Multi-technique Approach to Unravel the (Dis)order in Amorphous Materials.

The concept of order in disordered materials is the key to controlling the mechanical, electrical, and chemical properties of amorphous compounds widely exploited in industrial applications and daily life. Rather, it is far from being understood. Here, we propose a multi-technique numerical approach to study the order/disorder of amorphous materials on both the short- and the medium-range scale.

Biogenic Synthesis and Characterization of Antioxidant and Antimicrobial Silver Nanoparticles Using Flower Extract of Aubl.

Aubl. is an important medicinal tree. This tree is rich in various phytochemicals, and is therefore used as a potent antioxidant and antibacterial agent.

Computational Insight on the Interaction of Common Blood Proteins with Gold Nanoparticles.

Protein interactions with engineered gold nanoparticles (AuNPs) and the consequent formation of the protein corona are very relevant and poorly understood biological phenomena. The nanoparticle coverage affects protein binding modalities, and the adsorbed protein sites influence interactions with other macromolecules and cells. Here, we studied four common blood proteins, i.

Disclosing the Interaction of Gold Nanoparticles with Aβ(1-40) Monomers through Replica Exchange Molecular Dynamics Simulations.

Amyloid-β aggregation is one of the principal causes of amyloidogenic diseases that lead to the loss of neuronal cells and to cognitive impairments. The use of gold nanoparticles treating amyloidogenic diseases is a promising approach, because the chemistry of the gold surface can be tuned in order to have a specific binding, obtaining effective tools to control the aggregation. In this paper, we show, by means of Replica Exchange Solute Tempering Molecular Simulations, how electrostatic interactions drive the absorption of Amyloid-β monomers onto citrates-capped gold nanoparticles.

Computational Insights into the Binding of Monolayer-Capped Gold Nanoparticles onto Amyloid-β Fibrils.

Amyloids-β (Aβ) fibrils are involved in several neurodegenerative diseases. In this study, atomistic molecular dynamics simulations have been used to investigate how monolayer-protected gold nanoparticles interact with Aβ(1-40) and Aβ(1-42) fibrils. Our results show that small gold nanoparticles bind with the external side of amyloid-β fibrils that is involved in the fibrillation process.

Insights into the Effect of Curcumin and (-)-Epigallocatechin-3-Gallate on the Aggregation of Aβ(1-40) Monomers by Means of Molecular Dynamics.

In this study, we compared the effects of two well-known natural compounds on the early step of the fibrillation process of amyloid-β (1-40), responsible for the formation of plaques in the brains of patients affected by Alzheimer's disease (AD). The use of extensive replica exchange simulations up to the µs scale allowed us to characterize the inhibition activity of (-)-epigallocatechin-3-gallate (EGCG) and curcumin (CUR) on unfolded amyloid fibrils. A reduced number of β-strands, characteristic of amyloid fibrils, and an increased distance between the amino acids that are responsible for the intra- and interprotein aggregations are observed.

DARPin_9-29-Targeted Mini Gold Nanorods Specifically Eliminate HER2-Overexpressing Cancer Cells.

We have demonstrated that designed ankyrin repeat protein (DARPin) _9-29, which specifically targets human epidermal growth factor receptor 2 (HER2), binds tightly to gold mini nanorods (GNRs). Molecular dynamic simulations showed that a single layer of DARPin_9-29 molecules is formed on the surface of the nanorod and that conjugation with the nanorod does not involve the protein's domain responsible for specific binding to HER2. The nanorod-DARPin (DARPin-GNR) conjugate is specifically bound (in nanomolar concentrations) to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2.

Multiscale Molecular Dynamics Simulation of Multiple Protein Adsorption on Gold Nanoparticles.

A multiscale molecular dynamics simulation study has been carried out in order to provide in-depth information on the adsorption of hemoglobin, myoglobin, and trypsin over citrate-capped AuNPs of 15 nm diameter. In particular, determinants for single proteins adsorption and simultaneous adsorption of the three types of proteins considered have been studied by Coarse-Grained and Meso-Scale molecular simulations, respectively. The results, discussed in the light of the controversial experimental data reported in the current experimental literature, have provided a detailed description of the (i) recognition process, (ii) number of proteins involved in the early stages of corona formation, (iii) protein competition for AuNP adsorption, (iv) interaction modalities between AuNP and protein binding sites, and (v) protein structural preservation and alteration.

Curcumin derivatives and Aβ-fibrillar aggregates: An interactions' study for diagnostic/therapeutic purposes in neurodegenerative diseases.

Several neurodegenerative diseases, like Alzheimer's (AD), are characterized by amyloid fibrillar deposition of misfolded proteins, and this feature can be exploited for both diagnosis and therapy design. In this paper, structural modifications of curcumin scaffold were examined in order to improve its bioavailability and stability in physiological conditions, as well as its ability to interfere with β-amyloid fibrils and aggregates. The acid-base behaviour of curcumin derivatives, their pharmacokinetic stability in physiological conditions, and in vitro ability to interfere with Aβ fibrils at different incubation time were investigated.

Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1⁻40) Fibrils.

One of the principal hallmarks of Alzheimer's disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists of either blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests.

Prediction of survival in patients affected by glioblastoma: histogram analysis of perfusion MRI.

Purpose: The identification of prognostic biomarkers plays a pivotal role in the management of glioblastoma. The aim of this study was to assess the role of magnetic resonance dynamic susceptibility contrast imaging (DSC-MRI) with histogram analysis in the prognostic evaluation of patients suffering from glioblastoma.

Materials And Methods: Sixty-eight patients with newly diagnosed pathologically verified GBM were retrospectively evaluated.

Computational Insight into the Interaction of Cytochrome C with Wet and PVP-Coated Ag Surfaces.

In this work, the adsorption of cytochrome C (CytC) on wet {100}, {111}, {110}, and {120} silver surfaces has been investigated by computational simulations. The effect of polyvinylpyrrolidone (PVP) coating has also been studied. The main results obtained can be summarized as follow: (a) CytC strongly interacts with wet bare high index facets, while the adsorption over the {100} surface is disfavored due to the strong water structuring at the surface; (b) a nonselective protein adsorption mechanism is highlighted; (c) the native structure of CytC is well preserved during adsorption; (d) the heme group of CytC is never found to interact directly with the surface; (e) the interactions with the PVP-capped {100} surface is weak and specific.

Synthesis, Characterization, and Selective Delivery of DARPin-Gold Nanoparticle Conjugates to Cancer Cells.

We demonstrate that the designed ankyrin repeat protein (DARPin)_9-29, which specifically targets human epidermal growth factor receptor 2 (HER 2), binds tightly to gold nanoparticles (GNPs). Binding of the protein strongly increases the colloidal stability of the particles. The results of experimental analysis and molecular dynamics simulations show that approximately 35 DARPin_9-29 molecules are bound to the surface of a 5 nm GNP and that the binding does not involve the receptor-binding domain of the protein.

Site-Selective Surface-Enhanced Raman Detection of Proteins.

Strategies for protein detection via surface-enhanced Raman spectroscopy (SERS) currently exploit the formation of randomly generated hot spots at the interfaces of metal colloidal nanoparticles, which are clustered together by intrusive chemical or physical processes in the presence of the target biomolecule. We propose a different approach based on selective and quantitative gathering of protein molecules at regular hot spots generated on the corners of individual silver nanocubes in aqueous medium at physiological pH. Here, the protein, while keeping its native configuration, experiences an intense local E-field, which boosts SERS efficiency and detection sensitivity.

Predictive role of dynamic contrast enhanced T1-weighted MR sequences in pre-surgical evaluation of macroadenomas consistency.

Purpose: Our hypothesis was that pituitary macroadenomas show different areas of consistency detectable by enhanced magnetic resonance imaging (MRI) with Dynamic study during gadolinium administration.

Materials And Methods: We analysed 21 patients with pituitary macroadenomas between June 2013 and June 2015. All patients underwent trans-sphenoidal surgery and neurosurgeon described macroadenomas consistency.

Portosystemic encephalopathy in an 86-year-old patient : a clinical challenge.

Abernethy malformations are rare vascular abnormalities, classified into two types : type 1 if the portal vein is absent, type 2 when the portal blood is diverted into vena cava through a hypoplastic portal vein. These conditions present symptoms related to portosystemic shunting, and usually become clinically evident in children or young adults. Here we report the first case of Abernethy malformation diagnosed in an 86-year-old female patient affected by portosystemicencephalopaty.

The role of time-resolved imaging of contrast kinetics (TRICKS) magnetic resonance angiography (MRA) in the evaluation of head-neck vascular anomalies: a preliminary experience.

Objectives: In this preliminary report, we describe our experience with time-resolved imaging of contrast kinetics-MR angiography (TRICKS-MRA) in the assessment of head-neck vascular anomalies (HNVAs).

Methods: We prospectively studied six consecutive patients with clinically suspected or diagnosed HNVAs. All of them underwent TRICKS-MRA of the head and neck as part of the routine for treatment planning.

A multi-scale-multi-stable model for the rhodopsin photocycle.

We report a multi-scale simulation study of the photocycle of the rhodopsins. The quasi-atomistic representation ("united atoms" UA) of retinal is combined with a minimalist coarse grained (CG, one-bead-per amino acid) representation of the protein, in a hybrid UA/CG approach, which is the homolog of QM/MM, but at lower resolution. An accurate multi-stable parameterization of the model allows simulating each state and transition among them, and the combination of different scale representation allows addressing the entire photocycle.

Diffuse axonal injury with selective involvement of the corticospinal tract. A diffusion tensor imaging case study.

The identification of diffuse axonal injury (DAI) can be difficult, especially using conventional imaging (CT or MRI), which usually appears normal. Diffusion tensor imaging (DTI) is useful in identifying white matter abnormalities in patients with DAI. We describe the case of a 17-year-old female with severe closed head injury and right-side hemiparesis, studied with DTI and MR-tractography.

Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery.

Purpose: We assessed the performance of 6-[(18)F]-fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) PET for differentiating radionecrosis (RN) from tumour progression (PD) in a population of patients with brain metastases, treated with stereotactic radiosurgery. The accuracy of F-DOPA PET was compared with that of perfusion-weighted magnetic resonance (perfusion-MR).

Methods: In 42 patients with a total of 50 brain metastases from various primaries F-DOPA PET/CT was performed because of suspected radiological progression at the site of previously irradiated brain metastasis.

Role of multidetector CT in the recognition of hyperdense middle cerebral artery sign (HMCAS) in patients with acute cerebral ischaemia: correlation with DWI-MRI sequences and clinical data.

Purpose: The aim of this study was to verify the sensitivity and specificity of the hyperdense middle cerebral artery sign (HMCAS) obtained by multidetector computed tomography (CT) in predicting acute stroke, using diffusion-weighted (DW) magnetic resonance imaging (MRI) as a reference. The location of the HMCAS, the extension of the ischaemic lesion and its prognostic value were also assessed.

Materials And Methods: The CT examinations of 654 patients with symptoms related to acute cerebral stroke were retrospectively reviewed.

Apparent diffusion coefficient obtained by magnetic resonance imaging as a prognostic marker in glioblastomas: correlation with MGMT promoter methylation status.

Objective: To evaluate whether apparent diffusion coefficient (ADC) values can predict the status of MGMT of glioblastoma multiforme (GBM) and correlate with overall survival (OS) and progression-free survival (PFS).

Methods: This retrospective study included 47 patients with pathologically proven glioblastoma. All of them underwent MR DWI study before surgery (mean time 1 week) and the status of methylguanine-DNA-methyltransferase (MGMT) promoter methylation was searched for.