The C-terminus of p63 contains multiple regulatory elements with different functions

The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms contain a C-terminal inhibitory domain that negatively regulates their transcriptional activity. This inhibitory domain contains two individual components: one that uses an internal binding mechanism to interact with and mask the transactivation domain and one that is based on sumoylation. We have carried out an extensive alanine scanning study to identify critical regions within the inhibitory domain. These experiments show that a stretch of ~13 amino acids is crucial for the binding function. Further, investigation of transcriptional activity and the intracellular level of mutants that cannot be sumoylated suggests that sumoylation reduces the concentration of p63. We therefore propose that the inhibitory function of the C-terminal domain is in part due to direct inhibition of the transcriptional activity of the protein and in part due to indirect inhibition by controlling the concentration of p63. Keywords: p63, transcriptional regulation, auto-inhibition, sumoylatio

Taxonomic corrections and new records in vascular plants of Kyrgyzstan

A series of notes on distribution, taxonomy and nomenclature of some vascular plants in Kyrgyzstan is presented. Two new hybrids (Delphinium × pskemense Sennikov & Lazkov, Perovskia × intermedia Lazkov) are described. The variety Rhinactinidia limoniifolia var. brachyglossa Lazkov & Sennikov and forma Rubus praecox Bertol. f. rutiliflorus H.E.Weber & Sennikov are described for unusual morphotypes of these species. Five transfers from Pyrethrum to Richteria (R. brachanthemoides (Kamelin & Lazkov) Sennikov, R. neglecta (Tzvelev) Sennikov, R. sovetkinae (Kovalevsk.) Sennikov, R. sussamyrensis (Lazkov) Sennikov, R. sect. Trichanthemopsis (Tzvelev) Sennikov) are proposed in conformity with the phylogeny of Anthemideae. Nomenclature is discussed and lectotype is designated for Achillea biebersteinii Afan. Three transfers (Arctium nidulans (Regel) Sennikov, A. sect. Plagiocephalum (Rupr.) Sennikov, Harmsiella olgae (Regel) Sennikov) are proposed because of priority under the current phylogeny of Asteraceae and Lamiaceae. Ten native species (Centaurea chartolepis Greuter, Cousinia hamadae Juz., Hypopitys hypophegea (Wallr.) G.Don, Lemna turionifera Landolt, Lycopus exaltatus L. f., Portulaca granulatostellulata (Poelln.) C.Ricceri & P.V.Arrigoni, P. nitida (Danin & H.G.Baker) C.Ricceri & P.V.Arrigoni, Ranunculus acris L., Rubia laevissima Tschern., Zygophyllum miniatum Cham.) and two aliens (Calystegia spectabilis (Brummitt) Tzvelev, Rubus praecox Bertol.) are new to Kyrgyzstan. Ten species are new to certain mointain ranges. The presence of Sorbus turkestanica (Franch.) Hedl. in Kyrgyzstan is confirmed; this species and S. persica Hedl. are mapped anew for conservation purposes. Otostegia nikitinae Scharasch. and O. schennikovii Scharasch. are synonyms of Harmsiella olgae and therefore need no protection in Kyrgyzstan

Wigner Distribution Deconvolution Adaptation for Live Ptychography Reconstruction

We propose a modification of Wigner Distribution Deconvolution (WDD) to support live processing ptychography. Live processing allows to reconstruct and display the specimen transfer function gradually while diffraction patterns are acquired. For this purpose we reformulate WDD and apply a dimensionality reduction technique that reduces memory consumption and increases processing speed. We show numerically that this approach maintains the reconstruction quality of specimen transfer functions as well as reduces computational complexity during acquisition processes. Although we only present the reconstruction for Scanning Transmission Electron Microscopy (STEM) datasets, in general, the live processing algorithm we present in this paper can be applied to real-time ptychographic reconstruction for different fields of application

Sparkling extreme-ultraviolet bright dots observed with Hi-C

Observing the Sun at high time and spatial scales is a step toward understanding the finest and fundamental scales of heating events in the solar corona. The high-resolution coronal (Hi-C) instrument has provided the highest spatial and temporal resolution images of the solar corona in the EUV wavelength range to date. Hi-C observed an active region on 2012 July 11 that exhibits several interesting features in the EUV line at 193 Å. One of them is the existence of short, small brightenings "sparkling" at the edge of the active region; we call these EUV bright dots (EBDs). Individual EBDs have a characteristic duration of 25 s with a characteristic length of 680 km. These brightenings are not fully resolved by the SDO/AIA instrument at the same wavelength; however, they can be identified with respect to the Hi-C location of the EBDs. In addition, EBDs are seen in other chromospheric/coronal channels of SDO/AIA, which suggests a temperature between 0.5 and 1.5 MK. Based on their frequency in the Hi-C time series, we define four different categories of EBDs: single peak, double peak, long duration, and bursty. Based on a potential field extrapolation from an SDO/HMI magnetogram, the EBDs appear at the footpoints of large-scale, trans-equatorial coronal loops. The Hi-C observations provide the first evidence of small-scale EUV heating events at the base of these coronal loops, which have a free magnetic energy of the order of 1026 erg. © 2014. The American Astronomical Society. All rights reserved

Macroporous Composite Cryogels with Embedded Polystyrene Divinylbenzene Microparticles for the Adsorption of Toxic Metabolites from Blood

Composite monolithic adsorbents were prepared by the incorporation of neutral polystyrene divinylbenzene (PS-DVB) microparticles into macroporous polymer structures produced by cryogelation of agarose or poly(vinyl alcohol). The composite materials exhibited excellent flow-through properties. Scanning electron microscopy of the composite cryogels revealed that the microparticles were covered by thin films of poly(vinyl alcohol) or agarose and thus were withheld in the monolith structure. Plain PS-DVB microparticles showed efficient adsorption of albumin-bound toxins related to liver failure (bilirubin and cholic acid) and of cytokines (tumor necrosis factor-alpha and interleukin-6). The rates of adsorption and the amount of adsorbed factors were lower for the embedded microparticles as compared to the parent PS-DVB microparticles, indicating the importance of the accessibility of the adsorbent pores. Still, the macroporous composite materials showed efficient adsorption of albuminbound toxins related to liver failure as well as efficient binding of cytokines, combined with good blood compatibility. Thus, the incorporation of microparticles into macroporous polymer structures may provide an option for the development of adsorption modules for extracorporeal blood purification

Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole

<p>Abstract</p> <p>Background</p> <p>Elevated blood O₂affinity enhances survival at low O₂pressures, and is perhaps the best known and most broadly accepted evolutionary adjustment of terrestrial vertebrates to environmental hypoxia. This phenotype arises by increasing the intrinsic O₂affinity of the hemoglobin (Hb) molecule, by decreasing the intracellular concentration of allosteric effectors (e.g., 2,3-diphosphoglycerate; DPG), or by suppressing the sensitivity of Hb to these physiological cofactors.</p> <p>Results</p> <p>Here we report that strictly fossorial eastern moles (<it>Scalopus aquaticus</it>) have evolved a low O₂affinity, DPG-insensitive Hb - contrary to expectations for a mammalian species that is adapted to the chronic hypoxia and hypercapnia of subterranean burrow systems. Molecular modelling indicates that this functional shift is principally attributable to a single charge altering amino acid substitution in the β-type δ-globin chain (δ136Gly→Glu) of this species that perturbs electrostatic interactions between the dimer subunits via formation of an intra-chain salt-bridge with δ82Lys. However, this replacement also abolishes key binding sites for the red blood cell effectors Cl^-, lactate and DPG (the latter of which is virtually absent from the red cells of this species) at δ82Lys, thereby markedly reducing competition for carbamate formation (CO₂binding) at the δ-chain N-termini.</p> <p>Conclusions</p> <p>We propose this Hb phenotype illustrates a novel mechanism for adaptively elevating the CO₂carrying capacity of eastern mole blood during burst tunnelling activities associated with subterranean habitation.</p

Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole

Background: Elevated blood O2 affinity enhances survival at low O2 pressures, and is perhaps the best known and most broadly accepted evolutionary adjustment of terrestrial vertebrates to environmental hypoxia. This phenotype arises by increasing the intrinsic O2 affinity of the hemoglobin (Hb) molecule, by decreasing the intracellular concentration of allosteric effectors (e.g., 2,3-diphosphoglycerate; DPG), or by suppressing the sensitivity of Hb to these physiological cofactors. Results: Here we report that strictly fossorial eastern moles (Scalopus aquaticus) have evolved a low O2 affinity, DPG-insensitive Hb - contrary to expectations for a mammalian species that is adapted to the chronic hypoxia and hypercapnia of subterranean burrow systems. Molecular modelling indicates that this functional shift is principally attributable to a single charge altering amino acid substitution in the β-type δ-globin chain (δ136Gly→Glu) of this species that perturbs electrostatic interactions between the dimer subunits via formation of an intra-chain salt-bridge with δ82Lys. However, this replacement also abolishes key binding sites for the red blood cell effectors Cl-, lactate and DPG (the latter of which is virtually absent from the red cells of this species) at δ82Lys, thereby markedly reducing competition for carbamate formation (CO2 binding) at the δ-chain N-termini. Conclusions: We propose this Hb phenotype illustrates a novel mechanism for adaptively elevating the CO2 carrying capacity of eastern mole blood during burst tunnelling activities associated with subterranean habitation