Activation of Akt by the Bacterial Inositol Phosphatase, SopB, is Wortmannin Insensitive

Salmonella enterica uses effector proteins translocated by a Type III Secretion System to invade epithelial cells. One of the invasion-associated effectors, SopB, is an inositol phosphatase that mediates sustained activation of the pro-survival kinase Akt in infected cells. Canonical activation of Akt involves membrane translocation and phosphorylation and is dependent on phosphatidyl inositide 3 kinase (PI3K). Here we have investigated these two distinct processes in Salmonella infected HeLa cells. Firstly, we found that SopB-dependent membrane translocation and phosphorylation of Akt are insensitive to the PI3K inhibitor wortmannin. Similarly, depletion of the PI3K regulatory subunits p85α and p85ß by RNAi had no inhibitory effect on SopB-dependent Akt phosphorylation. Nevertheless, SopB-dependent phosphorylation does depend on the Akt kinases, PDK1 and rictor-mTOR. Membrane translocation assays revealed a dependence on SopB for Akt recruitment to Salmonella ruffles and suggest that this is mediated by phosphoinositide (3,4) P2 rather than phosphoinositide (3,4,5) P3. Altogether these data demonstrate that Salmonella activates Akt via a wortmannin insensitive mechanism that is likely a class I PI3K-independent process that incorporates some essential elements of the canonical pathway

Adolescent and Young Adult Perceptions of Hookah and Little Cigars/Cigarillos: Implications for Risk Messages

Use of hookah and little cigars/cigarillos (LCCs) is high among adolescents and young adults. Although these products have health effects similar to cigarettes, adolescents and young adults believe them to be safer. This study examined adolescent and young adult perceptions of hookah and LCCs to develop risk messages aimed at discouraging use among users and at-risk nonusers. Ten focus groups with 77 adolescents and young adults were conducted to explore their perceptions about the perceived risks and benefits of hookah and LCC use. Participants were users of other (non-cigarette) tobacco products (n=47) and susceptible nonusers (n=30). Transcripts were coded for emergent themes on participants’ perceptions of hookah and LCCs. Participants did not perceive health effects associated with hookah and LCC use to be serious or likely to happen given their infrequency of use and perceptions that they are less harmful than cigarettes. Participants generally had positive associations with smoking hookah and LCCs for several reasons, including that they are used in social gatherings, come in various flavors, and can be used to perform smoke tricks. Because adolescents and young adults underestimate and discount the long-term risks associated with hookah and LCC use, effective messages may be those that focus on the acute/immediate health and cosmetic effects

JWST Discovery of 40+40+ Microlensed Stars in a Magnified Galaxy, the "Dragon" behind Abell 370

International audienceStrong gravitational magnification by massive galaxy clusters enable us to detect faint background sources, resolve their detailed internal structures, and in the most extreme cases identify and study individual stars in distant galaxies. Highly magnified individual stars allow for a wide range of applications, including studies of stellar populations in distant galaxies and constraining small-scale dark matter structures. However, these applications have been hampered by the small number of events observed, as typically one or a few stars are identified from each distant galaxy. Here, we report the discovery of 46 significant microlensed stars in a single strongly-lensed high-redshift galaxy behind the Abell 370 cluster at redshift of 0.725 when the Universe was half of its current age (dubbed the ``Dragon arc''), based on two observations separated by one year with the James Webb Space Telescope ({\it JWST}). These events are mostly found near the expected lensing critical curves, suggesting that these are magnified individual stars that appear as transients from intracluster stellar microlenses. Through multi-wavelength photometry and colors, we constrain stellar types and find that many of them are consistent with red giants/supergiants magnified by factors of thousands. This finding reveals an unprecedented high occurrence of microlensing events in the Dragon arc, and proves that {\it JWST}'s time-domain observations open up the possibility of conducting statistical studies of high-redshift stars and subgalactic scale perturbations in the lensing dark matter field