bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton-Detected Solid-State NMR Spectroscopy of Bone with Ultrafast Magic Angle Spinning
Authors: Mroue Kamal H. , Nishiyama Yusuke , Kumar Pandey Manoj , Gong Bo , McNerny Erin , Kohn David H. , Morris Michael D. , Ramamoorthy Ayyalusamy 
Published: July 2015

AbstractWhile obtaining high-resolution structural details from bone is highly important to better understand its mechanical strength and the effects of aging and disease on bone ultrastructure, it has been a major challenge to do so with existing biophysical techniques. Though solid-state NMR spectroscopy has the potential to reveal the structural details of bone, it suffers from poor spectral resolution and sensitivity. Nonetheless, recent developments in magic angle spinning (MAS) NMR technology have made it possible to spin solid samples up to 110 kHz frequency. With such remarkable capabilities, 1H-detected NMR experiments that have traditionally been challenging on rigid solids can now be implemented. Here, we report the first application of multidimensional 1H-detected NMR measurements on bone under ultrafast MAS conditions to provide atomistic-level elucidation of the complex heterogeneous structure of bone. Our investigations demonstrate that two-dimensional 1H/1H chemical shift correlation spectra for bone are obtainable using fp-RFDR (finite-pulse radio-frequency-driven dipolar recoupling) pulse sequence under ultrafast MAS. Our results infer that water exhibits distinct 1H−1H dipolar coupling networks with the backbone and side-chain regions in collagen. These results show the promising potential of proton-detected ultrafast MAS NMR for monitoring structural and dynamic changes caused by mechanical loading and disease in bone.
Cyclic AMP Mimics the Anti-ageing Effects of Calorie Restriction by Up-Regulating Sirtuin
Authors: Wang Zhuoran , Zhang Lu , Liang Yaru , Zhang Chi , Xu Zhiyu , Zhang Lang , Fuji Ryosuke , Mu Wei , Li Liyuan , Jiang Junjun , Ju Yong , Wang Zhao 
Published: July 2015

AbstractCyclic adenosine monophosphate (cAMP) plays an important role in many biological processes as a second messenger and cAMP treatment has been reported to extend the lifespan of wild-type Drosophila melanogaster. Our study showed that exogenous cAMP improved ageing-related phenotypes by increasing the protein level of Sirtuins, which prevented metabolic disorders to mimic the effect of calorie restriction. Experiments in vitro showed that cAMP directly bound to SIRT1 and SIRT3 and consequently increased their activity. These findings suggest that cAMP slows the ageing process and is a good candidate to mimic calorie restriction. Our research provides a promising therapeutic strategy to target metabolic disorder-induced ageing-related diseases.
Azithromycin inhibits IL-1 secretion and non-canonical inflammasome activation
Authors: Gualdoni Guido A. , Lingscheid Tilman , Schmetterer Klaus G. , Hennig Annika , Steinberger Peter , Zlabinger Gerhard J. 
Published: July 2015

AbstractDeregulation of inflammasome activation was recently identified to be involved in the pathogenesis of various inflammatory diseases. Although macrolide antibiotics display well described immunomodulatory properties, presumably involved in their clinical effects, their impact on inflammasome activation has not been investigated. We compared the influence of macrolides on cytokine induction in human monocytes. The role of intracellular azithromycin-accumulation was examined by interference with Ca++-dependent uptake. We have also analysed the signalling cascades involved in inflammasome activation and substantiated the findings in a murine sepsis model. Azithromycin, but not clarithromycin or roxithromycin, specifically inhibited IL-1α and IL-1β secretion upon LPS stimulation. Interference with Ca++-dependent uptake abolished the cytokine-modulatory effect, suggesting a role of intracellular azithromycin accumulation in the modulatory role of this macrolide. Azithromycin’s inhibiting effects were observed upon LPS, but not upon flagellin, stimulation. Consistent with this observation, we found impaired induction of the LPS-sensing caspase-4 whereas NF-κB signalling was unaffected. Furthermore, azithromycin specifically affected IL-1β levels in a murine endotoxin sepsis model. We provide the first evidence of a differential impact of macrolides on the inflammasome/IL-1β axis, which may be of relevance in inflammasome-driven diseases such as chronic obstructive pulmonary disease or asthma.
A novel crosstalk between TLR4- and NOD2-mediated signaling in the regulation of intestinal inflammation
Authors: Kim Hajeong , Zhao Quanju , Zheng Hua , Li Xin , Zhang Tuo , Ma Xiaojing 
Published: July 2015

AbstractAlthough Toll-like receptor 4 (TLR4)- and nucleotide-binding oligomerization domain 2 (NOD2)-mediated signaling mechanisms have been extensively studied individually, the crosstalk between them in the regulation of intestinal mucosal defense and tissue homeostasis has been underappreciated. Here, we uncover some novel activities of NOD2 by gene expression profiling revealing the global nature of the cross-regulation between TLR4- and NOD2-mediated signaling. Specifically, NOD2 is able to sense the intensity of TLR4-mediated signaling, resulting in either synergistic stimulation of Interluekin-12 (IL-12) production when the TLR signaling intensity is low; or in the inhibition of IL-12 synthesis and maintenance of intestinal mucosal homeostasis when the TLR signaling intensifies. This balancing act is mediated through receptor-interacting serine/threonine kinase 2 and the transcriptional regulator CCAAT/enhancer-binding protein α (C/EBPα) via its serine 248 phosphorylation by Protein Kinase C. Mice deficient in C/EBPα in the hematopoietic compartment are highly susceptible to chemically induced experimental colitis in an IL-12-dependent manner. Additionally, in contrast to the dogma, we find that the major Crohn’s disease-associated NOD2 mutations could cause a primarily immunodeficient phenotype by selectively impairing TLR4-mediated IL-12 production and host defense. To restore the impaired homeostasis would be a way forward to developing novel therapeutic strategies for inflammatory bowel diseases.
Study of Protein Expresion in Peri-Infarct Tissue after Cerebral Ischemia
Authors: Brea David , Agulla Jesús , Staes An , Gevaert Kris , Campos Francisco , Sobrino Tomás , Blanco Miguel , Dávalos Antoni , Castillo José , Ramos-Cabrer Pedro 
Published: July 2015

AbstractIn this work, we report our study of protein expression in rat peri-infarct tissue, 48 h after the induction of permanent focal cerebral ischemia. Two proteomic approaches, gel electrophoresis with mass spectrometry and combined fractional diagonal chromatography (COFRADIC), were performed using tissue samples from the periphery of the induced cerebral ischemic lesions, using tissue from the contra-lateral hemisphere as a control. Several protein spots (3408) were identified by gel electrophoresis and 11 showed significant differences in expression between peri-infarct and contra-lateral tissues (at least 3-fold, p < 0.05). Using COFRADIC, 5412 proteins were identified, with 72 showing a difference in expression. Apart from blood-related proteins (such as serum albumin), both techniques showed that the 70 kDa family of heat shock proteins were highly expressed in the peri-infarct tissue. Further studies by 1D and 2D western blotting and immunohistochemistry revealed that only one member of this family (the inducible form, HSP72 or HSP70i) is specifically expressed by the peri-infarct tissue, while the majority of this family (the constitutive form, HSC70 or HSP70c) is expressed in the whole brain. Our data support that HSP72 is a suitable biomarker of peri-infarct tissue in the ischemic brain.
Spexin Enhances Bowel Movement through Activating L-type Voltage-dependent Calcium Channel via Galanin Receptor 2 in Mice
Authors: Lin Cheng-yuan , Zhang Man , Huang Tao , Yang Li-ling , Fu Hai-bo , Zhao Ling , Zhong Linda LD , Mu Huai-xue , Shi Xiao-ke , Leung Christina FP , Fan Bao-min , Jiang Miao , Lu Ai-ping , Zhu Li-xin , Bian Zhao-xiang 
Published: July 2015

AbstractA novel neuropeptide spexin was found to be broadly expressed in various endocrine and nervous tissues while little is known about its functions. This study investigated the role of spexin in bowel movement and the underlying mechanisms. In functional constipation (FC) patients, serum spexin levels were significantly decreased. Consistently, in starved mice, the mRNA of spexin was significantly decreased in intestine and colon. Spexin injection increased the velocity of carbon powder propulsion in small intestine and decreased the glass beads expulsion time in distal colon in mice. Further, spexin dose-dependently stimulated the intestinal/colonic smooth muscle contraction. Galanin receptor 2 (GALR2) antagonist M871, but not Galanin receptor 3 (GALR3) antagonist SNAP37899, effectively suppressed the stimulatory effects of spexin on intestinal/colonic smooth muscle contraction, which could be eliminated by extracellular [Ca2+] removal and L-type voltage-dependentCa2+ channel (VDCC) inhibitor nifedipine. Besides, spexin dramatically increased the [Ca2+]i in isolated colonic smooth muscle cells. These data indicate that spexin can act on GALR2 receptor to regulate bowel motility by activating L-type VDCC. Our findings provide evidence for important physiological roles of spexin in GI functions. Selective action on spexin pathway might have therapeutic effects on GI diseases with motility disorders.
Escherichia coli as host for membrane protein structure determination: a global analysis
Authors: Hattab Georges , Warschawski Dror E. , Moncoq Karine , Miroux Bruno 
Published: July 2015

AbstractThe structural biology of membrane proteins (MP) is hampered by the difficulty in producing and purifying them. A comprehensive analysis of protein databases revealed that 213 unique membrane protein structures have been obtained after production of the target protein in E. coli. The primary expression system used was the one based on the T7 RNA polymerase, followed by the arabinose and T5 promoter based expression systems. The C41λ(DE3) and C43λ(DE3) bacterial mutant hosts have contributed to 28% of non E. coli membrane protein structures. A large scale analysis of expression protocols demonstrated a preference for a combination of bacterial host-vector together with a bimodal distribution of induction temperature and of inducer concentration. Altogether our analysis provides a set of rules for the optimal use of bacterial expression systems in membrane protein production.
Pyrimidinone: versatile Trojan horse in DNA photodamage?
Authors: Micheel Mathias , Ziegenbein Christian Torres , Gilch Peter , Ryseck Gerald 
Published: July 2015

Abstract
(6-4) Photolesions between adjacent pyrimidine DNA bases are prone to secondary photochemistry. It has been shown that singlet excited (6-4) moieties form Dewar valence isomers as well as triplet excitations. We here report on the triplet state of a minimal model for the (6-4) photolesion, 1-methyl-2(1H)-pyrimidinone. Emphasis is laid on its ability to abstract hydrogen atoms from alcohols and carbohydrates. Steady-state and time-resolved experiments consistently yield bimolecular rate constants of ∼104 M−1 s−1 for the hydrogen abstraction. The process also occurs intramolecularly as experiments on zebularine (1-(β-d-ribofuranosyl)-2(1H)-pyrimidinone) show.
Examining the Echolalia Literature: Where Do Speech-Language Pathologists Stand?
Authors: Stiegler Lillian N. 
Published: July 2015

PurposeEcholalia is a common element in the communication of individuals with autism spectrum disorders. Recent contributions to the literature reflect significant disagreement regarding how echolalia should be defined, understood, and managed. The purpose of this review article is to give speech-language pathologists and others a comprehensive view of the available perspectives on echolalia.MethodPublished literature from the disciplines of behavioral intervention, linguistics, and speech-language intervention is discussed. Special areas of focus include operational definitions, rationales associated with various approaches, specific procedures used to treat or study echolalic behavior, and reported conclusions.ConclusionsDissimilarities in the definition and understanding of echolalia have led to vastly different approaches to management. Evidence-based practice protocols are available to guide speech-language interventionists in their work with individuals with autism spectrum disorders.
Folded meander line antenna for wireless M‐Bus in the VHF and UHF bands
Authors: Loutridis A. , John M. , Ammann M.J. 
Published: July 2015

The first dual‐band printed monopole antenna for wireless M‐Bus and M2M applications with operation in the VHF and lower UHF bands is presented. The antenna operates at 169 and 433 MHz. The miniaturisation of the proposed compact antenna is based on a double‐sided meandering structure offering an easily controlled large frequency ratio. The antenna provides high total efficiency and gain in both bands. Measured and simulated results are reported.
Können psychometrische Tests den Erfolg im Auswahlgespräch zum Medizinstudium vorhersagen? Eine Querschnittsstudie an einer deutschen Hochschule
Authors: Kötter T. , Obst K. , Brüheim L. , Eisemann N. , Voltmer E. , Katalinic A. 
Published: July 2015

Zusammenfassung
Ziel der Studie Die Abiturnote ist bei der Vergabe von Medizinstudienplätzen das Hauptauswahlkriterium. Für den Studienerfolg scheint sie ein zuverlässiger Prädiktor zu sein. Ihr Einsatz als alleiniges Auswahlkriterium steht jedoch in der Kritik. An einigen Hochschulen sind Auswahlgespräche Teil des Auswahlverfahrens (AdH). Diese sind jedoch zeitaufwändig und von unklarer Validität. Der (zusätzliche) Einsatz geeigneter psychometrischer Instrumente könnte den Aufwand verringern und die Validität erhöhen. Mit dieser Studie soll untersucht werden, inwieweit psychometrische Instrumente das Ergebnis des Auswahlgespräches vorhersagen bzw. unabhängige Information beinhalten.
Methodik Es handelt sich um eine Querschnittstudie zum Zusammenhang der Ergebnisse psychometrischer Testungen mit denen des Auswahlgespräches im Rahmen des AdH. Als Zielgröße wurde die Punktzahl des Auswahlgespräches verwendet. An Instrumenten wurden das NEO-Fünf-Faktoren-Inventar, die Hospital Anxiety and Depression Scale (HADS) und der Fragebogen zur Ermittlung arbeitsbezogener Verhaltens- und Erlebensmuster (AVEM) verwendet.
Ergebnisse Es zeigte sich ein statistisch signifikanter Zusammenhang mit dem Ergebnis des mündlichen Auswahlgespräches für die Dimension Lebenszufriedenheit des AVEM und den Summenscore der Subskala Depressivität der HADS. Zudem erzielten diejenigen TeilnehmerInnen ein besseres Ergebnis im Auswahlgespräch, die vorher kein Bewerbungstraining absolviert hatten.
Schlussfolgerung Die verwendeten Instrumente können Auswahlgespräche nicht ersetzen, da sie etwas anderes messen. Abzuwarten bleibt, ob die gewählten Parameter Studienerfolg vorhersagen.
Identification of a Novel Agonist-Like Autoantibody in Preeclamptic
Patients
Authors: Velloso Elizabeth Portugal , Pimentel Renata Lúcia , Braga Janaína F. , Cabral Antônio Carlos Vieira , Reis Zilma Silveira N. , Bader Michael , Santos Robson Augusto S. , Wallukat Gerd 
Published: July 2015

Abstract

BACKGROUND
Recent studies have shown that preeclampsia (PE) is associated with the presence of autoantibodies (AABs) that activate the angiotensin II AT 1 receptor, which could contribute to many of the symptoms of PE.

METHODS
To investigate the frequency and the targets of AABs in preeclamptic women (31 cases) and healthy pregnant normotensive women (29 cases) in Brazil, antibodies from serum samples were detected by a bioassay using spontaneously beating neonatal rat cardiomyocytes in culture. In the cardiomyocytes, the agonistic AABs induce a positive or negative chronotropic response, mimicking the corresponding receptor agonists. The specificity of the AAB response was identified by specific receptor antagonists.

RESULTS
Thirty preeclamptic patients (97%) presented AABs against the angiotensin II AT 1 receptor. The agonistic effect of the AAB was blocked by irbesartan and neutralized by a peptide corresponding to the second extracellular loop of this receptor. Strikingly, we discovered that all sera from the severe preeclamptic patients (16 cases) contained a novel agonist-like AAB directed against the endothelin-1 ETA receptor in addition to the AABs against the angiotensin II AT 1 receptor. This AAB was selectively blocked by the antagonist BQ-123, antagonized by the protein kinase C (PKC) inhibitor Calphostin C and neutralized by peptides corresponding to the second extracellular loop of the endothelin-1 ETA receptor subtype.

CONCLUSIONS
We described, for the first time, the presence of endothelin-1 ETA receptor AABs in PE. Our results suggest that the presence of both agonistic AABs may be involved in the pathogenesis of severe PE.
Guiding Hypertension Management Using Central Blood Pressure: Effect
of Medication Withdrawal on Left Ventricular Function
Authors: Kosmala Wojciech , Marwick Thomas H. , Stanton Tony , Abhayaratna Walter P. , Stowasser Michael , Sharman James E. 
Published: July 2015

Abstract

BACKGROUND
Central blood pressure (BP) is an acknowledged contributor to end-organ damage and independent determinant of prognosis. Primary analysis from the BPGUIDE study demonstrated no detriment on left ventricular (LV) structure from central BP-guided hypertension management, despite significant medication withdrawal. However, the effect of this on LV function has not been investigated. In this study, we sought to investigate the impact of central BP-guided hypertension management on LV systolic and diastolic performance.

METHODS
A total of 286 enrollees with uncomplicated hypertension were randomized to therapeutic decisions guided by best-practice usual care (UC) or, in addition, by central BP intervention (CBP) for 12 months. Each participant underwent baseline and follow-up 2-dimensional echocardiography, with assessment undertaken by an expert blinded to participant allocation.

RESULTS
Antihypertensive medication quantity remained unchanged for UC but significantly decreased with intervention. However, no significant between-group differences were noted for changes during follow-up in both brachial and central BP, as well as other central hemodynamic parameters: augmentation index and augmented pressure. Similarly, there were no differences between groups in parameters of LV diastolic function: tissue e ′ velocity (∆UC vs. ∆CBP; P = 0.27) and E / e ′ ratio (∆UC vs. ∆CBP; P = 0.60), and systolic parameters: LV longitudinal strain (∆UC vs. ∆CBP; P = 0.55), circumferential strain (∆UC vs. ∆CBP; P = 0.79), and ejection fraction (∆UC vs. ∆CBP; P = 0.15).

CONCLUSIONS
Hypertension management guided by central BP, resulting in significant withdrawal of medication to maintain appropriate BP control, had no adverse effect on LV systolic or diastolic function.
clinical trials registration
Australia New Zealand Clinical Trial Registry Number ACTRN12608 000041358
Overcoming barriers to implementing patient-reported outcomes in an electronic health record: a case report
Authors: Harle Christopher A , Listhaus Alyson , Covarrubias Constanza M , Schmidt Siegfried OF , Mackey Sean , Carek Peter J , Fillingim Roger B , Hurley Robert W 
Published: July 2015

Abstract
In this case report, the authors describe the implementation of a system for collecting patient-reported outcomes and integrating results in an electronic health record. The objective was to identify lessons learned in overcoming barriers to collecting and integrating patient-reported outcomes in an electronic health record. The authors analyzed qualitative data in 42 documents collected from system development meetings, written feedback from users, and clinical observations with practice staff, providers, and patients. Guided by the Unified Theory on the Adoption and Use of Information Technology, 5 emergent themes were identified. Two barriers emerged: (i) uncertain clinical benefit and (ii) time, work flow, and effort constraints. Three facilitators emerged: (iii) process automation, (iv) usable system interfaces, and (v) collecting patient-reported outcomes for the right patient at the right time. For electronic health record-integrated patient-reported outcomes to succeed as useful clinical tools, system designers must ensure the clinical relevance of the information being collected while minimizing provider, staff, and patient burden.
Infants Fed a Lower Calorie Formula With 2′FL Show Growth and 2′FL Uptake Like Breast‐Fed Infants
Authors: Marriage Barbara J. , Buck Rachael H. , Goehring Karen C. , Oliver Jeffery S. , Williams Jennifer A. 
Published: July 2015

ABSTRACTObjectives:The aim of the present study was to examine the growth and tolerance of infants fed infant formulas with a caloric density closer to human milk (HM) supplemented with human milk oligosaccharides (HMOs) and to study uptake of the HMOs.Methods:A prospective, randomized, controlled, growth and tolerance study was conducted in healthy, singleton infants (birth weight ≥2490 g), who were enrolled by day of life (DOL) 5. Formula‐fed infants were randomized to 1 of 3 formulas with a caloric density of 64.3 kcal/dL. Each formula contained galactooligosaccharides, and the 2 experimental formulas contained varying levels (0.2 and 1.0 g/L) of the HMO 2′‐fucosyllactose (2′FL). The 3 formula groups were compared with an HM‐fed reference group. Infants were exclusively fed either formula (n = 189) or HM (n = 65) from enrollment to 119 DOL. 2′FL was measured in the blood and urine collected from a subset of infants at DOL 42 and 119, and in HM collected from breast‐feeding mothers at DOL 42.Results:There were no significant differences among any groups for weight, length, or head circumference growth during the 4‐month study period. All of the formulas were well tolerated and comparable for average stool consistency, number of stools per day, and percent of feedings associated with spitting up or vomit. 2′FL was present in the plasma and urine of infants fed 2′FL, and there were no significant differences in 2′FL uptake relative to the concentration fed.Conclusions:This is the first report of infants fed 2′FL‐fortified formulas with a caloric density similar to HM. Growth and 2′FL uptake were similar to those of HM‐fed infants.
Leopard Skin–Like Colonic Mucosa
Authors: Obayashi Naho , Arai Katsuhiro , Nakano Natsuko , Mizukami Tomoyuki , Kawai Toshinao , Yamamoto Shojiro , Shimizu Hirotaka , Nunoi Hiroyuki , Shimizu Toshiaki , Tang Julian , Onodera Masafumi 
Published: July 2015

ABSTRACTBackground:Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes are unable to eradicate pathogens because of a deficit of nicotinamide adenine dinucleotide phosphate oxidase. Among CGD patients, ∼30% to 50% develop severe gastrointestinal tract symptoms. Although characteristic histologic findings of CGD‐associated colitis have been reported, information on endoscopic features remained vague.Methods:A total of 8 male patients with CGD (ages 2–23 years) from 2 Japanese institutions underwent colonoscopy for the evaluation of their fever, diarrhea, bloody stool, and abdominal pain. The endoscopic and histologic findings were retrospectively reviewed.Results:The endoscopic findings of CGD‐associated colitis appeared varied. Notably, brownish dots over a yellowish edematous mucosa were observed in 3 of the 8 patients. Prominent pigment‐laden macrophages were noted histologically on the mucosa.Conclusions:Although nonspecific endoscopic findings of CGD‐associated colitis have been reported before, our observation of brownish dots spread across a yellowish edematous mucosa, termed “leopard sign,” could be a unique feature of this condition.