Neural cytoskeleton capabilities for learning and memory

This paper proposes a physical model involving the key structures within the neural cytoskeleton as major players in molecular-level processing of information required for learning and memory storage. In particular, actin filaments and microtubules are macromolecules having highly charged surfaces that enable them to conduct electric signals. The biophysical properties of these filaments relevant to the conduction of ionic current include a condensation of counterions on the filament surface and a nonlinear complex physical structure conducive to the generation of modulated waves. Cytoskeletal filaments are often directly connected with both ionotropic and metabotropic types of membrane-embedded receptors, thereby linking synaptic inputs to intracellular functions. Possible roles for cable-like, conductive filaments in neurons include intracellular information processing, regulating developmental plasticity, and mediating transport. The cytoskeletal proteins form a complex network capable of emergent information processing, and they stand to intervene between inputs to and outputs from neurons. In this manner, the cytoskeletal matrix is proposed to work with neuronal membrane and its intrinsic components (e.g., ion channels, scaffolding proteins, and adaptor proteins), especially at sites of synaptic contacts and spines. An information processing model based on cytoskeletal networks is proposed that may underlie certain types of learning and memory

Effects of pseudomonas fluorescens seed bioinoculation on heavy metal accumulation for mirabilis jalapa phytoextraction in smelter-contaminated soil

Some Pseudomonas fluorescens strains, consistently isolated from the rhizosphere of wild plants grown in a soil that was highly polluted with illegal waste of smelter residues, were utilised for Mirabilis jalapa seed bioinoculation to verify their effects on seed germination and on promoting a higher heavy metal accumulation in the plant rhizosphere and/or uptake in the leaves. The high content of heavy metals in the soil induced a decrease in either the leaf dry weight or photosynthetic pigment concentration during all vegetative phase of M. jalapa. Bioinoculation with P. fluorescens strains significantly increased the germination of seeds and the root length in the contaminated soil. In some bacterial strain/seed combination, bioinoculation significantly increased the accumulation of heavy metals in M. jalapa rhizosphere. For Cd, the concentration of this metal in the rhizospheres of bioinoculated plants ranged from 270 to 910 μg g-1 of dry weight compared with 200 μg g-1 of dry weight for the non-coated plants. Two P. fluorescens strains, AA27 and MO49, which were isolated from Artemisia annua and Melilotus officinalis, respectively, induced a significantly higher rhizosphere availability also for Cr, Cu, Ni and Zn. However, despite the relevant accumulation of the heavy metals in the plant rhizosphere, generally the metal uptake into the leaves was rather low. Both analysis of variance and principal component analysis confirmed this finding. However, one P. fluorescens strain, CD1, which was isolated from the multi-metal accumulator Cynodon dactylon, significantly promoted the M. jalapa leaf uptake for Cr, Cu and Zn. The plant metal uptake assessment, confirmed the per se capability of M. jalapa to effectively uptake Cd (30 %) and Cu (12.72 %) from the rhizosphere to the leaves, whereas the uptake for the other metals was low: Ni (2.66 %), Zn (2.46 %), Cr (1.75 %), Pb (0.73 %). © 2013 Springer Science+Business Media Dordrecht

Genetic pathways to glioblastoma: a population-based study

We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months (80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms

Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas

We carried out a population-based study on low-grade diffuse gliomas in the Canton of Zurich, Switzerland (population 1.16 million). From 1980 to 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 122 (12.4%) were low-grade (WHO grade II). The incidence rates adjusted to the World Standard Population, per million population per year, were 2.28 for low-grade diffuse astrocytomas, 0.89 for oligoastrocytomas, and 2.45 for oligodendrogliomas. The survival rate (mean follow-up 7.5+/-4.8 years) was highest for patients with oligodendroglioma (78% at 5 years, 51% at 10 years), followed by those with oligoastrocytoma (70% at 5 years, 49% at 10 years) and fibrillary astrocytoma (65% at 5 years, 31% at 10 years). Survival of patients with gemistocytic astrocytoma was poor, with survival rates of 16% at 5 years and 0% at 10 years. Younger patients (50 years; P=0.013). DNA sequencing, performed in 84% of cases, revealed that TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but were infrequent (13%) in oligodendrogliomas. The presence of TP53 mutations was associated with shorter survival of patients with low-grade diffuse gliomas (log-rank test; P=0.047), but when each histological type was analyzed separately, an association was observed only for oligoastrocytoma ( P=0.05). Loss on 1p and 19q were assessed by quantitative microsatellite analysis in 67% of cases. These alterations were frequent in oligodendrogliomas (1p, 57%; 19q, 69%), less common in oligoastrocytomas (1p, 27%; 19q, 45%), rare in fibrillary astrocytomas (1p, 7%; 19q, 7%), and absent in gemistocytic astrocytomas. None of these alterations were predictive of survival. These results establish the frequency of key genetic alterations in low-grade diffuse gliomas at a population-based level. Multivariate Cox's regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors