p120-catenin regulates REST and CoREST, and modulates mouse embryonic stem cell differentiation

The canonical-Wnt pathway and beta-catenin have been extensively studied to determine their contributions to stem cell biology, but less is known about p120-catenin in the nuclear compartment. P120 is developmentally required as a consequence of its biochemical and functional interactions with cadherins, small-GTPases and transcriptional regulators. We report here that p120-catenin binds to and negatively regulates REST and CoREST, that others have indicated form a repressive complex having diverse key roles in developmental and pathologic gene regulation. We thus provide the first evidence for a direct upstream modulator of REST/CoREST function. Using mouse embryonic stem cells (mESCs), mammalian cell lines, Xenopus embryos, and in vitro systems, we show that p120 directly binds to the zinc finger/DNA-binding region of REST, as well as to CoREST. Chromatin immuno-precipitation and other approaches indicate that p120 protein levels negatively determine the extent of REST/CoREST bound to RE1 consensus binding sites and negatively influence REST/CoREST protein stability. As would be predicted, p120 overexpression and depletion have complementary effects upon REST/CoREST gene-target activity. Thus, p120 depletion in mESCs reduces REST/CoREST gene-target expression, while p120 overexpression has a converse effect. Importantly, p120 levels modulate the mRNA and protein levels of Oct4, Nanog, and Sox2, and have an impact upon the differentiation of mESCs towards neural fates. In assessing potential upstream inputs of this novel p120-REST/ CoREST pathway, REST gene targets were found to respond to the level of E-cadherin, with cadherin effects being dependent on p120-catenin as predicted. In summary, at both biochemical and functional levels, our findings reveal a central role of p120-catenin in the derepression (activation) of genes directly controlled by REST/CoREST, and in the modulation of stem cells

Revisiting the Impact of Divisional Affiliation on Secondary Market Ticket Prices in the National Football League

With the emergence of demand-based ticket pricing, professional sport organizations and marketers will benefit from a thorough understanding of pricing in the demand-driven secondary market. Ticket pricing studies often take divisional affiliation as a control variable; little research has focused on and examined the importance of divisional affiliation for secondary market ticket prices. Different from work indicating consumers’ preference for divisional games, this study revealed that higher ticket prices (i.e., consumer demand) accompanied non-divisional games. Additionally, the number of years between the away team’s visit to the home team’s stadium and the away team’s current winning percentage each played a significant role (explained by roughly 49% of the variance) in higher ticket prices for non-divisional games in the National Football League

Sign-tunable anomalous Hall effect induced by two-dimensional symmetry-protected nodal structures in ferromagnetic perovskite oxide thin films

Magnetism and spin-orbit coupling (SOC) are two quintessential ingredients underlying novel topological transport phenomena in itinerant ferromagnets. When spin-polarized bands support nodal points/lines with band degeneracy that can be lifted by SOC, the nodal structures become a source of Berry curvature; this leads to a large anomalous Hall effect (AHE). Contrary to three-dimensional systems that naturally host nodal points/lines, two-dimensional (2D) systems can possess stable nodal structures only when proper crystalline symmetry exists. Here we show that 2D spin-polarized band structures of perovskite oxides generally support symmetry-protected nodal lines and points that govern both the sign and the magnitude of the AHE. To demonstrate this, we performed angle-resolved photoemission studies of ultrathin films of SrRuO$_3$, a representative metallic ferromagnet with SOC. We show that the sign-changing AHE upon variation in the film thickness, magnetization, and chemical potential can be well explained by theoretical models. Our study is the first to directly characterize the topological band structure of 2D spin-polarized bands and the corresponding AHE, which could facilitate new switchable devices based on ferromagnetic ultrathin films

Plakophilin-3 Is Required for Late Embryonic Amphibian Development, Exhibiting Roles in Ectodermal and Neural Tissues

The p120-catenin family has undergone a significant expansion during the evolution of vertebrates, resulting in varied functions that have yet to be discerned or fully characterized. Likewise, members of the plakophilins, a related catenin subfamily, are found throughout the cell with little known about their functions outside the desmosomal plaque. While the plakophilin-3 (Pkp3) knockout mouse resulted in skin defects, we find larger, including lethal effects following its depletion in Xenopus. Pkp3, unlike some other characterized catenins in amphibians, does not have significant maternal deposits of mRNA. However, during embryogenesis, two Pkp3 protein products whose temporal expression is partially complimentary become expressed. Only the smaller of these products is found in adult Xenopus tissues, with an expression pattern exhibiting distinctions as well as overlaps with those observed in mammalian studies. We determined that Xenopus Pkp3 depletion causes a skin fragility phenotype in keeping with the mouse knockout, but more novel, Xenopus tailbud embryos are hyposensitive to touch even in embryos lacking outward discernable phenotypes, and we additionally resolved disruptions in certain peripheral neural structures, altered establishment and migration of neural crest, and defects in ectodermal multiciliated cells. The use of two distinct morpholinos, as well as rescue approaches, indicated the specificity of these effects. Our results point to the requirement of Pkp3 in amphibian embryogenesis, with functional roles in a number of tissue types

Wnt4 and ephrinB2 instruct apical constriction via Dishevelled and non-canonical signaling

Apical constriction is known to be critical for neural tube closure, but the signals that induce this process have not been fully characterized. Here Yoon et al. identify a signaling complex that instructs actomyosin contractions during apical constriction and show that it is required for neural tube closure

Geochronologic evidence for Early Cretaceous volcanic activity on Barton Peninsula, King George Island, Antarctica

Ages of six volcanic and plutonic rocks on Barton Peninsula, King George Island, were determined using 40Ar/39Ar and K-Ar isotopic systems. The 40Ar/39Ar and K-Ar ages of basaltic andesite and diorite range from 48 My to 74 My and systematically decrease toward the upper stratigraphic section. Two specimens of basaltic andesite which occur in the lowermost sequence of the peninsula, however, apparently define two distinct plateau ages of 52-53 My and 119-120 My. The latter is interpreted to represent the primary cooling age of basaltic andesite, whereas the former is interpreted as the thermally-reset age caused by the intrusion of Tertiary granitic pluton. The isochron ages calculated from the isotope correlation diagram corroborate our interpretation based on the apparent plateau ages. It is therefore likely that volcanism was active during the Early Cretaceous on Barton Peninsula. When the K-Ar ages of previous studies are taken into account with our result, the ages of basaltic andesite in the northern part of the Barton Peninsula are significantly older than those in the southern part. Across the north-west-south-east trending Barton fault bounding the two parts, there are significant differences in geochronologic and geologic aspects