Cardiovascular and Coordination Training Differentially Improve Cognitive Performance and Neural Processing in Older Adults

Recent studies revealed a positive influence of physical activity on cognitive functioning in older adults. Studies that investigate the behavioral and neurophysiological effects of type and long term duration of physical training, however, are missing. We performed a 12-month longitudinal study to investigate the effects of cardiovascular and coordination training (control group: relaxation and stretching) on cognitive functions (executive control and perceptual speed) in older adults. We analyzed data of 44 participants aged 62–79 years. Participants were trained three times a week for 12 months. Their physical and cognitive performance was tested prior to training, and after 6 and 12 months. Changes in brain activation patterns were investigated using functional MRI. On the behavioral level, both experimental groups improved in executive functioning and perceptual speed but with differential effects on speed and accuracy. In line with the behavioral findings, neurophysiological results for executive control also revealed changes (increases and reductions) in brain activity for both interventions in frontal, parietal, and sensorimotor cortical areas. In contrast to the behavioral findings, neurophysiological changes were linear without indication of a plateau. In both intervention groups, prefrontal areas showed decreased activation after 6 and 12 months when performing an executive control task, as compared to the control group, indicating more efficient information processing. Furthermore, cardiovascular training was associated with an increased activation of the sensorimotor network, whereas coordination training was associated with increased activation in the visual–spatial network. Our data suggest that besides cardiovascular training also other types of physical activity improve cognition of older adults. The mechanisms, however, that underlie the performance changes seem to differ depending on the intervention

La nitragina : Empleo de cultivos puros de bacterias de las leguminosas

Se sabe por qué fases ha pasado esta cuestión de la nutrición azoada de las leguminosas, desde las primeras investigaciones de Boussingault hasta las de d’Hellriegel y Wilfartg, que arrojaron una luz casi completa sobre este asunto. Como dignos continuadores del malogrado d'Hellriegel, es necesario citar á Beyerinck, que precisó la naturaleza de las nudosidades, y a Nobbe que ha procurado utilizar el descubrimiento del agrónomo de Pernbourg.Facultad de Ciencias Agrarias y Forestale

Effectiveness of porous silicon nanoparticle treatment at inhibiting the migration of a heterogeneous glioma cell population

Background: Approximately 80% of brain tumours are gliomas. Despite treatment, patient mortality remains high due to local metastasis and relapse. It has been shown that transferrin-functionalised porous silicon nanoparticles (Tf@pSiNPs) can inhibit the migration of U87 glioma cells. However, the underlying mechanisms and the effect of glioma cell heterogeneity, which is a hallmark of the disease, on the efficacy of Tf@pSiNPs remains to be addressed. Results: Here, we observed that Tf@pSiNPs inhibited heterogeneous patient-derived glioma cells’ (WK1) migration across small perforations (3 μm) by approximately 30%. A phenotypical characterisation of the migrated subpopulations revealed that the majority of them were nestin and fibroblast growth factor receptor 1 positive, an indication of their cancer stem cell origin. The treatment did not inhibit cell migration across large perforations (8 μm), nor cytoskeleton formation. This is in agreement with our previous observations that cellular-volume regulation is a mediator of Tf@pSiNPs’ cell migration inhibition. Since aquaporin 9 (AQP9) is closely linked to cellular-volume regulation, and is highly expressed in glioma, the effect of AQP9 expression on WK1 migration was investigated. We showed that WK1 migration is correlated to the differential expression patterns of AQP9. However, AQP9-silencing did not affect WK1 cell migration across perforations, nor the efficacy of cell migration inhibition mediated by Tf@pSiNPs, suggesting that AQP9 is not a mediator of the inhibition. Conclusion: This in vitro investigation highlights the unique therapeutic potentials of Tf@pSiNPs against glioma cell migration and indicates further optimisations that are required to maximise its therapeutic efficacies. Graphic Abstract: [Figure not available: see fulltext.

La nitragina : Empleo de cultivos puros de bacterias de las leguminosas

Se sabe por qué fases ha pasado esta cuestión de la nutrición azoada de las leguminosas, desde las primeras investigaciones de Boussingault hasta las de d’Hellriegel y Wilfartg, que arrojaron una luz casi completa sobre este asunto. Como dignos continuadores del malogrado d'Hellriegel, es necesario citar á Beyerinck, que precisó la naturaleza de las nudosidades, y a Nobbe que ha procurado utilizar el descubrimiento del agrónomo de Pernbourg.Facultad de Ciencias Agrarias y Forestale

A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye.

Author version made available in accordance with the Publisher's policy, after an embargo period of 12 months from the date of publication. © 2015. Licensed under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Dysfunction of corneal epithelial stem cells can result in painful and blinding disease of the ocular surface. In such cases, treatment may involve transfer of growth factor and normal adult stem cells to the ocular surface. Our purpose was to develop an implantable scaffold for the delivery of drugs and cells to the ocular surface. We examined the potential of novel composite biomaterials fabricated from electrospun polycaprolactone (PCL) fibres into which nanostructured porous silicon (pSi) microparticles of varying sizes (150-250 μm or <40 μm) had been pressed. The PCL fabric provided a flexible support for mammalian cells, whereas the embedded pSi provided a substantial surface area for efficient delivery of adsorbed drugs and growth factors. Measurements of tensile strength of these composites revealed that the pSi did not strongly influence the mechanical properties of the polymer microfiber component for the Si loadings evaluated. Human lens epithelial cells (SRA01/04) attached to the composite materials, and exhibited enhanced attachment and growth when the materials were coated with foetal bovine serum. To examine the ability of the materials to deliver a small-drug payload, pSi microparticles were loaded with fluorescein diacetate prior to cell attachment. After 6 hours (h), cells exhibited intracellular fluorescence, indicative of transfer of the fluorescein diacetate into viable cells and its subsequent enzymatic conversion to fluorescein. To investigate loading of large-molecule biologics, murine BALB/c 3T3 cells, responsive to epidermal growth factor, insulin and transferrin, were seeded on composite materials. The cells showed significantly more proliferation at 48 h when seeded on composites loaded with these biologics, than on unloaded composites. No cell proliferation was observed on PCL alone, indicating the biologics had loaded into the pSi microparticles. Drug release, measured by ELISA for insulin, indicated a burst followed by a slower, continuous release over six days. When implanted under the rat conjunctiva, the most promising composite material did not cause significant neovascularization but did elicit a macrophage and mild foreign body response. These novel pressed pSi-PCL materials have potential for delivery of both small and large drugs that can be released in active form, and can support the growth of mammalian cells

Non-viral gene therapy that targets motor neurons in vivo

A major challenge in neurological gene therapy is safe delivery of transgenes to sufficient cell numbers from the circulation or periphery. This is particularly difficult for diseases involving spinal cord motor neurons such as amyotrophic lateral sclerosis (ALS). We have examined the feasibility of non-viral gene delivery to spinal motor neurons from intraperitoneal injections of plasmids carried by "immunogene" nanoparticles targeted for axonal retrograde transport using antibodies. PEGylated polyethylenimine (PEI-PEG12) as DNA carrier was conjugated to an antibody (MLR2) to the neurotrophin receptor p75 (p75NTR). We used a plasmid (pVIVO2) designed for in vivo gene delivery that produces minimal immune responses, has improved nuclear entry into post mitotic cells and also expresses green fluorescent protein (GFP). MLR2-PEI-PEG12 carried pVIVO2 and was specific for mouse motor neurons in mixed cultures containing astrocytes. While only 8% of motor neurons expressed GFP 72 h post transfection in vitro, when the immunogene was given intraperitonealy to neonatal C57BL/6J mice, GFP specific motor neuron expression was observed in 25.4% of lumbar, 18.3% of thoracic and 17.0% of cervical motor neurons, 72 h post transfection. PEI-PEG12 carrying pVIVO2 by itself did not transfect motor neurons in vivo, demonstrating the need for specificity via the p75NTR antibody MLR2. This is the first time that specific transfection of spinal motor neurons has been achieved from peripheral delivery of plasmid DNA as part of a non-viral gene delivery agent. These results stress the specificity and feasibility of immunogene delivery targeted for p75NTR expressing motor neurons, but suggests that further improvements are required to increase the transfection efficiency of motor neurons in vivo.Mary-Louise Rogers, Kevin S. Smith, Dusan Matusica, Matthew Fenech, Lee Hoffman, Robert A. Rush and Nicolas H. Voelcke

Oral mucosal epithelial cells grown on porous silicon membrane for transfer to the rat eye

Dysfunction of limbal stem cells or their niche can result in painful, potentially sight-threatening ocular surface disease. We examined the utility of surface-modified porous-silicon (pSi) membranes as a scaffold for the transfer of oral mucosal cells to the eye. Male-origin rat oral mucosal epithelial cells were grown on pSi coated with collagen-IV and vitronectin, and characterised by immunocytochemistry. Scaffolds bearing cells were implanted into normal female rats, close to the limbus, for 8 weeks. Histology, immunohistochemistry and a multiplex nested PCR for sry were performed to detect transplanted cells. Oral mucosal epithelial cells expanded on pSi scaffolds expressed the corneal epithelial cell marker CK3/12. A large percentage of cells were p63⁺, indicative of proliferative potential, and a small proportion expressed ABCG2⁺, a putative stem cell marker. Cell-bearing scaffolds transferred to the eyes of live rats, were well tolerated, as assessed by endpoint histology. Immunohistochemistry for pan-cytokeratins demonstrated that transplanted epithelial cells were retained on the pSi membranes at 8 weeks post-implant, but were not detectable on the central cornea using PCR for sry. The pSi scaffolds supported and retained transplanted rat oral mucosal epithelial cells in vitro and in vivo and recapitulate some aspects of an artificial stem cell niche.Yazad D. Irani, Sonja Klebe, Steven J.P. McInnes, Marek Jasieniak, Nicolas H. Voelcker, Keryn A. William

Nitric oxide releasing plasma polymer coating with bacteriostatic properties and no cytotoxic side effects

Published on 19 March 2015We report a stable plasma polymer coating, using isopentyl nitrite as a volatile precursor, which releases nitric oxide at bacteriostatic concentrations when contacted with water, inhibiting bacterial growth without cytotoxic side effects to human mesenchymal stem/stromal cells.Thomas D. Michl, Bryan R. Coad, Michael Doran, Michael Osiecki, Morteza Hasanzadeh Kafshgari, Nicolas H. Voelcker, Amanda Hüsler, Krasimir Vasilev and Hans J. Griesse

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.</p