bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Feasibility for Pediatric Cardiac Regeneration Using Epicardial Delivery of Autologous Umbilical Cord Blood-Derived Mononuclear Cells Established in a Porcine Model System
Authors: Cantero Peral Susana , Burkhart Harold M. , Oommen Saji , Yamada Satsuki , Nyberg Scott L. , Li Xing , O'Leary Patrick W. , Terzic Andre , Cannon Bryan C. , Nelson Timothy J. ,   Wanek Program Porcine Pipeline Group
Published: January 2015

Congenital heart diseases (CHDs) requiring surgical palliation mandate new treatment strategies to optimize long-term outcomes. Despite the mounting evidence of cardiac regeneration, there are no long-term safety studies of autologous cell-based transplantation in the pediatric setting. We aimed to establish a porcine pipeline to evaluate the feasibility and long-term safety of autologous umbilical cord blood mononuclear cells (UCB-MNCs) transplanted into the right ventricle (RV) of juvenile porcine hearts. Piglets were born by caesarean section to enable UCB collection. Upon meeting release criteria, 12 animals were randomized in a double-blinded fashion prior to surgical delivery of test article (n = 6) or placebo (n = 6). The UCB-MNC (3 × 106 cells per kilogram) or control (dimethyl sulfoxide, 10%) products were injected intramyocardially into the RV under direct visualization. The cohorts were monitored for 3 months after product delivery with assessments of cardiac performance, rhythm, and serial cardiac biochemical markers, followed by terminal necropsy. No mortalities were associated with intramyocardial delivery of UCB-MNCs or placebo. Two animals from the placebo group developed local skin infection after surgery that responded to antibiotic treatment. Electrophysiological assessments revealed no arrhythmias in either group throughout the 3-month study. Two animals in the cell-therapy group had transient, subclinical dysrhythmia in the perioperative period, likely because of an exaggerated response to anesthesia. Overall, this study demonstrated that autologous UCB-MNCs can be safely collected and surgically delivered in a pediatric setting. The safety profile establishes the foundation for cell-based therapy directed at the RV of juvenile hearts and aims to accelerate cell-based therapies toward clinical trials for CHD.
A Brief Overview on Ferrite (Fe3O4) Based Polymeric Nanocomposites: Recent Developments and Challenges
Authors: Bajpai O. P. , Setua D. K. , Chattopadhyay S.
Published: January 2015

In this article, we have mainly discussed about ferrite (Fe3O4) and its polymer based nanocomposites. Ferrite particles have become an important research material because of their vast applications in the field of biotechnology, magnetic resonance imaging (MRI), and data storage. It has been observed that ferrite Fe3O4 particles show best performance for size less than 10-30 nm. This happens due to the super paramagnetic nature of such particles. In super paramagnetic range these particles exhibit zero remanence or coercivity. Therefore, various properties of ferrite (Fe3O4) nanoparticles and its polymer nanocomposites are very much dependent on the size, and distribution of the particles in the polymeric matrix. Moreover, it has been also observed that the shape of the nanocrystals plays important role in the determination of their fundamental properties. These particles show instability over longer times due to the formation of agglomerates generated by high surface energies. Therefore, protection strategies such as grafting and coatings with silica/carbon or polymers have been developed to stabilize them chemically. Recently, silylation technique is mainly used for the modification of nanoparticles. Experimentally, it has been observed that nanocomposites composed of polymer matrices and ferrite showed substantial improvements in stiffness, fracture toughness, sensing ability (magnetic as well as electric), impact energy absorption, and electro-catalytic activities to bio-species.
Taswir – perspektiver fra en meningsutveksling om figurativ fremstilling i sunni-islam
Authors: Brekketo Birte
Published: January 2015

På hvilke måter angår det oss hva islamske lærde måtte mene om figurativ fremstilling? Vi lever i massemedienes og de sosiale medienes tidsalder der visuelle budskap når ut til store og sammensatte betraktergrupper. Stadig flere av oss mestrer avanserte kommunikasjons­medier, men vår kunnskap om forskjellige visuelle tradisjoner har ikke økt i takt med den teknologiske utviklingen. Denne artikkelen går tett på tradisjonstrekk som er mindre kjente for mange i den vestlige verden, men som jevnlig kommer til uttrykk i både norsk og global offentlighet: Innenfor sunni-islamsk visuell tradisjon foregår det en fortløpende menings­utveksling om virkningene av figurativ fremstilling (taswir). De ulike synspunktene som lar seg høre, bygger på omhyggelig fortolkning av religiøse kilder, og de formidles ofte i polemiske former på internett. Den foreliggende oversikten over bredden og nyansene på taswir-feltet er blitt til ved samling og strukturering av stoff over lang tid. Målsettingene med å presentere denne oversikten er å inspirere leseren til å sende tankene i nye retninger. For det første får leseren innblikk i hvordan forestillinger om det visuelle utvikles, prøves ut og konsolideres i en sunni-islamsk tradisjonskontekst. For det andre plasseres taswir i en global samtidskontekst, i en posisjon som synliggjør det presserende behovet for en debatt om kompetanse og sensibilitet i samtidens visuelle kommunikasjonssituasjon.
Teaching ‘hardcore science’ to arts and design students: Reflections on the development of a basic programming course
Authors: Karlsen Sidsel , Nordby Anders
Published: January 2015

This article reports on the longitudinal development of a computer-programming course designed to meet the needs of students who enrolled in a specific higher education game development programme during the period of 2006 to 2010. The students came from three different arts and design-related strands of the programme, and had that in common that very few had taken advanced science classes as part of their upper-secondary education. This again meant that they were rather poorly equipped for learning computer programming, which they needed to master in order to tap into the full potential of the interactive and creative processes which their computers allowed for. Consequently, the programming course was designed in a way that allowed the students to practically engage in creating a computer game alongside being taught the actual programming skills, as well as the mathematics and physics needed in order to efficiently utilise those skills. A working hypothesis for the project was that if the responsible teachers were able to run the course in a way that cohered with the principles of problem-based learning, this would create an environment which would enhance the students’ motivation to learn basic programming as well as the operative and innovation skills needed for fulfilling the course requirements. In addition, ideas developed within the field of situated learning constituted theoretical points of departure for developing the course. The article describes the practical and theoretical points of departure for developing the programming course and reflects on the experiences made from running it. Summing up, the authors conclude that the why and how of teaching needs to be in line with students’ worlds in order for educational experiences to be considered as meaningful.
Non‐isotopic RNA In Situ Hybridization on Embryonic Sections
Authors: Touahri Yacine , Adnani Lata , Mattar Pierre , Markham Kathryn , Klenin Natalia , Schuurmans Carol
Published: January 2015

This unit describes methods for non‐isotopic RNA in situ hybridization on embryonic mouse sections. These methods can be used to follow the spatiotemporal dynamics of gene expression in an embryonic tissue of interest. They involve the use of labeled (e.g., digoxygenin, FITC) antisense riboprobes that hybridize to a specific mRNA in the target tissue. The probes are detected using an alkaline phosphatase−conjugated antibody recognizing the label and a chromogenic substrate. This method can be used to: (1) assess the expression of a single gene within a tissue, (2) compare the expression profiles of two genes within a tissue, or (3) compare the distribution of a transcript and protein within a tissue. While this approach is not quantitative, it provides a qualitative assessment of the precise cell types where a gene is expressed, which is not easily achievable with other more quantitative methods such as quantitative PCR. © 2015 by John Wiley & Sons, Inc.
Imaging the Insertion of Superecliptic pHluorin‐Labeled Dopamine D2 Receptor Using Total Internal Reflection Fluorescence Microscopy
Authors: Daly Kathryn M. , Li Yun , Lin Da‐Ting
Published: January 2015

A better understanding of mechanisms governing receptor insertion to the plasma membrane (PM) requires an experimental approach with excellent spatial and temporal resolutions. Here we present a strategy that enables dynamic visualization of insertion events for dopamine D2 receptors into the PM. This approach includes tagging a pH‐sensitive GFP, superecliptic pHluorin, to the extracellular domain of the receptor. By imaging pHluorin‐tagged receptors under total internal reflection fluorescence microscopy (TIRFM), we were able to directly visualize individual receptor insertion events into the PM in cultured neurons. This novel imaging approach can be applied to both secreted proteins and many membrane proteins with an extracellular domain labeled with superecliptic pHluorin, and will ultimately allow for detailed dissections of the key mechanisms governing secretion of soluble proteins or the insertion of different membrane proteins to the PM. © 2015 by John Wiley & Sons, Inc.
To Stress or Not to Stress: A Question of Models
Authors: Gray J. Megan , Chaouloff Francis , Hill Matthew N.
Published: January 2015

Stress research is a rapidly evolving field that encompasses numerous disciplines ranging from neuroscience to metabolism. With many new researchers migrating into the field, navigating the hows and whys of specific research questions can sometimes be enigmatic given the availability of so many models in the stress field. Additionally, as with every field, there are many seemingly minor experimental details that can have dramatic influences on data interpretation, although many of these are unknown to those not familiar with the field. The aim of this overview is to provide some suggestions and points to guide researchers moving into the stress field and highlight relevant methodological points that they should consider when choosing a model for stress and deciding how to structure a study. We briefly provide a primer on the basics of endpoint measurements in the stress field, factors to consider when choosing a model for acute stress, the difference between repeated and chronic stress, and importantly, influencing variables that modulate endpoints of analysis in stress work. © 2015 by John Wiley & Sons, Inc.
ATAC‐seq: A Method for Assaying Chromatin Accessibility Genome‐Wide
Authors: Buenrostro Jason D. , Wu Beijing , Chang Howard Y. , Greenleaf William J.
Published: January 2015

This unit describes Assay for Transposase‐Accessible Chromatin with high‐throughput sequencing (ATAC‐seq), a method for mapping chromatin accessibility genome‐wide. This method probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription‐factor binding and nucleosome position. The method is a fast and sensitive alternative to DNase‐seq for assaying chromatin accessibility genome‐wide, or to MNase‐seq for assaying nucleosome positions in accessible regions of the genome. © 2015 by John Wiley & Sons, Inc.
Quantification of Th1 and Th17 Cells with Intracellular Staining Following PMA/Ionomycin Stimulation
Authors: Karlsson Fridrik , Hassan‐Zahraee Mina
Published: January 2015

Cytokine‐producing cells are at the center of the adaptive immune responses, and quantifying these cells is an important aspect to build understanding of the immune response. In particular, Th1 and Th17 cells have been implicated in the pathogenesis of such diseases as inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. Quantification of Th1 and Th17 cells can provide important information in research of these diseases and other Th1‐ and Th17‐mediated immune disorders. In vitro stimulation of cells followed by surface and intracellular staining, presented here, has the advantage of detecting the cytokines directly instead of relying exclusively on surrogate surface markers which, although showing enrichment for the effector T cells, are not specific markers for the cytokine‐producing cells. © 2015 by John Wiley & Sons, Inc.
To pair or not to pair: Sources of social variability with white‐faced saki monkeys (Pithecia pithecia) as a case study
Authors: Thompson Cynthia L.
Published: January 2015

Intraspecific variability in social systems is gaining increased recognition in primatology. Many primate species display variability in pair‐living social organizations through incorporating extra adults into the group. While numerous models exist to explain primate pair‐living, our tools to assess how and why variation in this trait occurs are currently limited. Here I outline an approach which: (i) utilizes conceptual models to identify the selective forces driving pair‐living; (ii) outlines novel possible causes for variability in social organization; and (iii) conducts a holistic species‐level analysis of social behavior to determine the factors contributing to variation in pair‐living. A case study on white‐faced sakis (Pithecia pithecia) is used to exemplify this approach. This species lives in either male‐female pairs or groups incorporating “extra” adult males and/or females. Various conceptual models of pair‐living suggest that high same‐sex aggression toward extra‐group individuals is a key component of the white‐faced saki social system. Variable pair‐living in white‐faced sakis likely represents alternative strategies to achieve competency in this competition, in which animals experience conflicting selection pressures between achieving successful group defense and maintaining sole reproductive access to mates. Additionally, independent decisions by individuals may generate social variation by preventing other animals from adopting a social organization that maximizes fitness. White‐faced saki inter‐individual relationships and demographic patterns also lend conciliatory support to this conclusion. By utilizing both model‐level and species‐level approaches, with a consideration for potential sources of variation, researchers can gain insight into the factors generating variation in pair‐living social organizations. Am. J. Primatol. 78:561–572, 2016. © 2014 The Authors,American Journal of Primatology. published by Wiley Periodicals, Inc.
Magnetic resonance cisternogram with intrathecal gadolinium with delayed imaging for difficult to diagnose cerebrospinal fluid leaks of anterior skull base
Authors: DelGaudio John M. , Baugnon Kristen L. , Wise Sarah K. , Patel Zara M. , Aiken Ashley H. , Hudgins Patricia A.
Published: January 2015

Background

Workup of cerebrospinal fluid (CSF) leaks can be challenging. Patients with intermittent or infrequent clear rhinorrhea that cannot be collected, those with questionable or multiple skull‐base (SB) defects on imaging, and those with previous SB surgery can present diagnostic dilemmas. In this patient population, radiologic studies that allow repeat imaging over hours to days can increase the diagnostic yield. We report our experience with magnetic resonance cisternogram with intrathecal gadolinium (MRCgGd) in this patient population.

Methods

This study was a retrospective review of patients who underwent MRCgGd for workup of suspected CSF leaks at a tertiary care academic center.

Results

Over the past 3 years, 11 patients (10 females; mean age 50 years) underwent MRCgGd. Seven patients had suspected spontaneous CSF leaks from idiopathic intracranial hypertension and 2 had postsurgical defects. All patients had previous imaging that was indeterminate in localizing the site of the leak. Only 3 patients had positive beta‐2 transferrin studies, all with multiple potential leak sites. MRCgGd confirmed the absence of leaks at 4 previously repaired SB defects, identified spinal canal leaks but no SB leaks in 2 patients (1 of whom had a nonleaking SB defect), and identified 5 patients with one or more SB leaks. Repeat imaging, from 30 minutes to 20 hours, was beneficial in identifying 4 leaks not confirmed in the immediate imaging, and ruling out leaks in 5 cases, therefore guiding further treatment. No complications occurred.

Conclusion

MRCgGd is a useful diagnostic test in the workup of patients with difficult CSF leaks, with delayed imaging providing valuable diagnostic information.
Defining neurodegeneration on Guam by targeted genomic sequencing
Authors: Steele John C. , Guella Ilaria , Szu‐Tu Chelsea , Lin Michelle K. , Thompson Christina , Evans Daniel M. , Sherman Holly E. , Vilariño‐Güell Carles , Gwinn Katrina , Morris Huw , Dickson Dennis W. , Farrer Matthew J.
Published: January 2015

Objective

Amyotrophic lateral sclerosis/parkinsonism–dementia complex has been described in Guam, Western Papua, and the Kii Peninsula of Japan. The etiology and pathogenesis of this complex neurodegenerative disease remains enigmatic.

Methods

In this study, we have used targeted genomic sequencing to evaluate the contribution of genetic variability in the pathogenesis of amyotrophic lateral sclerosis, parkinsonism, and dementia in Guamanian Chamorros.

Results

Genes previously linked to or associated with amyotrophic lateral sclerosis, parkinsonism, dementia, and related neurodegenerative syndromes were sequenced in Chamorro subjects living in the Mariana Islands. Homozygous PINK1 p.L347P, heterozygous DCTN1 p.T54I, FUS p.P431L, and HTT (42 CAG repeats) were identified as pathogenic mutations.

Interpretation

The findings explain the clinical, pathologic, and genetic heterogeneity observed in some multi‐incident families and contribute to the excess incidence of neurodegeneration previously reported on Guam. Ann Neurol 2015;77:458–468
Dynamics of retinal injury after acute optic neuritis
Authors: Gabilondo Iñigo , Martínez‐Lapiscina Elena H. , Fraga‐Pumar Elena , Ortiz‐Perez Santiago , Torres‐Torres Ruben , Andorra Magi , Llufriu Sara , Zubizarreta Irati , Saiz Albert , Sanchez‐Dalmau Bernardo , Villoslada Pablo
Published: January 2015

Objective

We set out to assess the dynamics of retinal injury after acute optic neuritis (ON) and their association with clinical visual outcomes.

Methods

Thirty‐one consecutive patients with acute ON were prospectively analyzed over a 6‐month follow‐up period. Each month, we used optical coherence tomography (OCT) to assess the thickness of peripapillary retinal nerve fiber layer (pRNFL) and segmented macular layers, as well as high‐contrast visual acuity, low‐contrast visual acuity (LCVA), color visual acuity (CVA), and visual fields (VF).

Results

In this prospective study, we found that 6 months after clinical onset, ON eyes suffered a reduction in pRNFL (−45.3 μm) and macular thickness (−17.3 μm). Macular atrophy was due to the decrease of macular RNFL thickness (−7.8 μm) and that of the ganglion cell layer and inner plexiform layer (GCIP, −11.3 μm), whereas the thickness of the outer retinal layers increased slightly. The macular RNFL and GCIP thickness decreased in parallel, yet it always occurred more rapidly and more severely for the GCIP. The change in the GCIP thickness in the first month predicted the visual impairment by month 6; a decrease ≥ of 4.5 μm predicted poor LCVA (sensitivity of 93% and specificity of 88%), and a decrease of ≥ 7 μm predicted poor VF and CVA (sensitivity of 78% and 100% and specificity of 63% and 66%, respectively).

Interpretation

Retinal axonal and neuronal damage develops quickly after ON onset. Assessment of ganglion cell layer thickness by OCT after ON onset can be used as an imaging marker of persistent visual disability. Ann Neurol 2015;77:517–528
Shear flow‐induced orientation and structural recovery of multiwalled carbon nanotube in poly(ethylene oxide) matrix
Authors: Ranjbar Behnaz , Nazockdast Hossein
Published: January 2015

In the present work we studied the flow induced multiwalled carbon nanotube (MWCNT) orientation and the mechanisms governing the kinetics of nanotube reorientation and three‐dimensional network restructuring in poly(ethylene oxide) (PEO)/MWCNT nanocomposites. For this purpose, the linear and nonlinear viscoelastic experiments including frequency sweep, time sweep and transient tests were performed on PEO/MWCNT samples varying in MWCNT content. The extent as well as kinetics of network restructuring was found to be strongly dependent upon the amount of preshearing (shear rate and shearing time) and MWCNT concentration. The results also showed two mechanisms for structural recovery; a fast restructuring at the beginning due to rejoining of clusters and unoriented adjacent nanotube and much slower recovery in the longer annealing times due to Brownian motion. The latter mechanism was found to be uncompleted over 3600 s annealing. This was supported by aij (orientation tensors) calculated based on transmission electron micrograph. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41753.
Innovative approach for urease inhibition by Ficus carica extract–fabricated silver nanoparticles: An in vitro study
Authors: Borase Hemant P. , Salunkhe Rahul B. , Patil Chandrashekhar D. , Suryawanshi Rahul K. , Salunke Bipinchandra K. , Wagh Nilesh D. , Patil Satish V.
Published: January 2015

In the present study, a rapid, low‐cost, and ecofriendly method of stable silver nanoparticles (AgNPs) synthesis using leaves extract of Ficus carica (F. carica), a plant with diverse metabolic consortium, is reported for the first time. An absorption peak at 422 nm in UV–Vis spectroscopy, a spherical shape with an average size of 21 nm in transmission electron microscopy, and crystalline nature in X‐ray powder diffraction studies were observed for the synthesized AgNPs. Fourier transform infrared analysis indicated that proteins of F. carica might have a vital role in AgNP synthesis and stabilization. AgNPs were found to inhibit urease, a key enzyme responsible for the survival and pathogenesis of the bacterium, Helicobacter pylori. Inhibition of urease by AgNPs was monitored spectrophotometrically by the evaluation of ammonia release. The urease inhibition potential of AgNPs can be explored in the treatment of H. pylori by preparing novel combinations of standard drugs with AgNPs‐ or AgNPs‐encapsulated drug molecules.
Feasibility of ulnar artery for cardiac catheterization:AJmerULnarARtery (AJULAR) catheterization study
Authors: Gokhroo Rajendra , Bisht Devendra , Padmanabhan Deepak , Gupta Sajal , Kishor Kamal , Ranwa Bhanwar
Published: January 2015

Background

The ulnar artery is rarely selected for cardiac catheterization despite the expanding use of the transradial access (TRA). We tried to compare default transulnar access (TUA) with TRA in terms of feasibility and safety.

Materials and methods

This was a prospective, open label, single center, observational study. We analyzed a total of 410 patients with normal Allen's test, who were then scheduled for coronary angiography through TUA withad hocPCI if necessary. Procedures were performed by a single operator who had an adequate transradial experience (≥150 transradial coronary procedures per year) but not trained in transulnar procedures. We analyzed observed findings with a retrospective cohort of patients undergoing TRA angiography under a previous study done at our center. We also performed selective ulnar arteriography of 200 patients, through radial route, to predict the bottlenecks of TUA.

Observations

There is no statistically significant difference among the number of attempts made till the successful puncture, the total procedure time and the total fluoroscopy time for either radial or ulnar access angiography by an experienced operator (P > 0.05). However, the time taken in arterial access is statistically significant in the initial learning curve for the same (P < 0.05). On the contrary, the arterial access time, the total procedure time, and the total fluoroscopy time, all are statistically significant for the inexperienced operator (P < 0.05). There is a negligible incidence of nonmaneuverable anatomic obstruction in the real‐world scenario in TUA, and so fear of the same should not impede the use of this route. Vasospasm in the use of this route is also not different from the radial route, with the experience of the operator.

Conclusions

For an experienced operator, TUA is a safe and also an effective alternative to TRA in terms of feasibility and safety. © 2015 Wiley Periodicals, Inc.
Incidence of head and neck squamous cell carcinoma among subjects at high risk of lung cancer: Results from the Pittsburgh Lung Screening Study
Authors: Dixit Ronak , Weissfeld Joel L. , Wilson David O. , Balogh Paula , Sufka Pamela , Siegfried Jill M. , Grandis Jennifer R. , Diergaarde Brenda
Published: January 2015

BACKGROUND

Earlier detection and diagnosis of head and neck squamous cell carcinoma (HNSCC) should lead to improved outcomes. However, to the authors' knowledge, no effective screening strategy has been identified to date. In the current study, the authors evaluated whether it would be useful to screen subjects targeted for lung cancer screening for HNSCC as well.

METHODS

Medical records, death certificates, and cancer registry and questionnaire data were used to determine the number of observed incident HNSCC cases in the Pittsburgh Lung Screening Study (PLuSS), a cohort of current and former smokers aged ≥50 years with a ≥12.5 pack‐year smoking history. The expected number of cases was estimated using stratum‐specific incidence rates obtained from Surveillance, Epidemiology, and End Results data for 2000 through 2011. The standardized incidence ratio was calculated to examine the difference between the observed and expected number of cases.

RESULTS

Of the 3587 at‐risk participants in the PLuSS, 23 (0.64%) developed HNSCC over a total of 32,201 person‐years of follow‐up. This finding was significantly higher than expected based on incidence rates obtained from the Surveillance, Epidemiology, and End Results program (13.70 cases expected; standardized incidence ratio, 1.68 [95% confidence interval, 1.06‐2.52]). The excess burden of HNSCC in the PLuSS was 28.9 cases per 100,000 person‐years. Observed incident cases were significantly more often male, had started smoking at a younger age, smoked more per day, and had more pack‐years of smoking than the rest of the PLuSS at‐risk participants.

CONCLUSIONS

The results of the current study provide a rationale for offering head and neck cancer screening along with computed tomography screening for lung cancer. Randomized controlled trials that assess the effectiveness of adding examination of the head and neck area to lung cancer screening programs are warranted. Cancer 2015;121:1431–1435. © 2015 American Cancer Society.
Efferent innervation of turtle semicircular canal cristae: Comparisons with bird and mouse
Authors: Jordan Paivi M. , Fettis Margaret , Holt Joseph C.
Published: January 2015

In the vestibular periphery of nearly every vertebrate, cholinergic vestibular efferent neurons give rise to numerous presynaptic varicosities that target hair cells and afferent processes in the sensory neuroepithelium. Although pharmacological studies have described the postsynaptic actions of vestibular efferent stimulation in several species, characterization of efferent innervation patterns and the relative distribution of efferent varicosities among hair cells and afferents are also integral to understanding how efferent synapses operate. Vestibular efferent markers, however, have not been well characterized in the turtle, one of the animal models used by our laboratory. Here we sought to identify reliable efferent neuronal markers in the vestibular periphery of turtle, to use these markers to understand how efferent synapses are organized, and to compare efferent neuronal labeling patterns in turtle with two other amniotes using some of the same markers. Efferent fibers and varicosities were visualized in the semicircular canal of red‐eared turtles (Trachemys scripta elegans), zebra finches (Taeniopygia guttata), and mice (Mus musculus) utilizing fluorescent immunohistochemistry with antibodies against choline acetyltransferase (ChAT). Vestibular hair cells and afferents were counterstained using antibodies to myosin VIIa and calretinin. In all species, ChAT labeled a population of small diameter fibers giving rise to numerous spherical varicosities abutting type II hair cells and afferent processes. That these ChAT‐positive varicosities represent presynaptic release sites were demonstrated by colabeling with antibodies against the synaptic vesicle proteins synapsin I, SV2, or syntaxin and the neuropeptide calcitonin gene‐related peptide. Comparisons of efferent innervation patterns among the three species are discussed. J. Comp. Neurol. 523:1258–1280, 2015. © 2015 Wiley Periodicals, Inc.
Modeling the two‐locus architecture of divergent pollinator adaptation: how variation in SAD paralogs affects fitness and evolutionary divergence in sexually deceptive orchids
Authors: Xu Shuqing , Schlüter Philipp M.
Published: January 2015

Divergent selection by pollinators can bring about strong reproductive isolation via changes at few genes of large effect. This has recently been demonstrated in sexually deceptive orchids, where studies (1) quantified the strength of reproductive isolation in the field; (2) identified genes that appear to be causal for reproductive isolation; and (3) demonstrated selection by analysis of natural variation in gene sequence and expression. In a group of closely related Ophrys orchids, specific floral scent components, namely n‐alkenes, are the key floral traits that control specific pollinator attraction by chemical mimicry of insect sex pheromones. The genetic basis of species‐specific differences in alkene production mainly lies in two biosynthetic genes encoding stearoyl–acyl carrier protein desaturases (SAD) that are associated with floral scent variation and reproductive isolation between closely related species, and evolve under pollinator‐mediated selection. However, the implications of this genetic architecture of key floral traits on the evolutionary processes of pollinator adaptation and speciation in this plant group remain unclear. Here, we expand on these recent findings to model scenarios of adaptive evolutionary change at SAD2 and SAD5, their effects on plant fitness (i.e., offspring number), and the dynamics of speciation. Our model suggests that the two‐locus architecture of reproductive isolation allows for rapid sympatric speciation by pollinator shift; however, the likelihood of such pollinator‐mediated speciation is asymmetric between the two orchid species O. sphegodes and O. exaltata due to different fitness effects of their predominant SAD2 and SAD5 alleles. Our study not only provides insight into pollinator adaptation and speciation mechanisms of sexually deceptive orchids but also demonstrates the power of applying a modeling approach to the study of pollinator‐driven ecological speciation.
Basic Study on Loss Factor Evaluation of Concentrated Winding Permanent Magnet Synchronous Motor
Authors: Takahata Ryoichi , Wakui Shinichi , Ajima Toshiyuki , Miyata Kenji , Noma Keiji , Senoo Masaharu
Published: January 2015

This paper describes the influence of pulse width modulation (PWM) inverter harmonic loss on concentrated winding interior permanent magnet synchronous motor characteristics by using finite element method (FEM) analysis and several measurements. In the measurements, the PWM inverter harmonic loss was evaluated by using a PWM inverter and a sinusoidal power supply. By using the FEM analysis, it was confirmed that the PWM inverter harmonic mainly caused an increase of eddy current losses in the magnetic steel sheet and the permanent magnet. The results indicate that higher inductance of the motor is effective in reducing the harmful effects of PWM inverter harmonics.
N–T Characteristics of Magnetic Gear Motor with Inherent Overload Protection
Authors: Niguchi Noboru , Hirata Katsuhiro , Morimoto Eiki
Published: January 2015

This paper describes the N−T characteristics of magnetic gear motors in which permanent magnets are used only in the high‐speed rotor. The N−T characteristics for the cases with and without high‐speed rotor slip are computed by finite element analysis under vector control. These characteristics are verified by measurements on a prototype. Finally, the differences between the computed and measured N−T characteristics are discussed.
Ligand‐Promoted Reactivity of Alkenes in Dehydrogenative Heck Reactions of Furans and Thiophenes
Authors: Vasseur Alexandre , Laugel Caroline , Harakat Dominique , Muzart Jacques , Le Bras Jean
Published: January 2015

4,5‐Diazafluorenone was found to promote the dehydrogenative Heck reaction of furans and thiophenes with hindered alkenes. High stereoselectivity was achieved in the synthesis of β,β‐diaryl α,β‐unsaturated alkenes. A mechanism, based on ESI‐MS studies, kinetic experiments, and competitive reactions, was proposed. The ligand influences C–H bond activation, insertion of the alkenes, the stereodetermining step, and the aerobic regeneration of the catalyst.
Use of acetochlor and cancer incidence in the Agricultural Health Study
Authors: Lerro Catherine C. , Koutros Stella , Andreotti Gabriella , Hines Cynthia J. , Blair Aaron , Lubin Jay , Ma Xiaomei , Zhang Yawei , Beane Freeman Laura E.
Published: January 2015

Since its registration in 1994 acetochlor has become a commonly used herbicide in the US, yet no epidemiologic study has evaluated its carcinogenicity in humans. We evaluated the use of acetochlor and cancer incidence among licensed pesticide applicators in the Agricultural Health Study. In telephone interviews administered during 1999–2005, participants provided information on acetochlor use, use of other pesticides and additional potential confounders. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (95% CI) for cancers that occurred from the time of interview through 2011 in Iowa and 2010 in North Carolina. Among 33,484 men, there were 4,026 applicators who used acetochlor and 3,234 incident cancers, with 304 acetochlor‐exposed cases. Increased risk of lung cancer was observed among acetochlor users (RR = 1.74; 95% CI: 1.07–2.84) compared to nonusers, and among individuals who reported using acetochlor/atrazine product mixtures (RR = 2.33; 95% CI: 1.30–4.17), compared to nonusers of acetochlor. Colorectal cancer risk was significantly elevated among the highest category of acetochlor users (RR = 1.75; 95% CI: 1.08–2.83) compared to never users. Additionally, borderline significantly increased risk of melanoma (RR = 1.61; 95% CI: 0.98–2.66) and pancreatic cancer (RR = 2.36; 95% CI: 0.98–5.65) were observed among acetochlor users. The associations between acetochlor use and lung cancer, colorectal cancer, melanoma and pancreatic cancer are suggestive, however the lack of exposure‐response trends, small number of exposed cases and relatively short time between acetochlor use and cancer development prohibit definitive conclusions.
Androgen Receptor Silences Thioredoxin‐interacting Protein and Competitively Inhibits Glucocorticoid Receptor‐Mediated Apoptosis in Pancreatic β‐Cells
Authors: Harada Naoki , Katsuki Takahiro , Takahashi Yuji , Masuda Tatsuya , Yoshinaga Mariko , Adachi Tetsuya , Izawa Takeshi , Kuwamura Mitsuru , Nakano Yoshihisa , Yamaji Ryoichi , Inui Hiroshi
Published: January 2015

Androgen receptor (AR) is known to bind to the same cis‐element that glucocorticoid receptor (GR) binds to. However, the effects of androgen signaling on glucocorticoid signaling have not yet been elucidated. Here, we investigated the effects of testosterone on dexamethasone (DEX, a synthetic glucocorticoid)‐induced apoptosis of pancreatic β‐cells, which might be involved in the pathogenesis of type 2 diabetes mellitus in males. We used INS‐1 #6 cells, which were isolated from the INS‐1 pancreatic β‐cell line and which express high levels of AR. Testosterone and dihydrotestosterone inhibited apoptosis induced by DEX in INS‐1 #6 cells. AR knockdown and the AR antagonist hydroxyflutamide each diminished the anti‐apoptotic effects of testosterone. AR was localized in the nucleus of both INS‐1 #6 cells and pancreatic β‐cells of male rats. Induction of thioredoxin‐interacting protein (TXNIP) is known to cause pro‐apoptotic effects in β‐cells. Testosterone suppressed the DEX‐induced increase of TXNIP at the transcriptional level. A Chromatin immunoprecipitation assays showed that both AR and GR competitively bound to the TXNIP promoter in ligand‐dependent manners. Recombinant DNA‐binding domain of AR bound to the same cis‐element of the TXNIP promoter that GR binds to. Our results show that AR and GR competitively bind to the same cis‐element of TXNIP promoter as a silencer and enhancer, respectively. These results indicate that androgen signaling functionally competes with glucocorticoid signaling in pancreatic β‐cell apoptosis. J. Cell. Biochem. 116: 998–1006, 2015. © 2015 Wiley Periodicals, Inc.
Cinnamaldehyde and Nitric Oxide Attenuate Advanced Glycation End Products‐Induced the JAK/STAT Signaling in Human Renal Tubular Cells
Authors: Huang Jau‐Shyang , Lee Ying‐Ho , Chuang Lea‐Yea , Guh Jinn‐Yuh , Hwang Jean‐Yu
Published: January 2015

Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. It possesses anti‐diabetic properties in vitro and in vivo and has anti‐inflammatory and anti‐cancer effects. To explore whether cinnamaldehyde was linked to altered advanced glycation end products (AGE)‐mediated diabetic nephropathy, the molecular mechanisms of cinnamaldehyde responsible for inhibition of AGE‐reduced nitric oxide (NO) bioactivity in human renal proximal tubular cells were examined. We found that raising the ambient AGE concentration causes a dose‐dependent decrease in NO generation. Cinnamaldehyde significantly reverses AGE‐inhibited NO generation and induces high levels of cGMP synthesis and PKG activation. Treatments with cinnamaldehyde, the NO donor S‐nitroso‐N‐acetylpenicillamine, and the JAK2 inhibitor AG490 markedly attenuated AGE‐inhibited NOS protein levels and NO generation. Moreover, AGE‐induced the JAK2‐STAT1/STAT3 activation, RAGE/p27Kip1/collagen IV protein levels, and cellular hypertrophy were reversed by cinnamaldehyde. The ability of cinnamaldehyde to suppress STAT activation was also verified by the observation that it significantly increased SCOS‐3 protein level. These findings indicate for the first time that in the presence of cinnamaldehyde, the suppression of AGE‐induced biological responses is probably mediated by inactivating the JAK2‐STAT1/STAT3 cascade or activating the NO pathway. J. Cell. Biochem. 116: 1028–1038, 2015. © 2015 Wiley Periodicals, Inc.
MiR‐210 Links Hypoxia With Cell Proliferation Regulation in Human Laryngocarcinoma Cancer
Authors: Zuo Jianhong , Wen Meiling , Lei Mingsheng , Peng Xiang , Yang Xuefeng , Liu Zhigang
Published: January 2015

The microRNA hsa‐miR‐210 (miR‐210) is associated with hypoxia; however its function has not fully identified. In the present study, we aim to detect its role concerning proliferation in Laryngocarcinoma. We found that miR‐210 was highly expressed in hypoxia, which inhibited proliferation by inducing cell cycle arrest in G1/G0 as well as apoptosis. We further identified that miR‐210 targeted fibroblast growth factor receptor‐like 1 (FGFRL1). Down regulation of FGFRL1 decreased cell proliferation by promoting proportion of cells in G1/G0 phase and decreasing in S and G2/M phases. Moreover, overexpression of FGFRL1 effectively released the miR‐210‐induced suppression of SCC10A cell proliferation. Expression of miR‐210 repressed tumor xenograft growth in vivo as well. Together, our findings reveal a new mechanism of adaptation to hypoxia that miR‐210 inhibits the proliferation via inducing cell cycle arrest and apoptosis by the targeting of FGFRL1. J. Cell. Biochem. 116: 1039–1049, 2015. © 2015 Wiley Periodicals, Inc.
Retracted: MiR‐17–5p Up‐Regulates YES1 to Modulate the Cell Cycle Progression and Apoptosis in Ovarian Cancer Cell Lines
Authors: Li Lan , He Li , Zhao Jian‐Li , Xiao Jing , Liu Min , Li Xin , Tang Hua
Published: January 2015

MicroRNAs (miRNAs) are small, non‐coding RNAs that participate in the regulation of gene expression. Although many studies have demonstrated the involvement of miR‐17–5p in different cancers, little is known to its function in ovarian cancer. In this study, we demonstrated that overexpression of miR‐17–5p was able to enhance cell proliferation by promoting G1/S transition of the cell cycle and suppressing apoptosis in ES‐2 and OVCAR3 cell lines, whereas inhibition of miR‐17–5p yielded the reverse phenotype. YES1 was identified as a novel target gene of miR‐17–5p. Moreover, miR‐17–5p was found to directly bind to the 3′UTR of YES1 mRNA and up‐regulated its expression. Furthermore, knockdown of YES1 led to the suppression of proliferation and induced cell cycle arrest in ES‐2 and OVCAR3 cells. Ectopic expression of YES1 was able to reverse the effects of miR‐17–5p inhibition. Collectively, our results indicated that miR‐17–5p might play a role in human ovarian cancer by up‐regulating YES1 expression. J. Cell. Biochem. 116: 1050–1059, 2015. © 2015 Wiley Periodicals, Inc.
Caveolae May Enable Albumin to Enter Human Renal Glomerular Endothelial Cells
Authors: Moriyama Takahito , Takei Takashi , Itabashi Mitsuyo , Uchida Keiko , Tsuchiya Ken , Nitta Kosaku
Published: January 2015

Caveolae on human renal glomerular endothelial cells (HRGECs) are increased in glomerular disease and correlate with the degree of albuminuria. To assess the mechanism by which caveolae contribute to albuminuria, we investigated whether albumin enters into HRGECs through caveolae. HRGECs were incubated with Alexa Fluor 488 labeled BSA or transferrin, followed by immunofluorescence localization with antibody to caveolin‐1 (Cav‐1), the main structural protein of caveolae, or clathrin, the major structural protein of clathrin coated pits, to assess whether BSA colocalized with Cav‐1. HRGECs were also incubated with albumin and caveolae disrupting agents, including methyl beta cyclodextrin (MBCD) and nystatin, to determine whether disrupting caveolae interfered with albumin endocytosis into HRGECs. HRGECs were also incubated with albumin after transfection with Cav‐1 small interfering RNAs (siRNAs). Labeled BSA colocalized with Cav‐1, but not with clathrin. In contrast, labeled transferrin colocalized with clathrin, but not with Cav‐1. Incubation of HRGECs with MBCD or nystatin, or transfection with Cav‐1 siRNA, significantly reduced the intracellular amounts of albumin and Cav‐1, relative to normal HRGECs, as shown by western blotting and immunofluorescence. These findings indicate that albumin enters HRGECs through the caveolae, suggesting that caveolae play an important role in the pathogenesis of albuminuria by providing a pathway through which albumin can enter glomerular endothelial cells. J. Cell. Biochem. 116: 1060–1069, 2015. © 2015 Wiley Periodicals, Inc.
Inactivation of the Phosphatidylinositol 3‐Kinase/Akt Pathway is Involved in BMP9‐mediated Tumor‐suppressive Effects in Gastric Cancer Cells
Authors: Duan Liang , Ye Liwei , Wu Rui , Wang Haiyan , Li Xueru , Li Huan , Yuan Shimei , Zha He , Sun Hui , Zhang Yunyuan , Chen Xian , Zhang Yan , Zhou Lan
Published: January 2015

Bone morphogenetic proteins (BMPs) are members of the TGF‐β superfamily signaling factors. Expression of several BMPs (BMP2, BMP4, and BMP7) is correlated to poor prognosis in gastric cancer patients. The function of BMP9, the latest discovered and most powerful osteogenetic factor, in gastric cancer is relatively unclear. In this report, we investigated the expression, function and underlying molecular mechanisms of BMP9 in gastric cancer. The results show that BMP9 expression was markedly decreased in gastric cancer tissues and cell lines. Enforced BMP9 expression in the gastric cancer cell lines SGC‐7901 and MNK‐45 increased apoptosis and reduced viability and migration. The in vivo function of BMP9 was evaluated in a xenograft mouse model. Tumors derived from SGC‐7901 cells with enforced BMP9 expression (SGC‐7901/BMP9) showed significantly reduced size and weight compared to that from control cells. Enforced BMP9 expression resulted in decreased Akt activity shown as lower levels of phosphorylation at Ser473 and Thr308 in Akt. The PI3K/Akt inhibitor LY294002 potentiated BMP9's viability and migration suppression, and apoptosis induction, which was associated with reduced expression of snail and VEGF and increased expression of E‐cadherin. In addition, tumors derived from SGC‐7901/BMP9 showed reduced Akt activity and VEGF expression, and increased E‐cadherin expression. Therefore, our studies reveal for the first time that inhibition of the PI3K‐Akt pathway is involved in the tumor suppressor effects of BMP9 in gastric cancer. J. Cell. Biochem. 116: 1080–1089, 2015. © 2015 Wiley Periodicals, Inc.
Regulatory review time for approval of oncology drugs in Japan between 2001 and 2014. Considerations of changes, factors that affect review time, and difference with the United States
Authors: Maeda Hideki , Kurokawa Tatsuo
Published: January 2015

In this study, we comprehensively and historically studied the review time of oncology drugs approved by the regulatory authorities in Japan with publicly available information. A total of 120 applications of oncology drugs were approved in Japan between April 2001 and July 2014. The review time peaked with 732.0 days (24.4 months) in 2005, and showed a tendency to decline gradually each year thereafter. After 2012, a significant reduction of the review time was seen in comparison to the median of 13‐year median time. In addition, we compared the review time with that in the United States. The median review time lag with the United States was significantly peaked in 2005. After 2005, the review time lag with the FDA has decreased, but lag did not significantly reduce by 2014. We also examined factors influencing the review time in Japan with multiple regression analysis. It was found that the factors related to a use of overseas data and expedited program for accelerating the reviews influenced the direction of shortening the review time. We consider that regulatory authorities in Japan need to keep making efforts to reduce the review time further and eliminate the review time lag with the United States.