bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase III trial comparing the efficacy and safety of recombinant‐ or urine‐derived human chorionic gonadotropin for ovulation triggering in Japanese women diagnosed with anovulation or oligo‐ovulation and undergoing ovulation induction with follitropin‐alfa
Authors: Ikenaga Hideyuki , Tanaka Yudai , Shiotani Masahide , Rogoff Daniela , Shimizu Shin , Ishihara Osamu
Published: January 2017

Aim

Outside of Japan, recombinant‐human chorionic gonadotropin (r‐hCG) is widely used for the induction of final follicular maturation and early luteinization in women undergoing ovulation induction; whereas in Japan, urine‐derived hCG (u‐hCG) is predominantly used. The primary objective of this study was to demonstrate the non‐inferiority of r‐hCG to u‐hCG for ovulation induction, as assessed by the ovulation rate.

Methods

This was an open‐label, parallel‐group, randomized, multicenter, phase III trial in Japanese women with anovulation or oligo‐ovulation secondary to hypothalamic–pituitary dysfunction or polycystic ovary syndrome, undergoing ovulation induction with recombinant‐human follicle‐stimulating hormone. The women were randomized (2:1) to receive either a single 250 μg s.c. dose of r‐hCG or a single 5000 IU i.m. dose of u‐hCG for ovulation triggering.

Results

Eighty‐one women were randomized to either r‐hCG (n=54) or u‐hCG (n=27). Ovulation occurred in 100% of the participants and treatment with r‐hCG was observed to be non‐inferior to u‐hCG for ovulation induction. Overall, the type and severity of adverse events were as expected for women receiving fertility treatment.

Conclusion

This study demonstrated that r‐hCG was non‐inferior to u‐hCG for inducing ovulation. Furthermore, r‐hCG demonstrated an expected safety profile, with no new safety concerns identified.
Equilibrium between anti‐oxidants and reactive oxygen species: a requisite for oocyte development and maturation
Authors: Kala Manika , Shaikh Muhammad Vaseem , Nivsarkar Manish
Published: January 2017

Reactive oxygen species (ROS) are required for cellular functioning and are controlled by anti‐oxidants. TheROSinfluence the follicles, oocytes, endometrium, and their environment. The luteinizing hormone surge initiates a massive recruitment ofROSthat modulates major reproductive functions namely, oocyte maturation, ovarian steroidogenesis, corpus luteal function, and luteolysis. The anti‐oxidant system balancesROSgeneration and maintains the cellular functions. Both enzymatic and non‐enzymatic anti‐oxidants namely, vitamins and minerals are present in the follicles and protect the oocytes from the damaging effects ofROS. The overproduction ofROSleads to oxidative stress that affects the quality of oocytes and subsequent anovulation. Although researchers have tried to establish the role ofROSand anti‐oxidants in oocyte development, still this aspect needs to be revisited. This review discusses the importance of theROSand anti‐oxidant balance that is required for the development and maturation of oocytes. There are increasing data on the activity ofROSand anti‐oxidants in supporting oocyte development and maturation. However, extensive research is required to identify the safe physiological concentration and duration of both theROSand anti‐oxidants that are required to facilitate oocyte development and maturation during in vitro and in vivo conditions.
Efficient arithmetic on ARM‐NEON and its application for high‐speed RSA implementation
Authors: Seo Hwajeong , Liu Zhe , Großschädl Johann , Kim Howon
Published: January 2017

Advanced modern processors support single instruction, multiple data instructions (e.g., Intel‐AVX and ARM‐NEON) and a massive body of research on vector‐parallel implementations of modular arithmetic, which are crucial components for modern public‐key cryptography ranging from Rivest, Shamir, and Adleman (RSA), ElGamal, Digital Signature Algorithm (DSA), and elliptic curve cryptography, have been conducted. In this paper, we introduce a novel double operand scanning method to speed up multi‐precision squaring with non‐redundant representations on single instruction, multiple data architecture where the part of the operands are doubled to compute the squaring operation without read‐after‐write dependencies between source and destination variables. Afterwards, Karatsuba algorithm is applied to both multiplication and squaring operations. For modular multiplication, separated Montgomery algorithm is chosen. Finally, the Rivest, Shamir, and Adleman (RSA) implementations outperform the best‐known results on the ARM‐NEON platforms. Copyright © 2017 John Wiley & Sons, Ltd.
An access control scheme with dynamic user management and cloud‐aided decryption
Authors: Shi Jiaoli , Huang Chuanhe , Wang Jing , He Kai , Shen Xieyang
Published: January 2017

Ciphertext‐policy attribute‐based encryption is becoming a cryptographic solution to realize fine‐grained access control. However, some important problems have not been effectively solved yet such as (i) low efficiency of dynamic change of a user or his attribute and (ii) high computation cost at user end. In this paper, we propose an access control scheme with dynamic user management using a version key and especially realize direct cloud‐aided attribute revocation without updating another user's key or re‐encrypting ciphertexts. We present a cloud‐aided decryption method with which most of decrypting work can be transferred to cloud. Compared with the existing schemes, our scheme causes less computation cost at user end and supports efficient dynamic change of a user or his attribute. Simulation indicates that our direct cloud‐aided attribute revocation method takes less time. Copyright © 2017 John Wiley & Sons, Ltd.
Concise Synthesis of a Pentasaccharide Repeating Unit Corresponding to the O‐Antigen of Salmonella Enterica O51
Authors: Bhaumik Ishani , Misra Anup Kumar
Published: January 2017

A pentasaccharide repeating unit corresponding to the cell wall O‐antigen of Salmonella enterica O51 has been synthesized as its 2‐aminoethyl glycoside adopting a sequential stereoselective glycosylation strategy. Judiciously functionalized monosaccharide intermediates were prepared and stereoselectively assembled to get the desired pentasaccharide derivative in excellent yield. An elegant one‐pot reaction condition has been applied for the stereoselective glycosylation and p‐methoxybenzyl group deprotection.
Absorption competition quenching mechanism of porous covalent organic polymer as luminescent sensor for selective sensing Fe3+
Authors: Guo Lin , Zeng Xiaofei , Lan Jianhui , Yun Jimmy , Cao Dapeng
Published: January 2017

Developing luminescent sensors for highly selective detecting Fe3+ is a very important topic, because Fe3+ plays a key role in human's living environment. In this work, we use tetrakis (p‐broMophenyl) methane as a monomer, and 4,4′‐Dibromobiphenyl, 9,10‐Dibromoanthracene, and 1,4‐dibromonaphthalene as another monomer to synthesize three porous luminescent covalent‐organic polymers (COPs) by Ni‐catalyzed Yamamoto reaction respectively. Results indicate that these COPs exhibit excellent selectivity and sensitivity for detecting Fe3+ in 10 wt% ethanol aqueous solutions. By using the three COPs as representative sensors, we reveal the absorption competition quenching (ACQ) mechanism of the COPs for sensing Fe3+, i. e., the absorption spectrum overlap between the COPs and analytes leads to a competition of absorption of the light source between the analyte and the COP material, which causes the luminescence quenching of the COPs in detecting analytes. For all cases studied here, the ACQ mechanism takes effect. It is expected that the ACQ mechanism provided here can be used as an efficient strategy to design the new luminescent sensors for applications of interest.
ISCEV Standard for clinical electro-oculography (2017 update)
Authors: Constable Paul A. , Bach Michael , Frishman Laura J. , Jeffrey Brett G. , Robson Anthony G. ,   for the International Society for Clinical Electrophysiology of Vision
Published: January 2017

The clinical electro-oculogram (EOG) is an electrophysiological test of the outer retina and retinal pigment epithelium (RPE) in which changes in the electrical potential across the RPE are recorded during successive periods of dark and light adaptation. This document presents the 2017 EOG Standard from the International Society for Clinical Electrophysiology of Vision (ISCEV: www.iscev.org). This standard has been reorganized and updated to include an explanation of the mechanism of the EOG, but without substantive changes to the testing protocol from the previous version published in 2011. It describes methods for recording the EOG in clinical applications and gives detailed guidance on technical requirements, practical issues and reporting of results with the main clinical measure (the Arden ratio) now termed the light peak:dark trough ratio. The standard is intended to promote consistent quality of testing and reporting within and between clinical centers.
Granitoids of the Magba Shear Zone, West Cameroon, Central Africa: Evidences for Emplacement under Transpressive Tectonic Regime
Authors: Ntieche Benjamin , Mohan M. Ram , Amidou Moundi
Published: January 2017

The Magba Shear Zone is made up of granites, migmatites, orthogneiss, metagabbro, mafic dyke and mylonites with coarse grained texture, porphyroblastic, granoblastic, cataclastic and mylonitic texture respectively. Structural features and kinematic indicators testify the syntectonic emplacement of Magba granitoids and also provide detailed information on the relative timing of deformation as follows: (1) D1 of tangential movement immediately followed by (2) the D2 phase which is heterogeneous simple shear in dextral transpressive context with a NW-SE direction (3) D3 tectonic phase is marked by sinistral transpressive tectonic and superposed folding with a NE-SW kinematic direction. Combined ductile NE-SW shear movements and NW-SE compressional movements defined a transpressional tectonic regime during the D3 deformation (4) A brittle stage D4 is controlled by transcurrent tectonics and responsible for the emplacement of faults, and joints. The Magba granites would have intruded along sub-vertical mid-crustal feeder channels and were emplaced as a sheet or sheets along the shear zone during the early stage of the C3 shearing, followed by gabbro and mafic dyke at the late stage. Strike-slip dilatancy pumping under transpressive tectonic is suggested as a possible mechanism for the emplacement of the Magba granites.
Comorbidities of Atopic Dermatitis: Beyond Rhinitis and Asthma
Authors: Andersen Yuki M.F. , Egeberg Alexander , Skov Lone , Thyssen Jacob P.
Published: January 2017

Purpose of Review

In this review article, we summarize the current evidence about atopic dermatitis (AD)-associated comorbidities, beyond the traditional atopic and allergic conditions.

Recent Findings

Patients with AD may have an increased risk of cardiovascular diseases, certain malignancies, autoimmune diseases, and neuropsychiatric diseases. The causes of these associations are likely multifactorial and may include genetic predispositions, systemic low-grade inflammation, environmental exposures, medication, and lifestyle and behavioral risk factors. There appears to be geographical variations in prevalence of comorbidities in patients with AD, indicating that differences in ethnicity and lifestyle factors may significantly influence the risk of certain comorbidities.

The reported comorbidities in recent literature emphasize the burden of disease in patients with AD. Early appropriate AD therapy, in combination with reduction of risk factors, may help prevention of certain comorbidities. The reported observations may generate hypotheses for future investigations in underlying risk factors for AD-associated comorbidities.
Why locate manufacturing in a high‐cost country? A case study of 35 production location decisions
Authors: Ketokivi Mikko , Turkulainen Virpi , Seppälä Timo , Rouvinen Petri , Ali‐Yrkkö Jyrki
Published: January 2017

In this paper, we examine in detail 35 final assembly location decisions to gain understanding of the manufacturing location decision from strategy and economic policy perspectives. We are particularly interested in the decision to locate final assembly specifically in a high‐cost (high GDP per capita) environment. In contrast with the earlier literature, we focus not just on manufacturing activities themselves, but also the key linkages between production, market, supply chain, and product development. These linkages are examined using three key concepts from theories of organization design: formalization, specificity, and coupling. Using these concepts, an analysis of the micro‐structure of each case reveals important commonalities that inform our understanding of location decisions. We conclude by discussing the policy implications of our findings.
Transverse Incision for Minimally Invasive Plate Osteosynthesis of Osteoporotic Tibial Plateau Fractures
Authors: Saini Aaron K. , Ankit Desai , Trompeter Alex J. , Newman Kevin J. , Elliott David S.
Published: January 2017

Fractures of the tibial plateau frequently require surgical intervention. Open approaches are increasingly being replaced by minimally invasive techniques. Plate fixation may be uni- or bicondylar, and surgical incisions are traditionally orientated in the longitudinal plane. We describe osteoporotic fragility tibial plateau fractures managed with plate fixation applied through minimally invasive transverse incisions. All cases achieved acceptable fracture reduction, restoration of alignment, and timely bone union without infection or wound complications. This technique reduces the risk of wound complications at later arthroplasty, along with the established benefits of current minimally invasive techniques. This is the first report in the literature of the use of transverse incisions for minimally invasive plate fixation of the tibial plateau.
An amylin analog used as a challenge test for Alzheimer's disease
Authors: Zhu Haihao , Stern Robert A. , Tao Qiushan , Bourlas Alexandra , Essis Maritza D. , Chivukula Meenakshi , Rosenzweig James , Steenkamp Devin , Xia Weiming , Mercier Gustavo A. , Tripodis Yorghos , Farlow Martin , Kowall Neil , Qiu Wei Qiao
Published: January 2017

Introduction

Preclinical studies demonstrate the potential of amylin in the diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans.

Methods

We administered a single subcutaneous injection of 60 μg of pramlintide to nondiabetic subjects under fasting conditions.

Results

None of the participants developed hypoglycemia after the injection of pramlintide. The pramlintide challenge induced a significant surge of amyloid‐β peptide and a decrease in total tau in the plasma of AD subjects but not in control participants. The pramlintide injection provoked an increase in interleukin 1 receptor antagonist and a decrease in retinol‐binding protein 4, which separates AD subjects from control subjects.

Discussion

Pramlintide use appeared to be safe in the absence of diabetes. The biomarker changes as a result of the pramlintide challenge, which distinguished AD from control subjects and mild cognitive impairment.
Development of an Evacuation Tool to Facilitate Disaster Preparedness: Use in a Planned Evacuation to Support a Hospital Move
Authors: Rozenfeld Ranna A. , Reynolds Sally L. , Ewing Sherri , Crulcich Mary Margaret , Stephenson Michelle
Published: January 2017

Objectives

Our institution relocated to a new facility 3.5 miles from our original location in Chicago on June 9, 2012. We describe the tools we developed to prepare, execute, and manage our evacuation and relocation.

Methods

Tools developed for the planned evacuation included the following: level of acuity and team composition classification, patient departure checklist, evacuation handoff tool, and a patient tracking system within the electronic health record. Incident Command structure was utilized.

Results

Monthly census tracking exercises were held beginning 12 months before the evacuation. Simulation drills began 6 months before the evacuation. The entire evacuation took less than 14 hours and there were no safety issues. A total of 127 patients were transported to the new facility: 45 patients were moved via the Neonatal/Pediatric Critical Care Transport Team, and the rest were moved with various team configurations.

Conclusion

Documents developed for a planned evacuation can be used for any planned or unplanned evacuation. We believe the tools we used to prepare, execute, and manage our evacuation and relocation would assist any health care facility to be better prepared to safely and efficiently evacuate patients in the event of a disaster, or to create surge capacity, and relocate them to another facility. (Disaster Med Public Health Preparedness. 2017;11:479–486)
The Importance of Culturally Safe Assessment Tools for Inuit Students
Authors: Stoffer Jasmin
Published: January 2017

There are still no major assessment and diagnostic tools that educators can use to properly assess our Inuit students’ learning. Cultural safety as it is currently defined in New Zealand educational research (Macfarlane et al., 2007) is necessary in creating a classroom community that encourages the appreciation of culture and worldview, and ultimately enables success as defined by the culture and community of the students. Modern day assessment tools used with Inuit students must also conform to this standard of cultural safety in order to ensure the equity and authenticity of the assessment results. There is a need for ongoing research and development of culturally safe assessment tools. To date, recommendations that include collaboration with local populations, evaluation of the tools presently being used, and the due diligence of ensuring these tools are culturally unbiased are a few guidelines that have the potential of creating culturally safe assessments that portray students’ true learning abilities and assist both teacher and community in the support of their students’ learning and success.
Probability of Debonding and Effective Elastic Properties of Particle-Reinforced Composites
Authors: Bian L. C. , Liu W. , Pan J.
Published: January 2017

In this paper, the effective properties of particle-reinforced composites with a weakened interphase are investigated. The particle and interphase are regarded as an equivalent-inclusion, and the interphase zone around the particle is modeled as a linear elastic spring layer. A modified micro-mechanics model is proposed to obtain the effective elastic modulus. Moreover, a statistical debonding criterion is proposed to characterize the varying probability of the evolution of interphase debonding. Numerical examples are considered to illustrate the effect of imperfect interphases on the effective properties of particle-reinforced composites. It is found that the effective elastic properties obtained in the present work are in a good agreement with the existing data from the literatures.
Roughness of a subglacial conduit under Hansbreen, Svalbard
Authors: MANKOFF KENNETH D. , GULLEY JASON D. , TULACZYK SLAWEK M. , COVINGTON MATTHEW D. , LIU XIAOFENG , CHEN YUNXIANG , BENN DOUGLAS I. , GŁOWACKI PIOTR S.
Published: January 2017

Hydraulic roughness exerts an important but poorly understood control on water pressure in subglacial conduits. Where relative roughness values are <5%, hydraulic roughness can be related to relative roughness using empirically-derived equations such as the Colebrook–White equation. General relationships between hydraulic roughness and relative roughness do not exist for relative roughness >5%. Here we report the first quantitative assessment of roughness heights and hydraulic diameters in a subglacial conduit. We measured roughness heights in a 125 m long section of a subglacial conduit using structure-from-motion to produce a digital surface model, and hand-measurements of theb-axis of rocks. We found roughness heights from 0.07 to 0.22 m and cross-sectional areas of 1–2 m2, resulting in relative roughness of 3–12% and >5% for most locations. A simple geometric model of varying conduit diameter shows that when the conduit is small relative roughness is >30% and has large variability. Our results suggest that parameterizations of conduit hydraulic roughness in subglacial hydrological models will remain challenging until hydraulic diameters exceed roughness heights by a factor of 20, or the conduit radius is >1 m for the roughness elements observed here.
The court as a battlefield: the art of war and the art of politics in the Han Feizi
Authors: Galvany Albert
Published: January 2017

Most scholarly contributions analysing the Han Feizi tend not only to overlook the influence military literature might have had on its conception and unfolding, but also to assert that the figure of the ruler, as described in this text, and that of the commander, as portrayed in military treatises, are incompatible. In refuting this view, I shall attempt to demonstrate that the writings collected in the Han Feizi fully embrace the logic of military confrontation, which entails, among other things, the deployment of deception and irregular procedures as a necessary means to secure sovereign power and to achieve a complete control of the administration. Accordingly, I shall show that a comprehensive understanding of this important work in the history of classical Chinese thought is not possible unless one takes into account this convergence of shared ideas and concepts from both spheres, that of military strategy and that of political science as set forth in the Han Feizi.
Post-transitional adaptation of the left heart in uncomplicated, very preterm infants
Authors: De Waal Koert , Phad Nilkant , Lakkundi Anil , Tan Peter
Published: January 2017

Background

The postnatal period in preterm infants involves multiple physiological changes occurring immediately after birth and continuing for days or weeks. To recognise and treat compromise, it is important to measure cardiovascular function. The aim of this study was to describe longitudinal left ventricular function using conventional and novel echocardiography techniques in preterm infants who did not experience significant antenatal or postnatal complications and treatments.

Methods

We prospectively obtained cardiac ultrasound images at days 3, 7, 14, 21, and 28 in 25 uncomplicated, preterm infants <30 weeks of gestation. Speckle tracking analysis of the four chambers and short-axis images provided parameters of left ventricular volume, deformation, and basal myocardial velocities. The patent ductus arteriosus, cardiac dimensions, and atrial volume were also measured.

Results

Stroke volume increased by 24% during the study period (1.05–1.30 ml/kg, p<0.05). Cardiac length, diameter, and systolic basal myocardial velocity increased with unchanged wall stress and deformation parameters. Diastolic function parameters resembled that of the fetus with predominance of atrial contraction compared with early diastolic velocities. Blood pressure and estimates of left ventricular filing pressure increased, suggesting that left ventricular compliance did not change in this period.

Conclusion

Stroke volume increased in the first 28 days after preterm birth. The preterm heart adapted by increasing its size, while maintaining systolic and atrial function, independent of early diastolic maturation. Longitudinal deformation of the left ventricle remained unchanged, suggesting relatively preserved function with maturation.
A Longitudinal Study of Hardiness as a Buffer for Posttraumatic Stress Symptoms in Mothers of Children With Cancer
Authors: Stoppelbein Laura , McRae Elizabeth , Greening Leilani
Published: January 2017

Mothers of children diagnosed with cancer have been found to be at a heightened risk for posttraumatic stress symptoms (PTSS). In an effort to identify a potential buffer, hardiness was examined as a protective factor for PTSS among mothers of children that were diagnosed with cancer in the past 2 weeks. Using a prospective design, mothers completed measures of PTSS and hardiness at the time of their child’s cancer diagnosis and then again at 6 and 12 months postdiagnosis. Random effects regression analyses revealed that mothers who scored high on hardiness were less likely to experience PTSS after controlling for the effect of time. PTSS cluster-specific relations with hardiness were also examined, which revealed that mothers who scored high on hardiness experienced fewer avoidance/numbing symptoms at the time of their child’s diagnosis of cancer and across 12 months, but mothers who scored low on hardiness tended to experience more avoidance/numbing symptoms at the time of their child’s diagnosis. However, these symptoms declined gradually over the course of 12 months. The present findings support examining hardiness further as a buffer against specific PTSS clusters and exploring options for identifying and treating mothers of children with cancer that may be at risk for PTSS.
A fungal wheat pathogen evolved host specialization by extensive chromosomal rearrangements
Authors: Hartmann Fanny E , Sánchez-Vallet Andrea , McDonald Bruce A , Croll Daniel
Published: January 2017

Fungal pathogens can rapidly evolve virulence towards resistant crops in agricultural ecosystems. Gains in virulence are often mediated by the mutation or deletion of a gene encoding a protein recognized by the plant immune system. However, the loci and the mechanisms of genome evolution enabling rapid virulence evolution are poorly understood. We performed genome-wide association mapping on a global collection of 106 strains of Zymoseptoria tritici, the most damaging pathogen of wheat in Europe, to identify polymorphisms linked to virulence on two wheat varieties. We found 25 distinct genomic loci associated with reproductive success of the pathogen. However, no locus was shared between the host genotypes, suggesting host specialization. The main locus associated with virulence encoded a highly expressed, small secreted protein. Population genomic analyses showed that the gain in virulence was explained by a segregating gene deletion polymorphism. The deletion was likely adaptive by preventing detection of the encoded protein. Comparative genomics of closely related species showed that the locus emerged de novo since speciation. A large cluster of transposable elements in direct proximity to the locus generated extensive rearrangements leading to multiple independent gene losses. Our study demonstrates that rapid turnover in the chromosomal structure of a pathogen can drive host specialization.
Fractal nematic colloids
Authors: Hashemi S. M. , Jagodič U. , Mozaffari M. R. , Ejtehadi M. R. , Muševič I. , Ravnik M.
Published: January 2017

Fractals are remarkable examples of self-similarity where a structure or dynamic pattern is repeated over multiple spatial or time scales. However, little is known about how fractal stimuli such as fractal surfaces interact with their local environment if it exhibits order. Here we show geometry-induced formation of fractal defect states in Koch nematic colloids, exhibiting fractal self-similarity better than 90% over three orders of magnitude in the length scales, from micrometers to nanometres. We produce polymer Koch-shaped hollow colloidal prisms of three successive fractal iterations by direct laser writing, and characterize their coupling with the nematic by polarization microscopy and numerical modelling. Explicit generation of topological defect pairs is found, with the number of defects following exponential-law dependence and reaching few 100 already at fractal iteration four. This work demonstrates a route for generation of fractal topological defect states in responsive soft matter.
Transient structural variations have strong effects on quantitative traits and reproductive isolation in fission yeast
Authors: Jeffares Daniel C. , Jolly Clemency , Hoti Mimoza , Speed Doug , Shaw Liam , Rallis Charalampos , Balloux Francois , Dessimoz Christophe , Bähler Jürg , Sedlazeck Fritz J.
Published: January 2017

Large structural variations (SVs) within genomes are more challenging to identify than smaller genetic variants but may substantially contribute to phenotypic diversity and evolution. We analyse the effects of SVs on gene expression, quantitative traits and intrinsic reproductive isolation in the yeast Schizosaccharomyces pombe. We establish a high-quality curated catalogue of SVs in the genomes of a worldwide library of S. pombe strains, including duplications, deletions, inversions and translocations. We show that copy number variants (CNVs) show a variety of genetic signals consistent with rapid turnover. These transient CNVs produce stoichiometric effects on gene expression both within and outside the duplicated regions. CNVs make substantial contributions to quantitative traits, most notably intracellular amino acid concentrations, growth under stress and sugar utilization in winemaking, whereas rearrangements are strongly associated with reproductive isolation. Collectively, these findings have broad implications for evolution and for our understanding of quantitative traits including complex human diseases.
Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness
Authors: Nishita Michiru , Park Seung-Yeol , Nishio Tadashi , Kamizaki Koki , Wang ZhiChao , Tamada Kota , Takumi Toru , Hashimoto Ryuju , Otani Hiroki , Pazour Gregory J. , Hsu Victor W. , Minami Yasuhiro
Published: January 2017

Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
CD5 molecule-like and transthyretin as putative biomarkers of chronic myeloid leukemia - an insight from the proteomic analysis of human plasma
Authors: Fatima Iram , Sadaf Saima , Musharraf Syed Ghulam , Hashmi Naghma , Akhtar Muhammad Waheed
Published: January 2017

Better and sensitive biomarkers are needed to help understand the mechanism of disease onset, progression, prognosis and monitoring of the therapeutic response. Aim of this study was to identify the candidate circulating markers of chronic-phase chronic myeloid leukemia (CP-CML) manifestations, having potential to develop into predictive- or monitoring-biomarkers. A proteomic approach, two-dimensional gel electrophoresis in conjunction with mass spectrometry (2DE-MS), was employed for this purpose. Based on the spot intensity measurements, six proteins were found to be consistently dysregulated in CP-CML subjects compared to the healthy controls [false discovery rate (FDR) threshold ≤0.05]. These were identified as α-1-antichymotrypsin, α-1-antitrypsin, CD5 molecule-like, stress-induced phosphoprotein 1, vitamin D binding protein isoform 1 and transthyretin by MS analysis [PMF score ≥79; data accessible via ProteomeXchange with identifier PXD002757]. Quantitative ELISA, used for validation of candidate proteins both in the pre-treated and nilotinib-treated CP-CML cases, demonstrate that CD5 molecule-like, transthyretin and alpha-1-antitrypsin may serve as useful predictive markers and aid in monitoring the response of TKI-based therapy (ANOVA p < 0.0001). Two of the circulating marker proteins, identified in this study, had not previously been associated with chronic- or acute-phase myeloid leukemia. Exploration of their probable association with CP-CML, in a larger study cohort, may add to our understanding of the disease mechanism besides developing clinically useful biomarkers in future.
A systematic SNP selection approach to identify mechanisms underlying disease aetiology: linking height to post-menopausal breast and colorectal cancer risk
Authors: Elands Rachel J. J. , Simons Colinda C. J. M. , Riemenschneider Mona , Isaacs Aaron , Schouten Leo J. , Verhage Bas A. , Van Steen Kristel , Godschalk Roger W. L. , van den Brandt Piet A. , Stoll Monika , Weijenberg Matty P.
Published: January 2017

Data from GWAS suggest that SNPs associated with complex diseases or traits tend to co-segregate in regions of low recombination, harbouring functionally linked gene clusters. This phenomenon allows for selecting a limited number of SNPs from GWAS repositories for large-scale studies investigating shared mechanisms between diseases. For example, we were interested in shared mechanisms between adult-attained height and post-menopausal breast cancer (BC) and colorectal cancer (CRC) risk, because height is a risk factor for these cancers, though likely not a causal factor. Using SNPs from public GWAS repositories at p-values < 1 × 10−5 and a genomic sliding window of 1 mega base pair, we identified SNP clusters including at least one SNP associated with height and one SNP associated with either post-menopausal BC or CRC risk (or both). SNPs were annotated to genes using HapMap and GRAIL and analysed for significantly overrepresented pathways using ConsensuspathDB. Twelve clusters including 56 SNPs annotated to 26 genes were prioritised because these included at least one height- and one BC risk- or CRC risk-associated SNP annotated to the same gene. Annotated genes were involved in Indian hedgehog signalling (p-value = 7.78 × 10−7) and several cancer site-specific pathways. This systematic approach identified a limited number of clustered SNPs, which pinpoint potential shared mechanisms linking together the complex phenotypes height, post-menopausal BC and CRC.
Beta-agonist stimulation ameliorates the phenotype of spinal and bulbar muscular atrophy mice and patient-derived myotubes
Authors: Milioto Carmelo , Malena Adriana , Maino Eleonora , Polanco Maria J. , Marchioretti Caterina , Borgia Doriana , Pereira Marcelo Gomes , Blaauw Bert , Lieberman Andrew P. , Venturini Roberta , Plebani Mario , Sambataro Fabio , Vergani Lodovica , Pegoraro Elena , Sorarù Gianni , Pennuto Maria
Published: January 2017

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by the loss of lower motor neurons. SBMA is caused by expansions of a polyglutamine tract in the gene coding for androgen receptor (AR). Expression of polyglutamine-expanded AR causes damage to motor neurons and skeletal muscle cells. Here we investigated the effect of β-agonist stimulation in SBMA myotube cells derived from mice and patients, and in knock-in mice. We show that treatment of myotubes expressing polyglutamine-expanded AR with the β-agonist clenbuterol increases their size. Clenbuterol activated the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway and decreased the accumulation of polyglutamine-expanded AR. Treatment of SBMA knock-in mice with clenbuterol, which was started at disease onset, ameliorated motor function and extended survival. Clenbuterol improved muscle pathology, attenuated the glycolytic-to-oxidative metabolic alterations occurring in SBMA muscles and induced hypertrophy of both glycolytic and oxidative fibers. These results indicate that β-agonist stimulation is a novel therapeutic strategy for SBMA.
Body size and vocalization in primates and carnivores
Authors: Bowling D. L. , Garcia M. , Dunn J. C. , Ruprecht R. , Stewart A. , Frommolt K.-H. , Fitch W. T.
Published: January 2017

A fundamental assumption in bioacoustics is that large animals tend to produce vocalizations with lower frequencies than small animals. This inverse relationship between body size and vocalization frequencies is widely considered to be foundational in animal communication, with prominent theories arguing that it played a critical role in the evolution of vocal communication, in both production and perception. A major shortcoming of these theories is that they lack a solid empirical foundation: rigorous comparisons between body size and vocalization frequencies remain scarce, particularly among mammals. We address this issue here in a study of body size and vocalization frequencies conducted across 91 mammalian species, covering most of the size range in the orders Primates (n = 50; ~0.11–120 Kg) and Carnivora (n = 41; ~0.14–250 Kg). We employed a novel procedure designed to capture spectral variability and standardize frequency measurement of vocalization data across species. The results unequivocally demonstrate strong inverse relationships between body size and vocalization frequencies in primates and carnivores, filling a long-standing gap in mammalian bioacoustics and providing an empirical foundation for theories on the adaptive function of call frequency in animal communication.
Candidate pheromone receptors of codling moth Cydia pomonella respond to pheromones and kairomones
Authors: Cattaneo Alberto Maria , Gonzalez Francisco , Bengtsson Jonas M. , Corey Elizabeth A. , Jacquin-Joly Emmanuelle , Montagné Nicolas , Salvagnin Umberto , Walker William B. , Witzgall Peter , Anfora Gianfranco , Bobkov Yuriy V.
Published: January 2017

Olfaction plays a dominant role in the mate-finding and host selection behaviours of the codling moth (Cydia pomonella), an important pest of apple, pear and walnut orchards worldwide. Antennal transcriptome analysis revealed a number of abundantly expressed genes related to the moth olfactory system, including those encoding the olfactory receptors (ORs) CpomOR1, CpomOR3 and CpomOR6a, which belong to the pheromone receptor (PR) lineage, and the co-receptor (CpomOrco). Using heterologous expression, in both Drosophila olfactory sensory neurones and in human embryonic kidney cells, together with electrophysiological recordings and calcium imaging, we characterize the basic physiological and pharmacological properties of these receptors and demonstrate that they form functional ionotropic receptor channels. Both the homomeric CpomOrco and heteromeric CpomOrco + OR complexes can be activated by the common Orco agonists VUAA1 and VUAA3, as well as inhibited by the common Orco antagonists amiloride derivatives. CpomOR3 responds to the plant volatile compound pear ester ethyl-(E,Z)-2,4-decadienoate, while CpomOR6a responds to the strong pheromone antagonist codlemone acetate (E,E)-8,10-dodecadien-1-yl acetate. These findings represent important breakthroughs in the deorphanization of codling moth pheromone receptors, as well as more broadly into insect ecology and evolution and, consequently, for the development of sustainable pest control strategies based on manipulating chemosensory communication.
Differential growth of the northern Tibetan margin: evidence for oblique stepwise rise of the Tibetan Plateau
Authors: Wang Fei , Shi Wenbei , Zhang Weibin , Wu Lin , Yang Liekun , Wang Yinzhi , Zhu Rixiang
Published: January 2017

Models of how high elevations formed across Tibet predict: (a) the continuous thickening of a “viscous sheet”; (b) time-dependent, oblique stepwise growth; and (c) synchronous deformation across Tibet that accompanied collision. Our new observations may shed light on this issue. Here, we use 40Ar/39Ar and (U-Th)/He thermochronology from massifs in the hanging walls of thrust structures along the Kunlun Belt, the first-order orogenic range at the northern Tibetan margin, to elucidate the exhumation history. The results show that these massifs, and hence the plateau margin, were subject to slow, steady exhumation during the Early Cenozoic, followed by a pulse of accelerated exhumation during 40–35 Ma. The exhumation rate increases westward (from ~0.22 to 0.34 and 0.5 mm/yr). The two-fold increase in exhumation in the western part (0.5 mm/yr) compared to the eastern part suggests westward increases in exhumation and compressional stress along the Kunlun Belt. We relate these observations to the mechanisms responsible for the oblique stepwise rise of Tibet. After collision, oblique subduction beneath Kunlun caused stronger compressional deformation in the western part than in the eastern part, resulting in differential growth and lateral extrusion.
Charge transport in nanoscale vertical organic semiconductor pillar devices
Authors: Wilbers Janine G. E. , Xu Bojian , Bobbert Peter A. , de Jong Michel P. , van der Wiel Wilfred G.
Published: January 2017

We report charge transport measurements in nanoscale vertical pillar structures incorporating ultrathin layers of the organic semiconductor poly(3-hexylthiophene) (P3HT). P3HT layers with thickness down to 5 nm are gently top-contacted using wedging transfer, yielding highly reproducible, robust nanoscale junctions carrying high current densities (up to 106 A/m2). Current-voltage data modeling demonstrates excellent hole injection. This work opens up the pathway towards nanoscale, ultrashort-channel organic transistors for high-frequency and high-current-density operation.
Identification of consensus biomarkers for predicting non-genotoxic hepatocarcinogens
Authors: Huang Shan-Han , Tung Chun-Wei
Published: January 2017

The assessment of non-genotoxic hepatocarcinogens (NGHCs) is currently relying on two-year rodent bioassays. Toxicogenomics biomarkers provide a potential alternative method for the prioritization of NGHCs that could be useful for risk assessment. However, previous studies using inconsistently classified chemicals as the training set and a single microarray dataset concluded no consensus biomarkers. In this study, 4 consensus biomarkers of A2m, Ca3, Cxcl1, and Cyp8b1 were identified from four large-scale microarray datasets of the one-day single maximum tolerated dose and a large set of chemicals without inconsistent classifications. Machine learning techniques were subsequently applied to develop prediction models for NGHCs. The final bagging decision tree models were constructed with an average AUC performance of 0.803 for an independent test. A set of 16 chemicals with controversial classifications were reclassified according to the consensus biomarkers. The developed prediction models and identified consensus biomarkers are expected to be potential alternative methods for prioritization of NGHCs for further experimental validation.
Whole-exome sequencing of 228 patients with sporadic Parkinson’s disease
Authors: Sandor Cynthia , Honti Frantisek , Haerty Wilfried , Szewczyk-Krolikowski Konrad , Tomlinson Paul , Evetts Sam , Millin Stephanie , Keane Thomas , McCarthy Shane A. , Durbin Richard , Talbot Kevin , Hu Michele , Webber Caleb , Ponting Chris P. , Wade-Martins Richard
Published: January 2017

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, affecting 1% of the population over 65 years characterized clinically by both motor and non-motor symptoms accompanied by the preferential loss of dopamine neurons in the substantia nigra pars compacta. Here, we sequenced the exomes of 244 Parkinson’s patients selected from the Oxford Parkinson’s Disease Centre Discovery Cohort and, after quality control, 228 exomes were available for analyses. The PD patient exomes were compared to 884 control exomes selected from the UK10K datasets. No single non-synonymous (NS) single nucleotide variant (SNV) nor any gene carrying a higher burden of NS SNVs was significantly associated with PD status after multiple-testing correction. However, significant enrichments of genes whose proteins have roles in the extracellular matrix were amongst the top 300 genes with the most significantly associated NS SNVs, while regions associated with PD by a recent Genome Wide Association (GWA) study were enriched in genes containing PD-associated NS SNVs. By examining genes within GWA regions possessing rare PD-associated SNVs, we identified RAD51B. The protein-product of RAD51B interacts with that of its paralogue RAD51, which is associated with congenital mirror movements phenotypes, a phenotype also comorbid with PD.
UV and visible light photocatalytic activity of Au/TiO2 nanoforests with Anatase/Rutile phase junctions and controlled Au locations
Authors: Yu Yang , Wen Wei , Qian Xin-Yue , Liu Jia-Bin , Wu Jin-Ming
Published: January 2017

To magnify anatase/rutile phase junction effects through appropriate Au decorations, a facile solution-based approach was developed to synthesize Au/TiO2 nanoforests with controlled Au locations. The nanoforests cons®isted of anatase nanowires surrounded by radially grown rutile branches, on which Au nanoparticles were deposited with preferred locations controlled by simply altering the order of the fabrication step. The Au-decoration increased the photocatalytic activity under the illumination of either UV or visible light, because of the beneficial effects of either electron trapping or localized surface plasmon resonance (LSPR). Gold nanoparticles located preferably at the interface of anatase/rutile led to a further enhanced photocatalytic activity. The appropriate distributions of Au nanoparticles magnify the beneficial effects arising from the anatase/rutile phase junctions when illuminated by UV light. Under the visible light illumination, the LSPR effect followed by the consecutive electron transfer explains the enhanced photocatalysis. This study provides a facile route to control locations of gold nanoparticles in one-dimensional nanostructured arrays of multiple-phases semiconductors for achieving a further increased photocatalytic activity.
CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptoms
Authors: Lee Hong Kyung , Kim Hyung Sook , Kim Ji Sung , Kim Yong Guk , Park Ki Hwan , Lee Jae Hee , Kim Ki Hun , Chang In Young , Bae Sang-Cheol , Kim Youngsoo , Hong Jin Tae , Kehrl John H. , Han Sang-Bae
Published: January 2017

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production. Mesenchymal stem cells (MSCs) ameliorate SLE symptoms by targeting T cells, whereas the mechanisms of their efficacy remain incompletely understood. In this study, we show that transfer of human MSCs increased MRL.Faslpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL.Faslpr T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL.Faslpr T cells establishing long-lasting cellular contacts by enhancing T cell VCAM-1 expression in a CCL2-dependent manner. In contrast, CCL2 deficient MSCs did not induce T cell migration and VCAM-1 expression, resulting in insufficient cell-cell contact. Consequently, CCL2 deficient MSCs did not inhibit IFN-γ production by T cells and upon transfer no longer prolonged survival of MRL.Faslpr mice. Taken together, our imaging study demonstrates that CCL2 enables the prolonged MSC–T cell interactions needed for sufficient suppression of autoreactive T cells and helps to understand how MSCs ameliorate symptoms in lupus-prone MRL.Faslpr mice.