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.     

Local residence time,residence revolution,and residence volume distributions in twin‐screw extruders

This work was aimed at studying the overall, partial, and local residence time distributions (RTD); overall, partial and local residence revolution distributions (RRD) and overall, partial and local residence volume distributions (RVD) in a co‐rotating twin screw extruder, on the one hand; and establishing the relationships among them, on the other hand. Emphasis was placed on the effects of the type and geometry of mixing elements (a gear block and various types of kneading elements differing in staggering angle) and process parameters on the RTD, RRD and RVD. The overall and partial RTD were directly measured in‐line during the extrusion process and the local ones were calculated by deconvolution based on a statistical theory. The local RTD allowed comparing the mixing performance of mixing elements. Also it was confirmed both experimentally and theoretically that specific throughput, defined as a ratio of throughput (Q) over screw speed (N), controlled all the above three types of residence distributions, be they local, partial or overall. The RRD and RVD do not provide more information on an extrusion process than the corresponding RTD. Rather they are different ways of representing the same phenomena. POLYM. ENG. SCI., 48:19–28, 2008. © 2007 Society of Plastics Engineers     

Mixing of a self-assembled supramolecular polymer and a covalent polymer in organic solutions

We report on a neutron scattering study of the molecular structure of a self-assembled supramolecular polymer composed of a bicopper complex within a solution of a covalent polymer (atactic polystyrene/trans-decalin). The study is achieved by putting two binary phases in contact and allowing for diffusion of both components in either phase. It is shown that the one-dimensional bicopper filaments are compatible to a high extent with the atactic polymer. These results are discussed in the light of a recently devised encapsulation process of the bicopper filaments within the fibrils of a physical network of isotactic polystyrene.     

Students’ performance and satisfaction with Web vs. paper-based practice quizzes and lecture notes

The use of computers to deliver course-related materials is rapidly expanding in most universities. Yet the effects of computer vs. printed delivery modes on students’ performance and motivation are not yet fully known. We compared the impacts of Web vs. paper to deliver practice quizzes that require information search in lecture notes. Hundred and twenty two undergraduate students used either a web site or printed documents to answer 18 mathematics questions during a tutored session. A revised Web site was designed based on ergonomic criteria, to test the hypothesis that improved usability would decrease time spent on the task, the number of pages consulted, and students’ perceived cognitive load. The group working with printed documents had the highest performance. Furthermore, students perceived the paper materials as less effortful to read, and expressed preference for printing lecture notes and questions. However, students appreciated having a Web site available. No differences were found between the two sites. We conclude that Web delivery imposed higher perceived cognitive load due to the need to read lengthy documents. We suggest possible ways to improve Web-based practice materials, such as simultaneous display of questions and lecture notes.     

On the cultural guises of cognitive dissonance: The case of Easterners and Westerners.

Cognitive dissonance and effects of self-affirmation on dissonance arousal were examined cross-culturally. In Studies 1 and 2, European Canadians justified their choices more when they made them for themselves, whereas Asian Canadians (Study 1) or Japanese (Study 2) justified their choices more when they made them for a friend. In Study 3, an interdependent self-affirmation reduced dissonance for Asian Canadians but not for European Canadians. In Study 4, when Asian Canadians made choices for a friend, an independent self-affirmation reduced dissonance for bicultural Asian Canadians but not for monocultural Asian Canadians. These studies demonstrate that both Easterners and Westerners can experience dissonance, but culture shapes the situations in which dissonance is aroused and reduced. Implications of these cultural differences for theories of cognitive dissonance and self-affirmation are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Revisiting the Roles of Filaggrin in Atopic Dermatitis

The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin.     

BK Polyomavirus bkv-miR-B1-5p: A Stable Micro-RNA to Monitor Active Viral Replication after Kidney Transplantation

Background: Bkv-miR-B1-5p is a viral micro-RNA (miRNA) specifically produced during BK polyomavirus (BKPyV) replication. Recent studies have suggested using bkv-miR-B1-5p as a biomarker to monitor viral infection and predict complications in kidney transplant patients. To identify the technical limitations of this miRNA quantification in biological samples, knowledge of its stability and distribution in the extracellular compartment is necessary. Moreover, a proof of concept for using bkv-miR-B1-5p as a biomarker of active replication in chronic infection is still missing in the published literature. Methods: The stability of bkv-miR-B1-5p was evaluated in samples derived from cell cultures and in urine from BKPyV-infected kidney transplant recipients. The miRNA was quantified in different fractions of the extracellular compartment, including exosomes, and protein binding was evaluated. Finally, we developed an in vitro model for chronic culture of BKPyV clinical isolates to observe changes in the bkv-miR-B1-5p level during persistent infections. Results: Bkv-miR-B1-5p is a stable biomarker in samples from humans and in vitro experiments. Marginally associated with the exosomes, most of the circulating bkv-miR-B1-5p is bound to proteins, especially Ago2, so the miRNA quantification does not require specific exosome isolation. The bkv-miR-B1-5p level is predictable of viral infectivity, which makes it a potential specific biomarker of active BKPyV replication after kidney transplantation.     

Radio‐opaque fecal impaction and pseudo‐occlusion in a dialyzed patient taking lanthanum carbonate

Lanthanum therapy is an efficient therapy of hyperphosphoremia by chelating phosphore in the digestive tract. Lanthanum is a silvery white metallic element that belongs to group 3 of the periodic table. This drug is lightly absorbed and has low water solubility. It should be borne in mind that abdominal X‐rays of patients taking lanthanum carbonate may have a radio‐opaque appearance typical of imaging agents. This characteristic is suggested to confirm adherence of the patient by doing an abdominal X‐ray. We describe in our case a particular good compliant patient with slow digestive transit, which ends by pseudo‐occlusion.     

Geometry control of the junction between two fractal curves

The general objective of our work is to create a geometric modeller based on iterative processes. With this objective in mind, we have to provide tools that work with fractal objects in the same manner as with objects of classical topology. In this article we focus on the constructing of an intermediate curve between two other curves defined by different iterative construction processes. A similar problem often arises with subdivision surfaces, when the goal is to connect two surfaces with different subdivision masks. We start by dealing with curves, willing to later generalise our approach to surfaces. We formalise the problem with the Boundary Controlled Iterated Function System model. Then we deduct the conditions that guarantees continuity of the intermediate curve. These conditions determine the structure of subdivision matrices. By studying the eigenvalues of the subdivision operators, we characterise the differential behaviour at the connection points between the curves and the intermediate one. This behaviour depends on the nature of the initial curves and coefficients of the subdivision matrices. We also suggest a method to control the differential behaviour by adding intermediate control points.     

Quantification of grain boundary defect chemistry in a mixed proton-electron conducting oxide composite

Dual phase oxide membranes have shown promising hydrogen permeation fluxes in syngas applications due to their high mixed proton electron conduction (MPEC). However, the conductivity of grain boundaries can be many orders of magnitude lower than that of the bulk and so limits the total conductivity and hydrogen permeation. In this study, the three-dimensional nanoscale oxygen and cation distributions around grain and phase boundaries in a BaCe_0.8Y_0.2O_3-δ-Ce_0.8Y_0.2O_2-δ (BCY-YDC) membrane were quantified by atom probe tomography (APT) and related to average grain boundary conductivity measured by electrochemical impedance spectroscopy (EIS). Segregation varied among the general high-angle grain boundaries analyzed, but no trend from orientation analysis was determined. Correlative APT and electron energy loss spectroscopy (EELS) of one YDC grain boundary revealed composition and cerium valence information, respectively, allowing for the determination of vacancies at the grain boundary. While a specific MPEC membrane is characterized, the results are relevant to proton and electron conduction in a number of technologically important ceramics.