bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, double‐blind, placebo‐controlled phase 1 study to evaluate the safety and pharmacokinetics of high doses of ubiquinol in healthy adults
Authors: Mitsui Jun , Matsukawa Takashi , Tanaka Masaki , Saito‐Sato Naoko , Nakamoto Fumiko Kusunoki , Yasuda Tsutomu , Naruse Hiroya , Matsukawa Miho Kawabe , Ishiura Hiroyuki , Nagase Midori , Yamamoto Yorihiro , Kuzuyama Haruko , Wada Ikue , Ga Toshio , Yamazaki Tsutomu , Moritoyo Takashi , Tsuji Shoji 
Published: December 2021

AbstractBackgroundMultiple system atrophy (MSA) is an intractable neurodegenerative disease. Higher frequencies of carriers of the V393A variant in COQ2 and lower levels of coenzyme Q10 (CoQ10) in body tissues have been reported in patients with MSA than in healthy controls. On the basis of the hypothesis that CoQ10 supplementation may slow the progression of MSA, we have been developing CoQ10 as an investigational drug for MSA.MethodsA single‐center, randomized, double‐blind, placebo‐controlled phase 1 study of ubiquinol in healthy adult male volunteers was conducted. Participants were randomly assigned to groups that orally receive 900, 1200, and 1500 mg of ubiquinol or placebo daily for 14 days. Safety was assessed by examining the frequency and severity of adverse events. The levels of ubiquinol in plasma and total CoQ10 in peripheral blood mononuclear cells and cerebrospinal fluid were investigated.ResultsThirty‐two participants provided informed consent to participate in this study. No clinically relevant changes in standard laboratory tests, physical examination, vital signs, or electrocardiogram attributable to ubiquinol administration were observed in any groups. The trough of plasma ubiquinol levels after repeated administration for 14 days reached a steady state, and the plasma ubiquinol levels in the 1500 mg/day‐administered group tended to be the highest.ConclusionsHigh‐dose ubiquinol supplementation was shown to be safe and tolerated when administered orally to healthy adult males at a maximum dosage of 1500 mg/day for 14 days (UMIN Clinical Trials Registry number, UMIN000016695).
A plastidial retrograde signal potentiates biosynthesis of systemic stress response activators
Authors: Zeng Liping , Wang Jin‐Zheng , He Xiang , Ke Haiyan , Lemos Mark , Gray William M. , Dehesh Katayoon 
Published: December 2021

Summary

Plants employ an array of intricate and hierarchical signaling cascades to perceive and transduce informational cues to synchronize and tailor adaptive responses. Systemic stress response (SSR) is a recognized complex signaling and response network quintessential to plant’s local and distal responses to environmental triggers; however, the identity of the initiating signals has remained fragmented.

Here, we show that both biotic (aphids and viral pathogens) and abiotic (high light and wounding) stresses induce accumulation of the plastidial‐retrograde‐signaling metabolite methylerythritol cyclodiphosphate (MEcPP), leading to reduction of the phytohormone auxin and the subsequent decreased expression of the phosphatase PP2C.D1.

This enables phosphorylation of mitogen‐activated protein kinases 3/6 and the consequential induction of the downstream events ultimately, resulting in biosynthesis of the two SSR priming metabolites pipecolic acid and N‐hydroxy‐pipecolic acid.

This work identifies plastids as a major initiation site, and the plastidial retrograde signal MEcPP as an initiator of a multicomponent signaling cascade potentiating the biosynthesis of SSR activators, in response to biotic and abiotic triggers.
Forest system hydraulic conductance: partitioning tree and soil components
Authors: Binks Oliver , Cernusak Lucas A. , Liddell Michael , Bradford Matt , Coughlin Ingrid , Carle Hannah , Bryant Callum , Dunn Elliot , Oliveira Rafael , Mencuccini Maurizio , Meir Patrick 
Published: December 2021

Summary

Soil–leaf hydraulic conductance determines canopy–atmosphere coupling in vegetation models, but it is typically derived from ex‐situ measurements of stem segments and soil samples. Using a novel approach, we derive robust in‐situ estimates for whole‐tree conductance (ktree), ‘functional’ soil conductance (ksoil), and ‘system’ conductance (ksystem, water table to canopy), at two climatically different tropical rainforest sites.

Hydraulic ‘functional rooting depth’, determined for each tree using profiles of soil water potential (Ψsoil) and sap flux data, enabled a robust determination of ktree and ksoil. ktree was compared across species, size classes, seasons, height above nearest drainage (HAND), two field sites, and to alternative representations of ktree; ksoil was analysed with respect to variations in site, season and HAND.

ktree was lower and changed seasonally at the site with higher vapour pressure deficit (VPD) and rainfall; ktree differed little across species but scaled with tree circumference; rsoil (1/ksoil) ranged from 0 in the wet season to 10× less than rtree (1/ktree) in the dry season.

VPD and not rainfall may influence plot‐level k; leaf water potentials and sap flux can be used to determine ktree, ksoil and ksystem; Ψsoil profiles can provide mechanistic insights into ecosystem‐level water fluxes.
Modulation of plant plasma membrane structure by exogenous fatty acid hydroperoxide is a potential perception mechanism for their eliciting activity
Authors: Deboever Estelle , Van Aubel Géraldine , Rondelli Valeria , Koutsioubas Alexandros , Mathelie‐Guinlet Marion , Dufrene Yves F. , Ongena Marc , Lins Laurence , Van Cutsem Pierre , Fauconnier Marie‐Laure , Deleu Magali 
Published: December 2021

AbstractOxylipins are lipid‐derived molecules that are ubiquitous in eukaryotes and whose functions in plant physiology have been widely reported. They appear to play a major role in plant immunity by orchestrating reactive oxygen species (ROS) and hormone‐dependent signalling pathways. The present work focuses on the specific case of fatty acid hydroperoxides (HPOs). Although some studies report their potential use as exogenous biocontrol agents for plant protection, evaluation of their efficiency in planta is lacking and no information is available about their mechanism of action. In this study, the potential of 13(S)‐hydroperoxy‐(9Z, 11E)‐octadecadienoic acid (13‐HPOD) and 13(S)‐hydroperoxy‐(9Z, 11E, 15Z)‐octadecatrienoic acid (13‐HPOT), as plant defence elicitors and the underlying mechanism of action is investigated. Arabidopsis thaliana leaf resistance to Botrytis cinerea was observed after root application with HPOs. They also activate early immunity‐related defence responses, like ROS. As previous studies have demonstrated their ability to interact with plant plasma membranes (PPM), we have further investigated the effects of HPOs on biomimetic PPM structure using complementary biophysics tools. Results show that HPO insertion into PPM impacts its global structure without solubilizing it. The relationship between biological assays and biophysical analysis suggests that lipid amphiphilic elicitors that directly act on membrane lipids might trigger early plant defence events.
Experimental Evaluation of Tension and Shear Responses of Material Discontinuities in Origami-Based Sheet Metal Bending
Authors: Ablat Muhammad Ali , Alafaghani Ala’aldin , Sun Jian-Qiao , Qattawi Ala 
Published: December 2021

Abstract
Origami-based sheet metal (OSM) bending uses the origami concept to form three-dimensional (3D) structures from a two-dimensional (2D) sheet by performing a series of bending operations. The OSM bending relies on material discontinuity (MD) lines to perform the bending operation during which the MDs are subjected to tension and shear load. Even though OSM bending is a process that is simple, cost-effective, and easy to integrate into mass production, the understanding of the OSM bending mechanics is limiting its wide application. Particularly, the deformation behavior of MDs under tension and shear load remains unknown. Hence, this study investigates the response of MDs to these loads using the standard tensile and shear tests. From these tests, the critical values for two different ductile fracture criteria (DFC) models are determined, and the possibility of a failure occurring in OSM bending can be predicted using the DFC models and the critical values. Results show that the load-bearing capability of the MDs is related to change in the effective cross-sectional area of an MD. The tensile and shear tests can provide a technique to predict failure in OSM bending. The results also show that the self-contact that can occur under shear load influences the maximum shear force and the accuracy of failure prediction.
Petrology and volcanology of the Mesoproterozoic igneous rocks of the Saint Francois Mountains terrane, southeast Missouri, USA
Authors: Michelfelder* Gary S. 
Published: December 2021

ABSTRACTThe Saint Francois Mountains are the physiographic expression of the central part of the Ozark Dome of southeastern Missouri. The mountains are made up of a quaquaversal-dipping series of Paleozoic units cored by the Mesoproterozoic-aged rocks of the broader Saint Francois Mountains terrane. The Saint Francois Mountains terrane lies within the Eastern Granite-Rhyolite province along the eastern margin of Laurentia and contains at least four mapped caldera complexes (Eminence, Lake Killarney, Butler Hill, and Taum Sauk), associated volcanic and volcaniclastic rocks, and four distinct types of intrusive units. The Mesoproterozoic rocks represent two major pulses of magmatic activity: (1) an older 1.48–1.45 Ga episode of caldera-forming volcanism and associated subvolcanic to massif-type granitic intrusions; and (2) a younger 1.33–1.28 Ga episode of bimodal intrusions. Volcanism included primarily high-silica rhyolite and volcaniclastic sediments associated with caldera-forming volcanism with lesser amounts of basalt and basaltic andesite that formed as flows and subvolcanic intrusions. The older (ca. 1.4 Ga) intrusive rocks can be divided into three broad categories: (1) granite massifs including the Butler Hill/Breadtray massif-type granites, (2) caldera ring–type granites such as the Silvermine Granite, and (4) mafic- to intermediate-composition intrusive rocks such as the Silver Mines Mafic Series. The younger (ca. 1.3 Ga) bimodal intrusions are represented by the highly evolved felsic Graniteville-types granites and the gabbros of the Skrainka Mafic Group.This field guide provides an overview of the magmatic history of the Mesoproterozoic rocks exposed in the eastern Saint Francois Mountains. Field-trip stops are divided into two days, highlighting well-known stops and lesser-known localities that illustrate the magmatic activity of one the premier igneous locations in the midcontinent region. The field trip is focused on two main areas. Day 1 focuses on the rhyolite sequence and associated caldera-forming eruption of the Taum Sauk caldera. Day 2 focuses on the volcanic rocks and granitic intrusions related to the Butler Hill caldera and ends with a visit to one of the youngest granitoids in the terrane, the Graniteville Granite. The field guide presents a summary of the volcanic history and petrogenesis of the Saint Francois Mountains rhyolites and granites.
Upper Grand Coulee: New views of a channeled scabland megafloods enigma
Authors: Waitt* Richard B. , Atwater Brian F. , Lehnigk Karin , Larsen Isaac J. , Bjornstad Bruce N. , Hanson Michelle A. , O’Connor Jim E. 
Published: December 2021

ABSTRACT
New findings about old puzzles occasion rethinking of the Grand Coulee, greatest of the scabland channels. Those puzzles begin with antecedents of current upper Grand Coulee. By a recent interpretation, the upper coulee exploited the former high-level valley of a preflood trunk stream that had drained to the southwest beside and across Coulee anticline or monocline. In any case, a constriction and sharp bend in nearby Columbia valley steered Missoula floods this direction. Completion of upper Grand Coulee by megaflood erosion captured flood drainage that would otherwise have continued to enlarge Moses Coulee.
Upstream in the Sanpoil valley, deposits and shorelines of last-glacial Lake Columbia varied with the lake’s Grand Coulee outlet while also recording scores of Missoula floods. The Sanpoil evidence implies that upper Grand Coulee had approached its present intake depth early the last glaciation at latest, or more simply during a prior glaciation. An upper part of the Sanpoil section provides varve counts between the last tens of Missoula floods in a stratigraphic sequence that may now be linked to flood rhythmites of southern Washington by a set-S tephra from Mount St. Helens.
On the floor of upper Grand Coulee itself, recently found striated rock and lodgement till confirm the long-held view, which Bretz and Flint had shared, that cutting of upper Grand Coulee preceded its last-glacial occupation by the Okanogan ice lobe. A dozen or more late Missoula floods registered as sand and silt in the lee of Steamboat Rock.
Some of this field evidence about upper Grand Coulee may conflict with results of recent two-dimensional simulations for a maximum Lake Missoula. In these simulations only a barrier high above the present coulee intake enables floods to approach high-water marks near Wenatchee that predate stable blockage of Columbia valley by the Okanogan lobe. Above the walls of upper Grand Coulee, scabland limits provide high-water targets for two-dimensional simulations of watery floods. The recent models sharpen focus on water sources, prior coulee incision, and coulee’s occupation by the Okanogan ice lobe.
Field reappraisal continues downstream from Grand Coulee on Ephrata fan. There, some of the floods exiting lower Grand Coulee had bulked up with fine sediment from glacial Lake Columbia, upper coulee till, and a lower coulee lake that the fan itself impounded. Floods thus of debris-flow consistency carried outsize boulders previously thought transported by watery floods.
Below Ephrata fan, a backflooded reach of Columbia valley received Grand Coulee outflow of small, late Missoula floods. These late floods can—by varve counts in post-S-ash deposits of Sanpoil valley—be clocked now as a decade or less apart. Still farther downstream, Columbia River gorge choked the largest Missoula floods, passing peak discharge only one-third to one-half that released by the breached Lake Missoula ice dam.
Could the Réunion plume have thinned the Indian craton?
Authors: Paul Jyotirmoy , Ghosh Attreyee 
Published: December 2021

AbstractThick and highly viscous roots are the key to cratonic survival. Nevertheless, cratonic roots can be destroyed under certain geological scenarios. Eruption of mantle plumes underneath cratons can reduce root viscosity and thus make them more prone to deformation by mantle convection. It has been proposed that the Indian craton could have been thinned due to eruption of the Réunion plume underneath it at ca. 65 Ma. In this study, we constructed spherical time-dependent forward mantle convection models to investigate whether the Réunion plume eruption could have reduced the Indian craton thickness. Along with testing the effect of different strengths of craton and its surrounding asthenosphere, we examined the effect of temperature-dependent viscosity on craton deformation. Our results show that the plume-induced thermomechanical erosion could have reduced the Indian craton thickness by as much as ~130 km in the presence of temperature-dependent viscosity. We also find that the plume material could have lubricated the lithosphere-asthenosphere boundary region beneath the Indian plate. This could be a potential reason for acceleration of the Indian plate since 65 Ma.
Olivine in komatiite records origin and travel from the deep upper mantle
Authors: Wilson Allan , Bolhar Robert 
Published: December 2021

Abstract
The deep upper mantle is the main source of high-temperature magmatism, but the only known naturally occurring samples of high-pressure mantle constituents are mineral inclusions in diamonds. Trace elements in olivine crystals from the 3.33 Ga Commondale Greenstone Belt in South Africa reveal that these crystals formed in the deep upper mantle as high-pressure phenocrysts, and some perhaps even formed in the mantle transition zone (410–600 km) where they began as wadsleyite. The crystals were entrained within ascending komatiite magma and conveyed to the surface. The olivine crystals have the highest contents of Al2O3 (0.3 wt%) recorded in any terrestrial olivine, which is indicative of formation at high pressure. The deep mantle gave rise to Archean komatiites, extraordinarily hot magmas (up to 1700 °C), which provide insight into Earth's early mantle evolution and the formation of most ancient continental and oceanic crust. In spite of extensive research since their discovery over 50 years ago, the origins of komatiites have remained contentious. Plumes—thermochemical instabilities originating at the core-mantle boundary—are the most likely source, but no direct evidence of a deep mantle origin of komatiite has yet been recognized.
Experiences of seeking healthcare across the border: lessons to inform upstream policies and system developments on cross-border health in East Africa
Authors: Ssengooba Freddie , Tuhebwe Doreen , Ssendagire Steven , Babirye Susan , Akulume Martha , Ssennyonjo Aloysius , Rutaroh Arthur , Mutesa Leon , Nangami Mabel 
Published: December 2021

ObjectivesThis study explored the experiences of accessing care across the border in East Africa.ParticipantsFrom February to June 2018, a cross-sectional study using qualitative and quantitative methods was conducted among 279 household adults residing along selected national border sites of Uganda, Kenya and Rwanda and had accessed care from the opposite side of the border 5 years prior to this study.SettingAccess to HIV treatment, maternal delivery and childhood immunisation services was explored. We applied the health access framework and an appreciative inquiry approach to identify factors that enabled access to the services.MeasuresExploratory factor analysis and linear regression were used for quantitative data, while deductive content analysis was done for the qualitative data on respondent’s experiences navigating health access barriers.ResultsThe majority of respondents (83.9%; 234/279) had accessed care from public health facilities. Nearly one-third (77/279) had sought care across the border more than a year ago and 22.9% (64/279) less than a month ago. From the linear regression, the main predictor for ease of access for healthcare were ‘‘ease of border crossing’ (regression coefficient (RegCoef) 0.381); ‘services being free’ (RegCoef 0.478); ‘services and medicines availability’ (RegCoef 0.274) and ‘acceptable quality of services’ (RegCoef 0.364). The key facilitators for successful navigation of access barriers were related to the presence of informal routes, speaking a similar language and the ability to pay for the services.ConclusionCommunities resident near national borders were able to cross borders to seek healthcare. There is need for a policy environment to enable East Africa invest better and realise synergies for these communities. This will advance Universal Health Coverage goals for communities along the border who represent the far fang areas of the health system with multiple barriers to healthcare access.
Application of the multiphase optimisation strategy to develop, optimise and evaluate the effectiveness of a multicomponent initiative package to increase 2-to-5-year-old children’s vegetable intake in long day care centres: a study protocol
Authors: Zarnowiecki Dorota , Kashef Shabnam , Poelman Astrid AM , Cochet-Broch Maeva O , Arguelles Jennifer C , Cox David N , Golley Rebecca K 
Published: December 2021

IntroductionGlobally, children do not eat enough core foods, with vegetable intakes persistently low. Early life is critical for establishing vegetable acceptance and intake. Increased usage of formal childcare has led to the importance of childcare settings shaping children’s food intake. This study will use the multiphase optimisation strategy to develop, optimise and evaluate the effectiveness of a multicomponent initiative package to increase 2-to-5-year-old children’s vegetable intake in long day care centres.Methods and analysisThe preparation phase will use existing literature and best practice guidelines to develop three initiatives aiming to: (1) increase vegetable provision at mealtimes, (2) deliver a vegetable-focused sensory curriculum and (3) use supportive mealtime practices encouraging children’s tasting of vegetables. The optimisation phase (N=32 centres) will use a 12-week, eight-condition factorial experiment to test main and synergistic effects of the initiatives. The optimum combination of initiatives producing the largest increase in vegetable intake will be identified. The evaluation phase (N=20 centres) will test the effectiveness of the optimised package using a 12-week waitlist randomised controlled trial. Primary outcomes are children’s vegetable intake and food group intake at long day care. Secondary outcomes are menu guideline compliance, cook and educator knowledge and skills, and reach. Process evaluation will include fidelity, acceptability, barriers and facilitators, and compatibility with practice. Repeated measures ANOVA with interaction effects (optimisation phase) and linear mixed modelling (evaluation phase) will test effects of the initiatives on vegetable intake.Ethics and disseminationThis study has received ethics approval from the Flinders University Research Ethics Committee (Project No: 1873) for the optimisation phase. Approval for the evaluation phase will be obtained following completion of optimisation phase. Findings will be disseminated to stakeholders, including long day care centres and childcare organisations; and to researchers via peer-reviewed journals and conferences.Trial registration numbersACTRN12620001301954, ACTRN12620001323910p.