bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study
Authors: Ralph David J. , Eardley Ian , Taubel Jorg , Terrill Paul , Holland Tim
Published: January 2018

Background

Current treatments for erectile dysfunction (ED) have some limitations.

Aim

This study evaluated the efficacy and tolerability of MED2005, a 0.2% glyceryl trinitrate topical gel, formulated into an enhanced absorption topical delivery system (DermaSys), administered on demand, in the treatment of ED.

Methods

This randomized, double-blinded, placebo-controlled, phase II crossover trial involved 232 men with ED (231 treated, 230 assessed for efficacy) and their partners. After a 4-week run-in period, patients were randomized to 1 of 2 treatment sequences, MED2005-placebo or placebo-MED2005. Each treatment was given for 4 weeks, separated by a 1-week washout interval. Efficacy was assessed by the International Index of Erectile Function (IIEF), the Sexual Encounter Profile, a Global Assessment Questionnaire (GAQ), and specific questions about the onset and offset of action and treatment preferences (patients and partners).

Outcomes

The primary outcome measure was the IIEF erectile function domain (IIEF-EF) score. Other efficacy assessments were secondary outcomes.

Results

The mean baseline IIEF-EF score was 17.1 (SD = 5.7), and this increased to 19.6 (SD = 7.5) after MED2005 treatment and 18.5 (SD = 6.7) after placebo (P = .0132). Overall, 23.1% of patients showed a clinically relevant (≥4-point) increase in IIEF-EF scores after treatment with MED2005 only compared with 14.5% who responded after MED2005 and placebo, 14.0% who responded after placebo only, and 48.4% who did not respond after either treatment (P = .0272). MED2005 also was associated with significant improvements compared with placebo in the other IIEF domains, and this was consistent with patients’ and partners’ responses to the GAQ. For all assessments, significant effects of MED2005 were seen primarily in patients with mild ED. The start of erection was noticed within 5 and 10 minutes in 44.2% and 69.5%, respectively, of all intercourse attempts with MED2005. Patients and partners showed significant preferences for MED2005 over placebo. The most commonly reported adverse events during MED2005 treatment were headache (patients, n = 18 [7.9%]; partners, n = 3 [1.3%]) and nasopharyngitis (patients, n = 13 [5.7%]; partners, n = 2 [0.9%]).

Clinical Implications

These findings suggest that topical glyceryl trinitrate could be a useful treatment option in ED.

Strengths and Limitations

Strengths of this study include the use of a validated outcome measure. Limitations include the use of only 1 dosage.

Conclusion

Further studies are warranted to investigate the efficacy of topical glyceryl trinitrate to include higher doses, thereby improving clinical significance, especially in cases of moderate and severe ED.
Do leader expectations shape employee service performance? Enhancing self-expectations and internalization in employee role identity
Authors: Binyamin Galy
Published: January 2018

This paper expands the Theory of Planned Behavior to explore the role of leaders’ normative expectations in driving employees’ service performance. Two quantitative studies in the context of retailing indicate that leaders’ normative expectations for high-quality service are related to employee service performance, through employee self-expectations for quality service (Study 1;N=75), and service role identity (Study 2;N=226). Both studies apply Kelman’s Theory of Social Influence by exploring how leaders influence employees’ expectations and corresponding behaviors, through the three processes of social influence: compliance, identification, and internalization. Leaders’ normative expectations for high-quality service enhances employee service performance not only by adjusting self-expectations to comply with an authority figure’s expectations or by identification with the leader as a role model, but rather as a deep-rooted process where the leader’s normative expectations are internalized into employee’s role identity. The theoretical and practical implications are discussed.
THE GOLDEN RULE OF LONGEVITY
Authors: Gestsson Marias H. , Zoega Gylfi
Published: January 2018

How much should society invest in medical care that extends the lives of the older generations? We derive a golden rule for the level of health care expenditures and find that the optimal level of life-extending health care expenditures should increase with rising productivity, increase with the retirement age, and also increase with the population growth rate if a higher growth rate lowers the ratio of retirees to working-age people sufficiently, while the effects of an improvement in medical technology are ambiguous. Moreover, we find that a market economy may be inefficient in terms of the provision of life-extending health care because an individual ignores the effect of his own longevity on the income of others.
The re-co-construction of legitimacy of/through the Doing Business indicators
Authors: Perry-Kessaris Amanda
Published: January 2018

The present paper argues that the Doing Business indicators, their legitimacy (their ability to be defended through some logic or justification arising from standards) and the wider notions of legitimacy (the standards) that they promulgate are all best understood as social or, better still, ‘econosociolegal’ constructions. It tracks their, primarily post-financial crisis, re-co-construction within and beyond the World Bank from servant of the private sector and discipliner of states to something approaching social champion. But it warns that the perceptions of legitimacy that have been generated by those indicators may well linger.
The Effect of Segregation on Intergroup Relations
Authors: Enos Ryan D. , Celaya Christopher
Published: January 2018

Inter-ethnic residential segregation is correlated with intergroup bias and conflict, poorly functioning states and civil societies, weak economic development, and ethnocentric political behavior. As such, segregation has been a subject of long-standing interest. However, segregation has not been assigned in randomized controlled trials, so the observed correlations may be spurious and the mechanism behind these correlations is poorly understood. In two experiments, we randomly assign segregation in a laboratory and demonstrate that segregation affects perceptions of other people and causes intergroup bias in costly decision-making. Rather than segregation merely inhibiting intergroup contact, we demonstrate that segregation directly affects perception and thus can affect intergroup relations even when holding contact constant.
Medicina ex Machina: Machine Learning in der Medizin
Authors: Becker Anton S. , Blüthgen Christian , Mühlematter Urs , Boss Andreas
Published: January 2018

Zusammenfassung. Machine Learning (ML) ist ein aktives Forschungsgebiet in den Informationswissenschaften und hat unseren Alltag in den vergangenen Jahren bereits merklich verändert. Mit fortschreitender Entwicklung sind die neuesten Algorithmen imstande, immer komplexere Aufgaben zu übernehmen. Im vorliegenden Mini-Review beschreiben wir einige Grundlagen des ML und zeigen anhand praxisorienterter Beispiele, wie es in den nächsten Jahren Einzug in die klinische Routine halten könnte.
Employees’ Critical Thinking, Leaders’ Inspirational Motivation, and Voice Behavior
Authors: Jiang Jing , Gao Ang , Yang Baiyin
Published: January 2018

Abstract. This study uses implicit voice theory to examine the influence of employees’ critical thinking and leaders’ inspirational motivation on employees’ voice behavior via voice efficacy. The results of a pretest of 302 employees using critical thinking questionnaires and a field study of 273 dyads of supervisors and their subordinates revealed that both employees’ critical thinking and leaders’ inspirational motivation had a positive effect on employees’ voice and that voice efficacy mediates the relationships among employees’ critical thinking, leaders’ inspirational motivation, and employees’ voice. Implications for research and practice are discussed.
GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose
Authors: Iwasaki Yusaku , Sendo Mio , Dezaki Katsuya , Hira Tohru , Sato Takehiro , Nakata Masanori , Goswami Chayon , Aoki Ryohei , Arai Takeshi , Kumari Parmila , Hayakawa Masaki , Masuda Chiaki , Okada Takashi , Hara Hiroshi , Drucker Daniel J. , Yamada Yuichiro , Tokuda Masaaki , Yada Toshihiko
Published: January 2018

Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar d-allulose (d-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models. Subchronic d-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance. These effects are blunted by vagotomy or pharmacological GLP-1R blockade, and by genetic inactivation of GLP-1R signaling in whole body or selectively in vagal afferents. Our results identify d-allulose as prominent GLP-1 releaser that acts via vagal afferents to restrict feeding and hyperglycemia. Furthermore, when administered in a time-specific manner, chronic d-allulose corrects arrhythmic overeating, obesity and diabetes, suggesting that chronotherapeutic modulation of vagal afferent GLP-1R signaling may aid in treating metabolic disorders.
Engineering human pluripotent stem cells into a functional skeletal muscle tissue
Authors: Rao Lingjun , Qian Ying , Khodabukus Alastair , Ribar Thomas , Bursac Nenad
Published: January 2018

The generation of functional skeletal muscle tissues from human pluripotent stem cells (hPSCs) has not been reported. Here, we derive induced myogenic progenitor cells (iMPCs) via transient overexpression of Pax7 in paraxial mesoderm cells differentiated from hPSCs. In 2D culture, iMPCs readily differentiate into spontaneously contracting multinucleated myotubes and a pool of satellite-like cells endogenously expressing Pax7. Under optimized 3D culture conditions, iMPCs derived from multiple hPSC lines reproducibly form functional skeletal muscle tissues (iSKM bundles) containing aligned multi-nucleated myotubes that exhibit positive force–frequency relationship and robust calcium transients in response to electrical or acetylcholine stimulation. During 1-month culture, the iSKM bundles undergo increased structural and molecular maturation, hypertrophy, and force generation. When implanted into dorsal window chamber or hindlimb muscle in immunocompromised mice, the iSKM bundles survive, progressively vascularize, and maintain functionality. iSKM bundles hold promise as a microphysiological platform for human muscle disease modeling and drug development.
Observation of Dirac-like energy band and ring-torus Fermi surface associated with the nodal line in topological insulator CaAgAs
Authors: Takane Daichi , Nakayama Kosuke , Souma Seigo , Wada Taichi , Okamoto Yoshihiko , Takenaka Koshi , Yamakawa Youichi , Yamakage Ai , Mitsuhashi Taichi , Horiba Koji , Kumigashira Hiroshi , Takahashi Takashi , Sato Takafumi
Published: January 2018

One of key challenges in current material research is to search for new topological materials with inverted bulk-band structure. In topological insulators, the band inversion caused by strong spin–orbit coupling leads to opening of a band gap in the entire Brillouin zone, whereas an additional crystal symmetry such as point-group and nonsymmorphic symmetries sometimes prohibits the gap opening at/on specific points or line in momentum space, giving rise to topological semimetals. Despite many theoretical predictions of topological insulators/semimetals associated with such crystal symmetries, the experimental realization is still relatively scarce. Here, using angle-resolved photoemission spectroscopy with bulk-sensitive soft-x-ray photons, we experimentally demonstrate that hexagonal pnictide CaAgAs belongs to a new family of topological insulators characterized by the inverted band structure and the mirror reflection symmetry of crystal. We have established the bulk valence-band structure in three-dimensional Brillouin zone, and observed the Dirac-like energy band and ring-torus Fermi surface associated with the line node, where bulk valence and conducting bands cross on a line in the momentum space under negligible spin–orbit coupling. Intriguingly, we found that no other bands cross the Fermi level and therefore the low-energy excitations are solely characterized by the Dirac-like band. CaAgAs provides an excellent platform to study the interplay among low-energy electron dynamics, crystal symmetry, and exotic topological properties.
Conservation of pattern as a tool for inference on spatial snapshots in ecological data
Authors: Irvine Michael A. , Bull James C. , Keeling Matt J.
Published: January 2018

As climate change and other anthropogenic factors increase the uncertainty of vegetation ecosystem persistence, the ability to rapidly assess their dynamics is paramount. Vegetation and sessile communities form a variety of striking regular spatial patterns such as stripes, spots and labyrinths, that have been used as indicators of ecosystem current state, through qualitative analysis of simple models. Here we describe a new method for rigorous quantitative estimation of biological parameters from a single spatial snapshot. We formulate a synthetic likelihood through consideration of the expected change in the correlation structure of the spatial pattern. This then allows Bayesian inference to be performed on the model parameters, which includes providing parameter uncertainty. The method was validated against simulated data and then applied to real data in the form of aerial photographs of seagrass banding. The inferred parameters were found to be able to reproduce similar patterns to those observed and able to detect strength of spatial competition, competition-induced mortality and the local range of reproduction. This technique points to a way of performing rapid inference of spatial competition and ecological stability from a single spatial snapshots of sessile communities.
Selective targeting of Scn8a prevents seizure development in a mouse model of mesial temporal lobe epilepsy
Authors: Wong Jennifer C. , Makinson Christopher D. , Lamar Tyra , Cheng Qi , Wingard Jeffrey C. , Terwilliger Ernest F. , Escayg Andrew
Published: January 2018

We previously found that genetic mutants with reduced expression or activity of Scn8a are resistant to induced seizures and that co-segregation of a mutant Scn8a allele can increase survival and seizure resistance of Scn1a mutant mice. In contrast, Scn8a expression is increased in the hippocampus following status epilepticus and amygdala kindling. These findings point to Scn8a as a promising therapeutic target for epilepsy and raise the possibility that aberrant overexpression of Scn8a in limbic structures may contribute to some epilepsies, including temporal lobe epilepsy. Using a small-hairpin-interfering RNA directed against the Scn8a gene, we selectively reduced Scn8a expression in the hippocampus of the intrahippocampal kainic acid (KA) mouse model of mesial temporal lobe epilepsy. We found that Scn8a knockdown prevented the development of spontaneous seizures in 9/10 mice, ameliorated KA-induced hyperactivity, and reduced reactive gliosis. These results support the potential of selectively targeting Scn8a for the treatment of refractory epilepsy.
Roles of sliding-induced defects and dissociated water molecules on low friction of graphene
Authors: Yang Zaixiu , Bhowmick Sukanta , Sen Fatih G. , Banerji Anindya , Alpas Ahmet T.
Published: January 2018

Sliding contact experiments and first-principles calculations were performed to elucidate the roles of structural defects and water dissociative adsorption process on the tribo-chemical mechanisms responsible for low friction of graphene. Sliding friction tests conducted in ambient air and under a dry N2 atmosphere showed that in both cases a high running-in coefficient of friction (COF) occurred initially but a low steady-state COF was reached only when the sliding was continued in air with moisture. Density functional theory (DFT) calculations indicated that the energy barrier (E
b
) for dissociative adsorption of H2O was significantly lower in case of reconstructed graphene with a monovacancy compared to pristine graphene. Cross-sectional transmission electron microscopy of graphene transferred to the counterface revealed a partly amorphous structure incorporating damaged graphene layers with d-spacings larger than that of the original layers. DFT calculations on the reconstructed bilayer AB graphene systems revealed an increase of d-spacing due to the chemisorption of H, O, and OH at the vacancy sites and a reduction in the interlayer binding energy (E
B
) between the bilayer graphene interfaces compared to pristine graphene. Thus, sliding induced defects facilitated dissociative adsorption of water molecules and reduced COF of graphene for sliding tests under ambient and humid environments but not under an inert atmosphere.
Synchrotron-generated microbeams induce hippocampal transections in rats
Authors: Fardone Erminia , Pouyatos Benoît , Bräuer-Krisch Elke , Bartzsch Stefan , Mathieu Hervè , Requardt Herwig , Bucci Domenico , Barbone Giacomo , Coan Paola , Battaglia Giuseppe , Le Duc Geraldine , Bravin Alberto , Romanelli Pantaleo
Published: January 2018

Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats. An array of parallel microbeams carrying an incident dose of 600 Gy was delivered to the rat hippocampus. Immunohistochemistry of phosphorylated γ-H2AX showed cell death along the microbeam irradiation paths in rats 48 hours after irradiation. No evident behavioral or neurological deficits were observed during the 3-month period of observation. MR imaging showed no signs of radio-induced edema or radionecrosis 3 months after irradiation. Histological analysis showed a very well preserved hippocampal cytoarchitecture and confirmed the presence of clear-cut microscopic transections across the hippocampus. These data support the use of synchrotron-generated microbeams as a novel tool to slice the hippocampus of living rats in a minimally invasive way, providing (i) a novel experimental model to study hippocampal function and (ii) a new treatment tool for patients affected by refractory epilepsy induced by mesial temporal sclerosis.
Sediment Source Fingerprinting of the Lake Urmia Sand Dunes
Authors: Ahmady-Birgani Hesam , Agahi Edris , Ahmadi Seyed Javad , Erfanian Mahdi
Published: January 2018

Aeolian sand dunes are continuously being discovered in inner dry lands and coastal areas, most of which have been formed over the Last Glacial Maximum. Presently, due to some natural and anthropogenic implications on earth, newly-born sand dunes are quickly emerging. Lake Urmia, the world’s second largest permanent hypersaline lake, has started shrinking, vast lands comprising sand dunes over the western shore of the lake have appeared and one question has been playing on the minds of nearby dwellers: where are these sand dunes coming from, What there was not 15 years ago!! In the present study, the determination of the source of the Lake Urmia sand dunes in terms of the quantifying relative contribution of each upstream geomorphological/lithological unit has been performed using geochemical fingerprinting techniques. The findings demonstrate that the alluvial and the fluvial sediments of the western upstream catchment have been transported by water erosion and they accumulated in the lower reaches of the Kahriz River. Wind erosion, as a secondary agent, have carried the aeolian sand-sized sediments to the sand dune area. Hence, the Lake Urmia sand dunes have been originating from simultaneous and joint actions of alluvial, fluvial and aeolian processes.
A Quantum Biomimetic Electronic Nose Sensor
Authors: Patil Ashlesha , Saha Dipankar , Ganguly Swaroop
Published: January 2018

We propose a technologically feasible one-dimensional double barrier resonant tunneling diode (RTD) as electronic nose, inspired by the vibration theory of biological olfaction. The working principle is phonon-assisted inelastic electron tunneling spectroscopy (IETS), modeled here using the Non-Equilibrium Green Function formalism for quantum transport. While standard IETS requires low-temperature operation to obviate the thermal broadening of spectroscopic peaks, we show that quantum confinement in the well of the RTD provides electron energy filtering in this case and could thereby allow room-temperature operation. We also find that the IETS peaks - corresponding to adsorbed foreign molecules - shift monotonically along the bias voltage coordinate with their vibrational energy, promising a selective sensor.
Haplotype-based Noninvasive Prenatal Diagnosis of Hyperphenylalaninemia through Targeted Sequencing of Maternal Plasma
Authors: Ye Jun , Chen Chao , Yuan Yuan , Han Lianshu , Wang Yaoshen , Qiu Wenjuan , Zhang Huiwen , Asan  , Gu Xuefan
Published: January 2018

Here we developed a haplotype-based noninvasive prenatal diagnosis method for hyperphenylalaninemia (HPA) and demonstrated its accuracy and feasibility during early pregnancy. Capture sequencing was performed on genomic DNA from parents and probands using customized hybridization probes targeting highly heterozygous single-nucleotide polymorphisms located within the 1 M region flanking phenylalanine hydroxylase (PAH) and 6-pyruvoyltetrahydropterin (PTS) and its coding region to determine the parental haplotypes and linkage to pathogenic mutations. Maternal plasma DNA obtained at 12–20 weeks of gestation was also subjected to targeted sequencing to deduce the fetal haplotypes based on the parental haplotypes. The fetal genotypes were further validated by invasive prenatal diagnosis. Haplotype-based noninvasive prenatal testing was successfully performed in 13 families. Five fetuses were identified to harbor bi-allelic pathogenic variants of PAH, four fetuses were carriers of one heterozygous PAH variant, three fetuses were normal, and the fetus of the 6-pyruvoyl tetrahydrobiopterin synthase family was identified as normal. The fetal genotypes at two gestational weeks from the same PAH family were identical. All results were consistent with the prenatal diagnosis based on amniotic fluid. Haplotype-based noninvasive prenatal testing for HPA through targeted sequencing is accurate and feasible during early gestation.
Piperonylic acid stimulates keratinocyte growth and survival by activating epidermal growth factor receptor (EGFR)
Authors: Lee Dohyun , Lim Jinsun , Woo Kyung-Chul , Kim Kyong-Tai
Published: January 2018

Epidermal growth factor (EGF) stimulates cell growth, proliferation, and survival. The biological benefits of EGF have been utilized in medical uses for improving wound healing as well as in today’s skin cosmetics. EGF has been found in urine, saliva, milk, and plasma, but its efficient isolation remains a difficult task. With technical advances, recombinant protein purification technique has been used for EGF production. However, the recombinant EGF is still expensive and keeping it with stable activity is difficult to be used widely. Thus, a molecule that can mimic the EGF activity would be a useful alternative of EGF. Herein, we have discovered that a natural small molecule piperonylic acid shows EGF-like activity in HaCaT keratinocytes. Piperonylic acid induced EGF receptor (EGFR) activation and resulted in serial activation of the downstream modulators. The activated signaling pathway eventually up-regulated gene expression of egr-1, c-fos, c-jun, and c-myc, which are involved in cell growth and survival. Moreover, piperonylic acid showed promoting role in keratinocyte growth and survival from UVB-induced cellular damages. This study has revealed the EGF-like activity of piperonylic acid and proposed that the piperonylic acid could be a promising component for skin wound healing agents or cosmetic ingredient.
Exome-wide rare variant analyses of two bone mineral density phenotypes: the challenges of analyzing rare genetic variation
Authors: Sun Jianping , Oualkacha Karim , Forgetta Vincenzo , Zheng Hou-Feng , Richards J. Brent , Evans Daniel S. , Orwoll Eric , Greenwood Celia M. T.
Published: January 2018

Performance of a recently developed test for association between multivariate phenotypes and sets of genetic variants (MURAT) is demonstrated using measures of bone mineral density (BMD). By combining individual-level whole genome sequenced data from the UK10K study, and imputed genome-wide genetic data on individuals from the Study of Osteoporotic Fractures (SOF) and the Osteoporotic Fractures in Men Study (MrOS), a data set of 8810 individuals was assembled; tests of association were performed between autosomal gene-sets of genetic variants and BMD measured at lumbar spine and femoral neck. Distributions of p-values obtained from analyses of a single BMD phenotype are compared to those from the multivariate tests, across several region definitions and variant weightings. There is evidence of increased power with the multivariate test, although no new loci for BMD were identified. Among 17 genes highlighted either because there were significant p-values in region-based association tests or because they were in well-known BMD genes, 4 windows in 2 genes as well as 6 single SNPs in one of these genes showed association at genome-wide significant thresholds with the multivariate phenotype test but not with the single-phenotype test, Sequence Kernel Association Test (SKAT).
Past visual experiences weigh in on body size estimation
Authors: Alexi Joanna , Cleary Dominique , Dommisse Kendra , Palermo Romina , Kloth Nadine , Burr David , Bell Jason
Published: January 2018

Body size is a salient marker of physical health, with extremes implicated in various mental and physical health issues. It is therefore important to understand the mechanisms of perception of body size of self and others. We report a novel technique we term the bodyline, based on the numberline technique in numerosity studies. One hundred and three young women judged the size of sequentially presented female body images by positioning a marker on a line, delineated with images of extreme sizes. Participants performed this task easily and well, with average standard deviations less than 6% of the total scale. Critically, judgments of size were biased towards the previously viewed body, demonstrating that serial dependencies occur in the judgment of body size. The magnitude of serial dependence was well predicted by a simple Kalman-filter ideal-observer model, suggesting that serial dependence occurs in an optimal, adaptive way to improve performance in size judgments.
Precontractile optical response during excitation-contraction in human muscle revealed by non-invasive high-speed spatiotemporal NIR measurement
Authors: Lindkvist Markus , Granåsen Gabriel , Grönlund Christer
Published: January 2018

During muscle contraction the excitation-contraction process mediates the neural input and mechanical output. Proper muscle function and body locomotion depends on the status of the elements in the same process. However, non-invasive and in-vivo methods to study this are not available. Here we show the existence of an optical response occurring during the excitation-contraction process in human biceps brachii muscle. We developed a non-invasive instrument from a photodiode array and light emitting diodes to detect spatially propagating (~5 m/s) and precontractile (~6 ms onset) optical signals closely related to the action potential during electrostimulation. Although this phenomenon was observed 60 years ago on isolated frog muscle cells in the lab, it has not been shown in-vivo before now. We anticipate our results to be a starting point for a new category in-vivo studies, characterising alterations in the excitation-contraction process in patients with neuromuscular disease and to monitor effects of therapy.
Renal capsular invasion is a prognostic biomarker in localized clear cell renal cell carcinoma
Authors: Ha U-Syn , Lee Kyu Won , Jung Jin-hyung , Byun Seok-Soo , Kwak Cheol , Chung Jinsoo , Hwang Eu Chang , Kim Yong-June , Kwon Tae Gyun , Kang Seok Ho , Hong Sung-Hoo
Published: January 2018

Renal capsular invasion (RCI) and lymphovascular invasion (LVI) are potential prognostic factors of significance in renal cell carcinoma (RCC). We evaluated the independent prognostic implications of RCI and LVI in localized clear cell RCC based on a large multi-institutional cohort. 6, 849 patients who had undergone radical or partial nephrectomy for RCC were included. Associations between recurrence and RCI or LVI were analyzed by constructing statistical models that combined Cox proportional hazard regression and propensity score matching. To analyze RCI, 2, 733 patients including 603 patients with RCI were enrolled. To analyze LVI, 3, 586 patients including 121 patients with LVI were enrolled. Recurrence was observed in 75 (12.4%) patients with RCI and 134 (6.3%) patients without RCI. In all statistical models, RCI was significantly associated with an increased risk of recurrence. Recurrence was observed 29 (24.0%) patients with LVI and 207 (6.0%) patients without LVI. LVI was significantly associated with an increased risk of recurrence only in non-adjusted univariate models, but not in multivariate adjusted analysis or propensity score matching models. In conclusion, these findings suggest that RCI could be a significant risk factor for localized clear cell RCC recurrence. In contrast to RCI, LVI cannot be an independent prognostic variable.
Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA
Authors: Nerlich Andreas , Mieth Maren , Letsiou Eleftheria , Fatykhova Diana , Zscheppang Katja , Imai-Matsushima Aki , Meyer Thomas F. , Paasch Lisa , Mitchell Timothy J. , Tönnies Mario , Bauer Torsten T. , Schneider Paul , Neudecker Jens , Rückert Jens C. , Eggeling Stephan , Schimek Maria , Witzenrath Martin , Suttorp Norbert , Hippenstiel Stefan , Hocke Andreas C.
Published: January 2018

Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment.
A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese
Authors: Wolff Natascha A. , Garrick Michael D. , Zhao Lin , Garrick Laura M. , Ghio Andrew J. , Thévenod Frank
Published: January 2018

Much of iron and manganese metabolism occurs in mitochondria. Uptake of redox-active iron must be tightly controlled, but little is known about how metal ions enter mitochondria. Recently, we established that the divalent metal transporter 1 (DMT1) is present in the outer mitochondrial membrane (OMM). Therefore we asked if it mediates Fe2+ and Mn2+ influx. Mitochondria were isolated from HEK293 cells permanently transfected with inducible rat DMT1 isoform 1 A/+IRE (HEK293-rDMT1). Fe2+-induced quenching of the dye PhenGreen™SK (PGSK) occurred in two phases, one of which reflected OMM DMT1 with stronger Fe2+ uptake after DMT1 overexpression. DMT1-specific quenching showed an apparent affinity of ~1.5 µM for Fe2+and was blocked by the DMT1 inhibitor CISMBI. Fe2+ influx reflected an imposed proton gradient, a response that was also observed in purified rat kidney cortex (rKC) mitochondria. Non-heme Fe accumulation assayed by ICPOES and stable 57Fe isotope incorporation by ICPMS were increased in HEK293-rDMT1 mitochondria. HEK293-rDMT1 mitochondria displayed higher 59Fe2+ and 54Mn2+ uptake relative to controls with 54Mn2+ uptake blocked by the DMT1 inhibitor XEN602. Such transport was defective in rKC mitochondria with the Belgrade (G185R) mutation. Thus, these results support a role for DMT1 in mitochondrial Fe2+ and Mn2+ acquisition.
A direct effect of perception on action when grasping a cup
Authors: Rounis E. , van Polanen V. , Davare M.
Published: January 2018

Affordances represent features of an object that trigger specific actions. Here we tested whether the presence and orientation of a handle on a cup could bias grasping movements towards it in conditions where subjects were explicitly told to ignore the handle. We quantified the grip aperture profile of twelve healthy participants instructed to grasp a cup from its body while it either had no handle, a handle pointing towards, or away from the grasping hand (3 ‘move’ conditions, with large grip aperture). To ensure the smaller grip aperture afforded by the handle was implicitly processed, we interspersed trials in which participants had to grasp the cup from its handle or a handle not attached to a cup with a small grip aperture. We found that grip aperture was smaller in the presence of a handle in the ‘move’ conditions, independently of its orientation. Our finding, of an effect of the handle during the execution of a grasp action, extends previous evidence of such an influence measured during motor preparation using simple reaction times. It suggests that the specific action elicited by an object’s attribute can affect movement performance in a sustained manner throughout movement execution.
Syntaxins on granules promote docking of granules via interactions with munc18
Authors: Borisovska Maria
Published: January 2018

SNAREs and SNARE-binding accessory proteins are believed to be central molecular components of neurotransmitter release, although the precise sequence of molecular events corresponding to distinct physiological states is unclear. The mechanism of docking of vesicles to the plasma membrane remains elusive, as the anchoring protein residing on vesicles is unknown. Here I show that targeting small amounts of syntaxin to granules by transmembrane domain alteration leads to a substantial enhancement of syntaxin clustering beneath granules, as well as of morphological granule docking. The effect was abolished without munc18 and strongly reduced by removal of the N-terminal peptide in the syntaxin mutant. Thus, in contrast to the current paradigm, I demonstrate that syntaxin acts from the vesicular membrane, strongly facilitating docking of vesicles, likely via interaction of its N-peptide with munc18. Docking was assayed by quantifying the syntaxin clusters beneath granules, using two-color Total Internal Reflectance Fluorescence microscopy in live PC-12 cells and confirmed by electron microscopy. Hereby, I propose a new model of vesicle docking, wherein munc18 bridges the few syntaxin molecules residing on granules to the syntaxin cluster on the plasma membrane, suggesting that the number of syntaxins on vesicles determines docking and conceivably fusion probability.
The Regulation of Seventeen Inflammatory Mediators are Associated with Patient Outcomes in Severe Fever with Thrombocytopenia Syndrome
Authors: Hu Li-Fen , Wu Ting , Wang Bo , Wei Yuan-Yuan , Kong Qin-Xiang , Ye Ying , Yin Hua-Fa , Li Jia-Bin
Published: January 2018

Severe fever with thrombocytopenia syndrome (SFTS) as an emerging infection disease results in high morbidity and mortality in China. In this study, the circulating levels of 36 inflammatory mediators in 33 SFTS patients on days 3–7, 8–12 and 13–20 post-illness were measured by a multiplex Luminex® system dynamically. Among the patients, 15 severe patients recovered, 11 severe patients died within three weeks. We found IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, eotaxin, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β and fractalkine were significantly upregulated in SFTS patients. Elevated IL-15 and eotaxin in SFTS patients were reported firstly. The highest levels of pro-inflammatory and anti-inflammatory cytokines coexisted in fatal patients during the first week. Inflammatory mediators remained high levels when death occurred in fatal patients, they were recovered within three weeks in nonfatal patients. Our results showed the occurrence of inflammatory storm in SFTS patients were associated with the severity of SFTS. RANTES and PDGF were down regulated and remained significantly lower levels in fatal patients throughout the course of disease, the concentrations of RANTES and PDGF were remarkably positively correlated with the platelet count. Our results demonstrated that dysregulated inflammatory response was associated with disease pathogenesis and mortality in SFTS patients.
Highly flexible, wearable, and disposable cardiac biosensors for remote and ambulatory monitoring
Authors: Lee Stephen P. , Ha Grace , Wright Don E. , Ma Yinji , Sen-Gupta Ellora , Haubrich Natalie R. , Branche Paul C. , Li Weihua , Huppert Gilbert L. , Johnson Matthew , Mutlu Hakan B. , Li Kan , Sheth Nirav , Wright John A. , Huang Yonggang , Mansour Moussa , Rogers John A. , Ghaffari Roozbeh
Published: January 2018

Contemporary cardiac and heart rate monitoring devices capture physiological signals using optical and electrode-based sensors. However, these devices generally lack the form factor and mechanical flexibility necessary for use in ambulatory and home environments. Here, we report an ultrathin (~1 mm average thickness) and highly flexible wearable cardiac sensor (WiSP) designed to be minimal in cost (disposable), light weight (1.2 g), water resistant, and capable of wireless energy harvesting. Theoretical analyses of system-level bending mechanics show the advantages of WiSP’s flexible electronics, soft encapsulation layers and bioadhesives, enabling intimate skin coupling. A clinical feasibility study conducted in atrial fibrillation patients demonstrates that the WiSP device effectively measures cardiac signals matching the Holter monitor, and is more comfortable. WiSP’s physical attributes and performance results demonstrate its utility for monitoring cardiac signals during daily activity, exertion and sleep, with implications for home-based care.
Phosphatase and tensin homologue: a therapeutic target for SMA
Authors: Godena Vinay K , Ning Ke
Published: January 2018

Spinal muscular atrophy (SMA) is one of the most common juvenile neurodegenerative diseases, which can be associated with child mortality. SMA is caused by a mutation of ubiquitously expressed gene, Survival Motor Neuron1 (SMN1), leading to reduced SMN protein and the motor neuron death. The disease is incurable and the only therapeutic strategy to follow is to improve the expression of SMN protein levels in motor neurons. Significant numbers of motor neurons in SMA mice and SMA cultures are caspase positive with condensed nuclei, suggesting that these cells are prone to a process of cell death called apoptosis. Searching for other potential molecules or signaling pathways that are neuroprotective for central nervous system (CNS) insults is essential for widening the scope of developmental medicine. PTEN, a Phosphatase and Tensin homologue, is a tumor suppressor, which is widely expressed in CNS. PTEN depletion activates anti-apoptotic factors and it is evident that the pathway plays an important protective role in many neurodegenerative disorders. It functions as a negative regulator of PIP3/AKT pathway and thereby modulates its downstream cellular functions through lipid phosphatase activity. Moreover, previous reports from our group demonstrated that, PTEN depletion using viral vector delivery system in SMN delta7 mice reduces disease pathology, with significant rescue on survival rate and the body weight of the SMA mice. Thus knockdown/depletion/mutation of PTEN and manipulation of PTEN medicated Akt/PKB signaling pathway may represent an important therapeutic strategy to promote motor neuron survival in SMA.
Quantitative analysis of glyphosate, glufosinate and AMPA in irrigation water by in situ derivatization–dispersive liquid–liquid microextraction combined with UPLC-MS/MS
Authors: Pinto Edgar , Soares António Gomes , Ferreira Isabel M. P. L. V. O.
Published: January 2018

A novel method was developed for the sensitive, cheap and fast quantitation of glyphosate, glufosinate and aminomethylphosphonic acid (AMPA) in irrigation water by in situ derivatization and dispersive liquid–liquid microextraction (DLLME) combined with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).
Carbon nitride quantum dot-enhanced chemiluminescence of hydrogen peroxide and hydrosulfite and its application in ascorbic acid sensing
Authors: Chen Bing , Wang Feifei , Yao Wensong , Lin Zhen , Zhang Xiaomin , Luo Shu , Zheng Linlin , Lin Xinhua
Published: January 2018

Chemiluminescence of carbon nitride quantum dots in a hydrogen peroxide–hydrosulfite system was observed and used in ascorbic acid sensing.
Synergetic topography and chemistry cues guiding osteogenic differentiation in bone marrow stromal cells through ERK1/2 and p38 MAPK signaling pathway
Authors: Zhang Xinran , Li Haotian , Lin Chucheng , Ning Congqin , Lin Kaili
Published: January 2018

Ordered micro-patterned topography and Sr ion doping in HAp synergistically enhance osteogenesis through ERK1/2 and p38 MAPK signaling pathways.
Synergistic effects of stellated fibrous mesoporous silica and synthetic dsRNA analogues for cancer immunotherapy
Authors: Wang Xiupeng , Li Xia , Ito Atsuo , Sogo Yu , Watanabe Yohei , Hashimoto Kaoru , Yamazaki Atsushi , Ohno Tadao , Tsuji Noriko M.
Published: January 2018

Stellated fibrous mesoporous silica (MS) nanospheres and poly(I:C) show synergistic anti-cancer immunityin vivo.
Polymeric carbon nitride nanomesh as an efficient and durable metal-free catalyst for oxidative desulfurization
Authors: Shen Lijuan , Lei Ganchang , Fang Yuanxing , Cao Yanning , Wang Xinchen , Jiang Lilong
Published: January 2018

Polymeric carbon nitride nanomesh has been prepared and demonstrated to be a novel and outstanding catalyst for H2S selective oxidation.
Retracted Article: Insight into the reversible structural crystalline-state transformation from MIL-53(Al) to MIL-68(Al)
Authors: Perea-Cachero Adelaida , Romero Enrique , Téllez Carlos , Coronas Joaquín
Published: January 2018

The reversible crystalline transformation from MIL-53(Al) into MIL-68(Al) was accomplished.
On the growth morphology and crystallography of the epitaxial Cu7Te4/CdTe interface
Authors: Wang Fang , Lei Yimin , Wang Dapeng , Lei Zhibin , Sun Jie , Liu Zonghuai
Published: January 2018

The manipulation of interface structures in the epitaxial growth of thin films is very essential, especially for some special heterogeneous structures. Crystallographic calculation method is a powerful tool when analyzing and predicting the structures of the coherent interfaces.
Self-assembly of 1,3,5-benzenetribenzoic acid on Ag and Cu at the liquid/solid interface
Authors: Aitchison Hannah , Lu Hao , Ortiz de la Morena Rodrigo , Cebula Izabela , Zharnikov Michael , Buck Manfred
Published: January 2018

Big difference: molecules of benzenetribenzoic acid are disordered on Cu but highly organised on Ag, forming a monopodal row structure.
Inactivation of pure bacterial biofilms by impaction of aerosolized consumer products containing nanoparticulate metals
Authors: Therkorn Jennifer , Calderón Leonardo , Cartledge Benton , Thomas Nirmala , Majestic Brian , Mainelis Gediminas
Published: January 2018

Nanotechnology-enabled consumer sprays with Ag may have antibacterial potential, but it is not based solely on nano-silver presence and concentration.
Transformation of cellulose and related carbohydrates into lactic acid with bifunctional Al(iii)–Sn(ii) catalysts
Authors: Deng Weiping , Wang Pan , Wang Binju , Wang Yanliang , Yan Longfei , Li Yanyun , Zhang Qinghong , Cao Zexing , Wang Ye
Published: January 2018

The bifunctional Al(iii)–Sn(ii) combination efficiently catalyses the conversion of cellulose into lactic acid in waterviaa series of tandem steps.
Enhanced bending-tuned magnetic properties in epitaxial cobalt ferrite nanopillar arrays on flexible substrates
Authors: Shen Lvkang , Liu Ming , Ma Chunrui , Lu Lu , Fu Huarui , You Caiyin , Lu Xiaoli , Jia Chun-Lin
Published: January 2018

Epitaxial (111) CoFe2O4 nanopillar arrays were successfully grown on flexible fluorophlogopite substrates with strong bending-related magnetic properties.
Outlining migrainous through dihydroergotamine–serotonin receptor interactions using quantum biochemistry
Authors: Lima Neto José X. , Soares-Rachetti Vanessa P. , Albuquerque Eudenilson L. , Manzoni Vinicius , Fulco Umberto L.
Published: January 2018

We present the electronic structure of the complex dihydroergotamine–serotonin receptor to unveil new medications to treat migraine and related diseases.
CoP nanoparticles anchored on N,P-dual-doped graphene-like carbon as a catalyst for water splitting in non-acidic media
Authors: Liu Yanyan , Zhu Yihua , Shen Jianhua , Huang Jianfei , Yang Xiaoling , Li Chunzhong
Published: January 2018

CoP nanoparticles anchored on N,P-dual-doped graphene-like carbon as efficient bifunctional water splitting catalyst in non-acidic media.
Fluorescence imaging of hepatocellular carcinoma with a specific probe of COX-2
Authors: Wang Haibo , Dong Chengyong , Jiang Keqiu , Zhang Shuangzhe , Long Fei , Zhang Rixin , Sun Deguang , Liang Rui , Gao Zhenming , Shao Shujuan , Wang Liming
Published: January 2018

Hepatocellular carcinoma (HCC) is the major subtype of primary liver cancer.
Preferential occupancy of Eu3+ and energy transfer in Eu3+ doped Sr2V2O7, Sr9Gd(VO4)7 and Sr2V2O7/Sr9Gd(VO4)7 phosphors
Authors: Li Ling , Wang Wenjun , Pan Yu , Zhu Yuhan , Liu Xiaoguang , Noh Hyeon Mi , Moon Byung Kee , Choi Byung Chun , Jeong Jung Hyun
Published: January 2018

The vanadate-based phosphors Sr2V2O7:Eu3+ (SV:Eu3+), Sr9Gd(VO4)7:Eu3+ (SGV:Eu3+) and Sr9Gd(VO4)7/Sr2V2O7:Eu3+ (SGV/SV:Eu3+) were obtained by solid-state reaction.
Recent advances and effective strategies in the discovery and applications of natural products
Authors: Xie Jing , Zhang Ai-hua , Sun Hui , Yan Guang-li , Wang Xi-jun
Published: January 2018

Natural products are the most representative form of conventional therapy as compared to any other traditional or alternative medicine systems.
LC-ESI-MS/MS reveals the formation of reactive intermediates in brigatinib metabolism: elucidation of bioactivation pathways
Authors: Kadi Adnan A. , Attwa Mohamed W. , Darwish Hany W.
Published: January 2018

Four phase I BGB metabolites and three cyano adducts for BGB were detected using LC-MS/MS. The piperidine ring was found to be responsible for BGB bioactivation and the bioactivation pathways are proposed.