The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse

BACKGROUND: The hematopoietic stem cells (HSCs) niche of the bone marrow is comprised of HSCs, osteoblasts, endothelial cells and a stromal component of non-hematopoietic multipotent cells of mesenchymal origin named "mesenchymal stem cells" (MSCs). RESULTS: Here we studied the global transcriptional profile of murine MSCs with immuno-therapeutic potential and compared it with that of 486 publicly available microarray datasets from 12 other mouse tissues or cell types. Principal component analysis and hierarchical clustering identified a unique pattern of gene expression capable of distinctively classifying MSCs from other tissues and cells. We then performed an analysis aimed to identify absolute and relative abundance of transcripts in all cell types. We found that the set of transcripts uniquely expressed by MSCs is enriched in transcription factors and components of the Wnt signaling pathway. The analysis of differentially expressed genes also identified a set of genes specifically involved in the HSC niche and is complemented by functional studies that confirm the findings. Interestingly, some of these genes play a role in the maintenance of HSCs in a quiescent state supporting their survival and preventing them from proliferating and differentiating. We also show that MSCs modulate T cell functions in vitro and, upon in vivo administration, ameliorate experimental autoimmune encephalomyelitis (EAE). CONCLUSION: Altogether, these findings provide novel and important insights on the mechanisms of T cell function regulation by MSCs and help to cement the rationale for their application in the treatment of autoimmune diseases

Direct correlation of crystal structure and optical properties in wurtzite/zinc-blende GaAs nanowire heterostructures

A novel method for the direct correlation at the nanoscale of structural and optical properties of single GaAs nanowires is reported. Nanowires consisting of 100% wurtzite and nanowires presenting zinc-blende/wurtzite polytypism are investigated by photoluminescence spectroscopy and transmission electron microscopy. The photoluminescence of wurtzite GaAs is consistent with a band gap of 1.5 eV. In the polytypic nanowires, it is shown that the regions that are predominantly composed of either zinc-blende or wurtzite phase show photoluminescence emission close to the bulk GaAs band gap, while regions composed of a nonperiodic superlattice of wurtzite and zinc-blende phases exhibit a redshift of the photoluminescence spectra as low as 1.455 eV. The dimensions of the quantum heterostructures are correlated with the light emission, allowing us to determine the band alignment between these two crystalline phases. Our first-principles electronic structure calculations within density functional theory, employing a hybrid-exchange functional, predict band offsets and effective masses in good agreement with experimental results

The visibility of IQHE at sharp edges: Experimental proposals based on interactions and edge electrostatics

The influence of the incompressible strips on the integer quantized Hall effect (IQHE) is investigated, considering a cleaved-edge overgrown (CEO) sample as an experimentally realizable sharp edge system. We propose a set of experiments to clarify the distinction between the large-sample limit when bulk disorder defines the IQHE plateau width and the small-sample limit smaller than the disorder correlation length, when self-consistent edge electrostatics define the IQHE plateau width. The large-sample or bulk QH regime is described by the usual localization picture, whereas the small-sample or edge regime is discussed within the compressible/incompressible strips picture, known as the screening theory of QH edges. Utilizing the unusually sharp edge profiles of the CEO samples, a Hall bar design is proposed to manipulate the edge potential profile from smooth to extremely sharp. By making use of a side-gate perpendicular to the two dimensional electron system, it is shown that the plateau widths can be changed or even eliminated altogether. Hence, the visibility of IQHE is strongly influenced when adjusting the edge potential profile and/or changing the dc current direction under high currents in the non-linear transport regime. As a second investigation, we consider two different types of ohmic contacts, namely highly transmitting (ideal) and highly reflecting (non-ideal) contacts. We show that if the injection contacts are non-ideal, however still ohmic, it is possible to measure directly the non-quantized transport taking place at the bulk of the CEO samples. The results of the experiments we propose will clarify the influence of the edge potential profile and the quality of the contacts, under quantized Hall conditions.Comment: Substantially revised version of manuscript arXiv:0906.3796v1, including new figures et

Radioligand therapy (RLT) as neoadjuvant treatment for inoperable pancreatic neuroendocrine tumors: a literature review

In the last 10 years, several literature reports supported radioligand therapy (RLT) in neoadjuvant settings for pancreatic neuroendocrine tumors (PanNETs). Indeed, primary tumor shrinkage has been frequently reported following RLT in unresectable or borderline resectable PanNETs. Moreover, RLT-induced intratumoral modifications facilitate surgery, both on primary tumor and metastasis, having a great impact on progression free survival (PFS), overall survival (OS) and quality of life (QoL). However, prospective controlled investigations are necessary to confirm preliminary data and to define the best RLT scheme and the ideal patient that, in a multidisciplinary approach, should be referred to neoadjuvant RLT

Charge carrier generation, relaxation, and recombination in polytypic GaAs nanowires studied by photoluminescence excitation spectroscopy

We report results of a study of polytypic GaAs nanowires using low-temperature photoluminescence excitation spectroscopy. The nanowire ensemble shows a strong absorption at 1.517 eV, as a result of resonant generation of heavy-hole excitons in the zinc-blende segments of the nanowires. Excitons then diffuse along the length of the nanowire and are trapped by the type-II quantum discs arising from the zinc-blende/ wurtzite crystal structure alternation and recombine radiatively. Finally, experiments on single nanowires demonstrate that the energy of the Gamma(7) conduction band to Gamma(9) valence band exciton of wurtzite GaAs is 1.521 eV at 4K. (C) 2013 AIP Publishing LLC

Effect of the GaAsP shell on optical properties of self-catalyzed GaAs nanowires grown on silicon

We realize growth of self-catalyzed core-shell GaAs/GaAsP nanowires (NWs) on Si substrates using molecular-beam epitaxy. Transmission electron microscopy (TEM) of single GaAs/GaAsP NWs confirms their high crystal quality and shows domination of the zinc-blende phase. This is further confirmed in optics of single NWs, studied using cw and time-resolved photoluminescence (PL). A detailed comparison with uncapped GaAs NWs emphasizes the effect of the GaAsP capping in suppressing the non-radiative surface states: significant PL enhancement in the core-shell structures exceeding 2000 times at 10K is observed; in uncapped NWs PL is quenched at 60K whereas single core-shell GaAs/GaAsP NWs exhibit bright emission even at room temperature. From analysis of the PL temperature dependence in both types of NW we are able to determine the main carrier escape mechanisms leading to the PL quench

Creative and Stylistic Devices Employed by Children During a Storybook Narrative Task: A Cross-Cultural Study

Purpose: The purpose of this study was to analyze the effects of culture on the creative and stylistic features children employ when producing narratives based on wordless picture books. Method: Participants included 60 first- and second-grade African American, Latino American, and Caucasian children. A subset of narratives based on wordless picture books collected as part of a larger study was coded and analyzed for the following creative and stylistic conventions: organizational style (topic centered, linear, cyclical), dialogue (direct, indirect), reference to character relationships (nature, naming, conduct), embellishment (fantasy, suspense, conflict), and paralinguistic devices (expressive sounds, exclamatory utterances). Results: Many similarities and differences between ethnic groups were found. No significant differences were found between ethnic groups in organizational style or use of paralinguistic devices. African American children included more fantasy in their stories, Latino children named their characters more often, and Caucasian children made more references to the nature of character relationships. Conclusion: Even within the context of a highly structured narrative task based on wordless picture books, culture influences children’s production of narratives. Enhanced understanding of narrative structure, creativity, and style is necessary to provide ecologically valid narrative assessment and intervention for children from diverse cultural backgrounds

Raman spectroscopy of wurtzite and zinc-blende GaAs nanowires: polarization dependence, selection rules and strain effects

Polarization dependent Raman scattering experiments realized on single GaAs nanowires with different percentages of zinc-blende and wurtzite structure are presented. The selection rules for the special case of nanowires are found and discussed. In the case of zinc-blende, the transversal optical mode E1(TO) at 267 cm-1 exhibits the highest intensity when the incident and analyzed polarization are parallel to the nanowire axis. This is a consequence of the nanowire geometry and dielectric mismatch with the environment, and in quite good agreement with the Raman selection rules. We also find a consistent splitting of 1 cm-1 of the E1(TO). The transversal optical mode related to the wurtzite structure, E2H, is measured between 254 and 256 cm-1, depending on the wurtzite content. The azymutal dependence of E2H indicates that the mode is excited with the highest efficiency when the incident and analyzed polarization are perpendicular to the nanowire axis, in agreement with the selection rules. The presence of strain between wurtzite and zinc-blende is analyzed by the relative shift of the E1(TO) and E2H modes. Finally, the influence of the surface roughness in the intensity of the longitudinal optical mode on {110} facets is presented.Comment: 28 pages, 12 figures. to be published in Phys. Rev.

Detrimental and protective action of microglial extracellular vesicles on myelin lesions: astrocyte involvement in remyelination failure

Microglia are highly plastic immune cells which exist in a continuum of activation states. By shaping the function of oligodendrocyte precursor cells (OPCs), the brain cells which differentiate to myelin-forming cells, microglia participate in both myelin injury and remyelination during multiple sclerosis. However, the mode(s) of action of microglia in supporting or inhibiting myelin repair is still largely unclear. Here, we analysed the effects of extracellular vesicles (EVs) produced in vitro by either pro-inflammatory or pro-regenerative microglia on OPCs at demyelinated lesions caused by lysolecithin injection in the mouse corpus callosum. Immunolabelling for myelin proteins and electron microscopy showed that EVs released by pro-inflammatory microglia blocked remyelination, whereas EVs produced by microglia co-cultured with immunosuppressive mesenchymal stem cells promoted OPC recruitment and myelin repair. The molecular mechanisms responsible for the harmful and beneficial EV actions were dissected in primary OPC cultures. By exposing OPCs, cultured either alone or with astrocytes, to inflammatory EVs, we observed a blockade of OPC maturation only in the presence of astrocytes, implicating these cells in remyelination failure. Biochemical fractionation revealed that astrocytes may be converted into harmful cells by the inflammatory EV cargo, as indicated by immunohistochemical and qPCR analyses, whereas surface lipid components of EVs promote OPC migration and/or differentiation, linking EV lipids to myelin repair. Although the mechanisms through which the lipid species enhance OPC maturation still remain to be fully defined, we provide the first demonstration that vesicular sphingosine 1 phosphate stimulates OPC migration, the first fundamental step in myelin repair. From this study, microglial EVs emerge as multimodal and multitarget signalling mediators able to influence both OPCs and astrocytes around myelin lesions, which may be exploited to develop novel approaches for myelin repair not only in multiple sclerosis, but also in neurological and neuropsychiatric diseases characterized by demyelination