Impedimetric and Plasmonic Sensing of Collagen I Using a Half-Antibody-Supported, Au-Modified, Self-Assembled Monolayer System

This research presents an electrochemical immunosensor for collagen I detection using a self-assembled monolayer (SAM) of gold nanoparticles (AuNPs) and covalently immobilized half-reduced monoclonal antibody as a receptor; this allowed for the validation of the collagen I concentration through two different independent methods: electrochemically by Electrochemical Impedance Spectroscopy (EIS), and optically by Surface Plasmon Resonance (SPR). The high unique advantage of the proposed sensor is based on the performance of the stable covalent immobilization of the AuNPs and enzymatically reduced half-IgG collagen I antibodies, which ensured their appropriate orientation onto the sensor’s surface, good stability, and sensitivity properties. The detection of collagen type I was performed in a concentration range from 1 to 5 pg/mL. Moreover, SPR was utilized to confirm the immobilization of the monoclonal half-antibodies and sensing of collagen I versus time. Furthermore, EIS experiments revealed a limit of detection (LOD) of 0.38 pg/mL. The selectivity of the performed immunosensor was confirmed by negligible responses for BSA. The performed approach of the immunosensor is a novel, innovative attempt that enables the detection of collagen I with very high sensitivity in the range of pg/mL, which is significantly lower than the commonly used enzyme-linked immunosorbent assay (ELISA)

Multifactorial Regulation of a Hox Target Gene

Hox proteins play fundamental roles in controlling morphogenetic diversity along the anterior–posterior body axis of animals by regulating distinct sets of target genes. Within their rather broad expression domains, individual Hox proteins control cell diversification and pattern formation and consequently target gene expression in a highly localized manner, sometimes even only in a single cell. To achieve this high-regulatory specificity, it has been postulated that Hox proteins co-operate with other transcription factors to activate or repress their target genes in a highly context-specific manner in vivo. However, only a few of these factors have been identified. Here, we analyze the regulation of the cell death gene reaper (rpr) by the Hox protein Deformed (Dfd) and suggest that local activation of rpr expression in the anterior part of the maxillary segment is achieved through a combinatorial interaction of Dfd with at least eight functionally diverse transcriptional regulators on a minimal enhancer. It follows that context-dependent combinations of Hox proteins and other transcription factors on small, modular Hox response elements (HREs) could be responsible for the proper spatio-temporal expression of Hox targets. Thus, a large number of transcription factors are likely to be directly involved in Hox target gene regulation in vivo

Dpp Signaling Activity Requires Pentagone to Scale with Tissue Size in the Growing Drosophila Wing Imaginal Disc

The activity of the Dpp morphogen adapts to tissue size in the growing Drosophila wing imaginal disc, and Pentagone, an important secreted feedback regulator of the Dpp pathway, is required for this adaptation

Advances in tenascin-C biology

Tenascin-C is an extracellular matrix glycoprotein that is specifically and transiently expressed upon tissue injury. Upon tissue damage, tenascin-C plays a multitude of different roles that mediate both inflammatory and fibrotic processes to enable effective tissue repair. In the last decade, emerging evidence has demonstrated a vital role for tenascin-C in cardiac and arterial injury, tumor angiogenesis and metastasis, as well as in modulating stem cell behavior. Here we highlight the molecular mechanisms by which tenascin-C mediates these effects and discuss the implications of mis-regulated tenascin-C expression in driving disease pathology

The role of tenascin-C in tissue injury and tumorigenesis

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer

Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration

Objective: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression. Methods: Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN, and MAPT mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD). Linear mixed-effect models related NfL to clinical variables. Results: In both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or disease progression compared to nonprogressors (original: 11.4 ± 7 pg/mL vs 6.7 ± 5 pg/mL, p = 0.002; validation: 14.1 ± 12 pg/mL vs 8.7 ± 6 pg/mL, p = 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or those with prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR+NACC-FTLD sum of boxes scores, neuropsychological function, and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers. Conclusions: Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression and is a potential tool to select participants for prevention clinical trials. Trial registration information: ClinicalTrials.gov Identifier: NCT02372773 and NCT02365922. Classification of evidence: This study provides Class I evidence that in carriers of FTLD-causing mutations, elevation of plasma NfL predicts short-term risk of clinical progression

A Case for Real-Time Client-Server Databases

In this paper, we propose the use of Client-Server database systems in real-time transaction processing environments. Modern real-time applications often function along with large data sets. Hence, the use of database systems that can handle such sets within predefined deadlines is a key challenge. We examine real-time processing scheduling issues using the popular Client-Server model as our underlying framework and carry out a performance scalability study. Our experimental results indicate that Real-Time Client-Server Databases could indeed provide significant performance gains over centralized configurations. To appear in the 2nd International Real-Time Database Workshop, Burlington, VT, Sept. 18-19, 1997. This work was supported in part by the Center for Advanced Technology in Telecommunications (CATT). 1 1 Introduction The support of applications in large-scale financial environments [Sie96], wireless directory services, and Personal Communication Systems (PCS) [QL95], ..