Genescene: Biomedical Text and Data Mining

To access the content of digital texts efficiently, it is necessary to provide more sophisticated access than keyword based searching. GeneScene provides biomedical researchers with research findings and background relations automatically extracted from text and experimental data. These provide a more detailed overview of the information available. The extracted relations were evaluated by qualified researchers and are precise. A qualitative ongoing evaluation of the current online interface indicates that this method to search the literature is more useful and efficient than keyword based searching

miRNA Expression Profiling in Migrating Glioblastoma Cells: Regulation of Cell Migration and Invasion by miR-23b via Targeting of Pyk2

Glioblastoma (GB) is the most common and lethal type of primary brain tumor. Clinical outcome remains poor and is essentially palliative due to the highly invasive nature of the disease. A more thorough understanding of the molecular mechanisms that drive glioma invasion is required to limit dispersion of malignant glioma cells.We investigated the potential role of differential expression of microRNAs (miRNA) in glioma invasion by comparing the matched large-scale, genome-wide miRNA expression profiles of migrating and migration-restricted human glioma cells. Migratory and migration-restricted cell populations from seven glioma cell lines were isolated and profiled for miRNA expression. Statistical analyses revealed a set of miRNAs common to all seven glioma cell lines that were significantly down regulated in the migrating cell population relative to cells in the migration-restricted population. Among the down-regulated miRNAs, miR-23b has been reported to target potential drivers of cell migration and invasion in other cell types. Over-expression of miR-23b significantly inhibited glioma cell migration and invasion. A bioinformatics search revealed a conserved target site within the 3' untranslated region (UTR) of Pyk2, a non-receptor tyrosine kinase previously implicated in the regulation of glioma cell migration and invasion. Increased expression of miR-23b reduced the protein expression level of Pyk2 in glioma cells but did not significantly alter the protein expression level of the related focal adhesion kinase FAK. Expression of Pyk2 via a transcript variant missing the 3'UTR in miR-23b-expressing cells partially rescued cell migration, whereas expression of Pyk2 via a transcript containing an intact 3'UTR failed to rescue cell migration.Reduced expression of miR-23b enhances glioma cell migration in vitro and invasion ex vivo via modulation of Pyk2 protein expression. The data suggest that specific miRNAs may regulate glioma migration and invasion to influence the progression of this disease

Homologous organization of cerebellar pathways to sensory, motor, and associative forebrain.

Cerebellar outputs take polysynaptic routes to reach the rest of the brain, impeding conventional tracing. Here, we quantify pathways between the cerebellum and forebrain by using transsynaptic tracing viruses and a whole-brain analysis pipeline. With retrograde tracing, we find that most descending paths originate from the somatomotor cortex. Anterograde tracing of ascending paths encompasses most thalamic nuclei, especially ventral posteromedial, lateral posterior, mediodorsal, and reticular nuclei. In the neocortex, sensorimotor regions contain the most labeled neurons, but we find higher densities in associative areas, including orbital, anterior cingulate, prelimbic, and infralimbic cortex. Patterns of ascending expression correlate with c-Fos expression after optogenetic inhibition of Purkinje cells. Our results reveal homologous networks linking single areas of the cerebellar cortex to diverse forebrain targets. We conclude that shared areas of the cerebellum are positioned to provide sensory-motor information to regions implicated in both movement and nonmotor function

Polymorphism of microsattelite loci within the grape germplasm collection maintained at the Dagestan Experiment Station of VIR

Background. Ampelographical collection of the VIR experiment station in Dagestan comprises 320 accessions of grape cultivars and 25 ecotypes of wild grape species, that are highly polymorphic in their morphological traits. As for any other large germplasm collections, the problem of genetic identification of the accessions and their originality is critical for the ampelographical collection. Genome of Vitis vinifera L. contains many polymorphic microsatellite loci, their allele diversity could be used to reveal the genetic structure of the ex situ collection as well as for the identification of duplicates. The task of the study was to estimate the level of polymorphism of four microsatellite loci that were previously recommended for the genotyping purposes in grape. The grape collection of Dagestan experiment station of VIR was investigated.Materials and methods. The analysis of microsatellite loci was based on PCR with the primers that were published previously. The size of alleles was estimated with Nanophor 05 sequencer (Syntol, Moscow). The results of the collection screening with the microsatellite markers were analyzed with Structure 2.3.4 software. The main characteristics of microsatellite loci (Polymorphic Information Content, heterozygosity) were determined using GenAlEx 6.2 program.Results and conclusion. The high level of polymorphism of the microsatellite loci VVS2, VVMD27, VVMD31, VVMD28 were detected when studying 221 accessions of the grape collection at the Dagestan experiment station. Heterozygosity of the loci was 0,50-0,83, the number of alleles per locus varied between 17 and 19, in total 70 alleles was detected. No relationship was detected between the allele combinations of accessions and their eco-geographical origin or any particular cultivar group. To reveal the genetic structure of the grape germplasm collection the larger number of SSR loci should be involved

NHERF-1: Modulator of Glioblastoma Cell Migration and Invasion1,2

The invasive nature of malignant gliomas is a clinical problem rendering tumors incurable by conventional treatment modalities such as surgery, ionizing radiation, and temozolomide. Na+/H+ exchanger regulatory factor 1 (NHERF-1) is a multifunctional adaptor protein, recruiting cytoplasmic signaling proteins and membrane receptors/transporters into functional complexes. This study revealed that NHERF-1 expression is increased in highly invasive cells that reside in the rim of glioblastoma multiforme (GBM) tumors and that NHERF-1 sustains glioma migration and invasion. Gene expression profiles were evaluated from laser capture-microdissected human GBM cells isolated from patient tumor cores and corresponding invaded white matter regions. The role of NHERF-1 in the migration and dispersion of GBM cell lines was examined by reducing its expression with small-interfering RNA followed by radial migration, three-dimensional collagen dispersion, immunofluorescence, and survival assays. The in situ expression of NHERF-1 protein was restricted to glioma cells and the vascular endothelium, with minimal to no detection in adjacent normal brain tissue. Depletion of NHERF-1 arrested migration and dispersion of glioma cell lines and caused an increase in cell-cell cohesiveness. Glioblastoma multiforme cells with depleted NHERF-1 evidenced a marked decrease in stress fibers, a larger cell size, and a more rounded shape with fewer cellular processes. When NHERF-1 expression was reduced, glioma cells became sensitized to temozolomide treatment resulting in increased apoptosis. Taken together, these results provide the first evidence for NHERF-1 as a participant in the highly invasive phenotype of malignant gliomas and implicate NHERF-1 as a possible therapeutic target for treatment of GBM

Simultaneous determination of polyphenol content

Vitis amurensis Ruprecht contains a large number of polyphenolic compounds which are biologically active components. For the most efficient and safe extraction supercritical carbon dioxide was used. In this work, for the first time, a comparative metabolomic study of biologically active substances of wild grapes collected from five different places of the Primorsky and Khabarovsk territories is carried out. To identify target analytes in ethanol extracts of grape berries, high performance liquid chromatography (HPLC) was used in combination with an amaZon SL ion trap (manufactured by BRUKER DALTONIKS, Germany) equipped with an ESI electrospray ionization source in negative and positive ion modes. The mass spectrometer was used in the scan range m / z 100 - 1.700 for MS and MS / MS. Used fragmentation of the 4th order. Primary mass spectrometric results showed the presence of 94 biologically active compounds corresponding to the species V. amurensis, moreover, salvianolic acids F, D and G, oleanoic, ursolic, myristoleic acids, berbericinin, mearnsetin, esculin, nevadensin, stigmasterol, fucosterol, phlorizin, L-tryptophan identified for the first time in V. amurensis