bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maize w3 disruptshomogentisate solanesyl transferase (ZmHst) and reveals a plastoquinone‐9 independent path for phytoene desaturation and tocopherol accumulation in kernels
Authors: Hunter Charles T. , Saunders Jonathan W. , Magallanes‐Lundback Maria , Christensen Shawn A. , Willett Denis , Stinard Philip S. , Li Qin‐Bao , Lee Kwanghee , DellaPenna Dean , Koch Karen E. 
Published: January 2018

SummaryMaizewhite seedling 3(w3) has been used to study carotenoid deficiency for almost 100 years, although the molecular basis of the mutation has remained unknown. Here we show that thew3phenotype is caused by disruption of the maize gene for homogentisate solanesyl transferase (HST), which catalyzes the first and committed step in plastoquinone‐9 (PQ‐9) biosynthesis in the plastid. The resultingPQ‐9 deficiency prohibits photosynthetic electron transfer and eliminatesPQ‐9 as an oxidant in the enzymatic desaturation of phytoene during carotenoid synthesis. As a result, light‐grownw3seedlings are albino, deficient in colored carotenoids and accumulate high levels of phytoene. However, despite the absence ofPQ‐9 for phytoene desaturation, dark‐grownw3seedlings can produce abscisic acid (ABA) and homozygousw3kernels accumulate sufficient carotenoids to generateABAneeded for seed maturation. The presence ofABAand low levels of carotenoids inw3nulls indicates that phytoene desaturase is able to use an alternate oxidant cofactor, albeit less efficiently thanPQ‐9. The observation that tocopherols and tocotrienols are modestly affected inw3embryos and unaffected inw3endosperm indicates that, unlike leaves, grain tissues deficient inPQ‐9 are not subject to severe photo‐oxidative stress. In addition to identifying the molecular basis for the maizew3mutant, we: (1) show that low levels of phytoene desaturation can occur inw3seedlings in the absence ofPQ‐9; and (2) demonstrate thatPQ‐9 and carotenoids are not required for vitamin E accumulation.
Transfusion support for transgender men of childbearing age
Authors: Mays James A. , Greene Dina N. , Metcalf Ryan A. , Pagano Monica B. 
Published: January 2018

BACKGROUNDTo date, limited attention has been given to transgender recipients of blood components, particularly transgender men of childbearing age. Here, we highlight the essential information needed to provide transfusion support for this population.CASE REPORTA 40‐year‐old transgender man, who retained his uterus and ovaries, presented with severe vaginal hemorrhage following biopsies for a cervical mass. He was admitted to the Gynecology unit and emergency blood was ordered. Because the patient was listed as male in the electronic health record (EHR), the transfusion service prepared uncrossmatched type O, RhD‐positive red blood cells (RBC). After the sex/gender incongruence was recognized, the units were switched for Rh‐negative.CONCLUSIONThis case illustrates particular considerations when caring for transgender patients: gender/sex documentation, decision‐making processes when gender/sex‐specific care applies, and challenges to the pathology service.
Voltage‐gated sodium channels: (NaV)igating the field to determine their contribution to visceral nociception
Authors: Erickson Andelain , Deiteren Annemie , Harrington Andrea M. , Garcia‐Caraballo Sonia , Castro Joel , Caldwell Ashlee , Grundy Luke , Brierley Stuart M. 
Published: January 2018

AbstractChronic visceral pain, altered motility and bladder dysfunction are common, yet poorly managed symptoms of functional and inflammatory disorders of the gastrointestinal and urinary tracts. Recently, numerous human channelopathies of the voltage‐gated sodium (NaV) channel family have been identified, which induce either painful neuropathies, an insensitivity to pain, or alterations in smooth muscle function. The identification of these disorders, in addition to the recent utilisation of genetically modified NaVmice and specific NaVchannel modulators, has shed new light on how NaVchannels contribute to the function of neuronal and non‐neuronal tissues within the gastrointestinal tract and bladder. Here we review the current pre‐clinical and clinical evidence to reveal how the nine NaVchannel family members (NaV1.1–NaV1.9) contribute to abdominal visceral function in normal and disease states.image
The large‐conductance voltage‐ and Ca2+‐activated K+ channel and its γ1‐subunit modulate mouse uterine artery function during pregnancy
Authors: Lorca Ramón A. , Wakle‐Prabagaran Monali , Freeman William E. , Pillai Meghan K. , England Sarah K. 
Published: January 2018

Key points
The uterine artery (UA) markedly vasodilates during pregnancy to direct blood flow to the developing fetus. Inadequate UA vasodilatation leads to intrauterine growth restriction and fetal death.
The large‐conductance voltage‐ and Ca2+‐activated K+ (BKCa) channel promotes UA vasodilatation during pregnancy.
We report that BKCa channel activation increases the UA diameter at late pregnancy stages in mice.
Additionally, a BKCa channel auxiliary subunit, γ1, participates in this process by increasing channel activation and inducing UA vasodilatation at late pregnancy stages.
Our results highlight the importance of the BKCa channel and its γ1‐subunit for UA functional changes during pregnancy.
AbstractInsufficient vasodilatation of the uterine artery (UA) during pregnancy leads to poor utero‐placental perfusion, contributing to intrauterine growth restriction and fetal loss. Activity of the large‐conductance Ca2+‐activated K+ (BKCa) channel increases in the UA during pregnancy, and its inhibition reduces uterine blood flow, highlighting a role of this channel in UA adaptation to pregnancy. The auxiliary γ1‐subunit increases BKCa activation in vascular smooth muscle, but its role in pregnancy‐associated UA remodelling is unknown. We explored whether the BKCa and its γ1‐subunit contribute to UA remodelling during pregnancy. Doppler imaging revealed that, compared to UAs from wild‐type (WT) mice, UAs from BKCa knockout (BKCa−/−) mice had lower resistance at pregnancy day 14 (P14) but not at P18. Lumen diameters were twofold larger in pressurized UAs from P18 WT mice than in those from non‐pregnant mice, but this difference was not seen in UAs from BKCa−/− mice. UAs from pregnant WT mice constricted 20–50% in response to the BKCa blocker iberiotoxin (IbTX), whereas UAs from non‐pregnant WT mice only constricted 15%. Patch‐clamp analysis of WT UA smooth muscle cells confirmed that BKCa activity increased over pregnancy, showing three distinct voltage sensitivities. The γ1‐subunit transcript increased 7‐ to 10‐fold during pregnancy. Furthermore, γ1‐subunit knockdown reduced IbTX sensitivity in UAs from pregnant mice, whereas γ1‐subunit overexpression increased IbTX sensitivity in UAs from non‐pregnant mice. Finally, at P18, γ1‐knockout (γ1−/−) mice had smaller UA diameters than WT mice, and IbTX‐mediated vasoconstriction was prevented in UAs from γ1−/− mice. Our results suggest that the γ1‐subunit increases BKCa activation in UAs during pregnancy.
Muscle molecular adaptations to endurance exercise training are conditioned by glycogen availability: a proteomics‐based analysis in the McArdle mouse model
Authors: Fiuza‐Luces Carmen , Santos‐Lozano Alejandro , Llavero Francisco , Campo Rocío , Nogales‐Gadea Gisela , Díez‐Bermejo Jorge , Baladrón Carlos , González‐Murillo África , Arenas Joaquín , Martín Miguel A. , Andreu Antoni L. , Pinós Tomàs , Gálvez Beatriz G. , López Juan A. , Vázquez Jesús , Zugaza José L. , Lucia Alejandro 
Published: January 2018

Key points
Although they are unable to utilize muscle glycogen, McArdle mice adapt favourably to an individualized moderate‐intensity endurance exercise training regime. Yet, they fail to reach the performance capacity of healthy mice with normal glycogen availability.
There is a remarkable difference in the protein networks involved in muscle tissue adaptations to endurance exercise training in mice with and without glycogen availability.
Indeed, endurance exercise training promoted the expression of only three proteins common to both McArdle and wild‐type mice: LIMCH1, PARP1 and TIGD4.
In turn, trained McArdle mice presented strong expression of mitogen‐activated protein kinase 12 (MAPK12).
AbstractMcArdle's disease is an inborn disorder of skeletal muscle glycogen metabolism that results in blockade of glycogen breakdown due to mutations in the myophosphorylase gene. We recently developed a mouse model carrying the homozygous p.R50X common human mutation (McArdle mouse), facilitating the study of how glycogen availability affects muscle molecular adaptations to endurance exercise training. Using quantitative differential analysis by liquid chromatography with tandem mass spectrometry, we analysed the quadriceps muscle proteome of 16‐week‐old McArdle (n = 5) and wild‐type (WT) (n = 4) mice previously subjected to 8 weeks’ moderate‐intensity treadmill training or to an equivalent control (no training) period. Protein networks enriched within the differentially expressed proteins with training in WT and McArdle mice were assessed by hypergeometric enrichment analysis. Whereas endurance exercise training improved the estimated maximal aerobic capacity of both WT and McArdle mice as compared with controls, it was ∼50% lower than normal in McArdle mice before and after training. We found a remarkable difference in the protein networks involved in muscle tissue adaptations induced by endurance exercise training with and without glycogen availability, and training induced the expression of only three proteins common to McArdle and WT mice: LIM and calponin homology domains‐containing protein 1 (LIMCH1), poly (ADP‐ribose) polymerase 1 (PARP1 – although the training effect was more marked in McArdle mice), and tigger transposable element derived 4 (TIGD4). Trained McArdle mice presented strong expression of mitogen‐activated protein kinase 12 (MAPK12). Through an in‐depth proteomic analysis, we provide mechanistic insight into how glycogen availability affects muscle protein signalling adaptations to endurance exercise training.
Ageing of the carotid body
Authors: Di Giulio Camillo 
Published: January 2018

AbstractThe ageing process is characterized by a decline in several physiological functions resulting in a reduced capability to maintain homeostasis. The lowered homeostatic capacity seems to involve the carotid body (CB), whose role is to modulate ventilation and tissue oxygen supply. It thus plays a prime role in all ageing processes. Ageing causes marked changes in CB morphology. In older animals, it is enlarged and shows a concomitant decrease in the percentage of chemoreceptor tissue, as well as a proliferation of type II cells. The carotid glomitis is present with aggregates of lymphocytes and fibrosis of the lobules. Type I cells are dehydrated, with a profound vacuolization, a shrinking nucleus, and lipofuscin accumulation. With increased age, human CB shows a reduction in the number and volume of mitochondria, fewer synaptic junctions between glomi, along with a reduction in CB content of neurotransmitters, leading to a sort of ‘physiological denervation’. Ageing could be interpreted as a cumulative result of oxidative damage to cells, which derives from aerobic metabolism. Moreover, metabolic rate is tightly correlated with life duration; thus a loss in mitochondrial function is one of the prime factors affecting CB ageing processes. The age‐related reduction in synaptic junctions might be a self‐protective mechanism through which cells buffer themselves against an accumulation of reactive oxygen species. The correlation between hypoxia and the life duration of CB cells remains an open question until how and why cells sense oxygen is understood.
HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node
Authors: Kozasa Yuko , Nakashima Noriyuki , Ito Masayuki , Ishikawa Taisuke , Kimoto Hiroki , Ushijima Kazuo , Makita Naomasa , Takano Makoto 
Published: January 2018

Key points
The contribution of HCN4 pacemaker channels in the autonomic regulation of the sino‐atrial node (SAN) has been a matter of debate.
The transgenic overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability, while the conditional knockdown of HCN4 gave rise to sinus arrhythmia.
The response of the SAN to β‐adrenergic stimulation was not affected by overexpression or knockdown of HCN4 channels.
When HCN4 channels were knocked down, the parasympathetic response examined by cervical vagus nerve stimulation (CVNS) was enhanced; the CVNS induced complete sinus pause. The overexpression of HCN4 attenuated bradycardia induced by CVNS only during β‐adrenergic stimulation.
We concluded that HCN4 pacemaker channels stabilize the spontaneous firing by attenuating the parasympathetic response of the SAN.
AbstractThe heart rate is dynamically controlled by the sympathetic and parasympathetic nervous systems that regulate the sinoatrial node (SAN). HCN4 pacemaker channels are the well‐known causative molecule of congenital sick sinus syndrome. Although HCN4 channels are activated by cAMP, the sympathetic response of the SAN was preserved in patients carrying loss‐of‐function mutations of the HCN4 gene. In order to clarify the contribution of HCN4 channels in the autonomic regulation of the SAN, we developed novel gain‐of‐function mutant mice in which the expression level of HCN4 channels could be reversibly changed from zero to ∼3 times that in wild‐type mice, using tetracycline transactivator and the tetracycline responsive element. We recorded telemetric ECGs in freely moving conscious mice and analysed the heart rate variability. We also evaluated the response of the SAN to cervical vagus nerve stimulation (CVNS). The conditional overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability. The HCN4 overexpression also attenuated bradycardia induced by the CVNS only during the β‐adrenergic stimulation. In contrast, the knockdown of HCN4 gave rise to sinus arrhythmia, and enhanced the parasympathetic response; complete sinus pause was induced by the CVNS. In vitro, we compared the effects of acetylcholine on the spontaneous action potentials of single pacemaker cells, and found that similar phenotypic changes were induced by genetic manipulation of HCN4 expression both in the presence and absence of β‐adrenergic stimulation. Our study suggests that HCN4 channels attenuate the vagal response of the SAN, and thereby stabilize the spontaneous firing of the SAN.
Diesel Engine Performance Improvement for Constant Speed Application Using CFD
Authors: Dahifale Balasaheb S. , Patil Anand S. 
Published: January 2018

The detailed investigation of flow behavior inside the combustion chamber and performance of engine is most challenging problem due to constraints in Experimental Data collection during testing; However, Experimental testing is essential for establishment of correlation with CFD Predictions. Hence, the baseline engine was tested at different load conditions and validated with CFD results, before it was optimized for performance improvement. The objective of the CFD Prediction was not only to optimize performance (Fuel Efficiency, Power, Torque, etc.) & Emissions Reduction, but also to assess feasibility of Performance Upgrade Potential.
In the present CFD study, surface mesh and domain was prepared for the flame face, intake valve, intake valve seat, exhaust valve, exhaust valve seat and liner for closed volume cycle, between IVC and EVO using CFD code VECTIS. Finally simulations for three different load conditions were conducted using VECTIS solver. Initially, in-cylinder pressure vis a vis crank angle prediction was carried out for 100%, 75% and 50% load conditions. Then the fine tuning of (P-ϴ) diagram for different load conditions was conducted by varying different combustion parameters. Further, the engine performance validation was carried out for rated and part load conditions in terms of, IMEP, BMEP, break specific fuel consumption and power output, while NOx mass fractions were used to convert the NOx to g/kWh for comparison of emission levels with the test data. Finally optimized re-entrant combustion chamber and modified valve timing with optimum fuel injection system simulation was carried out to achieve target performance with reduced fuel consumption. A 3D CFD result showed reduction in BSFC and was in close agreement with the test data.
Numerical Investigation of Flow Through an Ultra-Micro Scale Gas Turbine
Authors: D’souza Rohann , Sharma Rajnish 
Published: January 2018

The ultra-micro scale gas turbine (UMGT) is an ongoing area of research, as an alternate power source for portable electronic devices. To advance our understanding that will help in its development, this paper focuses on a numerical analysis via computational fluid dynamics (CFD) of flow through a 3 dimensional (3D) blade profiled UMGT turbine. CFD modelling was based off an integrated turbine that consists of a volute, nozzle guide vanes (NGV) and rotor. Firstly, the flow through the integrated system as well as each component was analyzed. Secondly, the turbine was simulated under three different isothermal conditions and compared to the adiabatic situation, in order to understand the loss mechanisms. Lastly, the effect of tip clearance was studied, where it was varied between 0–10% of the blade height.
CFD results showed, the flow through the turbine was quite well behaved, however separation of flow at the NGV leading edge, and residual swirl at the rotor trailing edge, were observed. The effects of the isothermal wall boundary condition was very pronounced at the volute and NGV, resulting in a large amount of good heat to be conducted away, at the rotor however conduction was only a percentage of the viscous heat generated. Lastly tip clearance proved to have a linearly detrimental effect on power.
Mechanical Energy Absorption in Polyethylene Cell Pattern Structures for Biomedical Uses
Authors: Corro-Hernández Humberto , Vidal-Lesso Agustín , Ledesma-Orozco Elías R. 
Published: January 2018

Energy absorption and dissipation are characteristics that can be used to protect and extend the useful life of many systems. Two new models of shock absorption structures are proposed. These are based on honeycomb cell patterns with inherent negative stiffness, in theory enabling a large amplification of their damping and recoverability capabilities within a limited space.
A 2D finite element analysis (FEA) is carried on as a first approach for testing this concept. The reduction of kinetic energy of a falling block above the structure is taken as the main indicator of energy absorption.
After some verifications 3D models are developed and tested analogously. Numerical results are obtained with polyethylene (PE) material properties, looking forward for development of future applications in biomechanics.
Stress-Induced Change of the Microstructure and Strength of Modified 9Cr-1Mo Steel Under Fatigue and Creep Loadings at Elevated Temperatures
Authors: Shinozaki Taichi , Suzuki Ken , Miura Hideo 
Published: January 2018

The change of the lath martensitic structure in modified 9Cr-1Mo steel was observed in the specimens after the fatigue and creep tests using EBSD (Electron Back-Scatter Diffraction). The Kernel Average Misorientation (KAM) value obtained from the EBSD analysis were used for the quantitative evaluation of the change in the lath martensitic texture. It was found that the average KAM values of the fractured specimens decreased clearly after 107−108 cycles of the fatigue loading at temperatures higher than 500°C when the amplitude of the applied stress exceeded a critical value. This change corresponded to the disappearance of the lath martensitic structure. The critical value decreased monotonically with the increase of the test temperature. This microstructure change decreased the strength of the alloy drastically.
It was found that the change of the microstructure started at a certain time at each test temperature as a function of the amplitude of the applied stress. There was the critical stress at which the microstructure change started at each test temperature higher than 500°C, and the activation energy of the change was determined as a function of temperature and the amplitude of the applied stress. The dominant factor of the microstructure change was the stress-induced acceleration of the atomic diffusion of the component elements in the alloy. In order to improve the long-term reliability of the alloy, it is very important to increase the activation energy by modifying the microstructure of this alloy.
Repurposing of a Hybrid Vehicle Nickel Metal Hydride Battery Pack for Electrical Grid Storage
Authors: Balderston Dayton , Kelley John Eric , Crowder James , DeAgostino Thomas , Depcik Christopher 
Published: January 2018

Climate change concerns are driving incentives to increase the fuel economy of passenger vehicles. Consequently, this has resulted in a growing prevalence of electrified vehicles (EVs) consisting of hybrid, plug-in hybrid, and fully electric vehicles. Unfortunately, EVs are often removed from the road when 70 to 80% of the original energy capacity remains in their battery pack. In order to maintain or increase the value of EV battery packs in an end-of-vehicle life scenario, there are three potential solutions: remanufacturing for re-use, recycling, or repurposing. However, the complexity of handling dissimilar battery chemistries makes both remanufacturing and recycling a significant challenge. Hence, repurposing may prove to be a more viable short-term goal of the industry.
In order to explore this potential outcome, a team of undergraduate students studied the continuous cycling effects of used and refurbished Toyota® Prius nickel metal hydride battery packs. A Raspberry Pi 2 Model B microcomputer recorded relevant data, including battery pack voltage, energy input, and energy output. In combination, a Laboratory Virtual Instrument Engineering Workbench (LabVIEW™) control system used this logged information to regulate charging and discharging of the battery pack. In addition, to enhance the environmental sustainability of the project, this control system acquired solar information from a nearby weather station, subsequently ensuring that the battery pack only recharged during times of peak solar radiation. Analysis of the pack’s energy balance helped to characterize the cycle life of the pack and its potential in repurposing. Others can emulate the methodology employed as a way to instruct students about the potential left in used vehicular battery packs and their possible integration with the electrical grid.