One of the major uncertainties in the dense matter equation of state has been the nuclear symmetry energy. The density dependence of the symmetry energy is important in nuclear astrophysics, as it controls the neutronization of matter in core-collapse supernovae, the radii of neutron stars and the thicknesses of their crusts, the rate of cooling of neutron stars, and the properties of nuclei involved in r-process nucleosynthesis. We show that fits of nuclear masses to experimental masses, combined with other experimental information from neutron skins, heavy ion collisions, giant dipole resonances, and dipole polarizabilities, lead to stringent constraints on parameters that describe the symmetry energy near the nuclear saturation density. These constraints are remarkably consistent with inferences from theoretical calculations of pure neutron matter, and, furthermore, with astrophysical observations of neutron stars. The concordance of experimental, theoretical, and observational analyses suggests that the symmetry parameters S v and L are in the range 29.0-32.7 MeV and 40.5-61.9 MeV, respectively, and that the neutron star radius, for a 1.4 M star, is in the narrow window 10.7 km < R < 13.1 km (90% confidence). We can also set tight limits to the size of neutron star crusts and the fractional moment of inertia they contain, as well as the overall moment of inertia and quadrupole polarizability of 1.4 M stars. Our results also have implications for the disk mass and ejected mass of compact mergers involving neutron stars.

FAK is known as an integrin- and growth factor-associated tyrosine kinase promoting cell motility. Here we show that, during mouse development, FAK inactivation results in p53- and p21-dependent mesodermal cell growth arrest. Reconstitution of primary FAK-/-p21-/- fibroblasts revealed that FAK, in a kinase-independent manner, facilitates p53 turnover via enhanced Mdm2-dependent p53 ubiquitination. p53 inactivation by FAK required FAK FERM F1 lobe binding to p53, FERM F2 lobe-mediated nuclear localization, and FERM F3 lobe for connections to Mdm2 and proteasomal degradation. Staurosporine or loss of cell adhesion enhanced FERM-dependent FAK nuclear accumulation. In primary human cells, FAK knockdown raised p53-p21 levels and slowed cell proliferation but did not cause apoptosis. Notably, FAK knockdown plus cisplatin triggered p53-dependent cell apoptosis, which was rescued by either full-length FAK or FAK FERM re-expression. These studies define a scaffolding role for nuclear FAK in facilitating cell survival through enhanced p53 degradation under conditions of cellular stress.

We confront observational data from gravitational wave event GW170817 with microscopic modeling of the cold neutron star equation of state. We develop and employ a Bayesian statistical framework that enables us to implement constraints on the equation of state from laboratory measurements of nuclei and state-of-the-art chiral effective field theory methods. The energy density functionals constructed from the posterior probability distributions are then used to compute consistently the neutron star equation of state from the outer crust to the inner core, assuming a composition consisting of protons, neutrons, electrons, and muons. In contrast to previous studies, we find that the 95% credibility range of predicted neutron star tidal deformabilities (136<Λ<519) for a 1.4 solar-mass neutron star is already consistent with the upper bound deduced from observations of the GW170817 event. However, we find that lower bounds on the neutron star tidal deformability will very strongly constrain microscopic models of the dense matter equation of state. We also demonstrate a strong correlation between the neutron star tidal deformability and the pressure of beta-equilibrated matter at twice saturation density.

Integrin binding to matrix proteins such as fibronectin (FN) leads to formation of focal adhesion (FA) cellular contact sites that regulate migration. RhoA GTPases facilitate FA formation, yet FA-associated RhoA-specific guanine nucleotide exchange factors (GEFs) remain unknown. Here, we show that proline-rich kinase-2 (Pyk2) levels increase upon loss of focal adhesion kinase (FAK) in mouse embryonic fibroblasts (MEFs). Additionally, we demonstrate that Pyk2 facilitates deregulated RhoA activation, elevated FA formation, and enhanced cell proliferation by promoting p190RhoGEF expression. In normal MEFs, p190RhoGEF knockdown inhibits FN-associated RhoA activation, FA formation, and cell migration. Knockdown of p190RhoGEF-related GEFH1 does not affect FA formation in FAK−/− or normal MEFs. p190RhoGEF overexpression enhances RhoA activation and FA formation in MEFs dependent on FAK binding and associated with p190RhoGEF FA recruitment and tyrosine phosphorylation. These studies elucidate a compensatory function for Pyk2 upon FAK loss and identify the FAK–p190RhoGEF complex as an important integrin-proximal regulator of FA formation during FN-stimulated cell motility.

Syndecan-2 is a transmembrane heparan sulfate proteoglycan whose function at the cell surface is unclear. In this study, we examined the function of syndecan-2 in colon cancer cell lines. In several colon cancer cell lines, syndecan-2 was highly expressed compared with normal cell lines. In contrast, syndecan-1 and -4 were decreased. Cell biological studies using the extracellular domain of recombinant syndecan-2 (2E) or spreading assay with syndecan-2 antibody-coated plates showed that syndecan-2 mediated adhesion and cytoskeletal organization of colon cancer cells. This interaction was critical for the proliferation of colon carcinoma cells. Blocking with 2E or antisense syndecan-2 cDNA induced G 0 /G 1 cell cycle arrest with concomitantly increased expression of p21, p27, and p53. Furthermore, blocking of syndecan-2 through antisense syndecan-2 cDNA significantly reduced tumorigenic activity in colon carcinoma cells. Therefore, increased syndecan-2 expression appears to be a critical for colon carcinoma cell behavior, and syndecan-2 regulates tumorigenic activity through regulation of adhesion and proliferation in colon carcinoma cells.