bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isoprene is more affected by climate drivers than monoterpenes: A meta‐analytic review on plant isoprenoid emissions
Authors: Feng Zhaozhong , Yuan Xiangyang , Fares Silvano , Loreto Francesco , Li Pin , Hoshika Yasutomo , Paoletti Elena 
Published: February 2019

AbstractIsoprene and monoterpenes (MTs) are among the most abundant and reactive volatile organic compounds produced by plants (biogenic volatile organic compounds). We conducted a meta‐analysis to quantify the mean effect of environmental factors associated to climate change (warming, drought, elevated CO2, and O3) on the emission of isoprene and MTs. Results indicated that all single factors except warming inhibited isoprene emission. When subsets of data collected in experiments run under similar change of a given environmental factor were compared, isoprene and photosynthesis responded negatively to elevated O3 (−8% and −10%, respectively) and drought (−15% and −42%), and in opposite ways to elevated CO2 (−23% and +55%) and warming (+53% and −23%, respectively). Effects on MTs emission were usually not significant, with the exceptions of a significant stimulation caused by warming (+39%) and by elevated O3 (limited to O3‐insensitive plants, and evergreen species with storage organs). Our results clearly highlight individual effects of environmental factors on isoprene and MT emissions, and an overall uncoupling between these secondary metabolites produced by the same methylerythritol 4‐phosphate pathway. Future results from manipulative experiments and long‐term observations may help untangling the interactive effects of these factors and filling gaps featured in the current meta‐analysis.
Low temperature‐induced aberrations in male and female reproductive organ development cause flower abortion in chickpea
Authors: Kiran Asha , Kumar Sanjeev , Nayyar Harsh , Sharma Kamal Dev 
Published: February 2019

AbstractChickpea (Cicer arietinum L.) is susceptible to low temperature (LT) at reproductive stage. LT causes flower abortion and delays pod set in chickpea until terminal drought becomes an issue, thereby decreasing yield potential. In chickpea, flower and anther/pollen development as well as LT‐induced abnormalities on anther and pollen development are described inadequately. In the present manuscript, we report flower development stages, anther development stages, and aberrations in male gamete formation in chickpea under LT. Flower length was linearly correlated to flower and anther stages and can be used to predict these stages in chickpea. LT affected male gamete development in a flower/anther age‐dependent manner where outcome ranged from no pollen formation to pollen sterility or no anther dehiscence to delayed dehiscence. In anthers, LT inhibited microsporogenesis, microgametogenesis, tapetum degeneration, breakage of septum and stomium, and induced pollen sterility. Whereas disruption of male function was the prime cause of abortion in flowers below vacuolated pollen stage, flower abortion was due to a combination of male and female reproductive functions in flowers with mature pollen. The study will help in elucidating mechanisms governing flower development, anther and pollen development, and tolerance/susceptibility to LT.
Mechanism of action of 4‐substituted phenols to induce vitiligo and antimelanoma immunity
Authors: Kammeyer Arthur , Willemsen Karin J. , Ouwerkerk Wouter , Bakker Walbert J. , Ratsma Danielle , Pronk Sebas D. , Smit Nico P. M. , Luiten Rosalie M. 
Published: February 2019

AbstractMonobenzone is a 4‐substituted phenol that can induce vitiligo and antimelanoma immunity. We investigated the influence of the chemical structure on the biological activity of a series of structurally related 4‐substituted phenols. All phenols inhibited cellular melanin synthesis, and eight of ten phenols inhibited tyrosinase activity, using the MBTH assay. These phenols also induced glutathione (GSH) depletion, indicative of quinone formation and protein thiol binding, which can increase the immunogenicity of melanosomal proteins. Specific T‐cell activation was found upon stimulation with phenol‐exposed pigmented cells, which also reacted with unexposed cells. In contrast, 4‐tertbutylphenol induced immune activation was not restricted to pigment cells, analogous to contact sensitization. We conclude that 4‐substituted phenols can induce specific T‐cell responses against melanocytes and melanoma cells, also acting at distant, unexposed body sites, and may confer a risk of chemical vitiligo. Conversely, these phenols may be applicable to induce specific antimelanoma immunity.
Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti‐PD‐1 antibodies
Authors: Pires da Silva Ines , Glitza Isabella C. , Haydu Lauren E. , Johnpulle Romany , Banks Patricia D. , Grass George D. , Goldinger Simone M. A. , Smith Jessica L. , Everett Ashlyn S. , Koelblinger Peter , Roberts‐Thomson Rachel , Millward Michael , Atkinson Victoria G. , Guminski Alexander , Kapoor Rony , Conry Robert M. , Carlino Matteo S. , Wang Wei , Shackleton Mark J. , Eroglu Zeynep , Lo Serigne , Hong Angela M. , Long Georgina V. , Johnson Douglas B. , Menzies Alexander M. 
Published: February 2019

AbstractBackgroundBrain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti‐PD‐1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer‐term survivors with MBM treated with this combination.MethodsPatients with MBM treated with radiotherapy and anti‐PD‐1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148).ResultsFrom Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery.ConclusionsRadionecrosis is a significant toxicity in longer‐term melanoma survivors with MBM treated with anti‐PD‐1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required.
Ferrochelatase Deficiency Abrogated the Enhancement of Aminolevulinic Acid‐mediated Protoporphyrin IX by Iron Chelator Deferoxamine
Authors: Palasuberniam Pratheeba , Kraus Daniel , Mansi Matthew , Braun Alexander , Howley Richard , Myers Kenneth A. , Chen Bin 
Published: February 2019

AbstractAminolevulinic acid (ALA) is a prodrug that is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX) for tumor fluorescence detection and photodynamic therapy (PDT). The iron chelator deferoxamine (DFO) has been widely used to enhance PpIX accumulation by inhibiting the iron‐dependent bioconversion of PpIX to heme, a reaction catalyzed by ferrochelatase (FECH). Tumor response to DFO treatment is known to be highly variable, and some tumors even show no response. Given the fact that tumors often exhibit reduced FECH expression/enzymatic activity, we examined how reducing FECH level affected the DFO enhancement effect. Our results showed that reducing FECH level by silencing FECH in SkBr3 breast cancer cells completely abrogated the enhancement effect of DFO. Although DFO enhanced ALA‐PpIX fluorescence and PDT response in SkBr3 vector control cells, it caused a similar increase in MCF10A breast epithelial cells, resulting in no net gain in the selectivity toward tumor cells. We also found that DFO treatment induced less increase in ALA‐PpIX fluorescence in tumor cells with lower FECH activity (MDA‐MB‐231, Hs 578T) than in tumor cells with higher FECH activity (MDA‐MB‐453). Our study demonstrates that FECH activity is an important determinant of tumor response to DFO treatment.
Morphological and immunohistochemical characteristics of the equine corneal epithelium
Authors: Kammergruber Eva , Rahn Carolin , Nell Barbara , Gabner Simone , Egerbacher Monika 
Published: February 2019

AbstractObjectiveThe morphology of the corneal epithelium in two age groups of horses is described. Distribution patterns of proliferation‐, differentiation‐, stem cell‐associated markers and cell junction proteins were assessed.MethodsCorneal samples from 12 horses (six foals and six adult horses) were analyzed after H&E staining and immunohistochemistry using the following antibodies: E‐cadherin, β‐catenin, Connexin 43 (Cx43), tight junction protein 1 (TJP1), cytokeratin (CK) 14, CK 19, CK 3, CK 10, vimentin, Ki67, p63, nerve growth factor (NGF), ABCG2, and epithelial growth factor receptor. Semiquantitative analysis of crypt, limbal, peripheral, and central zone was performed. Semithin and ultrathin sections were used for ultrastructural evaluation of the epithelium.ResultsThe height of the epithelium varied between age groups and crypts were consistently present. In the peripheral and central epithelium, three types of basal cells resembling a pseudostratified epithelium were characterized. Potential stem cell markers (CK 14, p63, NGF, and ABCG2) were present in all zones with decreasing frequency toward the center. Cornea‐specific differentiation marker CK 3 was not expressed in the most basal cell layer of the limbal epithelium. E‐cadherin, β‐catenin, and Cx43 revealed a similar apico‐lateral signal pattern throughout the entire epithelium; only TJP1 was additionally seen at the basal surface.ConclusionsThis study presents a systematic semiquantitative evaluation of the equine corneal epithelium, showing the presence of crypts as potential stem cell niche with CK 14, p63, NGF, and ABCG2 as relevant markers for cells with regenerative capacity. The pseudostratified arrangement of the basal layer was a unique finding.
Cigarette pricing 1 year after new restrictions on tobacco industry retailer programmes in Quebec, Canada
Authors: Callard Cynthia D , Collishaw Neil 
Published: February 2019

ObjectivesOver the past 15 years, tobacco companies operating in Canada abandoned their long-standing unitary price model in favour of price differentiation. Concerns about low cigarette prices were identified by the Quebec government in 2015 when it introduced restrictions on the types of incentives that tobacco manufacturers may offer to retailers. This study sought to explore cigarette prices in Quebec 1 year after these restrictions came into effect.MethodsDetails on cigarette trading terms and programmes were obtained from websites maintained by retailer groups. Visits were made to tobacco retailers in four Quebec municipalities in the autumn of 2017. The price displayed for cigarettes was observed and recorded in 273 convenience stores.ResultsTwo forms of price differentiation were observed. The first was price-segmentation between brands, reflected in a difference of $3 or more in the average displayed price between premium and discount brands of each manufacturer (ie, $10.48 vs $7.43 for a package of 20 cigarettes of the most and least expensive brands sold by Philip Morris International). Price localisation was also observed, reflected in a $2 range of prices between retail outlets for the same package of cigarettes. Even among outlets of a given chain of convenience stores, the price of the least expensive brands varied by more than $1 per package. The size of the variance in prices rivals or exceeds the size of tobacco tax increases in Quebec over the past decade.ConclusionsRecent restrictions on tobacco industry incentive programmes for retailers have not ended price differentiation. Tobacco manufacturers’ and retailers’ pricing policies continue to provide price-sensitive smokers with ways to avoid the impact of tobacco tax increases.
‘Both Sides of the Argument’? A critical review of existing evidence on the illicit trade in tobacco products in Canada
Authors: Smith Julia , Thompson Sheryl , Lee Kelley 
Published: February 2019

IntroductionThe illicit trade in tobacco products (ITTP) is widely recognised as a substantial and complex problem in Canada. However, the independence of available data and quality of analyses remains unknown. Reliable and accurate data on the scale and causes of the problem are needed to inform effective policy responses.MethodsWe searched the scholarly and grey literature using keywords related to ITTP in Canada. We identified 26 studies published in English since 2008 that present original research drawing on primary data. We analysed these studies for their independence from the tobacco industry, methodology, findings and gaps in knowledge.ResultsThe study finds 42% of the literature reviewed has links to the tobacco industry. These studies provide insufficient methodological detail, present higher estimates of the volume of ITTP and attribute the causes to higher rates of tobacco taxation. The classification of all indigenous tobacco sales as illicit, by both industry linked and independent studies, contributes to overestimates and serves the interests of transnational tobacco companies. There is need for independent and comprehensive data on the ITTP in Canada over time, across population groups and geographies.ConclusionWhile there is evidence that the ITTP in Canada is a major and complex issue that requires effective tobacco control policies, there is a limited evidence base on which to develop such responses. This review finds industry-linked studies lack independence, employ biased methodologies and serve tobacco industry interests. Independent studies present more rigorous approaches, but primarily focus on youth and the province of Ontario.
Randomised controlled trial of real-time feedback and brief coaching to reduce indoor smoking
Authors: Hovell Melbourne F , Bellettiere John , Liles Sandy , Nguyen Benjamin , Berardi Vincent , Johnson Christine , Matt Georg E , Malone John , Boman-Davis Marie C , Quintana Penelope J E , Obayashi Saori , Chatfield Dale , Robinson Robert , Blumberg Elaine J , Ongkeko Weg M , Klepeis Neil E , Hughes Suzanne C 
Published: February 2019

BackgroundPrevious secondhand smoke (SHS) reduction interventions have provided only delayed feedback on reported smoking behaviour, such as coaching, or presenting results from child cotinine assays or air particle counters.DesignThis SHS reduction trial assigned families at random to brief coaching and continuous real-time feedback (intervention) or measurement-only (control) groups.ParticipantsWe enrolled 298 families with a resident tobacco smoker and a child under age 14.InterventionWe installed air particle monitors in all homes. For the intervention homes, immediate light and sound feedback was contingent on elevated indoor particle levels, and up to four coaching sessions used prompts and praise contingent on smoking outdoors. Mean intervention duration was 64 days.MeasuresThe primary outcome was ‘particle events’ (PEs) which were patterns of air particle concentrations indicative of the occurrence of particle-generating behaviours such as smoking cigarettes or burning candles. Other measures included indoor air nicotine concentrations and participant reports of particle-generating behaviour.ResultsPEs were significantly correlated with air nicotine levels (r=0.60) and reported indoor cigarette smoking (r=0.51). Interrupted time-series analyses showed an immediate intervention effect, with reduced PEs the day following intervention initiation. The trajectory of daily PEs over the intervention period declined significantly faster in intervention homes than in control homes. Pretest to post-test, air nicotine levels, cigarette smoking and e-cigarette use decreased more in intervention homes than in control homes.ConclusionsResults suggest that real-time particle feedback and coaching contingencies reduced PEs generated by cigarette smoking and other sources.Trial registration numberNCT01634334; Post-results.
Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents
Authors: Christiansen Charlotte Bayer , Trammell Samuel Addison Jack , Wewer Albrechtsen Nicolai Jacob , Schoonjans Kristina , Albrechtsen Reidar , Gillum Matthew Paul , Kuhre Rune Ehrenreich , Holst Jens Juul 
Published: February 2019

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion.NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.
Pulmonary vascular mechanical consequences of ischemic heart failure and implications for right ventricular function
Authors: Philip Jennifer L. , Murphy Thomas M. , Schreier David A. , Stevens Sydney , Tabima Diana M. , Albrecht Margie , Frump Andrea L. , Hacker Timothy A. , Lahm Tim , Chesler Naomi C. 
Published: February 2019

Left heart failure (LHF) is the most common cause of pulmonary hypertension, which confers an increase in morbidity and mortality in this context. Pulmonary vascular resistance has prognostic value in LHF, but otherwise the mechanical consequences of LHF for the pulmonary vasculature and right ventricle (RV) remain unknown. We sought to investigate mechanical mechanisms of pulmonary vascular and RV dysfunction in a rodent model of LHF to address the knowledge gaps in understanding disease pathophysiology. LHF was created using a left anterior descending artery ligation to cause myocardial infarction (MI) in mice. Sham animals underwent thoracotomy alone. Echocardiography demonstrated increased left ventricle (LV) volumes and decreased ejection fraction at 4 wk post-MI that did not normalize by 12 wk post-MI. Elevation of LV diastolic pressure and RV systolic pressure at 12 wk post-MI demonstrated pulmonary hypertension (PH) due to LHF. There was increased pulmonary arterial elastance and pulmonary vascular resistance associated with perivascular fibrosis without other remodeling. There was also RV contractile dysfunction with a 35% decrease in RV end-systolic elastance and 66% decrease in ventricular-vascular coupling. In this model of PH due to LHF with reduced ejection fraction, pulmonary fibrosis contributes to increased RV afterload, and loss of RV contractility contributes to RV dysfunction. These are key pathologic features of human PH secondary to LHF. In the future, novel therapeutic strategies aimed at preventing pulmonary vascular mechanical changes and RV dysfunction in the context of LHF can be tested using this model. NEW & NOTEWORTHY In this study, we investigate the mechanical consequences of left heart failure with reduced ejection fraction for the pulmonary vasculature and right ventricle. Using comprehensive functional analyses of the cardiopulmonary system in vivo and ex vivo, we demonstrate that pulmonary fibrosis contributes to increased RV afterload and loss of RV contractility contributes to RV dysfunction. Thus this model recapitulates key pathologic features of human pulmonary hypertension-left heart failure and offers a robust platform for future investigations.
Bacillus anthracis lethal toxin, but not edema toxin, increases pulmonary artery pressure and permeability in isolated perfused rat lungs
Authors: Cui Xizhong , Xu Wanying , Neupane Pranita , Weiser-Schlesinger Andie , Weng Ray , Pockros Benjamin , Li Yan , Moayeri Mahtab , Leppla Stephen H. , Fitz Yvonne , Eichacker Peter Q. 
Published: February 2019

Although lethal toxin (LT) and edema toxin (ET) contribute to lethality during Bacillus anthracis infection, whether they increase vascular permeability and the extravascular fluid accumulation characterizing this infection is unclear. We employed an isolated perfused Sprague-Dawley rat lung model to investigate LT and ET effects on pulmonary vascular permeability. Lungs ( n ≥ 6 per experimental group) were isolated, ventilated, suspended from a force transducer, and perfused. Lung weight and pulmonary artery (Ppa) and left atrial pressures were measured over 4 h, after which pulmonary capillary filtration coefficients (Kf.c) and lung wet-to-dry weight ratios (W/D) were determined. When compared with controls, LT increased Ppa over 4 h and Kf.c and W/D at 4 h ( P < 0.0001). ET decreased Ppa in a significant trend ( P = 0.09) but did not significantly alter Kf.c or W/D ( P ≥ 0.29). Edema toxin actually blocked LT increases in Ppa but not LT increases in Kf.c and W/D. When Ppa was maintained at control levels, LT still increased Kf.c and W/D ( P ≤ 0.004). Increasing the dose of each toxin five times significantly increased and a toxin-directed monoclonal antibody decreased the effects of each toxin ( P ≤ 0.05). Two rho-kinase inhibitors (GSK269962 and Y27632) decreased LT increases in Ppa ( P ≤ 0.02) but actually increased Kf.c and W/D in LT and control lungs ( P ≤ 0.05). A vascular endothelial growth factor receptor inhibitor (ZM323881) had no significant effect ( P ≥ 0.63) with LT. Thus, LT but not ET can increase pulmonary vascular permeability independent of increased Ppa and could contribute to pulmonary fluid accumulation during anthrax infection. However, pulmonary vascular dilation with ET could disrupt protective hypoxic vasoconstriction. NEW & NOTEWORTHY The most important findings from the present study are that Bacillus anthracis lethal toxin increases pulmonary artery pressure and pulmonary permeability independently in the isolated rat lung, whereas edema toxin decreases the former and does not increase permeability. Each effect could be a basis for organ dysfunction in patients with this lethal infection. These findings further support the need for adjunctive therapies that limit the effects of both toxins during infection.