bluuebunny/crossref_metadata_2025 huggingface dataset:
Population genomics reveals multiple drivers of population differentiation in a sex‐role‐reversed pipefish
Authors: Flanagan Sarah P. , Rose Emily , Jones Adam G.
Published: August 2016

A major goal of molecular ecology is to identify the causes of genetic and phenotypic differentiation among populations. Population genomics is suitably poised to tackle these key questions by diagnosing the evolutionary mechanisms driving divergence in nature. Here, we set out to investigate the evolutionary processes underlying population differentiation in the Gulf pipefish, Syngnathus scovelli. We sampled approximately 50 fish from each of 12 populations distributed from the Gulf coast of Texas to the Atlantic coast of Florida and performed restriction‐site‐associated DNA sequencing to identify SNPs throughout the genome. After imposing quality and stringency filters, we selected a panel of 6348 SNPs present in all 12 populations, 1753 of which were not physically linked. We identified a genome‐wide pattern of isolation by distance, in addition to a more substantial genetic break separating populations in the Gulf of Mexico from those in the Atlantic. We also used several divergence outlier approaches and tests for genotype–environment correlations to identify 400 SNPs putatively involved in local adaptation. Patterns of phenotypic differentiation and variation diverged from the overall genomic pattern, suggesting that selection, phenotypic plasticity or demographic factors may be shaping phenotypes in distinct populations. Overall, our results suggest that population divergence is driven by a variety of factors in S. scovelli, including neutral processes and selection on multiple traits.
Spatiotemporal characteristics of the pharyngeal event‐related potential in healthy subjects and older patients with oropharyngeal dysfunction
Authors: Rofes L. , Ortega O. , Vilardell N. , Mundet L. , Clavé P.
Published: August 2016

Background

Oropharyngeal dysphagia (OD) is a highly prevalent symptom in older people. Appropriate oropharyngeal sensory feedback is essential for safe and efficient swallowing. However, pharyngeal sensitivity decreases with advancing age and could play a fundamental role in the physiopathology of swallowing dysfunction associated with aging. We aimed to characterize pharyngeal sensitivity and cortical response to a pharyngeal electrical stimulus in healthy volunteers (HV) and older patients with and without OD.

Methods

Eight young HV, eight older HV without OD, and 14 older patients with OD were studied by electroencephalography through 32 scalp electrodes. Pharyngeal event‐related potentials (ERP) were assessed following electrical stimulation of the pharynx. Sensory and tolerance thresholds to the electrical stimulus and latency, amplitude, and scalp current density of each ERP component were analyzed and compared. An ERP source localization study was also performed using the sLORETA software.

Key Results

Older participants (with and without OD) presented an increased sensory threshold to pharyngeal electrical stimulation (10.2 ± 1.7 mA and 11.5 ± 1.9 mA respectively), compared with young HV (6.0 ± 1.2 mA). The cortical activation of older HV in response to pharyngeal electrical stimulus was reduced compared with young HV (N2 amplitude: 0.22 ± 0.79 vs −3.10 ± 0.59, P<.05). Older patients with OD also presented disturbances to the pharyngo‐cortical connection together with disrupted pattern of cortical activation.

Conclusions and Inferences

Older people present a decline in pharyngeal sensory function, more severe in older patients with OD. This sensory impairment might be a critical pathophysiological element and a potential target for treatment of swallowing dysfunction in older patients.
The genetic architecture of freezing tolerance varies across the range of Arabidopsis thaliana
Authors: Horton Matthew W. , Willems Glenda , Sasaki Eriko , Koornneef Maarten , Nordborg Magnus
Published: August 2016

The capacity to tolerate freezing temperatures limits the geographical distribution of many plants, including several species of agricultural importance. However, the genes involved in freezing tolerance remain largely unknown. Here, we describe the variation in constitutive freezing tolerance that occurs among worldwide accessions of Arabidopsis thaliana. We found that although plants from high latitudes tend to be more freezing tolerant than plants from low latitudes, the environmental factors that shape cold adaptation differ across the species range. Consistent with this, we found that the genetic architecture of freezing tolerance also differs across its range. Conventional genome‐wide association studies helped identify a priori and other promising candidate genes. However, simultaneously modelling climate variables and freezing tolerance together pinpointed other excellent a priori candidate genes. This suggests that if the selective factor underlying phenotypic variation is known, multi‐trait mixed models may aid in identifying the genes that underlie adaptation.
Non‐native fruit trees facilitate colonization of native forest on abandoned farmland
Authors: Jacob Aerin L. , Lechowicz Martin J. , Chapman Colin A.
Published: August 2016

Ecological restoration of abandoned, formerly forested farmland can improve the delivery of ecosystem services and benefit biodiversity conservation. Restoration programs can involve removing isolated, non‐native trees planted by farmers for fruit or wood. As such “legacy” trees can attract seed dispersers and create microclimates that help native seedlings to establish, removing them may actually slow forest recovery. Working on abandoned farmland in Kibale National Park, Uganda, we evaluated the effect of legacy trees on forest recovery by measuring the number, diversity, and biomass of native seedlings and saplings regenerating in plots centered on avocado (Persea americana), mango (Mangifera indica), and Eucalyptus legacy trees compared with adjacent plots without legacy trees. The assemblages of native, forest‐dependent tree species in plots around avocado and mango trees were distinct from each other and from those around eucalyptus and all the near‐legacy plots. In particular, avocado plots had higher stem density and species richness of forest‐dependent species than near‐avocado plots, particularly large‐seeded, shade‐tolerant, and animal‐dispersed species—key targets of many restoration plans. Furthermore, many of the species found in high numbers were among those failing to establish in ongoing large‐scale forest restoration in Kibale. Taken together, our results demonstrate that the legacy trees facilitate the dispersal and establishment of native tree species. Retaining the existing legacy trees for a number of years could usefully complement existing management strategies to restore more biodiverse native forest in degraded lands. However, careful monitoring is needed to ensure that the legacy trees do not themselves establish.
Exports and Job Training
Authors: Bastos Paulo , Silva Joana , Proença Rafael
Published: August 2016

This paper examines whether export participation matters for job training, drawing on longitudinal worker–firm data for Brazilian manufacturing linked with detailed records on training activity from the main provider. Using industry‐specific exchange‐rate movements to generate exogenous variation in export status at the firm level, we find that export participation tends to increase the share of workers who receive technical upgrading. We also provide evidence that technical upgrading has positive returns to trainees within exporting firms. These results support the hypothesis that exporting requires skill upgrading, and suggest that this is partially achieved by training firms’ existing workforce.
Psychological variables underlying political orientations in an old and a new democracy: A comparative study between Sweden and Latvia
Authors: Dimdins Girts , Sandgren Maria , Montgomery Henry
Published: August 2016

This study examines in detail the psychological variables underlying ideological political orientation, and structure and contents of this orientation, in Sweden and Latvia. Individual political orientation is conceptualized on two dimensions: acceptance vs. rejection of social change and acceptance vs. rejection of inequality. Swedish (N = 320) and Latvian (N = 264) participants completed measures of political orientation, Social Dominance Orientation (SDO), Right Wing Authoritarianism (RWA), self vs. other orientation, tolerance for ambiguity, humanism and normativism, core political values, system justification, as well as moral foundations questionnaire and portrait values questionnaire. The results showed that the relation among the measured variables was similar in both samples. Swedish participants showed stronger endorsement of egalitarian attitudes and social values, whereas we found more self‐enhancing and socially conservative values and attitudes among the Latvian participants.
In vivo strain in the deep and superficial regions of the human patellar tendon
Authors: Lee D. , Barrett R. , Ryan M. , Saxby D. J. , Newsham‐West R. , Obst S. J.
Published: August 2016

This study investigated strain differences within the patellar tendon (PT) mid‐region using an ultrasound‐based digital image correlation (DIC) method. Six healthy young participants performed six knee extensions to 60% of maximal voluntary isometric contraction on 2 days. Sagittal ultrasound videos recorded during each contraction were analyzed using the DIC method to determine the strain–torque relationships of the superficial, deep, and whole PT mid‐regions. Significantly greater strain was observed in the deep vs superficial layer of the PT mid‐region for all contraction intensities, with peak strains of 5.8% (SD 1.7) and 4.5% (SD 1.5), respectively. DIC‐based measures of peak tendon strain were repeatable within [intraclass coefficients (ICC) >0.97] and between sessions (ICCs >0.83) and agreed well with the conventional point‐to‐point method. This study confirmed that significant differences exist between deep and superficial layers of PT mid‐region during ramped isometric extensions. These findings support the use of DIC to examine regional strain patterns within the PT mid‐region that may be important in the context of tendon injury and adaptation.
A case of recurrent swimming‐induced pulmonary edema in a triathlete: the need for awareness
Authors: Smith R. , Brooke D. , Kipps C. , Skaria B. , Subramaniam V.
Published: August 2016

This report discusses a rare case of a 55‐year‐old female triathlete who developed recurrent episodes of swimming‐induced pulmonary edema (SIPE). She had two hospital admissions with pulmonary edema after developing breathlessness while swimming, including a near‐drowning experience in an open water swim. With increasing popularity of triathlon and open water sports, this case highlights the importance of a greater awareness of SIPE among health professionals, event organizers, and athletes. This report explores the previous reported cases in triathletes and those who have suffered recurrent episodes. It is paramount that an accurate diagnosis is made as these individuals may be at an increased risk of future life‐threatening episodes.
Social Class and Political Engagement in the United States
Authors: Laurison Daniel
Published: August 2016

The relationship between class and political engagement in the United States is well‐established: people with lower incomes, who have less education, or who work outside the professional and managerial occupations do less of all forms of political engagement. They vote less than better‐off people, are less likely to give money to candidates, pay less attention to politics, and contact their representatives less often than those with more resources. They are also less likely to believe they can influence political decisions or to feel entitled to participate in politics. This article reviews the dominant (individualist and institutionalist) approaches to explaining inequalities in political participation and highlights recent “relational” work that offers a more integrated perspective on political engagement and class position.
Experiments and Constitutive Model for Deep and Superficial Fascia. Digital Image Correlation and Finite Element Validation
Authors: Ruiz‐Alejos D. , Peña J. A. , Pérez M. M. , Peña E.
Published: August 2016

Fascia is a highly organized collagenous tissue that is intimately connected with muscles. The mechanical properties of fascia strongly affect muscular actions and development of pathologies. The objective of this paper is to determine the mechanical properties of the deep and superficial fascia by uniaxial and pure shear tests and to propose and address the feasibility of a material hyperelastic constitutive model using combined Digital Image Correlation strain measurements and Finite Element (FE) computations. Experiments on deep and superficial fascia samples from the hindlimbs of six adult sheep along or perpendicular to collagen fibres and FE simulations of each experiment were compared. An anisotropic strain energy function was proposed to reproduce the mechanical behaviour of deep and superficial fascia and the material parameters were fitted using an optimization method and included in the FE simulations.

The mechanical response of the deep and superficial fascia shows typical behaviour of soft connective tissues. It is shown that the samples in longitudinal direction are stiffer than the samples in transversal direction for both kinds of tissues. When considering the deep and superficial samples, it is evident a greater stiffness of deep samples for both longitudinal and transversal directions with respect to superficial samples. Overall good predictions were obtained with the model proposed which present relatively low ε values, ε = 0.1189 and ε = 0.0722 for deep and superficial fascia respectively. The experimental and FE results were compared. The simulated curves slightly underestimated or overestimated the load for uniaxial and pure shear tests, respectively, but very accurately captured the stiffness and the overall response. These results demonstrate that the proposed model and the fitted material properties applied have a good capability of reproducing the experimental conditions.
Brincidofovir treatment of acyclovir‐resistant disseminated varicella zoster virus infection in an immunocompromised host
Authors: Mullane K.M. , Nuss C. , Ridgeway J. , Prichard M.N. , Hartline C.B. , Theusch J. , Mommeja‐Marin H. , Larson R.A.
Published: August 2016

Brincidofovir (BCV) is a broad‐spectrum antiviral agent active in vitro against double‐stranded DNA viruses including herpesviruses, adenoviruses, polyomaviruses, and poxviruses. We report successful BCV use in management of disseminated acyclovir‐ and cidofovir‐resistant varicella zoster virus in an immunocompromised hematopoietic stem cell transplant patient with chronic graft‐versus‐host disease who was intolerant to foscarnet.
KIF1A mediates axonal transport of BACE1 and identification of independently moving cargoes in living SCG neurons
Authors: Hung Christy O. Y. , Coleman Michael P.
Published: August 2016

Neurons rely heavily on axonal transport to deliver materials from the sites of synthesis to the axon terminals over distances that can be many centimetres long. KIF1A is the neuron‐specific kinesin with the fastest reported anterograde motor activity. Previous studies have shown that KIF1A transports a subset of synaptic proteins, neurofilaments and dense‐core vesicles. Using two‐colour live imaging, we showed that beta‐secretase 1 (BACE1)‐mCherry moves together with KIF1A‐GFP in both the anterograde and retrograde directions in superior cervical ganglions (SCG) neurons. We confirmed that KIF1A is functionally required for BACE1 transport by using KIF1A siRNA and a KIF1A mutant construct (KIF1A‐T312M) to impair its motor activity. We further identified several cargoes that have little or no co‐migration with KIF1A‐GFP and also move independently from BACE1‐mCherry. Together, these findings support a primary role for KIF1A in the anterograde transport of BACE1 and suggest that axonally transported cargoes are sorted into different classes of carrier vesicles in the cell body and are transported by cargo‐specific motor proteins through the axon.
The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens
Authors: Srivastava Kshitij , Polin Helene , Sheldon Sherry Lynne , Wagner Franz Friedrich , Grabmer Christoph , Gabriel Christian , Denomme Gregory Andrew , Flegel Willy Albert
Published: August 2016

BACKGROUND

The Rh system is the most complex and polymorphic blood group system in humans with more than 460 alleles known for the RHD gene. The DAU cluster of RHD alleles is characterized by the single‐nucleotide change producing the p.Thr379Met amino acid substitution. It is called the DAU‐0 allele and has been postulated to be the primordial allele, from which all other alleles of the DAU cluster have eventually evolved.

STUDY DESIGN AND METHODS

For two novel DAU alleles, the nucleotide sequences of all 10 exons as well as adjacent intronic regions, including the 5′ and 3′ untranslated regions (UTR), were determined for the RHD and RHCE genes. A phylogenetic tree for all DAU alleles was established using the neighbor‐joining method with Pan troglodytes as root. Standard hemagglutination and flow cytometry tests were performed.

RESULTS

We characterized two DAU alleles, DAU‐11 and DAU‐5.1, closely related to DAU‐3 and DAU‐5, respectively. A phylogenetic analysis of the 18 known DAU alleles indicated point mutations and interallelic recombination contributing to diversification of the DAU cluster.

CONCLUSIONS

The DAU alleles encode a group of RhD protein variants, some forming partial D antigens known to permit anti‐D in carriers; all are expected to cause anti‐D alloimmunization in recipients of red blood cell transfusions. The DAU alleles evolved through genomic point mutations and recombination. These results suggest that the cluster of DAU alleles represent a clade, which is concordant with our previous postulate that they derived from the primordial DAU‐0 allele.
Use of a 2‐tier histologic grading system for canine cutaneous mast cell tumors on cytology specimens
Authors: Hergt Franziska , von Bomhard Wolf , Kent Michael S. , Hirschberger Johannes
Published: August 2016

Background

Mast cell tumors (MCT) represent the most common malignant skin tumor in the dog. Diagnosis of an MCT can be achieved through cytologic examination of a fine‐needle aspirate. However, the grade of the tumor is an important prognostic marker and currently requires histologic assessment. Recently a 2‐tier histologic grading system based on nuclear features including number of mitoses, multinucleated cells, bizarre nuclei, and karyomegaly was proposed.

Objectives

The aim of this study was to assess if the cytomorphologic criteria proposed in the 2‐tier histologic grading system are applicable to cytology specimens.

Methods

A total of 141 MCT specimens reported as grade I, II, or III according to the Patnaik system with both histologic specimens and fine‐needle aspirates available were histologically and cytologically reevaluated in a retrospective study.

Results

According to the 2‐tier grading system, 38 cases were diagnosed histologically as high‐grade and 103 as low‐grade MCT. Cytologic grading resulted in 36 high‐grade and 105 low‐grade tumors. Agreement between histologic and cytologic grading based on the 2‐tier grading system was achieved in 133 cases (sensitivity 86.8%, specificity 97.1%, kappa value 0.853), but 5 high‐grade tumors on histology were classified as low‐grade on cytology.

Conclusion

Cytologic grading of MCT in the dog is helpful for initial assessment. However, the reliability of cytology using the 2‐tier grading system is considered inadequate at this point. Prospective studies including clinical outcome should be pursued to further determine diagnostic accuracy of cytologic mast cell grading.
Influence of sorption on sound propagation in granular activated carbon
Authors: Venegas Rodolfo , Umnova Olga
Published: August 2016

Granular activated carbon (GAC) has numerous applications due to its ability to adsorb and desorb gas molecules. Recently, it has been shown to exhibit unusually high low frequency sound absorption. This behavior is determined by both the multi-scale nature of the material, i.e., the existence of three scales of heterogeneities, and physical processes specific to micro- and nanometer-size pores, i.e., rarefaction and sorption effects. To account for these processes a model for sound propagation in GAC is developed in this work. A methodology for characterizing GAC which includes optical granulometry, flow resistivity measurements, and the derivation of the inner-particle model parameters from acoustical and non-acoustical measurements is also presented. The model agrees with measurements of normal incidence surface impedance and sound absorption coefficient on three different GAC samples.
The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction
Authors: Salah Heba , Li Meishan , Cacciani Nicola , Gastaldello Stefano , Ogilvie Hannah , Akkad Hazem , Namuduri Arvind Venkat , Morbidoni Valeria , Artemenko Konstantin A. , Balogh Gabor , Martinez-Redondo Vicente , Jannig Paulo , Hedström Yvette , Dworkin Barry , Bergquist Jonas , Ruas Jorge , Vigh Laszlo , Salviati Leonardo , Larsson Lars
Published: August 2016

BGP-15 reduces ventilation-induced diaphragm dysfunction by improving diaphragm fiber and myosin function and enhancing mitochondrial activity.
A shocking way to suppress inflammation
Authors: Bhakta Nirav R.
Published: August 2016

Vagus nerve stimulation suppresses inflammation and improves disease activity in rheumatoid arthritis.
Biomarker changes in early Alzheimer’s disease
Authors: Lucey Brendan P.
Published: August 2016

Biomarker profiles in early preclinical Alzheimer’s disease may predict progression to Aβ deposition.
Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with
In Vivo
Persistence
Authors: Ben-Ami Ronen , Zimmerman Offer , Finn Talya , Amit Sharon , Novikov Anna , Wertheimer Noa , Lurie-Weinberger Mor , Berman Judith
Published: August 2016

Candida glabrata
causes persistent infections in patients treated with fluconazole and often acquires resistance following exposure to the drug. Here we found that clinical strains of
C. glabrata
exhibit cell-to-cell variation in drug response (heteroresistance). We used population analysis profiling (PAP) to assess fluconazole heteroresistance (FLC
HR
) and to ask if it is a binary trait or a continuous phenotype. Thirty (57.6%) of 52 fluconazole-sensitive clinical
C. glabrata
isolates met accepted dichotomous criteria for FLC
HR
. However, quantitative grading of FLC
HR
by using the area under the PAP curve (AUC) revealed a continuous distribution across a wide range of values, suggesting that all isolates exhibit some degree of heteroresistance. The AUC correlated with rhodamine 6G efflux and was associated with upregulation of the
CDR1
and
PDH1
genes, encoding ATP-binding cassette (ABC) transmembrane transporters, implying that HetR populations exhibit higher levels of drug efflux. Highly FLC
HR
C. glabrata
was recovered more frequently than nonheteroresistant
C. glabrata
from hematogenously infected immunocompetent mice following treatment with high-dose fluconazole (45.8% versus 15%,
P
= 0.029). Phylogenetic analysis revealed some phenotypic clustering but also variations in FLC
HR
within clonal groups, suggesting both genetic and epigenetic determinants of heteroresistance. Collectively, these results establish heteroresistance to fluconazole as a graded phenotype associated with ABC transporter upregulation and fluconazole efflux. Heteroresistance may explain the propensity of
C. glabrata
for persistent infection and the emergence of breakthrough resistance to fluconazole.

IMPORTANCE
Heteroresistance refers to variability in the response to a drug within a clonal cell population. This phenomenon may have crucial importance for the way we look at antimicrobial resistance, as heteroresistant strains are not detected by standard laboratory susceptibility testing and may be associated with failure of antimicrobial therapy. We describe for the first time heteroresistance to fluconazole in
C. glabrata
, a finding that may explain the propensity of this pathogen to acquire resistance following exposure to fluconazole and to persist despite treatment. We found that, rather than being a binary all-or-none trait, heteroresistance was a continuously distributed phenotype associated with increased expression of genes that encode energy-dependent drug efflux transporters. Moreover, we show that heteroresistance is associated with failure of fluconazole to clear infection with
C. glabrata
. Together, these findings provide an empirical framework for determining and quantifying heteroresistance in
C. glabrata
.
Ablation of STAT3 in the B Cell Compartment Restricts Gammaherpesvirus LatencyIn Vivo
Authors: Reddy Sandeep Steven , Foreman Hui-Chen Chang , Sioux Thubten Ozula , Park Gee Ho , Poli Valeria , Reich Nancy C. , Krug Laurie T.
Published: August 2016

A challenging property of gammaherpesviruses is their ability to establish lifelong persistence. The establishment of latency in B cells is thought to involve active virus engagement of host signaling pathways. Pathogenic effects of these viruses during latency or following reactivation can be devastating to the host. Many cancers, including those associated with members of the gammaherpesvirus family, Kaposi’s sarcoma-associated herpesvirus and Epstein-Barr virus, express elevated levels of active host signal transducer and activator of transcription-3 (STAT3). STAT3 is activated by tyrosine phosphorylation in response to many cytokines and can orchestrate effector responses that include proliferation, inflammation, metastasis, and developmental programming. However, the contribution of STAT3 to gammaherpesvirus pathogenesis remains to be completely understood. This is the first study to have identified STAT3 as a critical host determinant of the ability of gammaherpesvirus to establish long-term latency in an animal model of disease. Following an acute infection, murine gammaherpesvirus 68 (MHV68) established latency in resident B cells, but establishment of latency was dramatically reduced in animals with a B cell-specific STAT3 deletion. The lack of STAT3 in B cells did not impair germinal center responses for immunoglobulin (Ig) class switching in the spleen and did not reduce either total or virus-specific IgG titers. Although ablation of STAT3 in B cells did not have a global effect on these assays of B cell function, it had long-term consequences for the viral load of the host, since virus latency was reduced at 6 to 8 weeks postinfection. Our findings establish host STAT3 as a mediator of gammaherpesvirus persistence.

IMPORTANCEThe insidious ability of gammaherpesviruses to establish latent infections can have detrimental consequences for the host. Identification of host factors that promote viral latency is essential for understanding latency mechanisms and for therapeutic interventions. We provide the first evidence that STAT3 expression is needed for murine gammaherpesvirus 68 to establish latency in primary B cells during an active immune response to infection. STAT3 deletion in B cells does not impair adaptive immune control of the virus, but loss of STAT3 in B cells has a long-lasting impact on viral persistence. These results indicate a potential therapeutic benefit of STAT3 inhibitors for combating gammaherpesvirus latency and, thereby, associated pathologies.
A LuxR Homolog in a Cottonwood Tree Endophyte That Activates Gene Expression in Response to a Plant Signal or Specific Peptides
Authors: Schaefer Amy L. , Oda Yasuhiro , Coutinho Bruna Goncalves , Pelletier Dale A. , Weiburg Justin , Venturi Vittorio , Greenberg E. Peter , Harwood Caroline S.
Published: August 2016

Homologs of the LuxR acyl-homoserine lactone (AHL) quorum-sensing signal receptor are prevalent in
Proteobacteria
isolated from roots of the Eastern cottonwood tree,
Populus deltoides
. Many of these isolates possess an orphan LuxR homolog, closely related to OryR from the rice pathogen
Xanthomonas oryzae
. OryR does not respond to AHL signals but, instead, responds to an unknown plant compound. We discovered an OryR homolog, PipR, in the cottonwood endophyte
Pseudomonas
sp. strain GM79. The genes adjacent to
pipR
encode a predicted ATP-binding cassette (ABC) peptide transporter and peptidases. We purified the putative peptidases, PipA and AapA, and confirmed their predicted activities. A transcriptional
pipA-gfp
reporter was responsive to PipR in the presence of plant leaf macerates, but it was not influenced by AHLs, similar to findings with OryR. We found that PipR also responded to protein hydrolysates to activate
pipA-gfp
expression. Among many peptides tested, the tripeptide Ser-His-Ser showed inducer activity but at relatively high concentrations. An ABC peptide transporter mutant failed to respond to leaf macerates, peptone, or Ser-His-Ser, while peptidase mutants expressed higher-than-wild-type levels of
pipA-gfp
in response to any of these signals. Our studies are consistent with a model where active transport of a peptidelike signal is required for the signal to interact with PipR, which then activates peptidase gene expression. The identification of a peptide ligand for PipR sets the stage to identify plant-derived signals for the OryR family of orphan LuxR proteins.

IMPORTANCE
We describe the transcription factor PipR from a
Pseudomonas
strain isolated as a cottonwood tree endophyte. PipR is a member of the LuxR family of transcriptional factors. LuxR family members are generally thought of as quorum-sensing signal receptors, but PipR is one of an emerging subfamily of LuxR family members that respond to compounds produced by plants. We found that PipR responds to a peptidelike compound, and we present a model for Pip system signal transduction. A better understanding of plant-responsive LuxR homologs and the compounds to which they respond is of general importance, as they occur in dozens of bacterial species that are associated with economically important plants and, as we report here, they also occur in members of certain root endophyte communities.
Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination
Authors: Karlsson Erik A. , Hertz Tomer , Johnson Cydney , Mehle Andrew , Krammer Florian , Schultz-Cherry Stacey
Published: August 2016

Obesity is a risk factor for developing severe influenza virus infection, making vaccination of utmost importance for this high-risk population. However, vaccinated obese animals and adults have decreased neutralizing antibody responses. In these studies, we tested the hypothesis that the addition of either alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve neutralizing antibody responses and protect obese mice from challenge. Our studies demonstrate that adjuvanted vaccine does increase both neutralizing and nonneutralizing antibody levels compared to vaccine alone. Although obese mice mount significantly decreased virus-specific antibody responses, both the breadth and the magnitude of the responses against hemagglutinin (HA) and neuraminidase (NA) are decreased compared to the responses in lean mice. Importantly, even with a greater than fourfold increase in neutralizing antibody levels, obese mice are not protected against influenza virus challenge and viral loads remain elevated in the respiratory tract. Increasing the antigen dose affords no added protection, and a decreasing viral dose did not fully mitigate the increased mortality seen in obese mice. Overall, these studies highlight that, while the use of an adjuvant does improve seroconversion, vaccination does not fully protect obese mice from influenza virus challenge, possibly due to the increased sensitivity of obese animals to infection. Given the continued increase in the global obesity epidemic, our findings have important implications for public health.

IMPORTANCE
Vaccination is the most effective strategy for preventing influenza virus infection and is a key component for pandemic preparedness. However, vaccines may fail to provide optimal protection in high-risk groups, including overweight and obese individuals. Given the worldwide obesity epidemic, it is imperative that we understand and improve vaccine efficacy. No work to date has investigated whether adjuvants increase the protective capacity of influenza vaccines in the obese host. In these studies, we show that adjuvants increased the neutralizing and nonneutralizing antibody responses during vaccination of lean and obese mice to levels considered “protective,” and yet, obese mice still succumbed to infection. This vulnerability is likely due to a combination of factors, including the increased susceptibility of obese animals to develop severe and even lethal disease when infected with very low viral titers. Our studies highlight the critical public health need to translate these findings and better understand vaccination in this increasing population.
Feasibility of nephrinuria as a screening tool for the risk of pre-eclampsia: prospective observational study
Authors: Zhai Tianyue , Furuta Itsuko , Akaishi Rina , Kawabata Kosuke , Chiba Kentaro , Umazume Takeshi , Ishikawa Satoshi , Yamada Takahiro , Morikawa Mamoru , Minakami Hisanori
Published: August 2016

Objectives

To investigate the possibility of nephrinuria as a screening tool for the risk of pre-eclampsia (PE).

Design

Prospective observational study.

Setting

A single university hospital. Changes in urinary nephrin:creatinine ratio (NCR, ng/mg) and protein:creatinine ratio (PCR, mg/mg) in pregnancy were determined. Significant proteinuria in pregnancy (SPIP) was defined as PCR>0.27. PE was diagnosed in women with both SPIP and hypertension.

Participants

89 pregnant women in whom neither hypertension nor SPIP was present at enrolment, providing 31, 125 and 93 random urine samples during first, second and third trimesters, respectively.

Results

PE developed in 14 of the 89 women. NCR increased with increasing PCR in 14 women with PE (correlation coefficient, 0.862; p<0.0001). In contrast, NCR did not change significantly despite significant increases in PCR in 75 women with normotensive pregnancies defined as neither SPIP nor hypertension, indicating that there was little increase in nephrinuria over the physiological range of proteinuria in pregnancy. Relative risk of later development of PE among asymptomatic second and third trimester women with NCR (ng/mg) >122 (95th centile value for 75 women with normotensive pregnancies) was 5.93 (95% CI 2.59 to 13.6; 60% (6/10) vs 10% (8/79)) and 13.5 (95% CI 3.31 to 55.0; 75% (6/8) vs 5.5% (2/36)), respectively, compared with women with NCR≤122 at that time.

Conclusions

Nephrinuria was unlikely to increase in normal pregnancy. A certain NCR cut-off may efficiently differentiate women at higher risk of PE.
Visually Impaired OLder people's Exercise programme for falls prevenTion (VIOLET): a feasibility study protocol
Authors: Skelton Dawn A , Bailey Cathy , Howel Denise , Cattan Mima , Deary Vincent , Coe Dot , de Jong Lex D , Gawler Sheena , Gray Joanne , Lampitt Rosy , Wilkinson Jennifer , Adams Nicola
Published: August 2016

Introduction

In the UK, 1 in 5 people aged 75 and over live with sight loss. Visually impaired older people (VIOP) have an above average incidence of falls and 1.3–1.9 times more likely to experience hip fractures, than the general population. Older people with eye diseases are ∼3 times more likely than those with good vision, to limit activities due to fear of falling. This feasibility study aims to adapt the group-based Falls Management Exercise (FaME) programme to the needs of VIOP and carry out an external pilot trial to inform the design of a future definitive randomised controlled trial.

Methods and design

A UK based 2-centre mixed methods, randomised, feasibility study will be conducted over 28 months. Stakeholder panels, including VIOP, will make recommendations for adaptations to an existing exercise programme (FaME), to meet the needs of VIOP, promoting uptake and adherence, while retaining required effective components of the exercise programme. 80 VIOP aged 60 and over, living at home, ambulant with or without a walking aid, will be recruited in Newcastle (n=40) and Glasgow (n=40) through National Health Service (NHS) Trusts and third sector partners. Participants randomised into the intervention arm will receive the adapted FaME programme. Participants randomised into the control arm will continue with usual activity. Outcomes are, recruitment rate, adherence and validated measures including fear of falling and quality of life. Postintervention in-depth qualitative interviews will be conducted with a purposive sample of VIOP (N=10). Postural stability instructors will be interviewed, before trial-specific training and following the intervention.

Ethics and dissemination

Ethics approval was secured through the National Research Ethics Service (NRES) Committee North East, Newcastle and North Tyneside 2. Glasgow Caledonian University was approved as a non-NHS site with local ethics approval. Findings will be disseminated through peer-reviewed journals, national and international conferences.

Trial registration number

ISRCTN16949845.
Medical students writing on death, dying and palliative care: a qualitative analysis of reflective essays
Authors: Boland Jason W , Dikomitis Lisa , Gadoud Amy
Published: August 2016

Background

Medical students and doctors are becoming better prepared to care for patients with palliative care needs and support patients at the end of life. This preparation needs to start at medical school.

Objective

To assess how medical students learn about death, dying and palliative care during a clinical placement using reflective essays and to provide insights to improve medical education about end-of-life care and/or palliative care.

Methods

Qualitative study in which all reflective essays written by third-year medical students in 1 year from a UK medical school were searched electronically for those that included ‘death’, ‘dying’ and ‘palliative care’. The anonymised data were managed using QSR NVivo 10 software, and a systematic analysis was conducted in three distinct phases: (1) open coding; (2) axial coding and (3) selective coding. Ethical approval was received.

Results

54 essays met the inclusion criteria from 241 essays screened for the terms ‘death’, ‘dying’ or ‘palliative’; 22 students gave consent for participation and their 24 essays were included. Saturation of themes was reached. Three overarching themes were identified: emotions, empathy and experiential and reflective learning. Students emphasised trying to develop a balance between showing empathy and their emotional state. Students learnt a lot from clinical encounters and watching doctors manage difficult situations, as well as from their refection during and after the experience.

Conclusions

Reflective essays give insights into the way students learn about death, dying and palliative care and how it affects them personally as well as the preparation that is needed to be better equipped to deal with these kinds of experiences. Analysis of the essays enabled the proposal of new strategies to help make them more effective learning tools and to optimise students’ learning from a palliative care attachment.
Is the learning value of workplace-based assessment being realised? A qualitative study of trainer and trainee perceptions and experiences
Authors: Barrett Aileen , Galvin Rose , Scherpbier Albert J J A , Teunissen Pim W , O’Shaughnessy Ann , Horgan Mary
Published: August 2016

Purpose

Workplace-based assessments (WBAs) were originally intended to inform learning and development by structuring effective observation-based feedback. The success of this innovation has not yet been established due in part to the widely varied tools, implementation strategies and research approaches. Using a conceptual framework of experience, trajectories and reifications in workplace learning, we aimed to explore trainer and trainee experiences and perceptions of the learning value of WBAs.

Study design

Trainers and trainees who had used at least one WBA in the previous year were invited to participate in semistructured interviews for this phenomenological study. We used a template analysis method to explore and compare the experiences of the two groups, using the emergent themes to develop an understanding of the impact of these experiences on perceptions of learning value.

Results

Nine trainers and eight trainees participated in the study. Common themes emerged among the two groups around issues of responsibility and engagement along with (mis)understandings of the purpose of the individual tools. Trainer-specific themes emerged related to the concurrent implementation of a new e-portfolio and perceptions of increased workload. Trainees associated WBA with a training structure support value but could not translate experiences into learning values.

Conclusions

WBAs provide trainees with a justified reason to approach trainers for feedback. WBAs, however, are not being reified as the formative assessments originally intended. A culture change may be required to change the focus of WBA research and reconceptualise this set of tools and methods as a workplace learning practice.
Bianchi type VI cosmological model with electromagnetic field in Lyra geometry
Authors: Abdel-Megied M. , Hegazy E.A.
Published: August 2016

Bianchi type VI cosmological model in the presence of electromagnetic field with variable magnetic permeability in the framework of Lyra geometry is presented. An exact solution is introduced by considering that the eigenvalue [Formula: see text] of the shear tensor [Formula: see text] is proportional to the scalar expansion Θ of the model, that is, C = (AB)L, where A, B, and C are the coefficients of the metric and L is a constant. Bianchi type V, III, and I cosmological models are given as special cases of Bianchi type VI. Physical and geometrical properties of the models are discussed.
Killing fields generated by multiple solutions to the Fischer–Marsden equation II
Authors: Guan Daniel , Cernéa Paul
Published: August 2016

In the process of finding Einstein metrics in dimension [Formula: see text], we can search metrics critical for the scalar curvature among fixed-volume metrics of constant scalar curvature on a closed oriented manifold. This leads to a system of PDEs (which we call the Fischer–Marsden Equation, after a conjecture concerning this system) for scalar functions, involving the linearization of the scalar curvature. The Fischer–Marsden conjecture said that, if the equation admits a solution, the underlying Riemannian manifold is Einstein. Counter-examples are known by Kobayashi and Lafontaine, and by our first paper. Multiple solutions to this system yield Killing vector fields. We showed in our first paper that the dimension of the solution space [Formula: see text] can be at most [Formula: see text], with equality implying that [Formula: see text] is a sphere with constant sectional curvatures. Moreover, we also showed there that the identity component of the isometry group has a factor [Formula: see text]. In this second paper, we apply our results in the first paper to show that either [Formula: see text] is a standard sphere or the dimension of the space of Fischer–Marsden solutions can be at most [Formula: see text].
Accelerated rare event sampling: Refinement and Ising model analysis
Authors: Yevick David , Lee Yong Hwan
Published: August 2016

In this paper, a recently introduced accelerated sampling technique [D. Yevick, Int. J. Mod. Phys. C 27, 1650041 (2016)] for constructing transition matrices is further developed and applied to a two-dimensional [Formula: see text] Ising spin system. By permitting backward displacements up to a certain limit for each forward step while evolving the system to first higher and then lower energies within a restricted interval that is steadily displaced toward zero temperature as the computation proceeds, accuracy can be greatly enhanced. Simultaneously, the elements obtained from numerous independent calculations are collected in a single transition matrix. The relative accuracy of this novel method is established through a comparison to a transition matrix procedure based on the Metropolis algorithm in which the temperature is appropriately varied during the calculation and the results interpreted in terms of the distribution of realizations over both energy and magnetization.
Proposal for the proper gravitational energy–momentum tensor
Authors: Shimizu Katsutaro
Published: August 2016

We propose a gravitational energy–momentum (GEMT) tensor of the general relativity obtained using Noether’s theorem. It transforms as a tensor under general coordinate transformations. One of the two indices of the GEMT labels a local Lorentz frame that satisfies the energy–momentum conservation law. The energies for a gravitational wave, a Schwarzschild black hole and a Friedmann–Lemaitre–Robertson–Walker (FLRW) universe are calculated as examples. The gravitational energy of the Schwarzschild black hole exists only outside the horizon, its value being the negative of the black hole mass.
An approach to directly probe simultaneity
Authors: Kipreos Edward T. , Balachandran Riju S.
Published: August 2016

The theory of special relativity derives from the Lorentz transformation. The Lorentz transformation implies differential simultaneity and light speed isotropy. Experiments to probe differential simultaneity should be able to distinguish the Lorentz transformation from a kinematically-similar alternate transformation that predicts absolute simultaneity, the absolute Lorentz transformation. Here, we describe how published optical tests of light speed isotropy/anisotropy cannot distinguish between the two transformations. We show that the shared equations of the two transformations, from the perspective of the “stationary” observer, are sufficient to predict null results in optical resonator experiments and in tests of frequency changes in one-way light paths. In an influential 1910 exposition on differential simultaneity, Comstock described how a “stationary” observer would observe different clock readings for spatially-separated “moving” clocks. The difference in clock readings is an integral aspect of differential simultaneity. We derive the equation for the difference in clock readings and show that it is equivalent to the Sagnac correction that describes light speed anisotropies in satellite communications. We describe an experimental strategy that can measure the differences in spatially-separated clock times to allow a direct probe of the nature of simultaneity.
A combination theorem for affine tree-free groups
Authors: Rourke Shane O.
Published: August 2016

Let [Formula: see text] be an ordered abelian group. We show how a group admitting a free affine action without inversions on a [Formula: see text]-tree admits a natural graph of groups decomposition, where vertex groups inherit actions on [Formula: see text]-trees. We introduce a stronger condition (essential freeness) on an affine action and apply recent work of various authors to deduce that a finitely generated group admitting an essentially free affine action on a [Formula: see text]-tree is relatively hyperbolic with nilpotent parabolics, is locally relatively quasiconvex, and has solvable word, conjugacy and isomorphism problems.

Conversely, given a graph of groups satisfying certain conditions, we show how an affine action of its fundamental group can be constructed. Specialising to the case of free affine actions, we obtain a large class of groups that have a free affine action on a [Formula: see text]-tree but that do not act freely by isometries on any [Formula: see text]-tree. We also give an example of a group that admits a free isometric action on a [Formula: see text]-tree but which is not residually nilpotent.