julilili42/papers huggingface dataset:
Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation
2010-12-21

Abstract During a systemic inflammatory response endothelial-expressed surface molecules have been strongly implicated in orchestrating immune responses. Previous studies have shown enhanced extracellular nucleotide release during acute inflammatory conditions. Therefore, we hypothesized that endothelial nucleotide receptors could play a role in vascular inflammation. To address this hypothesis, we performed screening experiments and exposed human microvascular endothelia to inflammatory stimuli, followed by measurements of P2Y or P2X transcriptional responses. These studies showed a selective induction of the P2Y6 receptor (&gt; 4-fold at 24 hours). Moreover, studies that used real-time reverse transcription–polymerase chain reaction, Western blot analysis, or immunofluorescence confirmed time- and dose-dependent induction of P2Y6 with tumor necrosis factor α or Lipopolysaccharide (LPS) stimulation in vitro and in vivo. Studies that used MRS 2578 as P2Y6 receptor antagonist showed attenuated nuclear factor κB reporter activity and proinflammatory gene expression in human microvascular endothelial cells in vitro. Moreover, pharmacologic or genetic in vivo studies showed attenuated inflammatory responses in P2Y6−/− mice or after P2Y6 antagonist treatment during LPS-induced vascular inflammation. These studies show an important contribution of P2Y6 signaling in enhancing vascular inflammation during systemic LPS challenge and implicate the P2Y6 receptor as a therapeutic target during systemic inflammatory responses.
Pharmacological Modulation of Diacylglycerol-Sensitive TRPC3/6/7 Channels
2010-12-21

Members of the classic type of transient receptor potential channels (TRPC) represent important molecules involved in hormonal signal transduction. TRPC3/6/7 channels are of particular interest as they are components of phospholipase C driven signalling pathways. Upon receptor-activation, G-protein-mediated stimulation of phospholipase C results in breakdown of phosphatidylinositides leading to increased intracellular diacylglycerol and inositol-trisphosphate levels. Diacylglycerol activates protein kinase C, but more interestingly diacylglycerol directly activates TRPC2/3/6/7 channels. Molecular cloning, expression and characterization of TRP channels enabled reassignment of traditional inhibitors of receptor-dependent calcium entry such as SKF-96365 and 2-APB as blockers of TRPC3/6/7 and several members of non-classic TRP channels. Furthermore, several enzyme inhibitors have also been identified as TRP channel blockers, such as ACA, a phospholipase A(2) inhibitor, and W-7, a calmodulin antagonist. Finally, the naturally occurring secondary plant compound hyperforin has been identified as TRPC6-selective drug, providing an exciting proof of concept that it is possible to generate TRPC-selective channel modulators. The description of Pyr3 as the first TRPC3-selective inhibitor shows that not only nature but also man is able to generate TRP-selective modulators. The review summarizes the data on pharmacological modification of TRPC3/6/7. Sheds lights on the current knowledge and historical development of pharmacological modulators of TRPC3/6/7. Our analysis indicates that Pyr3 and hyperforin provide promising core structures for the development of new, skeletive and more potent modulators of TRPC3/6/7 activity.
Protocol and Methodology of the Stroke in Young Fabry Patients (sifap1) Study: A Prospective Multicenter European Study of 5,024 Young Stroke Patients Aged 18–55 Years
2010-12-21

&lt;i&gt;Background:&lt;/i&gt; Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports indicate that Fabry disease may be a significant cause for young stroke. The primary aim of our study was to determine the prevalence of Fabry disease in young stroke patients, while the secondary aim was to describe patterns of stroke in young patients. &lt;i&gt;Methods:&lt;/i&gt; We initiated the Stroke in Young Fabry Patients (sifap1) study as a multinational prospective European study of stroke patients aged 18–55 years and collected a broad range of clinical, laboratory, and radiological data using stringent standardized methods. All patients were tested for Fabry disease and blood was stored for future genetic testing. &lt;i&gt;Results:&lt;/i&gt; We managed to enroll 5,024 eligible young stroke patients in 15 countries and 47 centers across Europe between April 2007 and January 2010. The median number of patients included per center was 98 with a range between 8 and 315. The average duration of patient recruitment per center was 22 months, ranging between 5 and 33 months. The database was closed in July 2010. This paper describes protocol and methodology of the sifap1 study. &lt;i&gt;Conclusion:&lt;/i&gt; The sifap1 study included the largest series of young stroke patients so far and will allow for analyses on a large number of aspects of stroke in the young.
Vulnerability to Brain-Drain among Academics in Institutions of Higher Learning in Ethiopia
2010-12-21

This study investigated the extent, causes, and correlates of vulnerability to brain-drain among Ethiopian academics in higher education institutions (HEIs). The sample constituted a total of 103 faculty members (Females 9.3% and Males 90.7%) drawn from three colleges and four faculties affiliated to the Debub University. Data were collected through self-reported measures assessing vulnerability to brain-drain (external brain-drain conceptualized as intention to remain in a western country given that they would have opportunities for further study or research; and internal brain drain defined as a brain circulation within the country), affective job characteristics (job satisfaction and organizational commitment), and work environment factors. The results show that affective job characteristics and work environment variables significantly predicted vulnerability to internal brain-drain. While external brain drain is associated with vulnerability to internal brain drain and organizational citizenship behavior (OCB). A closer investigation into the prominence of the pull and push factors further disclosed that working condition and the salary are the outstanding ones. Implications of the findings for policy making are also discussed.
Myocardial Delayed Enhancement in Pulmonary Hypertension: Pulmonary Hemodynamics, Right Ventricular Function, and Remodeling
2010-12-22

In PH, total delayed enhancement burden at the RV septal insertions is predicted by RV remodeling in response to increased afterload. Local fibrosis mass at the anterior septal insertion is associated with reduced regional longitudinal contractility at the base.
Complement Tense in Contrast: The <tt>SOT</tt> parameter in Russian and English
2010-12-22

In an SOT-language like English, ‘past under past’ may have a simultaneous interpretation, i.e., we have temporal agreement. In a non-SOT language like Russian, we only have the shifted interpretation. In English, the temporal morphology of the embedded verb is determined by the matrix tense via a binding chain through verbal quantifiers such as ‘say’ or ‘think’. In Russian, these attitude verbs break the binding chain. The morphology of the embedded verb is determined locally by an embedded relative PRESENT, FUTURE or PAST. We propose that the difference between English and Russian is derived from:&#x0D; &#x0D; The SOT-parameter:&#x0D; A language L is an SOT-language if and only if the verbal quantifiers of L transmit temporal features. &#x0D; &#x0D; Verbal quantifiers quantify over times (e.g. fut. will) or world-times (e.g. verba dicendi).&#x0D; &#x0D; The paper will take up a recent challenge by Daniel Altschuler and Olga Khomitsevich against existing accounts: verbs of perception and, occasionally, factive verbs in Russian may express simultaneity by ‘past under past’. We will show that the problem is in fact non-existent when the complement is imperfective. Concerning factives, however, we argue that the complement tense is an independent de re past. Finally, perception verbs are normally not verbal quantifiers and hence not subject to the SOT-parameter.
Treatment efficiency, outcome and surgical treatment problems in patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma: A report from the cooperative soft tissue sarcoma trial CWS‐96
2010-12-22

Abstract Background To analyze the clinical course, treatment modalities, complications and outcome of patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma (BPRMS) treated on the CWS‐96 trial. Procedure There were 85 patients with BPRMS enrolled and 63 patients with embryonal non‐metastatic BPRMS were analyzed. Fifty‐six patients received neoadjuvant chemotherapy and response was assessed radiographically after 9 weeks. Local therapy with radiation and or surgery was performed based on age, tumor size, and response. Patients were treated with adjuvant chemotherapy following local control. Results Patient's age ranged from 0 to 16 years with a median follow up of 5.3 years. Eighty nine percent of the patients had IRS group III disease. The 5‐year overall survival (OS) for the whole group was 76.3 ± 5.6% and the 5‐year event‐free survival (EFS) 69.8 ± 6.2%. Seventeen patients underwent preoperative radiochemotherapy followed by tumor resection (5‐year‐OS: 87.8 ± 8.1%). Eight patients were treated with solely radiochemotherapy (87.5 ± 11.7%). Twenty‐five patients received chemotherapy and tumor resection (OS: 83.6 ± 7.5%). Thirteen patients underwent incomplete tumor resection and were treated with radiochemotherapy postoperatively (OS: 39.9 ± 14.8%, P &lt; 0.05 vs. other groups). Conclusions Local therapy is an important factor for prognosis of localized embryonal BPRMS. Inadequate primary or secondary surgery compromises the outcome and should be avoided. Radiotherapy alone, complete surgical tumor resection or combined preoperative radiotherapy with surgical resection lead to similar good local control rates and prognosis. Pediatr Blood Cancer 2011;56:718–724. © 2010 Wiley‐Liss, Inc.
APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo
2010-12-22

Death receptor targeting has emerged as one of the promising novel approaches of cancer therapy. The activation of one such prototypic death receptor, CD95 (Fas/APO-1), has remained controversial because CD95 agonistic molecules have exhibited either too strong toxicity or too little activity. The natural CD95 ligand (CD95L) is a cytokine, which needs to trimerize to mediate a cell death signal. Mega-Fas-Ligand, now referred to as APO010, is a synthetic hexameric CD95 agonist that exhibits strong antitumor activity in various tumor models. Here, we studied the effects of APO010 in human glioma models in vitro and in vivo. Compared with a cross-linked soluble CD95L or a CD95-agonistic antibody, APO010 exhibited superior activity in glioma cell lines expressing CD95 and triggered caspase-dependent cell death. APO010 reduced glioma cell viability in synergy when combined with temozolomide. The locoregional administration of APO010 induced glioma cell death in vivo and prolonged the survival of tumor-bearing mice. A further exploration of APO010 as a novel antiglioma agent is warranted.
Congruence, non‐homology, and the phylogeny of basal turtles
2010-12-22

Abstract Joyce, W.G. and Sterli J. 2010. Congruence, non‐homology, and the phylogeny of basal turtles.– Acta Zoologica (Stockholm) Modern cladistic analysis is characterized by the assembly of increasingly larger data sets coupled with the use of congruence as the final test of homology. Some critics of this development have recently called for a return to more detailed primary homology analysis while questioning the utility of congruence. This discussion appears to be central to the debate regarding the phylogenetic relationships of basal turtles, as the large data sets developed by us have been criticized recently for utilizing poorly constructed characters and including too many homoplasy‐prone characters. Our analysis of this critique reveals that (1) new information regarding poorly understood taxa has a greater impact on the outcome of turtle phylogenies than the characters under dispute; (2) most current turtle phylogenies differ in taxon sampling, not character sampling, and so it appears illogical to condemn a particular analysis for its character sampling; (3) even evolutionary taxonomists should agree that key characters utilized to resolve basal turtle relationships cannot be thought to be ‘infallible’; (4) whereas various criteria provide positive evidence for homology, only congruence provides positive evidence for non‐homology; and (5) a stalemate between conflicting camps within a congruence frame work is preferable to the ad hoc dismissal of data sets, because authoritative statements are untestable.
Clinical functional MRI of the language domain in children with epilepsy
2010-12-22

Abstract Functional MRI (fMRI) for the assessment of language functions is increasingly used in the diagnostic workup of patients with epilepsy. Termed “clinical fMRI,” such an approach is also feasible in children who may display specific patterns of language reorganization. This study was aimed at assessing language reorganization in pediatric epilepsy patients, using fMRI. We studied 26 pediatric epilepsy patients (median age, 13.05 years; range, 5.6–18.7 years) and 23 healthy control children (median age, 9.37 years; range, 6.2–15.4 years), using two child‐friendly fMRI tasks and adapted data‐processing streams. Overall, 81 functional series could be analyzed. Reorganization seemed to occur primarily in homotopic regions in the contralateral hemisphere, but lateralization in the frontal as well as in the temporal lobes was significantly different between patients and controls. The likelihood to find atypical language organization was significantly higher in patients. Additionally, we found significantly stronger activation in the healthy controls in a primarily passive task, suggesting a systematic confounding influence of antiepileptic medication. The presence of a focal cortical dysplasia was significantly associated with atypical language lateralization. We conclude that important confounds need to be considered and that the pattern of language reorganization may be distinct from the patterns seen in later‐onset epilepsy. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.
Design, Synthesis and Structure–Activity Relationship of Functionalized Tetrahydro‐β‐carboline Derivatives as Novel PDE5 Inhibitors
2010-12-22

Abstract Starting from tadalafil as a template, a series of functionalized tetrahydro‐β‐carboline derivatives have been prepared and identified as novel potent and selective PDE5 inhibitors. Replacing the 3,4‐methylenedioxyphenyl at position 6 of tadalafil, together with elongation of the N2 ‐methyl substituent and manipulation of the stereochemical aspects of the two chiral carbons led to the identification of compound XXI , a highly potent PDE5 inhibitor (IC 50 = 3 nM). Compound XXI was also highly selective for PDE5 versus PDE3B, PDE4B, and PDE11A, with a selectivity index of 52 and 235 towards PDE5 rather than PDE11 with both cAMP and cGMP as substrate, respectively.
Phenalinolactones A–D, terpenoglycoside antibiotics from Streptomyces sp. Tü 6071
2010-12-22

Four new terpenoglycoside antibiotics, phenalinolactones A-D were isolated from Streptomyces sp. Tü 6071. The structures were elucidated on the basis of detailed NMR and MS analyses. Phenalinolactones combine a diterpenoid tricycle, a 2,3,6-trideoxysugar, a pyrrole-carboxylic acid and an uncommonly oxidized unsaturated γ-lactone in a unique manner. Phenalinolactones show an inhibitory activity against gram-positive bacteria.
Mislocalization of near‐threshold tactile stimuli in humans: a central or peripheral phenomenon?
2010-12-22

Abstract Principles of brain function can be disclosed by studying their limits during performance. Tactile stimuli with near‐threshold intensities have been used to assess features of somatosensory processing. When stimulating fingers of one hand using near‐threshold intensities, localization errors are observed that deviate significantly from responses obtained by guessing – incorrectly located stimuli are attributed more often to fingers neighbouring the stimulated one than to more distant fingers. Two hypotheses to explain the findings are proposed. The ‘central hypothesis’ posits that the degree of overlap of cortical tactile representations depends on stimulus intensity, with representations less separated for near‐threshold stimuli than for suprathreshold stimuli. The ‘peripheral hypothesis’ assumes that systematic mislocalizations are due to activation of different sets of skin receptors with specific thresholds. The present experiments were designed to decide between the two hypotheses. Taking advantage of the frequency tuning of somatosensory receptors, their contribution to systematic misclocalizations was studied. In the first experiment, mislocalization profiles were investigated using vibratory stimuli with frequencies of 10, 20 and 100 Hz. Unambiguous mislocalization effects were only obtained for the 10‐Hz stimulation, precluding the involvement of Pacinian corpuscles in systematic mislocalization. In the second experiment, Pacinian corpuscles were functionally eliminated by applying a constant 100‐Hz vibratory masking stimulus together with near‐threshold pulses. Despite masking, systematic mislocation patterns were observed rendering the involvement of Pacinian corpuscles unlikely. The results of both experiments are in favor of the ‘central hypothesis’ assuming that the extent of overlap in somatosensory representations is modulated by stimulus intensity.
Fe-Ti oxide-silicate (QUIlF-type) equilibria in feldspathoid-bearing systems
2010-12-22

Silicate-oxide equilibria (abbreviated as QUIlF) have proven to be very powerful tools for reconstructing the temperature and oxygen fugacity evolution of magmatic systems containing magnetite and ilmenite with olivine, quartz, or pyroxenes. In this paper, we extend these QUIlF equilibria to include rocks where silica activity is controlled by equilibria between feldspars and feldspathoids. We present data on the orthomagmatic assemblage of titanomagnetite + ilmenite + feldspar + nepheline + compositionally variable olivine, which we call AUNIlF:
Pseudarthrosis after disruption of an incomplete luno-triquetral coalition: a case report
2010-12-22

Whilst bony luno-triquetral coalitions are known to be asymptomatic, fibro-cartilage unions can cause ulnar-sided wrist pain. The purpose is to present the rare case of painful pseudarthrosis after traumatic disruption of an incomplete luno-triquetral coalition. Recommendations for proper diagnosis and treatment options will be discussed. The case of a 35-year-old male patient is reported, where disruption of a fibro-cartilaginous luno-triquetral coalition resulted in a painful pseudarthrosis. Luno-triquetral fusion with a corticocancellous wedge from the iliac crest and a Herbert screw was undertaken. Using this method pain was relieved but resulted in minor loss of range of motion. We recommend luno-triquetral fusion in the rare case of fracture or pseudarthrosis of a luno-triquetral coalition. The use of a corticocancellous wedge should be considered depending on gap formation after resection of the pseudarthrosis.
Scales in the meaning of adjectives
2010-12-22

The goal of this paper is to show that a degree-based semantics for comparative constructions in English, based on a degree ontology going back to Cresswell (1976), meets the challenge of polarity effects in antonymous adjectives, once it is properly adapted to deal with measure expressions and the so called norm-related inferences. I present an alternative to theories that rely on a shift from degrees as points to degrees as intervals as proposed in von Stechow (1984). My approach builds on the assumption that degrees constitute simple ordinal scales and measures are introduced at the LF by necessity of interpreting numerals. The proposal is evaluated against the data from two languages with completely different polarity patterns, English and Russian.
Neutrophil responses to staphylococcal pathogens and commensals via the formyl peptide receptor 2 relates to phenol‐soluble modulin release and virulence
2010-12-23

ABSTRACT The mechanisms used by the immune system to discriminate between pathogenic and commensal bacteria have remained largely unclear. Recently, we have shown that virulence of Staphylococcus aureus depends on secretion of phenol‐soluble modulin (PSM) peptides that disrupt neutrophils at micromolar concentrations. Moreover, all S. aureus PSMs stimulate and attract neutrophils at nanomolar concentrations via interaction with the formyl‐peptide receptor 2 (FPR2). Here, we demonstrate that FPR2 allows neutrophils to adjust their responses in relation to the aggressiveness of staphylococcal species, which differ largely in their capacity to infect or colonize humans and animals. PSM‐related peptides were detected in all human and animal pathogenic staphylococci, but were absent from most commensal species. Three PSMβ‐like peptides produced by the serious human pathogen Staphylococcus lugdunensis were identified as the previously described S. lugdunensis‐synergistic hemolysins (SLUSHs). SLUSHs attracted and stimulated human leukocytes in a FPR2‐dependent manner, indicating that FPR2 is a general receptor for all PSM‐like peptide toxins. Remarkably, the release of PSMs correlated closely with the apparent capacity of staphylococcal species to cause invasive infections and with their ability to activate FPR2. These findings suggest that the innate immune system may be able to respond in different ways to pathogenic or innocuous staphylococci by monitoring the presence of PSMs via FPR2.—Rautenberg, M., Joo, H. S., Otto, M., Peschel, A. Neutrophil responses to staphylococcal pathogens and commensals via the formyl peptide receptor 2 relates to phenol‐soluble modulin release and virulence. FASEB J. 25, 1254–1263 (2011). www.fasebj.org
Escherichia coli Exports Cyclic AMP via TolC
2010-12-23

ABSTRACT In Escherichia coli more than 180 genes are regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. However, more than 90% of cAMP that is made by intracellular adenylyl cyclases is found in the culture medium. How is cAMP exported from E. coli ? In a tolC mutant, 0.03 mM IPTG (isopropyl-β- d -thiogalactopyranoside) was sufficient to induce β-galactosidase compared to 0.1 mM IPTG in the parent strain. In a cya mutant unable to produce cAMP about 1 mM extracellular cAMP was required to induce β-galactosidase, whereas in a cya tolC mutant 0.1 mM cAMP was sufficient. When cAMP in E. coli cya was generated intracellularly by a recombinant, weakly active adenylyl cyclase from Corynebacterium glutamicum , the critical level of cAMP necessary for induction of maltose degradation was only achieved in a tolC mutant and not in the parent strain. Deletion of a putative cAMP phosphodiesterase of E. coli , CpdA, resulted in a slightly similar, yet more diffuse phenotype. The data demonstrate that export of cAMP via TolC is a most efficient way of E. coli to lower high concentrations of cAMP in the cell and maintain its sensitivity in changing metabolic environments.
Faculty Opinions recommendation of Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo.
2010-12-23

Read the full review for this Faculty Opinions recommended article: Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo.