. Although this analysis provides information useful for decision-making concerning designation of critical habitat, there are likely other high-use areas that have not yet been identified due to seasonal limitations and availability of data from only 2 of the 3 main social clusters.Fieldwork was primarily funded by grants and contracts to Cascadia Research Collective from the National Marine Fisheries Service Pacific Islands Fisheries Science Center and the US Navy (N45) through the Southwest Fisheries Science Center, Woods Hole Oceano- graphic Institution, and the Naval Postgraduate School. The Wild Whale Research Foundation and Dolphin Quest provided additional support.Funded by Naval Postgraduate School.Office of Naval Research Grant N00014081120

A novel checkpoint in the Bcl-2–regulated apoptotic pathway revealed by murine cytomegalovirus infection of dendritic cells

Infection with murine cytomegalovirus (MCMV) has contributed to understanding many aspects of human infection and, additionally, has provided important insight to understanding complex cellular responses. Dendritic cells (DCs) are a major target for MCMV infection. Here, we analyze the effects of MCMV infection on DC viability, and show that infected DCs become resistant to apoptosis induced by growth factor deprivation. The precise contribution of changes in the expression of Bcl-2 family proteins has been assessed and a new checkpoint in the apoptotic pathway identified. Despite their resistance to apoptosis, MCMV-infected DCs showed Bax to be tightly associated with mitochondria and, together with Bak, forming high molecular weight oligomers, changes normally associated with apoptotic cell death. Exposure of a constitutively occluded Bax NH2-terminal epitope was blocked after infection. These results suggest that MCMV has evolved a novel strategy for inhibiting apoptosis and provide evidence that apoptosis can be regulated after translocation, integration, and oligomerization of Bax at the mitochondrial membrane

On the Exact Evaluation of Certain Instances of the Potts Partition Function by Quantum Computers

We present an efficient quantum algorithm for the exact evaluation of either the fully ferromagnetic or anti-ferromagnetic q-state Potts partition function Z for a family of graphs related to irreducible cyclic codes. This problem is related to the evaluation of the Jones and Tutte polynomials. We consider the connection between the weight enumerator polynomial from coding theory and Z and exploit the fact that there exists a quantum algorithm for efficiently estimating Gauss sums in order to obtain the weight enumerator for a certain class of linear codes. In this way we demonstrate that for a certain class of sparse graphs, which we call Irreducible Cyclic Cocycle Code (ICCC_\epsilon) graphs, quantum computers provide a polynomial speed up in the difference between the number of edges and vertices of the graph, and an exponential speed up in q, over the best classical algorithms known to date

Gas Disk Sizes from CO Line Observations: A Test of Angular Momentum Evolution

The size of a disk encodes important information about its evolution. Combining new Submillimeter Array (SMA) observations with archival Atacama Large Millimeter Array (ALMA) data, we analyze mm continuum and CO emission line sizes for a sample of 44 protoplanetary disks around stars with masses of 0.15--2\,$M_{\odot}$ in several nearby star-forming regions. Sizes measured from $^{12}$CO line emission span from 50 to 1000\,au. This range could be explained by viscous evolution models with different $\alpha$ values (mostly of $10^{-4}-10^{-3}$) and/or a spread of initial conditions. The CO sizes for most disks are also consistent with MHD wind models that directly remove disk angular momentum, but very large initial disk sizes would be required to account for the very extended CO disks in the sample. As no CO size evolution is observed across stellar ages of 0.5--20\,Myr in this sample, determining the dominant mechanism of disk evolution will require a more complete sample for both younger and more evolved systems. We find that the CO emission is universally more extended than the continuum emission by an average factor of $2.9\pm1.2$. The ratio of the CO to continuum sizes does not show any trend with stellar mass, mm continuum luminosity, or the properties of substructures. The GO Tau disk has the most extended CO emission in this sample, with an extreme CO to continuum size ratio of 7.6. Seven additional disks in the sample show high size ratios ($\gtrsim4$) that we interpret as clear signs of substantial radial drift.Comment: Accepted for publication in Ap

The Architecture of the GW Ori Young Triple Star System and Its Disk: Dynamical Masses, Mutual Inclinations, and Recurrent Eclipses

We present spatially and spectrally resolved Atacama Large Millimeter/submillimeter Array (ALMA) observations of gas and dust orbiting the pre-main sequence hierarchical triple star system GW Ori. A forward-modeling of the ${}^{13}$CO and C${}^{18}$O $J$=2-1 transitions permits a measurement of the total stellar mass in this system, $5.29 \pm 0.09\,M_\odot$, and the circum-triple disk inclination, $137.6 \pm 2.0^\circ$. Optical spectra spanning a 35 year period were used to derive new radial velocities and, coupled with a spectroscopic disentangling technique, revealed that the A and B components of GW Ori form a double-lined spectroscopic binary with a $241.50\pm0.05$ day period; a tertiary companion orbits that inner pair with a $4218\pm50$ day period. Combining the results from the ALMA data and the optical spectra with three epochs of astrometry in the literature, we constrain the individual stellar masses in the system ($M_\mathrm{A} \approx 2.7\,M_\odot$, $M_\mathrm{B} \approx 1.7\,M_\odot$, $M_\mathrm{C} \approx 0.9\,M_\odot$) and find strong evidence that at least one (and likely both) stellar orbital planes are misaligned with the disk plane by as much as $45^\circ$. A $V$-band light curve spanning 30 years reveals several new $\sim$30 day eclipse events 0.1-0.7~mag in depth and a 0.2 mag sinusoidal oscillation that is clearly phased with the AB-C orbital period. Taken together, these features suggest that the A-B pair may be partially obscured by material in the inner disk as the pair approaches apoastron in the hierarchical orbit. Lastly, we conclude that stellar evolutionary models are consistent with our measurements of the masses and basic photospheric properties if the GW Ori system is $\sim$1 Myr old.Comment: 26 pages, 15 figures, accepted to Ap

Kinematic and thermal signatures of the directly imaged protoplanet candidate around Elias 2-24

We report kinematic and thermal signatures associated with the directly imaged protoplanet candidate in the Elias 2-24 disc. Using the DSHARP ALMA observations of the $^{12}$CO J=2-1 line, we show that the disc kinematics are perturbed, with a detached CO emission spot at the location of the planet candidate and traces of spiral wakes, and also that the observed CO emission intensities require local heating. While the foreground extinction hides the velocity channels associated with the planet, preventing a planet mass estimate, the level of gas heating implied by the CO emission indicates the presence of a warm, embedded giant planet. Comparison with models show this could either be a $\gtrsim 5$M$_\mathrm{Jup}$, or a lower mass ( $\gtrsim 2$M$_\mathrm{Jup}$) but accreting proto-planet.Comment: 6 pages, 3 figures, accepted for publication in MNRAS Letter

Meloneis Gen. Nov., a New Epipsammic Genus of Rhaphoneidaceae (Bacillariophyceae)

The diatom family Rhaphoneidaceae is characterized by high generic diversity and low species diversity with most genera known to have long stratigraphic ranges. The genera within this family are neritic marine, and mostly epipsammic. A new modern and epipsammic genus, Meloneis gen. nov., is described herein and is compared to all genera within Rhaphoneidaceae and especially to Rhaphoneis Ehrenberg s.l. Within Meloneis three new species and one variety are distinguished and described herein: M. mimallis sp. nov., M. mimallis var. zephyria var. nov., M. akytos sp. nov., and M. gorgis sp. nov