Signatures of Anderson localization and delocalized random quantum states

We consider the notion of equilibration for an isolated quantum system exhibiting Anderson localization. The system is assumed to be in a pure state, i.e., described by a wave-function undergoing unitary dynamics. We focus on the simplest model of a 1D disordered chain and we analyse both the dynamics of an initially localized state and the dynamics of quantum states drawn at random from the ensemble corresponding to the minimum knowledge about the initial state. While in the former case the site distribution remains confined in a limited portion of the chain, the site distribution of random pure state fluctuates around an equilibrium average that is delocalized over the entire chain. A clear connection between the equilibration observed when the system is initialized in a fully localized state and the amplitude of dynamical fluctuations of a typical random pure state is established

An Impedimetric Biosensing Strategy Based on Bicyclic Peptides as Bioreceptors for Monitoring huPA Cancer Biomarker

In the era of liquid biopsies, the reliable and cost-effective detection and screening of cancer biomarkers has become of fundamental importance, thus paving the way for the advancement of research in the field of point-of-care testing and the development of new methodologies and technologies. Indeed, the latter ones can help designing advanced diagnostic tools that can offer portability, ease of use with affordable production and operating costs. In this respect, impedance-based biosensing platforms might represent an attractive alternative. In this work, we describe a proof-of-concept study aimed at designing portable impedimetric biosensors for the monitoring of human urokinase-type plasminogen activator (h-uPA) cancer biomarker by employing small synthetic receptors. Aberrant levels of h-uPA were correlated with different types of cancers. Herein, we report the use of two bicyclic peptides (P2 and P3) which have been engineered to bind h-uPA with high affinity and exquisite specificity. The synthetic receptors were immobilized via biotin-streptavidin chemistry on the surface of commercial screen-printed electrodes. The impedimetric changes in the electrode/solution interface upon incubation of spiked h-uPA samples in the presence of a redox probe were followed via electrochemical impedance spectroscopy. The P3-based impedimetric assay showed the best outcomes in terms of dynamic range and linearity (0.01–1 μg mL−1) and sensitivity (LOD = 9 ng mL−1). To fully assess the performances of P3 over P2, and to compare the label-free architecture vs. labelled architecture, a voltammetric assay was also developed

Mapping the gaps in chemical analysis for the characterisation of aptamer-target interactions

Aptamers are promising biorecognition elements with a wide applicability from therapeutics to biosensing. However, to successfully use these biomolecules, a complete characterisation of their binding performance in the presence of the target is crucial. Several multi-analytical approaches have been reported including techniques to describe kinetic and thermodynamic aspects of the aptamer-target interaction, and techniques which allow an in-depth understanding of the aptamer-target structures. Recent literature shows the need of a critical data interpretation, a combination of characterisation techniques and suggests the key role of the characterisation protocol design. Indeed, the final application of the aptamer should be considered before choosing the characterisation method. All the limitations and capabilities of the analytical tools in use for aptamer characterisation should be taken into account. Here, we present a critical overview of the current methods and multi-analytical approaches to study aptamer-target binding, aiming to provide researchers with guidelines for the design of characterisation protocols

Transglutaminase 2 maintains a colorectal cancer stem phenotype by regulating epithelial-mesenchymal transition

Transglutaminase 2 (TG2), a multifunctional protein, is reported in regulating the cancer stem cell (CSC) phenotype in various cancers. Our previous work suggested the link between TG2 and Epithelial-Mesenchymal Transition (EMT) in colorectal cancer (CRC). Here we demonstrate the importance of TG2 in CSC development in human CRC cell lines HCT116 and SW620. CRC spheroid cells showed increased CSC characteristics over their monolayer cells with increased expression of CD44 and over expression of Oct3/4, Sox2 and Nanog. They also showed increased EMT and invasiveness, and enhanced expression of TG2. TG2 inhibition by its selective inhibitor 1-155 reduced both spheroid formation and invasive potential of the spheroid cells. β-catenin, a mediator of stem cell maintenance, was overexpressed in the spheroid cells and could be attenuated by TG2 inhibition. Spheroid cells possessed increased angiogenesis stimulating ability via overexpression of Vascular Endothelial Growth Factor (VEGF). Increased VEGF was present in the culture media from spheroid cells when compared to monolayer cultures which could be reduced by selective inhibition by 1-155. Stemness and malignancy in the colorectal spheroid cells was associated with increased TG2, EMT, β-catenin and VEGF. Here we demonstrate that inhibiting TG2 reduces both stemness and angiogenic stimulating activity in CRC

Patient-Derived Xenografts of Non Small Cell Lung Cancer: Resurgence of an Old Model for Investigation of Modern Concepts of Tailored Therapy and Cancer Stem Cells

Current chemotherapy regimens have unsatisfactory results in most advanced solid tumors. It is therefore imperative to devise novel therapeutic strategies and to optimize selection of patients, identifying early those who could benefit from available treatments. Mouse models are the most valuable tool for preclinical evaluation of novel therapeutic strategies in cancer and, among them, patient-derived xenografts models (PDX) have made a recent comeback in popularity. These models, obtained by direct implants of tissue fragments in immunocompromised mice, have great potential in drug development studies because they faithfully reproduce the patient's original tumor for both immunohistochemical markers and genetic alterations as well as in terms of response to common therapeutics They also maintain the original tumor heterogeneity, allowing studies of specific cellular subpopulations, including their modulation after drug treatment. Moreover PDXs maintain at least some aspects of the human microenvironment for weeks with the complete substitution with murine stroma occurring only after 2-3 passages in mouse and represent therefore a promising model for studies of tumor-microenvironment interaction. This review summarizes our present knowledge on mouse preclinical cancer models, with a particular attention on patient-derived xenografts of non small cell lung cancer and their relevance for preclinical and biological studies

Structural Analysis of Human Serum Albumin in Complex with the Fibrate Drug Gemfibrozil

Gemfibrozil (GEM) is an orally administered lipid-regulating fibrate derivative drug sold under the brand name Lopid®, among others. Since its approval in the early 80s, GEM has been largely applied to treat hypertriglyceridemia and other disorders of lipid metabolism. Though generally well tolerated, GEM can alter the distribution and the free, active concentration of some co-administered drugs, leading to adverse effects. Most of them appear to be related to the ability of GEM to bind with high affinity human serum albumin (HSA), the major drug-carrier protein in blood plasma. Here, we report the crystal structure of HSA in complex with GEM. Two binding sites have been identified, namely Sudlow’s binding sites I (FA7) and II (FA3–FA4). A comparison of the crystal structure of HSA in complex with GEM with those of other previously described HSA–drug complexes enabled us to appreciate the analogies and differences in their respective binding modes. The elucidation of the molecular interaction between GEM and HSA might offer the basis for the development of novel GEM derivatives that can be safely and synergistically co-administered with other drugs, enabling augmented therapeutic efficacies

Temporal clustering of social interactions trades-off disease spreading and knowledge diffusion

Non-pharmaceutical measures such as preventive quarantines, remote working, school and workplace closures, lockdowns, etc. have shown effectivenness from an epidemic control perspective; however they have also significant negative consequences on social life and relationships, work routines, and community engagement. In particular, complex ideas, work and school collaborations, innovative discoveries, and resilient norms formation and maintenance, which often require face-to-face interactions of two or more parties to be developed and synergically coordinated, are particularly affected. In this study, we propose an alternative hybrid solution that balances the slowdown of epidemic diffusion with the preservation of face-to-face interactions. Our approach involves a two-step partitioning of the population. First, we tune the level of node clustering, creating "social bubbles" with increased contacts within each bubble and fewer outside, while maintaining the average number of contacts in each network. Second, we tune the level of temporal clustering by pairing, for a certain time interval, nodes from specific social bubbles. Our results demonstrate that a hybrid approach can achieve better trade-offs between epidemic control and complex knowledge diffusion. The versatility of our model enables tuning and refining clustering levels to optimally achieve the desired trade-off, based on the potentially changing characteristics of a disease or knowledge diffusion process

Redesigning an Electrochemical MIP Sensor for PFOS: Practicalities and Pitfalls

There is a growing interest in the technological transfer of highly performing electrochemical sensors within portable analytical devices for the in situ monitoring of environmental contaminants, such as perfluorooctanesulfonic acid (PFOS). In the redesign of biomimetic sensors, many parameters should be taken into account from the working conditions to the electrode surface roughness. A complete characterization of the surface modifiers can help to avoid time-consuming optimizations and better interpret the sensor responses. In the present study, a molecularly imprinted polymer electrochemical sensor (MIP) for PFOS optimized on gold disk electrodes was redesigned on commercial gold screen-printed electrodes. However, its performance investigated by dierential pulse voltammetry was found to be poor. Before proceeding with further optimization, a morphological study of the bare and modified electrode surfaces was carried out by scanning electron microscopy–energy-dispersive X-ray spectrometry (SEM–EDS), atomic force microscopy (AFM) and profilometry revealing an heterogeneous distribution of the polymer strongly influenced by the electrode roughness. The high content of fluorine of the target-template molecule allowed to map the distribution of the molecularly imprinted polymer before the template removal and to define a characterization protocol. This case study shows the importance of a multi-analytical characterization approach and identify significant parameters to be considered in similar redesigning studies