bluuebunny/crossref_metadata_2025 huggingface dataset:
Antifouling coatings for dental implants: Polyethylene glycol-like coatings on titanium by plasma polymerization
Authors: Buxadera-Palomero Judit , Canal Cristina , Torrent-Camarero Sergi , Garrido Beatriz , Javier Gil Francisco , Rodríguez Daniel
Published: March 2015

Titanium dental implants are commonly used for the replacement of lost teeth, but they present a considerable number of failures due to the infection on surrounding tissues. The aim of this paper is the development of a polyethylene glycol-like (PEG-like) coating on the titanium surface by plasma polymerization to obtain a novel improved surface with suitable low bacterial adhesion and adequate cell response. Surface analysis data of these coatings are presented, in particular, water contact angle, surface roughness, and film chemistry, demonstrating the presence of a PEG-like coating. Streptococcus sanguinis and Lactobacillus salivarius bacterial adhesion assays showed a decreased adhesion on the plasma polymerized samples, while cell adhesion of fibroblasts and osteoblasts on the treated surfaces was similar to control surfaces. Thus, the PEG-like antifouling coating obtained by plasma polymerization on Ti confers this biomaterial's highly suitable properties for dental applications, as they reduce the possibility of infection while allowing the tissue integration around the implant.
College Students’ Achievement Goal Orientation and Motivational Regulations in Physical Activity Classes: A Test of Gender Invariance
Authors: Su Xiaoxia , McBride Ron E. , Xiang Ping
Published: March 2015

The current study examined the measurement invariance across 361 male and female college students’ 2 × 2 achievement goal orientation and motivational regulations. Participants completed questionnaires assessing their achievement goals and motivational regulations. Multigroup CFA analyses showed that male and female students’ scores were fully invariant at the configural, metric, and scalar levels. Multigroup SEM analyses revealed that mastery-approach goals positively predicted intrinsic regulation and identified regulation. It also revealed that performance-approach goal was a stronger predictor of external regulation among female students than among male students. Collectively, these results provide evidence that researchers can make valid inferences about differences in achievement goal and self-regulation scores across male and female students. This study also supports the view that mastery-approach goals are motivationally beneficial, especially among female students, in college physical activity class settings.
A Critical Examination of Movement Content Knowledge Courses in Physical Education Teacher Education Programs
Authors: Kim Insook , Lee Yun Soo , Ward Phillip , Li Weidong
Published: March 2015

Despite increasing policy emphasis on improving teacher quality, little is known about how teachers acquire their movement content knowledge in physical education teacher education (PETE). To address this question we examined: (a) movement content courses designed to teach K-12 physical education content in the PETE curriculum, (b) the purpose of the movement content courses, (c) the focus of the movement content course syllabi, and (d) pedagogical tasks used to teach movement content knowledge. Data were collected from websites, program coordinators, and course syllabi in 26 PETE programs and analyzed using descriptive statistics or one-way chi-square test. A primary conclusion from this study is that not a lot of common content knowledge is taught in the PETE curriculums we examined. A second conclusion is that specialized content knowledge does not represent a significant focus in the movement content classes. These findings both support and challenge current policy initiatives that address teacher quality in PETE.
Teaching Personal and Social Responsibility and Transfer of Learning: Opportunities and Challenges for Teachers and Coaches
Authors: Gordon Barrie , Doyle Stephanie
Published: March 2015

The transfer of learning from the gym to other areas of participants’ lives has always been a core component of the Teaching Personal and Social Responsibility Model. The degree to which transfer of learning is successfully facilitated in the reality of Teaching Personal and Social Responsibility Model-based teaching and coaching is, however, uncertain. The research findings are mixed both in the commitment to transfer of learning and the level of success that has been achieved. The interest in transfer of learning is not restricted to the area of the Teaching Personal and Social Responsibility Model or physical education and sport in general, but is an area of strong academic interest with a long history of research and debate. This article draws on the knowledge and understandings of transfer of learning from this wider literature to explore ways in which to help facilitate transfer of learning for practitioners of the Teaching Personal and Social Responsibility Model.
Strongly correlated quantum walks in optical lattices
Authors: Preiss Philipp M. , Ma Ruichao , Tai M. Eric , Lukin Alexander , Rispoli Matthew , Zupancic Philip , Lahini Yoav , Islam Rajibul , Greiner Markus
Published: March 2015

Quantum walkers under a microscope

Generations of physics students have been taught to think of one-dimensional random walks in terms of a drunken sailor taking random steps to the right or to the left. But that doesn't compare with the complexity of a quantum walker, who can propagate down multiple paths at the same time. Preiss
et al.
detected particles in single sites of an optical lattice to study the dynamics of two interacting atoms of 87Rb performing a quantum walk (see the Perspective by Widera). Depending on the initial conditions and the interaction strength between the atoms, the atoms either ignored each other, stuck to each other, or tried to get as far away from each other as possible.

Science
, this issue p.
1229
; see also p.
1200
Militants leave trail of destruction at Iraqi sites
Authors: Lawler Andrew
Published: March 2015

The Islamic State group strikes one valuable archaeological site after another, destroying priceless ruins and artifacts.
Bird flu virus's promiscuity raises red flags
Authors: Normile Dennis
Published: March 2015

Novel variants of H7N9 and other strains are arising at alarming rate.
Disease Modeling With Patient-Specific Ips Cells
Authors: Perkel Jeffrey M.
Published: March 2015

Whether in mice or macaques, disease modeling traditionally has been a tedious and expensive affair, not to mention unreliable, as mutations that are crippling in humans could have negligible impacts in animals, and vice versa. As drug development often requires preclinical animal studies, that disconnect has had real implications for the pharmaceuticals industry, both in money and missed opportunities. Today, researchers increasingly are migrating their models from the mouse house to the culture room. Armed with induced pluripotent stem cells made from patient cells, these investigators are probing everything from basic biology and disease etiology to drug discovery and cell therapeutics.

Read the Feature (Full-Text HTML)

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Read New Products (PDF)
Charting the human proteome: Understanding disease using a tissue-based atlas
Authors: Uhlén Mathias , Pontén Fredrik , Lindskog Cecilia
Published: March 2015

A decade on from the completion of the Human Genome, the Human Protein Atlas, a multinational research project supported by the non-profit Knut and Alice Wallenberg Foundation, recently launched (November 6, 2014) an open source tissue-based interactive map of the human proteome. A team of multidisciplinary researchers with expertise spanning biotechnology, information technology, and medicine have used a combination of several 'omics technologies to map proteins down to the single cell level, showing both proteins restricted to certain tissues—such as the brain, heart, or liver—and those present in all tissues. It has taken this team over 1,000 person years to compile a searchable, open source database (www.proteinatlas.org) comprising 13 million annotated images of human tissues. The interactive database is aimed at researchers interested in basic research into human biology as well as those working in translational medicine. In this webinar, three of the researchers involved in this program will provide their insights regarding the lessons learned from this intensive effort to map the human proteome.

View the Webinar
Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis
Authors: Weber Georg F. , Chousterman Benjamin G. , He Shun , Fenn Ashley M. , Nairz Manfred , Anzai Atsushi , Brenner Thorsten , Uhle Florian , Iwamoto Yoshiko , Robbins Clinton S. , Noiret Lorette , Maier Sarah L. , Zönnchen Tina , Rahbari Nuh N. , Schölch Sebastian , Klotzsche-von Ameln Anne , Chavakis Triantafyllos , Weitz Jürgen , Hofer Stefan , Weigand Markus A. , Nahrendorf Matthias , Weissleder Ralph , Swirski Filip K.
Published: March 2015

A new therapeutic target for sepsis

Infections can sometimes unleash powerful immune responses that careen out of control, leading to sepsis, organ failure, and death. Although antibiotics can help to quash the infection, sepsis patients also need therapies that will rein in the immune response. Weber
et al.
now identify one potential target, the secreted protein interleukin-3 (IL-3) (see the Perspective by Hotchkiss). In sepsis patients, higher serum concentrations of IL-3 were correlated with higher rates of mortality. In septic mice, IL-3 caused the immune system to produce large amounts of cells called monocytes and neutrophils, which secrete highly inflammatory proteins. Blocking IL-3 protected mice from sepsis-induced death.

Science
, this issue p.
1260
; see also p.
1201
Precious metals
Rare: The High-Stakes Race to Satisfy Our Need for the Scarcest Metals on Earth
Keith Veronese
Prometheus Books, 2015. 278 pp.
Authors: Ali Saleem H.
Published: March 2015

Balancing the growing demand for rare earth minerals with sustainable mining practices
Synthesis of many different types of organic small molecules using one automated process
Authors: Li Junqi , Ballmer Steven G. , Gillis Eric P. , Fujii Seiko , Schmidt Michael J. , Palazzolo Andrea M. E. , Lehmann Jonathan W. , Morehouse Greg F. , Burke Martin D.
Published: March 2015

A block-by-block way to manufacture molecules

Carbon-based small molecules involved in biochemistry and drug design exhibit extraordinary structural diversity. But can we come up with a general set of building blocks from which a machine could put most of them together, in assembly-line fashion? Li
et al.
present progress toward this goal by showcasing the range of structures available via coupling reactions of fragments bearing a specific type of boronate group. They successfully made complex polycyclic structures by stringing together a linear precursor and then coaxing it to fold back on itself. They also developed a purification method that facilitates automation of the reaction and product isolation.

Science
, this issue p.
1221
A walk across a quantum lattice
Authors: Widera Artur
Published: March 2015

A simple two-atom system is used to probe complex quantum phenomena

[Also see Report by

Preiss
et al.

]
Getting sepsis therapy right
Authors: Hotchkiss Richard S. , Sherwood Edward R.
Published: March 2015

Is decreasing inflammation or increasing the host immune response the better approach?

[Also see Report by

Weber
et al.

]
Chemistry embraced by all
Authors: Matlin Stephen , Mehta Goverdhan , Hopf Henning
Published: March 2015

Chemistry is the great enabler. For two centuries, it has played a key role in conquering diseases, solving energy problems, addressing environmental challenges, and providing discoveries that have spawned new industries. To meet the demands of the future, this mature science must expand into new frontiers, a move that will be facilitated if the public and policy-makers understand its pivotal role in every facet of life. Such support will not be forthcoming from those who associate chemistry with harm—intentional or not—to people and the biosphere. Addressing the disparity between those perceptions and the reality of chemistry's contributions to society will garner broader support for spurring innovations in the 21st century. How can chemistry ensure that it has this support?
Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections
Authors: Agut Henri , Bonnafous Pascale , Gautheret-Dejean Agnès
Published: March 2015

Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropismin vivoand, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus.
Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV Risk and Prevention
Authors: Kyongo Jordan K. , Crucitti Tania , Menten Joris , Hardy Liselotte , Cools Piet , Michiels Johan , Delany-Moretlwe Sinead , Mwaura Mary , Ndayisaba Gilles , Joseph Sarah , Fichorova Raina , van de Wijgert Janneke , Vanham Guido , Ariën Kevin K. , Jespers Vicky
Published: March 2015

Data on immune mediators in the genital tract and the factors that modulate them in sub-Saharan women are limited. Cervicovaginal lavage (CVL) samples from 430 sexually active women from Kenya, South Africa, and Rwanda were analyzed for 12 soluble immune mediators using Bio-Plex and Meso Scale Discovery multiplex platforms, as well as single enzyme-linked immunosorbent assays. Ten bacterial species were quantified in vaginal swab samples. Bacterial vaginosis (BV) was defined by Nugent scoring. CVL samples from HIV-infected women showed a clear-cut proinflammatory profile. Pregnant women, adolescents, and women engaging in traditional vaginal practices differed in specific soluble markers compared to reference groups of adult HIV-negative women. Cervical mucus, cervical ectopy, abnormal vaginal discharge, and having multiple sex partners were each associated with an increase in inflammatory mediators. The levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12(p70), and IL-8 were elevated, whereas the IL-1RA/IL-1(α+β) ratio decreased in women with BV. The level of gamma interferon-induced protein 10 was lower in BV-positive than in BV-negative women, suggesting its suppression as a potential immune evasion mechanism by BV-associated bacteria.Lactobacillus crispatusandLactobacillus vaginaliswere associated with decreased proinflammatory cytokines and each BV-associated species with increased proinflammatory cytokines. Remarkably, thein vitroanti-HIV activity of CVL samples from BV-positive women was stronger than that of BV-negative women. In conclusion, we found significant associations of factors, including vaginal microbiota, which can influence immune mediators in the vaginal environment in sexually active women. These factors need to be considered when establishing normative levels or pathogenic cutoffs of biomarkers of inflammation and associated risks in African women.
Point-Counterpoint: Large Multiplex PCR Panels Should Be First-Line Tests for Detection of Respiratory and Intestinal Pathogens
Authors: Schreckenberger Paul C. , McAdam Alexander J.
Published: March 2015

The first FDA-approved multiplex PCR panel for a large number of respiratory pathogens was introduced in 2008. Since then, other PCR panels for detection of several respiratory and gastrointestinal pathogens have been approved by the FDA and are commercially available, and more such panels are likely to become available. These assays detect 12 to 20 pathogens, and some include pathogens that typically cause different manifestations of infection, although they infect the same organ system. Some of these tests are labor-intensive, while others require little labor, and all of them are expensive, both for the laboratory and for the patient or insurer. They include a bundle of tests with limited or no options for selecting which tests will be performed. Laboratories and hospitals have adopted different strategies for offering these assays. Some have implemented strategies to limit the use of the tests, such as limiting the frequency with which patients can be tested, restricting testing to specific groups of patients (e.g., immunocompromised patients), or providing education to encourage the use of less expensive tests before using large multiplex panels. Others have offered these assays without limiting their use, either relying on the ordering provider to exercise good judgment or because such assays are thought to be appropriate for first-line diagnostic testing. In this Point-Counterpoint, Paul Schreckenberger of Loyola University Medical Center explains why his laboratory offers these assays without restriction. Alex McAdam of Boston's Children Hospital explains the concerns about the use of these assays as first-line tests and why some limitations on their use might be appropriate.
The Resistant-Population Cutoff (RCOFF): a New Concept for Improved Characterization of Antimicrobial Susceptibility Patterns of Non-Wild-Type Bacterial Populations
Authors: Valsesia Giorgia , Hombach Michael , Maurer Florian P. , Courvalin Patrice , Roos Malgorzata , Böttger Erik C.
Published: March 2015

This study aimed to determine resistant-population cutoffs (RCOFFs) to allow for improved characterization of antimicrobial susceptibility patterns in bacterial populations. RCOFFs can complement epidemiological cutoff (ECOFF)-based settings of clinical breakpoints (CBPs) by systematically describing the correlation between non-wild-type and wild-type populations. We illustrate this concept by describing three paradigmatic examples of wild-type and non-wild-type
Escherichia coli
populations from our clinical strain database of disk diffusion diameters. The statistical determination of RCOFFs and ECOFFs and their standardized applications in antimicrobial susceptibility testing (AST) facilitates the assignment of isolates to wild-type or non-wild-type populations. This should improve the correlation of
in vitro
AST data and distinct antibiotic resistance mechanisms with clinical outcome facilitating the setting and validation of CBPs.
Tristetraprolin Recruits the Herpes Simplex Virion Host Shutoff RNase to AU-Rich Elements in Stress Response mRNAs To Enable Their Cleavage
Authors: Shu Minfeng , Taddeo Brunella , Roizman Bernard
Published: March 2015

Herpes simplex viruses (HSV) package and bring into cells an RNase designated virion host shutoff (VHS) RNase. In infected cells, the VHS RNase targets primarily stress response mRNAs characterized by the presence of AU-rich elements in their 3′ untranslated regions (UTRs). In uninfected cells, these RNAs are sequestered in exosomes or P bodies by host proteins that bind to the AU-rich elements. In infected cells, the AU-rich RNAs are deadenylated and cleaved close to the AU-rich elements, leading to long-term persistence of nontranslatable RNAs consisting of the 5′ portions of the cleavage products. The host proteins that bind to the AU-rich elements are either resident in cells (e.g., TIA-1) or induced (e.g., tristetraprolin). Earlier, this laboratory reported that tristetraprolin binds VHS RNase. To test the hypothesis that tristetraprolin directs VHS RNase to the AU-rich elements, we mapped the domains of VHS and tristetraprolin required for their interactions. We report that VHS binds to the domain of tristetraprolin that enables its interaction with RNA. A single amino acid substitution in that domain abolished the interaction with RNA but did not block the binding to VHS RNase. In transfected cells, the mutant but not the wild-type tristetraprolin precluded the degradation of the AU-rich RNAs by VHS RNase. We conclude that TTP mediates the cleavage of the 3′ UTRs of stress response mRNAs by recruiting the VHS RNase to the AU-rich elements.

IMPORTANCE
The primary host response to HSV infection is the synthesis of stress response mRNAs characterized by the presence of AU-rich elements in their 3′ UTRs. These mRNAs are the targets of the virion host shutoff (VHS) RNase. The VHS RNase binds both to mRNA cap structure and to tristetraprolin, an inducible host protein that sequesters AU-rich mRNAs in exosomes or P bodies. Here we show that tristetraprolin recruits VHS RNase to the AU-rich elements and enables the degradation of the stress response mRNAs.
Structure-Based Mutational Analysis of Several Sites in the E Protein: Implications for Understanding the Entry Mechanism of Japanese Encephalitis Virus
Authors: Liu Haibin , Liu Yi , Wang Shaobo , Zhang Yanjun , Zu Xiangyang , Zhou Zheng , Zhang Bo , Xiao Gengfu
Published: March 2015

Japanese encephalitis virus (JEV), which causes viral encephalitis in humans, is a serious risk to global public health. The JEV envelope protein mediates the viral entry pathway, including receptor-binding and low-pH-triggered membrane fusion. Utilizing mutagenesis of a JEV infectious cDNA clone, mutations were introduced into the potential receptor-binding motif or into residues critical for membrane fusion in the envelope protein to systematically investigate the JEV entry mechanism. We conducted experiments evaluating infectious particle, recombinant viral particle, and virus-like particle production and found that most mutations impaired virus production. Subcellular fractionation confirmed that five mutations—in I
0
, ij, BC, and FG and the R9A substitution—impaired virus assembly, and the assembled virus particles of another five mutations—in kl and the E373A, F407A, L221S, and W217A substitutions—were not released into the secretory pathway. Next, we examined the entry activity of six mutations yielding infectious virus. The results showed N154 and the DE loop are not the only or major receptor-binding motifs for JEV entry into BHK-21 cells; four residues, H144, H319, T410, and Q258, participating in the domain I (DI)-DIII interaction or zippering reaction are important to maintain the efficiency of viral membrane fusion. By continuous passaging of mutants, adaptive mutations from negatively charged amino acids to positively charged or neutral amino acids, such as E138K and D389G, were selected and could restore the viral entry activity.

IMPORTANCE
Recently, there has been much interest in the entry mechanism of flaviviruses into host cells, including the viral entry pathway and membrane fusion mechanism. Our study provides strong evidence for the critical role of several residues in the envelope protein in the assembly, release, and entry of JEV, which also contributes to our understanding of the flaviviral entry mechanism. Furthermore, we demonstrate that the H144A, H319A, T410A, and Q258A mutants exhibit attenuated fusion competence, which may be used to develop novel vaccine candidates for flaviviruses.
Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8
Authors: Janowicz Anna , Caporale Marco , Shaw Andrew , Gulletta Salvatore , Di Gialleonardo Luigina , Ratinier Maxime , Palmarini Massimo
Published: March 2015

Bluetongue virus (BTV) causes bluetongue, a major hemorrhagic disease of ruminants. In order to investigate the molecular determinants of BTV virulence, we used a BTV8 strain minimally passaged in tissue culture (termed BTV8
L
in this study) and a derivative strain passaged extensively in tissue culture (BTV8
H
) in
in vitro
and
in vivo
studies. BTV8
L
was pathogenic in both IFNAR
−/−
mice and in sheep, while BTV8
H
was attenuated in both species. To identify genetic changes which led to BTV8
H
attenuation, we generated 34 reassortants between BTV8
L
and BTV8
H
. We found that partial attenuation of BTV8
L
in IFNAR
−/−
mice was achieved by simply replacing genomic segment 2 (Seg2, encoding VP2) or Seg10 (encoding NS3) with the BTV8
H
homologous segments. Fully attenuated viruses required at least two genome segments from BTV8
H
, including Seg2 with either Seg1 (encoding VP1), Seg6 (encoding VP6 and NS4), or Seg10 (encoding NS3). Conversely, full reversion of virulence of BTV8
H
required at least five genomic segments of BTV8
L
. We also demonstrated that BTV8
H
acquired an increased affinity for glycosaminoglycan receptors during passaging in cell culture due to mutations in its VP2 protein. Replication of BTV8
H
was relatively poor in interferon (IFN)-competent primary ovine endothelial cells compared to replication of BTV8
L
, and this phenotype was determined by several viral genomic segments, including Seg4 and Seg9. This study demonstrated that multiple viral proteins contribute to BTV8 virulence. VP2 and NS3 are primary determinants of BTV pathogenesis, but VP1, VP5, VP4, VP6, and VP7 also contribute to virulence.

IMPORTANCE
Bluetongue is one of the major infectious diseases of ruminants, and it is listed as a notifiable disease by the World Organization for Animal Health (OIE). The clinical outcome of BTV infection varies considerably and depends on environmental and host- and virus-specific factors. Over the years, BTV serotypes/strains with various degrees of virulence (including nonpathogenic strains) have been described in different geographical locations. However, no data are available to correlate the BTV genotype to virulence. This study shows that BTV virulence is determined by different viral genomic segments. The data obtained will help to characterize thoroughly the pathogenesis of bluetongue. The possibility to determine the pathogenicity of virus isolates on the basis of their genome sequences will help in the design of control strategies that fit the risk posed by new emerging BTV strains.
Activation of
Tomato Bushy Stunt Virus
RNA-Dependent RNA Polymerase by Cellular Heat Shock Protein 70 Is Enhanced by Phospholipids
In Vitro
Authors: Pogany Judit , Nagy Peter D.
Published: March 2015

Similar to other positive-strand RNA viruses, tombusviruses are replicated by the membrane-bound viral replicase complex (VRC). The VRC consists of the p92 virus-coded RNA-dependent RNA polymerase (RdRp), the viral p33 RNA chaperone, and several co-opted host proteins. In order to become a functional RdRp after its translation, the p92 replication protein should be incorporated into the VRC, followed by its activation. We have previously shown in a cell-free yeast extract-based assay that the activation of the
Tomato bushy stunt virus
(TBSV) RdRp requires a soluble host factor(s). In this article, we identify the cellular heat shock protein 70 (Hsp70) as the co-opted host factor required for the activation of an N-terminally truncated recombinant TBSV RdRp. In addition, small-molecule-based blocking of Hsp70 function inhibits RNA synthesis by the tombusvirus RdRp
in vitro
. Furthermore, we show that neutral phospholipids, namely, phosphatidylethanolamine (PE) and phosphatidylcholine (PC), enhance RdRp activation
in vitro
. In contrast, phosphatidylglycerol (PG) shows a strong and dominant inhibitory effect on
in vitro
RdRp activation. We also demonstrate that PE and PC stimulate RdRp-viral plus-strand RNA [(+)RNA] interaction, while PG inhibits the binding of the viral RNA to the RdRp. Based on the stimulatory versus inhibitory roles of various phospholipids in tombusvirus RdRp activation, we propose that the lipid composition of targeted subcellular membranes might be utilized by tombusviruses to regulate new VRC assembly during the course of infection.

IMPORTANCE
The virus-coded RNA-dependent RNA polymerase (RdRp), which is responsible for synthesizing the viral RNA progeny in infected cells of several positive-strand RNA viruses, is initially inactive. This strategy is likely to avoid viral RNA synthesis in the cytosol that would rapidly lead to induction of RNA-triggered cellular antiviral responses. During the assembly of the membrane-bound replicase complex, the viral RdRp becomes activated through an incompletely understood process that makes the RdRp capable of RNA synthesis. By using TBSV RdRp, we show that the co-opted cellular Hsp70 chaperone and neutral phospholipids facilitate RdRp activation
in vitro
. In contrast, phosphatidylglycerol (PG) has a dominant inhibitory effect on
in vitro
RdRp activation and RdRp-viral RNA interaction, suggesting that the membranous microdomain surrounding the RdRp greatly affects its ability for RNA synthesis. Thus, the activation of the viral RdRp likely depends on multiple host components in infected cells.
Inflammatory pseudotumour-like follicular dendritic cell tumour of the spleen
Authors: Nishiyama Raisuke , Baba Satoshi , Watahiki Yoichi , Maruo Hirotoshi
Published: March 2015

We describe an unusual case of a 73-year-old woman presenting with a solitary splenic mass 8 cm in diameter and an elevation of serum soluble interleukin-2 receptor level. The preoperative diagnosis was primary malignant lymphoma of the spleen. Splenectomy was conducted. Histological analysis confirmed an inflammatory pseudotumour-like follicular dendritic cell tumour that showed different clinicopathological features from those of the classic follicular dendritic cell tumour. Only 33 cases of inflammatory pseudotumour-like follicular dendritic cell tumour have so far been reported. We discuss the incidence, presentation and management of this rare disease.
Triceps tendon rupture: an uncommon orthopaedic condition
Authors: Bunshah Jamshed Jal , Raghuwanshi Sagar , Sharma Deepak , Pandita Aakash
Published: March 2015

Triceps tendon disruption is a rare orthopaedic injury that can lead to poor outcomes if misdiagnosed or managed inappropriately. This case report illustrates the importance of early, precise diagnosis of triceps rupture by clinical and radiological examination with appropriate management. A weightlifter who had fallen while riding his bike presented with pain, swelling around the posterior aspect of the left arm just above the elbow. Physical examination revealed ecchymosis and weakness in elbow extension. A radiograph of the elbow showed a small fleck of bone proximal to the tip of the olecranon. The patient was initially stabilised. Early intervention in the form of primary tendon repair was performed within 3 days and rehabilitation was started. The patient improved significantly to his best possible functional status with Mayo elbow score of 85. Early intervention was the key to better prognosis.
The effects of maintenance schedules following pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomised controlled trial
Authors: Wilson Andrew M , Browne Paula , Olive Sandra , Clark Allan , Galey Penny , Dix Emma , Woodhouse Helene , Robinson Sue , Wilson Edward C F , Staunton Lindi
Published: March 2015

Objectives

Pulmonary rehabilitation (PR) provides benefit for patients with chronic obstructive pulmonary disease (COPD) in terms of quality of life (QoL) and exercise capacity; however, the effects diminish over time. Our aim was to evaluate a maintenance programme for patients who had completed PR.

Setting

Primary and secondary care PR programmes in Norfolk.

Participants

148 patients with COPD who had completed at least 60% of a standard PR programme were randomised and data are available for 110 patients. Patients had greater than 20 pack year smoking history and less than 80% predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection.

Interventions

Patients were randomised to receive a maintenance programme or standard care. The maintenance programme consisted of 2 h (1 h individually tailored exercise training and 1 h education programme) every 3 months for 1 year.

Primary and secondary outcome measures

The Chronic Respiratory Questionnaire (CRQ) (primary outcome), endurance shuttle walk test (ESWT), EuroQol (EQ5D), hospital anxiety and depression score (HADS), body mass index (BMI), body fat, activity levels (overall score and activity diary) and exacerbations were assessed before and after 12 months.

Results

There was no statistically significant difference between the groups for the change in CRQ dyspnoea score (primary end point) at 12 months which amounted to 0.19 (−0.26 to 0.64) units or other domains of the CRQ. There was no difference in the ESWT duration (−10.06 (−191.16 to 171.03) seconds), BMI, body fat, EQ5D, MET-minutes, activity rating, HADS, exacerbations or admissions.

Conclusions

A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months. We do not recommend that our maintenance programme is adopted. Other methods of sustaining the benefits of PR are required.

Trial registration number

NCT00925171.
Comparative cardiovascular morbidity and mortality in patients taking different insulin regimens for type 2 diabetes: a systematic review
Authors: Price Hilary I , Agnew Meghan D , Gamble John-Michael
Published: March 2015

Objectives

To summarise the literature evaluating the association between different insulin regimens and the incidence of cardiovascular morbidity and mortality in adults with type 2 diabetes.

Design

Systematic review.

Methods

Multiple biomedical databases (The Cochrane Library, PubMed, EMBASE, and International Pharmaceutical Abstracts) were searched from their inception to February 2014. References of included studies were hand searched. Randomised controlled trials (RCTs), cohort studies or case–control studies examining adults (≥18 years) with type 2 diabetes taking any type, dose and/or regimen of insulin were eligible for inclusion in this review.

Outcome measures

Primary outcomes were cardiovascular morbidity and mortality including fatal and/or non-fatal myocardial infarction, fatal and/or non-fatal stroke, major adverse cardiac events and cardiovascular death. All-cause mortality was assessed as a secondary outcome.

Results

Of the 3122 studies identified, 2 RCTs and 6 cohort studies were selected. No case–control studies met the inclusion criteria. The studies examined a total of 109 910 patients. Quantitative synthesis of the results from included studies was not possible due to a large amount of clinical heterogeneity. Each study evaluated cardiovascular outcomes across different insulin-exposure contrasts. RCTs did not identify any difference in cardiovascular risks among a fixed versus variable insulin regimen, or a prandial versus basal regimen, albeit clinically important risks and benefits cannot be ruled out due to wide CIs. Findings from cohort studies were variable with an increased and decreased risk of cardiovascular events and all-cause mortality being reported.

Conclusions

This systematic review of randomised and non-randomised studies identifies a substantive gap in the literature surrounding the cardiovascular morbidity and mortality of patients using different regimens of insulin. There is a need for more consistent high-quality evidence investigating the impact of insulin use on cardiovascular outcomes in patients with type 2 diabetes.

Trial registration number

PROSPERO: CRD42014007631.
Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus—the Hopkins Lupus Cohort
Authors: Al Sawah Sarah , Zhang Xiang , Zhu Baojin , Magder Laurence S , Foster Shonda A , Iikuni Noriko , Petri Michelle
Published: March 2015

Objectives

The impact of corticosteroids on the risk of organ damage in the context of clinical end points endorsed in some systemic lupus erythematosus (SLE) clinical trials is underexplored.

Methods

We analysed data from the Hopkins Lupus Cohort using Cox proportional hazards models to understand the impact of exposure to different corticosteroid doses on the risk of developing any new organ damage or any new organ damage at the individual organ systems over time.

Results

Mean prior prednisone dose, recent disease activity and immunosuppressant use during follow-up, as well as organ damage score at cohort entry, were significant independent predictors of the risk of developing any new organ damage. Even after adjustment for recent disease activity, there was a dose-response relationship across the different levels of exposure to prednisone during follow-up and the risk of developing any new organ damage. The risk more than doubled in patients exposed to a mean prior prednisone dose of ≥20 mg/day versus <7.5 mg/day (HR=2.514, p<0.001). It was estimated that a 1 mg/day increase in prior prednisone dose during follow-up was associated with a 2.8% increase in the risk of developing new organ damage. For individual organ systems, exposure to a mean prior prednisone dose of ≥7.5 mg/day versus <7.5 mg/day significantly increased the risk of developing cataracts (HR=2.41, p<0.001), osteoporotic fractures (HR=2.16, p<0.001) and cardiovascular damage (HR=1.54, p=0.041), but showed no significant difference for renal damage (HR=1.44, p=0.163) or for other individual organ systems.

Conclusions

Organ damage in SLE is multifactorial; corticosteroid treatment and disease activity play a role.
Influence of the proposed Site C hydroelectric project on the ice regime of the Peace River
Authors: Jasek Martin , Pryse-Phillips Amy
Published: March 2015

The objectives of the study were to describe the existing ice conditions in the Peace River and to predict changes as a result of the proposed Site C Clean Energy Project (the Project). The analyses of changes due to the Project were conducted using the CRISSP and PRTIGM models. Sixteen winters were simulated to provide a representative range of meteorological conditions on which to base the conclusions of the study. Potential changes are described in terms of the following ice characteristics: maximum upstream extent of ice cover; timing of ice cover formation and break-up; freeze-up and break-up water levels at the Town of Peace River; ice thickness; changes in ice conditions relevant for river ice crossings. The analyses also included predicting changes in these ice characteristics due to the combined influence of the Project and the proposed Dunvegan Hydro Project in Alberta. Two future climate scenarios were also considered.
Protective effects of polyethylene oxide on the vascular and organ function of rats with severe hemorrhagic shock
Authors: Li Qiang , Huang Tao , Dong Zhen
Published: March 2015

This study examined the effects of polyethylene oxide (PEO) on the survival rate, hemodynamics, blood gas indexes, lactic acid levels, microcirculation, and inflammatory cytokine levels in rats subjected to severe hemorrhagic shock. The shocked rats were resuscitated with either Ringer’s lactate solution or 20 ppm of PEO in Ringer’s lactate solution for 1 h. It was found that infusion of PEO effectively improved the survival, metabolic acidosis, oxygen delivery, hyperlactacidemia, tissue perfusion, and inflammatory responses of rats subjected to hemorrhagic shock. In addition, we found, for the first time, that PEO showed protective effects on hepatic and renal injury, as evidenced by the significant decreases in the elevated levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine caused by shock induction after infusion of PEO (p < 0.05, 60 min post-resuscitation by comparison with pre-resuscitation). All of these findings indicate that PEO exhibits strong therapeutic effects under conditions of severe hemorrhagic shock,which also provides theoretical and experimental bases for the clinical use of PEO.
Emodin is identified as the active component of ether extracts from Rhizoma Polygoni Cuspidati, for anti-MRSA activity
Authors: Cao Feng , Peng Wei , Li Xiaoli , Liu Ming , Li Bin , Qin Rongxin , Jiang Weiwei , Cen Yanyan , Pan Xichun , Yan Zifei , Xiao Kangkang , Zhou Hong
Published: March 2015

This study investigated the anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity and chemical compositions of ether extracts from Rhizoma Polygoni Cuspidati (ET-RPC). Significant anti-MRSA activities of ET-RPC against MRSA252 and MRSA clinical strains were tested in in vitro antibacterial experiments, such as inhibition zone diameter test, minimal inhibitory concentration test, and dynamic bacterial growth assay. Subsequently, 7 major compounds of ET-RPC were purified and identified as polydatin, resveratrol-4-O-d-(6′-galloyl)-glucopyranoside, resveratrol, torachryson-8-O-glucoside, emodin-8-O-glucoside, 6-hydroxy-emodin, and emodin using liquid chromatography – electrospray ionization – tandem mass spectrometry. After investigation of anti-MRSA activities of the 7 major compounds, only emodin had significant anti-MRSA activity. Further, transmission electron microscopy was used to observe morphological changes in the cell wall of MRSA252, and the result revealed that emodin could damage the integrity of cell wall, leading to loss of intracellular components. In summary, our results showed ET-RPC could significantly inhibit bacterial growth of MRSA strains. Emodin was identified as the major compound with anti-MRSA activity; this activity was related to destruction of the integrity of the cell wall and cell membrane.
Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes
Authors: Sturza Adrian , Duicu Oana M. , Vaduva Adrian , Dănilă Maria D. , Noveanu Lavinia , Varró András , Muntean Danina M.
Published: March 2015

Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H2O2 production (ferrous oxidation – xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H2O2, to the endothelial dysfunction associated with experimental diabetes.
Fractional Laplacian on the torus
Authors: Roncal Luz , Stinga Pablo Raúl
Published: March 2015

We study the fractional Laplacian [Formula: see text] on the [Formula: see text]-dimensional torus [Formula: see text], [Formula: see text]. First, we present a general extension problem that describes any fractional power [Formula: see text], [Formula: see text], where [Formula: see text] is a general nonnegative self-adjoint operator defined in an [Formula: see text]-space. This generalizes to all [Formula: see text] and to a large class of operators the previous known results by Caffarelli and Silvestre. In particular, it applies to the fractional Laplacian on the torus. The extension problem is used to prove interior and boundary Harnack’s inequalities for [Formula: see text], when [Formula: see text]. We deduce regularity estimates on Hölder, Lipschitz and Zygmund spaces. Finally, we obtain the pointwise integro-differential formula for the operator. Our method is based on the semigroup language approach.
EFFECTS OF ACUTE HYPERGLYCEMIA AND INSULIN INTERVENTION ON THE SPONTANEOUS FIELD POTENTIAL OF SINOATRIAL NODE TISSUE BY USING MICROELECTRODE ARRAYS
Authors: FENG YU , CAO HUI , ZHANG YANBIN
Published: March 2015

Traditional studies on the relationship between hyperglycemia and heart diseases generally focused on the impact of chronic and long-term effect of diabetes on cardiac functions. Most of the methods were culturing myocardial cells and giving outside stimulations. However, recent studies show that acute hyperglycemia might play a significant role in spontaneous cardiac electrophysiology. In this research we applied microelectrode arrays (MEA) to record the spontaneous sinoatrial node field potentials of C57/BL6J mice and analyzed the effects of different glucose concentrations in time domain and frequency domain by using statistical method, vector maps and fast Fourier transform (FFT). Meanwhile, we studied the effects of insulin interference in the experimental process. When the concentration of the glucose solution was greater than 40 mmol/L, the spontaneous sinoatrial node field potential changed markedly. In the time domain, the amplitude decreased rapidly and the conductive characteristics were disordered. In the frequency domain, the two spectrum peaks decreased rapidly. These changes were irreversible. However, insulin preconditioning could inhibit the impact of high glucose.