Effects of Cerebrospinal Fluids from Alzheimer and Non-Alzheimer Patients on Neurons-Astrocytes-Microglia Co-Culture.

Alzheimer's disease (AD) is the most common form of dementia, characterized by the accumulation of β-amyloid plaques, tau tangles, neuroinflammation, and synaptic/neuronal loss, the latter being the strongest correlating factor with memory and cognitive impairment. Through an in vitro study on a neurons-astrocytes-microglia (NAM) co-culture system, we analyzed the effects of cerebrospinal fluid (CSF) samples from AD and non-AD patients (other neurodegenerative pathologies). Treatment with CSF from AD patients showed a loss of neurofilaments and spheroids, suggesting the presence of elements including CX3CL1 (soluble form), destabilizing the neurofilaments, cellular adhesion processes, and intercellular contacts.

Do Naturally Modified Nucleotides Contribute to Stabilizing Complexes between Ribosomes and Small Molecules? A Case Study with the Antitumor Drug Homoharringtonine.

Modified nucleotides are ubiquitous with RNAs, also in contact with drugs that target the ribosome. Whether this represents a stabilization of the drug-ribosome complex, thus affecting the drug's affinity and possibly also intrinsic efficacy, remains an open question, however. The challenge of answering this question has been taken here with the only human-ribosome-targeting small-molecule currently in clinical use, the antitumor plant alkaloid homoharringtonine (HHT).

Cerebral and cognitive modifications in retired professional soccer players: TC-FOOT protocol, a transverse analytical study.

Introduction: Soccer is the most popular sport in the world. This contact sport carries the risk of exposure to repeated head impacts in the form of subconcussions, defined as minimal brain injuries following head impact, with no symptom of concussion. While it has been suggested that exposure to repetitive subconcussive events can result in long-term neurophysiological modifications, and the later development of chronic traumatic encephalopathy, the consequences of these repeated impacts remain controversial and largely unexplored in the context of soccer players.

Analysis of cavitation artifacts in Magnetic Resonance Imaging Thermometry during laser ablation monitoring.

Magnetic Resonance Thermometry Imaging (MRTI) holds great potential in laser ablation (LA) monitoring. It provides the real-time multidimensional visualization of the treatment effect inside the body, thus enabling accurate intraoperative prediction of the thermal damage induced. Despite its great potential.

A case of an injured calcaneus secundarius in a professional soccer player.

Background: The calcaneus secundarius (CS) is an accessory ossicle of the anterior facet of the calcaneus and is usually asymptomatic. This accessory bone can be frequently mistaken for a fracture of the anterior process of the calcaneus. Few reports of symptomatic CS have been published, and physicians need to be familiar with imaging strategies when encountering chronic ankle pain or in case of suspicion of fracture of the anterior process of the calcaneus.

Total Pancreatectomy for Ampullary Adenocarcinoma in a 74-Year-Old Patient: Case Report and Literature Review.

Primary ampullary neoplasms have origin in the ampulla of Vater, an anatomical structure where the common bile duct and the pancreatic duct join together as a common channel. It represents <0.5% of all gastrointestinal cancers and approximately 7% of all periampullary cancers.

Automated Intelligent Microscopy for the Recognition of Decoy Cells in Urine Samples of Kidney Transplant Patients.

Background: BK virus (BKV)-associated nephropathy is definitely involved in allograft failure after kidney transplant. Thus, the need for an early control of viral reactivation in immunocompromised patients is well established. Determination of urinary release of decoy cells (DC) and BK viral load in plasma and urine by polymerase chain reaction (PCR) usually precedes renal biopsy.

New Vistas on the Recruiting of Ferrous Iron and Dioxygen by Ferritins: A Case Study of the Escherichia coli 24-mer Ferritin by All-Atom Molecular Dynamics in Aqueous Medium.

It is shown here that Fe and O ligands are displaced from the ferroxidase center of the C1 four-helix bundle of E. coli 24-mer ferritin under molecular dynamics (MD) aided by a randomly oriented external force applied to the ligand. Under these conditions, ligand egress toward the external aqueous medium occurs preferentially from the same four-helix bundle, in the case of O , or other bundle, in the case of Fe .

On the Dynamical Behavior of the Cysteine Dioxygenase-l-Cysteine Complex in the Presence of Free Dioxygen and l-Cysteine.

In this work, viable models of cysteine dioxygenase (CDO) and its complex with l-cysteine dianion were built for the first time, under strict adherence to the crystal structure from X-ray diffraction studies, for all atom molecular dynamics (MD). Based on the CHARMM36 FF, the active site, featuring an octahedral dummy Fe(II) model, allowed us observing water exchange, which would have escaped attention with the more popular bonded models. Free dioxygen (O ) and l-cysteine, added at the active site, could be observed being expelled toward the solvating medium under Random Accelerated Molecular Dynamics (RAMD) along major and minor pathways.

Ga for Zn Cation Exchange Allows for Highly Luminescent and Photostable InZnP-Based Quantum Dots.

In this work, we demonstrate that a preferential Ga-for-Zn cation exchange is responsible for the increase in photoluminescence that is observed when gallium oleate is added to InZnP alloy QDs. By exposing InZnP QDs with varying Zn/In ratios to gallium oleate and monitoring their optical properties, composition, and size, we conclude that Ga preferentially replaces Zn, leading to the formation of InZnP/InGaP core/graded-shell QDs. This cation exchange reaction results in a large increase of the QD photoluminescence, but only for InZnP QDs with Zn/In ≥ 0.

Kidney Transplantation in Alström Syndrome: Case Report.

The Alström syndrome is a rare genetic disorder, inherited in an autosomal recessive manner. It has recently been classified as a ciliopathic disorder. Alström syndrome is a multiorgan pathology characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, short stature in adulthood, hypothyroidism, hypogonadism, dilated or restrictive cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction.

On Dioxygen Permeation of MaL Laccase from the Thermophilic Fungus Melanocarpus albomyces: An all-Atom Molecular Dynamics Investigation.

In this article, biased molecular dynamics (MD) simulations of O egress from the active center of MaL laccase toward the bulk solvent were described. Parameterization of the set of four Cu(II) ions, in the framework of CHARMM-36 FF, was carried out on a recent dummy-atom model that takes into account the Jahn-Teller effect. By carrying out a number of statistically relevant MD simulations, under a tiny randomly oriented external force applied to the molecule O , three preferred gates for O egress from the enzyme and a few intermediate binding pockets (BPs) for O were visible; all the gates and pockets were located on two of the three domains.

On Dioxygen and Substrate Access to Soluble Methane Monooxygenases: An all-Atom Molecular Dynamics Investigation in Water Solution.

In a preliminary exploration of the dummy model for diiron proteins, random-acceleration molecular dynamics (RAMD) revealed that a pure four-helix bundle structure, like hemerythrin, constitutes an efficient cage for dioxygen (O ), which can only leave from defined, albeit very broad, gates. However, this well ordered structure does not constitute an archetype on which to compare O permeation of other diiron proteins, like the complex of soluble methane monooxygenase hydroxylase with the regulatory protein (sMMOH-MMOB). The reason is that with this complex, unlike hemerythrin, the four helices of the four-helix bundle are heavily bent, and RAMD showed that most traps for O lie outside them.

Unveiling the Pathways of Dioxygen Through the C2 Component of the Environmentally Relevant Monooxygenase p-Hydroxyphenylacetate Hydroxylase from Acinetobacter baumannii: A Molecular Dynamics Investigation.

In this work, models of the homotetrameric C2 component of the monooxygenase p-hydroxyphenylacetate hydroxylase from Acinetobacter baumannii, in complex with dioxygen (O2 ) and, or not, the substrate p-hydroxyphenylacetate (HPA) were built. Both models proved to be amenable to random-acceleration molecular dynamics (RAMD) simulations, whereby a tiny randomly oriented external force, acting on O2 at the active site in front of flavin mononucleotide (FMNH(-) ), accelerated displacement of O2 toward the bulk solvent. This allowed us to carry out a sufficiently large number of RAMD simulations to be of statistical significance.

On the Permeation by Dioxygen of Urate Oxidase from Aspergillus flavus in Complex with Xanthine Anion: Dioxygen Pathways and a Portrait of the Enzyme Cavities from Molecular Dynamics Simulations in Water Solution.

This work describes molecular dynamics (MD) simulations in aqueous media for the complex of the homotetrameric urate oxidase (UOX) from Aspergillus flavus with xanthine anion (5) in the presence of dioxygen (O2 ). After 196.6 ns of trajectory from unrestrained MD, a O2 molecule was observed leaving the bulk solvent to penetrate the enzyme between two subunits, A/C.

Delayed Introduction of Everolimus in De Novo Renal Transplanted Patients: A Single-Center Experience.

Introduction: Immunosuppressive protocols containing everolimus (EVR) preserve good renal function in kidney transplantation (KT), although they are often complicated by several adverse events. We have evaluated the efficacy and safety of a protocol with late (1 month after KT) EVR introduction.

Material And Methods: This study randomized 49 de novo patients undergoing KT between September 2012 and June 2014 into 2 groups: group A (n = 24) with late EVR introduction and tacrolimus reduction, and group B (control group; n = 25) with a standard immunosuppressive regimen.

Tuning the Lattice Parameter of InxZnyP for Highly Luminescent Lattice-Matched Core/Shell Quantum Dots.

Colloidal quantum dots (QDs) show great promise as LED phosphors due to their tunable narrow-band emission and ability to produce high-quality white light. Currently, the most suitable QDs for lighting applications are based on cadmium, which presents a toxicity problem for consumer applications. The most promising cadmium-free candidate QDs are based on InP, but their quality lags much behind that of cadmium based QDs.

On the Permeation by Dioxygen of the Cofactor-Independent Unusual Oxygenase RhCC, in Complex with Substrate 4-Hydroxyphenylenolpyruvate. A Molecular Dynamics Investigation.

This work deals with a trimeric bacterial protein, RhCC, which, although belonging to the tautomerase superfamily, shows oxygenase activity. A model of the complex from RhCC and substrate 4-hydroxyphenylenolpyruvate (4HPP), fitting the observation of extra electron densities from X-ray diffraction of the crystal, could be built by autodocking. When subjected to molecular dynamics (MD) aided by an external random force applied to a O2 molecule placed above 4HPP, this model evolved with O2 egressing toward the bulk solvent from two nearly opposite gates.

Uptake of Organohalide Pollutants, and Release of Partially Dehalogenated Products, by NpRdhA, a 'Base-Off' Cob(II)alamin-Dependent Reductive Dehalogenase from a Deep Sea Bacterium. A Molecular Dynamics Investigation.

This work shows that, during MD aided by external tiny random forces, 3-bromo-4-hydroxybenzoic acid (LHB), the product of reductive dehalogenation of 3,5-dibromo-4-hydroxybenzoic acid (LBB) by the corrin-based marine enzyme NpRdhA, is expelled along mainly the wide channel that connects the corrin to the external medium. In accordance, unbiased MD showed that LBB migrates relatively rapidly from the external medium to the inside of the channel, finally getting to the corrin active center of NpRdhA. The LBB pose, with bromide head and carboxylate tail nearly equidistant from the corrin Co ion, does not fit the results of previous automatic docking.

On the Quest of Dioxygen by Monomeric Sarcosine Oxidase. A Molecular Dynamics Investigation.

It is reported here on random acceleration molecular dynamics (RAMD) simulations with the 2GF3 bacterial monomeric sarcosine oxidase (MSOX), O2 , and furoic acid in place of sarcosine, solvated by TIP3 H2 O in a periodic box. An external tiny force, acting randomly on O2 , accelerated its relocation, from the center of activation between residue K265 and the si face of the flavin ring of the flavin adenine dinucleotide cofactor, to the surrounding solvent. Only three of the four O2 gates previously described for this system along a composite method technique were identified, while two more major O2 gates were found.

Surgical treatment of renal carcinoma with atrial tumor thrombus avoiding cardiopulmonary bypass: step-by-step description.

Tumor thrombus in the inferior vena cava (IVC) occurs in 4-10% of patients with renal cell carcinoma (RCC) and poses a challenge for the surgical team. Because there is no systemic therapy available to significantly reduce tumor burden, surgical intervention is the only treatment. However, the surgical approach is associated with significant morbidity and mortality.

Spontaneous Bilateral Adrenal Haemorrhage after Duodenopancreatectomy: a case report.

it is difficult to diagnose because of its nonspecific presentation. This condition frequently occurs in association with an extreme physical stress and may lead to acute adrenal insufficiency or death if not promptly and properly treated. We report a rare case of acute bilateral adrenal hemorrhage with adrenal insufficiency following duodenopancreatectomy for ampulloma in absence of surgical complications.

Restoring histone deacetylase activity by waste product release. A view from molecular mechanics simulations with mammalian HDAC8.

HDAC8 is a Zn(II) -based, single-peptide mammalian histone deacetylase that is localized mainly in the cytoskeleton of smooth muscle cells, thus regulating muscle contractility. HDACs are also widely involved in cellular processes, ranging from cell differentiation to proliferation, senescence, and apoptosis; in particular, protecting a telomerase activator from ubiquitin-mediated degradation. How HDACs can eliminate the hydrolytic reaction products, in order that the process of deacetylation of the acetyllysine moiety of histones can take place again, has long been debated in the scientific literature, without reaching any firm conclusion, however.

From the sequence to the conformation of the unabridged transmembrane domains TM1 and TM2 of the cASIC1a ion channel - a parallel tempering approach.

This work was devised to unravel, along replica-exchange molecular-dynamics (REMD) simulations, the conformation in solution of the TM1 and TM2 transmembrane domains of the homotrimeric cASIC1a ion channel. This includes the head of TM1 and tail of TM2 that had previously defied X-ray diffraction analysis in the crystal. The structure of the open-channel complex of cASIC1a with psalmotoxin 1 (PcTx1) was chosen here as a basis, although, to make the simulations affordable, the procedure was limited to the missing portions, including a few adjacent α-helical turns.