julilili42/papers huggingface dataset:
Aromatic Prenylation in Phenazine Biosynthesis
2009-04-02

The bacterium Streptomyces anulatus 9663, isolated from the intestine of different arthropods, produces prenylated derivatives of phenazine 1-carboxylic acid. From this organism, we have identified the prenyltransferase gene ppzP. ppzP resides in a gene cluster containing orthologs of all genes known to be involved in phenazine 1-carboxylic acid biosynthesis in Pseudomonas strains as well as genes for the six enzymes required to generate dimethylallyl diphosphate via the mevalonate pathway. This is the first complete gene cluster of a phenazine natural compound from streptomycetes. Heterologous expression of this cluster in Streptomyces coelicolor M512 resulted in the formation of prenylated derivatives of phenazine 1-carboxylic acid. After inactivation of ppzP, only nonprenylated phenazine 1-carboxylic acid was formed. Cloning, overexpression, and purification of PpzP resulted in a 37-kDa soluble protein, which was identified as a 5,10-dihydrophenazine 1-carboxylate dimethylallyltransferase, forming a C-C bond between C-1 of the isoprenoid substrate and C-9 of the aromatic substrate. In contrast to many other prenyltransferases, the reaction of PpzP is independent of the presence of magnesium or other divalent cations. The K(m) value for dimethylallyl diphosphate was determined as 116 microm. For dihydro-PCA, half-maximal velocity was observed at 35 microm. K(cat) was calculated as 0.435 s(-1). PpzP shows obvious sequence similarity to a recently discovered family of prenyltransferases with aromatic substrates, the ABBA prenyltransferases. The present finding extends the substrate range of this family, previously limited to phenolic compounds, to include also phenazine derivatives.
Effects of pharmacotherapy and psychotherapy in depressed primary-care patients: a randomized, controlled trial including a patients' choice arm
2009-04-03

Mild depressive syndromes are highly prevalent among primary-care patients. Evidence-based treatment recommendations need to be derived directly from this diagnostically heterogeneous group. The primary aim was to assess the efficacy of sertraline and cognitive-behavioural group therapy for treatment of depressed primary-care patients, the secondary aim was to evaluate if receiving treatment according to free choice is associated with a better outcome than randomization to a particular treatment. We conducted a randomized, placebo-controlled, single-centre, 10-wk trial with five arms: sertraline (flexible dosages up to 200 mg/d) (n = 83); placebo (n = 83); manual-guided cognitive-behavioural group therapy (one individual session and nine group sessions per 90 min) (n = 61); guided self-help group (control condition, n = 59); and treatment with sertraline or cognitive-behavioural group therapy according to patients' choice (n = 82). From 1099 consecutively screened adult patients, 368 formed the intent-to-treat population with milder forms of depression. Primary outcome was a global efficacy measure combining z-converted Hamilton Depression Rating Scale and clinician-rated Inventory for Depressive Symptomatology scores. Sertraline was superior to placebo (p = 0.03). Outcome for guided self-help groups was worse compared to cognitive-behavioural group therapy (p = 0.002) and compared to all other treatment arms including pill placebo (secondary analyses). Outcome in the patients' choice arm was similar to that in the sertraline and cognitive-behavioural group therapy. Overall, sertraline is efficacious in primary-care patients with milder forms of depression. The superiority of cognitive-behavioural group therapy over guided self-help groups might partly be explained by 'nocebo' effects of the latter.
Lithium-induced suicidal erythrocyte death
2009-04-03

Lithium (Li + ), an effective drug for treatment of bipolar disorders, is known to alter several Ca 2+ transporting systems. Increased cellular Ca 2+ has in turn been shown to stimulate eryptosis, the suicidal death of erythrocytes. Eryptosis is characterised by exposure of phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage. The present experiments explored whether Li + influences eryptosis. In erythrocytes from healthy volunteers, cytosolic Ca 2+ activity (Fluo-3 fluorescence), cell volume (forward scatter) and PS exposure (annexin V binding) were determined by fluorescence-activated cell sorting analysis. Exposure to Li + (≥1 mM) did not significantly modify forward scatter but significantly increased cytosolic Ca 2+ activity (within 3 h) and annexin binding (within 48 h). The effect was paralleled by increase of cellular adenosine triphosphate concentration. Glucose depletion (24 h) strongly increased PS exposure, an effect significantly enhanced in the presence of Li + (≥1 mM). In conclusion, Li + triggers suicidal erythrocyte death, an effect at least partially due to increase of cytosolic Ca 2+ activity.
Phase diagram of geometricd-wave superconductor Josephson junctions
2009-04-03

We show that a constriction-type Josephson junction realized by an epitactic thin film of a d-wave superconductor with an appropriate boundary geometry exhibits intrinsic phase differences between 0 and pi depending on geometric parameters and temperature. Based on microscopic Eilenberger theory, we provide a general derivation of the relation between the change of the free energy of the junction and the current-phase relation. From the change of the free energy, we calculate phase diagrams and discuss transitions driven by geometric parameters and temperature.
Prediction of breast cancer by profiling of urinary RNA metabolites using Support Vector Machine-based feature selection
2009-04-05

Abstract Background Breast cancer belongs to the most frequent and severe cancer types in human. Since excretion of modified nucleosides from increased RNA metabolism has been proposed as a potential target in pathogenesis of breast cancer, the aim of the present study was to elucidate the predictability of breast cancer by means of urinary excreted nucleosides. Methods We analyzed urine samples from 85 breast cancer women and respective healthy controls to assess the metabolic profiles of nucleosides by a comprehensive bioinformatic approach. All included nucleosides/ribosylated metabolites were isolated by cis-diol specific affinity chromatography and measured with liquid chromatography ion trap mass spectrometry (LC-ITMS). A valid set of urinary metabolites was selected by exclusion of all candidates with poor linearity and/or reproducibility in the analytical setting. The bioinformatic tool of Oscillating Search Algorithm for Feature Selection (OSAF) was applied to iteratively improve features for training of Support Vector Machines (SVM) to better predict breast cancer. Results After identification of 51 nucleosides/ribosylated metabolites in the urine of breast cancer women and/or controls by LC- ITMS coupling, a valid set of 35 candidates was selected for subsequent computational analyses. OSAF resulted in 44 pairwise ratios of metabolite features by iterative optimization. Based on this approach ultimately estimates for sensitivity and specificity of 83.5% and 90.6% were obtained for best prediction of breast cancer. The classification performance was dominated by metabolite pairs with SAH which highlights its importance for RNA methylation in cancer pathogenesis. Conclusion Extensive RNA-pathway analysis based on mass spectrometric analysis of metabolites and subsequent bioinformatic feature selection allowed for the identification of significant metabolic features related to breast cancer pathogenesis. The combination of mass spectrometric analysis and subsequent SVM-based feature selection represents a promising tool for the development of a non-invasive prediction system.
Pretreatment frequency of circulating IL‐17+CD4+ T‐cells, but not Tregs, correlates with clinical response to whole‐cell vaccination in prostate cancer patients
2009-04-07

Abstract The aim of this study was to determine the prognostic implications of the pretreatment level of Th17 cells compared with regulatory T‐cell status in prostate cancer patients receiving active whole cell immunotherapy. Ten‐color flow cytometry was used to analyze IL‐17‐producing CD4 + T‐cells in the peripheral blood of hormone‐resistant non‐bone metastatic prostate cancer patients prior to immunotherapy with an allogeneic whole‐cell vaccine. Surface expression of the chemokine receptors CCR4 and CCR6 was used to further subdivide IL‐17‐producing cells into subsets with distinct homing properties. The frequency of circulating regulatory T‐cells (Tregs), defined as CD3 + CD4 + CD127 lo Foxp3 + CD25 + was compared in the same patients. The frequency of CCR4 − IL‐17 + CD4 + T‐cells prevaccination inversely correlated with time to disease progression (TTP) in 23 prostate cancer patients. Furthermore, responder (R) patients with statistically significant reductions in PSA velocity (PSAV) in response to the immunotherapy ( n = 9), showed a Th17 profile similar to healthy male controls and significantly different from non‐responder (NR) patients ( n = 14) (i.e., those without any significant reduction in PSAV). In contrast, the frequency of Tregs in peripheral blood in PSA‐R ( n = 11) and ‐NR ( n = 14) patients was similar (but in both cases, significantly higher than in age‐matched healthy men). Accordingly, there was no significant correlation between frequency of Tregs and TTP in these late‐stage prostate cancer patients undergoing active immunotherapy. These data imply an important role for IL‐17‐producing helper T‐cells in cancer immunology and highlight their potential use as a pretreatment screen to ensure appropriate treatment is offered to hormone‐resistant prostate cancer patients. © 2009 UICC
Prediction of dual protein targeting to plant organelles
2009-04-07

* Dual targeting of proteins to more than one subcellular localization has been found in animals, in fungi and in plants. In the latter, ambiguous N-terminal targeting signals have been described that result in the protein being located in both mitochondria and plastids. We have developed ambiguous targeting predictor (ATP), a machine-learning implementation that classifies such ambiguous targeting signals. * Ambiguous targeting predictor is based on a support vector machine implementation that makes use of 12 different amino acid features. Prediction results were validated using fluorescent protein fusion. * Both in silico and in vivo evaluations demonstrate that ambiguous targeting predictor is useful for predicting dual targeting to mitochondria and plastids. Proteins that are targeted to both organelles by tandemly arrayed signals (so-called twin targeting) can be predicted by both ambiguous targeting predictor and a combination of single targeting prediction tools. Comparison of ambiguous targeting predictor with previous experimental approaches, as well as in silico approaches, shows good congruence. * Based on the prediction results, land plant genomes are expected to encode, on average, > 400 proteins that are located in mitochondria and plastids. Ambiguous targeting predictor is helpful for functional genome annotation and can be used as a tool to further our understanding about dual protein targeting and its evolution.
Alfvén polar oscillations of relativistic stars
2009-04-07

We study polar Alfv\\'en oscillations of relativistic stars endowed with a strong global poloidal dipole magnetic field. Here we focus only on the axisymmetric oscillations which are studied by evolving numerically the two-dimensional perturbation equations. Our study shows that the spectrum of the polar Alfv\\'{e}n oscillations is discrete in contrast to the spectrum of axial Alfv\\'{e}n oscillations which is continuous. We also show that the typical fluid modes, such as the f and p modes, are not significantly affected by the presence of the strong magnetic field.
Formal Total Synthesis of Platencin
2009-04-07

Abstract The right bicycle : A concise formal synthesis of platencin was based on an efficient oxygen‐mediated palladium‐catalyzed cycloalkenylation of 1 to form a bicyclo[3.2.1]octane, and a deoxygenative rearrangement of tosylhydrazone 2 to construct the bicyclo[2.2.2]octane 3 . The total yield of the core structure 4 of platencin was 17.5 % for 13 steps from a commercially available compound. Ts= p ‐toluenesulfonyl, TBS= tert ‐butyldimethylsilyl, Piv=pivaloyl. magnified image
Notation-Independent Representation of Fractions in the Human Parietal Cortex
2009-04-08

Although the concept of whole numbers is intuitive and well suited for counting and ordering, it is with the invention of fractions that the number system gained precision and flexibility. Absolute magnitude is encoded by single neurons that discharge maximally to specific numbers. However, it is unknown how the ratio of two numbers is represented, whether by processing numerator and denominator in separation, or by extending the analog magnitude code to relative quantity. Using functional MRI adaptation, we now show that populations of neurons in human fronto-parietal cortex are tuned to preferred fractions, generalizing across the format of presentation. After blood oxygen level-dependent signal adaptation to constant fractions, signal recovery to deviant fractions was modulated parametrically as a function of numerical distance between the deviant and adaptation fraction. The distance effect was invariant to changes in notation from number to word fractions and strongest in the anterior intraparietal sulcus, a key region for the processing of whole numbers. These findings demonstrate that the human brain uses the same analog magnitude code to represent both absolute and relative quantity. Our results have implications for mathematical education, which may be tailored to better harness our ability to access automatically a composite quantitative measure.
Synthesis, Mechanism, and Gas‐Sensing Application of Surfactant Tailored Tungsten Oxide Nanostructures
2009-04-08

Abstract Widely applicable nonaqueous solution routes have been employed for the syntheses of crystalline nanostructured tungsten oxide particles from a tungsten hexachloride precursor. Here, a systematic study on the crystallization and assembly behavior of tungsten oxide products made by using the bioligand deferoxamine mesylate (DFOM) (product I ), the two chelating ligands hexadecyltrimethylammoniumbromide (CTAB) ( II ) and poly(alkylene oxide) block copolymer (Pluronic P123) ( III ) is presented. The mechanistic pathways for the material synthesis are also discussed in detail. The tungsten oxide nanomaterials and reaction solutions are characterized by Fourier transform IR, 1 H, and 13 C NMR spectroscopies, powder X‐ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), high‐resolution TEM, and selected‐area electron diffraction. The indexing of the line pattern suggests WO 3 is in its monoclinic structure with a = 0.7297 nm, b = 0.7539 nm, c = 0.7688 nm, and β‐i; = 90.91 °. The nanoparticles formed have various architectures, such as chromosomal shapes (product I ) and slates ( II ), which are quite different from the mesoporous one ( III ) that has internal pores or mesopores ranging from 5 to 15 nm. The nanoparticles obtained from all the synthetic procedures are in the range of 40–60 nm. The investigation of the gas‐sensing properties of these materials indicate that all the sensors have good baseline stability and the sensors fabricated from material III present very different response kinetics and different CO detection properties. The possibility of adjusting the morphology and by that tuning the gas‐sensing properties makes the preparation strategies used interesting candidates for fabricating gas‐sensing materials.
A Nuclear Actin Function Regulates Neuronal Motility by Serum Response Factor-Dependent Gene Transcription
2009-04-08

Neuronal motility relies on actin treadmilling. In addition to regulating cytoskeletal dynamics in the cytoplasm, actin modulates nuclear gene expression. We present a hitherto unappreciated cross talk of actin signaling with gene expression governing neuronal motility. Toward this end, we used a novel approach using mutant actins either favoring (G15S) or inhibiting (R62D) F-actin assembly. Overexpressing these mutant actins in mouse hippocampal neurons not only modulated growth-cone function but also neurite elongation, which was ambiguous by traditional pharmacological interference. G15S actin enhanced neurite outgrowth and filopodia number. In contrast, R62D reduced neurite length and impaired growth-cone filopodia formation. Growth-cone collapse induced by ephrin-As, a family of repulsive axon guidance molecules, is impaired upon R62D expression, resulting in perseverance of ring-shaped F-actin filaments. R62D-induced phenotypes strongly resemble neurons lacking SRF (Serum Response Factor). SRF controls gene transcription of various actin isoforms (e.g., Actb , Acta1 ) and actin-binding proteins (e.g., Gsn ) and is the archetypical transcription factor to study actin interplay with transcription. We show that neuronal motility evoked by these actin mutants requires SRF activity. Further, constitutively active SRF partially rescues R62D-induced phenotypes. Conversely, actin signaling regulates neuronal SRF-mediated gene expression. Notably, a nucleus-resident actin (R62D NLS ) also regulates SRF's transcriptional activity. Moreover, R62D NLS decreases neuronal motility similar to the cytoplasmic R62D actin mutant although R62D NLS has no access to cytoplasmic actin dynamics. Thus, herein we provide first evidence that neuronal motility not only depends on cytoplasmic actin dynamics but also on the availability of actin to modulate nuclear functions such as gene transcription.
The Synthesis and Luminescence of W6Cl12 and Mo6Cl12 Revisited
2009-04-08

Abstract The reduction of tungsten hexachloride with bismuth yields the new compound (BiCl)[W 6 Cl 14 ]. Dissolution of this compound in HCl yields the cluster acid (H 3 O) 2 [W 6 Cl 14 ]·7H 2 O and the new byproduct (H 5 O 2 ) 2 [W 6 Cl 12 O 6 ]·4H 2 O. The single‐crystal structures of all these compounds are reported. Their appearance provides some new insight into the mechanism and apparent problems of the synthesis of pure W 6 Cl 12 . Both Mo 6 Cl 12 and W 6 Cl 12 are strongly red luminescent materials.
AHSG Gene Variation is not Associated with Regional Body Fat Distribution – A Magnetic Resonance Study
2009-04-08

Obesity-resistance in AHSG-knockout mice indicate an important role of alpha2-Heremans-Schmid glycoprotein/fetuin-A (AHSG) in the development of obesity. We studied whether genetic variation within AHSG affects whole-body adiposity and regional fat distribution in humans. We genotyped 321 subjects at increased risk for type 2 diabetes for five single nucleotide polymorphisms (SNP) rs2248690, rs4831, rs2070635, rs4917, and rs1071592. Body fat distribution and ectopic hepatic and intramyocellular lipids were assessed by magnetic resonance techniques. AHSG levels were determined by immunoturbidimetry. The five chosen SNPs covered 100% of common genetic variation (minor allele frequency >/=0.05) within AHSG (r (2)>/=0.8). All SNPs were significantly associated with AHSG levels (p<0.0001), except for rs4831 (p=0.9) after adjustment for gender, age, and body mass index (BMI). AHSG levels were associated with liver fat content (p=0.0160) and BMI (p=0.0247) after adjustment for gender and age. While rs2248690 was nominally associated with BMI in the dominant model (p=0.0432), none of the SNPs was associated with regional fat distribution. Common genetic variation within AHSG does not appear to influence regional body fat distribution, but may affect whole-body adiposity in humans.
A Novel Buoyancy Technique Optimizes Simulated Microgravity Conditions for Whole Sensory Organ Culture in Rotating Bioreactors
2009-04-08

Whole-organ culture of a sensory organ in a rotating wall vessel bioreactor provides a powerful in vitro model for physiological and pathophysiological investigation as previously demonstrated for the postnatal inner ear. The model is of specific relevance as a tool for regeneration research. In the immature inner ear explant, the density was only 1.29 g/cm(3). The high density of 1.68 g/cm(3) of the functionally mature organ resulted in enhanced settling velocity and deviation from its ideal circular orbital path causing enhanced shear stress. The morphometric and physical properties, as well as the dynamic motion patterns of explants, were analyzed and numerically evaluated by an orbital path index. Application of a novel buoyancy bead technique resulted in a 6.5- to 14.8-fold reduction of the settling velocity. The deviation of the explant from its ideal circular orbital path was adjusted as indicated by an optimum value for the orbital path index (-1.0). Shear stress exerted on the inner ear explant was consequently reduced 6.4- to 15.0-fold. The culture conditions for postnatal stages were optimized, and the preconditions for transferring this in vitro model toward mature high-density stages established. This buoyancy technique may also be useful in tissue engineering of other high-density structures.
Strong and electromagnetic decays ofX(1835) as a baryonium state
2009-04-08

With the assumption that the recently observed X(1835) is a baryonium state we have studied the strong decays of and the electromagnetic decay of in the framework of effective Lagrangian formalism. In the present investigation we have included the contributions from the iso-singlet light scalar resonances but we have not included the isospin violating effect. Our result for the strong decay of is smaller than the observed data. The decay width for the radiative decay of is consistent with the assumption that it decays through the glueball. In addition, the width for the strong decay of is larger than that of the strong decay of due to the large phase space and coupling constant . From our investigation, it is not possible to interpret X(1835) as a baryonium.
Microsurgical and Endoscopic Anatomy of the Retrosigmoid Intradural Suprameatal Approach to Lesions Extending from the Posterior Fossa to the Central Skull Base
2009-04-09

This article evaluates the accessibility of the posterior part of the central skull base via the extended retrosigmoid intradural suprameatal approach. In formaldehyde-fixed specimens, the retrosigmoid intradural suprameatal approach was performed, and the feasibility of reaching central skull base structures was analyzed. Microscopic and endoscopic techniques were used. The main outcome measures were digital films and screenshots, which were analyzed regarding quantitative and qualitative aspects of visual structures. By drilling off the suprameatal tubercle and part of the petrous apex, Meckel's cave may be opened, the trigeminal nerve mobilized, and the tentorium divided. Thus the parasellar area may be exposed and the posterosuperior space of the cavernous sinus approached. Using an endoscope-assisted technique and following cisternal anatomy, the sellar and parasellar region may be explored even if the working space is narrow. The retrosigmoid intradural suprameatal approach provides optimal accessibility to medially located central skull base structures, in particular to the posterior part of the cavernous sinus. Use of the endoscope may remarkably optimize the accessibility.
Autosomal dominant spastic paraplegia with peripheral neuropathy maps to chr12q23-24
2009-04-09

We report mapping of a new locus for autosomal dominant hereditary spastic paraplegia (HSP) (SPG36) on chromosome 12q23-24 in a German family with autosomal dominant HSP complicated by peripheral neuropathy.