Sensory-organ-like response determines the magnetism of zigzag-edged honeycomb nanoribbons

We present an analytical effective theory for the magnetic phase diagram for zigzag-edge terminated honeycomb nanoribbons described by a Hubbard model with an interaction parameter U. We show that the edge magnetic moment varies as ln U and uncover its dependence on the width W of the ribbon. The physics of this owes its origin to the sensory-organ-like response of the nanoribbons, demonstrating that considerations beyond the usual Stoner-Landau theory are necessary to understand the magnetism of these systems. A first-order magnetic transition from an antiparallel orientation of the moments on opposite edges to a parallel orientation occurs upon doping with holes or electrons. The critical doping for this transition is shown to depend inversely on the width of the ribbon. Using variational Monte Carlo calculations, we show that magnetism is robust to fluctuations. Additionally, we show that the magnetic phase diagram is generic to zigzag-edge terminated nanostructures such as nanodots. Furthermore, we perform first-principles modeling to show how such magnetic transitions can be realized in substituted graphene nanoribbons. DOI: 10.1103/PhysRevB.87.085412

Monoclonal Antibodies against Hepatitis C Genotype 3a Virus Like Particle Inhibit Virus Entry in Cell Culture System

The envelope protein (E1-E2) of Hepatitis C virus (HCV) is a major component of the viral structure. The glycosylated envelope protein is considered to be important for initiation of infection by binding to cellular receptor(s) and also known as one of the major antigenic targets to host immune response. The present study was aimed at identifying mouse monoclonal antibodies which inhibit binding of virus like particles of HCV to target cells. The first step in this direction was to generate recombinant HCV-like particles (HCV-LPs) specific for genotypes 3a of HCV (prevalent in India) using the genes encoding core, E1 and E2 envelop proteins in a baculovirus expression system. The purified HCV-LPs were characterized by ELISA and electron microscopy and were used to generate monoclonal antibodies (mAbs) in mice. Two monoclonal antibodies (E8G9 and H1H10) specific for the E2 region of envelope protein of HCV genotype 3a, were found to reduce the virus binding to Huh7 cells. However, the mAbs generated against HCV genotype 1b (D2H3, G2C7, E1B11) were not so effective. More importantly, mAb E8G9 showed significant inhibition of the virus entry in HCV JFH1 cell culture system. Finally, the epitopic regions on E2 protein which bind to the mAbs have also been identified. Results suggest a new therapeutic strategy and provide the proof of concept that mAb against HCV-LP could be effective in preventing virus entry into liver cells to block HCV replication.

Damage identification of beam-like structures with contiguous and distributed damage

Structural health monitoring of existing infrastructure is currently an active field of research, where elaborate experimental programs and advanced analytical methods are used in identifying the current state of health of critical structures. Change of static deflection as the indicator of damage is the simplest tool in a structural health monitoring scenario of bridges that is least exploited in damage identification strategies. In this paper, some simple and elegant equations based on loss of symmetry due to damage are derived and presented for identification of damage in a bridge girder modeled as a simply supported beam using changes in static deflections and dynamic parameters. A single contiguous and distributed damage, typical of reinforced or prestressed concrete structures, is assumed for the structure. The methodology is extended for a base-line-free as well as base-line-inclusive measurement. Measurement strategy involves application of loads only at two symmetric points one at a time and deflection measurements at those symmetric points as well as at the midspan of the beam. A laboratory-based experiment is used to validate the approach. Copyright (c) 2012 John Wiley & Sons, Ltd.

Sonic hedgehog-Dependent Induction of MicroRNA 31 and MicroRNA 150 Regulates Mycobacterium bovis BCG-Driven Toll-Like Receptor 2 Signaling

Hedgehog (HH) signaling is a significant regulator of cell fate decisions during embryogenesis, development, and perpetuation of various disease conditions. Testing whether pathogen-specific HH signaling promotes unique innate recognition of intracellular bacteria, we demonstrate that among diverse Gram-positive or Gram-negative microbes, Mycobacterium bovis BCG, a vaccine strain, elicits a robust activation of Sonic HH (SHH) signaling in macrophages. Interestingly, sustained tumor necrosis factor alpha (TNF-alpha) secretion by macrophages was essential for robust SHH activation, as TNF-alpha(-/-) macrophages exhibited compromised ability to activate SHH signaling. Neutralization of TNF-alpha or blockade of TNF-alpha receptor signaling significantly reduced the infection-induced SHH signaling activation both in vitro and in vivo. Intriguingly, activated SHH signaling downregulated M. bovis BCG-mediated Toll-like receptor 2 (TLR2) signaling events to regulate a battery of genes associated with divergent functions of M1/M2 macrophages. Genome-wide expression profiling as well as conventional gain-of-function or loss-of-function analysis showed that SHH signaling-responsive microRNA 31 (miR-31) and miR-150 target MyD88, an adaptor protein of TLR2 signaling, thus leading to suppression of TLR2 responses. SHH signaling signatures could be detected in vivo in tuberculosis patients and M. bovis BCG-challenged mice. Collectively, these investigations identify SHH signaling to be what we believe is one of the significant regulators of host-pathogen interactions.

Tailoring the optical properties of amorphous heavily Er3+-doped Ge-Ga-S thin films

This study deals with the influence of Er-doping level and thermal annealing on the optical properties of amorphous Ge-Ga-S thin films. Nominal compositions of (GeS2)(75)(Ga2S3)(25) doped with high concentrations of 2.1 and 2.4 mol% Er2S3 (corresponding to 1.2 and 1.4 at% Er, respectively) have been chosen for this work. The results have been related to those obtained for the un-doped samples. The values of the refractive index, the absorption coefficient and optical band gap have been determined from the transmittance data. It has been found that the optical band gap of un-doped and 2.1 mol% Er2S3-doped films slightly increases with annealing temperature, whereas at 2.4 mol% Er2S3-doping level it is decreased. The dependences of the optical parameters on the erbium concentration and effect of annealing in the temperature range of 100-200 degrees C have been evaluated and discussed in relation to possible structural changes.

Regulation of protumorigenic pathways by Insulin like growth factor binding protein2 and its association along with beta-catenin in breast cancer lymph node metastasis

Background: Insulin like growth factor binding proteins modulate the mitogenic and pro survival effects of IGF. Elevated expression of IGFBP2 is associated with progression of tumors that include prostate, ovarian, glioma among others. Though implicated in the progression of breast cancer, the molecular mechanisms involved in IGFBP2 actions are not well defined. This study investigates the molecular targets and biological pathways targeted by IGFBP2 in breast cancer. Methods: Transcriptome analysis of breast tumor cells (BT474) with stable knockdown of IGFBP2 and breast tumors having differential expression of IGFBP2 by immunohistochemistry was performed using microarray. Differential gene expression was established using R-Bioconductor package. For validation, gene expression was determined by qPCR. Inhibitors of IGF1R and integrin pathway were utilized to study the mechanism of regulation of beta-catenin. Immunohistochemical and immunocytochemical staining was performed on breast tumors and experimental cells, respectively for beta-catenin and IGFBP2 expression. Results: Knockdown of IGFBP2 resulted in differential expression of 2067 up regulated and 2002 down regulated genes in breast cancer cells. Down regulated genes principally belong to cell cycle, DNA replication, repair, p53 signaling, oxidative phosphorylation, Wnt signaling. Whole genome expression analysis of breast tumors with or without IGFBP2 expression indicated changes in genes belonging to Focal adhesion, Map kinase and Wnt signaling pathways. Interestingly, IGFBP2 knockdown clones showed reduced expression of beta-catenin compared to control cells which was restored upon IGFBP2 re-expression. The regulation of beta-catenin by IGFBP2 was found to be IGF1R and integrin pathway dependent. Furthermore, IGFBP2 and beta-catenin are co-ordinately overexpressed in breast tumors and correlate with lymph node metastasis. Conclusion: This study highlights regulation of beta-catenin by IGFBP2 in breast cancer cells and most importantly, combined expression of IGFBP2 and beta-catenin is associated with lymph node metastasis of breast tumors.

Pulsed electric field mediated in vitro cellular response of fibroblast and osteoblast-like cells on conducting austenitic stainless steel substrate

This article reports the intermittent pulse electric field stimulus mediated in vitro cellular response of L929 mouse fibroblast/SaOS2 osteoblast-like cells on austenitic steel substrates in reference to the field strength dependent behavior. The cellular density and morphometric analyses revealed that the optimal electric (E) fields for the maximum cell density of adhered L929 (similar to 270 % to that of untreated sample) and SaOS2 (similar to 280 % to that of untreated sample) cells are 1 V (0.33 V/cm) and 2 V (0.67 V/cm), respectively. The trend in aspect ratio of elongated SaOS2 cells did not indicate any significant difference among the untreated and treated (up to 3.33 V/cm) cells. The average cell and nucleus areas (for SaOS2 cells) were increased with an increase in the applied voltage up to 8 V (2.67 V/cm) and reduced thereafter. However, the ratio of nucleus to total cell area was increased significantly on the application of higher voltages (2-10 V), indicating the possible influence of E-field on cell growth. Further, the cell density results were compared with earlier results obtained with sintered Hydroxyapatite (HA) and HA-BaTiO3 composites and such comparison revealed that the enhanced cell density on steel sample occurs upon application of much lower field strength and stimulation time. This indicates the possible role of substrate conductivity towards cell growth in pulsed E-field mediated culture conditions.

C-13-H-1 dipolar couplings for probing rod-like hydrogen bonded mesogens

Hydrogen bonding is the most important non-covalent interaction utilised in building supramolecular assemblies and is preferred often as a means of construction of molecular, oligomeric as well as polymeric materials that show liquid crystalline properties. In this work, a pyridine based nematogenic acceptor has been synthesized and mixed with non-mesogenic 4-methoxy benzoic acid to get a hydrogen bonded mesogen. The existence of hydrogen bonding between the pyridyl unit and the carboxylic acid was established using FT-IR spectroscopy from the observation of characteristic stretching vibrations of unionized type at 2425 and 1927 cm(-1). The mesogenic acceptor and the complex have been investigated using C-13 NMR in solution, solid and liquid crystalline states. Together with the 2D separated local field NMR experiments, the studies confirm the molecular structure in the mesophase and yield the local orientational order parameters. It is observed that the insertion of 4-methoxy benzoic acid not only enhances the mesophase stability but also induces a smectic phase due to an increase in the core length of the hydrogen bonded mesogen.

Drosophila Erect wing (Ewg) controls mitochondrial fusion during muscle growth and maintenance by regulation of the Opa1-like gene

Mitochondrial biogenesis and morphological changes are associated with tissue-specific functional demand, but the factors and pathways that regulate these processes have not been completely identified. A lack of mitochondrial fusion has been implicated in various developmental and pathological defects. The spatiotemporal regulation of mitochondrial fusion in a tissue such as muscle is not well understood. Here, we show in Drosophila indirect flight muscles (IFMs) that the nuclear-encoded mitochondrial inner membrane fusion gene, Opa1-like, is regulated in a spatiotemporal fashion by the transcription factor/co-activator Erect wing (Ewg). In IFMs null for Ewg, mitochondria undergo mitophagy and/or autophagy accompanied by reduced mitochondrial functioning and muscle degeneration. By following the dynamics of mitochondrial growth and shape in IFMs, we found that mitochondria grow extensively and fuse during late pupal development to form the large tubular mitochondria. Our evidence shows that Ewg expression during early IFM development is sufficient to upregulate Opa1-like, which itself is a requisite for both late pupal mitochondrial fusion and muscle maintenance. Concomitantly, by knocking down Opa1-like during early muscle development, we show that it is important for mitochondrial fusion, muscle differentiation and muscle organization. However, knocking down Opa1-like, after the expression window of Ewg did not cause mitochondrial or muscle defects. This study identifies a mechanism by which mitochondrial fusion is regulated spatiotemporally by Ewg through Opa1-like during IFM differentiation and growth.

Long ranged structural modulation in the pre-morphotropic phase boundary cubic-like state of the lead-free piezoelectric Na1/2Bi1/2TiO3-BaTiO3

The nature of the pre-morphotropic phase boundary (MPB) cubic-like state in the lead-free piezoelectric ceramics (1-x)Na1/2Bi1/2TiO3-(x)BaTiO3 at x similar to 0.06 has been examined in detail by electric field and temperature dependent neutron diffraction, x-ray diffraction, dielectric and ferroelectric characterization. The superlattice reflections in the neutron diffraction patterns cannot be explained with the tetragonal P4bm and the rhombohedral (R3c) phase coexistence model. The cubic like state is rather a result of long ranged modulated complex octahedral tilt. This modulated structure exhibits anomalously large dielectric dispersion. The modulated structure transforms to a MPB state on poling. The field-stabilized MPB state is destroyed and the modulated structure is restored on heating the poled specimen above the Vogel-Fulcher freezing temperature. The results show the predominant role of competing octahedral tilts in determining the nature of structural and polar states in Na1/2Bi1/2TiO3-based ferroelectrics. (C) 2013 AIP Publishing LLC.

Insulin like growth factor binding protein 4 promotes GBM progression and regulates key factors involved in EMT and invasion

Insulin like growth factor binding protein 4 (IGFBP4) regulates growth and development of tissues and organs by negatively regulating IGF signaling. Among most cancers, IGFBP4 has growth inhibitory role and reported as a down-regulated gene, except for renal cell carcinoma, wherein IGFBP4 promotes tumor progression. IGFBP4 expression has been shown to be higher in increasing grades of astrocytoma. However, the functional role of IGFBP4 in gliomas has not been explored. Surgical biopsies of 20 normal brain and 198 astrocytoma samples were analyzed for IGFBP4 expression by qRT-PCR. Highest expression of IGFBP4 mRNA was seen in GBM tumors compared to control brain tissues (median log2 of 2.035, p < 0.0001). Immunohistochemical analysis of 53 tissue samples revealed predominant nuclear staining of IGFBP4, seen maximally in GBMs when compared to DA and AA tumors (median LI = 29.12 +/- A 16.943, p < 0.001). Over expression of IGFBP4 in U343 glioma cells resulted in up-regulation of molecules involved in tumor growth, EMT and invasion such as pAkt, pErk, Vimentin, and N-cadherin and down-regulation of E-cadherin. Functionally, IGFBP4 over expression in these cells resulted in increased proliferation, migration and invasion as assessed by MTT, transwell migration, and Matrigel invasion assays. These findings were confirmed upon IGFBP4 knockdown in U251 glioma cells. Our data suggest a pro-tumorigenic role for IGFBP4 in glioma.

Filling-in Void and Sparse Regions in Protein Sequence Space by Protein-Like Artificial Sequences Enables Remarkable Enhancement in Remote Homology Detection Capability

Protein functional annotation relies on the identification of accurate relationships, sequence divergence being a key factor. This is especially evident when distant protein relationships are demonstrated only with three-dimensional structures. To address this challenge, we describe a computational approach to purposefully bridge gaps between related protein families through directed design of protein-like ``linker'' sequences. For this, we represented SCOP domain families, integrated with sequence homologues, as multiple profiles and performed HMM-HMM alignments between related domain families. Where convincing alignments were achieved, we applied a roulette wheel-based method to design 3,611,010 protein-like sequences corresponding to 374 SCOP folds. To analyze their ability to link proteins in homology searches, we used 3024 queries to search two databases, one containing only natural sequences and another one additionally containing designed sequences. Our results showed that augmented database searches showed up to 30% improvement in fold coverage for over 74% of the folds, with 52 folds achieving all theoretically possible connections. Although sequences could not be designed between some families, the availability of designed sequences between other families within the fold established the sequence continuum to demonstrate 373 difficult relationships. Ultimately, as a practical and realistic extension, we demonstrate that such protein-like sequences can be ``plugged-into'' routine and generic sequence database searches to empower not only remote homology detection but also fold recognition. Our richly statistically supported findings show that complementary searches in both databases will increase the effectiveness of sequence-based searches in recognizing all homologues sharing a common fold. (C) 2013 Elsevier Ltd. All rights reserved.