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

Surface Modification of Melt Extruded Poly(ε-caprolactone) Nanofibers: Toward a New Scalable Biomaterial Scaffold.

A photochemical modification of melt-extruded polymeric nanofibers is described. A bioorthogonal functional group is used to decorate fibers made exclusively from commodity polymers, covalently attach fluorophores and peptides, and direct cell growth. Our process begins by using a layered coextrusion method, where poly(ε-caprolactone) (PCL) nanofibers are incorporated within a macroscopic poly(ethylene oxide) (PEO) tape through a series of die multipliers within the extrusion line. The PEO layer is then removed with a water wash to yield rectangular PCL nanofibers with controlled cross-sectional dimensions. The fibers can be subsequently modified using photochemistry to yield a "clickable" handle for performing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction on their surface. We have attached fluorophores, which exhibit dense surface coverage when using ligand-accelerated CuAAC reaction conditions. In addition, an RGD peptide motif was coupled to the surface of the fibers. Subsequent cell-based studies have shown that the RGD peptide is biologically accessible at the surface, leading to increased cellular adhesion and spreading versus PCL control surfaces. This functionalized coextruded fiber has the advantages of modularity and scalability, opening a potentially new avenue for biomaterials fabrication

Learning the Fundamentals from Hands-on Learning

The projects featured in this piece represent the notion of design as an act of thinking-through-making. Through studies in design principles, craftsmanship, exercises, and projects, students engaged in hands-on learning, which included drawings, model-making, and producing artifacts. Fundamentals of Design Thinking: Architecture Majors Learning Community, Prof. Bronne Dytoc, Prof. Mine H. Hashas-Degertekin, Prof. Zamila Karimi, Prof. Marietta Monaghan, Prof. Willie Pittman, and Prof. Arief Setiawa

A modeling investigation of canopy-air oxygen isotopic exchange of water vapor and carbon dioxide in a soybean field

The oxygen isotopes of CO2 and H2O ( 18O-CO2 and 18O-H2O) provide unique information regarding the contribution of terrestrial vegetation to the global CO2 and H2O cycles. In this paper, a simple isotopic land surface model was used to investigate processes controlling the isotopic exchange of 18O-H2O and 18O-CO2 between a soybean ecosystem and the atmosphere. We included in a standard land surface model a nonsteady state theory of leaf water isotopic composition, a canopy kinetic fractionation factor, and a big-leaf parameterization of the 18O-CO2 isoforcing on the atmosphere. Our model simulations showed that the Pclet effect was less important than the nonsteady state effect on the temporal dynamics of the water isotopic exchange. The model reproduced the highly significant and negative correlation between relative humidity and the ecosystem-scale 18O-CO2 isoforcing measured with eddy covariance. But the model-predicted isoforcing was biased high in comparison to the observations. Model sensitivity analysis suggested that the CO2 hydration efficiency must have been much lower in the leaves of soybean in field conditions than previously reported. Understanding environmental controls on the hydration efficiency and the scaling from the leaf to the canopy represents an area in need of more research. Copyright 2010 by the American Geophysical Union

Dendritic planarity of Purkinje cells is independent of Reelin signaling

The dendritic planarity of Purkinje cells is critical for cerebellar circuit formation. In the absence of Crk and CrkL, the Reelin pathway does not function resulting in partial Purkinje cell migration and defective dendritogenesis. However, the relationships among Purkinje cell migration, dendritic development and Reelin signaling have not been clearly delineated. Here, we use synchrotron X-ray microscopy to obtain 3-D images of Golgi-stained Purkinje cell dendrites. Purkinje cells that failed to migrate completely exhibited conical dendrites with abnormal 3-D arborization and reduced dendritic complexity. Furthermore, their spines were fewer in number with a distorted morphology. In contrast, Purkinje cells that migrated successfully displayed planar dendritic and spine morphologies similar to normal cells, despite reduced dendritic complexity. These results indicate that, during cerebellar formation, Purkinje cells migrate into an environment that supports development of dendritic planarity and spine formation. While Reelin signaling is important for the migration process, it does not make a direct major contribution to dendrite formation.1111Ysciescopu

Constraining compressed supersymmetry using leptonic signatures

We study the impact of the multi-lepton searches at the LHC on supersymmetric models with compressed mass spectra. For such models the acceptances of the usual search strategies are significantly reduced due to requirement of large effective mass and missing E_T. On the other hand, lepton searches do have much lower thresholds for missing E_T and p_T of the final state objects. Therefore, if a model with a compressed mass spectrum allows for multi-lepton final states, one could derive constraints using multi-lepton searches. For a class of simplified models we study the exclusion limits using ATLAS multi-lepton search analyses for the final states containing 2-4 electrons or muons with a total integrated luminosity of 1-2/fb at \sqrt{s}=7 TeV. We also modify those analyses by imposing additional cuts, so that their sensitivity to compressed supersymmetric models increase. Using the original and modified analyses, we show that the exclusion limits can be competitive with jet plus missing E_T searches, providing exclusion limits up to gluino masses of 1 TeV. We also analyse the efficiencies for several classes of events coming from different intermediate state particles. This allows us to assess exclusion limits in similar class of models with different cross sections and branching ratios without requiring a Monte Carlo simulation.Comment: 18 pages, 5 figure

Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment

Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs. © 2011 Yang et al