Subcapsular Sinus Macrophage Fragmentation and CD169+ Bleb Acquisition by Closely Associated IL-17-Committed Innate-Like Lymphocytes

Subcapsular sinus macrophages (SSMs) in lymph nodes are rapidly exposed to antigens arriving in afferent lymph and have a role in their capture and display to B cells. In tissue sections SSMs exhibit long cellular processes and express high amounts of CD169. Here, we show that many of the cells present in lymph node cell suspensions that stain for CD169 are not macrophages but lymphocytes that have acquired SSM-derived membrane blebs. The CD169 bleb+ lymphocytes are enriched for IL-17 committed IL-7RαhiCCR6+ T cells and NK cells. In addition, the CD169 staining detected on small numbers of CD11chi dendritic cells is frequently associated with membrane blebs. Counter intuitively the CD169 bleb+ lymphocytes are mostly CD4 and CD8 negative whereas many SSMs express CD4. In situ, many IL-7Rαhi cells are present at the subcapsular sinus and interfollicular regions and migrate in close association with CD169+ macrophages. These findings suggest SSMs undergo fragmentation during tissue preparation and release blebs that are acquired by closely associated cells. They also suggest an intimate crosstalk between SSMs and IL-17 committed innate-like lymphocytes that may help provide early protection of the lymph node against lymph-borne invaders

Virally and physically transgenized equine adipose-derived stromal cells as a cargo for paracrine secreted factors

<p>Abstract</p> <p>Background</p> <p>Adipose-Derived Stromal Cells have been shown to have multiple lineage differentiation properties and to be suitable for tissues regeneration in many degenerative processes. Their use has been proposed for the therapy of joint diseases and tendon injuries in the horse. In the present report the genetic manipulation of Equine Adipose-Derived Stromal Cells has been investigated.</p> <p>Results</p> <p>Equine Adipose-Derived Stromal Cells were successfully virally transduced as well as transiently and stably transfected with appropriate parameters, without detrimental effect on their differentiation properties. Moreover, green fluorescent protein alone, fused to <it>neo </it>gene, or co-expressed as bi-cistronic reporter constructs, driven by viral and house-keeping gene promoters, were tested. The better expressed cassette was employed to stably transfect Adipose-Derived Stromal Cells for cell therapy purposes. Stably transfected Equine Adipose-Derived Stromal Cells with a heterologous secreted viral antigen were able to immunize horses upon injection into the lateral wall of the neck.</p> <p>Conclusion</p> <p>This study provides the methods to successfully transgenize Adipose-Derived Stromal Cells both by lentiviral vector and by transfection using optimized constructs with suitable promoters and reporter genes. In conclusion these findings provide a working platform for the delivery of potentially therapeutic proteins to the site of cells injection via transgenized Equine Adipose-Derived Stromal Cells.</p

Sulfuric acid treated G-CN as a precursor to generate high-efficient G-CN for hydrogen evolution from water under visible light irradiation

Modifying the physical, chemical structures of graphitic carbon nitride (g-CN) to improve its optoelectronic properties is the most efficient way to meet a high photoactivity for clean and sustainable energy production. Herein, a higher monomeric precursor for synthesizing improved micro-and electronic structure possessing g-CN was prepared by high-concentrated sulfuric acid (SA) treatment of bulk type g-CN (BCN). Several structural analyses show that after the SA treatment of BCN, the polymeric melon-based structure is torn down to cyameluric or cyanuric acid-based material. After re-polycondensation of this material as a precursor, the resulting g-CN has more condensed microstructure, carbon and oxygen contents than BCN, indicating that C, O co-doping by corrosive acid of SA. This g-CN shows a much better visible light absorption and diminished radiative charge recombination by the charge localization effect induced by heteroatoms. As a result, this condensed C, O co-doped g-CN shows the enhanced photocatalytic hydrogen evolution rate of 4.57 µmol/h from water under the visible light (>420 nm) by almost two times higher than that of BCN (2.37 µmol/h). This study highlights the enhanced photocatalytic water splitting performance as well as the provision of the higher monomeric precursor for improved g-CN

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Compactness Determines the Success of Cube and Octahedron Self-Assembly

Nature utilizes self-assembly to fabricate structures on length scales ranging from the atomic to the macro scale. Self-assembly has emerged as a paradigm in engineering that enables the highly parallel fabrication of complex, and often three-dimensional, structures from basic building blocks. Although there have been several demonstrations of this self-assembly fabrication process, rules that govern a priori design, yield and defect tolerance remain unknown. In this paper, we have designed the first model experimental system for systematically analyzing the influence of geometry on the self-assembly of 200 and 500 µm cubes and octahedra from tethered, multi-component, two-dimensional (2D) nets. We examined the self-assembly of all eleven 2D nets that can fold into cubes and octahedra, and we observed striking correlations between the compactness of the nets and the success of the assembly. Two measures of compactness were used for the nets: the number of vertex or topological connections and the radius of gyration. The success of the self-assembly process was determined by measuring the yield and classifying the defects. Our observation of increased self-assembly success with decreased radius of gyration and increased topological connectivity resembles theoretical models that describe the role of compactness in protein folding. Because of the differences in size and scale between our system and the protein folding system, we postulate that this hypothesis may be more universal to self-assembling systems in general. Apart from being intellectually intriguing, the findings could enable the assembly of more complicated polyhedral structures (e.g. dodecahedra) by allowing a priori selection of a net that might self-assemble with high yields

Neuraminidase-deficient Sendai virus HN mutants provide protection from homologous superinfection

Binding of hemagglutinin-neuraminidase proteins (HN) to sialylated receptors initiates the infection process of several paramyxoviruses, whereas later in the viral life cycle, the neuramindase (NA) activity of newly synthesized HN destroys all receptors. Prior to NA action, expressed HN has to bind the receptor. To evaluate this HN–receptor complex with respect to receptor inactivation, three temperature-sensitive Sendai virus HN mutants carrying amino acid exchanges at positions 262, 264 and/or 461 were created that uncoupled NA activity from receptor binding at 39°C. Interestingly, at elevated temperature, when there is no detectable neuramindase activity, all infected cells are protected against homologous superinfection. Mutated HN protein on the cell surface is mainly bound to sialylated cell-surface components but can be released by treatment with NA. Thus, continuous binding to HN already inactivates the receptors quantitatively. Furthermore, mutant HN bound to receptors is prevented from being incorporated into virus particles in the absence of NA. It is shown here for the first time that during paramyxoviral infection, quantitative receptor inactivation already occurs due to binding of receptors to expressed HN protein without involvement of NA and is independent of NA activity of viral progeny. NA subsequently functions in the release of HN from the complex, coupled with desialysation of receptors. These findings could have implications for further antiviral drug development

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure