A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C₇₀@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C₇₀@lysozyme are confirmed using UV-visible and 2D ¹H, ¹⁵N NMR spectroscopy. The excellent imaging contrast of C₇₀@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C₇₀@lysozyme and its ability to initiate cell death by means of singlet oxygen (¹O₂) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C₇₀@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.     

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

Evolutionary algorithms and de novo peptide design

One of the goals of computational chemistry is the automated de novo design of bioactive molecules. Despite significant progress in computational approaches to ligand design and efficient evaluation of binding energy, novel procedures for ligand design are required. Evolutionary computation provides a new approach to this design issue. This paper presents an automated methodology for computer-aided peptide design based on evolutionary algorithms. It provides an automatic tool for peptide de novo design, based on protein surface patches defined by user. Regarding the restrictive constrains of this problem a special emphasis has been made on the design of the evolutionary algorithms implemented.     

An integrated system to remote monitor and control anaerobic wastewater treatment plants through the internet.

The TELEMAC project brings new methodologies from the Information and Science Technologies field to the world of water treatment. TELEMAC offers an advanced remote management system which adapts to most of the anaerobic wastewater treatment plants that do not benefit from a local expert in wastewater treatment. The TELEMAC system takes advantage of new sensors to better monitor the process dynamics and to run automatic controllers that stabilise the treatment plant, meet the depollution requirements and provide a biogas quality suitable for cogeneration. If the automatic system detects a failure which cannot be solved automatically or locally by a technician, then an expert from the TELEMAC Control Centre is contacted via the internet and manages the problem.     

Enoxaparin in the prevention of deep venous thrombosis after major surgery: multicentric study. The Italian Study Group

Four hundred forty-six patients with Tourette Syndrome (TS) and/or their parents completed a 52-item self-report survey about vocal and motor tics, and the frequency of associated co-morbid conditions of aggression, obsessions and compulsions, attentional problems, sleep disturbance, mood disturbance, anxiety, and self-mutilative behaviours which have been frequently reported in the literature on TS. Respondents also responded to an open-ended question regarding the most disabling aspects of TS. Results were analyzed within two age groups; under 18 years of age (N = 245) and 18 years of age or older (N = 177). Tics and associated conditions were the most frequently reported disabling aspect by both age groups. Subjects under age 18, however, reported significantly more frequent problems with hyperactivity, temper control, aggressive behaviours and sleepwalking than adults with TS.     

Content of carbohydrates and trace elements in a group of non-alcoholic drinks

BACKGROUND: In order to elaborate recommendations for the dietetic care of diabetic patients and other clinical disorders we have measured the concentration of carbohydrates and trace elements in a group of non alcoholic refreshments of current use in Spain. MATERIAL AND METHODS: Thirty refreshments were classified into 10 groups. Glucose and phosphate were measured by hexokinase and reduction of phospho-molybdate methods respectively in an autoanalyzer Dax-72. Glucose and fructose were analyzed by cellulose thin-layer chromatography; glucose, fructose and sucrose by gas chromatographys. Sodium and potassium by emission spectrophotometry and calcium, magnesium, iron, copper and zinc by atomic absorption spectrophotometry. RESULTS: Light refreshments and soft drinks have no carbohydrates. Isotonic beverages, fruit juices, cool tea and non alcoholic beers had less than 10 g/dl. Tonic waters, Fanta, different coles, non alcoholic bitter and others had more than 10 g/dl. Sodium levels between 15-20 mEq/l were found in the isotonic beverages and 7-Up and levels of 7 mEq/l in the others. Potassium values between 15-40 mEq/l were found in the fruit juices, 3-4 mEq/l in Gatorade and less than 1 mEq/l in the others. CONCLUSIONS: Light refreshments and soft drinks contain low concentrations of carbohydrates and sodium. Fruit juices have high potassium concentration. Such information can be especially useful for dietetic care of diabetic patients.     

Gorillas (Gorilla gorilla) and Orangutans (Pongo pygmaeus) Encode Relevant Problem Features in a Tool-Using Task.

Two important elements in problem solving are the abilities to encode relevant task features and to combine multiple actions to achieve the goal. The authors investigated these 2 elements in a task in which gorillas (Gorilla gorilla) and orangutans (Pongo pygmaeus) had to use a tool to retrieve an out-of-reach reward. Subjects were able to select tools of an appropriate length to reach the reward even when the position of the reward and tools were not simultaneously visible. When presented with tools that were too short to retrieve the reward, subjects were more likely to refuse to use them than when tools were the appropriate length. Subjects were proficient at using tools in sequence to retrieve the reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)