bluuebunny/crossref_metadata_2025_split huggingface dataset:
NK1.1−CD4+NKG2D+ T cells suppress DSS‐induced colitis in mice through production of TGF‐β
Authors: Qian Xingxing , Hu Chunxia , Han Sen , Lin Zhijie , Xiao Weiming , Ding Yanbing , Zhang Yu , Qian Li , Jia Xiaoqing , Zhu Guoqiang , Gong Weijuan 
Published: February 2017

AbstractCD4+ NKG2D+ T cells are associated with tumour, infection and autoimmune diseases. Some CD4+ NKG2D+ T cells secrete IFN‐γ and TNF‐α to promote inflammation, but others produce TGF‐β and FasL to facilitate tumour evasion. Here, murine CD4+ NKG2D+ T cells were further classified into NK1.1− CD4+ NKG2D+ and NK1.1+ CD4+ NKG2D+ subpopulations. The frequency of NK1.1− CD4+ NKG2D+ cells decreased in inflamed colons, whereas more NK1.1+ CD4+ NKG2D+ cells infiltrated into colons of mice with DSS‐induced colitis. NK1.1− CD4+ NKG2D+ cells expressed TGF‐β and FasL without secreting IFN‐γ, IL‐21 and IL‐17 and displayed no cytotoxicity. The adoptive transfer of NK1.1− CD4+ NKG2D+ cells suppressed DSS‐induced colitis largely dependent on TGF‐β. NK1.1− CD4+ NKG2D+ cells did not expressed Foxp3, CD223 (LAG‐3) and GITR. The subpopulation was distinct from NK1.1+ CD4+ NKG2D+ cells in terms of surface markers and RNA transcription. NK1.1−CD4+ NKG2D+ cells also differed from Th2 or Th17 cells because the former did not express GATA‐3 and ROR‐γt. Thus, NK1.1− CD4+ NKG2D+ cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.
SLC2A3 single‐nucleotide polymorphism and duplication influence cognitive processing and population‐specific risk for attention‐deficit/hyperactivity disorder
Authors: Merker Sören , Reif Andreas , Ziegler Georg C. , Weber Heike , Mayer Ute , Ehlis Ann‐Christine , Conzelmann Annette , Johansson Stefan , Müller‐Reible Clemens , Nanda Indrajit , Haaf Thomas , Ullmann Reinhard , Romanos Marcel , Fallgatter Andreas J. , Pauli Paul , Strekalova Tatyana , Jansch Charline , Vasquez Alejandro Arias , Haavik Jan , Ribasés Marta , Ramos‐Quiroga Josep Antoni , Buitelaar Jan K. , Franke Barbara , Lesch Klaus‐Peter 
Published: February 2017

BackgroundAttention‐deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome‐wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter‐3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory–inhibitory balance impacting both brain development and activity‐dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD.MethodsCase–control association analyses of SLC2A3 single‐nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content.ResultsMeta‐analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population‐specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event‐related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high‐caloric food.ConclusionsTaken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk.
BIK1 cooperates with BAK1 to regulate constitutive immunity and cell death in Arabidopsis
Authors: Liu Jun , Chen Sufen , Chen Lijuan , Zhou Qi , Wang Menglong , Feng Dongru , Li Jian‐Feng , Wang Jinfa , Wang Hong‐Bin , Liu Bing 
Published: February 2017

SummaryIn Arabidopsis, both the membrane‐anchored receptor‐like kinase (RLK) BAK1 and the receptor‐like cytoplasmic kinase (RLCK) BIK1 are important mediators of transmembrane signal transduction that regulate plant development and immunity. However, little attention has been paid to their genetic association. This study found the bak1 bik1 double mutant of Arabidopsis displayed a severe dwarfism phenotype due to constitutive immunity and cell death in developing plants. These data suggest that BIK1 cooperates with BAK1 to regulate constitutive immunity and cell death.
Price Discrimination with Demarketing
Authors: Kim Jaesoo , Shin Dongsoo 
Published: February 2017

We study how demarketing interacts with pricing decisions to explain why and when it can be employed as the seller's optimal strategy. In our model, a monopolistic seller offers different price‐quality bundles of the product. A consumer's preference is private information. With demarketing, consumers must make a costly effort to purchase and/or utilize the product, whereas with marketing, the seller instead makes the effort so that the consumer's purchasing decision is independent of the cost of effort. Our result suggests that, for small or large effort costs, it is optimal for the seller to engage in marketing. For intermediate effort costs, however, demarketing can be optimal. With demarketing, the seller induces only the consumers with high valuation to make transaction effort. By doing so, the seller can price discriminate more effectively, thus extracting more surplus. We extend our analysis to the case where the seller can offer special deals through exclusive sales channels along with demarketing. Then, demarketing can be optimal even for large costs of effort.
In vitro Antifungal Activity of Essential oils and Major Components against Fungi Plant Pathogens
Authors: López‐Meneses Ana Karenth , Sánchez‐Mariñez Reyna Isabel , Quintana‐Obregón Eber Addi , Parra‐Vergara Norma Violeta , González‐Aguilar Gustavo Adolfo , López‐Saiz Carmen María , Cortez‐Rocha Mario Onofre 
Published: February 2017

AbstractThe indiscriminate use of synthetic fungicides has caused several problems to the environment, which place human and animal health at risk. Due to this fact, the search for natural alternatives to control phytopathogenic fungi growth has increased. This study aims to evaluate the antifungal activity of two essential oils (EOs) and three major components of EOs on the radial growth and spore germination of Fusarium verticillioides and Alternaria tenuissima. Minimum and half‐maximal inhibitory concentrations (CMI and CI50) at 96 h for each treatment were calculated. Lemongrass EO and citral caused the highest inhibition for A. tenuissima (CMI of 1000 μl/l and CI50 of 10 μl/l). For F. verticillioides, the most effective component was geraniol (CMI and CI50 of 1000 and 250 μl/l, respectively). Spore germination rate was delayed by the EOs and major components tested. The use of EOs was effective to control these two fungal species in their different grow stages.
A trait‐based approach to understand the consequences of specific plant interactions for community structure
Authors: Schöb Christian , Macek Petr , Pistón Nuria , Kikvidze Zaal , Pugnaire Francisco I. 
Published: February 2017

AbstractQuestionIn plant communities, the presence of a species has consequences for other species, with some being competitively excluded while others benefit from the close vicinity of neighbours. Even though such specificity in plant interactions is common and known, there is no empirical assessment of the mechanisms that would help us understand its importance for plant diversity. Here we asked whether analysing spatial associations between plant traits known to affect the environment (i.e. effect traits) and those known to respond to the environment (i.e. response traits) might explain plant–plant interactions and their role in community assembly.LocationSierra Nevada Mountains, Spain.MethodsIn a field study, we addressed the specificity of plant–plant interactions by quantifying effect traits of three co‐occurring cushion‐forming species and response traits of their associated plant assemblages. Traits were measured at the individual level and then aggregated to trait metrics (mean, range, dispersion) at the plot level. Finally, plot‐level metrics of effect traits were related to response traits and the species composition of plant communities.ResultsEach cushion‐forming species had a distinctive combination of effect traits and harboured a unique plant community with an exclusive composition of response traits. With multivariate statistics we showed that differences in effect traits (branch density and canopy height) among and within cushion species significantly explained response traits (specific leaf area, leaf dry matter content) of associated species and the local‐scale species composition.ConclusionsUsing effect and response traits measured at the individual level, we provide a mechanistic understanding of the species specificity of plant interactions and demonstrate how important such specificity is for species diversity in an ecosystem.
Assessing community and ecosystem sensitivity to climate change – toward a more comparative approach
Authors: Smith Melinda D. , Wilcox Kevin R. , Power Sally A. , Tissue David T. , Knapp Alan K. 
Published: February 2017

AbstractPlant communities can vary widely in their sensitivity to changing precipitation regimes, as reported by Byrne et al., Mulhouse et al. and Sternberg et al. in this issue of Journal of Vegetation Science. But to understand why communities differ in their sensitivity, we argue that clearly defined metrics of sensitivity and coordinated research approaches are needed to elucidate mechanisms.
Vascularization of the Selaginella rhizophore: anatomical fingerprints of polar auxin transport with implications for the deep fossil record
Authors: Matsunaga Kelly K. S. , Cullen Nevin P. , Tomescu Alexandru M. F. 
Published: February 2017

Summary

The Selaginella rhizophore is a unique and enigmatic organ whose homology with roots, shoots, or neither of the two remains unresolved. Nevertheless, rhizophore‐like organs have been documented in several fossil lycophytes. Here we test the homology of these organs through comparisons with the architecture of rhizophore vascularization in Selaginella.

We document rhizophore vascularization in nine Selaginella species using cleared whole‐mounts and histological sectioning combined with three‐dimensional reconstruction.

Three patterns of rhizophore vascularization are present in Selaginella and each is comparable to those observed in rhizophore‐like organs of fossil lycophytes. More compellingly, we found that all Selaginella species sampled exhibit tracheids that arc backward from the stem and side branch into the rhizophore base. This tracheid curvature is consistent with acropetal auxin transport previously documented in the rhizophore and is indicative of the redirection of basipetal auxin from the shoot into the rhizophore during development.

The tracheid curvature observed in Selaginella rhizophores provides an anatomical fingerprint for the patterns of auxin flow that underpin rhizophore development. Similar tracheid geometry may be present and should be searched for in fossils to address rhizophore homology and the conservation of auxin‐related developmental mechanisms from early stages of lycophyte evolution.
Clinical Performance of Magnetic Resonance Imaging Conditional and Nonconditional Cardiac Implantable Electronic Devices
Authors: SHAH ANAND D. , PATEL ADARSH U. , KNEZEVIC ANDREA , HOSKINS MICHAEL H. , HIRSH DAVID S. , MERCHANT FAISAL M. , EL CHAMI MIKHAEL F. , DELURGIO DAVID B. , PATEL ANSHUL M. , LEON ANGEL R. , LANGBERG JONATHAN J. , LLOYD MICHAEL S. 
Published: February 2017

ObjectivesThis study compared risks associated with magnetic resonance imaging (MRI) in patients with non‐MRI conditional and MRI conditional pacing and defibrillator systems with particular attention to clinically actionable outcomes.BackgroundWhile recipients of new MRI conditional pacemaker and defibrillator systems may undergo MRI scanning with very low risk, safety and regulatory concerns persist regarding such scanning in recipients of non‐MRI conditional systems.MethodsPatients with any cardiac device who were referred for MRI were prospectively enrolled at a single center and underwent scanning at 1.5 Tesla. Pre‐ and postscan lead characteristic changes, system integrity, and symptoms were analyzed. A comparison was made between non‐MRI conditional and MRI conditional devices.Results105 patients were evaluated allowing for comparison of 97 scans with non‐MRI conditional devices and 16 scans with MRI conditional devices. The cohort included those with pacemaker dependency, defibrillator, and cardiac resynchronization devices. Small, nonsignificant changes were observed in lead characteristics following scanning, and there was no significant difference when comparing non‐MRI and MRI conditional devices. Lead parameter changes did not require lead revision or programming changes. No device reset, failures, or premature scan termination was observed.Conclusions1.5 T MRI scanning in patients with MRI conditional and non‐MRI conditional cardiac devices was performed with similar, low clinical risk.
Which Regional Pain Rating Best Predicts Patient‐Reported Improvement in Lumbar Radiculopathy?
Authors: Bicket Mark C. , Pasquina Paul F. , Cohen Steven P. 
Published: February 2017

AbstractObjectiveTo determine the best regional pain score cutoff value that corresponds with patient‐reported improvement in lumbosacral radiculopathy (LSR).DesignRetrospective pooled data analysis from 3 randomized, controlled, multicenter trials using similar outcome assessments. All participants were exposed to interventions (epidural injections).SettingMilitary medical centers (6 U.S.A., 1 Germany) and large tertiary care hospitals (4 urban, 1 Veterans Affairs) between 2008 and 2014.SubjectsA total of 352 active duty military personnel and civilians ≥ 18 years of age with LSR.MethodsReceiver operating characteristics (ROC) with area under the curve (AUC) were calculated for 1‐month outcomes for pain (numeric rating scale) using absolute and relative change in regional pain scores (back, leg) to predict clinical improvement (global perceived effect).ResultsLeg pain demonstrated greater predictive ability to identify clinical improvement compared to back pain for both absolute (ROC AUC [95% confidence interval (CI)] 0.855 [0.813, 0.896] vs. 0.753 [0.702, 0.805]; P < 0.001) and relative (AUC [95% CI]; 0.867 [0.826, 0.909] vs. 0.780 [0.729, 0.831]; P = 0.002) reduction in reported pain. Clinical improvement was best identified using a leg pain reduction threshold of ≥ 1.75 points (absolute) and ≥ 23.5% (relative).ConclusionsRegion‐specific pain cutoff ratings predicted clinical improvement for patients with LSR. Cutoff points using newly identified, smaller reductions of 1.75 points and 23.5% more accurately predicted clinical improvement for LSR than conventionally used cutoffs (2 points and 30%). LSR patients report meaningful clinical improvement with smaller reductions in pain compared to other chronic pain diagnoses, suggesting LSR patients may have different expectations.
Drivers of Health‐Care Expenditure: What Role Does Baumol's Cost Disease Play?
Authors: Colombier Carsten 
Published: February 2017

ObjectivesWe devise an instrument to test for Baumol's cost disease in healthcare. Baumol's cost disease is a price effect that is assumed to be a major determinant of the secular rise in health‐care expenditure (HCE).MethodsThis price effect is notoriously difficult to estimate as the construction of medical price indices is flawed. However, our instrument—the adjusted Baumol variable—avoids this problem as we do not rely on medical price indices. We apply this instrument to a panel data set of 20 OECD countries ranging from 1970 to 2010.ResultsBaumol's cost disease partly affects healthcare. We estimate that the cost disease exerts from 15 to 40 percent of its potential full effect on HCE.ConclusionsPolicymakers have more leeway to curb ever‐increasing HCE than is suggested by the literature. Our instrument is also well suited to investigate other possibly affected sectors such as the government or education.
Surveillance of Omadacycline Activity against Clinical Isolates from a Global Collection (North America, Europe, Latin America, Asia-Western Pacific), 2010-2011
Authors: Pfaller Michael A. , Huband Michael D. , Rhomberg Paul R. , Flamm Robert K. 
Published: February 2017

ABSTRACT

Omadacycline is a broad-spectrum aminomethylcycline in late-stage clinical development for the treatment of acute bacterial skin and skin structure infections and community-acquired pneumonia as an oral and an intravenous once-daily formulation. In this study, omadacycline and comparators were tested against 69,246 nonduplicate bacterial isolates collected prospectively during 2010 and 2011 from medical centers in Asia-Pacific (11,397 isolates), Europe (23,490 isolates), Latin America (8,038 isolates), and North America (26,321 isolates). Omadacycline was tested by broth microdilution following Clinical and Laboratory Standards Institute M07-A10 (2015) methods. A total of 99.9% of
Staphylococcus aureus
isolates were inhibited by ≤2 μg/ml of omadacycline (MIC
50/90
, 0.12/0.25 μg/ml), including 100.0% of methicillin-susceptible
S. aureus
isolates and 99.8% of methicillin-resistant
S. aureus
isolates. Omadacycline potencies were comparable for
Streptococcus pneumoniae
(MIC
50/90
, 0.06/0.06 μg/ml), viridans group streptococci (MIC
50/90
, 0.06/0.12 μg/ml), and beta-hemolytic streptococci (MIC
50/90
, 0.06/0.12 μg/ml) regardless of species and susceptibility to penicillin. Omadacycline was active against
Enterobacteriaceae
and was most active against
Escherichia coli
(MIC
50/90
, 0.5/2 μg/ml),
Enterobacter aerogenes
(MIC
50/90
, 2/4 μg/ml),
Klebsiella oxytoca
(MIC
50/90
, 1/4 μg/ml), and
Citrobacter
spp. (MIC
50/90
, 1/4 μg/ml). Omadacycline was active against
Haemophilus influenzae
(MIC
50/90
, 1/1 μg/ml) regardless of β-lactamase status and against
Moraxella catarrhalis
(MIC
50/90
, 0.12/0.25 μg/ml). The potent activity of omadacycline against Gram-positive and Gram-negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative infections may be a concern.
Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections
Authors: Lee Dong-Hwan , Kim Yong Kyun , Jin Kyubok , Kang Myoung Joo , Joo Young-Don , Kim Yang Wook , Moon Young Soo , Shin Jae-Gook , Kiem Sungmin 
Published: February 2017

ABSTRACT

We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients (
n
= 37) with a creatinine clearance (CL
CR
) of 20 to 50 ml/min or >50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution (
V
/WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CL
CR
. The proposed equation to estimate doripenem CL in Korean patients was CL/WT = 0.109 × WT × (CL
CR
/57)
0.688
, where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was ≤1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility.
In Vitro
and
In Vivo
Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
Authors: Colley Thomas , Alanio Alexandre , Kelly Steven L. , Sehra Gurpreet , Kizawa Yasuo , Warrilow Andrew G. S. , Parker Josie E. , Kelly Diane E. , Kimura Genki , Anderson-Dring Lauren , Nakaoki Takahiro , Sunose Mihiro , Onions Stuart , Crepin Damien , Lagasse Franz , Crittall Matthew , Shannon Jonathan , Cooke Michael , Bretagne Stéphane , King-Underwood John , Murray John , Ito Kazuhiro , Strong Pete , Rapeport Garth 
Published: February 2017

ABSTRACT

The profile of PC945, a novel triazole antifungal designed for administration via inhalation, was assessed in a range of
in vitro
and
in vivo
studies. PC945 was characterized as a potent, tightly binding inhibitor of
Aspergillus fumigatus
sterol 14α-demethylase (CYP51A and CYP51B) activity (50% inhibitory concentrations [IC
50
s], 0.23 μM and 0.22 μM, respectively) with characteristic type II azole binding spectra. Against 96 clinically isolated
A. fumigatus
strains, the MIC values of PC945 ranged from 0.032 to >8 μg/ml, while those of voriconazole ranged from 0.064 to 4 μg/ml. Spectrophotometric analysis of the effects of PC945 against itraconazole-susceptible and -resistant
A. fumigatus
growth yielded IC
50
(determined based on optical density [OD]) values of 0.0012 to 0.034 μg/ml, whereas voriconazole (0.019 to >1 μg/ml) was less effective than PC945. PC945 was effective against a broad spectrum of pathogenic fungi (with MICs ranging from 0.0078 to 2 μg/ml), including
Aspergillus terreus
,
Trichophyton rubrum
,
Candida albicans
,
Candida glabrata
,
Candida krusei
,
Cryptococcus gattii
,
Cryptococcus neoformans
, and
Rhizopus oryzae
(1 or 2 isolates each). In addition, when
A. fumigatus
hyphae or human bronchial cells were treated with PC945 and then washed, PC945 was found to be absorbed quickly into both target and nontarget cells and to produce persistent antifungal effects. Among temporarily neutropenic immunocompromised mice infected with
A. fumigatus
intranasally, 50% of the animals survived until day 7 when treated intranasally with PC945 at 0.56 μg/mouse, while posaconazole showed similar effects (44%) at 14 μg/mouse. This profile affirms that topical treatment with PC945 should provide potent antifungal activity in the lung.