bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT

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

ABSTRACT
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

ObjectivesTo investigate the possibility of nephrinuria as a screening tool for the risk of pre-eclampsia (PE).DesignProspective observational study.SettingA 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.Participants89 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.ResultsPE 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.ConclusionsNephrinuria 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

IntroductionIn 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 designA 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 disseminationEthics 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 numberISRCTN16949845.
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

BackgroundMedical 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.ObjectiveTo 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.MethodsQualitative 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.Results54 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.ConclusionsReflective 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

ABSTRACTPurposeWorkplace-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 designTrainers 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.ResultsNine 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.ConclusionsWBAs 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.
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.
Recurrent PPP2R1A Mutations in Uterine Cancer Act through a Dominant-Negative Mechanism to Promote Malignant Cell Growth
Authors: Haesen Dorien , Abbasi Asbagh Layka , Derua Rita , Hubert Antoine , Schrauwen Stefanie , Hoorne Yana , Amant Frédéric , Waelkens Etienne , Sablina Anna , Janssens Veerle 
Published: August 2016

Abstract
Somatic missense mutations in the Ser/Thr protein phosphatase 2A (PP2A) Aα scaffold subunit gene PPP2R1A are among the few genomic alterations that occur frequently in serous endometrial carcinoma (EC) and carcinosarcoma, two clinically aggressive subtypes of uterine cancer with few therapeutic options. Previous studies reported that cancer-associated Aα mutants exhibit defects in binding to other PP2A subunits and contribute to cancer development by a mechanism of haploinsufficiency. Here we report on the functional significance of the most recurrent PPP2R1A mutations in human EC, which cluster in Aα HEAT repeats 5 and 7. Beyond predicted loss-of-function effects on the formation of a subset of PP2A holoenzymes, we discovered that Aα mutants behave in a dominant-negative manner due to gain-of-function interactions with the PP2A inhibitor TIPRL1. Dominant-negative Aα mutants retain binding to specific subunits of the B56/B′ family and form substrate trapping complexes with impaired phosphatase activity via increased recruitment of TIPRL1. Accordingly, overexpression of the Aα mutants in EC cells harboring wild-type PPP2R1A increased anchorage-independent growth and tumor formation, and triggered hyperphosphorylation of oncogenic PP2A-B56/B′ substrates in the GSK3β, Akt, and mTOR/p70S6K signaling pathways. TIPRL1 silencing restored GSK3β phosphorylation and rescued the EC cell growth advantage. Our results reveal how PPP2R1A mutations affect PP2A function and oncogenic signaling, illuminating the genetic basis for serous EC development and its potential control by rationally targeted therapies. Cancer Res; 76(19); 5719–31. ©2016 AACR.
A Novel Small Molecule Activator of Nuclear Receptor SHP Inhibits HCC Cell Migration via Suppressing Ccl2
Authors: Yang Zhihong , Koehler Angela N. , Wang Li 
Published: August 2016

Abstract
Small heterodimer partner (SHP, NR0B2) is a nuclear orphan receptor without endogenous ligands. Due to its crucial inhibitory role in liver cancer, it is of importance to identify small molecule agonists of SHP. As such, we initiated a probe discovery effort to identify compounds capable of modulating SHP function. First, we performed binding assays using small molecule microarrays (SMM) and discovered 5-(diethylsulfamoyl)-3-hydroxynaphthalene-2-carboxylic acid (DSHN) as a novel activator of SHP. DSHN transcriptionally activated Shp mRNA, but also stabilized the SHP protein by preventing its ubiquitination and degradation. Second, we identified Ccl2 as a new SHP target gene by RNA-seq. We showed that activation of SHP by DSHN repressed Ccl2 expression and secretion by inhibiting p65 activation of CCL2 promoter activity, as demonstrated in vivo in Shp−/− mice and in vitro in HCC cells with SHP overexpression and knockdown. Third, we elucidated a strong inhibitory effect of SHP and DSHN on HCC cell migration and invasion by antagonizing the effect of CCL2. Lastly, by interrogating a publicly available database to retrieve SHP expression profiles from multiple types of human cancers, we established a negative association of SHP expression with human cancer metastasis and patient survival. In summary, the discovery of a novel small molecule activator of SHP provides a therapeutic perspective for future translational and preclinical studies to inhibit HCC metastasis by blocking Ccl2 signaling. Mol Cancer Ther; 15(10); 2294–301. ©2016 AACR.
Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis
Authors: Nielsen Olav W. , Sajadieh Ahmad , Sabbah Muhammad , Greve Anders M. , Olsen Michael H. , Boman Kurt , Nienaber Christoph A. , Kesäniemi Y. Antero , Pedersen Terje R. , Willenheimer Ronnie , Wachtell Kristian 
Published: August 2016

Background:
Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal.

Methods:
A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate.

Results:

The incidence of all-cause mortality was highest for average follow-up systolic BP ≥160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1–6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6–2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP <120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9–6.1), diastolic BP ≥90 mm Hg (HR, 1.8; 95% CI, 1.1–2.9), and pulse pressure <50 mm Hg (HR, 1.8; 95% CI, 1.1–2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of 70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low systolic and diastolic BPs increased risk in patients with moderate aortic stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as reference, mortality was increased for systolic BP ≥160 mm Hg (HR, 1.7;
P
=0.033) and BP of 120 to 129 mm Hg (HR, 1.6;
P
=0.039).

Conclusions:
Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00092677.
The Non-Reading Reader: European Hebrew Literature at the Turn of the 20th Century
Authors: Nethanel Lilach 
Published: August 2016

Abstract
European Hebrew literature presents a challenge to the study of early-twentieth-century national literature. By the end of the nineteenth century, the reading of modern Hebrew in Europe was neither part of a religious practice, nor did it merely satisfy a purely aesthetic inclination. It mainly functioned as an ideological means used by a minority of Jews to support the linguistic-national Jewish revival. However, some fundamental contradictions put into question the actual influence of this literature on the political sphere. This article asks a series of questions about this period in the history of Hebrew readership: How did the non-spoken Hebrew language come to produce popular Hebrew writings? How did this literature engage the common Jewish reader? In this article I propose a new consideration of Hebrew reading practices. I argue for the inclusion of the non-reading readers as important contributors to the constitution of the Jewish literary nation.
Sensitivity of Axisymmetric Tropical Cyclone Spinup Time to Dry Air Aloft
Authors: Tang Brian H. , Rios-Berrios Rosimar , Alland Joshua J. , Berman Jeremy D. , Corbosiero Kristen L. 
Published: August 2016

AbstractThe sensitivity of tropical cyclone spinup time to the initial entropy deficit of the troposphere is examined in an axisymmetric hurricane model. Larger initial entropy deficits correspond to less moisture above the initial lifting condensation level of a subcloud-layer parcel. The spinup time is quantified in terms of thresholds of integrated horizontal kinetic energy within a radius of 300 km and below a height of 1.5 km. The spinup time increases sublinearly with increasing entropy deficit, indicating the greatest sensitivity lies with initial moisture profiles closer to saturation. As the moisture profile approaches saturation, there is a large increase in the low-level, area-averaged, vertical mass flux over the spinup period because of the predominance of deep convection. Higher entropy deficit experiments have a greater amount of cumulus congestus and reduced vertical mass flux over a longer duration. Consequently, the secondary circulation takes longer to build upward, and the radial influx of angular momentum is reduced. There is also a reduction in the conversion of potential available enthalpy to horizontal kinetic energy, as a result of reduced flow down the radial pressure gradient early in the spinup period. Later in the spinup period, the low-level vortex spins up relatively quickly near the nascent radius of maximum wind in the high-entropy deficit experiments, whereas the low-level vortex spins up over a wider area in the low-entropy deficit experiments.