Rapid degradation of FAD following lysis of Neurospora crassa cells: Consequences for evaluation of flavin composition in vivo.

Rapid degradation of FAD following lysis of Neurospora crassa cells: Consequences for evaluation of flavin composition in vivo

The Isospin Distribution of Fragments in Reactions 96Ru+96Ru, 96Ru+96Zr, 96Zr+96Ru, and 96Zr+96Zr at Beam Energy 400 AMeV

The isospin distribution of particles and fragments in collisions 96Ru+96Ru, 96Ru+96Zr, 96Zr+96Ru, and 96Zr+96Zr at beam energy 400 AMeV is studied with isospin dependent QMD model. We find that the rapidity distribution of differential neutron-proton counting in neutron rich nucleus-nucleus collisions at intermediate energies is sensitive to the isospin dependent part of nuclear potential. The study of the N/Z ratio of nucleons, light charged particles (LCP) and intermediate mass fragments (IMF) shows that the isospin dependent part of nuclear potential drives IMF to be more isospin symmetric and emitted nucleons to be more neutron rich. From the study of the time evolution of the isospin distribution in emitted nucleons, LCP and IMF we find that neutrons diffuse much faster than protons at beginning and the final isospin distribution is a result of dynamical balance of symmetry potential and Coulomb force under the charge conservation.Comment: 10 pages, 5 figure

Auditory language comprehension in children with developmental dyslexia: Evidence from event-related brain potentials

In the present study, event-related brain potentials (ERPs) were used to compare auditory sentence comprehension in 16 children with developmental dyslexia (age 9-12 years) and unimpaired controls matched on age, sex, and nonverbal intelligence. Passive sentences were presented, which were either correct or contained a syntactic violation (phrase structure) or a semantic violation (selectional restriction). In an overall sentence correctness judgment task, both control and dyslexic children performed well. In the ERPs, control children and dyslexic children demonstrated a similar N400 component for the semantic violation. For the syntactic violation, control children demonstrated a combined pattern, consisting of an early starting bilaterally distributed anterior negativity and a late centro-parietal positivity (P600). Dyslexic children showed a different pattern that is characterized by a delayed left lateralized anterior negativity, followed by a P600. These data indicate that dyslexic children do not differ from unimpaired controls with respect to semantic integration processes (N400) or controlled processes of syntactic reanalyses (P600) during auditory sentence comprehension. However, early and presumably highly automatic processes of phrase structure building reflected in the anterior negativity are delayed in dyslexic children. Moreover, the differences in hemispheric distribution of the syntactic negativity indicate different underlying processes in dyslexic children and controls. The bilateral distribution in controls suggests an involvement of right hemispherically established prosodic processes in addition to the left hemispherically localized syntactic processes, supporting the view that prosodic information may be used to facilitate syntactic processing during normal comprehension. The left hemispheric distribution observed for dyslexic children, in contrast, suggests that these children do not rely on information about the prosodic contour during auditory sentence comprehension as much as controls do. This finding points toward a phonological impairment in dyslexic children that might hamper the development of syntactic processes

Model-generated lexical activity predicts graded ERP amplitudes in lexical decision

Recent neurocognitive studies of visual word recognition provide information about neuronal networks correlated with processes involved in lexical access and their time course (e.g., [Holcomb, Ph.J., Grainger J. and O'Rourke, T. (2002). An Electrophysiological Study of the Effects of Orthographic Neighborhood Size on Printed Word Perception, J. of Cogn. Neurosci. 14 938–950; Binder, J.R., McKiernan, K.A., Parsons, M.E., Westbury, C.F., Possing, E.T., Kaufman, J.N. and Buchanan, L. (2003). Neural Correlates of Lexical Access during Visual Word Recognition, J. Cogn. Neurosci. 15 372–393.]). These studies relate the orthographic neighborhood density of letter strings to the amount of global lexical activity in the brain, generated by a hypothetical mental lexicon as speculated in an early paper by [Jacobs, A.M. and Carr, T.H. (1995). Mind mappers and cognitive modelers: Toward cross-fertilization, Behav. Brain. Sci. 18 362–363]. The present study uses model-generated stimuli theoretically eliciting graded global lexical activity and relates this activity to activation of lexical processing networks using event-related potentials (ERPs). The results from a lexical decision task provide evidence for an effect of lexicality around 350 ms post-stimulus and also a graded effect of global lexical activity for nonwords around 500 ms post-stimulus. The data are interpreted as reflecting two different decision processes: an identification process based on local lexical activity underlying the ‘yes’ response to words and a temporal deadline process underlying the ‘no’ response to nonwords based on global lexical activity

The brain generates its own sentence melody: A Gestalt phenomenon in speech perception

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Analysing Molecular Mechanism Related to Therapy- Resistance in In-vitro Models of Ovarian Cancer

Ovarian cancer is among the most common cause of cancer death and ranks first in the number of deaths each year in the field of gynaecological malignancies. This is due to its late diagnosis and the development of chemoresistance. Platinum derivates, including cisplatinum and carboplatin in combination with paclitaxel, are the first-line chemotherapeutic agents. Platinum derivates irreversibly intercalates into the DNA and creates inter- and intra-strand DNA cross-links. During cell division, platinum-DNA-adducts block the replication machinery, inducing DNA damage and apoptosis. Nearly all patients respond to first-line chemotherapy before it comes later to recurrence of the disease. At time of recurrence, tumours are usually more aggressive, form metastasis in secondary tissues and acquire resistance to conventional chemotherapeutics. Drug resistance is a common problem in tumour therapy not only restricted to ovarian cancer. It is characterized by gene mutations, increased DNA repair, reduced drug efficacy and enhanced drug clearance and detoxification. Up to now the complex molecular mechanism of chemoresistance is not well understood. Increasing evidence points towards AKT over-expression and alteration of the PI3K/AKT/mTOR cascade as a central mechanistic reason for this resistance

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. <p/>Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. <p/>Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Comparison of Fas(Apo-1/CD95)- and perforin-mediated cytotoxicity in primary T lymphocytes

Cytolytic T lymphocytes kill target cells by two independent cytolytic mechanisms. One pathway depends on the polarized secretion of granule-stored proteins including perforin and granzymes, causing target cell death through membrane and DNA damage. The second cytolytic effector system relies on the interaction of the Fas ligand (Fasl) on the effector cell with its receptor (Fas) on the target cell, leading to apoptotic cell death. Using mixed lymphocyte culture (MLC)-derived primary T lymphocytes of perforin-knockout and gld (with non-functional FasL) mice, the molecular basis of the two killing mechanisms was compared. The activity of both pathways was dependent on extracellular Ca2+. Incubation of MLC-stimulated primary T cells with protein synthesis inhibitors prior to TCR triggering impaired FasL cell surface expression and abolished cytolytic activity, although the cells exhibited an intracellular pool of FasL. The perforin-dependent mechanism induced cell death more rapidly, although both pathways ultimately showed similar killing efficiencies. Both pathways induced comparable levels of DNA degradation, but Fas-induced membrane damage was less pronounced. We conclude that upon TCR triggering FasL may be recruited in part from pre-existing intracellular stores. However, efficient induction of target cell death still depends on the continuous biosynthesis of FasL molecules

QuasR: quantification and annotation of short reads in R

Summary: QuasR is a package for the integrated analysis of high-throughput sequencing data in R, covering all steps from read preprocessing, alignment and quality control to quantification. QuasR supports different experiment types (including RNA-seq, ChIP-seq and Bis-seq) and analysis variants (e.g. paired-end, stranded, spliced and allele-specific), and is integrated in Bioconductor so that its output can be directly processed for statistical analysis and visualization. Availability and implementation: QuasR is implemented in R and C/C++. Source code and binaries for major platforms (Linux, OS X and MS Windows) are available from Bioconductor (www.bioconductor.org/packages/release/bioc/html/QuasR.html). The package includes a ‘vignette' with step-by-step examples for typical work flows. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin