bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of methotrexate and salazosulfapyridine on protein profiles of exosomes derived from a human synovial sarcoma cell line of SW982
Authors: Tsuno Hirotaka , Suematsu Naoya , Sato Toshiyuki , Arito Mitsumi , Matsui Toshihiro , Iizuka Nobuko , Omoteyama Kazuki , Okamoto Kazuki , Tohma Shigeto , Kurokawa Manae S. , Kato Tomohiro
Published: July 2015

Purpose

To elucidate effects of salazosulfapyridine (SASP) and methotrexate (MTX), major anti‐rheumatic drugs, on exosomes derived from SW982 of a human synovial sarcoma cell line.

Experimental design

SW982 was treated with SASP and/or MTX under interleukin‐1β (IL‐1β)‐treated or nontreated conditions. Exosomes were isolated from the culture media, and exosomal proteome was analyzed by 2D‐DIGE. Protein spots whose intensity was significantly altered by the above treatments were identified by MS.

Results

Two hundred ninety‐four protein spots were detected in the exosome preparations by 2D‐DIGE. Compared to the nontreated cells, SASP‐, MTX‐, and (SASP + MTX)‐treated cells displayed 8, 10, and 21 exosomal protein spots with more than ±2.0‐fold intensity differences (p < 0.05), respectively. Similarly, the IL‐1β‐treated cells displayed 58 exosomal protein spots with more than ±1.5‐fold intensity differences (p < 0.05). In about half of the 58 spots, the IL‐1β‐induced intensity changes were suppressed by simultaneous addition of SASP and/or MTX. Most of the identified proteins were immunity‐ or anti‐oxidation‐related proteins.

Conclusions and clinical relevance

The SASP and/or MTX treatments altered the protein profiles of exosomes and suppressed the effects of IL‐1β on the exosomal proteome. Exosomes may play roles in the actions of these anti‐rheumatic drugs.
Molecular architecture of KedS8, a sugar N‐methyltransferase from Streptoalloteichus sp. ATCC 53650
Authors: Delvaux Nathan A. , Thoden James B. , Holden Hazel M.
Published: July 2015

Kedarcidin, produced by Streptoalloteichus sp. ATCC 53650, is a fascinating chromoprotein of 114 amino acid residues that displays both antibiotic and anticancer activity. The chromophore responsible for its chemotherapeutic activity is an ansa‐bridged enediyne with two attached sugars, l‐mycarose, and l‐kedarosamine. The biosynthesis of l‐kedarosamine, a highly unusual trideoxysugar, is beginning to be revealed through bioinformatics approaches. One of the enzymes putatively involved in the production of this carbohydrate is referred to as KedS8. It has been proposed that KedS8 is an N‐methyltransferase that utilizes S‐adenosylmethionine as the methyl donor and a dTDP‐linked C‐4′ amino sugar as the substrate. Here we describe the three‐dimensional architecture of KedS8 in complex with S‐adenosylhomocysteine. The structure was solved to 2.0 Å resolution and refined to an overall R‐factor of 17.1%. Unlike that observed for other sugar N‐methyltransferases, KedS8 adopts a novel tetrameric quaternary structure due to the swapping of β‐strands at the N‐termini of its subunits. The structure presented here represents the first example of an N‐methyltransferase that functions on C‐4′ rather than C‐3′ amino sugars.
Structure of the external aldimine form of PglE, an aminotransferase required for N,N'‐diacetylbacillosamine biosynthesis
Authors: Riegert Alexander S. , Young N. Martin , Watson David C. , Thoden James B. , Holden Hazel M.
Published: July 2015

N,N'‐diacetylbacillosamine is a novel sugar that plays a key role in bacterial glycosylation. Three enzymes are required for its biosynthesis in Campylobacter jejuni starting from UDP‐GlcNAc. The focus of this investigation, PglE, catalyzes the second step in the pathway. It is a PLP‐dependent aminotransferase that converts UDP‐2‐acetamido‐4‐keto‐2,4,6‐trideoxy‐d‐glucose to UDP‐2‐acetamido‐4‐amino‐2,4,6‐trideoxy‐d‐glucose. For this investigation, the structure of PglE in complex with an external aldimine was determined to a nominal resolution of 2.0 Å. A comparison of its structure with those of other sugar aminotransferases reveals a remarkable difference in the manner by which PglE accommodates its nucleotide‐linked sugar substrate.
Structure alignment of membrane proteins: Accuracy of available tools and a consensus strategy
Authors: Stamm Marcus , Forrest Lucy R.
Published: July 2015

Protein structure alignment methods are used for the detection of evolutionary and functionally related positions in proteins. A wide array of different methods are available, but the choice of the best method is often not apparent to the user. Several studies have assessed the alignment accuracy and consistency of structure alignment methods, but none of these explicitly considered membrane proteins, which are important targets for drug development and have distinct structural features. Here, we compared 13 widely used pairwise structural alignment methods on a test set of homologous membrane protein structures (called HOMEP3). Each pair of structures was aligned and the corresponding sequence alignment was used to construct homology models. The model accuracy compared to the known structures was assessed using scoring functions not incorporated in the tested structural alignment methods. The analysis shows that fragment‐based approaches such as FR‐TM‐align are the most useful for aligning structures of membrane proteins. Moreover, fragment‐based approaches are more suitable for comparison of protein structures that have undergone large conformational changes. Nevertheless, no method was clearly superior to all other methods. Additionally, all methods lack a measure to rate the reliability of a position within a structure alignment. To solve both of these problems, we propose a consensus‐type approach, combining alignments from four different methods, namely FR‐TM‐align, DaliLite, MATT, and FATCAT. Agreement between the methods is used to assign confidence values to each position of the alignment. Overall, we conclude that there remains scope for the improvement of structural alignment methods for membrane proteins. Proteins 2015; 83:1720–1732. © 2015 Wiley Periodicals, Inc.
What Drives Human Migration in Sahelian Countries? A Meta‐analysis
Authors: Neumann Kathleen , Hermans Frans
Published: July 2015

The Sahel region has one of the most mobile populations in the world, with migration serving as a common household strategy to increase livelihood and social resilience. However, the Sahel region's population is extremely heterogeneous, and the processes and factors that contribute to migration are complex. Consequently, recent empirical studies yielded conflicting conclusions regarding the processes that drive migration. This study was designed to increase our understanding of the factors that drive migration in the Sahel region. We performed a systematic meta‐analysis of English‐language literature to synthesise the empirical evidence collected from 53 case studies covering eight Sahelian countries. We analysed the frequencies of a broad range of drivers that affected migration processes during the past three decades. Our results show that the primary impetus for driving migration is a combination of economic and social motivations, which together account for 80% of all drivers that were identified in the case studies. In contrast, only 11% of the identified drivers are related directly to demographic and/or environmental conditions. Moreover, we conclude that the majority of case studies do not explore causation among migration drivers, which clearly hampers our understanding of migration mechanisms taking place in the Sahel region. Copyright © 2015 John Wiley & Sons, Ltd.
Fabrication of diamond lateral p–n junction diodes on (111) substrates
Authors: Sato Kazuki , Iwasaki Takayuki , Shimizu Maki , Kato Hiromitsu , Makino Toshiharu , Ogura Masahiko , Takeuchi Daisuke , Yamasaki Satoshi , Hatano Mutsuko
Published: July 2015

Diamond lateral p–n junctions were fabricated on (111) substrates by selective growth of n‐type diamond around a p‐type layer. We investigated the effects of both the step‐flow growth direction of n‐type diamond and the crystal face of the p‐type sidewalls on the structure and electrical properties of the lateral p–n junctions. The direction of the step‐flow growth clearly influenced the morphologies of the p–n junctions. We also found that the crystal faces of the p‐type sidewalls had an effect on the quality of the lateral p–n junctions. The two facing p–n junctions obtained in this study becomes an n–p–n structure, which could be a key structure for metal‐oxide‐semiconductor field‐effect transistors with an inversion channel.
Carryover negligibility and relevance in bioequivalence studies
Authors: Ocaña Jordi , Sanchez O Maria P. , Carrasco Josep L.
Published: July 2015

The carryover effect is a recurring issue in the pharmaceutical field. It may strongly influence the final outcome of an average bioequivalence study. Testing a null hypothesis of zero carryover is useless: not rejecting it does not guarantee the non‐existence of carryover, and rejecting it is not informative of the true degree of carryover and its influence on the validity of the final outcome of the bioequivalence study. We propose a more consistent approach: even if some carryover is present, is it enough to seriously distort the study conclusions or is it negligible? This is the central aim of this paper, which focuses on average bioequivalence studies based on 2 × 2 crossover designs and on the main problem associated with carryover: type I error inflation. We propose an equivalence testing approach to these questions and suggest reasonable negligibility or relevance limits for carryover. Finally, we illustrate this approach on some real datasets. Copyright © 2015 John Wiley & Sons, Ltd.
Dual Effects of Liquiritigenin on the Proliferation of Bone Cells: Promotion of Osteoblast Differentiation and Inhibition of Osteoclast Differentiation
Authors: Uchino Kaho , Okamoto Kuniaki , Sakai Eiko , Yoneshima Erika , Iwatake Mayumi , Fukuma Yutaka , Nishishita Kazuhisa , Tsukuba Takayuki
Published: July 2015

Bone is constantly controlled by a balance between osteoblastic bone formation and osteoclastic bone resorption. Liquiritigenin is a plant‐derived flavonoid and has various pharmacological effects, such as antioxidative, antitumor, and antiinflammatory effects. Here, we show that liquiritigenin has dual effects on the proliferation of bone cells, regarding the promotion of osteoblast differentiation and the inhibition of osteoclast differentiation. Liquiritigenin‐treated murine osteoblastic MC3T3‐E1 cells showed an increased alkaline phosphatase activity and enhanced phosphorylation of Smad1/5 compared with untreated cells. Moreover, liquiritigenin inhibited osteoclast differentiation, its bone‐resorption activity through slightly decreased the phosphorylation of extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase, and inhibitor of nuclear factor kappa Bα; however, the phosphorylation of Akt and p38 slightly increased in bone marrow‐derived osteoclasts. The expression levels of the osteoclast marker proteins nuclear factor of activated T‐cell cytoplasmic‐1, Src, and cathepsin K diminished. These results suggest that liquiritigenin may be useful as a therapeutic and/or preventive agent for osteoporosis or inflammatory bone diseases. Copyright © 2015 John Wiley & Sons, Ltd.
A coupled data assimilation system for climate reanalysis
Authors: Laloyaux Patrick , Balmaseda Magdalena , Dee Dick , Mogensen Kristian , Janssen Peter
Published: July 2015

A coupled data assimilation system has been developed at the European Centre for Medium‐Range Weather Forecasts (ECMWF), which is intended to be used for the production of global reanalyses of the recent climate. The system assimilates a wide variety of ocean and atmospheric observations and produces ocean–atmosphere analyses with a coupled model. Employing the coupled‐model constraint in the analysis implies that assimilation of an ocean observation has immediate impact on the atmospheric state estimate and, conversely, assimilation of an atmospheric observation affects the ocean state. This covariance between atmosphere and ocean induced by the analysis method is illustrated with simple numerical experiments. Realistic data assimilation experiments based on the global observing system are then used to assess the quality of the assimilation method. Comparison with an uncoupled system shows a mostly neutral impact overall, with slightly improved temperature estimates in the upper ocean and lower atmosphere. These preliminary results are considered of interest for the ongoing community efforts focusing on coupled data assimilations.
Improved seasonal prediction of the hot summer of 2003 over Europe through better representation of uncertainty in the land surface
Authors: MacLeod David A. , Cloke Hannah L. , Pappenberger Florian , Weisheimer Antje
Published: July 2015

Methods to represent uncertainties in weather and climate models explicitly have been developed and refined over the past decade and have reduced biases and improved forecast skill when implemented in the atmospheric component of models. These methods have not yet been applied to the land‐surface component of models. Since the land surface is strongly coupled to the atmospheric state at certain times and in certain places (such as the European summer of 2003), improvements in the representation of land‐surface uncertainty may potentially lead to improvements in atmospheric forecasts for such events.

Here we analyze seasonal retrospective forecasts for 1981–2012 performed with the European Centre for Medium‐Range Weather Forecasts (ECMWF) coupled ensemble forecast model. We consider two methods of incorporating uncertainty into the land‐surface model (H‐TESSEL): stochastic perturbation of tendencies and static perturbation of key soil parameters.

We find that the perturbed parameter approach improves the forecast of extreme air temperature for summer 2003 considerably, through better representation of negative soil‐moisture anomalies and upward sensible heat flux. Averaged across all the reforecasts, the perturbed parameter experiment shows relatively little impact on the mean bias, suggesting perturbations of at least this magnitude can be applied to the land surface without any degradation of model climate. There is also little impact on skill averaged across all reforecasts and some evidence of overdispersion for soil moisture.

The stochastic tendency experiments show a large overdispersion for the soil temperature fields, indicating that the perturbation here is too strong. There is also some indication that the forecast of the 2003 warm event is improved for the stochastic experiments; however, the improvement is not as large as observed for the perturbed parameter experiment.
RNA helicase DDX3: at the crossroad of viral replication and antiviral immunity
Authors: Valiente‐Echeverría Fernando , Hermoso Marcela A. , Soto‐Rifo Ricardo
Published: July 2015

Asp‐Glu‐Ala‐Asp (DEAD)‐box polypeptide 3, or DDX3, belongs to the DEAD‐box family of ATP‐dependent RNA helicases and is known to play different roles in RNA metabolism ranging from transcription to nuclear export, translation, and assembly of stress granules. In addition, there is growing evidence that DDX3 is a component of the innate immune response against viral infections. As such, DDX3 has been shown to play roles both upstream and downstream of I‐kappa beta kinaseε(IKKε)/TANK‐binding kinase 1, leading to IFN‐βproduction. Interestingly, several RNA viruses, including human threats such as HIV‐1 and hepatitis C virus, hijack DDX3 to accomplish various steps of their replication cycles. Thus, it seems that viruses have evolved to exploit DDX3's functions while threatening the innate immune response. Understanding this interesting dichotomy in DDX3 function will help us not only to improve our knowledge of virus–host interactions but also to develop novel antiviral drugs targeting the multifaceted roles of DDX3 in viral replication. Copyright © 2015 John Wiley & Sons, Ltd.
Dynamic intratubular biomineralization following root canal obturation with pozzolan‐based mineral trioxide aggregate sealer cement
Authors: Yoo Yeon‐Jee , Baek Seung‐Ho , Kum Kee‐Yeon , Shon Won‐Jun , Woo Kyung‐Mi , Lee WooCheol
Published: July 2015

The application of mineral trioxide aggregates (MTA) cement during the root canal obturation is gaining concern due to its bioactive characteristic to form an apatite in dentinal tubules. In this regard, this study was to assess the biomineralization of dentinal tubules following root canal obturation by using pozzolan‐based (Pz‐) MTA sealer cement (EndoSeal MTA, Maruchi). Sixty curved roots (mesiobuccal, distobuccal) from human maxillary molars were instrumented and prepared for root canal obturation. The canals were obturated with gutta‐percha (GP) and Pz‐MTA sealer by using continuous wave of condensation technique. Canals obturated solely with ProRoot MTA (Dentsply Tulsa Dental) or Pz‐MTA sealer were used for comparison. In order to evaluate the biomineralization ability under different conditions, the PBS pretreatment before the root canal obturation was performed in each additional samples. At dentin‐material interfaces, the extension of intratubular biomineralization was analyzed using scanning electron microscopy (SEM) and energy dispersive spectroscopy. When the root canal was obturated with GP and Pz‐MTA sealer, enhanced biomineralization of the dentinal tubules beyond the penetrated sealer tag was confirmed under the SEM observation (p < 0.05). Mineralized apatite structures (calcium/phosphorous ratio, 1.45–1.89) connecting its way through the dentinal tubules were detected at 350–400 μm from the tubule orifice, and the pre‐crystallization seeds were also observed along the intra‐ and/or inter‐tubular collagen fiber. Intratubular biomineralization depth was significantly enhanced in all PBS pretreated canals (p < 0.05). Pz‐MTA cement can be used as a promising bioactive root canal sealer to enhance biomineralization of dentinal tubules under controlled environment. SCANNING 38:50–56, 2016. © 2015 The Authors. Scanning Published by Wiley Periodicals, Inc.
Secure broadcast in distributed networks with strong adversaries
Authors: Szalachowski Pawel , Kim Tiffany Hyun‐Jin
Published: July 2015

This paper proposes a framework that enables secure one‐to‐many communication for networks with limited capabilities in the face of a strong adversary that can capture an arbitrary set of nodes. Our approach consists of two main components: (a) group key establishment protocol and (b) special key management. Especially, we try to address the following question: How strong of security properties can we achieve for broadcast communication in hardware‐limited networks with a strong adversary? We propose approaches and their variants that neither require special hardware nor use costly cryptographic operations. With thorough security and efficiency analyses, we discuss how our solutions can be applied to a variety of hardware‐limited distributed systems. We also describe the implementation and evaluation results of the most promising variants. Copyright © 2015 John Wiley & Sons, Ltd.
A novel one‐to‐many and many‐to‐one asymmetric encryption model and its algorithms
Authors: Shi Run‐hua , Zhong Hong , Cui Jie , Zhang Shun
Published: July 2015

Traditional asymmetric encryption algorithms involve only two parties: one party is a sender (encrypter) and the other a receiver (decrypter), in which each party has two different keys: a private key and a public key. However, if applied in some multiparty‐oriented environments, there may be a serious problem that each party needs to store and manage many keys, which is not only an overload but also a potential safety hazard. In this paper, we built a new secure communication model for private client–server networks, in which each party only needs to store a private key, but it can still implement two‐way secure communications with two properties of “one‐to‐many encryption” (i.e., if the server encrypts a plaintext, all clients can decrypt the ciphertext by using their respective private keys) and “many‐to‐one encryption” (i.e., if each client encrypts a plaintext by using his or her private key, only the server can decrypt the ciphertext). Furthermore, by introducing the basic theories for solving linear equations and ElGamal cryptographic algorithms, we designed the corresponding encryption and decryption algorithms in detail. The analysis results show that our algorithms are secure and efficient, and there are many good potential applications in military and electronic commerce fields. Copyright © 2015 John Wiley & Sons, Ltd.
A joint model for interval‐censored functional decline trajectories under informative observation
Authors: Lesperance Mary Louise , Sabelnykova Veronica , Nathoo Farouk Salim , Lau Francis , Downing Michael G.
Published: July 2015

Multi‐state models are useful for modelling disease progression where the state space of the process is used to represent the discrete disease status of subjects. Often, the disease process is only observed at clinical visits, and the schedule of these visits can depend on the disease status of patients. In such situations, the frequency and timing of observations may depend on transition times that are themselves unobserved in an interval‐censored setting. There is a potential for bias if we model a disease process with informative observation times as a non‐informative observation scheme with pre‐specified examination times. In this paper, we develop a joint model for the disease and observation processes to ensure valid inference because the follow‐up process may itself contain information about the disease process. The transitions for each subject are modelled using a Markov process, where bivariate subject‐specific random effects are used to link the disease and observation models. Inference is based on a Bayesian framework, and we apply our joint model to the analysis of a large study examining functional decline trajectories of palliative care patients. Copyright © 2015 John Wiley & Sons, Ltd.
Electrostatic Limit of Detection of Nanowire‐Based Sensors
Authors: Henning Alex , Molotskii Michel , Swaminathan Nandhini , Vaknin Yonathan , Godkin Andrey , Shalev Gil , Rosenwaks Yossi
Published: July 2015

Scanning gate microscopy is used to determine the electrostatic limit of detection (LOD) of a nanowire (NW) based chemical sensor with a precision of sub‐elementary charge. The presented method is validated with an electrostatically formed NW whose active area and shape are tunable by biasing a multiple gate field‐effect transistor (FET). By using the tip of an atomic force microscope (AFM) as a local top gate, the field effect of adsorbed molecules is emulated. The tip induced charge is quantified with an analytical electrostatic model and it is shown that the NW sensor is sensitive to about an elementary charge and that the measurements with the AFM tip are in agreement with sensing of ethanol vapor. This method is applicable to any FET‐based chemical and biological sensor, provides a means to predict the absolute sensor performance limit, and suggests a standardized way to compare LODs and sensitivities of various sensors.
Layer‐by‐Layer Approach to (2+1)D Photonic Crystal Superlattice with Enhanced Crystalline Integrity
Authors: Zhang Lijing , Xiong Zhuo , Shan Liang , Zheng Lu , Wei Tongbo , Yan Qingfeng
Published: July 2015

Large‐area polystyrene (PS) colloidal monolayers with high mechanical strength are created by a combination of the air/water interface self‐assembly and the solvent vapor annealing technique. Layer‐by‐layer (LBL) stacking of these colloidal monolayers leads to the formation of (2+1)D photonic crystal superlattice with enhanced crystalline integrity. By manipulating the diameter of PS spheres and the repetition period of the colloidal monolayers, flexible control in structure and stop band position of the (2+1)D photonic crystal superlattice has been realized, which may afford new opportunities for engineering photonic bandgap materials. Furthermore, an enhancement of 97.3% on light output power of a GaN‐based light emitting diode is demonstrated when such a (2+1)D photonic crystal superlattice employed as a back reflector. The performance enhancement is attributed to the photonic bandgap enhancement and good angle‐independence of the (2+1)D photonic crystal superlattice.
Development of MDevSPICE® – the medical device software process assessment framework
Authors: Lepmets Marion , Clarke Paul , McCaffery Fergal , Finnegan Anita , Dorling Alec
Published: July 2015

Software that is incorporated into a medical device, or which is a standalone medical device in its own right, is of a safety critical nature and subject to regulation from various jurisdictions. In order to satisfy jurisdictional regulations, developers of medical device software adopt standards and guidance provided by international standards bodies and regulators. However, the various standards and guidance documents are often not developed as a single cohesive set resulting in a complex and costly challenge for medical device software developers when complying with regulation.

The aim of this paper is to describe the integration of medical device guidance documents and software engineering standards into a unified framework for medical device software process assessment called MDevSPICE®. The paper illustrates the development of both the process reference model and the process assessment model (PAM) of MDevSPICE®. The MDevSPICE® PAM can help software developers to prepare for the regulatory audits, which they must satisfy as a prerequisite to placing their products on the market. The MDevSPICE® PAM can also assist medical device manufacturers to select competent software suppliers. Copyright © 2015 John Wiley & Sons, Ltd.
Pharyngeal Satellite Cells Undergo Myogenesis Under Basal Conditions and Are Required for Pharyngeal Muscle Maintenance
Authors: Randolph Matthew E. , Phillips Brittany L. , Choo Hyo-Jung , Vest Katherine E. , Vera Yandery , Pavlath Grace K.
Published: July 2015

The pharyngeal muscles of the nasal, oral, and laryngeal pharynxes are required for swallowing. Pharyngeal muscles are preferentially affected in some muscular dystrophies yet spared in others. Muscle stem cells, called satellite cells, may be critical factors in the development of pharyngeal muscle disorders; however, very little is known about pharyngeal satellite cells (PSC) and their role in pharyngeal muscles. We show that PSC are distinct from the commonly studied hindlimb satellite cells both transcriptionally and biologically. Under basal conditions PSC proliferate, progress through myogenesis, and fuse with pharyngeal myofibers. Furthermore, PSC exhibit biologic differences dependent on anatomic location in the pharynx. Importantly, PSC are required to maintain myofiber size and myonuclear number in pharyngeal myofibers. Together, these results demonstrate that PSC are critical for pharyngeal muscle maintenance and suggest that satellite cell impairment could contribute to pharyngeal muscle pathology associated with various muscular dystrophies and aging. Stem Cells  2015;33:3581–3595
Concise Review: Induced Pluripotent Stem Cells as New Model Systems in Oncology
Authors: Laplane Lucie , Beke Allan , Vainchenker William , Solary Eric
Published: July 2015

The demonstration that pluripotent stem cells could be generated by somatic cell reprogramming led to wonder if these so-called induced pluripotent stem (iPS) cells would extend our investigation capabilities in the cancer research field. The first iPS cells derived from cancer cells have now revealed the benefits and potential pitfalls of this new model. iPS cells appear to be an innovative approach to decipher the steps of cell transformation as well as to screen the activity and toxicity of anticancer drugs. A better understanding of the impact of reprogramming on cancer cell-specific features as well as improvements in culture conditions to integrate the role of the microenvironment in their behavior may strengthen the epistemic interest of iPS cells as model systems in oncology. Stem Cells  2015;33:2887–2892
A Role for MOSPD1 in Mesenchymal Stem Cell Proliferation and Differentiation
Authors: Kara Madina , Axton Richard A. , Jackson Melany , Ghaffari Sahar , Buerger Katrin , Watt Alistair J. , Taylor A. Helen , Orr Brigid , Hardy Winters R. , Peault Bruno , Forrester Lesley M.
Published: July 2015

Mesenchymal stem cells (MSCs) isolated from many tissues including bone marrow and fat can be expanded in vitro and can differentiate into a range of different cell types such as bone, cartilage, and adipocytes. MSCs can also exhibit immunoregulatory properties when transplanted but, although a number of clinical trials using MSCs are in progress, the molecular mechanisms that control their production, proliferation, and differentiation are poorly understood. We identify MOSPD1 as a new player in this process. We generated MOSPD1-null embryonic stem cells (ESCs) and demonstrate that they are deficient in their ability to differentiate into a number of cell lineages including osteoblasts, adipocytes, and hematopoietic progenitors. The self-renewal capacity of MOSPD1-null ESCs was normal and they exhibited no obvious defects in early germ layer specification nor in epithelial to mesenchymal transition (EMT), indicating that MOSPD1 functions after these key steps in the differentiation process. Mesenchymal stem cell (MSC)-like cells expressing CD73, CD90, and CD105 were generated from MOSPD1-null ESCs but their growth rate was significantly impaired implying that MOSPD1 plays a role in MSC proliferation. Phenotypic deficiencies exhibited by MOSPD1-null ESCs were rescued by exogenous expression of MOSPD1, but not MOSPD3 indicating distinct functional properties of these closely related genes. Our in vitro studies were supported by RNA-sequencing data that confirmed expression of Mospd1 mRNA in cultured, proliferating perivascular pre-MSCs isolated from human tissue. This study adds to the growing body of knowledge about the function of this largely uncharacterized protein family and introduces a new player in the control of MSC proliferation and differentiation. Stem Cells  2015;33:3077–3086
Development of Speech Fluency Over a Short Period of Time: Effects of Pedagogic Intervention
Authors: Tavakoli Parvaneh , Campbell Colin , McCormack Joan
Published: July 2015

This study investigates the effects of a short‐term pedagogic intervention on development of second language (L2) fluency among learners studying English for academic purposes at a UK university. It also examines the interaction between development of fluency and complexity and accuracy. Through a pretest and posttest design, data were collected over a period of 4 weeks from learners performing monologic tasks. While the control group (CG) focused on developing general speaking and listening skills, the experimental group (EG) received awareness‐raising activities and fluency strategy training in addition to general speaking and listening practice. The data, coded in terms of a range of measures of fluency, accuracy, and complexity, were subjected to repeated‐measures multivariate analysis of variance (MANOVA), t‐tests, and correlations. The results indicate that after the intervention, although some fluency gains were achieved by the CG, the EG produced statistically more fluent language, demonstrating a faster speech and articulation rate, longer runs, and higher phonation time ratios. The significant correlations obtained between measures of accuracy and learners’ pauses in the CG suggest that pausing opportunities may have been linked to accuracy. The findings have significant implications for L2 pedagogy, highlighting the effective impact of instruction on development of fluency.
Ways of knowing climate: Hubert H. Lamb and climate research in theUK
Authors: Martin‐Nielsen Janet
Published: July 2015

Today, numerical modelling is widely seen as the leading method of climate research. Modelling enjoys a hegemonic status in the production of climate predictions and the discussion and policy application of climate knowledge. This dominance obscures past and present debates about which types of climate knowledge are important, which epistemic standards are used to judge that knowledge, and which applications of that knowledge are considered useful. In the existing historiography of climate research, the focus has overwhelmingly been on numerical modelling, and relatively little has been written about other ways of knowing climate. The hegemony that numerical models enjoy today is not the result of a linear ‘arrow of progress,’ beginning with the introduction of digital computers and leading naturally to today's situation, but rather of a more complex situation centered on changing ideas of climate, the identity of climate researchers, and the direction and scope of their work. This paper aims to shed light on these ideas by investigating and analyzing climate research debates in the 1960s and early 1970s through the lens of the English meteorologist and climatologist Hubert Horace Lamb (1913–1997). It pays particular attention to Lamb's understanding of climatology as a discipline and his assessment of that discipline through the latter half of the 20thcentury.WIREs Clim Change2015, 6:465–477. doi: 10.1002/wcc.349

This article is categorized under:

Climate, History, Society, Culture > Thought Leaders
Characterization of crystal lattice defects in calcium molybdate single crystals (CaMoO4) by means of X‐ray diffraction topography
Authors: Wierzbicka E. , Malinowska A. , Wieteska K. , Wierzchowski W. , Lefeld‐Sosnowska M. , Świrkowicz M. , Łukasiewicz T. , Paulmann C.
Published: July 2015

Calcium molybdate CaMoO4 crystals are perspective materials for many applications in acoustic‐electronics, acoustic‐optics and nonlinear optics. They are also used as laser hosts, scintillators, different kinds of substrates and active elements of ionizing radiation detectors. For all these applications large‐sized single crystals of high structural quality are required.

The samples of CaMoO4 crystals have been investigated by means of synchrotron white beam topography, monochromatic beam topography and conventional X‐ray Lang projection topography. The high‐resolution rocking curves have also been taken using synchrotron and conventional arrangements.

The topographs showed a rather good crystallographic perfection of the crystals. In particular, they did not reveal any segregation fringes proving high homogeneity of the chemical composition. Relatively high densities (<104 cm−2) of weak point‐like diffraction contrasts were observed, which can be most probably interpreted as dislocation outcrops.

The distinct main imperfection of the investigated crystals was variously developed block structure. The evaluation of lattice misorientation was realized by means of projection and section white beam synchrotron radiation topographs. The evaluated misorientation between various blocks was in the range of several arc minutes. Copyright © 2015 John Wiley & Sons, Ltd.
Genome‐wide screen of fission yeast mutants for sensitivity to 6‐azauracil, an inhibitor of transcriptional elongation
Authors: Zhou Huan , Liu Qi , Shi Tianfang , Yu Yao , Lu Hong
Published: July 2015

6‐Azauracil (6 AU) inhibits enzymes in nucleoside synthesis and depletes the intracellular GTP/UTP pool. Mutations in transcriptional elongation machinery, as well as mutations in a variety of other pathways, exaggerate the growth defect of cells in the presence of 6 AU. Thus, identification of mutations that render cells sensitive to 6 AU will benefit study on the basis of 6 AU‐sensitive phenotype. Here we performed a genome‐wide screen of a fission yeast deletion library. Of 3235 single‐gene deletions, 66 mutants displayed at least 50% drop of fitness in the presence of 6 AU and 60 mutants were reported for the first time; five deletions showed synthetic decrease of fitness when combined with deletion of set3+, which encodes a transcriptional regulator. Genes conferring tolerance to 6 AU were enriched in various processes, especially in chromosome segregation. Accordingly, genes encoding subunits of CLRC complex and spindle pole body were over‐represented. Mutants were subjected to an in vivo transcript length‐dependent reporter assay to assess the potential roles of deleted genes in transcriptional elongation. As with the deletions known to affect elongation, nab2Δ, nxt1Δ, rhp18Δ, SPAC24C9.08Δ, clr3Δ and ncs1Δset3Δ mutants exhibited defects in expressing long transcripts. New 6 AU‐sensitive mutants identified here will help to elucidate the mechanism of action of 6 AU in the cells. Meanwhile, our study revealed novel genes potentially involved in transcriptional elongation and provided valuable targets for transcription study. Copyright © 2015 John Wiley & Sons, Ltd.
New complexes containing the internal alternative NADH dehydrogenase (Ndi1) in mitochondria of Saccharomyces cerevisiae
Authors: Matus‐Ortega M. G. , Cárdenas‐Monroy C. A. , Flores‐Herrera O. , Mendoza‐Hernández G. , Miranda M. , González‐Pedrajo B. , Vázquez‐Meza H. , Pardo J. P.
Published: July 2015

Mitochondria of Saccharomyces cerevisiae lack the respiratory complex I, but contain three rotenone‐insensitive NADH dehydrogenases distributed on both the external (Nde1 and Nde2) and internal (Ndi1) surfaces of the inner mitochondrial membrane. These enzymes catalyse the transfer of electrons from NADH to ubiquinone without the translocation of protons across the membrane. Due to the high resolution of the Blue Native PAGE (BN–PAGE) technique combined with digitonin solubilization, several bands with NADH dehydrogenase activity were observed on the gel. The use of specific S. cerevisiae single and double mutants of the external alternative elements (ΔNDE1, ΔNDE2, ΔNDE1/ΔNDE2) showed that the high and low molecular weight complexes contained the Ndi1. Some of the Ndi1 associations took place with complexes III and IV, suggesting the formation of respirasome‐like structures. Complex II interacted with other proteins to form a high molecular weight supercomplex with a molecular mass around 600 kDa. We also found that the majority of the Ndi1 was in a dimeric form, which is in agreement with the recently reported three‐dimensional structure of the protein. Copyright © 2015 John Wiley & Sons, Ltd.
Preference assessments in the zoo: Keeper and staff predictions of enrichment preferences across species
Authors: Mehrkam Lindsay R. , Dorey Nicole R.
Published: July 2015

Environmental enrichment is widely used in the management of zoo animals, and is an essential strategy for increasing the behavioral welfare of these populations. It may be difficult, however, to identify potentially effective enrichment strategies that are also cost‐effective and readily available. An animal's preference for a potential enrichment item may be a reliable predictor of whether that individual will reliably interact with that item, and subsequently enable staff to evaluate the effects of that enrichment strategy. The aim of the present study was to assess the utility of preference assessments for identifying potential enrichment items across six different species—each representing a different taxonomic group. In addition, we evaluated the agreement between zoo personnel's predictions of animals' enrichment preferences and stimuli selected via a preference assessment. Five out of six species (nine out of 11 individuals) exhibited clear, systematic preferences for specific stimuli. Similarities in enrichment preferences were observed among all individuals of primates, whereas individuals within ungulate and avian species displayed individual differences in enrichment preferences. Overall, zoo personnel, regardless of experience level, were significantly more accurate at predicting least‐preferred stimuli than most‐preferred stimuli across species, and tended to make the same predictions for all individuals within a species. Preference assessments may therefore be a useful, efficient husbandry strategy for identifying viable enrichment items at both the individual and species levels. Zoo Biol. 34:418–430, 2015. © 2015 Wiley Periodicals, Inc.
Improving diet and activity of insectivorous primates in captivity: Naturalizing the diet of Northern Ceylon gray slender loris, Loris lydekkerianus nordicus
Authors: Williams Emma , Cabana Francis , Nekaris K. A. I.
Published: July 2015

Data on in‐situ diet and nutritional requirements should inform the provision of food to captive insectivorous primates. Despite the growing availability of such information an over‐reliance on commercially available primate foods and fruit continues in many captive establishments. Wild slender lorises are almost exclusively insectivorous, yet captive conspecifics are fed a primarily frugivorous diet that is likely to contribute to behavioral and health problems. We investigated the effect of naturalizing diet in the Northern Ceylon grey slender loris (Loris lydekkerianus nordicus) by providing live insect prey to a captive group of five individuals. We calculated activity budgets in accordance with six established categories and recorded positional behaviors. We collected data over 30 hours for each of three conditions: pre‐enrichment, enrichment, post‐enrichment. We hypothesized that increased opportunity for the display of natural behaviors would be stimulated by the dietary enrichment of live insects and made the following predictions; 1) Percentage time spent foraging would increase and time spent inactive would decrease; 2) behavioral repertoires would increase; 3) foraging patterns would be more constant over time with reduced feeding‐time peaks. We analyzed time budget and behavioral changes using Friedman tests. We found significant changes in activity budgets with inactivity reduced and foraging levels increased to levels seen in wild slender lorises. We found a significant increase in postures used in foraging and a wider behavioral repertoire. We discuss the benefits of providing free‐ranging live food in relation to enhancing the temporal‐spatial distribution of food acquisition, satisfying nutritional requirements, balancing energy intake, and expenditure, expanding sensory stimulation, and promoting behavioral competence. We discuss our findings in relation to other insectivorous primates. Zoo Biol. 34:473–482, 2015. © 2015 Wiley Periodicals, Inc.
Two-step production of gamma-aminobutyric acid from cassava powder using Corynebacterium glutamicum and Lactobacillus plantarum
Authors: Yang Taowei , Rao Zhiming , Kimani Bernard Gitura , Xu Meijuan , Zhang Xian , Yang Shang-Tian
Published: July 2015

Production of gamma-aminobutyric acid (GABA) from crop biomass such as cassava in high concentration is desirable, but difficult to achieve. A safe biotechnological route was investigated to produce GABA from cassava powder by C. glutamicum G01 and L. plantarum GB01-21. Liquefied cassava powder was first transformed to glutamic acid by simultaneous saccharification and fermentation with C. glutamicum G01, followed by biotransformation of glutamic acid to GABA with resting cells of L. plantarum GB01-21 in the reaction medium. After optimizing the reaction conditions, the maximum concentration of GABA reached 80.5 g/L with a GABA productivity of 2.68 g/L/h. This is the highest yield ever reported of GABA production from cassava-derived glucose. The bioprocess provides the added advantage of employing nonpathogenic microorganisms, C. glutamicum and L. plantarum, in microbial production of GABA from cassava biomass, which can be used in the food and pharmaceutical industries.
N8‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics
Authors: Abela Lucia , Simmons Luke , Steindl Katharina , Schmitt Bernhard , Mastrangelo Massimo , Joset Pascal , Papuc Mihaela , Sticht Heinrich , Baumer Alessandra , Crowther Lisa M. , Mathis Déborah , Rauch Anita , Plecko Barbara
Published: July 2015

Clinical metabolomics has emerged as a powerful tool to study human metabolism in health and disease. Comparative statistical analysis of untargeted metabolic profiles can reveal perturbations of metabolite levels in diseases and thus has the potential to identify novel biomarkers. Here we have applied a simultaneous genetic‐metabolomic approach in twin boys with epileptic encephalopathy of unclear etiology. Clinical exome sequencing identified a novel missense mutation in the spermine synthase gene (SMS) that causes Snyder‐Robinson syndrome (SRS). Untargeted plasma metabolome analysis revealed significantly elevated levels of N8‐acetylspermidine, a precursor derivative of spermine biosynthesis, as a potential novel plasma biomarker for SRS. This result was verified in a third patient with genetically confirmed SRS. This study illustrates the potential of metabolomics as a translational technique to support exome data on a functional and clinical level.
Cultural Concerns when Counseling Orthodox Jewish Couples for Genetic Screening and PGD
Authors: Grazi Richard V. , Wolowelsky Joel B.
Published: July 2015

There is a spectrum of attitudes within the Orthodox Jewish community towards genetic testing and PGD. Increased understanding of the belief systems of the Orthodox Jewish population will enhance the genetic counselors’ ability to better serve this unique group of patients. By improving cultural competence, genetic counselors can help patients choose the testing options that they deem appropriate, while simultaneously respecting the patient's belief system.
Habitat selection of cavity‐nesting birds in the Hyrcanian deciduous forests of northern Iran
Authors: Bani Assadi Saeedeh , Kaboli Mohammad , Etemad Vahid , Ghadiri Khanaposhtani Maryam , Tohidifar Mohammad
Published: July 2015

The Hyrcanian forests of northern Iran support a great diversity of bird species. Yet, the ecological relationships of cavity‐nesting birds (CNBs), the main components of forest bird communities in this area, remain unknown. We examined the importance of ecological factors in 90 study plots during the breeding season to predict the probability distribution and habitat suitability of primary cavity nesters (PCNs), secondary cavity nesters (SCNs) and weak primary cavity nesters (WPCNs). Ecological factors included forest structure, habitat complexity, geographical attributes and dead tree features. The significant habitat parameters determining the presence‐absence of each CNB species were also determined. PCN richness and abundance were most influenced by the density of larger trees, snags (standing dead trees) and logs (fallen dead trees). The densities of snags, logs and larger trees and the extent of the shrub layer influenced distributions of SCNs. The Eurasian nuthatch (Sitta europaea) was the only WPCN identified, and its distribution was strongly affected by altitude and by larger snags and trees in complex habitats. Our results showed that CNB species could be classified in three groups: (1) species dependent on mature forests, (2) species dependent on younger forests and (3) species adaptable to different forest stages. Overall, snags and logs played vital roles in the habitat preferences of CNB communities as well as in forest structure and complexity.