Revisiting Nonlinear Functional Brain Co-activations: Directed, Dynamic, and Delayed.

The center stage of neuro-imaging is currently occupied by studies of functional correlations between brain regions. These correlations define the brain functional networks, which are the most frequently used framework to represent and interpret a variety of experimental findings. In the previous study, we first demonstrated that the relatively stronger blood oxygenated level dependent (BOLD) activations contain most of the information relevant to understand functional connectivity, and subsequent work confirmed that a large compression of the original signals can be obtained without significant loss of information. In this study, we revisit the correlation properties of these epochs to define a measure of nonlinear dynamic directed functional connectivity (nldFC) across regions of interest. We show that the proposed metric provides at once, without extensive numerical complications, directed information of the functional correlations, as well as a measure of temporal lags across regions, overall offering a different and complementary perspective in the analysis of brain co-activation patterns. In this study, we provide further details for the computations of these measures and for a proof of concept based on replicating existing results from an Autistic Syndrome database, and discuss the main features and advantages of the proposed strategy for the study of brain functional correlations.

Effect of bioglass nanoparticles on the properties and bioactivity of poly(lactic acid) films.

Bioglass nanoparticles (n-BGs, 54SiO2 :40CaO:6P2 O5 mol %) with about 27 nm diameter were synthesized by the sol-gel method and incorporated into a poly(lactic acid) (PLA) matrix by the melting process in order to obtain nanocomposites with filler contents of 5, 10, and 25 wt %. Our results showed that during the cooling scan, the crystallization temperature (Tc ) of the PLA/n-BG nanocomposites decreased 13°C as compared to neat PLA. The presence of nanoparticles also decreased the thermal stability of the PLA matrix, as nanocomposites presented up to about 20°C lower degradation temperatures in a nitrogen atmosphere. The presence of n-BG increased the stiffness of the polymer matrix, and for instance the composite with 25 wt % of filler presented about 52.6% higher Young's modulus than neat PLA. n-BG incorporation into PLA increased also the hydrolytic degradation of the polymer over time. When the PLA composites were immersed in simulated body fluid, an apatite layer was formed on their surface, as verified by Fourier transform infrared, X-Ray Diffraction (XRD), and scanning electron microscopy-EDS, showing that the presence of n-BG induced bioactivity on the PLA matrix. Moreover, the viability of cervical uterine adenocarcinoma cells was higher on PLA/n-BG nanocomposite with 25 wt % of filler. The presence of n-BG barely gave an antibacterial effect on the polymer matrix, despite the well-known biocidal properties of these nanoparticles. Our results show that the presence of n-BGs is a proper route for improving the bioactivity of PLA with potential application in tissue engineering.

Prevention of senescence progression in reversibly immortalized human ensheathing glia permits their survival after deimmortalization.

Reversible immortalization holds great potential for primary tissue expansion to develop cell-based therapies as well as for basic research. Human olfactory ensheathing glia (hOEG) are promising candidates for treating spinal cord injury and for studying extrinsic neuroregenerative mechanisms. We used lentivectors with Cre/loxP technology to achieve reversible gene transfer of BMI1, SV40 large T antigen (TAg), a short hairpin RNA against p53 (shp53), and the catalytic subunit of telomerase (TERT) in primary cultures of hOEG from human donor cadaver olfactory bulbs. Several combinations of these genes were able to immortalize hOEG, conserving their antigenic markers and neuroregenerative properties but only those transduced by BMI1/TERT did not accumulate karyotypic alterations or increase senescence marker levels. Strikingly, these were also the only cells which continued to proliferate after transgene removal by Cre recombinase delivery, whereas hOEG immortalized by shp53 or TAg in combination with TERT entered into growth arrest and died. These data support the idea that immortalization and halting senescent changes are separate processes; hOEG immortalized by BMI1/TERT can revert back to their former primary cell replicative state when deimmortalized, whereas those transduced by the other combinations depend on the presence of these transgenes to maintain their aberrant proliferative state.