bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Permian subduction-related transtension in the Turpan Basin, East Tianshan (NW China): implications for accretionary tectonics of the southern Altaids
Authors: Mao Qigui , Xiao Wenjiao , Windley Brian F. , Yu Minjie , Sun Min , Ao Songjian , Zhang Ji’en
Published: November 2019

The interaction of the Palaeo-Pacific and Palaeo-Asian Oceans is an enigmatic issue as their temporal and spatial features are controversial. To address this issue, we present a systematic study of large volumes of early Permian volcanic rocks and intrusions developed in the East Tianshan. The represented samples of basaltic andesites and rhyolites yield zircon crystallization ages of 285.1 ± 5.9 Ma and 275.3 ± 1.8 Ma, respectively. The basalts have normal mid-ocean ridge basalt (N-MORB) and arc-related geochemical signatures with high TiO2contents, negative Rb, Th, U, Nb and Ta anomalies and positive Eu anomalies. Basaltic andesites and andesites have arc-related geochemical characteristics with moderate TiO2contents and relatively negative Nb, Ta and Ti anomalies, together with slightly negative to positive Eu anomalies. The rhyolites show an affinity with A2-type granite with high SiO2, K2O + Na2O, Fe/Mg, Ga, Zr, Nb, Y, HFSE, REE and Y/Nb levels (>1.2). These geochemical data suggest that the rocks formed in a supra-subduction zone. The presence of high ϵNd(t) values of +4.6 to +8.2 and low (87Sr/86Sr)i(0.70342–0.70591) values indicates that the volcanic rocks originated from a depleted mantle. We propose that oblique subduction with slabs breaking off gave rise to transtension and to the emplacement of large volumes of mantle-derived melts in the early Permian in the East Tianshan, serving as an important record of the subduction zone of the Palaeo-Pacific Ocean.
New information on the skull roof ofProtoichthyosaurus(Reptilia: Ichthyosauria) and intraspecific variation in some dermal skull elements
Authors: Lomax Dean R , Massare Judy A , Evans Mark
Published: November 2019

A previously unrecognized specimen ofProtoichthyosaurus prostaxalis, LEICT G142.1991, from the Lower Jurassic of Barrow-upon-Soar, Leicestershire, UK, includes an almost complete three-dimensional skull that provides new information on the configuration of the skull roof. The position of the pineal foramen (between the frontals and the parietals) and an elongated internasal foramen in a depression along the midline of the nasals are clearly shown. The maxilla makes up a significant portion of the external naris ventral margin, an unusual character for the genus/species. This reflects intraspecific variation, not evidence of a new taxon. The specimen enables comparisons of skull roof morphology withIchthyosaurusandStenopterygius, two common Early Jurassic taxa. In particular, the position of the pineal foramen is similar toStenopterygius, but distinguishesProtoichthyosaurusfromIchthyosaurus. The lack of a frontal–prefrontal contact and the posteriorly wide nasals distinguishesProtoichthyosaurusfromStenopterygius. We also present a revised reconstruction of the skull roof morphology ofIchthyosaurus. Three additional specimens ofProtoichthyosaurusare referred to the genus: another partial skull, referred toP. prostaxalis, and two isolated forefins, identified by their unique morphology.
Abortion among married young women: findings from a community-based study in Rajasthan and Uttar Pradesh, India
Authors: Zavier A. J. Francis , Santhya K. G. , Jejeebhoy Shireen J.
Published: November 2019

Abortion service provision has changed noticeably in the recent past and medication abortion currently accounts for four-fifths of all induced abortions taking place in India. How these changes have modified abortion experiences among young women – a group known to be more disadvantaged than adult women – remains unanswered. This paper fills this gap and examines the experiences of married young abortion seekers, including pre-abortion decision-making, abortion seeking and experiences of the procedure, and post-abortion complications. Data were drawn from a community-based survey of 4952 married young women aged 15–24 years conducted in Uttar Pradesh and Rajasthan in 2015. The study focused on 166 young women who had an induced abortion in the two years before the survey, and used descriptive statistics to describe their abortion experiences. Seventy-four per cent of abortion seekers had relied on medication abortion and 47% had obtained it over the counter without a physician’s prescription. Moreover, 90% accessed abortion services from private facilities, including drug sellers. A small proportion (4%) had undergone abortion in the second trimester of pregnancy. At the same time, 13% reported multiple abortion attempts; 17% underwent dilation and curettage; and 52% experienced self-reported complications, including 5% who experienced moderate to severe complications. The findings call for greater attention to providing contraceptive counselling and services to married young women, ensuring abortion services in public health facilities and exploring mechanisms to improve drug sellers’ knowledge and practices in providing medication abortion.
Comparison of cortisol concentrations in plasma and saliva in dairy cattle following ACTH stimulation
Authors: Riek Alexander , Schrader Lars , Zerbe Frank , Petow Stefanie
Published: November 2019

The experiments described in this research communication compared cortisol concentrations in plasma and saliva samples collected from dairy cattle before and after an adrenocorticotropic hormone (ACTH) application. For that purpose, blood and saliva samples were collected from five dairy cows at determined time intervals before (490 min and down to 0 min) and after (10 min and up to 500 min) an ACTH application. Mean baseline cortisol concentrations were greater in plasma compared to saliva. The relative increases and decreases in plasma and salivary cortisol concentrations following ACTH were similar. After ACTH, we observed an increase in cortisol concentrations in plasma after 10 min and in saliva after 20 min. The time of peak concentrations after ACTH were reached at 70 and 80 min for plasma and saliva, respectively. After peak concentrations, values steadily declined and returned to baseline values at 169 ± 15 min in plasma and 170 ± 14 min in saliva. Ratios between salivary and plasma cortisol concentrations were on average 0.09 and did not change substantially during the ACTH challenge. There was a strong positive relationship between salivary and plasma cortisol concentrations. These results indicate that salivary cortisol concentrations can be a good indicator of ACTH-induced plasma cortisol concentrations in dairy cattle.
Radiation and electron thermal conduction damping of acoustic perturbations in igniting deuterium–tritium gas
Authors: Galloway Conner D. , Hunter Robert O. , Valys Alexander V. , McCall Gene H.
Published: November 2019

We derive a dispersion relation for the damping of acoustic waves in equi-molar deuterium–tritium (DT) gas due to radiation coupling and electron thermal conduction and discuss its significance for inertial confinement fusion (ICF) targets with high-Z shells surrounding a central DT fuel region. As the shell implodes around DT fuel in such a target, shocks and waves are transmitted through the DT gas. If the shell is perturbed due to drive non-uniformity or manufacturing imperfection, these shocks and waves may be perturbed as well, and can potentially re-perturb the shell. This can complicate calculation of shell stability and implosion asymmetry and in general make the target less robust against implosion non-uniformity. Damping of perturbations in DT gas can alleviate these complications. Also, damping of low-order modes, which is primarily due to radiation coupling, can drive the DT gas to an isobaric and isothermal ‘equilibrium’ configuration during ignition. We find that for the range of common ignition temperatures in targets with high-Z shells,

$2.5\lesssim T_{ig}\lesssim 3.5$

 keV, damping of low-order modes is significant for areal densities (

$\unicode[STIX]{x1D70C}r$

) in the broad range of

$0.6\lesssim \unicode[STIX]{x1D70C}r\lesssim 1.8~\text{g}~\text{cm}^{-2}$

. This suggests it is advantageous to design these targets to achieve areal densities at ignition within this range. Furthermore, we derive a simple constraint between areal density and temperature,

$\unicode[STIX]{x1D70C}r=0.34T_{o}$

where

$T_{o}$

is in keV, such that DT gas undergoing equilibrium ignition is optimally robust against non-uniformity.
Performance Improvement of PD-Based Bilateral Teleoperator with Time Delay by Introducing High-Pass Filter
Authors: Imaida Takashi , Senda Kei
Published: November 2019

Stability is a major problem with bilateral teleoperator when there is a transmission time delay. By adding adequate damping gain into position servo, a stable bilateral control can be achieved under the existence of time delay. However, large damping gain is required to stabilize the system and the performance is degraded. In this paper, the performance improvement by introducing a high-pass filter into a proportional derivative-based teleoperator with time delay has been studied. We proposed new control law and derived the stability condition. We demonstrated the performance improvement using a hybrid matrix, 1-degree of freedom (DOF), 2-DOF simulations, and 2-DOF peg-in-hole experiments.
Cell Membrane Nanostructure is Altered by Heat-Induced Antigen Retrieval: A Possible Consequence for Immunocytochemical Detection of Membranous Antigens
Authors: Cizkova Katerina , Malohlava Jakub , Tauber Zdenek
Published: November 2019

Heat-induced antigen retrieval (HIAR) treatment improves the antigen immunodetection in formalin-fixed, paraffin-embedded tissue samples and it can also improve the detection of intracellular antigens in alcohol-fixed cytological samples, although it could deleteriously impact immunodetection, particularly that of membranous antigens. We examined the differences in cell surface topography on MCF7 cells fixed in methanol/acetone (M/A) or 4% paraformaldehyde (4% PFA), as well as the changes caused by HIAR treatment at three different temperatures (60, 90, and 120°C), using atomic force microscopy. Furthermore, the consequences for immunostaining of five membranous antigens [epidermal growth factor receptor (EGFR), E-cadherin, CD9, CD24, and CD44] were examined. Our results illustrate that while there was no one single optimal immunostaining condition for the tested antibodies, the surface topography could be an important factor in successful staining. Generally, the best conditions for successful immunostaining were M/A fixation with no HIAR treatment, whereas in 4% PFA-fixed cells, HIAR treatment at 120°C was optimal. These conditions showed similarity in cell surface skewness. A correlation factor between successful immunocytochemical staining and the skewness parameter was 0.8000. Our results indicate that the presence of valleys, depressions, scratches, and pits on the cell surface is unfavorable for the successful immunodetection of cell surface antigens.
The Structure of Work Engagement
Authors: Lazauskaitė-Zabielskė Jurgita , Urbanavičiūtė Ieva , Balsienė Rita Rekašiūtė
Published: November 2019

Abstract. The aim of this study was to validate the Lithuanian version of the Utrecht Work Engagement Scale (UWES-17), developed by Schaufeli and Bakker (2003) , and the newly developed UWES-3 ( Schaufeli et al., 2019 ). The data were derived from a sample of Lithuanian employees that was surveyed longitudinally. At Time 1, a total of 475 employees were surveyed. At Time 2, 166 employees completed the survey for a second time. Confirmatory factor analyses provided more support for unidimensional solution of the UWES-17. Moreover, the internal consistency of both versions was sufficiently high (α varied between .76 and .90), and the test-retest reliability with an interval of 8 months was .70 and .69 for the long and the ultra-short version respectively. Furthermore, the one-factor structure of the UWES-17 and UWES-3 was invariant across job status and time. Finally, as expected, the correlation analysis showed work engagement to be positively related to job resources. Based on the Lithuanian employee sample, this study replicates previous findings on the dimensionality of work engagement as measured by the UWES and adds evidence on the validity of its scores. In this way, it contributes to international effort aimed at studying this construct and validating its measures.
The Weitin Fault, Papua New Guinea, Ruptured Twice by Mw 8.0 and Mw 7.7 Earthquakes in 2000 and 2019
Authors: Chen Kejie , Milliner Chris , Avouac Jean‐Philippe
Published: November 2019

We determine the fault geometry and kinematic slip models of the 2019 Mw 7.7 and 2000 Mw 8.0 earthquakes in Papua New Guinea using measurements from optical image correlation and teleseismic waveforms. The 2000 earthquake ruptured an extensive fault system over a distance of ~150 km including the entire 60‐km long onshore segment of the Weitin fault and its offshore continuation southeast of New Ireland. The northern portion of the onshore Weitin fault segment ruptured again in 2019. Most of the moment was released by a compact, shallow, high stress‐drop slip patch on the northwestern continuation of the Weitin fault in the Saint George Channel, which was brought closer to failure by the 2000 earthquake. The two ruptures overlap over about 20 km but in fact mostly complement each other. Large dynamic stresses may have driven the partial rerupture of the Weitin fault during the 2019 event.
The Intermittency of Wind‐Driven Sand Transport
Authors: Comola F. , Kok J. F. , Chamecki M. , Martin R. L.
Published: November 2019

Wind‐blown sand is the main driver of dune development and dust emission from soils and is thus of fundamental importance for geomorphology, ecology, climate, and air quality. Even though sand transport is driven by nonstationary turbulent winds, and is thus inherently intermittent, current parameterizations in atmospheric models assume stationary wind and continuous transport. We draw on extensive field measurements to show that neglecting saltation intermittency causes biases in the timing and intensity of predicted fluxes. We present a simple parameterization that accounts for saltation intermittency and produces substantially improved agreement against measurements. We investigate the implications of accounting for transport intermittency in atmospheric models by analyzing 35 years of hourly wind speed data from climate simulations. We show that accounting for intermittency leads to significantly different predictions of sand mass fluxes throughout the year, with potential implications for timing and intensity of dust emission.
Constraining the Oceanic Lithosphere Seismogenic Zone Using Teleseismic Relocations of the 2012 Wharton Basin Great Earthquake Sequence
Authors: Kwong Kevin B. , DeShon Heather R. , Saul Joachim , Thurber Clifford H.
Published: November 2019

The great 2012 Mw 8.6 strike‐slip earthquake beneath the Wharton Basin generated a complex aftershock sequence that maps onto a system of conjugate faults. Analysis of high‐precision aftershock locations with improved depth constraint is used here to characterize the seismogenic limits of the oceanic lithosphere. The study presents teleseismic double‐difference earthquake relocation results for 695 events in and around the 2012 Wharton Basin intraplate earthquake sequence. We highlight seven major clusters of seismicity and show that the 2012 earthquake sequence ruptured in the oceanic crust and upper mantle. The refined aftershock locations projected onto available mainshock finite‐fault models show that aftershocks occur outside the largest coseismic slip region and tend to cluster in low slip areas, a pattern commonly seen for large continental and megathrust sequences. For events with depth phases, the relocated focal depths generally correspond to predicted depths from pP‐P time observations. Reported pP‐P observations for intraplate events correspond to depths ranging from ~5 to 35–40 km, such that the deepest events occur within the expected limit of brittle seismic failure at 600 °C, here defined by a half‐space cooling model of the region. The 74 low magnitude events in our catalog that locate below the 600 °C isotherm do not have consistent depth phase observations and cannot be interpreted as strong evidence of rupture into the ductile regime. The refined double‐difference catalog supports that, along with deep coseismic rupture, moderate‐sized earthquakes ruptured across the full extent of the elastic oceanic lithosphere in the Wharton Basin.
Multi‐Grid Nesting Ability to Represent Convections Across the Gray Zone
Authors: Liang Xin‐Zhong , Li Qi , Mei Haixia , Zeng Mingjian
Published: November 2019

This study investigated the multi‐grid nesting ability of a limited area model to effectively represent convections across the gray zone, the resolution around 1–10 km where both cumulus parameterization and explicit convection are problematic. It evaluated the sensitivity of Meiyu rainfall forecasts in Jiangsu, China to model configurations of grid nesting and convection treatment. These configurations consisted of grid spacings from 30, 15, 9, 5, 3 to 1 km, single or double or triple nested grids, and the traditional Kain‐Fritsch (KF) or scale‐aware Grell‐Freitas cumulus parameterization or the explicit convection in the outer domain [O]. In single nesting [O], coarse grids (>3–5 km) required parameterization to represent organized cumuli, while explicitly resolving convections in finer grids were necessary to improve forecasts. In double nesting [O] using cumulus parameterization at 30–9 km with the inner domain [I] using explicit convection at 1 km, the nesting ratio could be as large as 30 without significantly impacting [I] forecasts. This suggests a pragmatic approach to avoid the challenge in representing convections across the gray zone. Using Grell‐Freitas may improve mean [O] rainfall distributions, but this was not true for [I] forecasts due to counter errors in space and time, which were larger than using KF and at coarser grids. Triple nesting with a middle 3‐ or 5‐km grid was unnecessary and could even degrade [I] forecasts. Nesting [O] using KF to parameterize cumuli at 15 km with [I] explicitly resolving convections at 1 km achieved the best overall rainfall forecast in Jiangsu.
Neotectonics of Southeast Jamaica Derived From Marine Seismic Surveys and Gravity Cores
Authors: Wright Vanshan , Hornbach Matthew , Brown Lyndon , McHugh Cecilia , Mitchell Simon
Published: November 2019

Tectonics in Southeast Jamaica is poorly understood, but the region may contain currently unknown faults that could generate large‐magnitude earthquakes. This study constrains tectonics in Southeast Jamaica by collecting and analyzing seismic and shallow sediment core data in and around Kingston Harbor. Seismic results reveal a previously unrecognized strike‐slip fault system that accommodates strain via a complex mix of compression and extension. The faults appear to be a blind extension of one major fault (i.e., The Bull Bay Strike‐Slip Fault) within the Enriquillo‐Plantain Garden Fault Zone. This fault system may represent significant hazards to Kingston Jamaica because the fault is active, located less than 5 km from the city, and a complete rupture of the fault could generate aMw5.8–6.9 earthquake. Our analyses highlight the need for continued paleoseismic studies, both onshore and offshore Jamaica.
Overlapping spatial clusters of sugar-sweetened beverage intake and body mass index in Geneva state, Switzerland
Authors: Joost Stéphane , De Ridder David , Marques-Vidal Pedro , Bacchilega Beatrice , Theler Jean-Marc , Gaspoz Jean-Michel , Guessous Idris
Published: November 2019

Background

Obesity and obesity-related diseases represent a major public health concern. Recently, studies have substantiated the role of sugar-sweetened beverages (SSBs) consumption in the development of these diseases. The fine identification of populations and areas in need for public health intervention remains challenging. This study investigates the existence of spatial clustering of SSB intake frequency (SSB-IF) and body mass index (BMI), and their potential spatial overlap in a population of adults of the state of Geneva using a fine-scale geospatial approach.

Methods

We used data on self-reported SSB-IF and measured BMI from residents aged between 20 and 74 years of the state of Geneva (Switzerland) that participated in the Bus Santé cross-sectional population-based study (n = 15,423). Getis-Ord Gi spatial indices were used to identify spatial clusters of SSB-IF and BMI in unadjusted models and models adjusted for individual covariates (education level, gender, age, nationality, and neighborhood-level median income).

Results

We identified a significant spatial clustering of BMI and SSB-IF. 13.2% (n = 2034) of the participants were within clusters of higher SSB-IF and 10.7% (n = 1651) were within clusters of lower SSB-IF. We identified overlapping clusters of SSB-IF and BMI in specific areas where 11.1% (n = 1719) of the participants resided. After adjustment, the identified clusters persisted and were only slightly attenuated indicating that additional neighborhood-level determinants influence the spatial distribution of SSB-IF and BMI.

Conclusions

Our fine-scale spatial approach allowed to identify specific populations and areas presenting higher SSB-IF and highlighted the existence of an overlap between populations and areas of higher SSB-IF associated with higher BMI. These findings could guide policymakers to develop locally tailored interventions such as targeted prevention campaigns and pave the way for precision public health delivery.
Ultralong UV/mechano-excited room temperature phosphorescence from purely organic cluster excitons
Authors: Zhang Xuepeng , Du Lili , Zhao Weijun , Zhao Zheng , Xiong Yu , He Xuewen , Gao Peng Fei , Alam Parvej , Wang Can , Li Zhen , Leng Jing , Liu Junxue , Zhou Chuanyao , Lam Jacky W. Y. , Phillips David Lee , Zhang Guoqing , Tang Ben Zhong
Published: November 2019

Purely organic room temperature phosphorescence (RTP) has attracted wide attention recently due to its various application potentials. However, ultralong RTP (URTP) with high efficiency is still rarely achieved. Herein, by dissolving 1,8-naphthalic anhydride in certain organic solid hosts, URTP with a lifetime of over 600 ms and overall quantum yield of over 20% is realized. Meanwhile, the URTP can also be achieved by mechanical excitation when the host is mechanoluminescent. Femtosecond transient absorption studies reveal that intersystem crossing of the host is accelerated substantially in the presence of a trace amount of 1,8-naphthalic anhydride. Accordingly, we propose that a cluster exciton spanning the host and guest forms as a transient state before the guest acts as an energy trap for the RTP state. The cluster exciton model proposed here is expected to help expand the varieties of purely organic URTP materials based on an advanced understanding of guest/host combinations.
Room temperature and low-field resonant enhancement of spin Seebeck effect in partially compensated magnets
Authors: Ramos R. , Hioki T. , Hashimoto Y. , Kikkawa T. , Frey P. , Kreil A. J. E. , Vasyuchka V. I. , Serga A. A. , Hillebrands B. , Saitoh E.
Published: November 2019

Resonant enhancement of spin Seebeck effect (SSE) due to phonons was recently discovered in Y$${}_{3}$$

3

Fe$${}_{5}$$

5

O$${}_{12}$$

12

(YIG). This effect is explained by hybridization between the magnon and phonon dispersions. However, this effect was observed at low temperatures and high magnetic fields, limiting the scope for applications. Here we report observation of phonon-resonant enhancement of SSE at room temperature and low magnetic field. We observe in Lu$${}_{2}$$

2

BiFe$${}_{4}$$

4

GaO$${}_{12}$$

12

an enhancement 700% greater than that in a YIG film and at very low magnetic fields around 10$${}^{-1}$$

−
1

T, almost one order of magnitude lower than that of YIG. The result can be explained by the change in the magnon dispersion induced by magnetic compensation due to the presence of non-magnetic ion substitutions. Our study provides a way to tune the magnon response in a crystal by chemical doping, with potential applications for spintronic devices.
Packaging and delivering enzymes by amorphous metal-organic frameworks
Authors: Wu Xiaoling , Yue Hua , Zhang Yuanyu , Gao Xiaoyong , Li Xiaoyang , Wang Licheng , Cao Yufei , Hou Miao , An Haixia , Zhang Lin , Li Sai , Ma Jingyuan , Lin He , Fu Yanan , Gu Hongkai , Lou Wenyong , Wei Wei , Zare Richard N. , Ge Jun
Published: November 2019

Enzymatic catalysis in living cells enables the in-situ detection of cellular metabolites in single cells, which could contribute to early diagnosis of diseases. In this study, enzyme is packaged in amorphous metal-organic frameworks (MOFs) via a one-pot co-precipitation process under ambient conditions, exhibiting 5–20 times higher apparent activity than when the enzyme is encapsulated in corresponding crystalline MOFs. Molecular simulation and cryo-electron tomography (Cryo-ET) combined with other techniques demonstrate that the mesopores generated in this disordered and fuzzy structure endow the packaged enzyme with high enzyme activity. The highly active glucose oxidase delivered by the amorphous MOF nanoparticles allows the noninvasive and facile measurement of glucose in single living cells, which can be used to distinguish between cancerous and normal cells.
Transplanted interneurons improve memory precision after traumatic brain injury
Authors: Zhu Bingyao , Eom Jisu , Hunt Robert F.
Published: November 2019

Repair of the traumatically injured brain has been envisioned for decades, but regenerating new neurons at the site of brain injury has been challenging. We show GABAergic progenitors, derived from the embryonic medial ganglionic eminence, migrate long distances following transplantation into the hippocampus of adult mice with traumatic brain injury, functionally integrate as mature inhibitory interneurons and restore post-traumatic decreases in synaptic inhibition. Grafted animals had improvements in memory precision that were reversed by chemogenetic silencing of the transplanted neurons and a long-lasting reduction in spontaneous seizures. Our results reveal a striking ability of transplanted interneurons for incorporating into injured brain circuits, and this approach is a powerful therapeutic strategy for correcting post-traumatic memory and seizure disorders.
Piezo1 channel activation mimics high glucose as a stimulator of insulin release
Authors: Deivasikamani Vijayalakshmi , Dhayalan Savitha , Abudushalamu Yilizila , Mughal Romana , Visnagri Asjad , Cuthbertson Kevin , Scragg Jason L. , Munsey Tim S. , Viswambharan Hema , Muraki Katsuhiko , Foster Richard , Sivaprasadarao Asipu , Kearney Mark T. , Beech David J. , Sukumar Piruthivi
Published: November 2019

Glucose and hypotonicity induced cell swelling stimulate insulin release from pancreatic β-cells but the mechanisms are poorly understood. Recently, Piezo1 was identified as a mechanically-activated nonselective Ca2+ permeable cationic channel in a range of mammalian cells. As cell swelling induced insulin release could be through stimulation of Ca2+ permeable stretch activated channels, we hypothesised a role for Piezo1 in cell swelling induced insulin release. Two rat β-cell lines (INS-1 and BRIN-BD11) and freshly-isolated mouse pancreatic islets were studied. Intracellular Ca2+ measurements were performed using the fura-2 Ca2+ indicator dye and ionic current was recorded by whole cell patch-clamp. Piezo1 agonist Yoda1, a competitive antagonist of Yoda1 (Dooku1) and an inactive analogue of Yoda1 (2e) were used as chemical probes. Piezo1 mRNA and insulin secretion were measured by RT-PCR and ELISA respectively. Piezo1 mRNA was detected in both β-cell lines and mouse islets. Yoda1 evoked Ca2+ entry was inhibited by Yoda1 antagonist Dooku1 as well as other Piezo1 inhibitors gadolinium and ruthenium red, and not mimicked by 2e. Yoda1, but not 2e, stimulated Dooku1-sensitive insulin release from β-cells and pancreatic islets. Hypotonicity and high glucose increased intracellular Ca2+ and enhanced Yoda1 Ca2+ influx responses. Yoda1 and hypotonicity induced insulin release were significantly inhibited by Piezo1 specific siRNA. Pancreatic islets from mice with haploinsufficiency of Piezo1 released less insulin upon exposure to Yoda1. The data show that Piezo1 channel agonist induces insulin release from β-cell lines and mouse pancreatic islets suggesting a role for Piezo1 in cell swelling induced insulin release. Hence Piezo1 agonists have the potential to be used as enhancers of insulin release.
The effect of liver enzymes on adiposity: a Mendelian randomization study
Authors: Liu Junxi , Au Yeung Shiu Lun , Kwok Man Ki , Leung June Yue Yan , Lin Shi Lin , Hui Lai Ling , Leung Gabriel Matthew , Schooling C. Mary
Published: November 2019

Poorer liver function is positively associated with diabetes in Mendelian randomization (MR) studies. Observationally, adiposity is associated with poorer liver function. To clarify the etiology, we assessed the association of liver enzymes with adiposity observationally and using two-sample MR for validation. In the “Children of 1997” birth cohort, we used multivariable linear regression to assess the associations of alanine transaminase (ALT) and alkaline phosphatase (ALP) at ~17.5 years with body mass index (BMI) (n = 3,458). Using MR, genetic predictors of ALT, ALP and gamma glutamyltransferase (GGT), were applied to genome-wide association studies of BMI (n = 681,275), waist circumference (WC) (n = 224,459) and waist-hip ratio (WHR) (n = 224,459) to obtain unconfounded estimates. Observationally, ALT was positively associated with BMI (0.10 kg/m2 per IU/L, 95% confidence interval (CI) 0.09 to 0.11). ALP was inversely associated with BMI (−0.018 kg/m2 per IU/L, 95% CI −0.024 to −0.012). Using MR, ALT was inversely associated with BMI (−0.14 standard deviation per 100% change in concentration, 95% CI −0.20 to −0.07), but not WC or WHR. ALP and GGT were unrelated to adiposity. Poorer liver function might not cause adiposity; instead higher ALT might reduce BMI, raising the question as to the role of ALT in body composition.
Improved Health Outcomes from Hepatitis C Treatment Scale-Up in Spain’s Prisons: A Cost-Effectiveness Study
Authors: Dalgic Ozden O. , Samur Sumeyye , Spaulding Anne C. , Llerena Susana , Cobo Carmen , Ayer Turgay , Roberts Mark S. , Crespo Javier , Chhatwal Jagpreet
Published: November 2019

Hepatitis C virus (HCV) is 15 times more prevalent among persons in Spain’s prisons than in the community. Recently, Spain initiated a pilot program, JAILFREE-C, to treat HCV in prisons using direct-acting antivirals (DAAs). Our aim was to identify a cost-effective strategy to scale-up HCV treatment in all prisons. Using a validated agent-based model, we simulated the HCV landscape in Spain’s prisons considering disease transmission, screening, treatment, and prison-community dynamics. Costs and disease outcomes under status quo were compared with strategies to scale-up treatment in prisons considering prioritization (HCV fibrosis stage vs. HCV prevalence of prisons), treatment capacity (2,000/year vs. unlimited) and treatment initiation based on sentence lengths (>6 months vs. any). Scaling-up treatment by treating all incarcerated persons irrespective of their sentence length provided maximum health benefits–preventing 10,200 new cases of HCV, and 8,300 HCV-related deaths between 2019–2050; 90% deaths prevented would have occurred in the community. Compared with status quo, this strategy increased quality-adjusted life year (QALYs) by 69,700 and costs by €670 million, yielding an incremental cost-effectiveness ratio of €9,600/QALY. Scaling-up HCV treatment with DAAs for the entire Spanish prison population, irrespective of sentence length, is cost-effective and would reduce HCV burden.
Safety profile of sedative endoscopy including cognitive performance in liver cirrhosis: A double-blind randomized controlled trial
Authors: Yoo Jeong-Ju , Goong Hyeon Jeong , Moon Ji Eun , Kim Sang Gyune , Kim Young Seok
Published: November 2019

The indiscriminate use of sedative drugs during endoscopy can pose multiple risks including cognitive impairment in advanced liver cirrhosis. However, the data are scarce regarding which sedative drugs are safest in these populations. The aim of this study was to evaluate the safety profiles including cognitive performance among midazolam, propofol, and combination therapy in advanced cirrhotic patients. This double-blind randomized controlled study included 60 consecutive advanced cirrhotic patients who underwent upper gastrointestinal endoscopy. The Stroop application was used to screen for cognitive impairment. Patients were randomly assigned to one of 3 groups, midazolam, propofol, or the combination group, and underwent Stroop test before and two hours after the completion of endoscopy. Hemodynamic safety and the subjective satisfaction score were also evaluated. Patients did not show significant changes in on-time or off-time on the Stroop test before and two hours after sedatives, and there was no significant difference among the 3 treatment groups. Also, there were no significant vital sign changes after sedatives. Time-to-recovery was longest in midazolam group, and patient awakening and patient memory were highest in propofol group. However, all 3 groups showed no difference in patient satisfaction, but the combination group was more preferred in terms of subjective satisfaction by physicians. Factors affecting worsened Stroop speed after sedatives were older age, low education level and high MELD score. All sedative methods using midazolam, propofol, or combination therapy showed similar safety profile in advanced cirrhosis, and were not associated with increased risk of cognitive impairment.
Metabolite profiling of Andrographis paniculata (Burm. f.) Nees. young and mature leaves at different harvest ages using 1H NMR-based metabolomics approach
Authors: Tajidin Nor Elliza , Shaari Khozirah , Maulidiani Maulidiani , Salleh Nor Shariah , Ketaren Bunga Raya , Mohamad Munirah
Published: November 2019

Andrographis paniculata (Burm. F.) Nees. is considered as the herb of the future due to its precious chemical compounds, andrographolide (ANDRO), neoandrographolide (NAG) and 14-deoxyandrographolide (DAG). This study aims to profile the metabolites in young and mature leaf at six different harvest ages using 1HNMR-based metabolomics combined with multivariate data analysis. Principal component analysis (PCA) indicated noticeable and clear discrimination between young and mature leaves. A comparison of the leaves stage indicated that young leaves were separated from mature leaves due to its larger quantity of ANDRO, NAG, DAG, glucose and sucrose. These similar metabolites are also responsible for the PCA separation into five clusters representing the harvest age at 14, 16, 18, 20, 22 weeks of leaves extract. Loading plots revealed that most of the ANDRO and NAG signals were present when the plant reached at the pre-flowering stage or 18 weeks after sowing (WAS). As a conclusion, A. paniculata young leaves at pre-flowering harvest age were found to be richer in ANDRO, NAG and DAG compared to mature leaves while glucose and choline increased with harvest age. Therefore, young leaves of A. paniculata should be harvested at 18 WAS in order to produce superior quality plant extracts for further applications by the herbal, nutraceutical and pharmaceutical industries.
Contactless recording of sleep apnea and periodic leg movements by nocturnal 3-D-video and subsequent visual perceptive computing
Authors: Veauthier Christian , Ryczewski Juliane , Mansow-Model Sebastian , Otte Karen , Kayser Bastian , Glos Martin , Schöbel Christoph , Paul Friedemann , Brandt Alexander U. , Penzel Thomas
Published: November 2019

Contactless measurements during the night by a 3-D-camera are less time-consuming in comparison to polysomnography because they do not require sophisticated wiring. However, it is not clear what might be the diagnostic benefit and accuracy of this technology. We investigated 59 persons simultaneously by polysomnography and 3-D-camera and visual perceptive computing (19 patients with restless legs syndrome (RLS), 21 patients with obstructive sleep apnea (OSA), and 19 healthy volunteers). There was a significant correlation between the apnea hypopnea index (AHI) measured by polysomnography and respiratory events measured with the 3-D-camera in OSA patients (r = 0.823; p < 0.001). The receiver operating characteristic curve yielded a sensitivity of 90% for OSA with a specificity of 71.4%. In RLS patients 72.8% of leg movements confirmed by polysomnography could be detected by 3-D-video and a significant moderate correlation was found between PLM measured by polysomnography and by the 3-D-camera (RLS: r = 0.654; p = 0.004). In total, 95.4% of the sleep epochs were correctly classified by the machine learning approach, but only 32.5% of awake epochs. Further studies should investigate, if this technique might be an alternative to home sleep testing in persons with an increased pre-test probability for OSA.
Ubiquitylation and endocytosis of the human LAT1/SLC7A5 amino acid transporter
Authors: Barthelemy Céline , André Bruno
Published: November 2019

The human L-type amino acid transporter 1 (LAT1), also known as SLC7A5, catalyzes the transport of large neutral amino acids across the plasma membrane. As the main transporter of several essential amino acids, notably leucine, LAT1 plays an important role in mTORC1 activation. Furthermore, it is overexpressed in various types of cancer cells, where it contributes importantly to sustained growth. Despite the importance of LAT1 in normal and tumor cells, little is known about the mechanisms that might control its activity, for example by promoting its downregulation via endocytosis. Here we report that in HeLa cells, activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) triggers efficient endocytosis and degradation of LAT1. Under these conditions we found LAT1 downregulation to correlate with increased LAT1 ubiquitylation. This modification was considerably reduced in cells depleted of the Nedd4-2 ubiquitin ligase. By systematically mutagenizing the residues of the LAT1 cytosolic tails, we identified a group of three close lysines (K19, K25, K30) in the N-terminal tail that are important for PMA-induced ubiquitylation and downregulation. Our study thus unravels a mechanism of induced endocytosis of LAT1 elicited by Nedd4-2-mediated ubiquitylation of the transporter’s N-terminal tail.
Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos
Authors: Muller Bethany , Lewis Niamh , Adeniyi Tope , Leese Henry J. , Brison Daniel R. , Sturmey Roger G.
Published: November 2019

Mitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific molecular events remains lacking. Here, extracellular flux analysis (EFA) was applied to small groups of bovine, equine, mouse and human oocytes and bovine early embryos to measure OCR and its components. Using EFA, we report the changes in mitochondrial activity during the processes of oocyte maturation, fertilisation, and pre-implantation development to blastocyst stage in response to physiological demands in mammalian embryos. Crucially, we describe the real time partitioning of overall OCR to spare capacity, proton leak, non-mitochondrial and coupled respiration – showing that while activity changes over the course of development in response to physiological demand, the overall efficiency is unchanged. EFA is shown to be able to measure mitochondrial function in small groups of mammalian oocytes and embryos in a manner which is robust, rapid and easy to use. EFA is non-invasive and allows real-time determination of the impact of compounds on OCR, facilitating an assessment of the components of mitochondrial activity. This provides proof-of-concept for EFA as an accessible system with which to study mammalian oocyte and embryo metabolism.
Accurate whole-night sleep monitoring with dry-contact ear-EEG
Authors: Mikkelsen Kaare B. , Tabar Yousef R. , Kappel Simon L. , Christensen Christian B. , Toft Hans O. , Hemmsen Martin C. , Rank Mike L. , Otto Marit , Kidmose Preben
Published: November 2019

Sleep is a key phenomenon to both understanding, diagnosing and treatment of many illnesses, as well as for studying health and well being in general. Today, the only widely accepted method for clinically monitoring sleep is the polysomnography (PSG), which is, however, both expensive to perform and influences the sleep. This has led to investigations into light weight electroencephalography (EEG) alternatives. However, there has been a substantial performance gap between proposed alternatives and PSG. Here we show results from an extensive study of 80 full night recordings of healthy participants wearing both PSG equipment and ear-EEG. We obtain automatic sleep scoring with an accuracy close to that achieved by manual scoring of scalp EEG (the current gold standard), using only ear-EEG as input, attaining an average Cohen’s kappa of 0.73. In addition, this high performance is present for all 20 subjects. Finally, 19/20 subjects found that the ear-EEG had little to no negative effect on their sleep, and subjects were generally able to apply the equipment without supervision. This finding marks a turning point on the road to clinical long term sleep monitoring: the question should no longer be whether ear-EEG could ever be used for clinical home sleep monitoring, but rather when it will be.
Integrated Counts of Carbohydrate-Active Protein Domains as Metabolic Readouts to Distinguish Probiotic Biology and Human Fecal Metagenomes
Authors: Liu Hong-Hsing , Lin Yu-Chen , Chung Chen-Shuan , Liu Kevin , Chang Ya-Hui , Yang Chung-Hsiang , Chen Yun , Ni Yen-Hsuan , Chang Pi-Feng
Published: November 2019

Bowel microbiota is a “metaorgan” of metabolisms on which quantitative readouts must be performed before interventions can be introduced and evaluated. The study of the effects of probiotic Clostridium butyricum MIYAIRI 588 (CBM588) on intestine transplantees indicated an increased percentage of the “other glycan degradation” pathway in 16S-rRNA-inferred metagenomes. To verify the prediction, a scoring system of carbohydrate metabolisms derived from shotgun metagenomes was developed using hidden Markov models. A significant correlation (R = 0.9, p < 0.015) between both modalities was demonstrated. An independent validation revealed a strong complementarity (R = −0.97, p < 0.002) between the scores and the abundance of “glycogen degradation” in bacteria communities. On applying the system to bacteria genomes, CBM588 had only 1 match and ranked higher than the other 8 bacteria evaluated. The gram-stain properties were significantly correlated to the scores (p < 5 × 10−4). The distributions of the scored protein domains indicated that CBM588 had a considerably higher (p < 10−5) proportion of carbohydrate-binding modules than other bacteria, which suggested the superior ability of CBM588 to access carbohydrates as a metabolic driver to the bowel microbiome. These results demonstrated the use of integrated counts of protein domains as a feasible readout for metabolic potential within bacteria genomes and human metagenomes.
iTRAQ-Based Quantitative Proteomic Comparison of 2D and 3D Adipocyte Cell Models Co-cultured with Macrophages Using Online 2D-nanoLC-ESI-MS/MS
Authors: Lee Sun Young , Park Sung Bum , Kim Young Eun , Yoo Hee Min , Hong Jongki , Choi Kyoung-Jin , Kim Ki Young , Kang Dukjin
Published: November 2019

The demand for novel three-dimensional (3D) cell culture models of adipose tissue has been increasing, and proteomic investigations are important for determining the underlying causes of obesity, type II diabetes, and metabolic disorders. In this study, we performed global quantitative proteomic profiling of three 3D-cultured 3T3-L1 cells (preadipocytes, adipocytes and co-cultured adipocytes with macrophages) and their 2D-cultured counterparts using 2D-nanoLC-ESI-MS/MS with iTRAQ labelling. A total of 2,885 shared proteins from six types of adipose cells were identified and quantified in four replicates. Among them, 48 proteins involved in carbohydrate metabolism (e.g., PDHα, MDH1/2, FH) and the mitochondrial fatty acid beta oxidation pathway (e.g., VLCAD, ACADM, ECHDC1, ALDH6A1) were relatively up-regulated in the 3D co-culture model compared to those in 2D and 3D mono-cultured cells. Conversely, 12 proteins implicated in cellular component organisation (e.g., ANXA1, ANXA2) and the cell cycle (e.g., MCM family proteins) were down-regulated. These quantitative assessments showed that the 3D co-culture system of adipocytes and macrophages led to the development of insulin resistance, thereby providing a promising in vitro obesity model that is more equivalent to the in vivo conditions with respect to the mechanisms underpinning metabolic syndromes and the effect of new medical treatments for metabolic disorders.
Machine Learning-Based Analysis of Sperm Videos and Participant Data for Male Fertility Prediction
Authors: Hicks Steven A. , Andersen Jorunn M. , Witczak Oliwia , Thambawita Vajira , Halvorsen Pål , Hammer Hugo L. , Haugen Trine B. , Riegler Michael A.
Published: November 2019

Methods for automatic analysis of clinical data are usually targeted towards a specific modality and do not make use of all relevant data available. In the field of male human reproduction, clinical and biological data are not used to its fullest potential. Manual evaluation of a semen sample using a microscope is time-consuming and requires extensive training. Furthermore, the validity of manual semen analysis has been questioned due to limited reproducibility, and often high inter-personnel variation. The existing computer-aided sperm analyzer systems are not recommended for routine clinical use due to methodological challenges caused by the consistency of the semen sample. Thus, there is a need for an improved methodology. We use modern and classical machine learning techniques together with a dataset consisting of 85 videos of human semen samples and related participant data to automatically predict sperm motility. Used techniques include simple linear regression and more sophisticated methods using convolutional neural networks. Our results indicate that sperm motility prediction based on deep learning using sperm motility videos is rapid to perform and consistent. Adding participant data did not improve the algorithms performance. In conclusion, machine learning-based automatic analysis may become a valuable tool in male infertility investigation and research.