julilili42/papers huggingface dataset:
Dysarthria
2010-03-16

10.1002/9781444318975.ch16.abs This chapter contains sections titled: The Brain Network of Speech Motor Control in Normal Speakers Dysarthria: Classification and Taxonomy Auditory-Perceptual and Instrumental Analysis of Motor Speech Disorders Dysarthric Deficits in Neurological Disorders Therapeutic Approaches to Dysarthric Motor Speech Disorders References
Proteogenomics ofPristionchus pacificusreveals distinct proteome structure of nematode models
2010-03-17

Pristionchus pacificus is a nematode model organism whose genome has recently been sequenced. To refine the genome annotation we performed transcriptome and proteome analysis and gathered comprehensive experimental information on gene expression. Transcriptome analysis on a 454 Life Sciences (Roche) FLX platform generated &gt;700,000 expressed sequence tags (ESTs) from two normalized EST libraries, whereas proteome analysis on an LTQ-Orbitrap mass spectrometer detected &gt;27,000 nonredundant peptide sequences from more than 4000 proteins at sub-parts-per-million (ppm) mass accuracy and a false discovery rate of &lt;1%. Retraining of the SNAP gene prediction algorithm using the gene expression data led to a decrease in the number of previously predicted protein-coding genes from 29,000 to 24,000 and refinement of numerous gene models. The P. pacificus proteome contains a high proportion of small proteins with no known homologs in other species (“pioneer” proteins). Some of these proteins appear to be products of highly homologous genes, pointing to their common origin. We show that &gt;50% of all pioneer genes are transcribed under standard culture conditions and that pioneer proteins significantly contribute to a unimodal distribution of predicted protein sizes in P. pacificus , which has an unusually low median size of 240 amino acids (26.8 kDa). In contrast, the predicted proteome of Caenorhabditis elegans follows a distinct bimodal protein size distribution, with significant functional differences between small and large protein populations. Combined, these results provide the first catalog of the expressed genome of P. pacificus , refinement of its genome annotation, and the first comparison of related nematode models at the proteome level.
Dynamic cellular translocation of caldendrin is facilitated by the Ca2+‐myristoyl switch of recoverin
2010-03-17

J. Neurochem. (2010) 113 , 1150–1162. Abstract Caldendrin and recoverin are Ca 2+ ‐sensor proteins operating in neuronal systems. In a search for novel binding partners of recoverin, we employed an affinity column and identified caldendrin as a possible interaction partner. Caldendrin and recoverin co‐localized in the retina in a subset of bipolar cells and in the pineal gland as revealed by immunofluorescence studies. The binding process was controlled by Ca 2+ as revealed by pull‐down assays, and surface plasmon resonance studies. Importantly, caldendrin existed as a Ca 2+ ‐independent homodimer whereas a complex of recoverin and caldendrin formed with low to moderate affinity in the presence of Ca 2+ . Co‐transfection of COS‐7 cells with plasmids harboring the gene for fluorescently labeled recoverin and caldendrin was used to study the cellular distribution by time‐lapse fluorescence microscopy. Apparently, the increase of intracellular Ca 2+ facilitates the translocation of caldendrin to intracellular membranes, which is under control of complex formation with recoverin.
Parental Genome Dosage Imbalance Deregulates Imprinting in Arabidopsis
2010-03-18

In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2) and FLOWERING WAGENINGEN (FWA) controlled by DNA methylation, and MEDEA (MEA) and PHERES1 (PHE1) controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.
Is detection of melanoma metastasis during surveillance in an early phase of development associated with a survival benefit?
2010-03-18

Surveillance schedules in patients with cutaneous melanoma (CM) aim to detect metastatic spread in an early phase of development. Few studies investigated whether detection in an early phase is associated with prolonged survival and whether the observed longer survival times are a mere consequence of detection at an earlier time point (lead time bias). This is a long-term survival analysis of 1969 patients with stage I-III CM documented during 1996-1998 in the frame of a prospective surveillance study. Development of metastatic spread was detected in 112 patients during this period and classified as early phase or advanced phase based on tumor load and operability. The impact of lead time bias on differences in survival probabilities was examined using different statistical approaches. Of 59 patients with metastases detected in an early phase of development, 64.4% died of CM, of 43 patients with advanced phase metastases 86% died (P=0.013). The 10-year overall survival probability was 42.6% for early and 25.6% for advanced phase metastases (P=0.012). This comparison remained significant after adjustment for sojourn time. Multivariate analysis identified detection of early phase metastases (P=0.022) and stage at primary diagnosis (P<0.0001) as independent prognostic factors. In conclusion, this long-term follow-up study showed a factual gain in survival time for the detection of metastasis in an early phase of development beyond lead time bias. The classification of metastasis detected in early and advanced phase may be used in future studies aiming to improve melanoma surveillance.
Determination of 6-Thioguanosine Diphosphate and Triphosphate and Nucleoside Diphosphate Kinase Activity in Erythrocytes: Novel Targets for Thiopurine Therapy?
2010-03-18

6-Thioguanine nucleotides are the sum of 6-thioguanosine 5'-monophosphate (TGMP), -diphosphate (TGDP), and -triphosphate (TGTP) representing essential metabolites involved in drug action of thiopurines. Elevated levels of TGDP have been associated with poor response to azathioprine therapy in patients with inflammatory bowel disease. The conversion of TGDP to TGTP is supposed to be catalyzed by nucleoside diphosphate kinase (NDPK). The aim of this work was to investigate simultaneously individual 6-thioguanosine phosphate levels and NDPK activity in red blood cells (RBCs) of patients on azathioprine therapy. Ion-pair high-performance liquid chromatography methods with fluorescence and ultraviolet detection were applied to quantify individual levels of 6-thioguanosine 5'-phosphates and NDPK activity, respectively, in RBCs. Recombinantly expressed NDPK isoforms A and B were unequivocally identified to catalyze the formation of TGTP (30.6 +/- 3.88 nmol x min x mg for NDPK A versus 41.2 +/- 1.05 nmol x min x mg for NDPK B). Comprehensive analyses on the stability of TGMP, TGDP, and TGTP and the reproducibility of NDPK activity in RBCs were performed to provide a reliable sampling protocol for clinical practice. Of note, isolation of RBCs within 6 hours followed by immediate storage at -80 degrees C is crucial for prevention of degradation of 5'-phosphates. In a clinical study of 37 patients on azathioprine, TGTP was the predominant 6-thioguanosine phosphate in RBCs. In contrast, three patients showed TGTP/(TGDP + TGTP) ratios of 57.2%, 64.3%, and 66% corresponding to elevated TGDP levels. NDPK activity ranged from 4.1 to 11.3 nmol x min x mg hemoglobin. No correlation between NDPK activity and the 6-thioguanosine phosphate levels was found. The question whether interindividual variability of NDPK activity may explain differences in 6-thioguanosine 5'-phosphates levels has to be investigated in a prospective large-scale study.
Glossopharyngeal Insufflation and Pulmonary Hemodynamics in Elite Breath Hold Divers
2010-03-18

Acute voluntary lung hyperinflation mimics changes seen in pulmonary arterial hypertension, but unlike the latter, these changes are fully reversible shortly after cessation of voluntary lung hyperinflation. Persistent changes due to repetitive GI could not be detected.
Akt2/PKBβ‐sensitive regulation of renal phosphate transport
2010-03-18

Abstract Aim: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. Methods: The renal phosphate transporter NaPi‐IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na + phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBβ knockout mice ( akt2 −/− ) and corresponding wild‐type mice ( akt2 +/+ ). Transporter protein abundance was determined using Western blotting and phosphate transport by 32 P uptake into brush border membrane vesicles. Results: The phosphate‐induced current in NaPi‐IIa‐expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [μmol per 24 h per g BW] was higher by 91% in akt2 −/− than in akt2 +/+ mice. The phosphaturia of akt2 −/− mice occurred despite normal transport activity and expression of the renal phosphate transporters NaPi‐IIa, NaPi‐IIc and Pit2 in the brush border membrane, a significantly decreased plasma PTH concentration (by 46%) and a significantly enhanced plasma 1,25‐dihydroxyvitamin D 3 concentration (by 46%). Moreover, fractional renal Ca 2+ excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2 −/− mice. Conclusions: Akt2/PKBβ plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone.
Cetuximab Promotes Immunotoxicity Against Rhabdomyosarcoma In Vitro
2010-03-18

Multidrug resistance is a common problem in the treatment of childhood rhabdomyosarcoma (RMS). Therefore, novel treatment regimes such as immunotherapy have to be evaluated. The aim of this study was to detect possible targets on RMS cells and to investigate whether corresponding humanized antibodies could be used to treat RMS. Screening for potential targets common for different subtypes of RMS was carried out with Affymetrix mRNA expression arrays on 12 primary RMS samples. Subsequent pathway analysis revealed the epidermal growth factor receptor (EGFR) as a potential target for antibody therapy. Expression of EGFR and binding of its specific antibody Cetuximab to embryonal RMS cell lines RD and A-204 and alveolar RMS Rh30 were monitored by flow cytometry. Cetuximab activity was quantified by proliferation assay on RMS cells, and by antibody dependent cellular cytotoxicity assay with peripheral blood mononuclear cells (PBMCs). Gene expression analysis revealed a high expression of EGFR in all embryonal RMS compared with alveolar RMS. The EGFR specific antibody, Cetuximab binds to Rh30 and to RD but not to A-204 cells. Proliferation of these cells was influenced neither by Cetuximab nor by the growth factor EGF. However, cell dependent cytotoxicity of PBMCs to RMS cells such as Rh30 and RD was enhanced specifically by Cetuximab. These promising Cetuximab effects justify analysis under in vivo conditions using suitable models.
Effect of osmotic shock and urea on phosphatidylserine scrambling in thrombocyte cell membranes
2010-03-18

Blood passing the renal medulla enters a strongly hypertonic environment challenging functional properties and survival of blood cells. In erythrocytes, exposure to hyperosmotic shock stimulates Ca 2+ entry and ceramide formation with subsequent cell membrane scrambling, an effect partially reversed by high concentrations of Cl − or urea. Cell membrane scrambling with phosphatidylserine exposure is part of the procoagulant phenotype of platelets. Coagulation in the hypertonic renal medulla would jeopardize blood flow in the vasa recta. The present study thus explored whether hypertonic environment and urea modify phosphatidylserine exposure of human platelets. FACS analysis was employed to estimate cytosolic Ca 2+ activity with Fluo3 fluorescence, ceramide formation, P-selectin, and glycoprotein IIb/IIIa activation with fluorescent antibodies and phosphatidylserine exposure with annexin V-binding. The spontaneous platelet aggregation was measured by impedance aggregometry. Hyperosmotic shock (addition of 500 mM sucrose or 250 mM NaCl) significantly enhanced cytosolic Ca 2+ activity, ceramide formation, phosphatidylserine exposure, platelet degranulation, and aggregability. Addition of 500 mM urea to isotonic saline did not significantly modify cytosolic Ca 2+ activity, ceramide abundance, or annexin V-binding but significantly blunted the respective effects of hypertonic shock following addition of 500 mM sucrose. In isotonic solutions, both ceramide (20 μM) and Ca 2+ ionophore ionomycin (0.5 μM) increased annexin V-binding, effects again significantly blunted by 500 mM urea. Moreover, oxidative stress by addition of 0.5 mM peroxynitrite increased cytosolic Ca 2+ activity and triggered annexin V-binding, effects again blunted in the presence of 500 mM urea. The observations reveal that hyperosmotic shock and oxidative stress trigger a procoagulant platelet phenotype, an effect blunted by the presence of high urea concentrations.
Critical features for biological motion
2010-03-18

Since the seminal work by Johansson, it has been widely accepted that mostly motion information is relevant for the perception of point light walkers. Beintema & Lappe (2002) have proposed a novel point light stimulus (sequential position walker, SPW) that strongly degrades local motion information by randomly displacing the dots along the limbs. Despite this degradation, their subjects were still able to judge the direction of walking, suggesting that the perception of these stimuli was based purely on form information, presumably by fitting an internal kinematic model. To test this hypothesis we designed another point light stimulus that is composed of regions containing either purely randomly moving dots, or dots with deterministic opponent motion along the horizontal axes, but random vertical motion. Despite the fact that this stimulus is highly incompatible with the kinematics of a walker subjects perceived it as a walking person. By slight variation of the stimulus outline the percept could be reliably shifted between rightward and leftward walking. Psychophysical experiments show no difference in recognition between the two stimuli (N=5, p>0.7). This result points against a relevance of kinematic models in the recognition of point light stimuli. Additional evidence against the necessity of form information was obtained in a quantitative modeling study using a neurophysiologically plausible model with a motion and a form pathway. The motion pathway of the model that analyzes local motion information achieves reliable recognition of SPW stimuli, whereas the form pathway contributes only weakly. We conclude that, though form information undoubtely can be exploited for the recognition of biological stimuli, it might not be sufficient for the recognition of point light walkers. Instead, our experimental results suggest that their recognition might implicate the use of opponent motion features that can be extracted by relatively simple neural detectors.
Metric category spaces of biological motion
2010-03-18

Converging experimental evidence suggests that shape categories are mentally represented as continuous spaces that preserve the parametric similarities among individual object shapes. Here we show that perception of biologal motion likewise preserves the metric of spatio-temporal similarities among motion patterns. We presented subjects with animated patterns of point lights corresponding to trajectories generated by spatio-temporal morphing among three prototypical human locomotion patterns. Using a novel morphing algorithm that computes linear combinations of complex movement trajectories in space-time, we generated motion stimuli that corresponded to two-dimensional geometrical configurations in a parametric pattern space defined by the weights of the linear combination. Two configurations were used, one consisting of 7 patterns arranged in the form of a (T)riangle, and the other in the form of the letter L. For each configuration, observers were asked to judge the similarity between all pairs of stimuli using a comparison-of-pairs paradigm. A measure of perceived dissimilarity computed from these judgments was submitted to multidimensional scaling. The recovered 2D configurations in the reconstructed perceptual space were quantitatively compared with the configurations in the original linear morphing space. The recovered metric structure closely matched the original metric structure in the morphing space. (Coefficients of congruence 0.98 and 0.88 for T (n=14) and L (n=19); Procrustes distances 0.41 and 0.96; corresponding to bootstrap-estimated d′ equivalents between 2.99 and 8.15). We recovered a very similar metric structure from the neural responses of a physiologically plausible model of biological motion recognition. We conclude: (a) The visual system represents related categories of locomotion in a common metric space that reflects spatio-temporal similarities of motion trajectories. (b) These representations can be realized with known cortical mechanisms.
Gene Expression within the Amacrine Cell Layer of Chicks after Myopic and Hyperopic Defocus
2010-03-19

PURPOSE. Ocular growth is regulated locally by signals produced in the retina. The highly heterogeneous nature of the retina may mask important changes in gene expression during global analysis. This study was conducted to investigate changes in gene expression specifically within the amacrine cell layer (ACL), the most likely generator of growth signals, during optical manipulation of ocular growth. METHOD. Chicks were monocularly treated with either -7-D (n = 6) or +7-D (n = 6) lenses for 24 hours. Untreated age-matched chicks served as control subjects (n = 6). Total RNA from the ACL was isolated from 10-mum-thick sections, obtained using laser capture microdissection. Labeled cRNA was prepared from three samples per condition and hybridized to chicken genome microarrays. Changes in gene expression were validated by using semiquantitative real-time RT-PCR. RESULTS. One hundred twenty-eight genes were differentially expressed in the ACL of the minus lens-treated eyes, whereas the plus lens-treated eyes displayed 58 changes 24 hours after treatment. Only 11 genes were differentially expressed under both experimental conditions, whereas the expression of only one gene (clone ChEST927g14) was modulated by the sign of defocus. Compared with previous studies in the field, the magnitude of changes observed in the present work were larger, with more than 30% of differentially expressed genes showing a twofold or greater modulation in expression. The results, obtained from independent validation by real-time RT-PCR technology, correlated highly with the original microarray data. The differential expression of four of eight genes was validated in plus lens-treated eyes, and eight of nine genes were independently validated in minus lens-treated eyes. CONCLUSIONS. The targeted investigation of the ACL enabled the identification of several novel genes that may form part of the growth regulatory pathways of the eye. Different retinal pathways may underlie the response of the eyes to plus and minus lens compensation, as there was limited overlap in the regulated genes observed within the ACL under both conditions.
Interferon therapy in rheumatic diseases: state-of-the-art 2010
2010-03-19

Among several rheumatologic diseases, IFNalpha has found more widespread use in Behçet's syndrome and hepatitis C virus-associated mixed cryoglobulinemia despite a paucity of formal studies. Patients should be carefully monitored for the frequent and dose-dependent adverse effects.
The neural basis of disturbed efference copy mechanism in patients with schizophrenia
2010-03-19

Core psychopathological symptoms in patients with schizophrenia suggest that their sense of self may be disturbed. A disturbance in predictive motor mechanisms may be the cause of such symptoms. Ten patients with schizophrenia and ten healthy right-handed control subjects opened and closed their hand. This movement was filmed with an MRI compatible video camera and projected online onto a monitor. BOLD contrast was measured with fMRI. The temporal delay between movement and feedback was parametrically varied. Participants judged whether or not there was a delay. Patients were less sensitive to these delays than a matched control group. Comparing neural activation between the two groups showed a reduced attenuation of movement-sensitive perceptual areas in patients with increasing delay and a higher activation in the putamen in controls. The results provide further evidence that impaired efference copy mechanisms may contribute to the pathogenesis of schizophrenia and its first rank symptoms.
Electronic structure of higher acenes and polyacene: The perspective developed by theoretical analyses
2010-03-20

The hypothetical polymer obtained by linear annelation of benzene units, polyacene (PAC) (C 4 H 2 ) n , has received considerable attention over the last 50 years. This interest is due to the unusual electronic structure that is assumed to result in usual physical properties. The review summarizes the theoretical investigations of PAC research. The most recent computational analyses available in the literature are based on density functional theory (DFT) for PAC and on the complete active space self-consistent field (CASSCF) method for oligoacenes and suggest an undistorted symmetrical structure with an antiferromagnetic (AFM) coupling of electrons.