Down-regulation of Fas-L in glioma cells by ribozyme reduces cell apoptosis, tumour-infiltrating cells, and liver damage but accelerates tumour formation in nude mice

Fas-L (CD95L, APO-1L) expresses in a variety of tumours and has been proposed to play a role in tumour formation and metastasis. The contribution of Fas-L to tumour growth, however, is not conclusive especially in systems using cells with over-expressed Fas-L. In this study we down-regulated the expression o Fas-L in human glioma cells by a hammerhead ribozyme (Fas-Lribozyme) targeting against Fas-L mRNA. Fas-Lribozyme-carrying cells exhibited slightly enhanced growth rate and less degree of spontaneous apoptosis in vitro as compared with vector controls. In nude mice, Fas-Lribozyme-carrying cells grew faster with lesser apoptosis, formed bigger tumour with significantly fewer infiltrating cells in the tumour area, and triggered relatively milder tumour-associated liver damage than vector controls did. Thus, down-regulation of Fas-L not only improved viability of glioma cells but also reduces local immune responses that may consequently affect tumour formation. Taken together, our findings imply that endogenous expression of Fas-L in malignant cells is not always growth promoting. © 2001 Cancer Research Campaign  http://www.bjcancer.co

SERS biosensors based on cucurbituril-mediated nanoaggregates for wastewater-based epidemiology

Hierarchical self-assembly of nanoparticles (NPs) mediated by macrocyclic molecules, cucurbiturils (CBs), provides a facile method to fabricate surface-enhanced Raman spectroscopy (SERS) sensors for potential applications in biosensing and environmental monitoring. In contrast to conventional techniques for wastewater-based epidemiology (WBE), CB-NP SERS sensors offer great opportunities for on-site quantification of trace chemical and biological markers due to its high sensitivity, selectivity, reproducibility, multiplexing capability and tolerance against contamination. The working principles of the CB-Au NP nanocomposites including fabrication, sensing mechanisms and structure-property relationships are explained while the design guidelines and selected examples of CB-Au NP SERS sensors are discussed. The review concludes by highlighting recent advances in this area and exploring opportunities in the context of WBE

El puente con pretensado extradosado. Un nuevo tipo estructural

La idea de estos puentes y su denominación proviene de Mathivat quien, en 1988, propone comosolución de concurso del viaducto de L'Arret-DarréW1 puente con esta tipología, que se caracterizapor disponer el pretensado, sobre las secciones de apoyo en pila, exteriormente al canto de lasección y por la pane superior del tablero, intentando ganar excentricidad. Resulta, así, unaespecie de puente de tirantes con pila baja y canto holgado, que busca, además de la compensaciónde cargas, que la variación de tensión en el acero de los tendones extradosados, debida a lasobrecarga, sea lo suficientemente baja para que no se requieran los caros anclajes resistentes afatiga empleados en los puentes de tirantes. El artículo ilustra la concepción y desarrollo de este tipo de puente a partir de la evolución delconcepto de compensación de cargas mediante el pretensado con tendones de acero y de laconstrucción por avance en voladizo. Hace una presentación de los puentes construidos o enfase de construcción que pueden ser catalogados dentro de esta tipología de puentes. Además, ydado que la filosofía de diseño de este tipo de puentes busca agotar las posibilidades de laresistencia afatiga de los tendones de pretensado exterior, se presenta un resumen de la revisiónbibliográfica existente sobre fatiga en tendones y tirantes de acero y sus dispositivos de apoyo yanclaje. Por último, se establecen las principales conclusiones de la investigación.The idea of ​​these bridges and their designation comes from Mathivat who, in 1988, proposes as a solution to the L'Arret-DarréW1 viaduct bridge with this typology, which is characterized by the provision of prestressing, on the support sections in stack , Externally to the edge of the section and to the upper part of the board, trying to gain eccentricity. Thus, it is a kind of tie-rod bridge with low pile and loose edge, which seeks, besides the compensation of loads, that the variation of stress in the steel of the extrados tendons, due to the overload, is sufficiently low so that the expensive fatigue resistant anchors used in the jumpers are not required. The article illustrates the conception and development of this type of bridge from the evolution of the concept of load compensation by prestressing with steel tendons and the construction by cantilever advancement. It gives a presentation of the bridges built or under construction that can be cataloged within this type of bridge. In addition, given that the design philosophy of this type of bridges seeks to exhaust the possibilities of fatigue resistance of the external prestressing tendons, a summary of the existing literature review on fatigue in tendons and steel straps and their devices Support and anchorage. Finally, the main conclusions of the investigation are establishe

Quantitative SERS Detection of Uric Acid via Formation of Precise Plasmonic Nanojunctions within Aggregates of Gold Nanoparticles and Cucurbit[n]uril

This work describes a rapid and highly sensitive method for the quantitative detection of an important biomarker, uric acid (UA), via surface-enhanced Raman spectroscopy (SERS) with a low detection limit of ~0.2 μM for multiple characteristic peaks in the fingerprint region, using a modular spectrometer. This biosensing scheme is mediated by the host-guest complexation between a macrocycle, cucurbit[7]uril (CB7), and UA, and the subsequent formation of precise plasmonic nanojunctions within the self-assembled Au NP: CB7 nanoaggregates. A facile Au NP synthesis of desirable sizes for SERS substrates has also been performed based on the classical citrate-reduction approach with an option to be facilitated using a lab-built automated synthesizer. This protocol can be readily extended to multiplexed detection of biomarkers in body fluids for clinical applications

Age-related penetrance of the C9orf72 repeat expansion

A pathogenic hexanucleotide repeat expansion within the C9orf72 gene has been identified as the major cause of two neurodegenerative syndromes, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation is known to have incomplete penetrance, with some patients developing disease in their twenties and a small portion of carriers surviving to their ninth decade without developing symptoms. Describing penetrance by age among C9orf72 carriers and identifying parameters that alter onset age are essential to better understanding this locus and to enhance predictive counseling. To do so, data from 1,170 individuals were used to model penetrance. Our analysis showed that the penetrance was incomplete and age-dependent. Additionally, familial and sporadic penetrance did not significantly differ from one another; ALS cases exhibited earlier age of onset than FTD cases; and individuals with spinal-onset exhibited earlier age of onset than those with bulbar-onset. The older age of onset among female cases in general, and among female bulbar-onset cases in particular, was the most striking finding, and there may be an environmental, lifestyle, or hormonal factor that is influencing these penetrance patterns. These results will have important applications for future clinical research, the identification of disease modifiers, and genetic counseling.Peer reviewe

SERS multiplexing of methylxanthine drug isomers via host-guest size matching and machine learning

Multiplexed detection and quantification of structurally similar drug molecules, methylxanthine MeX, incl. theobromine TBR, theophylline TPH and caffeine CAF, have been demonstrated via solution-based surface-enhanced Raman spectroscopy (SERS), achieving highly reproducible SERS signals with detection limits down to ∼50 nM for TBR and TPH, and ∼1 μM for CAF. Our SERS substrates are formed by aqueous self-assembly of gold nanoparticles (Au NPs) and supramolecular host molecules, cucurbit[n]urils (CBn, n = 7, 8). We demonstrate that the binding constants can be significantly increased using a host–guest size matching approach, which enables effective enrichment of analyte molecules in close proximity to the plasmonic hotspots. The dynamic range and the robustness of the sensing scheme can be extended using machine learning algorithms, which shows promise for potential applications in therapeutic drug monitoring, food processing, forensics and veterinary science

Artificial molecular and nanostructures for advanced nanomachinery

Artificial nanomachines can be broadly defined as manmade molecular and nanosystems that are capable of performing useful tasks, very often, by means of doing mechanical work at the nanoscale. Recent advances in nanoscience allow these tiny machines to be designed and made with unprecedented sophistication and complexity, showing promise in novel applications, including molecular assemblers, self-propelling nanocarriers and in vivo molecular computation. This Feature Article overviews and compares major types of nanoscale machines, including molecular machines, self-assembled nanomachines and hybrid inorganic nanomachines, to reveal common structural features and operating principles across different length scales and material systems. We will focus on systems with feature size between 1 and 100 nm, where classical laws of physics meet those of quantum mechanics, giving rise to a spectrum of exotic physiochemical properties. Concepts of nanomachines will be illustrated by selected seminal work along with state-of-the-art progress, including our own contribution, across the fields. The Article will conclude with a brief outlook of this exciting research area