Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery.

Injectable hydrogels with tunable physiochemical and biological properties are potential tools for improving neural stem/progenitor cell (NSPC) transplantation to treat central nervous system (CNS) injury and disease. Here, we developed injectable diblock copolypeptide hydrogels (DCH) for NSPC transplantation that contain hydrophilic segments of modified l-methionine (Met). Multiple Met-based DCH were fabricated by post-polymerization modification of Met to various functional derivatives, and incorporation of different amino acid comonomers into hydrophilic segments. Met-based DCH assembled into self-healing hydrogels with concentration and composition dependent mechanical properties. Mechanical properties of non-ionic Met-sulfoxide formulations (DCHMO) were stable across diverse aqueous media while cationic formulations showed salt ion dependent stiffness reduction. Murine NSPC survival in DCHMO was equivalent to that of standard culture conditions, and sulfoxide functionality imparted cell non-fouling character. Within serum rich environments in vitro, DCHMO was superior at preserving NSPC stemness and multipotency compared to cell adhesive materials. NSPC in DCHMO injected into uninjured forebrain remained local and, after 4 weeks, exhibited an immature astroglial phenotype that integrated with host neural tissue and acted as cellular substrates that supported growth of host-derived axons. These findings demonstrate that Met-based DCH are suitable vehicles for further study of NSPC transplantation in CNS injury and disease models

The Complete transmission spectrum of WASP-39b with a precise water constraint

This is the author accepted manuscript. The final version is available from American Astronomical Society via the DOI in this record.WASP-39b is a hot Saturn-mass exoplanet with a predicted clear atmosphere based on observations in the optical and infrared. Here we complete the transmission spectrum of the atmosphere with observations in the near-infrared (NIR) over three water absorption features with the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) G102 (0.8-1.1 microns) and G141 (1.1-1.7 microns) spectroscopic grisms. We measure the predicted high amplitude H2O feature centered at 1.4 microns, and the smaller amplitude features at 0.95 and 1.2 microns, with a maximum water absorption amplitude of 2.4 planetary scale heights. We incorporate these new NIR measurements into previously published observational measurements to complete the transmission spectrum from 0.3-5 microns. From these observed water features, combined with features in the optical and IR, we retrieve a well constrained temperature Teq = 1030(+30,-20) K, and atmospheric metallicity 151 (+48,-46)x solar which is relatively high with respect to the currently established mass-metallicity trends. This new measurement in the Saturn-mass range hints at further diversity in the planet formation process relative to our solar system giants.This work is based on observations made with the NASA/ESA Hubble Space Telescope that were obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc. These observations are associated with programs GO-14169 (PI. HR Wakeford) and GO-14260 (PI. D Deming). D.K.S., H.R.W., T.E., B.D., and N.N., acknowledge funding from the European Research Council (ERC) under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. J.G. acknowledges support from Leverhulme Trust. A.L.C. acknowledges support from the STFC. H.R.W. also acknowledges support from the Giacconi Fellowship at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc

Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via Controlled NCA Polymerization

This article summarizes advances in the synthesis of well-defined polypeptides and block copolypeptides. Traditional methods used to polymerize α-amino acid-N-carboxyanhydrides (NCAs) are described, and limitations in the utility of these systems for the preparation of polypeptides are discussed. Improved initiators and methods that allow polypeptide synthesis with good control over chain length, chain length distribution, and chain-end functionality are also discussed. Using these methods, block and random copolypeptides of controlled dimensions (including molecular weight, sequence, composition, and molecular weight distribution) can now be prepared. The ability of well-defined block copolypeptides to assemble into supramolecular copolypeptide micelles, copolypeptide vesicles, and copolypeptide hydrogels is described. Many of these assemblies have been found to possess unique properties that are derived from the amino acid building blocks and ordered conformations of the polypeptide segments. © Springer-Verlag Berlin Heidelberg 2013

Mapping Exoplanets

The varied surfaces and atmospheres of planets make them interesting places to live, explore, and study from afar. Unfortunately, the great distance to exoplanets makes it impossible to resolve their disk with current or near-term technology. It is still possible, however, to deduce spatial inhomogeneities in exoplanets provided that different regions are visible at different times---this can be due to rotation, orbital motion, and occultations by a star, planet, or moon. Astronomers have so far constructed maps of thermal emission and albedo for short period giant planets. These maps constrain atmospheric dynamics and cloud patterns in exotic atmospheres. In the future, exo-cartography could yield surface maps of terrestrial planets, hinting at the geophysical and geochemical processes that shape them.Comment: Updated chapter for Handbook of Exoplanets, eds. Deeg & Belmonte. 17 pages, including 6 figures and 4 pages of reference

Stabilization of Peptide Vesicles by Introducing Inter-Peptide Disulfide Bonds

PURPOSE: Previously, we have shown that the amphiphilic oligopeptide SA2 (Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu-COOH) spontaneously self-assemble into nano-sized vesicles in aqueous environment. Relative weak individual intermolecular interactions dominate such oligopeptide assemblies. In this study we aimed at improving the stability of such peptide vesicles by covalently crosslinking the oligopeptide vesicles using disulfide bonds. Two and three cysteines were introduced in the SA2 peptide sequence to allow crosslinking (Ac-Ala-Cys-Val-Cys-Leu-(Leu/Cys)-Leu-Trp-Glu-Glu-COOH). RESULTS: Upon disulfide formation the crosslinked vesicles remained stable under conditions that disrupted the non-crosslinked peptide vesicles. The stabilized vesicles were more closely examined in terms of particle size (distribution) using atomic force microscopy, cryogenic electron microscopy, as well as dynamic light scattering analysis, showing an average particle radius in number between 15 and 20 nm. Using entrapment of calcein it was shown that intermolecular crosslinking of peptides within the vesicles did not affect the permeability for calcein. CONCLUSION: Introduction of cysteines into the hydrophobic domain of the SA2 amphiphilic oligopeptides is a feasible strategy for crosslinking the peptide vesicles. Such small crosslinked oligopeptide vesicles may hold promise for drug delivery applications

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

When climate science became climate politics: British media representations of climate change in 1988

Climate change has become a pressing environmental concern for scientists, social commentators and politicians. Previous social science research has explored media representations of climate change in various temporal and geographical contexts. Through the lens of Social Representations Theory, this article provides a detailed qualitative thematic analysis of media representations of climate change in the 1988 British broadsheet press, given that this year constitutes an important juncture in this transition of climate change from the domain of science to that of the socio-political sphere. The following themes are outlined: (i) “Climate change: a multi-faceted threat”; (ii) “Collectivisation of threat”; (iii) “Climate change and the attribution of blame”; and (iv) “Speculative solutions to a complex socio-environmental problem.” The article provides detailed empirical insights into the “starting-point” for present-day disputes concerning climate change and lays the theoretical foundations for tracking the continuities and discontinuities characterising social representations of climate change in the future

Biocatalytic Synthesis of Polymers of Precisely Defined Structures

The fabrication of functional nanoscale devices requires the construction of complex architectures at length scales characteristic of atoms and molecules. Currently microlithography and micro-machining of macroscopic objects are the preferred methods for construction of small devices, but these methods are limited to the micron scale. An intriguing approach to nanoscale fabrication involves the association of individual molecular components into the desired architectures by supramolecular assembly. This process requires the precise specification of intermolecular interactions, which in turn requires precise control of molecular structure

Mitotic catenation is monitored and resolved by a PKCε-regulated pathway.

Exit from mitosis is controlled by silencing of the spindle assembly checkpoint (SAC). It is important that preceding exit, all sister chromatid pairs are correctly bioriented, and that residual catenation is resolved, permitting complete sister chromatid separation in the ensuing anaphase. Here we determine that the metaphase response to catenation in mammalian cells operates through PKCε. The PKCε-controlled pathway regulates exit from the SAC only when mitotic cells are challenged by retained catenation and this delayed exit is characterized by BubR1-high and Mad2-low kinetochores. In addition, we show that this pathway is necessary to facilitate resolution of retained catenanes in mitosis. When delayed by catenation in mitosis, inhibition of PKCε results in premature entry into anaphase with PICH-positive strands and chromosome bridging. These findings demonstrate the importance of PKCε-mediated regulation in protection from loss of chromosome integrity in cells failing to resolve catenation in G2

An Expanded Set of Amino Acid Analogs for the Ribosomal Translation of Unnatural Peptides

BACKGROUND: The application of in vitro translation to the synthesis of unnatural peptides may allow the production of extremely large libraries of highly modified peptides, which are a potential source of lead compounds in the search for new pharmaceutical agents. The specificity of the translation apparatus, however, limits the diversity of unnatural amino acids that can be incorporated into peptides by ribosomal translation. We have previously shown that over 90 unnatural amino acids can be enzymatically loaded onto tRNA. METHODOLOGY/PRINCIPAL FINDINGS: We have now used a competition assay to assess the efficiency of tRNA-aminoacylation of these analogs. We have also used a series of peptide translation assays to measure the efficiency with which these analogs are incorporated into peptides. The translation apparatus tolerates most side chain derivatives, a few alpha,alpha disubstituted, N-methyl and alpha-hydroxy derivatives, but no beta-amino acids. We show that over 50 unnatural amino acids can be incorporated into peptides by ribosomal translation. Using a set of analogs that are efficiently charged and translated we were able to prepare individual peptides containing up to 13 different unnatural amino acids. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that a diverse array of unnatural building blocks can be translationally incorporated into peptides. These building blocks provide new opportunities for in vitro selections with highly modified drug-like peptides