bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mouse trigeminal neurons respond to kokumi substances
Authors: Leijon Sara C.M. , Chaudhari Nirupa , Roper Stephen D. 
Published: February 2019

1.AbstractUsing in vivo confocal Ca2+ imaging, we investigated whether oral application of kokumi substances elicits responses in trigeminal somatosensory ganglion neurons of the mouse. Our results show that 100 μM γEVG (γ-Glu-Val-Gly), a potent kokumi stimulus, evokes responses in a very small fraction (0.6 %) of neurons in area V3 (oral sensory field) of the trigeminal ganglion. By comparison, cooled artificial saliva elicited thermal-evoked responses in >7 % of V3 trigeminal ganglion neurons. γEVG-evoked responses were small and quite variable, with latencies ranging from 2 to over 200 sec. Co-application of the calcium sensing receptor (CaSR) inhibitor NPS-2143 significantly decreased γEVG-evoked activity. Furthermore, we show that 4 additional kokumi substances evoked responses in mouse trigeminal ganglion neurons. All neurons responding to kokumi compounds were small cells, with mean diameters below 20 μm. In summary, our data show that certain physiological and pharmacological properties of responses to kokumi compounds can be recorded from sensory neurons in the trigeminal ganglion of living mice. Thus, sensory neurons in the somatosensory trigeminal ganglia may transmit signals from the oral cavity to the central nervous system to generate the texture perceptions that are part of the enigmatic sensations evoked by kokumi substances.
Age-structure as key to delayed logistic proliferation of scratch assays
Authors: Bobadilla Ana Victoria Ponce , Carraro Thomas , Byrne Helen M. , Maini Philip K. , Alarcón Tomás 
Published: February 2019

AbstractScratch assays are in-vitro methods for studying cell migration. In these experiments, a scratch is made on a cell monolayer and recolonisation of the scratched region is imaged to quantify cell migration rates. Typically, scratch assays are modelled by reaction diffusion equations depicting cell migration by Fickian diffusion and modelling proliferation by a logistic term. In a recent paper (Jin, W. et al. Bull Math Biol (2017)), the authors observed experimentally that during the early stage of the recolonisation process, there is a disturbance phase where proliferation is not logistic, and this is followed by a growth phase where proliferation appears to be logistic. The authors did not identify the precise mechanism that causes the disturbance phase but showed that ignoring it can lead to incorrect parameter estimates. The aim of this work is to show that a non-linear age-structured population model can account for the two phases of proliferation in scratch assays. The model consists of an age-structured cell cycle model of a cell population, coupled with an ordinary differential equation describing the resource concentration dynamics in the substrate. The model assumes a resource-dependent cell cycle threshold age, above which cells are able to proliferate. By studying the dynamics of the full system in terms of the subpopulations of cells that can proliferate and the ones that can not, we are able to find conditions under which the model captures the two-phase behaviour. Through numerical simulations we are able to show that the resource concentration in the substrate regulates the biphasic dynamics.
Topological data analysis reveals principles of chromosome structure throughout cellular differentiation
Authors: Sauerwald Natalie , Shen Yihang , Kingsford Carl 
Published: February 2019

AbstractThree-dimensional chromosome structure has a significant influence in many diverse genomic processes and has recently been shown to relate to cellular differentiation. Many methods for describing the chromosomal architecture focus on specific substructures such as topologically-associating domains (TADs) or compartments, but we are still missing a global view of all geometric features of chromosomes. Topological data analysis (TDA) is a mathematically well-founded set of methods to derive robust information about the structure and topology of data sets, making it well-suited to better understand the key features of chromosome structure. By applying TDA to the study of chromosome structure through differentiation across three cell lines, we provide insight into principles of chromosome folding generally, and observe structural changes across lineages. We identify both global and local differences in chromosome topology through differentiation, identifying trends consistent across human cell lines.AvailabilityScripts to reproduce the results from this study can be found at https://github.com/Kingsford-Group/hictdaContactcarlk@cs.cmu.edu
Optimal Scheduling of Bevacizumab and Pemetrexed/cisplatin Dosing in Non-Small Cell Lung Cancer
Authors: Schneider Benjamin K , Boyer Arnaud , Ciccolini Joseph , Barlesi Fabrice , Wang Kenneth , Benzekry Sebastien , Mochel Jonathan P 
Published: February 2019

AbstractBevacizumab-pemetrexed/cisplatin (BEV-PEM/CIS) is a first line therapeutic for advanced non-squamous non-small cell lung cancer (NSCLC). Bevacizumab potentiates PEM/CIS cytotoxicity by inducing transient tumor vasculature normalization. BEV-PEM/CIS has a narrow therapeutic window. Therefore, it is an attractive target for administration schedule optimization. The present study leverages our previous work on BEV-PEM/CIS pharmacodynamic modeling in NSCLC-bearing mice to estimate the optimal gap in the scheduling of sequential BEV-PEM/CIS. We predicted the optimal gap in BEV-PEM/CIS dosing to be 2.0 days in mice and 1.2 days in humans. Our simulations suggest that the efficacy loss in scheduling BEV-PEM/CIS at too great of a gap is much less than the efficacy loss in scheduling BEV-PEM/CIS at too short of a gap.
Genomic programming of antigen cross-presentation in IRF4-expressing human Langerhans cells
Authors: Polak Marta E , Sirvent Sofia , Clayton Kalum , Davies James , Vallejo Andres F. , Wu Zhiguo , Woo Jeongmin , Riddell Jeremy , Stumpf Patrick , Rose-Zerilli Matthew , West Jonathan , Pujato Mario , Chen Xiaoting , Woelk Christopher H. , MacArthur Ben , Ardern-Jones Michael , Friedmann Peter S , Weirauch Matthew T. , Singh Harinder 
Published: February 2019

AbstractLangerhans cells (LCs) in the epidermis present MHC I and MHC II-restricted antigens thereby priming either CD8 or CD4 T cell immune responses. The genomic programs and transcription factors regulating antigen presentation in LCs remain to be elucidated. We show human LCs are highly efficient in MHC I-antigen cross-presentation but lack the transcription factor IRF8 that is critical in dendritic cells. LC migration from the epidermis enhances their ability to cross-present antigens and is accompanied by the induction of the transcription factor IRF4, whose expression is correlated by scRNA-seq with genes involved in ubiquitin-dependent protein degradation. Chromatin profiling reveals enrichment of EICE and AICE composite DNA binding motifs in regulatory regions of antigen-presentation genes, which can be recognized by IRF4 in conjunction with PU.1 or BATF3 expressed in LCs. Thus, the genomic programming of human LCs including inducible expression of IRF4 with enhanced cross-presentation distinguishes them from conventional dendritic cells.
Spatiotemporal Coupling of Vessel Cavitation and Discharge of Stored Xylem Water in a Tree Sapling
Authors: Knipfer Thorsten , Reyes Clarissa , Earles J. Mason , Berry Z. Carter , Johnson Daniel M. , Brodersen Craig R. , McElrone Andrew J. 
Published: February 2019

Abstract
Water discharge from stem internal storage compartments is thought to minimize the risk of vessel cavitation. Based on this concept, one would expect that water storage compartments involved in the buffering of xylem tensions empty before the onset of vessel cavitation under drought stress, and potentially refill after soil saturation. However, scant in vivo data exist that elucidate this localized spatiotemporal coupling. In this study on intact saplings of American chestnut (Castanea dentata), x-ray computed microtomography (microCT) showed that the xylem matrix surrounding vessels releases stored water and becomes air-filled either concurrent to or after vessel cavitation under progressive drought stress. Among annual growth rings, the xylem matrix of the current year remained largely water-filled even under severe drought stress. In comparison, microtomography images collected on excised stems showed that applied pressures of much greater than 0 MPa were required to induce water release from the xylem matrix. Viability staining highlighted that water release from the xylem matrix was associated primarily with emptying of dead fibers. Refilling of the xylem matrix and vessels was detected in intact saplings when the canopy was bagged and stem water potential was close to 0 MPa, and in leafless saplings over the winter period. In conclusion, this study indicates that the bulk of water stored in the xylem matrix is released after the onset of vessel cavitation, and suggests that capillary water contributes to overall stem water storage under drought but is not used primarily for the prevention of drought-induced vessel cavitation in this species.
Varying the spatial arrangement of synthetic herbivore‐induced plant volatiles and companion plants to improve conservation biological control
Authors: Jaworski Coline C. , Xiao Da , Xu Qingxuan , Ramirez‐Romero Ricardo , Guo Xiaojun , Wang Su , Desneux Nicolas 
Published: February 2019

Abstract

Conservation biological control aims to control pests by promoting wild populations of natural enemies. One challenge is to attract and retain efficient natural enemies in crop fields, which often are a suboptimal environment. Towards this goal, the attract‐and‐reward strategy relies on combining attractive synthetically produced herbivore‐induced plant volatiles (HIPVs) with companion plants (non‐crop plants which provide alternative resources to the targeted natural enemies). Although severely overlooked, the spatial arrangement of HIPV dispensers and rewards inside crop fields may strongly influence the foraging behaviour and persistence of natural enemies and thus the success of this pest management strategy.

We tested the impact of two contrasting spatial arrangements of HIPV dispensers and rewards, alternatively inside and around a block of target apple trees, on the efficacy of the biological control of Aphis citricola populations by the common predatory ladybird Propylea japonica in apple orchards in northern China. We used synthetic methyl salicylate (MeSA) as an attractant and the companion plant Calendula officinalis as a reward. To better understand how the spatial arrangement of MeSA dispensers and companion plants affected the attraction and foraging behaviour of adult ladybirds, we conducted indoor experiments in a flight mill, an olfactometer and a wind‐tunnel.

Blocks of target trees treated with MeSA dispensers inside and companion plants around provided the most efficient pest control in orchards, compared with the opposite spatial arrangement.

The synthetic MeSA dispenser and the companion plant synergistically attracted ladybirds in the olfactometer and enhanced their flight activity in the flight mill. In the wind‐tunnel, MeSA served as a spatial cue for ladybirds to find nearby prey, while companion plants were sought in the absence of prey.

Synthesis and applications. This study aims to further improve aphid control in apple orchards through a careful spatial arrangement of herbivore‐induced plant volatiles dispensers (HIPVs) and rewards (companion plants) in optimized attract‐and‐reward strategies. Without such assessment, these strategies may be hazardous even with well‐identified targeted natural enemies. Associated lab experiments highlight that interactions between HIPVs and companion plants influence ladybird foraging pattern, and that their spatial arrangement can modulate the ability of such key predators to find their prey.
An Olympic‐sized Challenge: Effect of Organizational Pathology on Maintaining and Repairing Organizational Legitimacy in Sports Governing Bodies
Authors: Anastasiadis Stephanos , Spence Laura J. 
Published: February 2019

AbstractPrivate organizations increasingly wield public authority, with substantial impact on the lives of individual persons. Such authority is often paired with enhanced public scrutiny and decreased trust in the relevant organization, leading to a loss of legitimacy. This paper uses sports governing bodies to contribute to the literature on governance by developing theory on the interaction between organizational legitimacy and pathological internal structures. It takes a nuanced view of legitimacy and extends a model of organizational pathology. While primarily conceptual, the paper uses the well‐documented cases of the International Olympic Committee and, to a lesser extent, FIFA to illustrate how organizational pathology can not only undermine an organization's legitimacy, but can also interfere with its ability to perceive a path to legitimacy repair, even when it recognizes the necessity of doing so. The paper concludes with recommendations for practice and suggestions for future research looking beyond sports governing bodies.
Is Investor Attention for Sale? The Role of Advertising in Financial Markets
Authors: MADSEN JOSHUA , NIESSNER MARINA 
Published: February 2019

ABSTRACTPrior research documents capital market benefits of increased investor attention to accounting disclosures and media coverage; however, little is known about how investors and markets respond to attention‐grabbing events that reveal little nonpublic information. We use daily firm advertising data to test how advertisements, which are designed to attract consumers' attention, influence investors' attention and financial markets (i.e., spillover effects). Exploiting the fact that firms often advertise at weekly intervals, we use an instrumental variables approach to provide evidence that print ads, especially in business publications, trigger temporary spikes in investor attention. We further find that trading volume and quoted dollar depths increase on days with ads in a business publication. We contribute to research on how management choices influence firms' information environments, determinants and consequences of investor attention, and consequences of advertising for financial markets.
Early referral for endoscopy is the most appropriate management strategy in cases of food bolus obstruction
Authors: Fulforth James M , Chen Amanda J , Falvey James D 
Published: February 2019

AbstractObjectiveTo investigate the characteristics of patients presenting with oesophageal food bolus obstruction (FBO) who achieve early resolution of symptoms, and to assess the impact of medical therapies on the overall time course of FBO.MethodsA retrospective observational study was performed in a university teaching hospital with regional acute endoscopy services. Patients presenting with symptoms of FBO were identified through clinical coding and demographic, clinical and endoscopic data extracted from the electronic medical record. The primary outcome was the time to resolution defined as the earliest of symptom resolution, endoscopic or surgical intervention or discharge.ResultsA total of 116 patients presented with symptoms of FBO. Twenty‐seven (23.3%) had early resolution of symptoms and were discharged from the ED without acute endoscopy, the remainder were admitted for further management. Patients discharged from the ED presented to hospital sooner after the onset of symptoms (137 vs 288 min, P < 0.05), but did not differ from those admitted in any other characteristic. Seventy‐one (61.2%) patients received medical therapy. There was no statistical difference in the time to resolution between those who received medical therapy and those who did not. Furthermore, the use of medical therapy was associated with a delay in referral for endoscopy (140 vs 100 min, P < 0.05).ConclusionsTime from symptom onset to presentation is the only predictor of early resolution from FBO, while medical therapy is ineffective in relieving obstruction and may delay definitive therapy. We recommend the use of an institutional management plan to facilitate early access to endoscopy in cases of FBO.
Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging
Authors: Semba Richard D. , Zhang Pingbo , Adelnia Fatemeh , Sun Kai , Gonzalez‐Freire Marta , Salem Norman , Brennan Nicholas , Spencer Richard G. , Fishbein Kenneth , Khadeer Mohammed , Shardell Michelle , Moaddel Ruin , Ferrucci Luigi 
Published: February 2019

AbstractThe decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy (31P‐MRS) in 385 participants (256 women, 129 men), aged 24–97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), kPCr, was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography–tandem mass spectrometry. Adults in the highest quartile of kPCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine‐learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of kPCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults.
Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants
Authors: Norman Elisabeth , Kindblom Jenny M. , Rane Anders , Berg Ann‐Cathrine , Schubert Ulf , Hallberg Boubou , Fellman Vineta 
Published: February 2019

AbstractAimFentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain.MethodsPreterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin‐breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.ResultsThe median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15–31 minutes, two and four hours and the half‐lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low‐ and high‐dose groups, respectively. A significant correlation was seen between weight at study inclusion and half‐life (Spearman′s r = −0.9, p < 0.001), volume of distribution (r = −0.8, p < 0.01) and clearance (r = −0.9, p < 0.01) in the low‐dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated.ConclusionThe inter‐individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 μg/kg seems not effective for skin‐breaking procedures.
Preserved cardiovascular homeostasis despite blunted acetylcholine‐induced dilation in mice with endothelial muscarinic M3 receptor deletion
Authors: Rhoden Alexandra , Speiser Jakob , Geertz Birgit , Uebeler June , Schmidt Kjestine , de Wit Cor , Eschenhagen Thomas 
Published: February 2019

AbstractAimMuscarinic acetylcholine receptors (AChMR1‐5) are fundamental for cellular responses upon release of the neurotransmitter acetylcholine (ACh) from parasympathetic nerve fibers. ACh is the prototypical agonist stimulating endothelium‐dependent dilation, but most blood vessels lack parasympathetic innervation, raising the question as to the physiologic function of endothelial AChMR in vivo. Global deletion of AChM3R revealed a role in ACh‐induced vasodilation in vitro and food uptake, but overall cardiovascular homeostasis has not been examined thoroughly.MethodsTo characterize the function of endothelial AChM3R in vivo, we deleted AChM3R specifically in endothelial cells with an inducible or a non‐inducible Cre‐loxP system, driven by the endothelium‐specific promoters VE‐cadherin (indEC‐M3R−/−) or TIE2 (tek2; EC‐M3R−/−) and examined arteriolar dilation in the cremaster microcirculation, arterial pressure and cardiac function in these mice in vivo.ResultsIn both EC‐M3R−/−, ACh‐induced dilation was strongly impaired in arterioles in vivo, while responses to other dilators were mostly preserved. However, arterial pressure (indEC‐M3R−/−) and arteriolar tone as a surrogate for peripheral vascular resistance did not differ between EC‐M3R−/− and control mice. Aged EC‐M3R−/− mice (74‐78 weeks) did not differ in body weight, heart weight, cardiac structure or contractile function from controls.ConclusionWe conclude that AChM3R elicits the endothelium‐dependent dilation upon ACh also in arterioles in vivo. Despite this prominent role, the endothelial deletion of AChM3R does not affect overall cardiovascular homeostasis. Thus, their physiologic function in endothelial cells remains obscure.
Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach
Authors: Tang Dan , Song Bai‐Li , Yan Miao , Zou Jian‐Jun , Zhang Min , Zhou Hua‐Ying , Wang Feng , Xiao Yi‐Wen , Xu Ping , Zhang Bi‐Kui , Chen Xi‐Jing , Xiang Da‐Xiong , Linh Banh Hoan 
Published: February 2019

AbstractVoriconazole is a broad‐spectrum antifungal agent commonly used to treat invasive fungal infections. Voriconazole has significant intraindividual and interindividual pharmacokinetics variability in different patient populations. Pharmacokinetic data of voriconazole in patients with liver dysfunction were limited. The aims of this study were to evaluate the population pharmacokinetics of voriconazole in patients with liver dysfunction and to identify the factors that affect voriconazole pharmacokinetics. A total of 166 samples taken from 57 patients with liver dysfunction were included in the study. A one‐compartment pharmacokinetic model with first‐order absorption and elimination was used to describe the data. Voriconazole clearance (CL) was 0.58 L/h, the volume of distribution (Vd) was 134 L, and oral bioavailability (F) was 80.8%. This study showed that platelet count was significantly associated with voriconazole pharmacokinetic parameters. CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Voriconazole CL was significantly decreased in patients with liver dysfunction. This study provides useful pharmacokinetics information for patients with liver dysfunction while highlighting the value of therapeutic drug monitoring in adjusting doses.