bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Performance of Roche Cobas 4800 HPV Test
Authors: Cui Miao , Chan Nicholas , Liu Momo , Thai Khanh , Malaczynska Joanna , Singh Ila , Zhang David , Ye Fei
Published: April 2014

Evaluation of the Cobas 4800 test demonstrated that Cobas had a low rate of cross-reactivity with low-risk human papillomavirus (lrHPV), a 3.74% disconcordance rate between prealiquots and postaliquots, and failure rates of 4.57% and 1.16%, respectively, after vortexing and swirling. This study demonstrated that the Cobas test has good sensitivity, accuracy, and reproducibility for detecting 14 high-risk HPV (hrHPV) genotypes.
Comparison of Commercial Antimicrobial Susceptibility Test Methods for Testing of Staphylococcus aureus and Enterococci against Vancomycin, Daptomycin, and Linezolid
Authors: Riedel Stefan , Neoh Kar Mun , Eisinger Stephen W. , Dam Lisa M. , Tekle Tsigereda , Carroll Karen C.
Published: April 2014

Three commercial antimicrobial susceptibility testing (AST) methods were compared to broth microdilution for testing of
Staphylococcus aureus
and enterococci against vancomycin, daptomycin, and linezolid. Despite high levels of categorical agreement and essential agreement, vancomycin MICs determined by MicroScan were often 1 log
2
concentration higher and MICs determined by Phoenix 1 log
2
concentration lower. Daptomycin MICs were 1 to 2 log
2
concentrations higher by all AST methods, except Etest, potentially impacting definitive antimicrobial therapy for bloodstream infections due to these organisms.
Streptococcus suis-Related Prosthetic Joint Infection and Streptococcal Toxic Shock-Like Syndrome in a Pig Farmer in the United States
Authors: Gomez Eric , Kennedy Cassie C. , Gottschalk Marcelo , Cunningham Scott A. , Patel Robin , Virk Abinash
Published: April 2014

Streptococcus suis
is an emerging swine-associated zoonotic agent that can cause meningitis and septicemia in humans. We present, to our knowledge, the first case of
S. suis
arthroplasty infection and streptococcal toxic shock-like syndrome due to an nonencapsulated serotype 5 strain in North America.
Alternative Recognition of the Conserved Stem Epitope in Influenza A Virus Hemagglutinin by a V
H
3-30-Encoded Heterosubtypic Antibody
Authors: Wyrzucki Arkadiusz , Dreyfus Cyrille , Kohler Ines , Steck Marco , Wilson Ian A. , Hangartner Lars
Published: April 2014

A human monoclonal heterosubtypic antibody, MAb 3.1, with its heavy chain encoded by V
H
3-30, was isolated using phage display with immobilized hemagglutinin (HA) from influenza virus A/Japan/305/1957(H2N2) as the target. Antibody 3.1 potently neutralizes influenza viruses from the H1a clade (i.e., H1, H2, H5, H6) but has little neutralizing activity against the H1b clade. Its crystal structure in complex with HA from a pandemic H1N1 influenza virus, A/South Carolina/1/1918(H1N1), revealed that like other heterosubtypic anti-influenza virus antibodies, MAb 3.1 contacts a hydrophobic groove in the HA stem, primarily using its heavy chain. However, in contrast to the closely related monoclonal antibody (Mab) FI6 that relies heavily on HCDR3 for binding, MAb 3.1 utilizes residues from HCDR1, HCDR3, and framework region 3 (FR3). Interestingly, HCDR1 of MAb 3.1 adopts an α-helical conformation and engages in hydrophobic interactions with the HA very similar to those of the
de novo in silico
-designed and affinity-matured synthetic protein HB36.3. These findings improve our understanding of the molecular requirements for binding to the conserved epitope in the stem of the HA protein and, therefore, aid the development of more universal influenza vaccines targeting these epitopes.

IMPORTANCE
Influenza viruses rapidly evade preexisting immunity by constantly altering the immunodominant neutralizing antibody epitopes (antigenic drift) or by acquiring new envelope serotypes (antigenic shift). As a consequence, the majority of antibodies elicited by immunization or infection protect only against the immunizing or closely related strains. Here, we describe a novel monoclonal antibody that recognizes the conserved heterosubtypic epitope in the stem of influenza A virus hemagglutinin. This antibody, referred to as MAb 3.1, recognizes its epitope in a manner that resembles recognition of a similar epitope by the
de novo in silico
-designed and affinity-matured synthetic protein HB36.3. Thus, besides providing novel insights into the molecular interactions between heterosubtypic antibodies and influenza virus hemagglutinin, MAb 3.1 demonstrates that
de novo in silico
-designed and affinity-matured synthetic proteins can foretell naturally selected antibody binding. This knowledge will aid development of a pan-influenza virus vaccine.
Enhanced Immunogenicity of an HIV-1 DNA Vaccine Delivered with Electroporation via Combined Intramuscular and Intradermal Routes
Authors: Mann Jamie F. S. , McKay Paul F. , Fiserova Anezka , Klein Katja , Cope Alethea , Rogers Paul , Swales Julie , Seaman Michael S. , Combadiere Behazine , Shattock Robin J.
Published: April 2014

It is accepted that an effective prophylactic HIV-1 vaccine is likely to have the greatest impact on viral transmission rates. As previous reports have implicated DNA-priming, protein boost regimens to be efficient activators of humoral responses, we sought to optimize this regimen to further augment vaccine immunogenicity. Here we evaluated single versus concurrent intradermal (i.d.) and intramuscular (i.m.) vaccinations as a DNA-priming strategy for their abilities to elicit humoral and cellular responses against a model HIV-1 vaccine antigen, CN54-gp140. To further augment vaccine-elicited T and B cell responses, we enhanced cellular transfection with electroporation and then boosted the DNA-primed responses with homologous protein delivered subcutaneously (s.c.), intranasally (i.n.), i.m., or transcutaneously (t.c.). In mice, the concurrent priming regimen resulted in significantly elevated gamma interferon T cell responses and high-avidity antigen-specific IgG B cell responses, a hallmark of B cell maturation. Protein boosting of the concurrent DNA strategy further enhanced IgG concentrations but had little impact on T cell reactivity. Interestingly protein boosting by the subcutaneous route increased antibody avidity to a greater extent than protein boosting by either the i.m., i.n., or t.c. route, suggesting that this route may be preferential for driving B cell maturation. Using an alternative and larger animal model, the rabbit, we found the concurrent DNA-priming strategy followed by s.c. protein boosting to again be capable of eliciting high-avidity humoral responses and to also be able to neutralize HIV-1 pseudoviruses from diverse clades (clades A, B, and C). Taken together, we show that concurrent multiple-route DNA vaccinations induce strong cellular immunity, in addition to potent and high-avidity humoral immune responses.

IMPORTANCE
The route of vaccination has profound effects on prevailing immune responses. Due to the insufficient immunogenicity and protection of current DNA delivery strategies, we evaluated concurrent DNA delivery via simultaneous administration of plasmid DNA by the i.m. and i.d. routes. The rationale behind this study was to provide clear evidence of the utility of concurrent vaccinations for an upcoming human clinical trial. Furthermore, this work will guide future preclinical studies by evaluating the use of model antigens and plasmids for prime-boost strategies. This paper will be of interest not only to virologists and vaccinologists working in the HIV field but also to researchers working in other viral vaccine settings and, critically, to the wider field of vaccine delivery.
Cullin4A and Cullin4B Are Interchangeable for HIV Vpr and Vpx Action through the CRL4 Ubiquitin Ligase Complex
Authors: Sharifi Hamayun John , Furuya Andrea K. M. , Jellinger Robert M. , Nekorchuk Michael D. , de Noronha Carlos M. C.
Published: April 2014

Human immunodeficiency virus (HIV) seizes control of cellular cullin-RING E3 ubiquitin ligases (CRLs) to promote viral replication. HIV-1 Vpr and HIV-2/simian immunodeficiency virus (SIV) Vpr and Vpx engage the cullin4 (CUL4)-containing ubiquitin ligase complex (CRL4) to cause polyubiquitination and proteasomal degradation of host proteins, including ones that block infection. HIV-1 Vpr engages CRL4 to trigger the degradation of uracil-
N
-glycosylase 2 (UNG2). Both HIV-1 Vpr and HIV-2/SIV Vpr tap CRL4 to initiate G
2
cell cycle arrest. HIV-2/SIV Vpx secures CRL4 to degrade the antiviral protein SAMHD1. CRL4 includes either cullin4A (CUL4A) or cullin4B (CUL4B) among its components. Whether Vpr or Vpx relies on CUL4A, CUL4B, or both to act through CRL4 is not known. Reported structural, phenotypic, and intracellular distribution differences between the two CUL4 types led us to hypothesize that Vpr and Vpx employ these in a function-specific manner. Here we determined CUL4 requirements for HIV-1 and HIV-2/SIV Vpr-mediated G
2
cell cycle arrest, HIV-1 Vpr-mediated UNG2 degradation, and HIV-2 Vpx-mediated SAMHD1 degradation. Surprisingly, CUL4A and CUL4B are exchangeable for CRL4-dependent Vpr and Vpx action, except in primary macrophages, where Vpx relies on both CUL4A and CUL4B for maximal SAMHD1 depletion. This work highlights the need to consider both CUL4 types for Vpr and Vpx functions and also shows that the intracellular distribution of CUL4A and CUL4B can vary by cell type.

IMPORTANCE
The work presented here shows for the first time that HIV Vpr and Vpx do not rely exclusively on CUL4A to cause ubiquitination through the CRL4 ubiquitin ligase complex. Furthermore, our finding that intracellular CUL4 and SAMHD1 distributions can vary with cell type provides the basis for reconciling previous disparate findings regarding the site of SAMHD1 depletion. Finally, our observations with primary immune cells provide insight into the cell biology of CUL4A and CUL4B that will help differentiate the functions of these similar proteins.
HIV-1 Protease-Substrate Coevolution in Nelfinavir Resistance
Authors: Kolli Madhavi , Özen Ayşegül , Kurt-Yilmaz Nese , Schiffer Celia A.
Published: April 2014

Resistance to various human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. The virus accumulates mutations within the protease (PR) that render the PIs less potent. Occasionally, Gag sequences also coevolve with mutations at PR cleavage sites contributing to drug resistance. In this study, we investigated the structural basis of coevolution of the p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations by determining crystal structures of wild-type and NFV-resistant HIV-1 protease in complex with p1-p6 substrate peptide variants with L449F and/or S451N. Alterations of residue 30's interaction with the substrate are compensated by the coevolving L449F and S451N cleavage site mutations. This interdependency in the PR–p1-p6 interactions enhances intermolecular contacts and reinforces the overall fit of the substrate within the substrate envelope, likely enabling coevolution to sustain substrate recognition and cleavage in the presence of PR resistance mutations.

IMPORTANCE
Resistance to human immunodeficiency virus type 1 (HIV-1) protease inhibitors challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. Mutations in HIV-1 protease selected under the pressure of protease inhibitors render the inhibitors less potent. Occasionally, Gag sequences also mutate and coevolve with protease, contributing to maintenance of viral fitness and to drug resistance. In this study, we investigated the structural basis of coevolution at the Gag p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations. Our structural analysis reveals the interdependency of protease-substrate interactions and how coevolution may restore substrate recognition and cleavage in the presence of protease drug resistance mutations.
Potential Role for CA-SP in Nucleating Retroviral Capsid Maturation
Authors: England Matthew R. , Purdy John G. , Ropson Ira J. , Dalessio Paula M. , Craven Rebecca C.
Published: April 2014

During virion maturation, the Rous sarcoma virus (RSV) capsid protein is cleaved from the Gag protein as the proteolytic intermediate CA-SP. Further trimming at two C-terminal sites removes the spacer peptide (SP), producing the mature capsid proteins CA and CA-S. Abundant genetic and structural evidence shows that the SP plays a critical role in stabilizing hexameric Gag interactions that form immature particles. Freeing of CA-SP from Gag breaks immature interfaces and initiates the formation of mature capsids. The transient persistence of CA-SP in maturing virions and the identification of second-site mutations in SP that restore infectivity to maturation-defective mutant viruses led us to hypothesize that SP may play an important role in promoting the assembly of mature capsids. This study presents a biophysical and biochemical characterization of CA-SP and its assembly behavior. Our results confirm cryo-electron microscopy (cryo-EM) structures reported previously by Keller et al. (J. Virol. 87:13655–13664, 2013, doi:10.1128/JVI.01408-13) showing that monomeric CA-SP is fully capable of assembling into capsid-like structures identical to those formed by CA. Furthermore, SP confers aggressive assembly kinetics, which is suggestive of higher-affinity CA-SP interactions than observed with either of the mature capsid proteins. This aggressive assembly is largely independent of the SP amino acid sequence, but the formation of well-ordered particles is sensitive to the presence of the N-terminal β-hairpin. Additionally, CA-SP can nucleate the assembly of CA and CA-S. These results suggest a model in which CA-SP, once separated from the Gag lattice, can actively promote the interactions that form mature capsids and provide a nucleation point for mature capsid assembly.

IMPORTANCE
The spacer peptide is a documented target for antiretroviral therapy. This study examines the biochemical and biophysical properties of CA-SP, an intermediate form of the retrovirus capsid protein. The results demonstrate a previously unrecognized activity of SP in promoting capsid assembly during maturation.
A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein
Authors: Du Lanying , Zhao Guangyu , Yang Yang , Qiu Hongjie , Wang Lili , Kou Zhihua , Tao Xinrong , Yu Hong , Sun Shihui , Tseng Chien-Te K. , Jiang Shibo , Li Fang , Zhou Yusen
Published: April 2014

Prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have developed a neutralizing monoclonal antibody (MAb), designated Mersmab1, which potently blocks MERS-CoV entry into human cells. Biochemical assays reveal that Mersmab1 specifically binds to the receptor-binding domain (RBD) of the MERS-CoV spike protein and thereby competitively blocks the binding of the RBD to its cellular receptor, dipeptidyl peptidase 4 (DPP4). Furthermore, alanine scanning of the RBD has identified several residues at the DPP4-binding surface that serve as neutralizing epitopes for Mersmab1. These results suggest that if humanized, Mersmab1 could potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies of the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines.

IMPORTANCE
MERS-CoV is spreading in the human population and causing severe respiratory diseases with over 40% fatality. No vaccine is currently available to prevent MERS-CoV infections. Here, we have produced a neutralizing monoclonal antibody with the capacity to effectively block MERS-CoV entry into permissive human cells. If humanized, this antibody may be used as a prophylactic and therapeutic agent against MERS-CoV infections. Specifically, when given to a person (e.g., a patient's family member or a health care worker) either before or after exposure to MERS-CoV, the humanized antibody may prevent or inhibit MERS-CoV infection, thereby stopping the spread of MERS-CoV in humans. This antibody can also serve as a useful tool to guide the design of effective MERS-CoV vaccines.
Mixed Triple: Allied Viruses in Unique Recent Isolates of Highly Virulent Type 2 Bovine Viral Diarrhea Virus Detected by Deep Sequencing
Authors: Jenckel Maria , Höper Dirk , Schirrmeier Horst , Reimann Ilona , Goller Katja V. , Hoffmann Bernd , Beer Martin
Published: April 2014

In February 2013, very severe acute clinical symptoms were observed in calves, heifers, and dairy cattle in several farms in North Rhine Westphalia and Lower Saxony, Germany. Deep sequencing revealed the coexistence of three distinct genome variants within recent highly virulent bovine viral diarrhea virus type 2 (BVDV-2) isolates. While the major portion (ca. 95%) of the population harbored a duplication of a 222-nucleotide (nt) segment within the p7-NS2-encoding region, the minority reflected the standard structure of a BVDV-2 genome. Additionally, unusual mutations were found in both variants, within the highly conserved p7 protein and close to the p7-NS2 cleavage site. Using a reverse genetic system with a BVDV-2a strain harboring a similar duplication, it could be demonstrated that during replication, genomes without duplication are generated
de novo
from genomes with duplication. The major variant with duplication is compulsorily escorted by the minor variant without duplication. RNA secondary structure prediction allowed the analysis of the unique but stable mixture of three BVDV variants and also provided the explanation for their generation. Finally, our results suggest that the variant with duplication plays the major role in the highly virulent phenotype.

IMPORTANCE
This study emphasizes the importance of full-genome deep sequencing in combination with manual in-depth data analysis for the investigation of viruses in basic research and diagnostics. Here we investigated recent highly virulent bovine viral diarrhea virus isolates from a 2013 series of outbreaks. We discovered a unique special feature of the viral genome, an unstable duplication of 222 nucleotides which is eventually deleted by viral polymerase activity, leading to an unexpectedly mixed population of viral genomes for all investigated isolates. Our study is of high importance to the field because we demonstrate that these insertion/deletion events allow another level of genome plasticity of plus-strand RNA viruses, in addition to the well-known polymerase-induced single nucleotide variations which are generally considered the main basis for viral adaptation and evolution.
Identification of Diverse Alphacoronaviruses and Genomic Characterization of a Novel Severe Acute Respiratory Syndrome-Like Coronavirus from Bats in China
Authors: He Biao , Zhang Yuzhen , Xu Lin , Yang Weihong , Yang Fanli , Feng Yun , Xia Lele , Zhou Jihua , Zhen Weibin , Feng Ye , Guo Huancheng , Zhang Hailin , Tu Changchun
Published: April 2014

Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been identified in bats in China, Europe, and Africa, most have a genetic organization significantly distinct from human/civet SARS CoVs in the receptor-binding domain (RBD), which mediates receptor binding and determines the host spectrum, resulting in their failure to cause human infections and making them unlikely progenitors of human/civet SARS CoVs. Here, a viral metagenomic analysis of 268 bat rectal swabs collected from four counties in Yunnan Province has identified hundreds of sequences relating to alpha- and betacoronaviruses. Phylogenetic analysis based on a conserved region of the RNA-dependent RNA polymerase gene revealed that alphacoronaviruses had diversities with some obvious differences from those reported previously. Full genomic analysis of a new SARS-like CoV from Baoshan (LYRa11) showed that it was 29,805 nucleotides (nt) in length with 13 open reading frames (ORFs), sharing 91% nucleotide identity with human/civet SARS CoVs and the most recently reported SARS-like CoV Rs3367, while sharing 89% with other bat SARS-like CoVs. Notably, it showed the highest sequence identity with the S gene of SARS CoVs and Rs3367, especially in the RBD region. Antigenic analysis showed that the S1 domain of LYRa11 could be efficiently recognized by SARS-convalescent human serum, indicating that LYRa11 is a novel virus antigenically close to SARS CoV. Recombination analyses indicate that LYRa11 is likely a recombinant descended from parental lineages that had evolved into a number of bat SARS-like CoVs.

IMPORTANCE
Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been discovered in bats worldwide, there are significant different genic structures, particularly in the S1 domain, which are responsible for host tropism determination, between bat SARS-like CoVs and human SARS CoVs, indicating that most reported bat SARS-like CoVs are not the progenitors of human SARS CoV. We have identified diverse alphacoronaviruses and a close relative (LYRa11) to SARS CoV in bats collected in Yunnan, China. Further analysis showed that alpha- and betacoronaviruses have different circulation and transmission dynamics in bat populations. Notably, full genomic sequencing and antigenic study demonstrated that LYRa11 is phylogenetically and antigenically closely related to SARS CoV. Recombination analyses indicate that LYRa11 is a recombinant from certain bat SARS-like CoVs circulating in Yunnan Province.
Interferon Regulatory Factor 1 Restricts Gammaherpesvirus Replication in Primary Immune Cells
Authors: Mboko Wadzanai P. , Mounce Bryan C. , Emmer Joseph , Darrah Eric , Patel Shailendra B. , Tarakanova Vera L.
Published: April 2014

Gammaherpesviruses are ubiquitous pathogens that establish a lifelong infection and are associated with cancer. In spite of the high seroprevalence of infection, the risk factors that predispose the host toward gammaherpesvirus-induced malignancies are still poorly understood. Interferon (IFN) regulatory factor 1 (IRF-1) is a tumor suppressor that is also involved in the regulation of innate and adaptive immune responses. On the basis of its biology, IRF-1 represents a plausible host factor to attenuate gammaherpesvirus infection and tumorigenesis. In this study, we show that IRF-1 restricts gammaherpesvirus replication in primary macrophages, a physiologically relevant immune cell type. In spite of the known role of IRF-1 in stimulating type I IFN expression, induction of a global type I IFN response was similar in IRF-1-deficient and -proficient macrophages during gammaherpesvirus infection. However, IRF-1 was required for optimal expression of cholesterol-25-hydroxylase, a host enzyme that restricted gammaherpesvirus replication in primary macrophages and contributed to the antiviral effects of IRF-1. In summary, the current study provides an insight into the mechanism by which IRF-1 attenuates gammaherpesvirus replication in primary immune cells, a mechanism that is likely to contribute to the antiviral effects of IRF-1 in other virus systems.

IMPORTANCE
Interferon regulatory factor 1 (IRF-1) is a transcription factor that regulates innate and adaptive immune responses and functions as a tumor suppressor. IRF-1 restricts the replication of diverse viruses; however, the mechanisms responsible for the antiviral effects of IRF-1 are still poorly understood. Gammaherpesviruses are ubiquitous pathogens that are associated with the induction of several malignancies. Here we show that IRF-1 expression attenuates gammaherpesvirus replication in primary macrophages, in part by increasing expression of cholesterol-25-hydroxylase (CH25H). CH25H and its product, 25-hydroxycholesterol, restrict replication of diverse virus families. Thus, our findings offer an insight into the mechanism by which IRF-1 attenuates the replication of gammaherpesviruses, a mechanism that is likely to be applicable to other virus systems.
N-Myc Interactor Inhibits Prototype Foamy Virus by Sequestering Viral Tas Protein in the Cytoplasm
Authors: Hu Xiaomei , Yang Wei , Liu Ruikang , Geng Yunqi , Qiao Wentao , Tan Juan
Published: April 2014

Foamy viruses (FVs) are complex retroviruses that establish lifelong persistent infection without evident pathology. However, the roles of cellular factors in FV latency are poorly understood. This study revealed that N-Myc interactor (Nmi) could inhibit the replication of prototype foamy virus (PFV). Overexpression of Nmi reduced PFV replication, whereas its depletion by small interfering RNA increased PFV replication. The Nmi-mediated impairment of PFV replication resulted from the diminished transactivation by PFV Tas of the viral long terminal repeat (LTR) and an internal promoter (IP). Nmi was determined to interact with Tas and abrogate its function by sequestration in the cytoplasm. In addition, human and bovine Nmi proteins were found to inhibit the replication of bovine foamy virus (BFV) and PFV. Together, these results indicate that Nmi inhibits both human and bovine FVs by interfering with the transactivation function of Tas and may have a role in the host defense against FV infection.

IMPORTANCE
From this study, we report that the N-Myc interactor (Nmi), an interferon-induced protein, can interact with the regulatory protein Tas of the prototype foamy virus and sequester it in the cytoplasm. The results of this study suggest that Nmi plays an important role in maintaining foamy virus latency and may reveal a new pathway in the interferon-mediated antiviral barrier against viruses. These findings are important for understanding virus-host relationships not only with FVs but potentially for other retroviruses as well.
Association of Satellites with a Mastrevirus in Natural Infection: Complexity of Wheat Dwarf India Virus Disease
Authors: Kumar Jitendra , Kumar Jitesh , Singh Sudhir P. , Tuli Rakesh
Published: April 2014

In contrast to begomoviruses, mastreviruses have not previously been shown to interact with satellites. This study reports the first identification of the association of satellites with a mastrevirus in field-grown plants. Two alphasatellite species were detected in different field samples of wheat infected with
Wheat Dwarf India Virus
(WDIV), a Cotton leaf curl Multan alphasatellite (CLCuMA) and a Guar leaf curl alphasatellite (GLCuA). In addition to the alphasatellites, a betasatellite, Ageratum yellow leaf curl betasatellite (AYLCB), was also identified in the wheat samples. No begomovirus was detected in the wheat samples, thus establishing association of the above-named satellites with WDIV. Agrobacterium-mediated inoculation of WDIV in wheat, in the presence of either of the alphasatellites or the betasatellite, resulted in infections inducing more severe symptoms. WDIV efficiently maintained each of the alphasatellites and the betasatellite in wheat. The satellites enhanced the level of WDIV DNA in wheat. Inoculation of the satellites isolated from wheat with various begomoviruses into
Nicotiana tabacum
demonstrated that these remain capable of interacting with the viruses with which they were first identified. Virus-specific small RNAs accumulated in wheat upon infection with WDIV but were lower in abundance in plants coinfected with the satellites, suggesting that both the alphasatellites and the betasatellite suppress RNA silencing. These results suggest that the selective advantage for the maintenance of the alphasatellites and the betasatellite by WDIV in the field is in overcoming RNA silencing-mediated host defense.

IMPORTANCE
Wheat is the most widely cultivated cereal crop in the world. A number of viruses are important pathogens of wheat, including the viruses of the genus
Mastrevirus
, family
Geminiviridae
. This study reports the association of subgenomic components, called satellites (alpha- and betasatellites), with a mastrevirus,
Wheat Dwarf India Virus
(WDIV), isolated from two distant locations in India. This study reports the first identification of the satellites in a monocot plant. The satellites enhanced accumulation of WDIV and severity of disease symptoms. The satellites lowered the concentration of virus-specific small RNAs in wheat plants, indicating their silencing suppressor activity. The involvement of the satellites in symptom severity of the mastrevirus can have implications in the form of economic impact of the virus on crop yield. Understanding the role of the satellites in disease severity is important for developing disease management strategies.
Outer Membrane Protein OmpW Is the Receptor for Typing Phage VP5 in the Vibrio cholerae O1 El Tor Biotype
Authors: Xu Donglei , Zhang Jingyun , Liu Jie , Xu Jialiang , Zhou Haijian , Zhang Lijuan , Zhu Jun , Kan Biao
Published: April 2014

Phage typing is used for the subtyping of clones of epidemic bacteria. In this study, we identified the outer membrane protein OmpW as the receptor for phage VP5, one of the typing phages for the
Vibrio cholerae
O1 El Tor biotype. A characteristic 11-bp deletion in
ompW
was observed in all epidemic strains resistant to VP5, suggesting that this mutation event can be used as a tracing marker in cholera surveillance.
De Garengeot hernia: a forgotten rare entity?
Authors: Madiha Ahmedi , Rares Hard , Abdus Samee
Published: April 2014

We report the case of a 79-year-old woman who presented with an increasingly painful lump in her right groin for 24 h. An incidental femoral hernia was detected on her CT scan nearly 8 months ago while investigating her medical conditions. However, its management was deferred on account of ongoing medical illness. Exploration of the lump revealed a gangrenous appendix strangulated within the femoral canal (de Garengeot hernia). The hernia was repaired primarily after appendicectomy. The patient was discharged after making an uneventful recovery.
Single stage substernal thyroidectomy and off-pump coronary artery bypass grafting: is it worth using cardiopulmonary bypass unless absolutely necessary?
Authors: Cetin Erdem , Ozyuksel Arda , Dalbasi Erkan
Published: April 2014

It is a rare entity to observe the coexistence of thyroid gland pathologies and coronary artery disease, whose surgical treatment may be performed simultaneously. In this case, we present a case of a patient with substernal thyroidectomy concurrent with off-pump coronary artery bypass grafting. A 57-year-old female patient was admitted to the hospital with exertional dyspnoea, intermittent coughing and stable angina pectoris. The substernal goitre measuring 5×5×4 cm was accompanied by a 95% in-stent restenosis at the left anterior descending artery. Thyroidectomy and off-pump coronary artery bypass grafting procedures were performed simultaneously. The postoperative period was uneventful and the patient was discharged 5 days after the operation. This case indicates that off-pump revascularisation seems to be a better option in cases where surgical interventions for thyroid and coronary artery diseases are necessary instead of on-pump revascularisation where the adverse effects of the cardiopulmonary bypass are considered.
CANOMAD responding to weekly treatment with intravenous immunoglobulin (IVIg)
Authors: Krenn Martin , Keir Geoff , Wieshmann Udo Carl
Published: April 2014

A 48-year-old man presented with numbness in fingers and diplopia 1 week after a flu-like illness. He made a full recovery but 8 years later developed progressive and disabling sensory ataxia. He had superimposed acute flare-ups with numbness, double vision and ptosis, all following infections. A blood test showed antidisialosyl antibodies including GD1b, GD3, GT1b and GQ1b in keeping with the diagnosis of chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and antidisialosyl antibodies (CANOMAD). Initial treatment with monthly courses of intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 days every 4 weeks helped temporarily but there were marked disabling fluctuations of symptoms. With IVIg 0.6 g/kg/day weekly his symptoms are stable. He remains mobile and has no eye symptoms without need for any other medication. This case demonstrates that weekly IVIg infusions instead of one 5-day course monthly may be able to avoid fluctuations of symptoms in CANOMAD.
Alveolar soft part sarcoma
Authors: Singh Aarti , Gupta Sunita , Ghosh Sujoy , Yuwanati Monal Bhaurao
Published: April 2014

Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma and is most often seen in adolescents and young adults. Despite its unique histology and well-characterised genetic translocation, many questions remain regarding the pathogenesis and treatment of this tumour type. Surgical excision of the primary tumour and pulmonary metastases has resulted in prolonged survival of some patients while the benefit of adjuvant chemotherapy and/or radiotherapy has been disputed. A 35-year-old woman presented with a tumour in the right leg and right side of the mandible along with active metastasis to lungs and multiple skeletal sites.
CNS intravascular lymphoma: an underappreciated cause of rapidly progressive dementia
Authors: Panda Akhila Kumar , Malik Seema
Published: April 2014

Intravascular lymphoma is a rare subtype of extranodal large cell non-Hodgkin's lymphoma that is usually seen in the elderly. It can occasionally present with neurological symptoms in the form of dementia, focal neurological deficit and seizure. Diagnosis is difficult because of non-specific clinical manifestation. We report a case of a 38-year-old woman presenting with rapidly progressive dementia and seizure. MRI of the brain showed bilateral diffuse involvement of cortex and subcortical white matter. Brain biopsy disclosed the aetiological confirmation of intravascular B-cell lymphoma. The patient was treated with monthly cyclophosphamide, doxorubicin, vincristine and prednisolone regimen, but unfortunately, she died after two chemotherapy cycles. So, high index of suspicion is warranted to diagnose and treat the condition early to have a better outcome.
Lipoid proteinosis: pathognomonic clinical and radiological features
Authors: Hegde Rahul Ganapati , Yadav Vikas J , Gajbhiye Meenakshi I
Published: April 2014

A 22-year-old woman presented with a facial rash and hoarseness of voice. On examination, coarse waxy thickening and scarring was noted on the forehead and both the cheeks. The eyelid margins revealed a row of beaded papules termed ‘moniliform blepharosis’. CT scan of the brain revealed bilateral, symmetric calcification of the amygdala of the hippocampal nuclei. This led to the diagnosis of lipoid proteinosis which is a rare genetic disorder.
The effect of weekly text-message communication on treatment completion among patients with latent tuberculosis infection: study protocol for a randomised controlled trial (WelTel LTBI)
Authors: van der Kop Mia L , Memetovic Jasmina , Patel Anik , Marra Fawziah , Sadatsafavi Mohsen , Hajek Jan , Smillie Kirsten , Thabane Lehana , Taylor Darlene , Johnston James , Lester Richard T
Published: April 2014

Introduction

Interventions to improve adherence to treatment for latent tuberculosis infection (LTBI) are necessary to improve treatment completion rates and optimise tuberculosis (TB) control efforts. The high prevalence of cell phone use presents opportunities to develop innovative ways to engage patients in care. A randomised controlled trial (RCT), WelTel Kenya1, demonstrated that weekly text messages improved antiretroviral adherence and clinical outcomes among patients initiating HIV treatment. The aim of this study is to determine whether the WelTel intervention can improve treatment completion among patients with LTBI and to evaluate the intervention's cost-effectiveness.

Methods and analysis

This open, two-site, parallel RCT (WelTel LTBI) will be conducted at TB clinics in Vancouver and New Westminster, British Columbia, Canada. Over 2 years, we aim to recruit 350 individuals initiating a 9-month isoniazid regimen. Participants will be randomly allocated to an intervention or control (standard care) arm in a 1:1 ratio. Intervention arm participants will receive a weekly text-message ‘check-in’ to which they will be asked to respond within 48 h. A TB clinician will follow-up instances of non-response and problems that are identified. Participants will be followed until treatment completion (up to 12 months) or discontinuation. The primary outcome is self-reported treatment completion (taking ≥80% of doses within 12 months). Secondary outcomes include daily adherence (percentage of days participants used medication as prescribed) and time to treatment completion. Patient satisfaction with the intervention will be evaluated, and the intervention's cost-effectiveness will be analysed through decision-analytic modelling.

Ethics and dissemination

Ethical approval has been obtained from the University of British Columbia. This trial will test the efficacy and cost-effectiveness of the WelTel intervention to improve treatment completion among patients with LTBI. Trial results and economic evaluation will help inform policy and practice on the use of WelTel in this population.

Trial registration number

ClinicalTrials.govNCT01549457.
Group behaviour of hollow-bar micropiles in cohesive soils
Authors: Abd Elaziz Ahmed Yehia , El Naggar M. Hesham
Published: April 2014

The use of hollow-core bars in micropiles has greatly increased over the past 10 years. In this study, the group behaviour of hollow-bar micropiles is investigated. The research methodology encompasses a full-scale field study on single hollow-bar micropiles and pairs of micropiles installed in cohesive soils and numerical investigations using three-dimensional (3D) finite element analysis. Four hollow-bar micropiles were installed in stiff silty clay deposit using large drilling carbide bits. Four axial monotonic tests on pairs of hollow-bar micropiles were conducted as part of the field study. The field test results were utilized to calibrate–verify a 3D finite element model (FEM). A parametric study was performed using the verified FEM to characterize capacity and performance of hollow-bar micropile groups. Group efficiency factors and interaction factors were established to evaluate the capacity and response of hollow-bar micropile groups under vertical loading. The results from the field tests and numerical investigations revealed that for hollow-bar micropiles, group efficiency factor, GE, can be taken equal to 1. A method for calculating the group settlement utilizing the interaction factors approach is proposed and a family of interaction factor diagrams is established to evaluate the group settlement.
Application of generalized additive models to examine ontogenetic and seasonal distributions of spiny dogfish (Squalus acanthias) in the Northeast (US) shelf large marine ecosystem
Authors: Sagarese Skyler R. , Frisk Michael G. , Cerrato Robert M. , Sosebee Kathy A. , Musick John A. , Rago Paul J.
Published: April 2014

Increased commercial importance of spiny dogfish (Squalus acanthias) combined with an often debated, and controversial, ecological impact has warranted an investigation of the relationship among distribution, environment, and prey to better understand the species ecology and inform management. To elucidate mechanisms behind distributional changes, we modeled seasonal occurrence and abundance of neonate, immature, and mature spiny dogfish as functions of abiotic and biotic factors using generalized additive models and Northeast Fisheries Science Center bottom trawl survey data. Significant nonlinear relationships were widespread throughout dogfish stages and seasons. Seasonal occurrence was tightly linked to depth and bottom temperature, with year and Julian day influential for some stages. While these factors also influenced abundance, ecological factors (e.g., squid abundances) significantly contributed to trends for many stages. Potential impacts of climate change were evaluated by forecasting distributions under different temperature scenarios, which revealed higher regional probabilities of occurrence for most stages during a warmer than average year. Our results can be used to better understand the relationship between sampling periods and movement drivers to survey catchability of the population in the Northeast (US) shelf large marine ecosystem.
Effect of magnetic field on a rotating thermoelastic medium with voids under thermal loading due to laser pulse with energy dissipation
Authors: Othman Mohamed I.A. , Zidan Magda E.M. , Hilal Mohamed I.M.
Published: April 2014

This investigation deals with the rotation of magneto-thermoelastic solid with voids subjected to thermal loading due to laser pulse. The bounding plane surface is heated by a non-Gaussian laser beam. The entire porous medium is rotated with a uniform angular velocity. The problem is studied in the context of Green–Naghdi (GN) theory of types II and III, with the effect of rotation, magnetic field, thermal loading and voids. Normal mode analysis is used to solve the physical problem to obtain the exact expressions for the displacement components, stresses, temperature distribution, and change in the volume fraction field, which have been shown graphically by comparison between two types of GN theory (types II and III) in the presence and the absence of rotation and magnetic field and for two values of time on thermoelastic material with voids.
A network perspective on the calamity, induced inaccessibility of communities and the robustness of centralized, landbound relief efforts
Authors: Valenzuela Jesus Felix , Legara Erika Fille , Fu Xiuju , Goh Rick Siow Mong , De Souza Robert , Monterola Christopher
Published: April 2014

We examine the robustness of centralized, landbound relief operations' capability to promptly reach areas affected by a disaster event from a network perspective. We initially look at two idealized road networks: a two-dimensional grid and a scale-free network, and compare them to an actual road network obtained from OpenStreetMap. We show that, from a node designated as the center for relief operations (a "relief center"), damage to a road network causes a substantial fraction of the other nodes (about 20% in the three networks we examined) to become initially inaccessible from any relief effort, although the remaining majority can still be reached readily. Furthermore, we show the presence of a threshold in the two idealized road networks but not in the real one. Below this threshold, all nodes can robustly be reached in a short span of time, and above it, not only the partitioning mentioned above sets in, but also the time needed to reach the nodes becomes susceptible to the amount of damage sustained by the road network. Under damage sustained by random segments of the network, this threshold is higher in the scale-free network compared to the grid, due to the robustness of the former against random attacks. Our results may be of importance in formulating contingency plans for the logistics of disaster relief operations.
Comment on "Cosmic-ray-driven reaction and greenhouse effect of halogenated molecules: Culprits for atmospheric ozone depletion and global climate change"
Authors: Nuccitelli Dana , Cowtan Kevin , Jacobs Peter , Richardson Mark , Way Robert G. , Blackburn Anne-Marie , Stolpe Martin B. , Cook John
Published: April 2014

Lu (2013) (L13) argued that solar effects and anthropogenic halogenated gases can explain most of the observed warming of global mean surface air temperatures since 1850, with virtually no contribution from atmospheric carbon dioxide ( CO2) concentrations. Here we show that this conclusion is based on assumptions about the saturation of the CO2-induced greenhouse effect that have been experimentally falsified. L13 also confuses equilibrium and transient response, and relies on data sources that have been superseeded due to known inaccuracies. Furthermore, the statistical approach of sequential linear regression artificially shifts variance onto the first predictor. L13's artificial choice of regression order and neglect of other relevant data is the fundamental cause of the incorrect main conclusion. Consideration of more modern data and a more parsimonious multiple regression model leads to contradiction with L13's statistical results. Finally, the correlation arguments in L13 are falsified by considering either the more appropriate metric of global heat accumulation, or data on longer timescales.
RECOGNITION OF OCCLUSIONS IN CT IMAGES USING A CURVE-BASED PARAMETERIZATION METHOD
Authors: LIU HAO , ZHU GUANHUA , ZHAO JIANNING , QIAN HONGBO , DAI NING
Published: April 2014

It is an important way for segmentations of CT images to extract contours of objects slice-by-slice. For such a way, an important idea is analogy. That is to say, correct the contour in current slice (current contour) according to the contour in previous slice (previous contour). The key to properly correct the current contour is the ability to recognize occlusions (or say leaking parts) in the current contour. We present a curve-based curve parameterization method to recognize occlusions. The previous contour is evolved to the current contour using line projections. In the process of evolution, the parameterization is realized, which includes two types of information for every point in the evolved contour: the arc length parameter on the previous contour, and distance moved from the initial position to the present position. Using these two parameters, we are able to recognize occlusions in the current contour. Many experiments indicate that the method can recognize all of the occlusions in a given contour. Consequently, the method is robust and can be used as a part of an algorithm to automatically extract contours for CT images.
SEMI-AUTOMATIC CRACKS CORRECTION BASED ON SEAM PROCESSING, STOCHASTIC ANALYSIS AND LEARNING PROCESS
Authors: HADDAD BASHAR , JARRAH AMIN
Published: April 2014

The restoration process of cracked images is a challenge and an important field of image and video processing. Old images that experienced bad treatment and environmental conditions, or images of old buildings and statues have the problem of cracks. This problem restricts the ability of extracting information and processing of the image. Many algorithms have been proposed to restore cracked images but most of them failed to remove these cracks efficiently based on realistic assumptions. So, we developed and implemented a new algorithm in order to repair cracked images efficiently by proposing new techniques such as seam processing, stochastic analysis and learning process. The basic motivation of this work is to design a simple algorithm of efficient computation complexity and memory usage that can be used in an interactive fashion where a simple set of parameters is used to control behavior and performance of the algorithm. The algorithm uses seam processing to discover cracks and local spatial information to compensate and handle information shortage based on statistical analysis and data generation. In general, the algorithm can be divided into three phases: cracks detection, cracks filling, and post-processing phase to enhance the quality. The results show how the algorithm deals with two cracked images of extreme deterioration. The results are based on subjective tests where 85 persons graded and evaluated the results under different conditions through three separate sessions.