bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide discovery of DNA polymorphisms by whole genome sequencing differentiates weedy and cultivated rice
Authors: Chai Chenglin , Shankar Rama , Jain Mukesh , Subudhi Prasanta K. 
Published: September 2018

AbstractAnalyzing the genome level DNA polymorphisms between weedy and cultivated rice is crucial to elucidate the molecular basis of weedy and agronomic traits, which in turn can enhance our ability to control weedy rice and its utilization for rice improvement. Here, we presented the genome-wide genetic variations between a weedy rice accession PSRR-1 and two cultivated rice accessions, Bengal and Nona Bokra, belonging to japonica and indica subspecies, respectively. The total number of SNPs and InDels in PSRR/Bengal was similar to that of Nona Bokra/Bengal, but was three times greater than that of PSRR/Nona Bokra. There were 11546 large-effect SNPs/InDels affecting 5673 genes, which most likely differentiated weedy rice from cultivated rice. These large effect DNA polymorphisms were mostly resulted in stop codon gain and least by start codon loss. Analysis of the molecular functions and biological processes of weedy rice specific SNPs/InDels indicated that most of these genes were involved in protein modification/phosphorylation, protein kinase activity, and protein/nucleotide binding. By integrating previous QTL mapping results with the DNA polymorphisms data, the candidate genes for seed dormancy and seed shattering were narrowed down. The genomic resource generated in this study will facilitate discovery of functional variants for weedy and agronomic traits.
Faithful animal modelling of human glioma by using primary initiating cells and its implications for radiosensitization therapy
Authors: Frosina Guido , Ravetti Jean Louis , Corvò Renzo , Fella Mauro , Garrè Maria Luisa , Levrero Fabrizio , Marcello Diana , Marubbi Daniela , Morana Giovanni , Mussap Michele , Neumaier Carlo Emanuele , Profumo Aldo , Raso Alessandro , Rosa Francesca , Vagge Stefano , Vecchio Donatella , Verrico Antonio , Zona Gianluigi , Daga Antonio 
Published: September 2018

AbstractIt has been reported that the ATM kinase inhibitor KU60019 preferentially radiosensitizes orthotopic high grade gliomas (HGG) driven by established U87 and U1242 cell lines bearing specificTP53mutations. We wished to determine whether those results could be extended to tumors driven by primary glioma initiating cells (GIC) that closely mimic clinical tumors. Orthotopic HGG were developed in immunodeficient non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice by intracranial injection of primary GIC isolated from the adult glioblastoma COMI (acronym of patient’s name) and the pediatric anaplastic astrocytoma 239/12. Similar to the clinical tumors of origin, the orthotopic tumors COMI and 239/12 displayed different growth properties with a voluminous expansive lesion that exerted considerable mass effect on the adjacent structures and an infiltrating, gliomatosis-like growth pattern with limited compressive attitude, respectively. Significant elongations of median animal survival bearing the adult COMI tumor was observed after one KU60019 convection enhanced delivery followed by total 7.5 Gy of ionizing radiation delivered in fifteen 0.5 Gy fractions, as compared to animals treated with vehicle + ionizing radiation (105 vs 89 days; ratio: 0.847; 95% CI of ratio 0.4969 to 1.198; P:0.0417). Similarly, a trend to increased median survival was observed with the radiosensitized pediatric tumor 239/12 (186 vs 167 days; ratio: 0.8978; 95% CI of ratio: 0.5352 to 1.260; P: 0.0891). Our results indicate that radiosensitization by KU60019 is effective towards different orthotopic gliomas that faithfully mimic the clinical tumors and that multiple GIC-based animal models may be essential to develop novel therapeutic protocols for HGG transferable to the clinics.
A Bioluminescent Cell Assay to Quantify Prion Protein Dimerization
Authors: Wüsten Katharina Annick , Reddy Pasham Parameshwar , Smiyakin Andrej , Bernis Maria Eugenia , Tamgüney Gültekin 
Published: September 2018

AbstractThe prion protein (PrP) is a cell surface protein that in disease misfolds and becomes infectious causing Creutzfeldt-Jakob disease in humans, scrapie in sheep, and chronic wasting disease in deer and elk. Little is known regarding the dimerization of PrP and its role in disease. We developed a bioluminescent prion assay (BPA) to quantify PrP dimerization by bimolecular complementation of split Gaussia luciferase (GLuc) halves that are each fused to PrP. Fusion constructs between PrP and N- and C-terminal GLuc halves were expressed on the surface of RK13 cells (RK13-DC cells) and dimerized to yield a bioluminescent signal that was decreased in the presence of eight different antibodies to PrP. Dimerization of PrP was independent of divalent cations and was induced under stress. Challenge of RK13-DC cells with seven different prion strains did not lead to detectable infection but was measurable by bioluminescence. Finally, we used BPA to screen a compound library for compounds inhibiting PrP dimerization. One of the most potent compounds to inhibit PrP dimerization was JTC-801, which also inhibited prion replication in RML-infected ScN2a and SMB cells with an EC50 of 370 nM and 220 nM, respectively. We show here that BPA is a versatile tool to study prion biology and to identify anti-prion compounds.
Heme-dependent Inactivation of 5-Aminolevulinate Synthase from Caulobacter crescentus
Authors: Ikushiro Hiroko , Nagami Atsushi , Takai Tomoko , Sawai Taiki , Shimeno Yuki , Hori Hiroshi , Miyahara Ikuko , Kamiya Nobuo , Yano Takato 
Published: September 2018

AbstractThe biosynthesis of heme is strictly regulated, probably because of the toxic effects of excess heme and its biosynthetic precursors. In many organisms, heme biosynthesis starts with the production of 5-aminolevulinic acid (ALA) from glycine and succinyl-coenzyme A, a process catalyzed by a homodimeric enzyme, pyridoxal 5′-phosphate (PLP)-dependent 5-aminolevulinate synthase (ALAS). ALAS activity is negatively regulated by heme in various ways, such as the repression of ALAS gene expression, degradation of ALAS mRNA, and inhibition of mitochondrial translocation of the mammalian precursor protein. There has been no clear evidence, however, that heme directly binds to ALAS to negatively regulate its activity. We found that recombinant ALAS from Caulobacter crescentus was inactivated via a heme-mediated feedback manner, in which the essential coenzyme PLP was rel eased to form the inactive heme-bound enzyme. The spectroscopic properties of the heme-bound ALAS showed that a histidine-thiolate hexa-coordinated ferric heme bound to each subunit with a one-to-one stoichiometry. His340 and Cys398 were identified as the axial ligands of heme, and mutant ALASs lacking either of these ligands became resistant to heme-mediated inhibition. ALAS expressed in C. crescentus was also found to bind heme, suggesting that heme-mediated feedback inhibition of ALAS is physiologically relevant in C. crescentus.
Homoarginine/ADMA ratio and homoarginine/SDMA ratio as independent predictors of cardiovascular mortality and cardiovascular events in lower extremity arterial disease
Authors: Jud Philipp , Hafner Franz , Verheyen Nicolas , Meinitzer Andreas , Gary Thomas , Brodmann Marianne , Seinost Gerald , Hackl Gerald 
Published: September 2018

AbstractEndothelial dysfunction plays a key role in development of atherosclerosis and lower extremity arterial disease (LEAD). Homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are sensitive markers for endothelial dysfunction and independent risk factors for cardiovascular death. However, homoarginine may influence the proatherogenic effects of ADMA and SDMA suggesting homoarginine/ADMA ratio or homoarginine/SDMA ratio as further predictors for cardiovascular mortality. Therefore, we investigated the predictive value of homoarginine/ADMA ratio and homoarginine/SDMA ratio related to cardiovascular mortality and cardiovascular events in claudicant patients with LEAD. 151 patients with intermittent claudication were included in a prospective observational study (observation time 7.7 ± 2.5 years) with cardiovascular mortality as main outcome parameter and the occurrence of cardiovascular events as secondary outcome parameter. Homoarginine, ADMA and SDMA were measured by high-performance liquid chromatography at baseline. Low homoarginine/ADMA ratio and homoarginine/SDMA ratio were independently associated with higher cardiovascular mortality (HR 2.803 [95% CI 1.178–6.674], p = 0.020; HR 2.782 [95% CI 1.061–7.290], p = 0.037, respectively) and higher incidence of cardiovascular events (HR 1.938 [95% CI 1.015–3.700], p = 0.045; HR 2.397 [95% CI 1.243–4.623], p = 0.009, respectively). We observed that homoarginine/ADMA ratio and homoarginine/SDMA ratio are independent predictors for long-term cardiovascular mortality and events in claudicant patients with LEAD.
Learning deficits in rats overexpressing the dopamine transporter
Authors: Bernhardt Nadine , Lieser Maike Kristin , Hlusicka Elizabeth-Barroeta , Habelt Bettina , Wieske Franziska , Edemann-Callesen Henriette , Garthe Alexander , Winter Christine 
Published: September 2018

AbstractWith its capacity to modulate motor control and motivational as well as cognitive functions dopamine is implicated in numerous neuropsychiatric diseases. The present study investigated whether an imbalance in dopamine homeostasis as evident in the dopamine overexpressing rat model (DAT-tg), results in learning and memory deficits associated with changes in adult hippocampal neurogenesis. Adult DAT-tg and control rats were subjected to the Morris water maze, the radial arm maze and a discrimination reversal paradigm and newly generated neurons in hippocampal circuitry were investigated post mortem. DAT-tg rats were found to exhibit a striking inability to acquire information and deploy spatial search strategies. At the same time, reduced integration of adult-born neurons in hippocampal circuitry was observed, which together with changes in striatal dopamine signalling might explain behavioural deficits.
Lower serum calcium levels are a risk factor for a decrease in eGFR in a general non-chronic kidney disease population
Authors: Mizushiri Satoru , Daimon Makoto , Murakami Hiroshi , Kamba Aya , Osonoi Sho , Yamaichi Masato , Matsumura Koki , Tanabe Jutaro , Matsuhashi Yuki , Yanagimachi Miyuki , Tokuda Itoyo , Kurauchi Shizuka , Sawada Kaori 
Published: September 2018

AbstractAssociation between serum calcium (Ca) levels and kidney dysfunction progression in a non-chronic kidney disease (CKD) population has not been well elucidated, especially in consideration for classical metabolic risk conditions such as hypertension, dyslipidemia, and diabetes, and those related to Ca metabolism. Among participants of the population-based Iwaki study of Japanese people, those with an estimated glomerular filtration rate (eGFR) ≧60 ml/min/1.73 m2 and age ≧40 years, and who attended the study consecutively in 2014 and 2015 were enrolled (gender (M/F): 218/380; age: 58.9 ± 10.2). Regression analysis showed a significant correlation between serum Ca levels and a change in eGFR in the 1-year period (∆eGFR) after adjustment with multiple factors including those related to Ca metabolism (β = 0.184, p < 0.001). When subjects were stratified into tertiles based on their serum Ca levels (higher >9.6 mg/dL, middle 9.4–9.6 mg/dL, lower <9.4 mg/dL), lower serum Ca levels were a significant risk for a rapid decliner of eGFR designated as the lower one third of ∆eGFR (<−4.40 ml/min/1.73 m2) (odds ratio 2.41, 95% confidence interval 1.47–3.94). Lower serum Ca levels are a significant risk for rapid decrease in eGFR, independent of previously reported metabolic risk factors in this general population with non-CKD, or eGFR ≧60 ml/min/1.73 m2.
Comparison of interleukin-2-inducible kinase (ITK) inhibitors and potential for combination therapies for T-cell lymphoma
Authors: Mamand Sami , Allchin Rebecca L. , Ahearne Matthew J. , Wagner Simon D. 
Published: September 2018

AbstractPatients with peripheral T-cell lymphomas generally have poor clinical outcomes with conventional chemotherapy. Recent advances have demonstrated that a large subgroup of PTCL are derived from follicular helper (Tfh) T-cells. These cases show a characteristic pattern of gene expression, which includes high-level protein expression of interleukin-2-inducible kinase (ITK). ITK is a member of the TEC family of kinases and normally has essential functions in regulating T-cell receptor signalling and T-cell differentiation. Here we report a side-by-side comparison of four ITK inhibitors. We investigate effects on apoptosis, phosphorylation of signaling molecules, calcium flux and migration. In line with a specific mechanism of action ONO7790500 and BMS509744 did not inhibit MEK1/2 or AKT phosphorylation although other ITK inhibitors, ibrutinib and PF-06465469, did have this effect. Specific ITKi had modest effects on apoptosis alone but there was definite synergy with doxorubicin, pictilisib (PI3Ki) and idelalisib (PI3Kδi). ITKi repressed migration of Jurkat cells caused by CXCL12 and the CXCR4 antagonist, plerixafor enhanced this effect. Overall ITKi may have several mechanisms of action that will be therapeutically useful in PTCL including reduction in survival and perturbation of trafficking.
Global-scale multidecadal variability missing in state-of-the-art climate models
Authors: Kravtsov S. , Grimm C. , Gu S. 
Published: September 2018

AbstractReliability of future global warming projections depends on how well climate models reproduce the observed climate change over the twentieth century. In this regard, deviations of the model-simulated climate change from observations, such as a recent “pause” in global warming, have received considerable attention. Such decadal mismatches between model-simulated and observed climate trends are common throughout the twentieth century, and their causes are still poorly understood. Here we show that the discrepancies between the observed and simulated climate variability on decadal and longer timescale have a coherent structure suggestive of a pronounced Global Multidecadal Oscillation. Surface temperature anomalies associated with this variability originate in the North Atlantic and spread out to the Pacific and Southern oceans and Antarctica, with Arctic following suit in about 25–35 years. While climate models exhibit various levels of decadal climate variability and some regional similarities to observations, none of the model simulations considered match the observed signal in terms of its magnitude, spatial patterns and their sequential time development. These results highlight a substantial degree of uncertainty in our interpretation of the observed climate change using current generation of climate models.
Institution of a Surgical Curriculum for Trabecular Microbypass Stent Placement
Authors: Hakim Farida , Malhotra Varun , Colby Kathryn , Riaz Kamran 
Published: September 2018

Purpose This article evaluates whether a targeted, stepwise curriculum for microbypass stent placement leads to successful insertion of the iStent (Glaukos, Laguna Hills, CA) by resident surgeons.
Participants Senior (postgraduate year 4) ophthalmology residents (9 residents) from three classes during the 2015 to 2016, 2016 to 2017, and 2017 to 2018 academic years.
Design Residents participated in a three-stage surgical curriculum. First, a wet laboratory was held for residents to gain familiarity with the device and develop bimanual surgical proficiency. The wet laboratory involved several stations, with each station requiring increased dexterity for successful completion. Next, residents practiced bimanual intraoperative gonioscopy after routine phacoemulsification procedures. Finally, residents performed combined phacoemulsification and iStent insertion under the supervision of an experienced attending surgeon. Primary success was determined by correct anatomical placement of the device confirmed via subsequent intraoperative gonioscopy by the supervising surgeon. Secondary success was measured by change in intraocular pressure (IOP) and number of topical hypotensive medications used after surgery. Residents provided feedback about the effectiveness of the curriculum via an online survey.
Results There were a total of 43 cases. There were no significant intraoperative complications, including hyphema. The iStent location was confirmed during both intraoperative and postoperative gonioscopy and was noted to be in appropriate position for the duration of the follow-up period (6–12 months) for all patients. Average preoperative IOP in our subjects was 17.5 ± 4.0 mm Hg and mean number of preoperative medications was 1.4 ± 1.0. At 6 months' postoperative, average IOP was 14.5 ± 2.2 mm Hg (13% reduction from baseline [±15%]). At 12 months' postoperative, average IOP was 14.4 ± 3.5 mm Hg, with a reduction of 14% (±18%). The mean number of medications at follow-up was 1.2 ± 1.1. Mean postoperative IOP at 6 and 12 months was significantly lower compared with baseline (p = 0.0002, p = 0.0001). Residents agreed that the curriculum prepared them to perform iStent insertion during residency and most residents felt prepared after residency.
Conclusion This stepwise surgical curriculum for trabecular microbypass stent placement leads to successful performance of the procedure by residents and is a useful model for other residency programs.
Sexualmedizin in der Psychiatrie, Psychosomatik, Psychotherapie und Nervenheilkunde
Authors: Berner M.M. 
Published: September 2018

ZusammenfassungSexuelle Probleme sind in der Allgemeinbevölkerung wie auch in der psychiatrisch-psychotherapeutischen Praxis häufig. Die ICD-10 listet die Mehrzahl der sexuellen Störungen im F-Kapitel der psychischen Störungen auf. In der psychiatrisch-psychotherapeutischen Aus-, Fort- und Weiterbindung nehmen sie jedoch keinen großen Raum ein. Viele Ärzte setzen sich nur wenig mit der Sexualanamnese der Patienten auseinander. Der Artikel erläutert an drei Beispielen die Relevanz der Sexualmedizin für Psychiatrie, Psychosomatik und Psychotherapie: Sexuelle Funktionsstörungen als häufigste Problemstellungen, Paraphilien als forensisch relevante Symptomatik mit großen Vorurteilen in der Bevölkerung und Transsexualität, deren Behandlung konsequent interdisziplinäre Ansätze erfordert und lebensverändernde Konsequenzen für die Betroffenen hat. Aus diesen Beispielen wird die Wichtigkeit der vertieften Beschäftigung mit der Thematik und der Auseinandersetzung mit diesem Aspekt der Psychosomatik für den Praktiker ersichtlich. Das gilt jedoch auch für das gesamte Fach mit seinen entsprechenden Curricula.
Evidence-based psychopharmacotherapy. A valid and reliable approach?
Authors: Möller H.-J. 
Published: September 2018

Summary
Objective: Psychopharmacotherapy should now be regulated in the sense of evidence-based medicine (EBM), as is the case in other areas of clinical treatment in medicine.
Methods: Descriptive overview of limitations and problems of EBM in pharmacopsychiatry.
Results: In general this is a meaningful development, which principally will have a positive impact on routine health care in psychiatry. But several related problems should not be ignored. So far consensus on an internationally accepted evidence graduation could not be reached, due to several difficulties related to this. For example, to focus on the results of meta-analyses instead of considering relevant single studies results in a decision-making logic which is in conflict with the rationale applied by drug authorities in the licensing process. Attempts to regulate psychopharmacotherapy in the sense of EBM come closer to their limits the more complex the clinical situation and the respective decision-making logic are.
Conclusion: EBM has severe problems and limitations. Even in times of EBM a large part of complex clinical decision-making in psychopharmacotherapy still relies more on clinical experience and a consensus about clinical experience, traditions and belief systems than on results of efficacy oriented phase-III and effectiveness-oriented phase-IV clinical studies.
Immunologische Aspekte psychischer Störungen bei rheumatischen Erkrankungen
Authors: Straub R. H. , Zielasek J. 
Published: September 2018

ZusammenfassungEs gibt vielfältige Wechselwirkungen zwischen entzündlichen Erkrankungen und psychischen Störungen. Nicht nur sind post- oder periinfektiöse Depressionen oder „Fatigue“- Symptome sehr häufig, zunehmend wird auch entschlüsselt, auf welche Weise Immunsystem und Psyche einander beeinflussen. Auf der Grundlage solcher Erkenntnisfortschritte ergeben sich neue therapeutische Möglichkeiten, die erst ansatzweise untersucht sind. In diesem Übersichtsartikel werden zunächst die grundlegenden Mechanismen der Interaktionen zwischen psychischen Störungen beschrieben. Am Beispiel der rheumatologischen Erkrankungen werden diese konkretisiert und die therapeutischen Erfahrungen mit psychischen Störungen bei entzündlichen Erkrankungen im Allgemeinen thematisiert.
A translational medicine approach to molecular psychiatry
Authors: Honer W. G. 
Published: September 2018

SummaryThe place of molecular medicine in psychiatry is rapidly evolving. Research findings appear with great frequency, but the integration and impact of molecular research into the clinical practice of psychiatry is negligible. The present paper uses a translational medicine framework to provide a critical review of the possibilities for molecular medicine in psychiatry, focused on schizophrenia as an example illness.
Psychosomatik – quo vadis?
Authors: Bohus M. 
Published: September 2018

ZusammenfassungDas Fachgebiet der Psychosomatischen Medizin und Psychotherapie steht vor einem massiven Überalterungs- und Nachwuchsproblem. Schon heute kann die Versorgung in psychosomatischen Kliniken nur durch Rekrutierung von anderen Fachärzten bzw. Psychologen gewährleistet werden. Die Ursachen dieser bedauerlichen Entwicklung sind vielfältig. Zum einen hat sich unser Verständnis über die Bedeutung somatischer Parameter in der Entwicklung psychischer und somato-psychischer Erkrankungen erweitert und sich in der Etablierung fachgebundener Psychotherapie niedergeschlagen. Zum anderen ist durch die Etablierung der Psychologischen Psychotherapie eine hochkompetente Konkurrenz für die ärztliche Psychotherapie erwachsen, die sicherlich Einfluss nimmt auf die Karriere-Planung junger Kollegen. Wenn psychosomatisches Wissen und Handeln weiter Bestandteil der ärztlichen Kernkompetenz bleiben soll, sind tiefgreifende Veränderungen der Facharztstruktur notwendig.