Effects of traumatic brain injury on working memory-related brain activation in adolescents.

Eight adolescents (ages 13-18 years) who sustained traumatic brain injury (TBI) and eight gender- and age-matched typically developing (TD) adolescents underwent event-related functional MRI (fMRI) while performing a Sternberg letter recognition task. Encoding, maintenance, and retrieval were examined with memory loads of one or four items during imaging. Both groups performed above a 70% accuracy criterion and did not differ in performance. TD adolescents showed greater increase in frontal and parietal activation during high-load relative to low-load maintenance than the TBI group. The TBI patients showed greater increase in activation during high-load relative to low-load encoding and retrieval than the TD group. Results from this preliminary study suggest that the capability to differentially allocate neural resources according to memory load is disrupted by TBI for the maintenance subcomponent of working memory. The overrecruitment of frontal and extrafrontal regions during encoding and retrieval following TBI may represent a compensatory process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Insights into the Pharmacokinetics and In Vitro Cell-Based Studies of the Imidazoline I2 Receptor Ligand B06

The impact of neurodegenerative diseases (ND) is becoming unbearable for humankind due to their vast prevalence and the lack of efficacious treatments. In this scenario, we focused on imidazoline I₂ receptors (I₂-IR) that are widely distributed in the brain and are altered in patients with brain disorders. We took the challenge of modulating I₂-IR by developing structurally new molecules, in particular, a family of bicyclic α-iminophosphonates, endowed with high affinity and selectivity to these receptors. Treatment of two murine models, one for age-related cognitive decline and the other for Alzheimer’s disease (AD), with representative compound B06 ameliorated their cognitive impairment and improved their behavioural condition. Furthermore, B06 revealed beneficial in vitro ADME-Tox properties. The pharmacokinetics (PK) and metabolic profile are reported to de-risk B06 for progressing in the preclinical development. To further characterize the pharmacological properties of B06, we assessed its neuroprotective properties and beneficial effect in an in vitro model of Parkinson’s disease (PD). B06 rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine (6-OHDA) and showed a crucial anti-inflammatory effect in a cellular model of neuroinflammation. This research reveals B06 as a putative candidate for advancing in the difficult path of drug discovery and supports the modulation of I₂-IR as a fresh approach for the therapy of ND.     

Raman spectroscopy and X-ray diffraction studies of stress effects in PbTiO3 thin films

A systematic study of domain structure and residual stress evolution with film thickness and of phase transition in c/a epitaxial PbTiO(3)/LaAlO(3) films using X-ray diffraction and Raman spectroscopy is reported. Both techniques revealed that the films are under tensile residual stress in the film plane and that a-domains are more stressed than c-domains. The two components of the large A(1)(TO) Ramanmodes are associated with a- and c-domains and their intensity ratio correlates to the volume fraction of a-domains. The evolution of the Raman signature with temperature revealed that the spectrum of a-domains disappears around 480 degrees C, whereas c-domains present an anomaly in their spectrum at 500 degrees C but maintain a well-defined Raman signature up to 600 degrees C.     

Plant DNA Methylation: An Epigenetic Mark in Development,Environmental Interactions,and Evolution

DNA methylation is an epigenetic modification of the genome involved in the regulation of gene expression and modulation of chromatin structure. Plant genomes are widely methylated, and the methylation generally occurs on the cytosine bases through the activity of specific enzymes called DNA methyltransferases. On the other hand, methylated DNA can also undergo demethylation through the action of demethylases. The methylation landscape is finely tuned and assumes a pivotal role in plant development and evolution. This review illustrates different molecular aspects of DNA methylation and some plant physiological processes influenced by this epigenetic modification in model species, crops, and ornamental plants such as orchids. In addition, this review aims to describe the relationship between the changes in plant DNA methylation levels and the response to biotic and abiotic stress. Finally, we discuss the possible evolutionary implications and biotechnological applications of DNA methylation.     

LncRNA H19 Impairs Chemo and Radiotherapy in Tumorigenesis

Various treatments based on drug administration and radiotherapy have been devoted to preventing, palliating, and defeating cancer, showing high efficiency against the progression of this disease. Recently, in this process, malignant cells have been found which are capable of triggering specific molecular mechanisms against current treatments, with negative consequences in the prognosis of the disease. It is therefore fundamental to understand the underlying mechanisms, including the genes—and their signaling pathway regulators—involved in the process, in order to fight tumor cells. Long non-coding RNAs, H19 in particular, have been revealed as powerful protective factors in various types of cancer. However, they have also evidenced their oncogenic role in multiple carcinomas, enhancing tumor cell proliferation, migration, and invasion. In this review, we analyze the role of lncRNA H19 impairing chemo and radiotherapy in tumorigenesis, including breast cancer, lung adenocarcinoma, glioma, and colorectal carcinoma.     

Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach

A key aspect of cytokine-induced changes as observed in sepsis is the dysregulated activation of endothelial cells (ECs), initiating a cascade of inflammatory signaling leading to leukocyte adhesion/migration and organ damage. The therapeutic targeting of ECs has been hampered by concerns regarding organ-specific EC heterogeneity and their response to inflammation. Using in vitro and in silico analysis, we present a comprehensive analysis of the proteomic changes in mouse lung, liver and kidney ECs following exposure to a clinically relevant cocktail of proinflammatory cytokines. Mouse lung, liver and kidney ECs were incubated with TNF-α/IL-1β/IFN-γ for 4 or 24 h to model the cytokine-induced changes. Quantitative label-free global proteomics and bioinformatic analysis performed on the ECs provide a molecular framework for the EC response to inflammatory stimuli over time and organ-specific differences. Gene Ontology and PANTHER analysis suggest why some organs are more susceptible to inflammation early on, and show that, as inflammation progresses, some protein expression patterns become more uniform while additional organ-specific proteins are expressed. These findings provide an in-depth understanding of the molecular changes involved in the EC response to inflammation and can support the development of drugs targeting ECs within different organs. Data are available via ProteomeXchange (identifier PXD031804).     

Robust invariant sets for constrained storage systems

Several items are produced and stored into n buffers in order to supply an external demand without interruptions. We consider the classical problem of determining control laws and smallest buffer levels guaranteeing that an unknown bounded demand is always satisfied. A simple model with n decoupled integrators and n additive bounded disturbances is employed. The coupling arises from bounds on the total production capacity and on the total demand. Invariant set theory for linear and switched linear systems is exploited to compute robust positive invariant sets and controlled robust invariant sets for two commonly adopted scheduling policies. This paper provides the explicit expression of the invariant sets for any arbitrary n.     

A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications

Three-dimensional (3D) bioprinting is an innovative technology in the biomedical field, allowing the fabrication of living constructs through an approach of layer-by-layer deposition of cell-laden inks, the so-called bioinks. An ideal bioink should possess proper mechanical, rheological, chemical, and biological characteristics to ensure high cell viability and the production of tissue constructs with dimensional stability and shape fidelity. Among the several types of bioinks, hydrogels are extremely appealing as they have many similarities with the extracellular matrix, providing a highly hydrated environment for cell proliferation and tunability in terms of mechanical and rheological properties. Hydrogels derived from natural polymers, and polysaccharides, in particular, are an excellent platform to mimic the extracellular matrix, given their low cytotoxicity, high hydrophilicity, and diversity of structures. In fact, polysaccharide-based hydrogels are trendy materials for 3D bioprinting since they are abundant and combine adequate physicochemical and biomimetic features for the development of novel bioinks. Thus, this review portrays the most relevant advances in polysaccharide-based hydrogel bioinks for 3D bioprinting, focusing on the last five years, with emphasis on their properties, advantages, and limitations, considering polysaccharide families classified according to their source, namely from seaweed, higher plants, microbial, and animal (particularly crustaceans) origin.     

Thiophene‐ and silarylene‐containing polyesters. Resonance effect on conductivity after polarization in an external electric field

Polyesters were synthesized by direct polycondensation of thiophene‐2,5‐dicarboxylic acid and five different silarylene‐containing diphenols using a tosyl chloride/pyridine/N,N‐dimethylformamide system as a condensing agent. Polymers were obtained in good yields and were characterized using Fourier transform infrared and NMR (¹H, ¹³C, 135‐DEPT and ²⁹Si) spectroscopy and elemental analysis. All polymers were completely soluble in aprotic organic polar solvents such as dimethylformamide, dimethylsulfoxide and N‐methyl‐2‐pyrrolidone. The range of effective mass of the polymers (m/z) was 1 × 10⁵–2 × 10⁵, determined using electrospray ionization mass spectrometry. Asymmetry and steric hindrance prevented dense packing of the polymeric chains, showing glass transition temperatures between ? 78 and ? 51 °C and loss of thermal stability at 177–199 °C (10% weight loss). Additionally, the melting points of the polyesters were found to be in the range 62–67 °C. Because of this, the samples were semi‐solid at room temperature. The optical band gaps of the polymers were observed between 4.54 and 4.48 eV, corresponding in all cases to insulator behavior. The molecular structure of the samples was studied using X‐ray diffraction, showing a degree of order that was associated with two monoclinic lattices. Additionally, the conductivity was studied using a two‐point method with contacts on top of polymer films. Prior to the electrical measurement, the samples were polarized in an external electric field of 0.8 to 6.4 V cm^?1, and the alignment of the dipoles increased the electrical conductivity. Copyright © 2012 Society of Chemical Industry