Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional?

Background: The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become recognized by their incorporation into the 2013 ACR/EULAR classification criteria. Clear prognostic and phenotypic associations with cutaneous subtype and internal organ involvement have been also described. However, little is known about the potential of autoantibodies to exert a direct pathogenic role in SSc. The aim of the study is to assess the pathogenic capacity of anti-DNA-topoisomerase I (anti-Topo-I) and anti-centromeric protein B (anti-Cenp-B) autoantibodies to induce pro-fibrotic markers in dermal fibroblasts. Methods: Dermal fibroblasts were isolated from unaffected and affected skin samples of (n = 10) limited cutaneous SSc (LcSSc) patients, from affected skin samples of diffuse cutaneous (DcSSc) patients (n = 10) and from healthy subjects (n = 20). Fibroblasts were stimulated with anti-Topo-I, anti-Cenp-B IgGs, and control IgGs in ratios 1:100 and 1:200 for 24 h. Cells were also incubated with 10% SSc anti-Topo-I+ and anti-Cenp-B+ whole serum and with 10% control serum for 24 h. Viability was assessed by MTT test, while apoptosis was assessed by flow cytometry. Activation of pro-fibrotic genes ACTA2, COL1A1, and TAGLN was evaluated by quantitative real-time PCR (qPCR), while the respective protein levels alpha-smooth-muscle actin (\u3b1-SMA), type-I-collagen (Col-I), and transgelin (SM22) were assessed by immunocytochemistry (ICC). Results: MTT showed that anti-Cenp-B/anti-Topo-I IgGs and anti-Cenp-B+/anti-Topo-I+ sera reduced viability (in a dilution-dependent manner for IgGs) for all the fibroblast populations. Apoptosis is induced in unaffected LcSSc and control fibroblasts, while affected LcSSc/DcSSc fibroblasts showed apoptosis resistance. Basal mRNA (ACTA2, COL1A1, and TAGLN) and protein (\u3b1-SMA, Col-1, and SM22) levels were higher in affected LcSSc/DcSSc fibroblasts compared to LcSSc unaffected and to control ones. Stimulation with anti-Cenp-B/anti-Topo-I IgGs and with anti-Cenp-B+/anti-Topo-I+ sera showed a better induction in unaffected LcSSc and control fibroblasts. However, a statistically significant increase of all pro-fibrotic markers is reported also in affected LcSSc/DcSSc fibroblasts upon stimulation with both IgGs and sera. Conclusions: This study suggests a pathogenic role of SSc-specific autoantibodies to directly induce pro-fibrotic activation in human dermal fibroblasts. Therefore, besides the diagnostic and prognostic use of those autoantibodies, these data might further justify the importance of immunosuppressive drugs in the early stages of the autoimmune disease, including SSc

Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex

The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body

Multimode quantum interference of photons in multiport integrated devices

We report the first demonstration of quantum interference in multimode interference (MMI) devices and a new complete characterization technique that can be applied to any photonic device that removes the need for phase stable measurements. MMI devices provide a compact and robust realization of NxM optical circuits, which will dramatically reduce the complexity and increase the functionality of future generations of quantum photonic circuits

Designing all-graphene nanojunctions by covalent functionalization

We investigated theoretically the effect of covalent edge functionalization, with organic functional groups, on the electronic properties of graphene nanostructures and nano-junctions. Our analysis shows that functionalization can be designed to tune electron affinities and ionization potentials of graphene flakes, and to control the energy alignment of frontier orbitals in nanometer-wide graphene junctions. The stability of the proposed mechanism is discussed with respect to the functional groups, their number as well as the width of graphene nanostructures. The results of our work indicate that different level alignments can be obtained and engineered in order to realize stable all-graphene nanodevices

Label swapper device for spectral amplitude coded optical packet networks monolithically integrated on InP

This paper was published in OPTICS EXPRESS and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://dx.doi.org/10.1364/OE.19.013540. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under lawIn this paper the design, fabrication and experimental characterization of an spectral amplitude coded (SAC) optical label swapper monolithically integrated on Indium Phosphide (InP) is presented. The device has a footprint of 4.8x1.5 mm 2 and is able to perform label swapping operations required in SAC at a speed of 155 Mbps. The device was manufactured in InP using a multiple purpose generic integration scheme. Compared to previous SAC label swapper demonstrations, using discrete component assembly, this label swapper chip operates two order of magnitudes faster. © 2011 Optical Society of America.The activities have been carried out in the framework of the Joint Research Activity (JRA) 'Active-phased Arrayed Devices' (WP 44) of the European Commission FP6 Network of Excellence ePIXnet (European Network of Excellence on Photonic Integrated Components and Circuits), Project Reference: 004525, http://www.epixnet.org/. This work has been partially funded through the Spanish Plan Nacional de I+D+i 2008-2011 project TEC2008-06145/TEC. It has also been partially supported by the Canadian Institute for Photonic Innovations. Devices are presently being fabricated through the InP Photonic Integration Platform JePPIX (coordinator D J Robbins), at the COBRA fab, http://www.jeppix.eu/Muñoz Muñoz, P.; Garcia-Olcina, R.; Habib, C.; Chen, LR.; Leijtens, XJM.; De Vries, T.; Robbins, D.... (2011). Label swapper device for spectral amplitude coded optical packet networks monolithically integrated on InP. Optics Express. 19(14):13540-13550. https://doi.org/10.1364/OE.19.013540S13540135501914Yoo, S. J. B. (2006). Optical Packet and Burst Switching Technologies for the Future Photonic Internet. Journal of Lightwave Technology, 24(12), 4468-4492. doi:10.1109/jlt.2006.886060Blumenthal, D. J., Olsson, B.-E., Rossi, G., Dimmick, T. E., Rau, L., Masanovic, M., … Barton, J. (2000). All-optical label swapping networks and technologies. Journal of Lightwave Technology, 18(12), 2058-2075. doi:10.1109/50.908817Srivatsa, A., d. Waardt, H., Hill, M. T., Khoe, G. D., & Dorren, H. J. S. (2001). All-optical serial header processing based on two-pulse correlation. Electronics Letters, 37(4), 234. doi:10.1049/el:20010178Gordon, R. E., & Chen, L. R. (2006). Demonstration of all-photonic spectral label-switching for optical MPLS networks. IEEE Photonics Technology Letters, 18(4), 586-588. doi:10.1109/lpt.2006.870188Habib, C., Baby, V., Chen, L. R., Delisle-Simard, A., & LaRochelle, S. (2008). All-Optical Swapping of Spectral Amplitude Code Labels Using Nonlinear Media and Semiconductor Fiber Ring Lasers. IEEE Journal of Selected Topics in Quantum Electronics, 14(3), 879-888. doi:10.1109/jstqe.2008.918047Cole, C., Huebner, B., & Johnson, J. (2009). Photonic integration for high-volume, low-cost applications. IEEE Communications Magazine, 47(3), S16-S22. doi:10.1109/mcom.2009.4804385Calabretta, N., Jung, H.-D., Llorente, J. H., Tangdiongga, E., Koonen, T. A. M. J., & Dorren, H. J. S. (2009). All-Optical Label Swapping of Scalable In-Band Address Labels and 160-Gb/s Data Packets. Journal of Lightwave Technology, 27(3), 214-223. doi:10.1109/jlt.2008.2009319Smit, M. K., & Van Dam, C. (1996). PHASAR-based WDM-devices: Principles, design and applications. IEEE Journal of Selected Topics in Quantum Electronics, 2(2), 236-250. doi:10.1109/2944.577370Eisenstein, G. (1989). Semiconductor optical amplifiers. IEEE Circuits and Devices Magazine, 5(4), 25-30. doi:10.1109/101.29899Munoz, P., Pastor, D., & Capmany, J. (2002). Modeling and design of arrayed waveguide gratings. Journal of Lightwave Technology, 20(4), 661-674. doi:10.1109/50.996587Soldano, L. B., & Pennings, E. C. M. (1995). Optical multi-mode interference devices based on self-imaging: principles and applications. Journal of Lightwave Technology, 13(4), 615-627. doi:10.1109/50.372474Zilkie, A. J., Meier, J., Mojahedi, M., Poole, P. J., Barrios, P., Poitras, D., … Aitchison, J. S. (2007). Carrier Dynamics of Quantum-Dot, Quantum-Dash, and Quantum-Well Semiconductor Optical Amplifiers Operating at 1.55 $\mu{\hbox {m}}$. IEEE Journal of Quantum Electronics, 43(11), 982-991. doi:10.1109/jqe.2007.90447

IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

Notulae to the Italian alien vascular flora: 4

In this contribution, new data concerning the Italian distribution of alien vascular flora are presented. It includes new records and exclusions for Italy or for Italian administrative regions of taxa in the genera Cedrus, Cenchrus, Citrus, Cyrtomium, Diospyros, Elaeagnus, Erigeron, Iris, Oenothera, Pavonia, Phytolacca, Styphnolobium, and Verbena. Furthermore, a new combination in the genus Amaranthus is proposed

Contribution to the floristic knowledge of the Maddalena Mountains (Basilicata and Campania, southern Italy)

The inventory of the taxa collected during the annual field trip of the working group for Floristics, Systematics and Evolution of the Italian Botanical Society is reported. It was held in 2013 along the Maddalena Mountains, a mountain ridge of the southern Apennines located between the Basilicata and Campania administrative regions (southern Italy), considered as being poorly characterized in terms of vascular flora. A total of 701 units belonging to 74 plant families were recorded including two varieties and four hybrids.Thirty-five taxa resulted endemic to Italy and only 11 alien species were detected, while 36 taxa are new or confirmed for the regional floras of Basilicata and/or Campania. In particular, 12 taxa are new for Basilicata, while four are confirmed. Regarding Campania, 14 taxa resulted new for the regional flora and five were confirmed

Orbital overlap effects in electron transfer reactions across a metal nanowire/electrolyte solution interface

In this paper, we report on calculations of the orbital overlap between Fe(III) and Cr(III) aquacomplexes and different electrode surfaces: Cu(111), Ag (111), Au(111), Pt(111), and corresponding monatomic wires. The electronic structure of the monocrystalline surfaces and nanowires are described in terms of the electronic spillover and density of electronic states at the Fermi level obtained from periodic density functional theory (DFT) calculations. The transmission coefficients (κ) characterizing the first stage of outer-sphere electron transfer for the reduction of aquacomplexes are calculated on the basis of Landau–Zener theory as a function of electrode–reactant separation; the electronic transmission coefficients for the [Cr(H2O)6]3+/2+ redox couple were found to be smaller than those for [Fe(H2O)6]3+/2+. Two different intervals can be clearly distinguished for Cu, Au and Pt: “a catalytic region”, where κ(wire) > κ(Me slab) and “an inhibition region”, where κ(wire) < κ(Me slab). A similar behavior exhibits the coupling constant estimated for a hydrogen atom adsorbed at the Au(111) surface and the Au monatomic wire. These effects originate from some specific features of electronic density profile for metal nanowires: at short distances the electronic density of nanowires is higher compared with the (111) metal surfaces, while at larger separations it decreases more sharply.Fil: Nazmutdinov, Renat R.. Kazan National Research Technological University; RusiaFil: Berezin, Alexander S.. Kazan National Research Technological University; RusiaFil: Soldano, Germán. Universitat Ulm; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schmickler, Wolfgang. Universitat Ulm; Alemani