Combined Nano‐ and Micro‐Scale Topographic Cues for Engineered Vascular Constructs by Electrospinning and Imprinted Micro‐Patterns

The major cause of synthetic vessel failure is thrombus and neointima formation. To prevent these problems the creation of a continuous and elongated endothelium inside lumen vascular grafts might be a promising solution for tissue engineering. Different micro‐ and nano‐surface topographic cues including grooved micro‐patterns and electrospun fibers have been previously demonstrated to guide the uniform alignment of endothelial cells (ECs). Here, with a very simple and highly versatile approach we combined electrospinning with soft lithography to fabricate nanofibrous scaffolds with oriented fibers modulated by different micro‐grooved topographies. The effect of these scaffolds on the behavior of the ECs are analyzed, including their elongation, spreading, proliferation, and functioning using unpatterned random and aligned nanofibers (NFs) as controls. It is demonstrated that both aligned NFs and micro‐patterns effectively influence the cellular response, and that a proper combination of topographic parameters, exploiting the synergistic effects of micro‐scale and sub‐micrometer features, can promote EC elongation, allowing the creation of a confluent ECs monolayer in analogy with the natural endothelium as assessed by the positive expression of vinculin. Combining different micro‐ and nano‐topographic cues by complementary soft patterning and spinning technologies could open interesting perspectives for engineered vascular replacement constructions.     

A large-scale investigation of lateralization in cortical anatomy and word reading: Are there sex differences?

The authors report findings of a large-scale, multitask investigation of sex differences in both structural asymmetries and lateralization of word reading. Two hundred participants were tested in eight divided visual field lexical tasks, and each received a structural magnetic resonance imaging scan. The authors examined whether there was evidence for sex differences in overall measures of neuroanatomical and behavioral lateralization, in specific language tasks and brain regions, and in variation in asymmetry within and across tasks and brain regions. There was very little evidence for sex differences on any behavioral measure. The few indications of sex differences in the current report accounted for 2% or less of the individual variation in asymmetry and could not be replicated in independent subsamples. No sex differences were observed in the asymmetry of structures in Broca's and Wernicke's areas such as pars triangularis, pars opercularis, the planum temporale, planum parietale, or Heschl's gyrus. There were also no sex differences in the variability of neuroanatomical asymmetries within or between brain regions. However, a significant relationship between planum temporale and behavioral asymmetry was restricted to men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The use and nature of present-focused interventions in cognitive and behavioral therapies for depression.

To improve cognitive and behavioral therapies (CBT) for depression, several approaches recommend an increased focus on the occurrence of problems as they occur in the therapeutic relationship or in relation to the live therapy process, referred to as present-focused. A lingering question has been the degree to which CBT therapists already engage in present-focused work. This study utilized sessions from recent trials of CBT for depression and, in Phase I, raters identified present-focused interventions on a turn-by-turn basis. Phase II raters used a qualitative analysis to determine categories of present-focused interventions. Results indicated that therapists rarely focused on the therapeutic relationship; when they did, it was often transient and lacking in the elaborations suggested by newer approaches. Therapists more often performed therapy process and emotion focused interventions, but these also tended to lack elaboration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Candida albicans homologue of GGP1/GAS1 gene is functional in Saccharomyces cerevisiae and contains the determinants for glycosylphosphatidylinositol attachment

The GGP1/GAS1/CWH52 gene of Saccharomyces cerevisiae encodes a major exocellular 115 kDa glycoprotein (gp115) anchored to the plasma membrane through a glycosylphosphatidylinositol (GPI). The function of gp115 is still unknown but the analysis of null mutants suggests a possible role in the control of morphogenesis. PHR1 gene isolated from Candida alibicans is homologous to the GGP1 gene. In this report we have analysed the ability of PHR1 to complement a ggp1Δ mutation in S. cerevisiae. The expression of PHR1 controlled by its natural promoter or by the GGP1 promoter has been studied. In both cases we have observed a complete complementation of the mutant phenotype. Moreover, immunological analysis has revealed that PHR1 in budding yeast gives rise to a 75–80 kDa protein anchored to the membrane through a GPI, indicating that the signal for GPI attachment present in the C. albicans gene product is functional in S. cerevisiae.     

Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs

The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ_1-42-induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins’ levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs.     

SI-ATRP Decoration of Magnetic Nanoparticles with PHEMA and Post-Polymerization Modification with Folic Acid for Tumor Cells’ Specific Targeting

Targeted nanocarriers could reach new levels of drug delivery, bringing new tools for personalized medicine. It is known that cancer cells overexpress folate receptors on the cell surface compared to healthy cells, which could be used to create new nanocarriers with specific targeting moiety. In addition, magnetic nanoparticles can be guided under the influence of an external magnetic field in different areas of the body, allowing their precise localization. The main purpose of this paper was to decorate the surface of magnetic nanoparticles with poly(2-hydroxyethyl methacrylate) (PHEMA) by surface-initiated atomic transfer radical polymerization (SI-ATRP) followed by covalent bonding of folic acid to side groups of the polymer to create a high specificity magnetic nanocarrier with increased internalization capacity in tumor cells. The biocompatibility of the nanocarriers was demonstrated by testing them on the NHDF cell line and folate-dependent internalization capacity was tested on three tumor cell lines: MCF-7, HeLa and HepG2. It has also been shown that a higher concentration of folic acid covalently bound to the polymer leads to a higher internalization in tumor cells compared to healthy cells. Last but not least, magnetic resonance imaging was used to highlight the magnetic properties of the functionalized nanoparticles obtained.     

Fundamental Clock of Biological Aging: Convergence of Molecular,Neurodegenerative, Cognitive and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology

In humans, age-associated degrading changes, widely observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psychological abilities, and memory. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, genome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirality, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs ^SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition of protein structure, makes them prone to multiple types of enzymatic and spontaneous PTMs, including racemization and isomerization. Spontaneous racemization leads to the loss of the balanced prevalent chirality. Advanced biological aging related to irreversible PTMs ^SP has been associated with the nontrivial interplay between somatic (molecular aging) and mental (psychological aging) health conditions. Through stress response systems (SRS), the environmental and psychological stressors contribute to the age-associated “collapse” of protein homochirality. The role of prevalent protein chirality and entropy of protein folding in biological aging is mainly overlooked. In a more generalized context, the time-dependent shift from enzymatic to the non-enzymatic transformation of biochirality might represent an important and yet underappreciated hallmark of aging. We provide the experimental arguments in support of the racemization theory of aging.