Actin at cell-cell junctions is composed of two dynamic and functional populations

The ability of epithelial cells to polarize requires cell-cell adhesion mediated by cadherin receptors. During cell-cell contact, the mechanism via which a flat, spread cell shape is changed into a tall, cuboidal epithelial morphology is not known. We found that cadherin-dependent adhesion modulates actin dynamics by triggering changes in actin organization both locally at junctions and within the rest of the cell. Upon induction of cell-cell contacts, two spatial actin populations are distinguishable: junctional actin and peripheral thin bundles. With time, the relative position of these two populations changes and becomes indistinguishable to form a cortical actin ring that is characteristic of mature, fully polarized epithelial cells. Junctional actin and thin actin bundles differ in their actin dynamics and mechanism of formation, and interestingly, have distinct roles during epithelial polarization. Whereas junctional actin stabilizes clustered cadherin receptors at cell-cell contacts, contraction of peripheral actin bundle is essential for an increase in the maximum height at the lateral domain during polarization (cuboidal morphology). Thus, both junctional actin and thin bundles are necessary, and cooperate with each other to generate a polarized epithelial morphology

Cosmological evolution of scalar fields and gravitino dark matter in gauge mediation at low reheating temperatures

We consider the dynamics of the supersymmetry-breaking scalar field and the production of dark matter gravitinos via its decay in a gauge-mediated supersymmetry breaking model with metastable vacuum. We find that the scalar field amplitude and gravitino density are extremely sensitive to the parameters of the hidden sector. For the case of an O'Raifeartaigh sector, we show that the observed dark matter density can be explained by gravitinos even for low reheating temperatures T_{R} < 10 GeV. Such low reheating temperatures may be implied by detection of the NLSP at the LHC if its thermal freeze-out density is in conflict with BBN.Comment: 11 pages RevTex. Extended discussion and minor corrections, conclusions unaltered. Version to be published in JCA

Analyzing powers in inclusive pion production at high energy and the nucleon spin structure

Analyzing powers in inclusive pion production in high energy transversely polarized proton-proton collisions are studied theoretically in the framework of the quark recombination model. Calculations by assuming the SU(6) spin-flavor symmetry for the nucleon structure disagree with the experiments. We solve this difficulty by taking into account the %We overcome this difficulty by taking into account the realistic spin distribution functions of the nucleon, which differs from the SU(6) expectation at large $x$, %but coincides with a perturbative QCD constraint on the ratio of the unpolarized valence distributions, $u/d \to 5$ as $x \to 1$. We also discuss the kaon spin asymmetry and find $A_N(K^+) = -A_N(K^0)$ in the polarized proton-proton collisions at large $x_F$.Comment: 13 pages, 4 figures, late

Protention and retention in biological systems

This paper proposes an abstract mathematical frame for describing some features of cognitive and biological time. We focus here on the so called "extended present" as a result of protentional and retentional activities (memory and anticipation). Memory, as retention, is treated in some physical theories (relaxation phenomena, which will inspire our approach), while protention (or anticipation) seems outside the scope of physics. We then suggest a simple functional representation of biological protention. This allows us to introduce the abstract notion of "biological inertia".Comment: This paper was made possible only as part of an extended collaboration with Francis Bailly (see references), a dear friend and "ma\^itre \'a penser", who contributed to the key ideas. Francis passed away in february 2008: we continue here our inspiring discussions and joint wor

Mesenchymal Stem Cell–Like Properties of Orbital Fibroblasts in Graves’ Orbitopathy

PURPOSE. Graves’ orbitopathy (GO) is a sight-threatening autoimmune disorder causing extraocular muscle fibrosis, upper lid retraction and eye bulging due to orbital fat expansion. These clinical features are mediated by aspects of orbital fibroblasts differentiation, including adipogenesis and fibrosis. Our previous work suggested that this dual phenotype might be a manifestation of mixed cell populations, partially linked to the expression of mesenchymal stem cell (MSC) marker CD90. Thus, we set out to determine whether GO orbital fibroblasts displayed MSC properties. METHODS. Control and GO orbital fibroblasts previously characterized for CD90 and CD45 expression were analyzed by flow cytometry for classical MSC positive (CD73, CD105) and negative (CD14, CD19, HLA-DR, and CD34) markers. Graves’ orbitopathy fibroblasts were tested further for their ability to undergo lineage specific differentiation following standard protocols. RESULTS. Control and GO fibroblasts strongly expressed CD73 and CD105, with a higher percentage of positive cells and stronger expression levels in GO. Neither cell type expresses CD14, CD19, and HLA-DR. Protein CD34 was expressed at low levels by 45% to 70% of the cells, with its expression significantly lower in GO cells. Graves’ orbitopathy fibroblasts displayed features of osteogenesis (calcium deposits, and osteocalcin [BGLAP] and osteonectin [SPARC] expression), chondrogenesis (glycosaminoglycan production; SOX9 and aggrecan [ACAN] expression), myogenesis (α-smooth muscle actin expression), and neurogenesis (β-III tubulin expression) upon differentiation. CONCLUSIONS. Our findings suggest that orbital fibroblasts contain a population of cells that fulfil the criteria defining MSC. This subpopulation may be increased in GO, possibly underlying the complex differentiation phenotype of the diseas

A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery

Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new treatments to target scarring requires both a better understanding of wound healing and scarring in the conjunctiva, and new means of delivering anti-scarring drugs locally and sustainably. By combining plastic compression of collagen gels with a soft collagen-based layer, we have developed a physiologically relevant model of the sub-epithelial bulbar conjunctiva/Tenon's capsule interface, which allows a more holistic approach to the understanding of subconjunctival tissue behaviour and local drug delivery. The biomimetic tissue hosts both primary human conjunctival fibroblasts and an immune component in the form of macrophages, morphologically and structurally mimicking the mechanical proprieties and contraction kinetics of ex vivo porcine conjunctiva. We show that our model is suitable for the screening of drugs targeting scarring and/or inflammation, and amenable to the study of local drug delivery devices that can be inserted in between the two layers of the biomimetic. We propose that this multicellular-bilayer engineered tissue will be useful to study complex biological aspects of scarring and fibrosis, including the role of inflammation, with potentially significant implications for the management of scarring following glaucoma filtration surgery and other anterior ocular segment scarring conditions. Crucially, it uniquely allows the evaluation of new means of local drug delivery within a physiologically relevant tissue mimetic, mimicking intraoperative drug delivery in vivo

Induction of unique structural changes in guanine-rich DNA regions by the triazoloacridone C-1305, a topoisomerase II inhibitor with antitumor activities

We recently reported that the antitumor triazoloacridone, compound C-1305, is a topoisomerase II poison with unusual properties. In this study we characterize the DNA interactions of C-1305 in vitro, in comparison with other topoisomerase II inhibitors. Our results show that C-1305 binds to DNA by intercalation and possesses higher affinity for GC- than AT-DNA as revealed by surface plasmon resonance studies. Chemical probing with DEPC indicated that C-1305 induces structural perturbations in DNA regions with three adjacent guanine residues. Importantly, this effect was highly specific for C-1305 since none of the other 22 DNA interacting drugs tested was able to induce similar structural changes in DNA. Compound C-1305 induced stronger structural changes in guanine triplets at higher pH which suggested that protonation/deprotonation of the drug is important for this drug-specific effect. Molecular modeling analysis predicts that the zwitterionic form of C-1305 intercalates within the guanine triplet, resulting in widening of both DNA grooves and aligning of the triazole ring with the N7 atoms of guanines. Our results show that C-1305 binds to DNA and induces very specific and unusual structural changes in guanine triplets which likely plays an important role in the cytotoxic and antitumor activity of this unique compound

Reheating Temperature and Gauge Mediation Models of Supersymmetry Breaking

For supersymmetric theories with gravitino dark matter, the maximal reheating temperature consistent with big bang nucleosynthesis bounds arises when the physical gaugino masses are degenerate. We consider the cases of a stau or sneutrino next-to-lightest superpartner, which have relatively less constraint from big bang nucleosynthesis. The resulting parameter space is consistent with leptogenesis requirements, and can be reached in generalized gauge mediation models. Such models illustrate a class of theories that overcome the well-known tension between big bang nucleosynthesis and leptogenesis.Comment: 30 pages, 4 figures; v2: refs adde

Elliptic logarithms, diophantine approximation and the Birch and Swinnerton-Dyer conjecture

Most, if not all, unconditional results towards the abc-conjecture rely ultimately on classical Baker's method. In this article, we turn our attention to its elliptic analogue. Using the elliptic Baker's method, we have recently obtained a new upper bound for the height of the S-integral points on an elliptic curve. This bound depends on some parameters related to the Mordell-Weil group of the curve. We deduce here a bound relying on the conjecture of Birch and Swinnerton-Dyer, involving classical, more manageable quantities. We then study which abc-type inequality over number fields could be derived from this elliptic approach.Comment: 20 pages. Some changes, the most important being on Conjecture 3.2, three references added ([Mas75], [MB90] and [Yu94]) and one reference updated [BS12]. Accepted in Bull. Brazil. Mat. So