bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon gamma induces protective non‐canonical signaling pathways in primary neurons
Authors: O'Donnell Lauren A. , Henkins Kristen M. , Kulkarni Apurva , Matullo Christine M. , Balachandran Siddharth , Pattisapu Anil K. , Rall Glenn F. 
Published: July 2015

AbstractThe signal transduction molecule, Stat1, is critical for the expression of type I and II interferon (IFN)‐responsive genes in most cells; however, we previously showed that primary hippocampal mouse neurons express low basal Stat1, with delayed and attenuated expression of IFN‐responsive genes. Moreover, IFNγ‐dependent resolution of a neurotropic viral challenge in permissive mice is Stat1‐independent. Here, we show that exogenous IFNγ has no deleterious impact on neuronal viability, and staurosporine‐induced apoptosis in neurons is significantly blunted by the addition of IFNγ, suggesting that IFNγ confers a pro‐survival signal in neurons. To identify the pathways induced by IFNγ in neurons, the activation of alternative signal transducers associated with IFNγ signaling was assessed. Rapid and pronounced activation of extracellular signal regulated kinase (Erk1/2) was observed in neurons, compared to a modest response in fibroblasts. Moreover, the absence of Stat1 in primary fibroblasts led to enhanced Erk activation following IFNγ addition, implying that the cell‐specific availability of signal transducers can diversify the cellular response following IFN engagement.
image
Interferon gamma (IFNγ) signaling varies depending upon cell type and the inflammatory milieu. In neurons, IFNγ activates extracellular regulated kinase‐1/2 (Erk‐1/2) in the context of low expression of the classical IFNγ signaling molecule Signal Transducers and Activators of Transcription‐1 (STAT1). We propose that such alternative signaling pathways could protect against inflammation, and may be dictated by basal expression of intracellular signal transducers.
Dialogic Accountings for Stakeholders: On Opening Up and Closing Down Participatory Governance
Authors: Brown Judy , Dillard Jesse 
Published: July 2015

ABSTRACTInterpretivist and critical accounting researchers have long challenged the shareholder focus of conventional accounting, calling for new approaches that promote accountability to stakeholders and participatory governance. One proposal is for dialogic accountings that take pluralism seriously and enable critical reflection on organizational practices from diverse socio‐political perspectives. Dialogic accounting aims to counter narrow managerialist framings and address constituencies poorly served by traditional accounting. However, those favouring pluralist approaches face significant challenges in addressing entrenched ideologies and power relations. Rather than trying to address these challenges solely from within accounting, much can be learned from disciplinary fields that demonstrate sustained interest in pluralistic analysis and engagement. Here, we focus on the insights science and technology studies (STS) provides on opening up and closing down participatory governance, understanding knowledge‐power dynamics and implications for stakeholder value creation.
Topography and climate are more important drivers of long‐term, post‐fire vegetation assembly than time‐since‐fire in the Sonoran Desert, US
Authors: Shryock Daniel F. , Esque Todd C. , Chen Felicia C. 
Published: July 2015

AbstractQuestionsDo abiotic environmental filters or time‐since‐fire (TSF) explain more variability in post‐fire vegetation assembly? Do these influences vary between vegetation structure and composition, and across spatial scales?LocationSonoran Desert of southwestern Arizona, US.MethodsWe measured perennial vegetation in a chronosequence of 13 fires (8–33 yr TSF) spanning a broad regional gradient. The relative influence of environmental filters (topography and climate) and TSF were compared as predictors of long‐term, post‐fire vegetation assembly. Analyses considered different measures of vegetation structure (cover, height and density) and scales of community organization (species composition, structure and landscape).ResultsSpecies and growth form composition did not exhibit directional responses with increasing TSF, but sorted along abiotic gradients. Differences in vegetation cover and height between burned and unburned control areas were attributed primarily to gradients of topography and climate. In contrast, vegetation density initially increased in burned areas but declined to pre‐burn levels with increasing TSF. The strongest predictors of landscape‐scale recovery of vegetation cover, height and density were elevation, post‐fire precipitation and average annual precipitation, respectively. Recovery of vegetation height was positively correlated with precipitation in the first year following fire, suggesting that abiotic conditions of the immediate post‐fire environment may drive long‐term variability in vegetation structure.ConclusionsWe find substantial evidence that environmental filters, rather than TSF, drive the majority of variability in long‐term, post‐fire vegetation assembly within the Sonoran Desert. Careful consideration of spatial variability in abiotic conditions may benefit post‐fire vegetation modelling, as well as fire management and restoration strategies.
VEGF Pathways in the Lymphatics of Healthy and Diseased Heart
Authors: Dashkevich Alexey , Hagl Christian , Beyersdorf Friedhelm , Nykänen Antti I. , Lemström Karl B. 
Published: July 2015

AbstractCardiac lymphatic system is a rare focus of the modern cardiovascular research. Nevertheless, the growing body of evidence is depicting lymphatic endothelium as an important functional unit in healthy and diseased myocardium. Since the discovery of angiogenic VEGF‐A in 1983 and lymphangiogenic VEGF‐C in 1997, an increasing amount of knowledge has accumulated on the essential roles of VEGF ligands and receptors in physiological and pathological angiogenesis and lymphangiogenesis. Tissue adaptation to several stimuli such as hypoxia, pathogen invasion, degenerative process and inflammation often involves coordinated changes in both blood and lymphatic vessels. As lymphatic vessels are involved in the initiation and resolution of inflammation and regulation of tissue edema, VEGF family members may have important roles in myocardial lymphatics in healthy and in cardiac disease. We will review the properties of VEGF ligands and receptors concentrating on their lymphatic vessel effects first in normal myocardium and then in cardiac disease.
Randomized placebo‐controlled trial of zonisamide in patients with Parkinson's disease
Authors: Murata Miho , Hasegawa Kazuko , Kanazawa Ichiro , Shirakura Kenji , Kochi Kenji , Shimazu Rieko ,   The Zonisamide PD Study Group
Published: July 2015

AbstractBackgroundWe previously showed that zonisamide significantly improved parkinsonian symptoms by a multicenter, double‐blind clinical trial.AimTo confirm the efficacy of zonisamide on Parkinson's disease, a phase 3, randomized, placebo‐controlled, multicenter, double‐blind trial was carried out in Japan.MethodsParticipants had advanced Parkinson's disease taking L‐dopa with at least one other antiparkinson drug, but were developing a deterioration of response to L‐dopa therapy. The trial consisted of a 2‐week initial phase (single‐blind, with administration of placebo) and a 12‐week treatment phase (double‐blind, with patients randomly assigned to either placebo, or zonisamide 25 or 50 mg/day). Patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS).ResultsA total of 185 patients (mean age 64.8 years; mean duration 7.5 years) were included in the efficacy analysis (placebo, zonisamide 25 mg, 50 mg; 63, 61, 61 patients, respectively). When compared with the placebo group, the UPDRS Part III total score at final assessment (the primary end‐point for efficacy) significantly improved (P = 0.029) in the zonisamide 25 mg group. After 12 weeks of therapy, the UPDRS Part III total score significantly improved in both the zonisamide 25 mg (P = 0.038) and 50 mg groups (P = 0.049), compared with the placebo group. Neither the zonisamide 25 mg nor 50 mg group differed significantly from the placebo group in the incidence of adverse events (P = 0.363 and P = 0.713, respectively).ConclusionThese findings confirmed that zonisamide is well tolerated and efficacious in the treatment of advanced Parkinson's disease.
Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease
Authors: Cheng L. S. , Hotta R. , Graham H. K. , Nagy N. , Goldstein A. M. , Belkind‐Gerson J. 
Published: July 2015

AbstractBackgroundTransplantation of enteric neural stem cells (ENSC) holds promise as a potential therapy for enteric neuropathies, including Hirschsprung disease. Delivery of transplantable cells via laparotomy has been described, but we propose a novel, minimally invasive endoscopic method of cell delivery.MethodsEnteric neural stem cells for transplantation were cultured from dissociated gut of postnatal donor mice. Twelve recipient mice, including Ednrb−/− mice with distal colonic aganglionosis, underwent colonoscopic injection of ENSC under direct vision using a 30‐gauge Hamilton needle passed through a rigid cystoureteroscope. Cell engraftment, survival, and neuroglial differentiation were studied 1–4 weeks after the procedure.Key ResultsAll recipient mice tolerated the procedure without complications and survived to sacrifice. Transplanted cells were found within the colonic wall in 9 of 12 recipient mice with differentiation into enteric neurons and glia.Conclusions & InferencesEndoscopic injection of ENSC is a safe and reliable method for cell delivery, and can be used to deliver a large number of cells to a specific area of disease. This minimally invasive endoscopic approach may prove beneficial to future human applications of cell therapy for neurointestinal disease.
Blur, eye movements and performance on a driving visual recognition slide test
Authors: Lee Samantha Sze‐Yee , Wood Joanne M. , Black Alexander A. 
Published: July 2015

AbstractPurposeOptical blur and ageing are known to affect driving performance but their effects on drivers' eye movements are poorly understood. This study examined the effects of optical blur and age on eye movement patterns and performance on the DriveSafe slide recognition test which is purported to predict fitness to drive.MethodsTwenty young (27.1 ± 4.6 years) and 20 older (73.3 ± 5.7 years) visually normal drivers performed the DriveSafe under two visual conditions: best‐corrected vision and with +2.00 DS blur. The DriveSafe is a Visual Recognition Slide Test that consists of brief presentations of static, real‐world driving scenes containing different road users (pedestrians, bicycles and vehicles). Participants reported the types, relative positions and direction of travel of the road users in each image; the score was the number of correctly reported items (maximum score of 128). Eye movements were recorded while participants performed the DriveSafe test using a Tobii TX300 eye tracking system.ResultsThere was a significant main effect of blur on DriveSafe scores (best‐corrected: 114.9 vs blur: 93.2; p < 0.001). There was also a significant age and blur interaction on the DriveSafe scores (p < 0.001) such that the young drivers were more negatively affected by blur than the older drivers (reductions of 22% and 13% respectively; p < 0.001): with best‐corrected vision, the young drivers performed better than the older drivers (DriveSafe scores: 118.4 vs 111.5; p = 0.001), while with blur, the young drivers performed worse than the older drivers (88.6 vs 95.9; p = 0.009). For the eye movement patterns, blur significantly reduced the number of fixations on road users (best‐corrected: 5.1 vs blur: 4.5; p < 0.001), fixation duration on road users (2.0 s vs 1.8 s; p < 0.001) and saccade amplitudes (7.4° vs 6.7°; p < 0.001). A main effect of age on eye movements was also found where older drivers made smaller saccades than the young drivers (6.7° vs 7.4°; p < 0.001).ConclusionsBlur reduced DriveSafe scores for both age groups and this effect was greater for the young drivers. The decrease in number of fixations and fixation duration on road users, as well as the reduction in saccade amplitudes under the blurred condition, highlight the difficulty experienced in performing the task in the presence of optical blur, which suggests that uncorrected refractive errors may have a detrimental impact on aspects of driving performance.
Modulation of Melanogenesis and Antioxidant Status of Melanocytes in Response to Phototoxic Action of Doxycycline
Authors: Rok Jakub , Buszman Ewa , Beberok Artur , Delijewski Marcin , Otręba Michał , Wrześniok Dorota 
Published: July 2015

AbstractDoxycycline is a commonly used tetracycline antibiotic showing the broad spectrum of antibacterial action. However, the use of this antibiotic is often connected with the risk of phototoxic reactions that lead to various skin disorders. One of the factors influencing the photosensitivity reactions is the melanin content in melanocytes. In this study, the impact of doxycycline and UVA irradiation on cell viability, melanogenesis and antioxidant defense system in cultured normal human epidermal melanocytes (HEMn‐DP) was examined. The exposure of cells to doxycycline and UVA radiation resulted in concentration‐dependent loss in melanocytes viability and induced melanin biosynthesis. Significant changes were stated in cellular antioxidant enzymes activity: SOD, CAT and GPx, which indicates alterations of antioxidant defense system. The results obtained in vitro may explain the mechanisms of phototoxic reactions that occur in normal human epidermal melanocytes in vivo after exposure of skin to doxycycline and UVA radiation.
Model for Optimization of the UV‐A/Riboflavin Strengthening (cross‐linking) of the Cornea: Percolation Threshold
Authors: Semchishen Anton , Mrochen Michael , Semchishen Vladimir 
Published: July 2015

AbstractTo achieve the maximum level of collagen strengthening within the shortest treatment time possible, we have developed a mathematical model which is used to optimize the process of corneal cross‐linking. This model is able to predict the temporal and spatial distribution of generated cross‐links within the corneal stroma and hence the increase in the elasticity modulus. Theory predicts corneal strengthening at low radiation intensities and the absence of the strengthening effect at radiation intensities above the threshold level, which agrees with the experimental results. The model takes account of the initial riboflavin concentration and bleaching, light intensity and time of illumination.
Activation of the General Stress Response of Bacillus subtilis by Visible Light
Authors: van der Steen Jeroen B. , Hellingwerf Klaas J. 
Published: July 2015

AbstractA key challenge for microbiology is to understand how evolution has shaped the wiring of regulatory networks. This is amplified by the paucity of information of power‐spectra of physicochemical stimuli to which microorganisms are exposed. Future studies of genome evolution, driven by altered stimulus regimes, will therefore require a versatile signal transduction system that allows accurate signal dosing. Here, we review the general stress response of Bacillus subtilis, and its upstream signal transduction network, as a candidate system. It can be activated by red and blue light, and by many additional stimuli. Signal integration therefore is an intricate function of this system. The blue‐light response is elicited via the photoreceptor YtvA, which forms an integral part of stressosomes, to activate expression of the stress regulon of B. subtilis. Signal transfer through this network can be assayed with reporter enzymes, while intermediate steps can be studied with live‐cell imaging of fluorescently tagged proteins. Different parts of this system have been studied in vitro, such that its computational modeling has made significant progress. One can directly relate the microscopic characteristics of YtvA with activation of the general stress regulon, making this system a very well‐suited system for network evolution studies.
Effects of postharvest onion curing parameters on bulb rot caused by Pantoea agglomerans, Pantoea ananatis and Pantoea allii in storage
Authors: Vahling‐Armstrong C. , Dung J. K. S. , Humann J. L. , Schroeder B. K. 
Published: July 2015

Crop loss of onion bulbs during storage carries an exceptionally high economic impact because a large portion of the production expenses has been expended before storage. Because of this, it is important to define practices that can reduce onion bulb losses caused by storage rots. This study investigates the impact of various curing parameters on disease development resulting from infection by Pantoea agglomerans, P. ananatis and P. allii on onion bulb cultivars Vaquero and Redwing, during storage. Overall, both the incidence and mean rot severity were similar amongst the bulbs under comparable conditions regardless of the species of Pantoea inoculated, although a significant difference was detected between the two onion bulb cultivars. In addition, a significant reduction of storage rot was observed when curing temperatures were ≤35°C. At temperatures >35°C, a shorter curing duration (2 days vs 14 days) decreased the severity of bulb rot due to Pantoea. This increased understanding of the inter‐relationships between the parameters used for curing, and the incidence and severity of bulb rot caused by Pantoea helps provide guidance towards using the curing process as a means to reduce the level of damage resulting from post‐harvest storage rot.
The development of a population of 4D pediatric XCAT phantoms for imaging research and optimization
Authors: Segars W. P. , Norris Hannah , Sturgeon Gregory M. , Zhang Yakun , Bond Jason , Minhas Anum , Tward Daniel J. , Ratnanather J. T. , Miller M. I. , Frush D. , Samei E. 
Published: July 2015

Purpose:We previously developed a set of highly detailed 4D reference pediatric extended cardiac‐torso (XCAT) phantoms at ages of newborn, 1, 5, 10, and 15 yr with organ and tissue masses matched to ICRP Publication 89 values. In this work, we extended this reference set to a series of 64 pediatric phantoms of varying age and height and body mass percentiles representative of the public at large. The models will provide a library of pediatric phantoms for optimizing pediatric imaging protocols.Methods:High resolution positron emission tomography‐computed tomography data obtained from the Duke University database were reviewed by a practicing experienced radiologist for anatomic regularity. The CT portion of the data was then segmented with manual and semiautomatic methods to form a target model defined using nonuniform rational B‐spline surfaces. A multichannel large deformation diffeomorphic metric mapping algorithm was used to calculate the transform from the best age matching pediatric XCAT reference phantom to the patient target. The transform was used to complete the target, filling in the nonsegmented structures and defining models for the cardiac and respiratory motions. The complete phantoms, consisting of thousands of structures, were then manually inspected for anatomical accuracy. The mass for each major tissue was calculated and compared to linearly interpolated ICRP values for different ages.Results:Sixty four new pediatric phantoms were created in this manner. Each model contains the same level of detail as the original XCAT reference phantoms and also includes parameterized models for the cardiac and respiratory motions. For the phantoms that were 10 yr old and younger, we included both sets of reproductive organs. This gave them the capability to simulate both male and female anatomy. With this, the population can be expanded to 92. Wide anatomical variation was clearly seen amongst the phantom models, both in organ shape and size, even for models of the same age and sex. The phantoms can be combined with existing simulation packages to generate realistic pediatric imaging data from different modalities.Conclusions:This work provides a large cohort of highly detailed pediatric phantoms with 4D capabilities of varying age, height, and body mass. The population of phantoms will provide a vital tool with which to optimize 3D and 4D pediatric imaging devices and techniques in terms of image quality and radiation‐absorbed dose.
A Complex Signaling Cascade Governs Pristinamycin Biosynthesis in Streptomyces pristinaespiralis
Authors: Mast Yvonne , Guezguez Jamil , Handel Franziska , Schinko Eva 
Published: July 2015

ABSTRACT

Pristinamycin production in
Streptomyces pristinaespiralis
Pr11 is tightly regulated by an interplay between different repressors and activators. A γ-butyrolactone receptor gene (
spbR
), two TetR repressor genes (
papR3
and
papR5
), three SARP (

S

treptomyces
a
ntibiotic
r
egulatory
p
rotein) genes (
papR1
,
papR2
, and
papR4
), and a response regulator gene (
papR6
) are carried on the large 210-kb pristinamycin biosynthetic gene region of
Streptomyces pristinaespiralis
Pr11. A detailed investigation of all pristinamycin regulators revealed insight into a complex signaling cascade, which is responsible for the fine-tuned regulation of pristinamycin production in
S. pristinaespiralis
.
The Pathway-Specific Regulator ClaR of Streptomyces clavuligerus Has a Global Effect on the Expression of Genes for Secondary Metabolism and Differentiation
Authors: Martínez-Burgo Yolanda , Álvarez-Álvarez Rubén , Rodríguez-García Antonio , Liras Paloma 
Published: July 2015

ABSTRACT

Streptomyces clavuligerus
claR
::
aph
is a
claR
-defective mutant, but in addition to its
claR
defect it also carries fewer copies of the resident linear plasmids pSCL2 and pSCL4 (on the order of 4 × 10
5
-fold lower than the wild-type strain), as shown by qPCR. To determine the function of ClaR without potential interference due to plasmid copy number, a new strain,
S. clavuligerus
Δ
claR
::
aac
, with
claR
deleted and carrying the wild-type level of plasmids, was constructed. Transcriptomic analyses were performed in
S. clavuligerus
Δ
claR
::
aac
and
S. clavuligerus
ATCC 27064 as the control strain. The new Δ
claR
mutant did not produce clavulanic acid (CA) and showed a partial expression of genes for the early steps of the CA biosynthesis pathway and a very poor expression (1 to 8%) of the genes for the late steps of the CA pathway. Genes for cephamycin C biosynthesis were weakly upregulated (1.7-fold at 22.5 h of culture) in the Δ
claR
mutant, but genes for holomycin biosynthesis were expressed at levels from 3- to 572-fold higher than in the wild-type strain, supporting the observed overproduction of holomycin by
S. clavuligerus
Δ
claR
::
aac
. Interestingly, three secondary metabolites produced by gene clusters SMCp20, SMCp22, and SMCp24, encoding still-cryptic compounds, had partially or totally downregulated their genes in the mutant, suggesting a regulatory role for ClaR wider than previously reported. In addition, the
amfR
gene was downregulated, and consequently, the mutant did not produce aerial mycelium. Expression levels of about 100 genes in the genome were partially up- or downregulated in the Δ
claR
mutant, many of them related to the upregulation of the sigma factor-encoding
rpoE
gene.