bluuebunny/crossref_metadata_2025_split huggingface dataset:
First report of Rhnull individuals in the Indian population and characterization of the underlying molecular mechanisms
Authors: Kulkarni Swati S. , Vasantha Kasiviswanathan , Gogri Harita , Parchure Disha , Madkaikar Manisha , Férec Claude , Fichou Yann 
Published: May 2017

BACKGROUNDRhnull phenotype is an extremely rare condition characterized by no expression of Rh antigens at the surface of red blood cells. Although rare, genetic bases of this phenotype are well known and include mutations within either the RH (RHD and RHCE) genes or the RHAG gene. So far Rhnull has been reported in individuals of Caucasian, African, and Asian origin. Here, we report individuals from two families of Indian origin representing such a rare phenotype.STUDY DESIGN AND METHODSSerologic analysis was carried out by testing with anti‐D, ‐C, ‐c, ‐E, and ‐e in Rhnull individuals and their family members. RH genes were analyzed by standard molecular approaches, including Sanger sequencing and quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments. RHAG gene was investigated by exon‐specific PCR amplification and Sanger sequencing.RESULTSIn one family, RHAG gene was found to be deleted at the homozygous state in the propositus, suggesting Rhnull of the regulator type. In the other family, a novel splice site variant in RHCE in cis with whole RHD gene deletion was identified at the homozygous state. Further functional analysis by minigene splicing assay showed that this variation, that is, c.801 + 1G>A, completely impairs normal splicing, then inactivating the expression of RhCE protein. Contrary to the former case, these data suggest Rhnull of the amorph type.CONCLUSIONOverall, we report for the first time the molecular mechanisms responsible for Rhnull phenotype in individuals of Indian origin. This study contributes to extend the molecular spectrum of variations in Rhnull individuals.
In vitro comparison of the dermal penetration of three different topical formulations containing lasalocid
Authors: Knight Evie C. , Trott Darren J. , Page Stephen W. , Garg Sanjay , Zhang Qian , Song Yunmei , Ebrahimie Esmaeil , Mills Paul C. , Shipstone Michael A. 
Published: May 2017

BackgroundTopical antimicrobial preparations are of utmost importance in treating suspected and confirmed meticillin‐resistant Staphylococcus pseudintermedius (MRSP) infections due to the increasing incidence of widespread resistance to systemic antimicrobials. Lasalocid is active against MRSP in vitro and this may become an important topical antimicrobial for the treatment of canine pyoderma.Hypothesis/ObjectivesTo determine effects of various formulation types on penetration and retention of lasalocid applied to canine skin in vitro.AnimalsNormal canine skin was collected from the thorax of five dogs that had been euthanized on the basis of health and/or intractable behavioural issues.MethodsSolution, lotion and ointment containing 2% lasalocid were applied to ex vivo canine skin. Transdermal penetration was assessed for a 24 h period and retention of lasalocid was assessed at the conclusion of the study.ResultsThe solution had significantly higher skin retention of lasalocid and proportion of applied dose retained in skin than lotion and ointment (Tukey–Kramer Honest Significant Difference test, P < 0.01). Lasalocid could not be detected in the receptor fluid of any Franz cell at any time point.Conclusions and clinical importanceLasalocid was not identified in the receptor fluid of any sample, indicating that systemic absorption of the active ingredient in vivo is unlikely. Lasalocid may be useful in the treatment of MRSP infections if in vivo studies support safety and efficacy.
Canine oral mucosa evaluation as a potential autograft tissue for the treatment of unresponsive keratoconjunctivitis sicca
Authors: Cherry Rose L. , Smith Jodi D. , Ben‐Shlomo Gil 
Published: May 2017

AbstractPurposeLabial mucosa transplantation for the treatment of canine keratoconjunctivitis sicca (KCS) has been reported recently. Postoperative alleviation of clinical signs was noted and assumed to be the result of labial salivary glands providing lubrication to the ocular tissue. The aim of this study was to evaluate the presence of minor salivary glands (MSG) in the canine oral mucosa.MethodsOral mucosal biopsies were collected from six dogs that died (n = 1) or were euthanized (n = 5) for reasons unrelated to this study. The breeds included were two Doberman Pinschers, one Labrador Retriever, one Portuguese Water Dog, one German Shepherd Dog, and one mixed canine. Three were spayed females, and three were castrated males with the median age of 9 years (range, 6–13 years). Samples were obtained by an 8‐mm punch biopsy at the following locations of the canine oral cavity: upper rostral labial mucosa at midline, lower rostral labial mucosa at midline, upper labial mucosa near the commissure, lower labial mucosa near the commissure, and buccal mucosa approximately 1 cm caudal to the commissure. Samples were routinely processed with hematoxylin and eosin, and periodic acid–Schiff stains. Samples were evaluated by light microscopy.ResultsAt the selected locations, no MSG or other secreting cells were detected.ConclusionsMinor salivary glands are not associated with alleviation of canine KCS symptoms following labial mucosa transplantation. Further studies are needed to determine the mechanism leading to the transient improvement of KCS symptoms in canine patients following labial mucosa transplantation.
English in The Voice of China
Authors: ZHOU SIJING , MOODY ANDREW 
Published: May 2017

ABSTRACTIn the first season (2012) of The Voice of China – a televised singing competition presented in a ‘reality TV’ format – 186 songs were performed on the program's stage to make the show one of the most popular in the history of Chinese television. While roughly one‐third of those songs were performed entirely in Chinese, the other two‐thirds contained some English elements (including a sizable number performed entirely in English). English lyrics function to achieve three linguistic goals: expressing referential meaning, voicing private feelings and directing routine speech acts. In doing this, however, some English lyrics deliberately blur the boundary between Chinese and English in order to develop an innovative and flexible style of performance.
Fuzzy species limits in Mediterranean gorgonians (Cnidaria, Octocorallia): inferences on speciation processes
Authors: Aurelle Didier , Pivotto Isabelle D. , Malfant Marine , Topçu Nur E. , Masmoudi Mauatassem B. , Chaoui Lamya , Kara Hichem M. , Coelho Márcio A.G. , Castilho Rita , Haguenauer Anne 
Published: May 2017

The study of the interplay between speciation and hybridization is of primary importance in evolutionary biology. Octocorals are ecologically important species whose shallow phylogenetic relationships often remain to be studied. In the Mediterranean Sea, three congeneric octocorals can be observed in sympatry: Eunicella verrucosa, Eunicella cavolini and Eunicella singularis. They display morphological differences and E. singularis hosts photosynthetic Symbiodinium, contrary to the two other species. Two nuclear sequence markers were used to study speciation and gene flow between these species, through network analysis and Approximate Bayesian Computation (ABC). Shared sequences indicated the possibility of hybridization or incomplete lineage sorting. According to ABC, a scenario of gene flow through secondary contact was the best model to explain these results. At the intraspecific level, neither geographical nor ecological isolation corresponded to distinct genetic lineages in E. cavolini. These results are discussed in the light of the potential role of ecology and genetic incompatibilities in the persistence of species limits.
Magnetic resonance imaging evaluation of renal ischaemia–reperfusion injury in a rabbit model
Authors: Pan Liang , Chen Jie , Xing Wei , Xing Zhaoyu , Zhang Jinggang , Peng Yan , Zhang Zhuoli 
Published: May 2017

New Findings
What is the central question of this study?
Renal ischaemia–reperfusion injury occurs in various clinical settings. The clinical diagnosis of ischaemia–reperfusion injury is routinely based on biochemical and haematological tests, which cannot evaluate the function of a single kidney. New magnetic resonance imaging techniques to identify the pathophysiological changes in the renal outer medulla were evaluated.

What is the main finding and its importance?
This study demonstrated that susceptibility‐weighted imaging is a feasible non‐invasive tool for imaging and evaluating physipathological changes in the renal outer medulla after ischaemia–reperfusion injury.

The aim was to evaluate the feasibility of susceptibility‐weighted imaging (SWI) as a tool to identify the changes in the renal outer medulla (OM) in a rabbit model of renal ischaemia–reperfusion injury (IRI). New Zealand rabbits were used (control group n = 10; IRI group n = 40). The rabbits in the IRI group were subjected to left renal artery clamping for 60 min. T2‐weighted (T2WI) and SWI examinations were performed at 1, 12, 24 or 48 h after reperfusion (each n = 10). After the examinations, the kidneys were submitted to histological evaluation. The contrast‐to‐noise ratio (CNR) for the left renal OM was measured using T2WI and SWI. The T2WI and SWI scores of the integrity of the renal OM were evaluated. There were significant differences between T2WI CNRs and SWI CNRs in the control group and the IRI 1, 12 and 48 h time points (all P < 0.05). No significant difference was found between T2WI and SWI CNRs at IRI 24 h (P > 0.05). The mean SWI scores of renal OM in the IRI 1 and 12 h subgroups were both significantly lower than that in the control group (all P < 0.05). The only significant difference in the mean T2WI scores of renal OM was observed between the control and IRI 1 h groups (P < 0.05). Susceptibility‐weighted imaging has a significant advantage in evaluation of healthy renal OM over conventional magnetic resonance imaging, and it is a feasible non‐invasive tool for imaging and evaluating changes in the renal OM after IRI.
Ticks and radio-frequency signals: behavioural response of ticks (Dermacentor reticulatus) in a 900 MHz electromagnetic field
Authors: Vargová Blažena , Kurimský Juraj , Cimbala Roman , Kosterec Michal , Majláth Igor , Pipová Natália , Tryjanowski Piotr , Jankowiak Łukasz , Majlathova Viktoria 
Published: May 2017

The electromagnetic field (EMF) is present in the environment throughout the world and encompasses both natural and human-made sources of electromagnetic fields. It has been shown that EMF influences a variety of biological systems, including the behavioural responses of both vertebrates and invertebrates. As such, determining the effects of the EMF on the ecosystem in detail may be important for understanding the ecology and biology of organisms, particularly those, such as ticks, that are important in disease transmission. Our main goal was to determine if the tick, Dermacentor reticulatus, interacts with the EMF. An experimental behavioural test of tick sensitivity to radio frequency power radiation was performed under laboratory conditions. Tests were performed in an electromagnetic compatibility laboratory in a radio frequency electromagnetic field (RF-EMF) anechoic chamber. Ticks were irradiated using a Double-Ridged Waveguide Horn Antenna with 900 MHz RF-EMF. The applied radio-frequency power was tuned below the proposed limit for public exposure to mobile phone base stations. We found that exposure induces an immediate tick locomotor response manifested either in a previously unreported jerking movement of the whole body or in jerking of the first pair of legs. Overall, ticks exhibited significantly greater movement in the presence of the RF-EMF. Significant sex differences relative to RF-EMF exposure were observed in both response variables. In the presence of RF-EMF, body jerking by females was greater than in males and vice versa for leg jerks. This study represents the first experimental evidence of a behavioural response of D. reticulatus ticks to exposure to RF-EMF.
A Simple Phosphate-Buffered-Saline-Based Extraction Method Improves Specificity of HIV Viral Load Monitoring Using Dried Blood Spots
Authors: Makadzange A. Tariro , Boyd F. Kathryn , Chimukangara Benjamin , Masimirembwa Collen , Katzenstein David , Ndhlovu Chiratidzo E. 
Published: May 2017

ABSTRACT

Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (<20 copies/ml in plasma or <400 copies/ml in DBS), and VL of <1,000 copies/ml, and VL of <5,000 copies/ml. Reported plasma VL ranged from TND, or <20, to 5,781,592 copies/ml, and DBS VL ranged from TND, or <400, to 467,600 copies/ml. At <1000 copies/ml, agreement between DBS and plasma was 96.7% (kappa coefficient, 0.93;
P
< 0.0001). The mean difference between DBS and plasma VL values was −1.06 log
10
copies/ml (95% confidence interval [CI], −1.17, −0.97;
P
< 0.0001). At a treatment failure threshold of >1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system.
Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation
Authors: Gordon N. C. , Pichon B. , Golubchik T. , Wilson D. J. , Paul J. , Blanc D. S. , Cole K. , Collins J. , Cortes N. , Cubbon M. , Gould F. K. , Jenks P. J. , Llewelyn M. , Nash J. Q. , Orendi J. M. , Paranthaman K. , Price J. R. , Senn L. , Thomas H. L. , Wyllie S. , Crook D. W. , Peto T. E. A. , Walker A. S. , Kearns A. M. 
Published: May 2017

ABSTRACT

Whole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks. However, for
Staphylococcus aureus
, the accumulation of within-host diversity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host diversity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks. We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA). The findings were compared with the routine investigation results and epidemiological evidence. Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC (
P
= 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1. We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles; however, these had only modestly increased pairwise diversity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) (
P
< 0.0001). Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype. The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted. Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.
The Poisoned Well: Enhancing the Predictive Value of Antimicrobial Susceptibility Testing in the Era of Multidrug Resistance
Authors: Brennan-Krohn Thea , Smith Kenneth P. , Kirby James E. 
Published: May 2017

ABSTRACT
Antimicrobial susceptibility testing (AST) is a fundamental mission of the clinical microbiology laboratory. Reference AST methods are based on bacterial growth in antibiotic doubling dilution series, which means that any error in the reference method inherently represents at least a 2-fold difference. We describe the origins of current AST reference methodology, highlight the sources of AST variability, and propose ideas for improving AST predictive power.
Selective Activation of Type II Interferon Signaling by Zika Virus NS5 Protein
Authors: Chaudhary Vidyanath , Yuen Kit-San , Chan Jasper Fuk-Woo , Chan Ching-Ping , Wang Pei-Hui , Cai Jian-Piao , Zhang Shuo , Liang Mifang , Kok Kin-Hang , Chan Chi-Ping , Yuen Kwok-Yung , Jin Dong-Yan 
Published: May 2017

ABSTRACTSevere complications of Zika virus (ZIKV) infection might be caused by inflammation, but how ZIKV induces proinflammatory cytokines is not understood. In this study, we show opposite regulatory effects of the ZIKV NS5 protein on interferon (IFN) signaling. Whereas ZIKV and its NS5 protein were potent suppressors of type I and type III IFN signaling, they were found to activate type II IFN signaling. Inversely, IFN-γ augmented ZIKV replication. NS5 interacted with STAT2 and targeted it for ubiquitination and degradation, but it had no influence on STAT1 stability or nuclear translocation. The recruitment of STAT1-STAT2-IRF9 to IFN-β-stimulated genes was compromised when NS5 was expressed. Concurrently, the formation of STAT1-STAT1 homodimers and their recruitment to IFN-γ-stimulated genes, such as the gene encoding the proinflammatory cytokine CXCL10, were augmented. Silencing the expression of an IFN-γ receptor subunit or treatment of ZIKV-infected cells with a JAK2 inhibitor suppressed viral replication and viral induction of IFN-γ-stimulated genes. Taken together, our findings provide a new mechanism by which the ZIKV NS5 protein differentially regulates IFN signaling to facilitate viral replication and cause diseases. This activity might be shared by a group of viral IFN modulators.IMPORTANCEMammalian cells produce three types of interferons to combat viral infection and to control host immune responses. To replicate and cause diseases, pathogenic viruses have developed different strategies to defeat the action of host interferons. Many viral proteins, including the Zika virus (ZIKV) NS5 protein, are known to be able to suppress the antiviral property of type I and type III interferons. Here we further show that the ZIKV NS5 protein can also boost the activity of type II interferon to induce cellular proteins that promote inflammation. This is mediated by the differential effect of the ZIKV NS5 protein on a pair of cellular transcription factors, STAT1 and STAT2. NS5 induces the degradation of STAT2 but promotes the formation of STAT1-STAT1 protein complexes, which activate genes controlled by type II interferon. A drug that specifically inhibits the IFN-γ receptor or STAT1 shows an anti-ZIKV effect and might also have anti-inflammatory activity.
Immune Escape Variants of H9N2 Influenza Viruses Containing Deletions at the Hemagglutinin Receptor Binding Site Retain Fitness
In Vivo
and Display Enhanced Zoonotic Characteristics
Authors: Peacock Thomas P. , Benton Donald J. , James Joe , Sadeyen Jean-Remy , Chang Pengxiang , Sealy Joshua E. , Bryant Juliet E. , Martin Stephen R. , Shelton Holly , Barclay Wendy S. , Iqbal Munir 
Published: May 2017

ABSTRACT
H9N2 avian influenza viruses are enzootic in poultry across Asia and North Africa, where they pose a threat to human health as both zoonotic agents and potential pandemic candidates. Poultry vaccination against H9N2 viruses has been employed in many regions; however, vaccine effectiveness is frequently compromised due to antigenic drift arising from amino acid substitutions in the major influenza virus antigen hemagglutinin (HA). Using selection with HA-specific monoclonal antibodies, we previously identified H9N2 antibody escape mutants that contained deletions of amino acids in the 220 loop of the HA receptor binding sites (RBSs). Here we analyzed the impact of these deletions on virus zoonotic infection characteristics and fitness. We demonstrated that mutant viruses with RBS deletions are able to escape polyclonal antiserum binding and are able to infect and be transmitted between chickens. We showed that the deletion mutants have increased binding to human-like receptors and greater replication in primary human airway cells; however, the mutant HAs also displayed reduced pH and thermal stability. In summary, we infer that variant influenza viruses with deletions in the 220 loop could arise in the field due to immune selection pressure; however, due to reduced HA stability, we conclude that these viruses are unlikely to be transmitted from human to human by the airborne route, a prerequisite for pandemic emergence. Our findings underscore the complex interplay between antigenic drift and viral fitness for avian influenza viruses as well as the challenges of predicting which viral variants may pose the greatest threats for zoonotic and pandemic emergence.

IMPORTANCE
Avian influenza viruses, such as H9N2, cause disease in poultry as well as occasionally infecting humans and are therefore considered viruses with pandemic potential. Many countries have introduced vaccination of poultry to try to control the disease burden; however, influenza viruses are able to rapidly evolve to escape immune pressure in a process known as “antigenic drift.” Previously, we experimentally generated antigenic-drift variants in the laboratory, and here, we test our “drifted” viruses to assess their zoonotic infection characteristics and transmissibility in chickens. We found that the drifted viruses were able to infect and be transmitted between chickens and showed increased binding to human-like receptors. However, the drift mutant viruses displayed reduced stability, and we predict that they are unlikely to be transmitted from human to human and cause an influenza pandemic. These results demonstrate the complex relationship between antigenic drift and the potential of avian influenza viruses to infect humans.