Geminin Promotes an Epithelial-to-Mesenchymal Transition in an Embryonic Stem Cell Model of Gastrulation

Geminin is a nuclear protein that performs the related functions of modulating cell cycle progression by binding Cdt1, and controlling differentiation by binding transcription factors. Since embryonic stem cells (ESC) and the epiblast share a similar gene expression profile and an attenuated cell cycle, ESC form an accessible and tractable model system to study lineage choice at gastrulation. We derived several ESC lines in which Geminin can be inducibly expressed, and employed short hairpin RNAs targeting Geminin. As in the embryo, a lack of Geminin protein resulted in DNA damage and cell death. In monolayer culture, in defined medium, Geminin supported neural differentiation; however, in three-dimensional culture, overexpression of Geminin promoted mesendodermal differentiation and epithelial-to-mesenchymal transition. In vitro, ESC overexpressing Geminin rapidly recolonized a wound, downregulated E-cadherin expression, and activated Wnt signaling. We suggest that Geminin may promote differentiation via binding Groucho/TLE proteins and upregulating canonical Wnt signaling.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140196/1/scd.2012.0050.pd

Low-Temperature Expansion for a First Order Surface Transition

The question concerning the possibility of a first order surface transition in a semi--infinite Blume--Capel model is addressed by means of low temperature expansions. It is found that such a transition can exist, according to mean field and cluster variation approximations, and contrarily to renormalization group results.Comment: 9 pages (plain TeX) + 1 figure (PostScript, appended), POLFIS-TH.03/9

Almost any quantum spin system with short-range interactions can support toric codes

Inspired by Kitaev's argument that physical error correction is possible in a system of interacting anyons, we demonstrate that such "self-correction" is fairly common in spin systems with classical Hamiltonians that admit the Peierls argument and where errors are modelled by quantum perturbations.Comment: 8 pages; elsart.sty; revised version submitted to Phys. Lett.

Influence of anisotropic next-nearest-neighbor hopping on diagonal charge-striped phases

We consider the model of strongly-correlated system of electrons described by an extended Falicov-Kimball Hamiltonian where the stability of some axial and diagonal striped phases was proved. Introducing a next-nearest-neighbor hopping, small enough not to destroy the striped structure, we examine rigorously how the presence of the next-nearest-neighbor hopping anisotropy reduces the $\pi/2$-rotation degeneracy of the diagonal-striped phase. The effect appears to be similar to that in the case of anisotropy of the nearest-neighbor hopping: the stripes are oriented in the direction of the weaker next-nearest-neighbor hopping.Comment: 9 pages, 3 figures, 1 tabl

Classical and Quantum Mechanics from the universal Poisson-Rinehart algebra of a manifold

The Lie and module (Rinehart) algebraic structure of vector fields of compact support over C infinity functions on a (connected) manifold M define a unique universal non-commutative Poisson * algebra. For a compact manifold, a (antihermitian) variable Z, central with respect to both the product and the Lie product, relates commutators and Poisson brackets; in the non-compact case, sequences of locally central variables allow for the addition of an element with the same role. Quotients with respect to the (positive) values taken by Z* Z define classical Poisson algebras and quantum observable algebras, with the Planck constant given by -iZ. Under standard regularity conditions, the corresponding states and Hilbert space representations uniquely give rise to classical and quantum mechanics on M.Comment: Talk given by the first author at the 40th Symposium on Mathematical Physics, Torun, June 25-28, 200

Transplacental RNAi: Deciphering Gene Function in the Postimplantation-Staged Embryo

RNAi offers the opportunity to examine the role in postimplantation development of genes that cause preimplantation lethality and to create allelic series of targeted embryos. We have delivered constituitively expressed short hairpin (sh) RNAs to pregnant mice during the early postimplantation period of development and observed gene knockdown and defects that phenocopy the null embryo. We have silenced genes that have not yet been “knocked out” in the mouse (geminin and Wnt8b), those required during earlier cleavage stages of development (nanog), and genes required at implantation (Bmp4, Bmp7) singly and in combination (Bmp4 + Bmp7), and obtained unique phenotypes. We have also determined a role in postimplantation development of two transcripts identified in a differential display RT-PCR screen of genes induced in ES cells by noggin exposure, Aggf1 and an Est (GenBank AK008955). Systemic delivery of shRNAs provides a valuable approach to gene silencing in the embryo

Drilling operations for the South Pole Ice Core (SPICEcore) project

Over the course of the 2014/15 and 2015/16 austral summer seasons, the South Pole Ice Core project recovered a 1751 m deep ice core at the South Pole. This core provided a high-resolution record of paleoclimate conditions in East Antarctica during the Holocene and late Pleistocene. The drilling and core processing were completed using the new US Intermediate Depth Drill system, which was designed and built by the US Ice Drilling Program at the University of Wisconsin–Madison. In this paper, we present and discuss the setup, operation, and performance of the drill system

Analysis of the Factors that Limit the Ability of Feeder Cells to Maintain the Undifferentiated State of Human Embryonic Stem Cells

Human embryonic stem cell (hESC) culture is routinely performed using inactivated mouse embryonic fibroblasts (MEFs) as a feeder cell layer (FL). Although these cells maintain pluripotency of hESCs, the molecular basis for this is unknown. Objectives of this study were to determine whether timing between MEF inactivation and their use as a FL influenced hESC growth and differentiation, and to begin defining the mechanism(s) involved. hESCs were plated on MEFs prepared 1 (MEF-1), 4 (MEF-4), and 7 (MEF-7) days earlier. hESC colony morphology and Oct3/4 expression levels were evaluated to determine the influence of different FLs. Significant enhancement of hESC growth (self-renewal) was observed on MEF-1 compared with MEF-4 and/or MEF-7. Conditioned media (CM) collected from MEF-1 supported significantly better hESC growth in a FL-free system compared to MEF-7 CM. Effects of MEFs on hESC growth were not caused by differences in cell density or viability, although indications of apoptosis were observed in MEF-7. Scanning electron microscopy demonstrated that MEF-7 were morphologically distinct from MEF-1 and MEF-4. Microarray analysis identified 19 genes related to apoptosis with significantly different levels of expression between MEF-1 and MEF-7. Several differentially expressed RNAs had gene ontology classifications associated with extracellular matrix (ECM) structural constituents and growth factors. Because members of Wnt signaling pathway were identified in the array analysis, we examined the ability of the Wnt1 CM and secreted frizzled-related proteins to affect hESC growth and differentiation. The addition of Wnt1 CM to both MEF-1 and MEF-7 significantly increased the number of undifferentiated colonies, while the addition of Sfrps promoted differentiation. Together, these results suggest that microenvironment, ECM, and soluble factors expressed by MEF-1 are significantly better at maintaining self-renewal and pluripotency of hESCs. Our findings have important implications in the optimization of hESC culture when MEFs are used as FL or CM is used in FL-free culture.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78130/1/scd.2008.0010.pd

The Physical Principles of Quantum Mechanics. A critical review

The standard presentation of the principles of quantum mechanics is critically reviewed both from the experimental/operational point and with respect to the request of mathematical consistency and logical economy. A simpler and more physically motivated formulation is discussed. The existence of non commuting observables, which characterizes quantum mechanics with respect to classical mechanics, is related to operationally testable complementarity relations, rather than to uncertainty relations. The drawbacks of Dirac argument for canonical quantization are avoided by a more geometrical approach.Comment: Bibliography and section 2.1 slightly improve