Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.

Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets, but molecules such as the transcription factor TFIIB show no preference. Using a single-molecule DNA curtain assay, we find that both unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, although with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin-mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands on the basis of nuclear context

Phenotypic Transition of the Collecting Duct Epithelium in Congenital Urinary Tract Obstruction

Epithelial-mesenchymal transition (EMT) has emerged in recent years as an important process in the development of organ fibrosis in many human diseases. Our previous experience in a nonhuman primate model of obstructive nephropathy suggested that EMT of collecting duct epithelium contributes to the development of interstitial fibrosis. In this study we demonstrate for the first time in humans that obstructed fetal collecting duct epithelium undergoes transition to mesenchymal phenotype, characterized by decreased expression of epithelial markers, de novo expression of mesenchymal markers with subsequent loss of cell-cell interaction, disruption of the basement membrane, and increased deposition of extracellular matrix into the expanded interstitium of the obstructed kidney. The results of this study therefore support the previous findings from animal studies and suggest that EMT of the collecting duct epithelium might contribute to the development of interstitial fibrosis in human fetal obstructive nephropathy

La asociación : revista de primera enseñanza: Año XI Número 541 - (07/07/23)

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end-stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next-generation sequencing have enabled rapid and cost-effective sequencing of large amounts of DNA. Next-generation sequencing-based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early-onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at-risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health-care systems

Study of in-medium ω\omega meson properties in Ap, pA and AA collisions

We propose to investigate the in-medium properties of vector $\omega$ mesons at the normal nuclear density in Ap(pA) collisions and at higher density in AA collisions at the ITEP accelerator facility TWAC. Using of the inverse Ap kinematics will permit us to study the $\omega$ meson production in a wide momentum interval included the not yet explored range of small meson momenta relative to the projectile nuclei where the mass modification effect in nuclear matter is expected to be the strongest. Momentum dependence of the in-medium $\omega$ meson width will be studied in the traditional pA kinematics. We intend to use the electromagnetic calorimeter for reconstruction of the $\omega$ meson invariant mass by detecting photons from the $\omega \to \pi^{0}\gamma \to 3\gamma$ decay. The model calculations and simulations with RQMD generator show feasibility of the proposed experiment. Available now intensity of the ion beams provides a possibility to collect large statistics and make decisive conclusion about the $\omega$ meson properties at density of normal nuclei. At the second stage of the investigation the $\omega$ meson properties will be studied in AA collisions at higher density. Interpretation of these measurements will be based on the results obtained in Ap(pA) interactions. Further investigation of the in-medium properties of light unflavored and charmed mesons can be performed at ITEP and at GSI(FAIR) where higher ion energies will be accessible in near future.Comment: 26 pages, 10 figures, 2 table

On different lagrangian formalisms for vector resonances within chiral perturbation theory

We study the relation of vector Proca field formalism and antisymmetric tensor field formalism for spin-one resonances in the context of the large N_C inspired chiral resonance Lagrangian systematically up to the order O(p6) and give a transparent prescription for the transition from vector to antisymmetric tensor Lagrangian and vice versa. We also discuss the possibility to describe the spin-one resonances using an alternative "mixed" first order formalism, which includes both types of fields simultaneously, and compare this one with the former two. We also briefly comment on the compatibility of the above lagrangian formalisms with the high-energy constraints for concrete VVP correlator.Comment: 34 pages, 3 figure

Spectroscopic, Morphological and Mechanistic Investigation of the Solvent.Promoted Aggregation of Porphyrins Modified in meso-positions by Glucosylated steroids

Solvent-driven aggregation of a series of porphyrin derivatives was studied by UV/Vis and circular dichroism spectroscopy. The porphyrins are characterised by the presence in the meso positions of steroidal moieties further conjugated with glucosyl groups. The presence of these groups makes the investigated macrocycles amphiphilic and soluble in aqueous solvent, namely, dimethyl acetamide/ water. Aggregation of the macrocycles is triggered by a change in bulk solvent composition leading to formation of large architectures that express supramolecular chirality, steered by the presence of the stereogenic centres on the periphery of the macrocycles. The aggregation behaviour and chiroptical features of the aggregates are strongly dependent on the number of moieties decorating the periphery of the porphyrin framework. In particular, experimental evidence indicates that the structure of the steroid linker dictates the overall chirality of the supramolecular architectures. Moreover, the porphyrin concentration strongly affects the aggregation mechanism and the CD intensities of the spectra. Notably, AFM investigations reveal strong differences in aggregate morphology that are dependent on the nature of the appended functional groups, and closely in line with the changes in aggregation mechanism. The suprastructures formed at lower concentration show a network of long fibrous structures spanning over tens of micrometres, whereas the aggregates formed at higher concentration have smaller rodshaped structures that can be recognised as the result of coalescence of smaller globular structures. The fully steroid substituted derivative forms globular structures over the whole concentration range explored. Finally, a rationale for the aggregation phenomena was given by semiempirical calculations at the PM6 level

Generic multiloop methods and application to N=4 super-Yang-Mills

We review some recent additions to the tool-chest of techniques for finding compact integrand representations of multiloop gauge-theory amplitudes - including non-planar contributions - applicable for N=4 super-Yang-Mills in four and higher dimensions, as well as for theories with less supersymmetry. We discuss a general organization of amplitudes in terms of purely cubic graphs, review the method of maximal cuts, as well as some special D-dimensional recursive cuts, and conclude by describing the efficient organization of amplitudes resulting from the conjectured duality between color and kinematic structures on constituent graphs.Comment: 42 pages, 18 figures, invited review for a special issue of Journal of Physics A devoted to "Scattering Amplitudes in Gauge Theories", v2 minor corrections, v3 added reference

Amplitudes at Weak Coupling as Polytopes in AdS_5

We show that one-loop scalar box functions can be interpreted as volumes of geodesic tetrahedra embedded in a copy of AdS_5 that has dual conformal space-time as boundary. When the tetrahedron is space-like, it lies in a totally geodesic hyperbolic three-space inside AdS_5, with its four vertices on the boundary. It is a classical result that the volume of such a tetrahedron is given by the Bloch-Wigner dilogarithm and this agrees with the standard physics formulae for such box functions. The combinations of box functions that arise in the n-particle one-loop MHV amplitude in N=4 super Yang-Mills correspond to the volume of a three-dimensional polytope without boundary, all of whose vertices are attached to a null polygon (which in other formulations is interpreted as a Wilson loop) at infinity.Comment: 16 pages, 5 figure

Hidden Simplicity of Gauge Theory Amplitudes

These notes were given as lectures at the CERN Winter School on Supergravity, Strings and Gauge Theory 2010. We describe the structure of scattering amplitudes in gauge theories, focussing on the maximally supersymmetric theory to highlight the hidden symmetries which appear. Using the BCFW recursion relations we solve for the tree-level S-matrix in N=4 super Yang-Mills theory, and describe how it produces a sum of invariants of a large symmetry algebra. We review amplitudes in the planar theory beyond tree-level, describing the connection between amplitudes and Wilson loops, and discuss the implications of the hidden symmetries.Comment: 46 pages, 15 figures. v2 ref added, typos fixe

In-medium ω\omega mass from the γ+Nb→π0γ+X\gamma + Nb \to \pi^{0}\gamma + X reaction

Data on the photoproduction of $\omega$ mesons on nuclei have been re-analyzed in a search for in-medium modifications. The data were taken with the Crystal Barrel(CB)/TAPS detector system at the ELSA accelerator facility in Bonn. First results from the analysis of the data set were published by D. Trnka et al. in Phys. Rev. Lett 94 (2005) 192303 \cite{david}, claiming a lowering of the $\omega$ mass in the nuclear medium by 14$$ at normal nuclear matter density. The extracted $\omega$ line shape was found to be sensitive to the background subtraction. For this reason a re-analysis of the same data set has been initiated and a new method has been developed to reduce the background and to determine the shape and absolute magnitude of the background directly from the data. Details of the re-analysis and of the background determination are described. The $\omega$ signal on the $Nb$ target, extracted in the re-analysis, does not show a deviation from the corresponding line shape on a $LH_2$ target, measured as reference. The earlier claim of an in-medium mass shift is thus not confirmed. The sensitivity of the $\omega$ line shape to different in-medium modification scenarios is discussed.Comment: 13 pages and 11 figures, submitted for publicatio