Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence.

Rickettsia are obligate intracellular bacteria that evade antimicrobial autophagy in the host cell cytosol by unknown mechanisms. Other cytosolic pathogens block different steps of autophagy targeting, including the initial step of polyubiquitin-coat formation. One mechanism of evasion is to mobilize actin to the bacterial surface. Here, we show that actin mobilization is insufficient to block autophagy recognition of the pathogen Rickettsia parkeri. Instead, R. parkeri employs outer membrane protein B (OmpB) to block ubiquitylation of the bacterial surface proteins, including OmpA, and subsequent recognition by autophagy receptors. OmpB is also required for the formation of a capsule-like layer. Although OmpB is dispensable for bacterial growth in endothelial cells, it is essential for R. parkeri to block autophagy in macrophages and to colonize mice because of its ability to promote autophagy evasion in immune cells. Our results indicate that OmpB acts as a protective shield to obstruct autophagy recognition, thereby revealing a distinctive bacterial mechanism to evade antimicrobial autophagy

AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major components, collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C-type lectin-like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognize glycosylated collagens, reversed actinomyosin-based contractility [myosin-light chain-2 (MLC2) phosphorylation], loss of cell polarity, loss of cell–cell junctions, luminal infiltration and basal invasion induced by AGE-modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180ΔEx2–6/ΔEx2–6 mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour in non-transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer and other pathologies in which increased basal lamina thickness and tissue stiffness are driving factors

Odorant transport in a hagfish

Odorant transport is of fundamental and applied importance. Using computational simulations, we studied odorant transport in an anatomically accurate model of the nasal passage of a hagfish (probably Eptatretus stoutii). We found that ambient water is sampled widely, with a significant ventral element. Additionally, there is a bilateral element to olfactory flow, which enters the single nostril in two narrow, laminar streams that are then split prior to the nasal chamber by the anterior edge of the central olfactory lamella. An appendage on this lamella directs a small portion (10–14%) of the overall nasal flow to the olfactory sensory channels. Much of the remaining flow is diverted away from the sensory channels by two peripheral channels. The anterior edge of the central olfactory lamella, together with a jet-impingement mechanism, disperses flow over the olfactory surfaces. Diffusion of odorant from bulk water to the olfactory surfaces is facilitated by the large surface area:volume ratio of the sensory channels, and by a resistance-based hydrodynamic mechanism that leads to long residence times (up to 4.5 s) in the sensory channels. With increasing volumetric flow rate, the rate of odorant transfer to the olfactory surfaces increases, but the efficiency of odorant uptake decreases, falling in the range 2–6%. Odorant flux decreases caudally across the olfactory surfaces, suggesting in vivo a preponderance of olfactory sensory neurons on the anterior part of each olfactory surface. We conclude that the hagfish has a subtle anatomy for locating and capturing odorant molecules

Panoramic Views of the Cygnus Loop

We present a complete atlas of the Cygnus Loop supernova remnant in the light of [O III] (5007), H alpha, and [S II] (6717, 6731). Despite its shell-like appearance, the Cygnus Loop is not a current example of a Sedov-Taylor blast wave. Rather, the optical emission traces interactions of the supernova blast wave with clumps of gas. The surrounding interstellar medium forms the walls of a cavity through which the blast wave now propagates, including a nearly complete shell in which non-radiative filaments are detected. The Cygnus Loop blast wave is not breaking out of a dense cloud, but is instead running into confining walls. The interstellar medium dominates not only the appearance of the Cygnus Loop but also the continued evolution of the blast wave. If this is a typical example of a supernova remnant, then global models of the interstellar medium must account for such significant blast wave deceleration.Comment: 28 pages AAS Latex, 28 black+white figures, 6 color figures. To be published in The Astrophysical Journal Supplement Serie

Resistance to Peer influence Moderates the Relationship Between Perceived (But Not Actual) Peer Norms and Binge Drinking in a College Student Social Network

Introduction: Adolescent and young adult binge drinking is strongly associated with perceived social norms and the drinking behavior that occurs within peer networks. The extent to which an individual is influenced by the behavior of others may depend upon that individual’s resistance to peer influence (RPI). Methods: Students in their first semester of college (N = 1323; 54.7% female, 57% White, 15.1% Hispanic) reported on their own binge drinking, and the perceived binge drinking of up to 10 important peers in the first-year class. Using network autocorrelation models, we investigated cross-sectional relationships between participant’s binge drinking frequency and the perceived and actual binge drinking frequency of important peers. We then tested the moderating role of RPI, expecting that greater RPI would weaken the relationship between perceived and actual peer binge drinking on participant binge drinking. Results: Perceived and actual peer binge drinking were statistically significant predictors of participant binge drinking frequency in the past month, after controlling for covariates. RPI significantly moderated the association between perceptions of peer binge drinking and participant’s own binge drinking; this association was weaker among participants with higher RPI compared to those with lower RPI. RPI did not interact with the actual binge drinking behavior of network peers

Semisimplicity of the quantum cohomology for smooth Fano toric varieties associated with facet symmetric polytopes

The degree zero part of the quantum cohomology algebra of a smooth Fano toric symplectic manifold is determined by the superpotential function, W, of its moment polytope. In particular, this algebra is semisimple, i.e. splits as a product of fields, if and only if all the critical points of W are non-degenerate. In this paper we prove that this non-degeneracy holds for all smooth Fano toric varieties with facet-symmetric duals to moment polytopes.Comment: 16 pages; corrected version, published in Electron. Res. Announc. Math. Sc

Do Misperceptions of Peer Drinking Influence Personal Drinking Behavior? Results From a Complete Social Network of First-Year College Students

This study considered the influence of misperceptions of typical versus self-identified important peers\u27 heavy drinking on personal heavy drinking intentions and frequency utilizing data from a complete social network of college students. The study sample included data from 1,313 students (44% male, 57% White, 15% Hispanic/Latinx) collected during the fall and spring semesters of their freshman year. Students provided perceived heavy drinking frequency for a typical student peer and up to 10 identified important peers. Personal past-month heavy drinking frequency was assessed for all participants at both time points. By comparing actual with perceived heavy drinking frequencies, measures of misperceptions of heavy drinking (accurately estimate, overestimate, underestimate) were constructed for both general and important peers. These misperceptions were then used as predictors of concurrent and prospective personal heavy drinking frequency and intentions using network autocorrelation analyses. The majority of students (84.8%) overestimated, 11.3% accurately estimated, and 3.9% underestimated heavy drinking among their general peers, whereas 42.0% accurately estimated, 36.9% overestimated, and 21.1% underestimated important peers\u27 heavy drinking. For both referents, overestimation of peer heavy drinking was associated with more frequent heavy drinking and higher drinking intentions at both time points. Importantly, the effects of underestimating and overestimating close peers\u27 drinking on personal alcohol use were significant after controlling for the influence of misperceptions of general peers\u27 heavy drinking. Close peers are a critical referent group in assessments related to social norms for young adult alcohol use. Implications for prevention and intervention are discussed