bluuebunny/crossref_metadata_2025 huggingface dataset:
Even‐electron [M–H]+ ions generated by loss of AgH from argentinated peptides with N‐terminal imine groups
Authors: Plaviak Alexandra , Osburn Sandra , Patterson Khiry , van Stipdonk Michael J.
Published: December 2015

Rationale

Experiments were performed to probe the creation of apparent even‐electron, [M–H]+ ions by CID of Ag‐cationized peptides with N‐terminal imine groups (Schiff bases).

Methods

Imine‐modified peptides were prepared using condensation reactions with aldehydes. Ag+‐cationized precursors were generated by electrospray ionization (ESI). Tandem mass spectrometry (MSn) and collision‐induced dissociation (CID) were performed using a linear ion trap mass spectrometer.

Results

Loss of AgH from peptide [M + Ag]+ ions, at the MS/MS stage, creates closed‐shell [M–H]+ ions from imine‐modified peptides. Isotope labeling unambiguously identifies the imine C‐H group as the source of H eliminated in AgH. Subsequent CID of the [M–H]+ ions generated sequence ions that are analogous to those produced from [M + H]+ ions of the imine‐modified peptides.

Conclusions

Experiments show (a) formation of novel even‐electron peptide cations by CID and (b) the extent to which sequence ions (conventional b, a and y ions) are generated from peptides with fixed charge site and thus lacking a conventional mobile proton. Copyright © 2015 John Wiley & Sons, Ltd.
Multinational Enterprises’ Entry Mode Strategies in Syria and Jordan: The Impact of Ownership Advantages
Authors: Al‐Habash Omar , Mmieh Frederick , Cleeve Emmanuel
Published: December 2015

This study addresses the issue of ownership advantages affecting multinational enterprises’ (MNEs) entry mode strategies in developing countries. Although a few studies have focused on such effects, very little attention has been devoted to the ownership advantages generated from the institutional environment of MNEs’ home countries. To bridge this gap, this study concentrates on three types of ownership advantages: intangible asset advantages (IAA), advantages of common governance (ACG), and home‐country‐specific advantages (HCSA). Using a sample of 303 foreign affiliates, this study empirically examines the choice of MNEs between a wholly owned subsidiary (WOS) and a joint venture (JV). The data were collected from senior executives of MNEs’ subsidiaries operating in Syria and Jordan. The findings of this study reveal that MNEs’ choice of entry mode strategies is significantly influenced by intangible asset advantages, advantages of common governance, and home‐country‐specific advantages. Hence, senior executives perceiving an increased importance of these assets will opt for a WOS rather than a JV when entering a new market in the Middle East. © 2015 Wiley Periodicals, Inc.
The Stepmother Tongue
Authors: Skinner John
Published: December 2015

There are numerous twentieth century writers in English who are not technically native speakers of the language, and whose relation to it is ambivalent, problematic or even hostile: by a simple kinship analogy one may often speak of the 'stepmother tongue'. Whilst fully aware of the current debates in postcolonial theory, John Skinner is also conscious of its sometimes unhelpful complexities and contradictions. The focus of this study is thus firmly on the fictional practice of the writers discussed. He offers the reader an insight into the diversity and rewards of contemporary anglophone fiction, whilst analysing some eighty individual texts. A uniquely comprehensive guide, the book will be welcomed by students and teachers of postcolonial literature.
Burkholderia multivorans SB6 Lipase as a Detergent Ingredient: Characterization and Stabilization
Authors: Boran Rukiye , Ugur Aysel
Published: December 2015

In this study, 265 bacterial isolates were collected from kitchen wastewater samples using Rhodamine B agar medium. Of these, 115 isolates were found to respond positively to the addition of commercial detergents. Using 16S rRNA sequence analysis, the isolate demonstrating the high stability towards commercial detergents was identified as Burkholderia multivorans. An SB6 lipase with a molecular mass of 70 kDa was purified from B. multivorans. The purified enzyme showed optimal activity at pH 9.0 and 40 °C and remained stable in the presence of various metal ions, surfactants, and oxidizing agents. The addition of boron compounds improved the pH stability and thermostability of the enzyme, which displayed stability against some commercial detergents; moreover, this stability increased when boron compounds were added to the incubation medium as stabilizers. These properties make SB6 lipase an ideal choice as an additive in detergent formulations.
Are Canadians more willing to provide chest-compression-only cardiopulmonary resuscitation (CPR)?—a nation-wide public survey
Authors: Cheskes Lindsay , Morrison Laurie J. , Beaton Dorcas , Parsons Janet , Dainty Katie N.
Published: December 2015

Background

Bystander cardiopulmonary resuscitation (CPR) improves the likelihood of survival from out-of-hospital cardiac arrest (OHCA), yet it is performed in only 30% of cases. The 2010 guidelines promote chest-compression-only bystander CPR—a change intended to increase willingness to provide CPR.

Objectives

1) To determine whether the Canadian general public is more willing to perform chest-compression-only CPR compared to traditional CPR; 2) to characterize public knowledge of OHCA; and 3) to identify barriers and facilitators to bystander CPR.

Methods

A 32-item survey assessing resuscitation knowledge, and willingness to provide CPR were disseminated in five Canadian regions. Descriptive statistics were used to characterize response distribution. Logistic regression analysis was applied to assess shifts in intention to provide CPR.

Results

A total of 428 completed surveys were analysed. When presented with a scenario of being a bystander in an OHCA, a greater proportion of respondents were willing to provide chest-compression-only CPR compared to traditional CPR for all victims (61.5% v. 39.7%,p<0.001), when the victim was a stranger (55.1% v. 38.8%,p<0.001), or when the victim was an unkempt individual (47.9% v. 28.5%,p<0.001). When asked to describe an OHCA, 41.4% said the heart stopped beating, and 20.8% said it was a heart attack. Identified barriers and facilitators included fear of litigation and lack of skill confidence.

Conclusions

This study identified gaps in knowledge, which may impair the ability of bystanders to act in OHCA. Most respondents expressed greater willingness to provide chest-compression-only CPR, but this was mediated by victim characteristics, skill confidence, and recognition of a cardiac arrest.
Probabilistic Measurement of Central Line–Associated Bloodstream Infections
Authors: Hota Bala , Malpiedi Paul , Fridkin Scott K. , Martin John , Trick William
Published: December 2015

OBJECTIVE

To develop a probabilistic method for measuring central line–associated bloodstream infection (CLABSI) rates that reduces the variability associated with traditional, manual methods of applying CLABSI surveillance definitions.

DESIGN

Multicenter retrospective cohort study of bacteremia episodes among patients hospitalized in adult patient-care units; the study evaluated presence of CLABSI.

SETTING

Hospitals that used SafetySurveillor software system (Premier) and who also reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network (NHSN).

PATIENTS

Patients were identified from a stratified sample from all eligible blood culture isolates from all eligible hospital units to generate a final set with an equal distribution (ie, 20%) from each unit type. Units were divided a priori into 5 major groups: medical intensive care unit, surgical intensive care unit, medical-surgical intensive care unit, hematology unit, or general medical wards.

INTERVENTIONS

Episodes were reviewed by 2 experts, and a selection of discordant reviews were re-reviewed. Data were joined with NHSN data for hospitals for in-plan months. A predictive model was created; model performance was assessed using the c statistic in a validation set and comparison with NHSN reported rates for in-plan months.

RESULTS

A final model was created with predictors of CLABSI. The c statistic for the final model was 0.75 (0.68–0.80). Rates from regression modeling correlated better with expert review than NHSN-reported rates.

CONCLUSIONS

The use of a regression model based on the clinical characteristics of the bacteremia outperformed traditional infection preventionist surveillance compared with an expert-derived reference standard.

Infect. Control Hosp. Epidemiol. 2016;37(2):149–155
Regaining Jerusalem: Eschatology and Slavery in Jewish Colonization in Seventeeth-Century Suriname
Authors: Davis Natalie Zemon
Published: December 2015

Through the person of the ex-converso David Nassy, “Regaining Jerusalem” asks how seventeenth-century Portuguese Jews could seek their own religious liberty at the same time they were enslaving Africans in the plantation economies of the Caribbean and the Guyana coast. Living in Amsterdam by the 1630s, Nassy was part of the Jewish community in Dutch Brazil, and then in the 1660s led the Jewish settlement in Dutch Suriname. Nassy was moved in part by eschatological hopes shared with other ex-conversos freed from Catholic tyranny, in part by his interest in plants and geography, and in part by entrepreneurial desire for profit. Nassy and his fellow Jews distinguished their own biblical exodus out of slavery from the destiny of their African captives, incorporating their slaves into the patriarchal Abrahamic household. This paper describes patterns of Jewish culture on the sugar plantations and the varied reactions of African men and women to it.
Modified approach to powered endoscopic dacryocystorhinostomy
Authors: Janakiram T N , Suri N , Sharma S B
Published: December 2015

Objective:

This paper presents modifications to powered endoscopic dacryocystorhinostomy without stenting for the management of acquired nasolacrimal duct obstruction.

Study design:

A retrospective, non-randomised review.

Method:

A total of 105 patients with epiphora secondary to acquired nasolacrimal duct obstruction were operated on by our modified powered endoscopic dacryocystorhinostomy approach.

Results:

Of 105 patients, 100 (95.2 per cent) have remained asymptomatic. One patient with a narrow ostium had improved symptoms, while four patients continued to experience persistent symptoms (treatment failures).

Conclusion:

The modified powered endoscopic dacryocystorhinostomy approach led to excellent results, without bone exposure and granulations, and with early mucosalisation.
Synthetic HI observations of spiral structure in the outer disk in galaxies
Authors: Khoperskov Sergey A. , Bertin Giuseppe
Published: December 2015

By means of 3D hydrodynamical simulations, in a separate paper we have discussed the properties of non-axisymmetric density wave trains in the outermost regions of galaxy disks, based on the picture that self-excited global spiral modes in the bright optical stellar disk are accompanied by low-amplitude short trailing wave signals outside corotation; in the gas, such wave trains can penetrate through the outer Lindblad resonance and propagate outwards, forming prominent spiral patterns. In this paper we present the synthetic 21 cm velocity maps expected from simulated models of the outer gaseous disk, focusing on the case when the disk is dominated by a two-armed spiral pattern, but considering also other more complex situations. We discuss some aspects of the spiral pattern in the gaseous periphery of galaxy disks noted in our simulations that might be interesting to compare with specific observed cases.
DEGREE PROFILE OF m-ARY SEARCH TREES: A VEHICLE FOR DATA STRUCTURE COMPRESSION
Authors: Kalpathy Ravi , Mahmoud Hosam
Published: December 2015

We revisit the random m-ary search tree and study a finer profile of its node outdegrees with the purpose of exploring possibilities of data structure compression. The analysis is done via Pólya urns. The analysis shows that the number of nodes of each individual node outdegree has a phase transition: Up to m = 26, the number of nodes of outdegree k, for k = 0, 1, …, m, is asymptotically normal; that behavior changes at m = 27. Based on the analysis, we propose a compact m-ary tree that offers significant space saving.
A Novel Tracking Controller for Autonomous Underwater Vehicles with Thruster Fault Accommodation
Authors: Sun Bing , Zhu Daqi , Yang Simon X.
Published: December 2015

In this paper, for the over-actuated Autonomous Underwater Vehicle (AUV) system, a novel tracking controller with thruster fault accommodation is proposed. Firstly, a cascaded control method is proposed for AUV robust tracking control. Then, we deal with the tracking control problem when one or more thrusters are completely or partly malfunctioning. Different control strategies are used to reallocate the thruster forces. For the cases that thrusters are partly malfunctioning, a weighted pseudo-inverse is firstly used to generate the normalised thruster forces. When the normalised thruster forces are out of maximum limits, the Quantum-behaviour Particle Swarm Optimisation (QPSO) is used for the restricted usage of the faulty thruster and to find the solution of the control reallocation problem within the limits. Compared with the weighted pseudo-inverse method, the QPSO algorithm does not need truncation or scaling to ensure the feasibility of the solution due to its particle search in the feasible solution space. The proposed controller is implemented in order to evaluate its performance in different faulty situations and its efficiency is demonstrated through simulation results.
MGR-DCB: A Precise Model for Multi-Constellation GNSS Receiver Differential Code Bias
Authors: Abdelazeem Mohamed , Çelik Rahmi N. , El-Rabbany Ahmed
Published: December 2015

In this study, we develop a Multi-constellation Global Navigation Satellite System (GNSS) Receiver Differential Code Bias (MGR-DCB) model. The model estimates the receiver DCBs for the Global Positioning System (GPS), BeiDou and Galileo signals from the ionosphere-corrected geometry-free linear combinations of the code observations. In order to account for the ionospheric delay, a Regional Ionospheric Model (RIM) over Europe is developed. GPS observations from 60 International GNSS Servoce (IGS) and EUREF reference stations are processed in the Bernese-5·2 Precise Point Positioning (PPP) module to estimate the Vertical Total Electron Content (VTEC). The RIM has spatial and temporal resolutions of 1° × 1° and 15 minutes, respectively. The receiver DCBs for three stations from the International GNSS Service Multi-GNSS Experiment (IGS-MGEX) are estimated for three different days. The estimated DCBs are compared with the MGEX published values. The results show agreement with the MGEX values with mean difference and Root Mean Square Error (RMSE) values less than 1 ns. In addition, the combined GPS, BeiDou and Galileo VTEC values are evaluated and compared with the IGS Global Ionospheric Maps (IGS-GIM) counterparts. The results show agreement with the GIM values with mean difference and RMSE values less than 1 Total Electron Content Unit (TECU).
Smooth coalgebra: testing vector analysis
Authors: PAVLOVIC DUSKO , FAUSER BERTFRIED
Published: December 2015

Processes are often viewed as coalgebras, with the structure maps specifying the state transitions. In the simplest case, the state spaces are discrete, and the structure map simply takes each state to the next states. But the coalgebraic view is also quite effective for studying processes over structured state spaces, e.g. measurable, or continuous. In the present paper, we consider coalgebras over manifolds. This means that the captured processes evolve over state spaces that are not just continuous, but also locally homeomorphic to normed vector spaces, and thus carry a differential structure. Both dynamical systems and differential forms arise as coalgebras over such state spaces, for two different endofunctors over manifolds. A duality induced by these two endofunctors provides a formal underpinning for the informal geometric intuitions linking differential forms and dynamical systems in the various practical applications, e.g. in physics. This joint functorial reconstruction of tangent bundles and cotangent bundles uncovers the universal properties and a high-level view of these fundamental structures, which are implemented rather intricately in their standard form. The succinct coalgebraic presentation provides unexpected insights even about the situations as familiar as Newton's laws.
MAXIMAL SEMIGROUP SYMMETRY AND DISCRETE RIESZ TRANSFORMS
Authors: KOBAYASHI TOSHIYUKI , NILSSON ANDREAS , SATO FUMIHIRO
Published: December 2015

We raise a question of whether the Riesz transform on $\mathbb{T}^{n}$ or $\mathbb{Z}^{n}$ is characterized by the ‘maximal semigroup symmetry’ that the transform satisfies. We prove that this is the case if and only if the dimension is one, two or a multiple of four. This generalizes a theorem of Edwards and Gaudry for the Hilbert transform on $\mathbb{T}$ and $\mathbb{Z}$ in the one-dimensional case, and extends a theorem of Stein for the Riesz transform on $\mathbb{R}^{n}$. Unlike the $\mathbb{R}^{n}$ case, we show that there exist infinitely many linearly independent multiplier operators that enjoy the same maximal semigroup symmetry as the Riesz transforms on $\mathbb{T}^{n}$ and $\mathbb{Z}^{n}$ if the dimension $n$ is greater than or equal to three and is not a multiple of four.
Collaborating and Co-operating to Make the Connection: How Law Librarians and Academics Can Work Together to Develop Communities of Legal Practice
Authors: Donaldson Angela , Ferris Graham
Published: December 2015

The Library is of value as a physical and social space, as a place that can facilitate learning; independently and in distinct ways to its role as repository of, and point of access to, information. The problems that defenders of this “learning place” aspect of the Library face are bound up with a very powerful, and indeed prevalent, metaphor. This metaphor is of teaching and learning as the transfer of information from one place or head, to another place or head. Therefore, Graham Ferris and Angela Donaldson put forward a far more realistic account of learning, and combine it with an example of learning being enacted in practice. We need to articulate the value of the Library as a place of learning because it is under threat from pressures on resources that are being deployed on a “common sense” but fallacious assumption that Libraries are about the storage and manipulation of information only.
The Library Without Walls: Striving for an Excellent Law Library Service Post-Earthquake
Authors: Roberts Sara
Published: December 2015

This paper is adapted from a presentation given by Sara Roberts at the 2015 BIALL Annual Conference. On September 4th 2010 Christchurch suffered the first of a series of catastrophic earthquakes which continued over the next two years and damaged much of the city. During this time the University of Canterbury suffered greatly, both through physical damage to the campus and from a loss of students willing to come and study in Christchurch. Subsequently, the dedicated Law Library on campus was closed and it was necessary to reassess the service in the light of severely reduced resources. More than four years on from that first earthquake, the law collection is situated in the central library on campus, and the number of professional law librarians supporting the service has reduced from four to two. Yet despite the changes the service has not diminished and, indeed, is stronger in some areas.
SLS/BIALL Academic Law Library Survey 2013/2014
Authors: Gee David
Published: December 2015

This is the latest report analysing the results of the Society of Legal Scholars and BIALL Survey. It has been written by David Gee, Deputy Librarian at the Institute of Advanced Legal Studies, School of Advanced Study, University of London.
Treatment for Comorbid Pediatric Gastrointestinal and Anxiety Disorders: A Pilot Study of a Flexible Health Sensitive Cognitive-Behavioral Therapy Program
Authors: Reigada Laura C. , Polokowski Ashley R. , Walder Deborah J. , Szigethy Eva M. , Benkov Keith J. , Bruzzese Jean-Marie , Masia Warner Carrie
Published: December 2015

Anxiety is a prevalent and impairing psychiatric condition among children and adolescents with inflammatory bowel disease (IBD). Despite the need for effective treatment, no studies have examined the benefit of cognitive-behavioral therapy (CBT) for anxiety disorders among children or adults with IBD. The aim of this paper is twofold: (a) to briefly describe a newly adapted CBT protocol, treatment of anxiety and physical symptoms related to IBD (TAPS + IBD), that concurrently addresses anxiety (including IBD-specific anxiety) and disease management among children and adolescents with IBD in pediatric medical offices; and (b) to present initial pilot data examining the feasibility and potential efficacy of TAPS + IBD compared to nondirective supportive therapy (NDST) among youth with comorbid IBD and anxiety. Twenty-two youth (59% female; mean age 13.2 ± 2.1) with comorbid IBD and anxiety disorder were randomly assigned to a 13-session TAPS + IBD or NDST program. Following treatment, participants in TAPS + IBD demonstrated higher treatment response rates relative to the NDST control treatment. Compared with NDST, TAPS + IBD was associated with significantly greater reductions in IBD-specific anxiety immediately following treatment and 3 months later. TAPS + IBD shows initial promise for the treatment of anxiety in youth with IBD. The direct integration of behavioral health strategies into medical settings and use of a flexible CBT approach sensitive to acute disease fluctuations appears to be beneficial among youth with comorbid IBD and anxiety.
Positive-bias gate-controlled metal–insulator transition in ultrathin VO2 channels with TiO2 gate dielectrics
Authors: Yajima Takeaki , Nishimura Tomonori , Toriumi Akira
Published: December 2015

The next generation of electronics is likely to incorporate various functional materials, including those exhibiting ferroelectricity, ferromagnetism and metal–insulator transitions. Metal–insulator transitions can be controlled by electron doping, and so incorporating such a material in transistor channels will enable us to significantly modulate transistor current. However, such gate-controlled metal–insulator transitions have been challenging because of the limited number of electrons accumulated by gate dielectrics, or possible electrochemical reaction in ionic liquid gate. Here we achieve a positive-bias gate-controlled metal–insulator transition near the transition temperature. A significant number of electrons were accumulated via a high-permittivity TiO2 gate dielectric with subnanometre equivalent oxide thickness in the inverse-Schottky-gate geometry. An abrupt transition in the VO2 channel is further exploited, leading to a significant current modulation far beyond the capacitive coupling. This solid-state operation enables us to discuss the electrostatic mechanism as well as the collective nature of gate-controlled metal–insulator transitions, paving the pathway for developing functional field effect transistors.
RCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome
Authors: Patel Ami , Yamashita Naoya , Ascaño Maria , Bodmer Daniel , Boehm Erica , Bodkin-Clarke Chantal , Ryu Yun Kyoung , Kuruvilla Rejji
Published: December 2015

Down syndrome is the most common chromosomal disorder affecting the nervous system in humans. To date, investigations of neural anomalies in Down syndrome have focused on the central nervous system, although dysfunction of the peripheral nervous system is a common manifestation. The molecular and cellular bases underlying peripheral abnormalities have remained undefined. Here, we report the developmental loss of sympathetic innervation in human Down syndrome organs and in a mouse model. We show that excess regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of the calcineurin phosphatase that is triplicated in Down syndrome, impairs neurotrophic support of sympathetic neurons by inhibiting endocytosis of the nerve growth factor (NGF) receptor, TrkA. Genetically correcting RCAN1 levels in Down syndrome mice markedly improves NGF-dependent receptor trafficking, neuronal survival and innervation. These results uncover a critical link between calcineurin signalling, impaired neurotrophin trafficking and neurodevelopmental deficits in the peripheral nervous system in Down syndrome.
Testing necessary regional frontal contributions to value assessment and fixation-based updating
Authors: Vaidya Avinash R. , Fellows Lesley K.
Published: December 2015

Value-based decisions are biased by the time people spend viewing each option: Options fixated longer are chosen more often, even when previously rated as less appealing. This bias is thought to reflect ‘value updating’ as new evidence is accumulated. Prior work has shown that ventromedial prefrontal cortex (PFC) carries a fixation-dependent value comparison signal, while other studies implicate dorsomedial PFC in representing the value of alternative options. Here, we test whether these regions are necessary for fixation-related value updating in 33 people with frontal lobe damage and 27 healthy controls performing a simple choice task. We show that damage to dorsomedial PFC leads to an exaggerated influence of fixations on choice, while damage to ventromedial or lateral PFC has no effect on this bias. These findings suggest a critical role for dorsomedial, and not ventromedial PFC, in mediating the relative influence of current fixations and a priori value on choice.
Topological states on the gold surface
Authors: Yan Binghai , Stadtmüller Benjamin , Haag Norman , Jakobs Sebastian , Seidel Johannes , Jungkenn Dominik , Mathias Stefan , Cinchetti Mirko , Aeschlimann Martin , Felser Claudia
Published: December 2015

Gold surfaces host special electronic states that have been understood as a prototype of Shockley surface states. These surface states are commonly employed to benchmark the capability of angle-resolved photoemission spectroscopy (ARPES) and scanning tunnelling spectroscopy. Here we show that these Shockley surface states can be reinterpreted as topologically derived surface states (TDSSs) of a topological insulator (TI), a recently discovered quantum state. Based on band structure calculations, theZ2-type invariants of gold can be well-defined to characterize a TI. Further, our ARPES measurement validates TDSSs by detecting the dispersion of unoccupied surface states. The same TDSSs are also recognized on surfaces of other well-known noble metals (for example, silver, copper, platinum and palladium), which shines a new light on these long-known surface states.
Ultra-narrow metallic armchair graphene nanoribbons
Authors: Kimouche Amina , Ervasti Mikko M. , Drost Robert , Halonen Simo , Harju Ari , Joensuu Pekka M. , Sainio Jani , Liljeroth Peter
Published: December 2015

Graphene nanoribbons (GNRs)—narrow stripes of graphene—have emerged as promising building blocks for nanoelectronic devices. Recent advances in bottom-up synthesis have allowed production of atomically well-defined armchair GNRs with different widths and doping. While all experimentally studied GNRs have exhibited wide bandgaps, theory predicts that every third armchair GNR (widths of N=3m+2, where m is an integer) should be nearly metallic with a very small bandgap. Here, we synthesize the narrowest possible GNR belonging to this family (five carbon atoms wide, N=5). We study the evolution of the electronic bandgap and orbital structure of GNR segments as a function of their length using low-temperature scanning tunnelling microscopy and density-functional theory calculations. Already GNRs with lengths of 5 nm reach almost metallic behaviour with ∼100 meV bandgap. Finally, we show that defects (kinks) in the GNRs do not strongly modify their electronic structure.
Erratum: Cooper pair splitting in parallel quantum dot Josephson junctions
Authors: Deacon R. S. , Oiwa A. , Sailer J. , Baba S. , Kanai Y. , Shibata K. , Hirakawa K. , Tarucha S.
Published: December 2015

Nature Communications 6: Article Number: 7446 (2015); Published 1 July 2015; Updated 14 December 2015 The financial support for this Article was not fully acknowledged. The Acknowledgements should have included the following: ST acknowledges financial support from Grant-in-Aid Research S No. 26220710.
The effects of high-fat feeding on physical function and skeletal muscle extracellular matrix
Authors: Tam C S , Power J E , Markovic T P , Yee C , Morsch M , McLennan S V , Twigg S M
Published: December 2015

Skeletal muscle extracellular matrix (ECM) remodelling has been proposed as a feature of the pathogenic milieu associated with obesity and metabolic dysfunction. Whether muscle ECM is associated with impaired physical function in obese conditions is unknown. C57BL/6 mice were fed a high-fat diet (HFD) or chow for 5, 10 and 25 weeks. Non-invasive physiological tests (hang wire, hang mesh and grip strength) to assess neuromuscular function and motor co-ordination were performed. Genes related to ECM structure (COL1, COL3, COL6A2, SPARC), growth factors (TGFB1, TGFB2, CTGF, VEGF) and muscle function (DMD (Dp147), CPN3, DAG1) were measured in gastrocnemius muscle using real-time PCR and COL1, 3 and 6 protein were measured by western immunoblot. Compared with chow, HFD mice had two to six-fold lower muscle strength (hang wire test; raw data and multiplied by body weight) at all time-points (P<0.001) and two-fold lower hang mesh and grip strength at 10 weeks (P<0.05). At 5 weeks, COL1, COL3 and COL6 gene expression, but not protein levels were three to eight-fold lower in HFD compared with chow. In the HFD group at 5 weeks, greater COL3 and 6 gene expression were associated with poorer hang wire performance. For the first time, our results demonstrate links between muscle ECM structure and physical function in obesity.
A comparison of effects of lard and hydrogenated vegetable shortening on the development of high-fat diet-induced obesity in rats
Authors: Kubant R , Poon A N , Sánchez-Hernández D , Domenichiello A F , Huot P S P , Pannia E , Cho C E , Hunschede S , Bazinet R P , Anderson G H
Published: December 2015

Background:

Obesity is associated with increased consumption and preference for dietary fat. Experimental models of fat-induced obesity use either lard or vegetable shortening. Yet, there are no direct comparisons of these commonly used fat sources, or the influence of their fatty acid composition, on the development of diet-induced obesity.

Objective:

To compare the effects of lard and hydrogenated vegetable-shortening diets, which differ in their fatty acid composition, on weight gain and the development of obesity and insulin resistance in rats.

Methods and design:

Male Wistar rats were fedad libitumfor 14 weeks high-fat diets containing either (1) high vegetable fat (HVF, 60 kcal% from vegetable shortening) or (2) high lard fat (HLF, 60 kcal% from lard). Rats fed normal-fat (NF, 16 kcal% from vegetable shortening) diet served as control. Body weight, food intake, adipose tissue mass, serum 25[OH]D3, glucose, insulin and fatty acid composition of diets were measured.

Results:

Rats fed either of the two high-fat diets had higher energy intake, weight gain and fat accretion than rats fed normal-fat diet. However, rats fed the HLF diet consumed more calories and gained more weight and body fat with greater increases of 32% in total (158.5±8.2 vs 120.2±6.6 g,P<0.05), 30% in visceral (104.4±5.2 vs 80.3±4.2 g,P<0.05) and 36% in subcutaneous fat mass (54.1±3.6 vs 39.9±3.1 g,P<0.05), compared with rats fed the HVF diet. Higher visceral adiposity was positively correlated with serum insulin (r=0.376,P<0.05) and homeostatic model assessment insulin resistance (r=0.391,P<0.05).

Conclusion:

We conclude that lard-based high-fat diets accentuate the increase in weight gain and the development of obesity and insulin resistance more than hydrogenated vegetable-shortening diets. These results further point to the importance of standardizing fatty acid composition and type of fat used in determining outcomes of consuming high-fat diets.
TERT promoter mutations and monoallelic activation of TERT in cancer
Authors: Huang F W , Bielski C M , Rinne M L , Hahn W C , Sellers W R , Stegmeier F , Garraway L A , Kryukov G V
Published: December 2015

Here we report that promoter mutations in telomerase (TERT), the most common noncoding mutations in cancer, give rise to monoallelic expression of TERT. Through deep RNA sequencing, we find that TERT activation in human cancer cell lines can occur in either mono- or biallelic manner. Without exception, hotspot TERT promoter mutations lead to the re-expression of only one allele, accounting for approximately half of the observed cases of monoallelic TERT expression. Furthermore, we show that monoallelic TERT expression is highly prevalent in certain tumor types and widespread across a broad spectrum of cancers. Taken together, these observations provide insights into the mechanisms of TERT activation and the ramifications of noncoding mutations in cancer.
Correction: Corrigendum: Human Mitochondrial DNA-Protein Complexes Attach to a Cholesterol-Rich Membrane Structure
Authors: Gerhold Joachim M. , Cansiz-Arda Şirin , Lõhmus Madis , Engberg Oskar , Reyes Aurelio , van Rennes Helga , Sanz Alberto , Holt Ian J. , Cooper Helen M. , Spelbrink Johannes N.
Published: December 2015

The helicase Twinkle is indispensable for mtDNA replication in nucleoids. Previously, we showed that Twinkle is tightly membrane-associated even in the absence of mtDNA, which suggests that Twinkle is part of a membrane-attached replication platform. Here we show that this platform is a cholesterol-rich membrane structure. We fractionated mitochondrial membrane preparations on flotation gradients and show that membrane-associated nucleoids accumulate at the top of the gradient. This fraction was shown to be highly enriched in cholesterol, a lipid that is otherwise low abundant in mitochondria. In contrast, more common mitochondrial lipids, and abundant inner-membrane associated proteins concentrated in the bottom-half of these gradients. Gene silencing of ATAD3, a protein with proposed functions related to nucleoid and mitochondrial cholesterol homeostasis, modified the distribution of cholesterol and nucleoids in the gradient in an identical fashion. Both cholesterol and ATAD3 were previously shown to be enriched in ER-mitochondrial junctions, and we detect nucleoid components in biochemical isolates of these structures. Our data suggest an uncommon membrane composition that accommodates platforms for replicating mtDNA, and reconcile apparently disparate functions of ATAD3. We suggest that mtDNA replication platforms are organized in connection with ER-mitochondrial junctions, facilitated by a specialized membrane architecture involving mitochondrial cholesterol.
Time-resolved X-ray Tracking of Expansion and Compression Dynamics in Supersaturating Ion-Networks
Authors: Matsushita Y. , Sekiguchi H. , Ichiyanagi K. , Ohta N. , Ikezaki K. , Goto Y. , Sasaki Y. C.
Published: December 2015

Supersaturation of a solution system is a metastable state containing more solute than can be normally solubilized. Moreover, this condition is thermodynamically important for a system undergoing a phase transition. This state plays critical roles in deposition morphology in inorganic, organic, polymer and protein solution systems. In particular, microscopic solution states under supersaturated conditions have recently received much attention. In this report, we observed the dynamic motion of individual ion-network domains (INDs) in a supersaturated sodium acetate trihydrate solution (6.4 M) by using microsecond time-resolved and high accuracy (picometre scale) X-ray observations (diffracted X-ray tracking; DXT). We found that there are femto-Newton (fN) anisotropic force fields in INDs that correspond to an Angstrom-scale relaxation process (continuous expansion and compression) of the INDs at 25 μs time scale. The observed anisotropic force-field (femto-Newton) from DXT can lead to new explanations of how material crystallization is triggered. This discovery could also influence the interpretation of supercooling, bio-polymer and protein aggregation processes and supersaturated systems of many other materials.
Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells
Authors: Zhang Yiqiang , Zhong Jiang F , Qiu Hongyu , Robb MacLellan W. , Marbán Eduardo , Wang Charles
Published: December 2015

It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration.
Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure
Authors: Fu Feng , Zhao Kun , Li Jia , Xu Jie , Zhang Yuan , Liu Chengfeng , Yang Weidong , Gao Chao , Li Jun , Zhang Haifeng , Li Yan , Cui Qin , Wang Haichang , Tao Ling , Wang Jing , Quon Michael J , Gao Feng
Published: December 2015

A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF.
GSTM1 and GSTT1 polymorphisms contribute to renal cell carcinoma risk: evidence from an updated meta-analysis
Authors: Huang Wentao , Shi Hua , Hou Qi , Mo Zu , Xie Xiangwei
Published: December 2015

Emerging evidences suggest that GSTM1 and GSTT1 are involved in the detoxification of carcinogens and polymorphisms in this gene that result in a loss of enzyme activity may increase the risk of renal cell carcinoma (RCC). Thus, to evaluate the association of GSTM1 and GSTT1 polymorphisms and RCC, we performed an updated meta-analysis of 10 case-control studies by RevMan 5.2 and the publication bias was tested using STATA 11.0. The meta-analysis showed that the single locus GSTM1 and GSTT1 polymorphisms were not significantly associated with a risk of RCC in a recessive model. However, that wild-type genotype versus the dual null genotype of GSTM1-GSTT1 showed a positive association with RCC risk (OR = 0.70; 95% CI = 0.51–0.98; P = 0.04). In another analysis of subjects exposed to pesticides, we found that the GSTM1 wild-type genotype was associated with increased RCC risk in Europeans (OR = 2.72; 95% CI = 1.54–4.82; P = 0.0006). We also identified an association between the GSTT1 wild-type and lower RCC TNM staging (I + II versus III + IV: OR = 1.88; 95% CI = 1.09–3.26; P = 0.02). This meta-analysis suggests that there may be a relationship between the GSTM1 and GSTT1 wild-type genotype and RCC.
Development of insect resistant maize plants expressing a chitinase gene from the cotton leaf worm, Spodoptera littoralis
Authors: Osman Gamal H. , Assem Shireen K. , Alreedy Rasha M. , El-Ghareeb Doaa K. , Basry Mahmoud A. , Rastogi Anshu , Kalaji Hazem M.
Published: December 2015

Due to the importance of chitinolytic enzymes for insect, nematode and fungal growth, they are receiving attention concerning their development as biopesticides or chemical defense proteins in transgenic plants and as microbial biocontrol agents. Targeting chitin associated with the extracellular matrices or cell wall by insect chitinases may be an effective approach for controlling pest insects and pathogenic fungi. The ability of chitinases to attack and digest chitin in the peritrophic matrix or exoskeleton raises the possibility to use them as insect control method. In this study, an insect chitinase cDNA from cotton leaf worm (Spodoptera littoralis) has been synthesized. Transgenic maize plant system was used to improve its tolerance against insects. Insect chitinase transcripts and proteins were expressed in transgenic maize plants. The functional integrity and expression of chitinase in progenies of the transgenic plants were confirmed by insect bioassays. The bioassays using transgenic corn plants against corn borer (Sesamia cretica) revealed that ~50% of the insects reared on transgenic corn plants died, suggesting that transgenic maize plants have enhanced resistance against S. cretica.
Electrogenic transport and K+ ion channel expression by the human endolymphatic sac epithelium
Authors: Kim Sung Huhn , Kim Bo Gyung , Kim Jin Young , Roh Kyung Jin , Suh Michelle J. , Jung JinSei , Moon In Seok , Moon Sung K. , Choi Jae Young
Published: December 2015

The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K+ channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K+ channels in the electrogenic transport of human ES epithelium. The identified K+ channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2 and KCNK6 and the K+ transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid.
Long-term xeno-free culture of human pluripotent stem cells on hydrogels with optimal elasticity
Authors: Higuchi Akon , Kao Shih-Hsuan , Ling Qing-Dong , Chen Yen-Ming , Li Hsing-Fen , Alarfaj Abdullah A. , Munusamy Murugan A. , Murugan Kadarkarai , Chang Shih-Chang , Lee Hsin-Chung , Hsu Shih-Tien , Kumar S. Suresh , Umezawa Akihiro
Published: December 2015

The tentative clinical application of human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human induced pluripotent stem cells, is restricted by the possibility of xenogenic contamination resulting from the use of mouse embryonic fibroblasts (MEFs) as a feeder layer. Therefore, we investigated hPSC cultures on biomaterials with different elasticities that were grafted with different nanosegments. We prepared dishes coated with polyvinylalcohol-co-itaconic acid hydrogels grafted with an oligopeptide derived from vitronectin (KGGPQVTRGDVFTMP) with elasticities ranging from 10.3 to 30.4 kPa storage moduli by controlling the crosslinking time. The hPSCs cultured on the stiffest substrates (30.4 kPa) tended to differentiate after five days of culture, whereas the hPSCs cultured on the optimal elastic substrates (25 kPa) maintained their pluripotency for over 20 passages under xeno-free conditions. These results indicate that cell culture matrices with optimal elasticity can maintain the pluripotency of hPSCs in culture.
Encoding of frequency-modulation (FM) rates in human auditory cortex
Authors: Okamoto Hidehiko , Kakigi Ryusuke
Published: December 2015

Frequency-modulated sounds play an important role in our daily social life. However, it currently remains unclear whether frequency modulation rates affect neural activity in the human auditory cortex. In the present study, using magnetoencephalography, we investigated the auditory evoked N1m and sustained field responses elicited by temporally repeated and superimposed frequency-modulated sweeps that were matched in the spectral domain, but differed in frequency modulation rates (1, 4, 16 and 64 octaves per sec). The results obtained demonstrated that the higher rate frequency-modulated sweeps elicited the smaller N1m and the larger sustained field responses. Frequency modulation rate had a significant impact on the human brain responses, thereby providing a key for disentangling a series of natural frequency-modulated sounds such as speech and music.
Direct and accurate measurement of size dependent wetting behaviors for sessile water droplets
Authors: Park Jimin , Han Hyung-Seop , Kim Yu-Chan , Ahn Jae-Pyeong , Ok Myoung-Ryul , Lee Kyung Eun , Lee Jee-Wook , Cha Pil-Ryung , Seok Hyun-Kwang , Jeon Hojeong
Published: December 2015

The size-dependent wettability of sessile water droplets is an important matter in wetting science. Although extensive studies have explored this problem, it has been difficult to obtain empirical data for microscale sessile droplets at a wide range of diameters because of the flaws resulting from evaporation and insufficient imaging resolution. Herein, we present the size-dependent quantitative change of wettability by directly visualizing the three phase interfaces of droplets using a cryogenic-focused ion beam milling and SEM-imaging technique. With the fundamental understanding of the formation pathway, evaporation, freezing and contact angle hysteresis for sessile droplets, microdroplets with diameters spanning more than three orders of magnitude on various metal substrates were examined. Wetting nature can gradually change from hydrophobic at the hundreds-of-microns scale to super-hydrophobic at the sub-μm scale and a nonlinear relationship between the cosine of the contact angle and contact line curvature in microscale water droplets was demonstrated. We also showed that the wettability could be further tuned in a size-dependent manner by introducing regular heterogeneities to the substrate.