bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ambient temperature and genotype differentially affect developmental and phenotypic plasticity inArabidopsis thaliana
Authors: Ibañez Carla , Poeschl Yvonne , Peterson Tom , Bellstädt Julia , Denk Kathrin , Gogol-Döring Andreas , Quint Marcel , Delker Carolin 
Published: April 2015

AbstractBackgroundGlobal increase in ambient temperatures constitute a significant challenge to wild and cultivated plant species. Forward genetic analyses of individual temperature-responsive traits have resulted in the identification of several signaling and response components. However, a comprehensive knowledge about temperature sensitivity of different developmental stages and the contribution of natural variation is still scarce and fragmented at best.ResultsHere, we systematically analyze thermomorphogenesis throughout a complete life cycle in ten naturalArabidopsis thalianaaccessions grown in four different temperatures ranging from 16 to 28 °C. We used Q10, GxE, phenotypic divergence and correlation analyses to assess temperature sensitivity and genotype effects of more than 30 morphometric and developmental traits representing five phenotype classes. We found that genotype and temperature differentially affected plant growth and development with variing strengths. Furthermore, overall correlations among phenotypic temperature responses was relatively low which seems to be caused by differential capacities for temperature adaptations of individual accessions.ConclusionGenotype-specific temperature responses may be attractive targets for future forward genetic approaches and accession-specific thermomorphogenesis maps may aid the assessment of functional relevance of known and novel regulatory components.
pH Regulation by NHX-Type Antiporters Is Required for Receptor-Mediated Protein Trafficking to the Vacuole in Arabidopsis
Authors: Reguera Maria , Bassil Elias , Tajima Hiromi , Wimmer Monika , Chanoca Alexandra , Otegui Marisa S. , Paris Nadine , Blumwald Eduardo 
Published: April 2015

AbstractProtein trafficking requires proper ion and pH homeostasis of the endomembrane system. The NHX-type Na+/H+ antiporters NHX5 and NHX6 localize to the Golgi, trans-Golgi network, and prevacuolar compartments and are required for growth and trafficking to the vacuole. In the nhx5 nhx6 T-DNA insertional knockouts, the precursors of the 2S albumin and 12S globulin storage proteins accumulated and were missorted to the apoplast. Immunoelectron microscopy revealed the presence of vesicle clusters containing storage protein precursors and vacuolar sorting receptors (VSRs). Isolation and identification of complexes of VSRs with unprocessed 12S globulin by 2D blue-native PAGE/SDS-PAGE indicated that the nhx5 nhx6 knockouts showed compromised receptor-cargo association. In vivo interaction studies using bimolecular fluorescence complementation between VSR2;1, aleurain, and 12S globulin suggested that nhx5 nhx6 knockouts showed a significant reduction of VSR binding to both cargoes. In vivo pH measurements indicated that the lumens of VSR compartments containing aleurain, as well as the trans-Golgi network and prevacuolar compartments, were significantly more acidic in nhx5 nhx6 knockouts. This work demonstrates the importance of NHX5 and NHX6 in maintaining endomembrane luminal pH and supports the notion that proper vacuolar trafficking and proteolytic processing of storage proteins require endomembrane pH homeostasis.
Control of downy mildew (Peronospora sparsa) in arctic bramble (Rubus arcticus ssp. arcticus)
Authors: Kostamo K. , Toljamo A. , Palonen P. , Valkonen J.P.T. , Kärenlampi S.O. , Kokko H. 
Published: April 2015

AbstractDowny mildew, inflicted by Peronospora sparsa, causes yield losses in arctic bramble (Rubus arcticus ssp. arcticus), boysenberry (Rubus spp. hybrid) and blackberry (Rubus fruticosus), and is a serious threat to the cultivation. Arctic bramble is a high‐value crop but its commercial potential is not realisable partly due to downy mildew. Although P. sparsa has been associated with yield losses in arctic bramble, this has not been experimentally proven, nor have the downy mildew symptoms in arctic bramble fruits been described in a controlled experiment. In this study, downy mildew was found to affect the fruits and reduce the yield of arctic bramble. There was a direct correlation between the number of infected leaves and hard fruits resulting from the infection. Owing to the new pesticide legislation in the European Union, it is important to find alternatives to fungicides in the control of downy mildew. The products ALIETTE (fungicide), PHOSFIK (leaf fertiliser) and BION (pathogen defence elicitor) were effective in downy mildew control, Aliette and Phosfik being more effective than Bion especially in preventing yield losses. No arctic bramble cultivars known to be resistant to downy mildew are available. Evaluation of cultivars Alli, Mesma and Pima in the field showed that Mesma is more resistant to downy mildew than are Alli and Pima. Currently the main cultivar grown in Finland, Pima, was the most susceptible variety. The results of this study suggest that the yields and profitability of arctic bramble production could be improved by selecting more resistant varieties, combined with the application of agrochemicals that can suppress the development of downy mildew.
Trends and timing of cigarette smoking uptake among US young adults: survival analysis using annual national cohorts from 1976 to 2005
Authors: Terry‐McElrath Yvonne M. , O'Malley Patrick M. 
Published: April 2015

AbstractAimsTo measure changes over time in cigarette smoking uptake prevalence and timing during young adulthood (ages 19–26 years), and associations between time‐invariant/‐varying characteristics and uptake prevalence/timing.DesignDiscrete‐time survival modeling of data collected from United States high school seniors (modal age 17/18) enrolled in successive graduating classes from 1976 to 2005 and participating in four follow‐up surveys (to modal age 25/26).SettingThe longitudinal component of the Monitoring the Future study.ParticipantsA total of 10 758 individuals reporting no life‐time smoking when first surveyed as high school seniors.MeasurementsSmoking uptake (any, experimental, occasional and regular); socio‐demographic variables; marital, college and work status; time spent socializing.FindingsThe percentage of young adults moving from non‐smoker to experimental smoking [slope estimate 0.11, standard error (SE) = 0.04, P = 0.005] or occasional smoking (slope estimate 0.17, SE = 0.03, P < 0.001) increased significantly across graduating classes; the percentage moving from non‐smoker to regular smoker remained stable. All forms of smoking uptake were most likely to occur at age 19/20, but uptake prevalence at older ages increased over time [e.g. cohort year predicting occasional uptake at modal age 25/26 adjusted hazard odds ratio (AHOR) = 1.05, P = 0.002]. Time‐invariant/‐varying characteristics had unique associations with the timing of various forms of smoking uptake (e.g. at modal age 21/22, currently attending college increased occasional uptake risk (AHOR = 2.11, P < 0.001) but decreased regular uptake risk (AHOR = 0.69, P = 0.026).ConclusionsYoung adult occasional and experimental smoking uptake increased in the United States for non‐smoking high school seniors graduating from 1976 to 2005. Smoking uptake for these cohorts remained most likely to occur at age 19/20, but prevalence of uptake at older ages increased.
Refraction and visual acuity in a national Danish cohort of 4‐year‐old children of extremely preterm delivery
Authors: Fledelius Hans C. , Bangsgaard Regitze , Slidsborg Carina , laCour Morten 
Published: April 2015

AbstractPurposeA recent threefold increase in laser treatment for advanced retinopathy of prematurity (ROP) triggered a nationwide preschool ophthalmic and developmental status among extremely preterm survivors. Here, we discuss refraction and visual acuity.MethodsSurvivors (n = 178) from a national birth cohort (February 2004 to March 2006) of gestational age <28 weeks (PT) and 56 full‐term (FT) controls attended for evaluation at age 4 years. Cycloplegic refraction and keratometry were achieved by Retinomax autokeratorefractor and visual acuities by symbol recognition (HOTV, logMAR).ResultsThe refractive distribution presented a myopic tail (4.5%) and a hyperopic tail (11.9% ≥+2.5 D) as special preterm features, and corneas were more curved. Astigmatism and anisometropia were only marginally increased, and visual acuities were generally good. Best‐corrected binocular median logMAR visual acuity was 0.1 in FT and 0.2 in PT, in Snellen equivalents 0.8 and 0.63. Snellen acuity ≤0.5 occurred across the ROP subgroups, but mainly in those with at least ROP stage 3. Two children had low vision.ConclusionsThe overall fair outcome for refraction and function is in accordance with other recent northern Europe experience. The results differ in particular from the poorer ophthalmic outcomes reported in the pioneer US treatment studies (cryotherapy for ROP and ETROP). The diode laser ablations (n = 32) appeared effective in our series; except one child, all treated subjects had good or fair social vision at the age of 4 years.
Brain imaging in cooled encephalopathic neonates does not differ between four and 11 days after birth
Authors: Skranes Janne Helen , Cowan Frances Mary , Stiris Tom , Fugelseth Drude , Thoresen Marianne , Server Andres 
Published: April 2015

AbstractAimThe optimal timing of magnetic resonance imaging (MRI) in encephalopathic infants treated with hypothermia is unknown, and this study examined whether early scans differed from later scans.MethodsWe assessed paired MRI scans carried out on 41 cooled encephalopathic infants at a median of four and 11 days using two scoring systems: the Rutherford injury scores for the basal ganglia and thalami (BGT), white matter and the posterior limb of the internal capsule, and the Bonifacio injury scores for the BGT and watershed area.ResultsBoth systems produced consistent injury severity scores in 37 of 41 infants on both days, with Rutherford scores predicting poor outcome in six early scans and seven later scans (K = 0.91) and Bonifacio doing the same in seven and nine scans (K = 0.85). A white matter/watershed score of two or a BGT score of one indicated severe changes by day 11 in three infants, but lower scores did not.ConclusionMagnetic resonance imaging scans indicated that the Rutherford and Bonifacio systems produced similar scores in 37 of 41 cooled encephalopathic infants at a median of four and 11 days. Infants with an early white matter/watershed scores of two or a BGT score of one may worsen and should be rescanned.
The long‐acting β2‐adrenoceptor agonist olodaterol attenuates pulmonary inflammation
Authors: Wex Eva , Kollak Ines , Duechs Matthias J , Naline Emmanuel , Wollin Lutz , Devillier Philippe 
Published: April 2015

Background and Purposeβ2‐adrenoceptor agonists are widely used in the management of obstructive airway diseases. Besides their bronchodilatory effect, several studies suggest inhibitory effects on various aspects of inflammation. The aim of our study was to determine the efficacy of the long‐acting β2‐adrenoceptor agonist olodaterol to inhibit pulmonary inflammation and to elucidate mechanism(s) underlying its anti‐inflammatory actions.Experimental ApproachOlodaterol was tested in murine and guinea pig models of cigarette smoke‐ and LPS‐induced lung inflammation. Furthermore, effects of olodaterol on the LPS‐induced pro‐inflammatory mediator release from human parenchymal explants, CD11b adhesion molecule expression on human granulocytes TNF‐α release from human whole blood and on the IL‐8‐induced migration of human peripheral blood neutrophils were investigated.Key ResultsOlodaterol dose‐dependently attenuated cell influx and pro‐inflammatory mediator release in murine and guinea pig models of pulmonary inflammation. These anti‐inflammatory effects were observed at doses relevant to their bronchodilatory efficacy. Mechanistically, olodaterol attenuated pro‐inflammatory mediator release from human parenchymal explants and whole blood and reduced expression of CD11b adhesion molecules on granulocytes, but without direct effects on IL‐8‐induced neutrophil transwell migration.Conclusions and ImplicationsThis is the first evidence for the anti‐inflammatory efficacy of a β2‐adrenoceptor agonist in models of lung inflammation induced by cigarette smoke. The long‐acting β2‐adrenoceptor agonist olodaterol attenuated pulmonary inflammation through mechanisms that are separate from direct inhibition of bronchoconstriction. Furthermore, the in vivo data suggest that the anti‐inflammatory properties of olodaterol are maintained after repeated dosing for 4 days.
Acute morphine affects the rat circadian clock via rhythms of phosphorylated ERK1/2 and GSK3β kinases and Per1 expression in the rat suprachiasmatic nucleus
Authors: Pačesová Dominika , Volfová Barbora , Červená Kateřina , Hejnová Lucie , Novotný Jiří , Bendová Zdeňka 
Published: April 2015

Background and PurposeOpioids affect the circadian clock and may change the timing of many physiological processes. This study was undertaken to investigate the daily changes in sensitivity of the circadian pacemaker to an analgesic dose of morphine, and to uncover a possible interplay between circadian and opioid signalling.Experimental ApproachA time‐dependent effect of morphine (1 mg·kg−1, i.p.) applied either during the day or during the early night was followed, and the levels of phosphorylated ERK1/2, GSK3β, c‐Fos and Per genes were assessed by immunohistochemistry and in situ hybridization. The effect of morphine pretreatment on light‐induced pERK and c‐Fos was examined, and day/night difference in activity of opioid receptors was evaluated by [35S]‐GTPγS binding assay.Key ResultsMorphine stimulated a rise in pERK1/2 and pGSK3β levels in the suprachiasmatic nucleus (SCN) when applied during the day but significantly reduced both kinases when applied during the night. Morphine at night transiently induced Period1 but not Period2 in the SCN and did not attenuate the light‐induced level of pERK1/2 and c‐Fos in the SCN. The activity of all three principal opioid receptors was high during the day but decreased significantly at night, except for the δ receptor. Finally, we demonstrated daily profiles of pERK1/2 and pGSK3β levels in the rat ventrolateral and dorsomedial SCN.Conclusions and ImplicationsOur data suggest that the phase‐shifting effect of opioids may be mediated via post‐translational modification of clock proteins by means of activated ERK1/2 and GSK3β.
The diagnostic role of 18F fluorodeoxyglucose positron emission tomography in patients with fever of unknown origin
Authors: Sioka Chrissa , Assimakopoulos Assimakis , Fotopoulos Andreas 
Published: April 2015

AbstractBackgroundIdentification of aetiology for fever of unknown origin (FUO) is challenging, due to the high rates of undiagnosed cases. The current diagnostic approach includes initially first‐line procedures such as general examination and various laboratory tests and basic imaging techniques followed by second‐line tests such as more advanced imaging techniques including 18F fluorodeoxyglucose positron emission tomography (FDG PET) and tissue biopsies. If no diagnosis is obtained, more invasive measures may be in order such as liver biopsy and exploratory laparotomy.Materials and methodsThis review article is based on the relative published material found on MEDLINE and PubMed up to August 2014. We looked for the terms ‘fever of unknown origin, FDG PET’ in combination with ‘cancer, infection and autoimmune disease’.ResultsSeveral clinical studies have investigated the utility of the FDG PET during the diagnostic approach of FUO. Recent evidence suggests that FDG PET has the advantage of total body imaging and may depict all common causes of FUO such as infections, noninfectious inflammatory causes and tumours because they all exhibit glucose hypermetabolism. Depiction of an abnormal lesion on FDG PET could guide clinicians to the next diagnostic procedure (another imaging method, culture, biopsy or surgery) to establish the diagnosis.ConclusionsEmerging evidence suggests that FDG PET, when available, may provide critical diagnostic information early during evaluation of FUO.
The Ras/MAPK pathway and hepatocarcinoma: pathogenesis and therapeutic implications
Authors: Delire Bénédicte , Stärkel Peter 
Published: April 2015

AbstractBackgroundHepatocellular carcinoma (HCC) is still a major health problem, often diagnosed at an advanced stage. The multikinase inhibitor sorafenib is to date the sole approved systemic therapy. Several signalling pathways are implicated in tumour development and progression. Among these pathways, the Ras/MAPK pathway is activated in 50–100% of human HCCs and is correlated with a poor prognosis. The aim of this work was to review the main intracellular mechanisms leading to aberrant Ras pathway activation in HCC and the potential therapeutic implications.Materials and methodsThis review is based on the material found on PubMed up to December 2014. ‘Ras signaling, Ras dysregulation, Ras inhibition, MAPK pathway, cancer, hepatocarcinoma and liver cancer’ alone or in combination were the main terms used for online research.ResultsMultiple mechanisms lead to the deregulation of the Ras pathway in liver cancer. Ras and Raf gene mutations are rare events in human hepatocarcinogenesis in contrast to experimental models in rodents. Downregulation of several Ras/MAPK pathway inhibitors such as GAPs, RASSF proteins, DUSP1, Sprouty and Spred proteins is largely implicated in the aberrant activation of this pathway in the context of wild‐type Ras and Raf genes. Epigenetic or post‐transcriptional mechanisms lead to the downregulation of these tumour suppressor genes.ConclusionRas/MAPK pathway effectors may be considered as potential therapeutic targets in the field of HCC. In particular after the arrival of sorafenib, more Ras/MAPK inhibitors have emerged and are still in preclinical or clinical investigation for HCC therapy.
Soluble triggering receptor expressed on myeloid cells‐1 is a biomarker of anti‐CCP‐positive, early rheumatoid arthritis
Authors: Molad Yair , Ofer‐Shiber Shachaf , Pokroy‐Shapira Elisheva , Oren Shirly , Shay‐Aharoni Hagit , Babai Ilan 
Published: April 2015

AbstractObjectivesTo assess serum soluble triggering receptor expressed on myeloid cells‐1 (sTREM‐1) levels in disease‐modifying antirheumatic drug (DMARD)‐naïve early rheumatoid arthritis (ERA), to investigate the association of sTREM‐1 levels with Disease Activity Score in 28 joints (DAS28) and seropositivity for anti‐cyclic citrullinated peptide (CCP) antibody and to determine the predictive value of sTREM‐1 with respect to clinical response to DMARD therapy.MethodsTwenty‐two consecutive patients with DMARD‐naïve ERA were prospectively evaluated for serum sTREM‐1 by means of ELISA at diagnosis and at the following clinic visit after prednisone and/or DMARD has been administered, and related to DAS28 and serum level of anti‐CCP antibody. We compared the sTREM‐1 level to that of 31 patients with established RA as well as to 24 controls.ResultsSerum sTREM‐1 level was significantly higher in the DMARD‐naïve ERA group (2122·9 ± 388·9 ρg/mL) compared to established RA group (1478·0 ± 280·0 ρg/mL, P = 0·001) and normal control (34·4 ± 7·4 ρg/mL, P < 0·001). In the ERA group, elevated basal sTREM‐1 level correlated with higher DAS28‐CRP score (P = 0·001, HR 3·23, 95% CI 1·4–8·12), DAS28‐ESR (P = 0·04, HR 2·34 95% CI 0·1–8·12), as well as predicted higher DAS28 score at the following encounter after DMARD treatment was administered (P = 0·001, HR 3·2 95% CI 1·1–7·2). Higher serum level of sTREM‐1 correlated with higher titres of anti‐CCP antibody (P < 0·001).ConclusionsOur results suggest that serum sTREM‐1 may provide a novel biomarker for DMARD‐naïve ERA as well as for seropositivity for anti‐CCP antibody and RA activity.
Genetic mapping of ASIC4 and contrasting phenotype to ASIC1a in modulating innate fear and anxiety
Authors: Lin Shing‐Hong , Chien Ya‐Chih , Chiang Wei‐Wei , Liu Yan‐Zhen , Lien Cheng‐Chang , Chen Chih‐Cheng 
Published: April 2015

AbstractAlthough ASIC4 is a member of the acid‐sensing ion channel (ASIC) family, we have limited knowledge of its expression and physiological function in vivo. To trace the expression of this ion channel, we generated the ASIC4‐knockout/CreERT2‐knockin (Asic4CreERT2) mouse line. After tamoxifen induction in the Asic4CreERT2::CAG‐STOPfloxed‐Td‐tomato double transgenic mice, we mapped the expression of ASIC4 at the cellular level in the central nervous system (CNS). ASIC4 was expressed in many brain regions, including the olfactory bulb, cerebral cortex, striatum, hippocampus, amygdala, thalamus, hypothalamus, brain stem, cerebellum, spinal cord and pituitary gland. Colocalisation studies further revealed that ASIC4 was expressed mainly in three types of cells in the CNS: (i) calretinin (CR)‐positive and/or vasoactive intestine peptide (VIP)‐positive interneurons; (ii) neural/glial antigen 2 (NG2)‐positive glia, also known as oligodendrocyte precursor cells; and (iii) cerebellar granule cells. To probe the possible role of ASIC4, we hypothesised that ASIC4 could modulate the membrane expression of ASIC1a and thus ASIC1a signaling in vivo. We conducted behavioral phenotyping of Asic4CreERT2 mice by screening many of the known behavioral phenotypes found in Asic1a knockouts and found ASIC4 not involved in shock‐evoked fear learning and memory, seizure termination or psychostimulant‐induced locomotion/rewarding effects. In contrast, ASIC4 might play an important role in modulating the innate fear response to predator odor and anxious state because ASIC4‐mutant mice showed increased freezing response to 2,4,5‐trimethylthiazoline and elevated anxiety‐like behavior in both the open‐field and elevated‐plus maze. ASIC4 may modulate fear and anxiety by counteracting ASIC1a activity in the brain.