bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza Hemagglutinin (HA) Stem Region Mutations That Stabilize or Destabilize the Structure of Multiple HA Subtypes
Authors: Byrd-Leotis Lauren , Galloway Summer E. , Agbogu Evangeline , Steinhauer David A.
Published: February 2015

Influenza A viruses enter host cells through endosomes, where acidification induces irreversible conformational changes of the viral hemagglutinin (HA) that drive the membrane fusion process. The prefusion conformation of the HA is metastable, and the pH of fusion can vary significantly among HA strains and subtypes. Furthermore, an accumulating body of evidence implicates HA stability properties as partial determinants of influenza host range, transmission phenotype, and pathogenic potential. Although previous studies have identified HA mutations that can affect HA stability, these have been limited to a small selection of HA strains and subtypes. Here we report a mutational analysis of HA stability utilizing a panel of expressed HAs representing a broad range of HA subtypes and strains, including avian representatives across the phylogenetic spectrum and several human strains. We focused on two highly conserved residues in the HA stem region: HA2 position 58, located at the membrane distal tip of the short helix of the hairpin loop structure, and HA2 position 112, located in the long helix in proximity to the fusion peptide. We demonstrate that a K58I mutation confers an acid-stable phenotype for nearly all HAs examined, whereas a D112G mutation consistently leads to elevated fusion pH. The results enhance our understanding of HA stability across multiple subtypes and provide an additional tool for risk assessment for circulating strains that may have other hallmarks of human adaptation. Furthermore, the K58I mutants, in particular, may be of interest for potential use in the development of vaccines with improved stability profiles.

IMPORTANCE
The influenza A hemagglutinin glycoprotein (HA) mediates the receptor binding and membrane fusion functions that are essential for virus entry into host cells. While receptor binding has long been recognized for its role in host species specificity and transmission, membrane fusion and associated properties of HA stability have only recently been appreciated as potential determinants. We show here that mutations can be introduced at highly conserved positions to stabilize or destabilize the HA structure of multiple HA subtypes, expanding our knowledge base for this important phenotype. The practical implications of these findings extend to the field of vaccine design, since the HA mutations characterized here could potentially be utilized across a broad spectrum of influenza virus subtypes to improve the stability of vaccine strains or components.
AP-2-Associated Protein Kinase 1 and Cyclin G-Associated Kinase Regulate Hepatitis C Virus Entry and Are Potential Drug Targets
Authors: Neveu Gregory , Ziv-Av Amotz , Barouch-Bentov Rina , Berkerman Elena , Mulholland Jon , Einav Shirit
Published: February 2015

Hepatitis C virus (HCV) enters its target cell via clathrin-mediated endocytosis. AP-2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK) are host kinases that regulate clathrin adaptor protein (AP)-mediated trafficking in the endocytic and secretory pathways. We previously reported that AAK1 and GAK regulate HCV assembly by stimulating binding of the μ subunit of AP-2, AP2M1, to HCV core protein. We also discovered that AAK1 and GAK inhibitors, including the approved anticancer drugs sunitinib and erlotinib, could block HCV assembly. Here, we hypothesized that AAK1 and GAK regulate HCV entry independently of their effect on HCV assembly. Indeed, silencing AAK1 and GAK expression inhibited entry of pseudoparticles and cell culture grown-HCV and internalization of Dil-labeled HCV particles with no effect on HCV attachment or RNA replication. AAK1 or GAK depletion impaired epidermal growth factor (EGF)-mediated enhanced HCV entry and endocytosis of EGF receptor (EGFR), an HCV entry cofactor and erlotinib's cancer target. Moreover, either RNA interference-mediated depletion of AP2M1 or NUMB, each a substrate of AAK1 and/or GAK, or overexpression of either an AP2M1 or NUMB phosphorylation site mutant inhibited HCV entry. Last, in addition to affecting assembly, sunitinib and erlotinib inhibited HCV entry at a postbinding step, their combination was synergistic, and their antiviral effect was reversed by either AAK1 or GAK overexpression. Together, these results validate AAK1 and GAK as critical regulators of HCV entry that function in part by activating EGFR, AP2M1, and NUMB and as the molecular targets underlying the antiviral effect of sunitinib and erlotinib (in addition to EGFR), respectively.

IMPORTANCE
Understanding the host pathways hijacked by HCV is critical for developing host-centered anti-HCV approaches. Entry represents a potential target for antiviral strategies; however, no FDA-approved HCV entry inhibitors are currently available. We reported that two host kinases, AAK1 and GAK, regulate HCV assembly. Here, we provide evidence that AAK1 and GAK regulate HCV entry independently of their role in HCV assembly and define the mechanisms underlying AAK1- and GAK-mediated HCV entry. By regulating temporally distinct steps in the HCV life cycle, AAK1 and GAK represent “master regulators” of HCV infection and potential targets for antiviral strategies. Indeed, approved anticancer drugs that potently inhibit AAK1 or GAK inhibit HCV entry in addition to assembly. These results contribute to an understanding of the mechanisms of HCV entry and reveal attractive host targets for antiviral strategies as well as approved candidate inhibitors of these targets, with potential implications for other viruses that hijack clathrin-mediated pathways.
Scanning Mutagenesis Studies Reveal a Potential Intramolecular Interaction within the C-Terminal Half of Dengue Virus NS2A Involved in Viral RNA Replication and Virus Assembly and Secretion
Authors: Wu Ren-Huang , Tsai Ming-Han , Chao Day-Yu , Yueh Andrew
Published: February 2015

The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMSs; pTMS1 to pTMS8). NS2A has been shown to participate in RNA replication, virion assembly, and the host antiviral response. However, the role of the amino acid residues within the pTMS regions of NS2A during the virus life cycle is poorly understood. In the study described here, we explored the function of DENV NS2A by introducing a series of double or triple alanine substitutions into the C-terminal half (pTMS4 to pTMS8) of NS2A in the context of a DENV infectious clone or subgenomic replicon. Fourteen (8 within pTMS8) of 35 NS2A mutants displayed a lethal phenotype due to impairment of RNA replication by a replicon assay. Three NS2A mutants with mutations within pTMS7, the CM20, CM25, and CM27 mutants, displayed similar phenotypes, low virus yields (>100-fold reduction), wild-type-like replicon activity, and low infectious virus-like particle yields by transient
trans
-packaging experiments, suggesting a defect in virus assembly and secretion. The sequencing of revertant viruses derived from CM20, CM25, and CM27 mutant viruses revealed a consensus reversion mutation, leucine (L) to phenylalanine (F), at codon 181 within pTMS7. The introduction of an L181F mutation into a full-length NS2A mutant, i.e., the CM20, CM25, and CM27 constructs, completely restored wild-type infectivity. Notably, L181F also substantially rescued the other severely RNA replication-defective mutants with mutations within pTMS4, pTMS6, and pTMS8, i.e., the CM2, CM3, CM13, CM31, and CM32 mutants. In conclusion, the results revealed the essential roles of pTMS4 to pTMS8 of NS2A in RNA replication and/or virus assembly and secretion. The intramolecular interaction between pTMS7 and pTMS4, pTMS6, or pTMS8 of the NS2A protein was also implicated.

IMPORTANCE
The reported characterization of the C-terminal half of dengue virus NS2A is the first comprehensive mutagenesis study to investigate the function of flavivirus NS2A involved in the steps of the virus life cycle. In particular, detailed mapping of the amino acid residues within the predicted transmembrane segments (pTMSs) of NS2A involved in RNA replication and/or virus assembly and secretion was performed. A revertant genetics study also revealed that L181F within pTMS7 is a consensus reversion mutation that rescues both RNA replication-defective and virus assembly- and secretion-defective mutants with mutations within the other three pTMSs of NS2A. Collectively, these findings elucidate the role played by NS2A during the virus life cycle, possibly through the intricate intramolecular interaction between pTMS7 and other pTMSs within the NS2A protein.
Isolation, Genetic Characterization, and Seroprevalence of Adana Virus, a Novel Phlebovirus Belonging to the Salehabad Virus Complex, in Turkey
Authors: Alkan Cigdem , Alwassouf Sulaf , Piorkowski Géraldine , Bichaud Laurence , Tezcan Seda , Dincer Ender , Ergunay Koray , Ozbel Yusuf , Alten Bulent , de Lamballerie Xavier , Charrel Rémi N.
Published: February 2015

A new phlebovirus, Adana virus, was isolated from a pool of
Phlebotomus
spp. (
Diptera
;
Psychodidae
) in the province of Adana, in the Mediterranean region of Turkey. Genetic analysis based on complete coding of genomic sequences indicated that Adana virus belongs to the
Salehabad virus
species of the genus
Phlebovirus
in the family
Bunyaviridae
. Adana virus is the third virus of the
Salehabad virus
species for which the complete sequence has been determined. To understand the epidemiology of Adana virus, a seroprevalence study using microneutralization assay was performed to detect the presence of specific antibodies in human and domestic animal sera collected in Adana as well as Mersin province, located 147 km west of Adana. The results demonstrate that the virus is present in both provinces. High seroprevalence rates in goats, sheep, and dogs support intensive exposure to Adana virus in the region, which has not been previously reported for any virus included in the Salehabad serocomplex; however, low seroprevalence rates in humans suggest that Adana virus is not likely to constitute an important public health problem in exposed human populations, but this deserves further studies.

IMPORTANCE
Until recently, in the genus
Phlebovirus
, the
Salehabad virus
species consisted of two viruses: Salehabad virus, isolated from sand flies in Iran, and Arbia virus, isolated from sand flies in Italy. Here we present the isolation and complete genome characterization of the Adana virus, which we propose to be included in the
Salehabad virus
species. To our knowledge, this is the first report of the isolation and complete genome characterization, from sand flies in Turkey, of a Salehabad virus-related phlebovirus with supporting seropositivity in the Mediterranean, Aegean, and Central Anatolia regions, where phleboviruses have been circulating and causing outbreaks. Salehabad species viruses have generally been considered to be a group of viruses with little medical or veterinary interest. This view deserves to be revisited according to our results, which indicate a high animal infection rate of Adana virus and recent evidence of human infection with Adria virus in Greece.
Rice Stripe Tenuivirus Nonstructural Protein 3 Hijacks the 26S Proteasome of the Small Brown Planthopper via Direct Interaction with Regulatory Particle Non-ATPase Subunit 3
Authors: Xu Yi , Wu Jianxiang , Fu Shuai , Li Chenyang , Zhu Zeng-Rong , Zhou Xueping
Published: February 2015

The ubiquitin/26S proteasome system plays a vital role in regulating host defenses against pathogens. Previous studies have highlighted different roles for the ubiquitin/26S proteasome in defense during virus infection in both mammals and plants, but their role in the vectors that transmit those viruses is still unclear. In this study, we determined that the 26S proteasome is present in the small brown planthopper (SBPH) (
Laodelphgax striatellus
) and has components similar to those in plants and mammals. There was an increase in the accumulation of
Rice stripe virus
(RSV) in the transmitting vector SBPH after disrupting the 26S proteasome, indicating that the SBPH 26S proteasome plays a role in defense against RSV infection by regulating RSV accumulation. Yeast two-hybrid analysis determined that a subunit of the 26S proteasome, named RPN3, could interact with RSV NS3. Transient overexpression of RPN3 had no effect on the RNA silencing suppressor activity of RSV NS3. However, NS3 could inhibit the ability of SBPH
rpn
3 to complement an
rpn
3 mutation in yeast. Our findings also indicate that the direct interaction between RPN3 and NS3 was responsible for inhibiting the complementation ability of RPN3.
In vivo
, we found an accumulation of ubiquitinated protein in SBPH tissues where the RSV titer was high, and silencing of
rpn
3 resulted in malfunction of the SBPH proteasome-mediated proteolysis. Consequently, viruliferous SBPH in which RPN3 was repressed transmitted the virus more effectively as a result of higher accumulation of RSV. Our results suggest that the RSV NS3 protein is able to hijack the 26S proteasome in SBPH via a direct interaction with the RPN3 subunit to attenuate the host defense response.

IMPORTANCE
We show, for the first time, that the 26S proteasome components are present in the small brown planthopper and play a role in defense against its vectored plant virus (RSV). In turn, RSV encodes a protein that subverts the SBPH 26S proteasome via direct interaction with the 26S proteasome subunit RPN3. Our results imply that the molecular arms race observed in plant hosts can be extended to the insect vector that transmits those viruses.
Dynamics of the Cytotoxic T Cell Response to a Model of Acute Viral Infection
Authors: DeWitt William S. , Emerson Ryan O. , Lindau Paul , Vignali Marissa , Snyder Thomas M. , Desmarais Cindy , Sanders Catherine , Utsugi Heidi , Warren Edus H. , McElrath Juliana , Makar Karen W. , Wald Anna , Robins Harlan S.
Published: February 2015

A detailed characterization of the dynamics and breadth of the immune response to an acute viral infection, as well as the determinants of recruitment to immunological memory, can greatly contribute to our basic understanding of the mechanics of the human immune system and can ultimately guide the design of effective vaccines. In addition to neutralizing antibodies, T cells have been shown to be critical for the effective resolution of acute viral infections. We report the first in-depth analysis of the dynamics of the CD8
+
T cell repertoire at the level of individual T cell clonal lineages upon vaccination of human volunteers with a single dose of YF-17D. This live attenuated yellow fever virus vaccine yields sterile, long-term immunity and has been previously used as a model to understand the immune response to a controlled acute viral infection. We identified and enumerated unique CD8
+
T cell clones specifically induced by this vaccine through a combined experimental and statistical approach that included high-throughput sequencing of the CDR3 variable region of the T cell receptor β-chain and an algorithm that detected significantly expanded T cell clones. This allowed us to establish that (i) on average, ∼2,000 CD8
+
T cell clones were induced by YF-17D, (ii) 5 to 6% of the responding clones were recruited to long-term memory 3 months postvaccination, (iii) the most highly expanded effector clones were preferentially recruited to the memory compartment, and (iv) a fraction of the YF-17D-induced clones could be identified from peripheral blood lymphocytes solely by measuring clonal expansion.

IMPORTANCE
The exhaustive investigation of pathogen-induced effector T cells is essential to accurately quantify the dynamics of the human immune response. The yellow fever vaccine (YFV) has been broadly used as a model to understand how a controlled, self-resolving acute viral infection induces an effective and long-term protective immune response. Here, we extend this previous work by reporting the identity of activated effector T cell clones that expand in response to the YFV 2 weeks postvaccination (as defined by their unique T cell receptor gene sequence) and by tracking clones that enter the memory compartment 3 months postvaccination. This is the first study to use high-throughput sequencing of immune cells to characterize the breadth of the antiviral effector cell response and to determine the contribution of unique virus-induced clones to the long-lived memory T cell repertoire. Thus, this study establishes a benchmark against which future vaccines can be compared to predict their efficacy.
Stress Granule Components G3BP1 and G3BP2 Play a Proviral Role Early in Chikungunya Virus Replication
Authors: Scholte Florine E. M. , Tas Ali , Albulescu Irina C. , Žusinaite Eva , Merits Andres , Snijder Eric J. , van Hemert Martijn J.
Published: February 2015

Stress granules (SGs) are protein-mRNA aggregates that are formed in response to environmental stresses, resulting in translational inhibition. SGs are generally believed to play an antiviral role and are manipulated by many viruses, including various alphaviruses. GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) is a key component and commonly used marker of SGs. Its homolog G3BP2 is a less extensively studied SG component. Here, we demonstrate that Chikungunya virus (CHIKV) infection induces cytoplasmic G3BP1- and G3BP2-containing granules that differ from bona fide SGs in terms of morphology, composition, and behavior. For several Old World alphaviruses it has been shown that nonstructural protein 3 (nsP3) interacts with G3BPs, presumably to inhibit SG formation, and we have confirmed this interaction in CHIKV-infected cells. Surprisingly, CHIKV also relied on G3BPs for efficient replication, as simultaneous depletion of G3BP1 and G3BP2 reduced viral RNA levels, CHIKV protein expression, and viral progeny titers. The G3BPs colocalized with CHIKV nsP2 and nsP3 in cytoplasmic foci, but no colocalization with nsP1, nsP4, or dsRNA was observed. Furthermore, G3BPs could not be detected in a cellular fraction enriched for CHIKV replication/transcription complexes, suggesting that they are not directly involved in CHIKV RNA synthesis. Depletion of G3BPs did not affect viral entry, translation of incoming genomes, or nonstructural polyprotein processing but resulted in severely reduced levels of negative-stranded (and consequently also positive-stranded) RNA. This suggests a role for the G3BPs in the switch from translation to genome amplification, although the exact mechanism by which they act remains to be explored.

IMPORTANCE
Chikungunya virus (CHIKV) causes a severe polyarthritis that has affected millions of people since its reemergence in 2004. The lack of approved vaccines or therapeutic options and the ongoing explosive outbreak in the Caribbean underline the importance of better understanding CHIKV replication. Stress granules (SGs) are cytoplasmic protein-mRNA aggregates formed in response to various stresses, including viral infection. The RNA-binding proteins G3BP1 and G3BP2 are essential SG components. SG formation and the resulting translational inhibition are generally considered an antiviral response, and many viruses manipulate or block this process. Late in infection, we and others have observed CHIKV nonstructural protein 3 in cytoplasmic G3BP1- and G3BP2-containing granules. These virally induced foci differed from true SGs and did not appear to represent replication complexes. Surprisingly, we found that G3BP1 and G3BP2 were also needed for efficient CHIKV replication, likely by facilitating the switch from translation to genome amplification early in infection.
Fine Mapping and Characterization of the L-Polymerase-Binding Domain of the Respiratory Syncytial Virus Phosphoprotein
Authors: Sourimant Julien , Rameix-Welti Marie-Anne , Gaillard Anne-Laure , Chevret Didier , Galloux Marie , Gault Elyanne , Eléouët Jean-François
Published: February 2015

The minimum requirement for an active RNA-dependent RNA polymerase of respiratory syncytial virus (RSV) is a complex made of two viral proteins, the polymerase large protein (L) and the phosphoprotein (P). Here we have investigated the domain on P that is responsible for this critical P-L interaction. By use of recombinant proteins and serial deletions, an L binding site was mapped in the C-terminal region of P, just upstream of the N-RNA binding site. The role of this molecular recognition element of about 30 amino acid residues in the L-P interaction and RNA polymerase activity was evaluated
in cellula
using an RSV minigenome system and site-directed mutagenesis. The results highlighted the critical role of hydrophobic residues located in this region.

IMPORTANCE
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants. Since no vaccine and no good antivirals against RSV are available, it is essential to better understand how the viral machinery functions in order to develop new antiviral strategies. Like all negative-strand RNA viruses, RSV codes for its own machinery to replicate and transcribe its genome. The core of this machinery is composed of two proteins, the phosphoprotein (P) and the large protein (L). Here, using recombinant proteins, we have mapped and characterized the P domain responsible for this L-P interaction and the formation of an active L-P complex. These findings extend our understanding of the mechanism of action of RSV RNA polymerase and allow us to define a new target for the development of drugs against RSV.
Fighting Fire with Fire: Endogenous Retrovirus Envelopes as Restriction Factors
Authors: Malfavon-Borja Ray , Feschotte Cédric
Published: February 2015

A considerable portion of vertebrate genomes are made up of endogenous retroviruses (ERVs). While aberrant or uncontrolled ERV expression has been perceived as a potential cause of disease, there is mounting evidence that some ERVs have become integral components of normal host development and physiology. Here, we revisit the longstanding concept that some of the gene products encoded by ERVs and other endogenous viral elements may offer to the host protection against viral infection. Notably, proteins produced from
envelope
(
env
) genes have been shown to act as restriction factors against related exogenous retroviruses in chickens, sheep, mice, and cats. Based on the proposed mode of restriction and the domain architecture of known antiretroviral
env
, we argue that many more
env
gene-derived restriction factors await discovery in vertebrate genomes, including the human genome.
Exploring the Existence of Lipid Rafts in Bacteria
Authors: Bramkamp Marc , Lopez Daniel
Published: February 2015

An interesting concept in the organization of cellular membranes is the proposed existence of lipid rafts. Membranes of eukaryotic cells organize signal transduction proteins into membrane rafts or lipid rafts that are enriched in particular lipids such as cholesterol and are important for the correct functionality of diverse cellular processes. The assembly of lipid rafts in eukaryotes has been considered a fundamental step during the evolution of cellular complexity, suggesting that bacteria and archaea were organisms too simple to require such a sophisticated organization of their cellular membranes. However, it was recently discovered that bacteria organize many signal transduction, protein secretion, and transport processes in functional membrane microdomains, which are equivalent to the lipid rafts of eukaryotic cells. This review contains the most significant advances during the last 4 years in understanding the structural and biological role of lipid rafts in bacteria. Furthermore, this review shows a detailed description of a number of molecular and genetic approaches related to the discovery of bacterial lipid rafts as well as an overview of the group of tentative lipid-protein and protein-protein interactions that give consistency to these sophisticated signaling platforms. Additional data suggesting that lipid rafts are widely distributed in bacteria are presented in this review. Therefore, we discuss the available techniques and optimized protocols for the purification and analysis of raft-associated proteins in various bacterial species to aid in the study of bacterial lipid rafts in other laboratories that could be interested in this topic. Overall, the discovery of lipid rafts in bacteria reveals a new level of sophistication in signal transduction and membrane organization that was unexpected for bacteria and shows that bacteria are more complex than previously appreciated.
The failing heart: a bad case of the ‘flu’
Authors: Wilson Julie , Akhtar Mohammed Majid , Modi Bhavik , Emmanuel Julian
Published: February 2015

A 24-year-old Nepali man presented to hospital with a short history of feeling unwell with a flu-like illness. He subsequently went into acute renal failure requiring several sessions of renal replacement therapy by haemofiltration. The underlying aetiology of his renal failure was unclear. His renal function recovered following haemofiltration and he was discharged home with a plan for outpatient follow-up and investigations. He re-presented to hospital 6 days later with severe fluid overload. Echocardiogram was suggestive of impaired left ventricular systolic function; subsequent cardiac MRI confirmed this and was indicative of a dilated cardiomyopathy. A diagnosis of dilated cardiomyopathy with cardiorenal syndrome was made, most likely secondary to viral myocarditis in view of his initial presentation. He was diuresed and treated with prognostic medications for heart failure. His symptoms resolved and on subsequent outpatient review he was feeling well.
Electroacupuncture as a complement to usual care for patients with non-acute pain after back surgery: a study protocol for a pilot randomised controlled trial
Authors: Hwang Man-Suk , Heo Kwang-Ho , Cho Hyun-Woo , Shin Byung-Cheul , Lee Hyeon-Yeop , Heo In , Kim Nam-Kwen , Choi Byung-Kwan , Son Dong-Wuk , Hwang Eui-Hyoung
Published: February 2015

Introduction

Recurrent or persistent low back pain is common after back surgery but is typically not well controlled. Previous randomised controlled trials on non-acute pain after back surgery were flawed. In this article, the design and protocol of a randomised controlled trial to treat pain and improve function after back surgery are described.

Methods and analysis

This study is a pilot randomised, active-controlled, assessor-blinded trial. Patients with recurring or persistent low back pain after back surgery, defined as a visual analogue scale value of ≥50 mm, with or without leg pain, will be randomly assigned to an electroacupuncture-plus-usual-care group or to a usual-care-only group. Patients assigned to both groups will have usual care management, including physical therapy and patient education, twice a week during a 4-week treatment period that would begin at randomisation. Patients assigned to the electroacupuncture-plus-usual-care group will also have electroacupuncture twice a week during the 4-week treatment period. The primary outcome will be measured with the 100 mm pain visual analogue scale of low back pain by a blinded evaluator. Secondary outcomes will be measured with the EuroQol 5-Dimension and the Oswestry Disability Index. The primary and secondary outcomes will be measured at 4 and 8 weeks after treatment.

Ethics and dissemination

Written informed consent will be obtained from all participants. This study was approved by the Institutional Review Board (IRB) of Pusan National University Korean Hospital in September 2013 (IRB approval number 2013012). The study findings will be published in peer-reviewed journals and presented at national and international conferences.

Trial registration number

This trial was registered with the US National Institutes of Health Clinical Trials Registry:NCT01966250.
The equine reception experience
Authors: Lambert Alison
Published: February 2015

Often the first port of call for clients, reception is an important part of any practice. It is all the more vital for equine practices as horse owners may rarely visit the premises. Alison Lambert explains how to make the most of this crucial point of contact, to increase client experience and appointments.
Feather plucking in parrots
Authors: Kubiak Marie
Published: February 2015

Feather plucking, a common problem in pet parrots, can be a result of behavioural or medical influences. This article focuses primarily on the psychological and behavioural causes of feather‐damaging behaviour, where stress or frustration triggers secondary self‐trauma.
Management of non‐lymphomatous small intestinal tumours in dogs and cats
Authors: Shales Chris
Published: February 2015

Non‐lymphoid small intestinal neoplasia form a small but important part of the veterinary surgical caseload. These tumours/cancers provide particular challenges to clinicians due to the paucity, heterogeneity and retrospective nature of the research available in this field. In addition, many published studies were primarily intended as pathology rather than clinical publications. This article aims to review the literature and draw conclusions where appropriate relating to the biological behaviour, investigation and treatment of these tumours.
Comments on the dilemma in the January issue: ‘Value and treatment’
Authors: Brown Richard
Published: February 2015

The dilemma in the January issue considered the use of antimicrobials in farm animals in light of current concerns about resistance. In particular, it asked whether some sick animals would be more valuable to society if they were killed rather than being treated with antimicrobials, and whether that would make this practice desirable (In Practice, January 2015, volume 37, pages 46‐47). Paul Roger noted that the dilemma started with the assumption that certain classes of animal were kept for the benefit of people and that society determined the nature of that relationship. He pointed out that working within evidence‐based veterinary medicine would make it difficult to choose the killing of sick animals when there might be realistic expectations of successful treatment, but that the situation was complicated by the fact that clinical diagnosis and treatment were not exact sciences. He proposed using the five freedoms of the Animal Welfare Act 2006 as a basis for tackling the dilemma, adding that the motives for killing an animal under such circumstances would have to be in line with the principles of biomedical ethics.
High sensitivity C reactive protein as a prognostic marker in patients with mild to moderate aortic valve stenosis during lipid-lowering treatment: an SEAS substudy
Authors: Blyme Adam , Asferg Camilla , Nielsen Olav W , Sehestedt Thomas , Kesäniemi Y Antero , Gohlke-Bärwolf Christa , Boman Kurt , Willenheimer Ronnie , Ray Simon , Nienaber Christoph A , Rossebø Anne , Wachtell Kristian , Olsen Michael H
Published: February 2015

Aims

To assess the prognostic importance of high-sensitive C reactive protein (hsCRP) in patients with mild to moderate aortic valve stenosis during placebo or simvastatin/ezetimibe treatment in Simvastatin and Ezetimibe in Aortic Stenosis (SEAS).

Methods and results

In 1620 SEAS patients, we measured lipids and hsCRP at baseline and after 1 year of treatment and registered during 4 years of follow-up major cardiovascular events (MCE) composed of ischaemic cardiovascular events (ICE) and aortic valve-related events (AVE). Simvastatin/ezetimibe reduced low-density lipoprotein cholesterol (3.49 (2.94 to 4.15) to 1.32 (1.02 to 1.69) vs 3.46 (2.92 to 4.08) to 3.34 (2.81 to 3.92) mmol/L) and hsCRP (2.1 (0.9 to 4.1) to 1.2 (0.6 to 2.4) vs 2.2 (0.9 to 4.9) to 1.8 (0.85 to 4.35) mg/L, all p<0.05) during the first year of treatment. In multivariable Cox regression analysis adjusting for traditional risk factors and baseline hsCRP, ICE was associated with a 1-year increase of hsCRP (HR=1.19 (95% CI 1.12 to 1.25), p<0.001) but not with active treatment (HRTreatment=0.86 (0.67 to 1.13), p=0.28). Patients in the top quartile of baseline hsCRP versus the rest were associated with a higher risk of MCE (HR=1.34(1.09 to 1.64), p=0.02). The prognostic benefit of reduction in hsCRP after 1 year was significantly larger (p<0.01 for interaction) in patients with high versus low baseline hsCRP; hence, a reduction in hsCRP abolished the difference in incidence of MCE between high versus low baseline hsCRP in patients with reduced hsCRP (31.1 vs 31.9%, NS) in contrast to patients with increased hsCRP.

Conclusions

The treatment-associated reduction in ICE was in part related to a reduction in hsCRP but not in lipids. hsCRP reduction was associated with less MCE, especially in patients with high baseline hsCRP.

Trial registration

NCT00092677.
Point of care information services: a platform for self-directed continuing medical education for front line decision makers
Authors: Moja Lorenzo , Kwag Koren Hyogene
Published: February 2015

The structure and aim of continuing medical education (CME) is shifting from the passive transmission of knowledge to a competency-based model focused on professional development. Self-directed learning is emerging as the foremost educational method for advancing competency-based CME. In a field marked by the constant expansion of knowledge, self-directed learning allows physicians to tailor their learning strategy to meet the information needs of practice. Point of care information services are innovative tools that provide health professionals with digested evidence at the front line to guide decision making. By mobilising self-directing learning to meet the information needs of clinicians at the bedside, point of care information services represent a promising platform for competency-based CME. Several points, however, must be considered to enhance the accessibility and development of these tools to improve competency-based CME and the quality of care.
The journey that took a Barr to the bar
Authors: Barr Alistair
Published: February 2015

To build on an active veterinary career, and to sidestep the risk of succumbing to a bout of what he calls ‘past‐presidentitis’ – failing to let go – Alistair Barr became a student again and did a law degree, before being called to the bar in 2012
Entanglement entropy of fractional quantum Hall systems with short range disorder
Authors: Friedman B. A. , Levine G. C.
Published: February 2015

The critical value of the mobility for which the ν = 5/2 quantum Hall effect is destroyed by short range disorder is determined from an earlier calculation of the entanglement entropy. The value μ = 2.0 ×106 cm 2/ Vs agrees well with experiment. This agreement is particularly significant in that there are no adjustable parameters. Entanglement entropy versus disorder strength for ν = 1/2, ν = 9/2 and ν = 7/3 is calculated. For ν = 1/2 there is no evidence for a transition for the disorder strengths considered; for ν = 9/2 there appears to be a stripe-liquid transition. For ν = 7/3 there again appears to be a transition at similar value of the disorder strength as the ν = 5/2 transition but there are stronger finite size effects.
Improved Particle Swarm Optimizer with Dynamically Adjusted Search Space and Velocity Limits for Global Optimization
Authors: Adewumi Aderemi Oluyinka , Arasomwan Akugbe Martins
Published: February 2015

This paper presents an improved particle swarm optimization (PSO) technique for global optimization. Many variants of the technique have been proposed in literature. However, two major things characterize many of these variants namely, static search space and velocity limits, which bound their flexibilities in obtaining optimal solutions for many optimization problems. Furthermore, the problem of premature convergence persists in many variants despite the introduction of additional parameters such as inertia weight and extra computation ability. This paper proposes an improved PSO algorithm without inertia weight. The proposed algorithm dynamically adjusts the search space and velocity limits for the swarm in each iteration by picking the highest and lowest values among all the dimensions of the particles, calculates their absolute values and then uses the higher of the two values to define a new search range and velocity limits for next iteration. The efficiency and performance of the proposed algorithm was shown using popular benchmark global optimization problems with low and high dimensions. Results obtained demonstrate better convergence speed and precision, stability, robustness with better global search ability when compared with six recent variants of the original algorithm.
Integration of Particle Swarm Optimization and Immune Genetic Algorithm-Based Dynamic Clustering for Customer Clustering
Authors: Kuo R. J. , Lin S. H. , Chen Zhen-Yao
Published: February 2015

This study intends to present a dynamic clustering (DC) approach based on particle swarm optimization (PSO) and immune genetic (IG) (DCPIG) algorithm, which is able to cluster the data into adequate clusters through data characteristics with pre-specified numbers of clusters. The proposed DCPIG algorithm is compared with three DC algorithms in the literature using Iris, Wine, Glass and Vowel benchmark data sets. The experiment results show that the DCPIG algorithm can achieve higher stability and accuracy than the other algorithms. In addition, the DCPIG algorithm is also applied to a real-world problem considering the customer clustering for a cyber flower shop. Lastly, we recommend different products and services to customers based on the clustering results.
Coherent band pathways between knots and links
Authors: Buck Dorothy , Ishihara Kai
Published: February 2015

We categorize coherent band (aka nullification) pathways between knots and 2-component links. Additionally, we characterize the minimal coherent band pathways (with intermediates) between any two knots or 2-component links with small crossing number. We demonstrate these band surgeries for knots and links with small crossing number. We apply these results to place lower bounds on the minimum number of recombinant events separating DNA configurations, restrict the recombination pathways and determine chirality and/or orientation of the resulting recombinant DNA molecules.
Acoustic Source Localization and Deconvolution-Based Separation
Authors: Bai Mingsian R. , Kuo Chia-Hao
Published: February 2015

This paper examines two fundamental issues in sound field analysis: acoustic sources localization and separation. Algorithms are developed to locate and separate acoustic signals on the basis of plane-wave decomposition. In the localization stage, directions of plane waves are determined using either minimum variance distortionless response (MVDR) method or multiple signal classification (MUSIC) method. For broadband scenarios, coherent and incoherent techniques are utilized in the localization procedure. In the separation stage, two approaches with overdetermined and underdetermined settings can be employed. In the overdetermined approach, Tikhonov regularization (TIKR) is utilized to recover the source signals. In the underdetermined approach, the steering matrix is augmented by including the directions that have been determined in the localization stage. Hence, the separation problem is formulated into a compressive sensing (CS) problem which can be effectively solved by using convex (CVX) optimization. Simulation and experiments are conducted for a 24-element circular array. Objective tests using perceptual evaluation of speech quality (PESQ) tests and subjective listening tests demonstrate that the proposed methods yield speech signals with well separated and improved quality, as compared to the mixed signals.
LIFETIME CONSUMPTION AND INVESTMENT FOR WORST-CASE CRASH SCENARIOS
Authors: DESMETTRE SASCHA , KORN RALF , SEIFRIED FRANK THOMAS
Published: February 2015

We investigate worst-case optimal consumption and portfolio decisions under the threat of a market crash on an infinite time horizon. We provide a closed-form solution for constant relative risk aversion and establish a rigorous verification result. More specifically, using martingale arguments we demonstrate that the optimal consumption-portfolio strategy can be characterized as the indifference strategy that achieves the best performance in the no-crash scenario. In addition, we find a dual characterization of the optimal strategy as the indifference strategy that minimizes the crash exposure. Finally, we quantify the impact of the crash on consumption and portfolio choice and analyze it in terms of the investor's risk and time preferences and prudence.
Quantum oblivion: A master key for many quantum riddles
Authors: Elitzur Avshalom C. , Cohen Eliahu
Published: February 2015

A simple quantum interaction is analyzed, where the paths of two superposed particles asymmetrically cross, while a detector set to detect an interaction between them remains silent. Despite this negative result, the particles' states leave no doubt that a peculiar interaction has occurred: One particle's momentum is changed while the other's remains unaffected, in apparent violation of momentum conservation. Revisiting the foundations of the standard quantum measurement process offers the resolution. Prior to the macroscopic recording of no interaction, a brief critical interval (CI) prevails, during which the particles and the detector's pointer form a subtle entanglement which immediately dissolves. It is this self-cancellation, henceforth "quantum oblivion (QO)," that lies at the basis of some well-known intriguing quantum effects. Such is interaction-free measurement (IFM)1 and its more paradoxical variants like Hardy's Paradox2 and the quantum liar paradox.3 Even the Aharonov–Bohm (AB) effect4 and weak measurement (WM)5 turn out to belong to this group. We next study interventions within the CI that produce some other peculiar effects. Finally, we discuss some of the conceptual issues involved. Under a greater time-resolution of the CI, some non-local phenomena turn out to be local. Momentum is conserved due to the quantum uncertainties inflicted by the particle–pointer interaction, which sets the experiment's final boundary condition.
Spatio-spectral characterization of twin-beam states of light for quantum state engineering
Authors: Allevi Alessia , Lamperti Marco , Jedrkiewicz Ottavia , Galinis Justinas , Machulka Radek , Haderka Ondřej , Peřina Jan , Bondani Maria
Published: February 2015

We present an experimental investigation of the spatio-spectral coherence properties of bright twin-beam states (TWBs) as functions of different parameters, such as pump mean power and tuning angle of the employed nonlinear crystal. Our attention is mainly focused on the possible relations among the different quantities under investigation. Particular attention is devoted to the evolution of the number of spatio-spectral modes describing the radiation field, as it represents an interesting property to be controlled in view of possible applications to quantum state engineering protocols.
Pyritiferous mudstone–siltstone: expansion rate measurement and prediction
Authors: McCabe Bryan A. , McKeon Éanna P. , Virbukiene Rasa J. , Mannion Patrick J. , O’Connell Aidan M.
Published: February 2015

The expansion rates of a pyritiferous Irish mudstone–siltstone fill material have been measured over a period of 19 months in an apparatus devised to replicate underfloor conditions. The testing, performed in a temperature-controlled environment, has shown that both fill density and depth submerged in water have significant influences on the progress of the expansion. It appears that whereas thermal expansion or contraction has an effect on expansion rates immediately after a temperature change, there is no long-term temperature effect on the rate of expansion. In addition, an examination of chemical test results for 60 houses in a housing development in the Dublin area has confirmed that pyrite content is the dominant control over the degree of expansion. A molecular–molar analysis of the pyrite chemical process equations, in addition to a knowledge of the original pyrite content and rate of oxidation, has been used to give a lower-bound estimate of the amount of heave in the laboratory experiments.
A neuroprotective role of the NMDA receptor subunit GluN3A (NR3A) in ischemic stroke of the adult mouse
Authors: Lee Jin Hwan , Wei Zheng Z. , Chen Dongdong , Gu Xiaohuan , Wei Ling , Yu Shan Ping
Published: February 2015

GluN3A or NR3A is a developmentally regulated N-methyl-d-aspartate receptor (NMDAR) subunit, showing a unique inhibitory role that decreases NMDAR current and the receptor-mediated Ca2+ influx. In the neonatal brain, GluN3A is shown to associate with synaptic maturation and spine formation and plays a neuroprotective role. Its functional role in the adult brain, however, is largely unknown. We tested the hypothesis that, disrespecting the relatively lower expression level of GluN3A in the adult brain, this inhibitory NMDAR subunit shows a protective action against ischemia-induced brain injury. In littermate wild-type (WT) and GluN3A knockout (KO) mice, focal cerebral ischemia was induced by permanent occlusion of right distal branches of the middle cerebral artery (MCA) plus 10-min ligation of both common carotid arteries (CCAs). Twenty-four hours after focal cerebral ischemia, the infarction volume assessed using 2,3,5-triphenyltetrazolium chloride (TTC) staining was significantly larger in GluN3A KO mice compared with WT mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining demonstrated enhanced cell death in GluN3A KO mice. Moreover, the deletion of GluN3A hindered sensorimotor functional recovery after stroke. It is suggested that, although the expression level is relatively lower in the adult brain, GluN3A is still a noteworthy regulator in ischemia-induced excitotoxicity and brain injury.
Inhibitor-κB kinase attenuates Hsp90-dependent endothelial nitric oxide synthase function in vascular endothelial cells
Authors: Natarajan Mohan , Konopinski Ryszard , Krishnan Manickam , Roman Linda , Bera Alakesh , Hongying Zheng , Habib Samy L. , Mohan Sumathy
Published: February 2015

Endothelial nitric oxide (NO) synthase (eNOS) is the predominant isoform that generates NO in the blood vessels. Many different regulators, including heat shock protein 90 (Hsp90), govern eNOS function. Hsp90-dependent phosphorylation of eNOS is a critical event that determines eNOS activity. In our earlier study we demonstrated an inhibitor-κB kinase-β (IKKβ)-Hsp90 interaction in a high-glucose environment. In the present study we further define the putative binding domain of IKKβ on Hsp90. Interestingly, IKKβ binds to the middle domain of Hsp90, which has been shown to interact with eNOS to stimulate its activity. This new finding suggests a tighter regulation of eNOS activity than was previously assumed. Furthermore, addition of purified recombinant IKKβ to the eNOS-Hsp90 complex reduces the eNOS-Hsp90 interaction and eNOS activity, indicating a competition for Hsp90 between eNOS and IKKβ. The pathophysiological relevance of the IKKβ-Hsp90 interaction has also been demonstrated using in vitro vascular endothelial growth factor-mediated signaling and an Ins2Akita in vivo model. Our study further defines the preferential involvement of α- vs. β-isoforms of Hsp90 in the IKKβ-eNOS-Hsp90 interaction, even though both Hsp90α and Hsp90β stimulate NO production. These studies not only reinforce the significance of maintaining a homeostatic balance of eNOS and IKKβ within the cell system that regulates NO production, but they also confirm that the IKKβ-Hsp90 interaction is favored in a high-glucose environment, leading to impairment of the eNOS-Hsp90 interaction, which contributes to endothelial dysfunction and vascular complications in diabetes.