bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological pacing in young patients with complex congenital heart defects
Authors: Silvetti Massimo Stefano , Pazzano Vincenzo , Battipaglia Irma , Di Mambro Corrado , Calvieri Camilla , Saputo Fabio Anselmo , Verticelli Letizia , Carotti Adriano , Torcinaro Sergio , Drago Fabrizio 
Published: June 2018

AbstractAimYoung patients with operated complex congenital heart defects (CHD) often develop sinus node dysfunction (SND) requiring permanent pacing with rate‐responsive function. Activity‐driven sensors cannot account for nonmovement stress and cannot modulate heart rate physiologically. Closed Loop Stimulation (CLS, Biotronik, Berlin, Germany) is a physiological rate‐responsive pacemaker based on the indirect measure of ventricular contractility. No data are available on the effects of such pacing strategy in young patients.MethodsWe report a series of nine patients with CHD and SND who underwent single‐chamber CLS‐atrial pacing with endocardial or epicardial lead. During the first 30 days, the pacemaker was programmed in AAI pacing mode and then was switched to CLS‐atrial pacing mode. An in‐hospital control was scheduled 1–2 months later to evaluate the CLS response to neurovegetative stresses (i.e., nonmovement stress [Stroop color test, handgrip] and exercise stress test) and Holter monitor. CLS pacing was compared with rate‐responsive accelerometer‐driven pacing (AAIR).ResultsAt telemetric interrogation, CLS pacing showed a more physiological pattern of 24‐h heart rate trends than accelerometer sensors. The data obtained during nonmovement/exercise stress demonstrated a physiological increase in the pacing rate with CLS, in synergy with spontaneous events. The accelerometer sensor histogram, during nonmovement stress, showed a “nonresponse” behavior (only lower rate events), and during exercise test showed most events in lower rate range. Holter monitoring showed increase of average and maximum heart rate compared with AAIR.ConclusionIn young CHD patients, endocardial/epicardial CLS‐atrial pacing demonstrated a physiological response of heart rate to neurovegetative and physical stresses.
Up‐regulation of lipid biosynthesis increases the oil content in leaves of Sorghum bicolor
Authors: Vanhercke Thomas , Belide Srinivas , Taylor Matthew C. , El Tahchy Anna , Okada Shoko , Rolland Vivien , Liu Qing , Mitchell Madeline , Shrestha Pushkar , Venables Ingrid , Ma Lina , Blundell Cheryl , Mathew Anu , Ziolkowski Lisa , Niesner Nathalie , Hussain Dawar , Dong Bei , Liu Guoquan , Godwin Ian D. , Lee Jiwon , Rug Melanie , Zhou Xue‐Rong , Singh Surinder P. , Petrie James R. 
Published: June 2018

SummarySynthesis and accumulation of the storage lipid triacylglycerol in vegetative plant tissues has emerged as a promising strategy to meet the world's future need for vegetable oil. Sorghum (Sorghum bicolor) is a particularly attractive target crop given its high biomass, drought resistance and C4 photosynthesis. While oilseed‐like triacylglycerol levels have been engineered in the C3 model plant tobacco, progress in C4 monocot crops has been lagging behind. In this study, we report the accumulation of triacylglycerol in sorghum leaf tissues to levels between 3 and 8.4% on a dry weight basis depending on leaf and plant developmental stage. This was achieved by the combined overexpression of genes encoding the Zea mays WRI1 transcription factor, Umbelopsis ramanniana UrDGAT2a acyltransferase and Sesamum indicum Oleosin‐L oil body protein. Increased oil content was visible as lipid droplets, primarily in the leaf mesophyll cells. A comparison between a constitutive and mesophyll‐specific promoter driving WRI1 expression revealed distinct changes in the overall leaf lipidome as well as transitory starch and soluble sugar levels. Metabolome profiling uncovered changes in the abundance of various amino acids and dicarboxylic acids. The results presented here are a first step forward towards the development of sorghum as a dedicated biomass oil crop and provide a basis for further combinatorial metabolic engineering.
Transgenic creeping bentgrass overexpressing Osa‐miR393a exhibits altered plant development and improved multiple stress tolerance
Authors: Zhao Junming , Yuan Shuangrong , Zhou Man , Yuan Ning , Li Zhigang , Hu Qian , Bethea Frank G. , Liu Haibo , Li Shigui , Luo Hong 
Published: June 2018

SummaryMicroRNA393 (miR393) has been implicated in plant growth, development and multiple stress responses in annual species such as Arabidopsis and rice. However, the role of miR393 in perennial grasses remains unexplored. Creeping bentgrass (Agrostis stolonifera L.) is an environmentally and economically important C3 cool‐season perennial turfgrass. Understanding how miR393 functions in this representative turf species would allow the development of novel strategies in genetically engineering grass species for improved abiotic stress tolerance. We have generated and characterized transgenic creeping bentgrass plants overexpressing rice pri‐miR393a (Osa‐miR393a). We found that Osa‐miR393a transgenics had fewer, but longer tillers, enhanced drought stress tolerance associated with reduced stomata density and denser cuticles, improved salt stress tolerance associated with increased uptake of potassium and enhanced heat stress tolerance associated with induced expression of small heat‐shock protein in comparison with wild‐type controls. We also identified two targets of miR393, AsAFB2 and AsTIR1, whose expression is repressed in transgenics. Taken together, our results revealed the distinctive roles of miR393/target module in plant development and stress responses between creeping bentgrass and other annual species, suggesting that miR393 would be a promising candidate for generating superior crop cultivars with enhanced multiple stress tolerance, thus contributing to agricultural productivity.
More than Pathological Formalization: Understanding Organizational Structure and Red Tape
Authors: Kaufmann Wesley , Borry Erin L. , DeHart‐Davis Leisha 
Published: June 2018

AbstractMost research has conceptualized red tape as being a pathological subset of organizational formalization. This article argues that focusing on a single dimension of organizational structure as a red tape driver is unrealistically narrow. Specifically, the article advances hypotheses as to how organizational centralization and hierarchy affect perceived red tape, in addition to formalization. This reasoning is tested using survey data from employees of three local government organizations in the southeastern United States. All three hypotheses are supported: higher levels of organizational formalization, centralization, and hierarchy are associated with more red tape. Open‐ended comments also indicate that red tape is not solely perceived as related to formalization. The findings imply that red tape is a multifaceted perception of organizational structure rather than perceived pathological formalization.
The Birth of Being and Time: Heidegger's Pivotal 1921 Reading of Aristotle's On the Soul
Authors: Gonzalez Francisco J. 
Published: June 2018

AbstractDuring the 1920s Heidegger gave no less than twelve seminars and lecture courses devoted either exclusively or in large part to the reading of Aristotle's texts. Seven of these, especially the smaller seminars for advanced students, have not been published and apparently will never be included in the Gesamtausgabe. My focus here is on the very first of these. Billed as a reading of Aristotle's De Anima, much of it was devoted to Aristotle's Metaphysics. This decision not to separate Aristotle's “psychology” from his “ontology” is a key move of the seminar that anticipates the project of Being and Time. This and many other ways in which Heidegger's early reading of De Anima anticipates the key moves of the later book constitute one of the reasons for its importance. Another is that the seminar allows us to see what gets suppressed in Heidegger's reading of Aristotle, most significantly, the phenomenon of life itself in favor of an eventual focus on the being of human life or Dasein. This early seminar thus enables us not only to better understand Heidegger's project, but also to raise some fundamental questions concerning it.
Are All Primitives Created Equal?
Authors: Miller J. T. M. 
Published: June 2018

AbstractPrimitives are both important and unavoidable, and which set of primitives we endorse will greatly shape our theories and how those theories provide solutions to the problems that we take to be important. After introducing the notion of a primitive posit, I discuss the different kinds of primitives that we might posit. Following Cowling (), I distinguish between ontological and ideological primitives, and, following Benovsky (), between functional and content views of primitives. I then propose that these two distinctions cut across each other leading to four types of primitive posits. I then argue that theoretical virtues should be taken to be metatheoretical ideological primitives. I close with some reflections on the global nature of comparing sets of primitives.
Extracellular signal‐regulated kinase 2 has duality in function between neuronal and astrocyte expression following neonatal hypoxic–ischaemic cerebral injury
Authors: Thei Laura , Rocha‐Ferreira Eridan , Peebles Donald , Raivich Gennadij , Hristova Mariya 
Published: June 2018

Key points
This study identifies phosphorylated extracellular signal‐regulated kinase (ERK) to be immediately diminished followed by a rapid if transient increase for up to 4 h following hypoxic–ischaemic insult (HI) in the neonatal mouse.
Phosphorylated ERK up‐regulation was prevented with systemic injection of the mitogen‐activated protein kinase kinase (MEK) inhibitor SL327. Treatment with SL327 both pre‐ and post‐HI gave a strong reduction in the number of dying cells and microgliosis.
By utilising transgenic mouse mutations, we observe that neuronal ERK2 significantly contributes to tissue damage, while ERK1 and astrocytic ERK2 are neuroprotective.
Compared to global inactivation, selective cell‐specific interference with ERK activity could result in stronger neuroprotection.
AbstractHypoxia–ischaemia (HI) is a major cause of neonatal brain injury resulting in cerebral palsy, epilepsy, cognitive impairment and other neurological disabilities. The role of extracellular signal‐regulated kinase (ERK) isoforms and their mitogen‐activated protein kinase kinase (MEK)‐dependent phosphorylation in HI has previously been explored but remains unresolved at cellular level. This is pertinent given the growing awareness of the role of non‐neuronal cells in neuroprotection. Using a modified Rice–Vannucci model of HI in the neonatal mouse we observed time‐ and cell‐dependent ERK phosphorylation (pERK), with strongly up‐regulated pERK immunoreactivity first in periventricular white matter axons within 15–45 min of HI, followed by forebrain astrocytes and neurons (1–4 h post‐HI), and return to baseline by 16 h. We explored the effects of pharmacological ERK blockade through the MEK inhibitor SL327 on neonatal HI‐brain damage following HI alone (30 or 60 min) or lipopolysaccharide (LPS)‐sensitised HI insult (30 min). Global inhibition of ERK phosphorylation with systemically applied SL327 abolished forebrain pERK immunoreactivity, and significantly reduced cell death and associated microglial activation at 48 h post‐HI. We then explored the effects of cell‐specific ERK2 deletion alone or in combination with global ERK1 knockout under the same conditions of HI insult. Neuronal ERK2 deletion strongly decreased infarct size, neuronal cell death and microglial activation in grey matter following both HI alone or LPS‐sensitised HI. ERK1 deletion attenuated the protective effect of neuronal ERK2 deletion. Removal of astroglial ERK2 produced a reverse response, with a 3‐ to 4‐fold increase in microglial activation and cell death. Our data suggest a cell‐specific and time‐dependent role of ERK in neonatal HI, with a predominant, neurotoxic effect of neuronal ERK2, which is counteracted by neuroprotection by ERK1 and astrocytic ERK2. Overall, global pharmacological inhibition of ERK phosphorylation is strongly neuroprotective.
Bicarbonate directly modulates activity of chemosensitive neurons in the retrotrapezoid nucleus
Authors: Gonçalves Christopher M. , Mulkey Daniel K. 
Published: June 2018

Key Points
Changes in CO2 result in corresponding changes in both H+ and HCO3− and despite evidence that HCO3− can function as an independent signalling molecule, there is little evidence suggesting HCO3− contributes to respiratory chemoreception.
We show that HCO3− directly activates chemosensitive retrotrapezoid nucleus (RTN) neurons.
Identifying all relevant signalling molecules is essential for understanding how chemoreceptors function, and because HCO3− and H+ are buffered by separate cellular mechanisms, having the ability to sense both modalities adds additional information regarding changes in CO2 that are not necessarily reflected by pH alone.
HCO3− may be particularly important for regulating activity of RTN chemoreceptors during sustained intracellular acidifications when TASK‐2 channels, which appear to be the sole intracellular pH sensor, are minimally active.
AbstractCentral chemoreception is the mechanism by which the brain regulates breathing in response to changes in tissue CO2/H+. The retrotrapezoid nucleus (RTN) is an important site of respiratory chemoreception. Mechanisms underlying RTN chemoreception involve H+‐mediated activation of chemosensitive neurons and CO2/H+‐evoked ATP‐purinergic signalling by local astrocytes, which activates chemosensitive neurons directly and indirectly by maintaining vascular tone when CO2/H+ levels are high. Although changes in CO2 result in corresponding changes in both H+ and HCO3− and despite evidence that HCO3− can function as an independent signalling molecule, there is little evidence suggesting HCO3− contributes to respiratory chemoreception. Therefore, the goal of this study was to determine whether HCO3− regulates activity of chemosensitive RTN neurons independent of pH. Cell‐attached recordings were used to monitor activity of chemosensitive RTN neurons in brainstem slices (300 μm thick) isolated from rat pups (postnatal days 7–11) during exposure to low or high concentrations of HCO3−. In a subset of experiments, we also included 2′,7′‐bis(2carboxyethyl)‐5‐(and 6)‐carboxyfluorescein (BCECF) in the internal solution to measure pHi under each experimental condition. We found that HCO3− activates chemosensitive RTN neurons by mechanisms independent of intracellular or extracellular pH, glutamate, GABA, glycine or purinergic signalling, soluble adenylyl cyclase activity, nitric oxide or KCNQ channels. These results establish HCO3− as a novel independent modulator of chemoreceptor activity, and because the levels of HCO3− along with H+ are buffered by independent cellular mechanisms, these results suggest HCO3− chemoreception adds additional information regarding changes in CO2 that are not necessarily reflected by pH.
Complete Genome Sequence of Listeria monocytogenes DFPST0073, Isolated from Imported Mexican Soft Cheese
Authors: Salazar Joelle K. , Gonsalves Lauren J. , Schill Kristin M. , Sanchez Leon Maria , Anderson Nathan , Keller Susanne E. 
Published: June 2018

ABSTRACT

The genome of
Listeria monocytogenes
strain DFPST0073, isolated from imported fresh Mexican soft cheese in 2003, was sequenced using the Illumina MiSeq platform. Reads were assembled using SPAdes, and genome annotation was performed using the NCBI Prokaryotic Genome Annotation Pipeline.
Five-year visual outcomes after anti-VEGF therapy with or without photodynamic therapy for polypoidal choroidal vasculopathy
Authors: Miyata Manabu , Ooto Sotaro , Yamashiro Kenji , Tamura Hiroshi , Hata Masayuki , Ueda-Arakawa Naoko , Yoshikawa Munemitsu , Numa Shogo , Tsujikawa Akitaka 
Published: June 2018

Background/aimsTo evaluate the 5-year visual and anatomical outcomes after anti-vascular endothelial growth factor (VEGF) therapy alone or in combination with photodynamic therapy (PDT), followed by pro re nata (PRN) anti-VEGF therapy with or without PDT, for polypoidal choroidal vasculopathy (PCV).MethodsThis retrospective, observational study included 61 consecutive patients with treatment-naïve symptomatic PCV who were followed for 5 years. Twenty eyes (20 patients) initially received PDT and intravitreal injection of ranibizumab (IVR), followed by a PRN regimen of anti-VEGF therapy with or without PDT (combination group), while 41 eyes (41 patients) initially received only IVR every 3 months, followed by a PRN regimen of anti-VEGF monotherapy (IVR group). Macular atrophy including the fovea was confirmed using colour fundus photography and spectral-domain optical coherence tomography.ResultsIn both groups, the visual acuity (VA) at 1 year was better than the baseline VA, whereas the 3-year, 4-year and 5-year VA values were similar to the baseline VA. There was no significant difference in the 5-year VA, 5-year central retinal thickness and incidence of macular atrophy between the two groups (p=0.63, 0.72 and 0.06, respectively). In the combination group, the 5-year VA was correlated with the 5-year incidence of macular atrophy (p=0.02, r=0.51).ConclusionsA PRN regimen for PCV may have a limited effect for the long-term maintenance of improved VA. Macular atrophy may occur more frequently with combination therapy and is possibly associated with the 5-year VA. Thus, combination therapy should be carefully selected for patients susceptible to macular atrophy.
Exploring visitation at rivers to understand drowning risk
Authors: Peden Amy E , Franklin Richard C , Leggat Peter A 
Published: June 2018

IntroductionGlobally, rivers are a common drowning location. In Australia, rivers are the leading location for fatal drowning. Limited information exists on exposure and impact on river drowning risk.MethodsAustralian unintentional fatal river drowning data (sourced from coronial records) and nationally representative survey data on river visitation were used to estimate river drowning risk based on exposure for adults (18 years and older). Differences in river drowning rates per 100 000 (population and exposed population) were examined by sex, age group, activity prior to drowning, alcohol presence and watercraft usage.ResultsBetween 1 January 2014 and 31 December 2016, 151 people drowned in Australian rivers; 86% male and 40% aged 18–34 years. Of survey respondents, 73% had visited a river within the last 12 months. After adjusting for exposure: males were 7.6 times more likely to drown at rivers; female drowning rate increased by 50% (0.06–0.09 per 100 000); males aged 75+ years and females aged 55–74 years were at highest risk of river drowning; and swimming and recreating pose a high risk to both males and females. After adjusting for exposure, males were more likely to drown with alcohol present (RR=8.5; 95% CI 2.6 to 27.4) and in a watercraft-related incident (RR=25.5; 95% CI 3.5 to 186.9).ConclusionsCalculating exposure for river drowning is challenging due to diverse usage, time spent and number of visits. While males were more likely to drown, the differences between males and females narrow after adjusting for exposure. This is an important factor to consider when designing and implementing drowning prevention strategies to effectively target those at risk.
Establishing the role of PLVAP in protein-losing enteropathy: a homozygous missense variant leads to an attenuated phenotype
Authors: Kurolap Alina , Eshach-Adiv Orly , Gonzaga-Jauregui Claudia , Dolnikov Katya , Mory Adi , Paperna Tamar , Hershkovitz Tova , Overton John D , Kaplan Marielle , Glaser Fabian , Zohar Yaniv , Shuldiner Alan R , Berger Gidon , Baris Hagit N 
Published: June 2018

BackgroundIntestinal integrity is essential for proper nutrient absorption and tissue homeostasis, with damage leading to enteric protein loss, that is, protein-losing enteropathy (PLE). Recently, homozygous nonsense variants in the plasmalemma vesicle-associated protein gene (PLVAP) were reported in two patients with severe congenital PLE. PLVAP is the building block of endothelial cell (EC) fenestral diaphragms; its importance in barrier function is supported by mouse models of Plvap deficiency.ObjectiveTo genetically diagnose two first-degree cousins once removed, who presented with PLE at ages 22 and 2.5 years.MethodsFamily-based whole exome sequencing was performed based on an autosomal recessive inheritance model. In silico analyses were used to predict variant impact on protein structure and function.ResultsWe identified a rare homozygous variant (NM_031310.2:c.101T>C;p.Leu34Pro) in PLVAP, which co-segregated with the disease. Leu34 is predicted to be located in a highly conserved, hydrophobic, α-helical region within the protein’s transmembrane domain, suggesting Leu34Pro is likely to disrupt protein function and/or structure. Electron microscopy and PLVAP immunohistochemistry demonstrated apparently normal diaphragm morphology, predicted to be functionally affected.ConclusionsBiallelic missense variants in PLVAP can cause an attenuated form of the PLE and hypertriglyceridaemia syndrome. Our findings support the role of PLVAP in the pathophysiology of PLE, expand the phenotypic and mutation spectrums and underscore PLVAP’s importance in EC barrier function in the gut.
Inversion of Taconian extensional structures during Paleozoic orogenesis in western Newfoundland
Authors: White Shawna E. , Waldron John W. F. 
Published: June 2018

Abstract
West Newfoundland was critical in developing the Wilson Cycle concept. Neoproterozoic rifting established a passive margin adjacent to the Iapetus Ocean. Ordovician (Taconian) arc–continent collision emplaced ophiolites and the thin-skinned Humber Arm Allochthon. Subsequent Devonian (Acadian) ocean closure produced basement-cutting thrust faults that control the present-day distribution of units. New mapping, and aeromagnetic and seismic interpretation, around Parsons Pond enabled the recognition of structures in poorly exposed areas.

Following Cambrian to Middle Ordovician passive-margin deposition, Taconian deformation produced a flexural bulge unconformity. Subsequent extensional faults shed localized conglomerate into the foreland basin. The Humber Arm Allochthon contains a series of stacked and folded duplexes, typical of thrust belts. To the east, the Parsons Pond Thrust has transported shelf and foreland-basin units
c.
8 km westwards above the allochthon. The Long Range Thrust shows major topographical expression but <1 km offset. Stratigraphic relationships indicate that most thrusts originated as normal faults, active during Neoproterozoic rifting, and subsequently during Taconian flexure. Devonian continental collision inverted the Parsons Pond and Long Range thrusts. Basement-cored fault-propagation folds in Newfoundland are structurally analogous to basement uplifts in other orogens, including the Laramide Orogen in western USA. Similar deep-seated inversion structures may extend through the northern Appalachians.