bluuebunny/crossref_metadata_2025 huggingface dataset:
Methoxyfenozide has minimal effects on replacement queens but may negatively affect sperm storage
Authors: Carroll Mark J. , Corby-Harris Vanessa , Brown Nicholas , Snyder Lucy , Reitz Dylan C.
Published: June 2022

Honey bees are incidentally exposed to pesticides such as the insect growth regulator methoxyfenozide (MEOF) during crop pollination, exposures that extend into the hive via contaminated stored food. We examined the sublethal effects of MEOF-contaminated pollen and queen cell wax on replacement queen development. MEOF-exposed colonies were largely able to produce replacement queens of similar physiological and reproductive quality as unexposed colonies. Newly established queens did not differ in their body mass, ovariole development, or protein and fatty acid contents in their ovaries and fat bodies. MEOF and control queens had similar glandular contents of queen mandibular pheromone (QMP) and queen retinue pheromone (QRP) compounds. However, MEOF queens stored less sperm in their spermathecae than control queens. Given that queen productivity is ultimately limited by sperm availability, MEOF contamination might shorten the functional lifespan of exposed queens.
Identification of Age-Associated Proteins and Functional Alterations in Human Retinal Pigment Epithelium
Authors: Jin Xiuxiu , Liu Jingyang , Wang Weiping , Li Jiangfeng , Liu Guangming , Qiu Ruiqi , Yang Mingzhu , Liu Meng , Yang Lin , Du Xiaofeng , Lei Bo
Published: June 2022

Retinal pigment epithelium (RPE) has essential functions, such as nourishing and supporting the neural retina, and is of vital importance in the pathogenesis of age-related retinal degeneration. However, the exact molecular changes of RPE during aging remain poorly understood. Here, we isolated human primary RPE (hRPE) cells from 18 eye donors distributed over a wide age range (10–67 years old). A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins. Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells. The results of proteomic data analysis and verifications suggest that RNF123- and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage during aging. In older hRPE cells, apoptotic signaling-related pathways were up-regulated, and endoplasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes. Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.
GREPore-Seq: A Robust Workflow to Detect Changes After Gene Editing Through Long-Range PCR and Nanopore Sequencing
Authors: Quan Zi-Jun , Li Si-Ang , Yang Zhi-Xue , Zhao Juan-Juan , Li Guo-Hua , Zhang Feng , Wen Wei , Cheng Tao , Zhang Xiao-Bing
Published: June 2022

To achieve the enormous potential of gene-editing technology in clinical therapies, one needs to evaluate both the on-target efficiency and unintended editing consequences comprehensively. However, there is a lack of a pipelined, large-scale, and economical workflow for detecting genome editing outcomes, in particular insertion or deletion of a large fragment. Here, we describe an approach for efficient and accurate detection of multiple genetic changes after CRISPR/Cas9 editing by pooled nanopore sequencing of barcoded long-range PCR products. Recognizing the high error rates of Oxford nanopore sequencing, we developed a novel pipeline to capture the barcoded sequences by grepping reads of nanopore amplicon sequencing (GREPore-seq). GREPore-seq can assess nonhomologous end-joining (NHEJ)-mediated double-stranded oligodeoxynucleotide (dsODN) insertions with comparable accuracy to Illumina next-generation sequencing (NGS). GREPore-seq also reveals a full spectrum of homology-directed repair (HDR)-mediated large gene knock-in, correlating well with the fluorescence-activated cell sorting (FACS) analysis results. Of note, we discovered low-level fragmented and full-length plasmid backbone insertion at the CRISPR cutting site. Therefore, we have established a practical workflow to evaluate various genetic changes, including quantifying insertions of short dsODNs, knock-ins of long pieces, plasmid insertions, and large fragment deletions after CRISPR/Cas9-mediated editing. GREPore-seq is freely available at GitHub (https://github.com/lisiang/GREPore-seq) and the National Genomics Data Center (NGDC) BioCode (https://ngdc.cncb.ac.cn/biocode/tools/BT007293).
Homer, Parmenides, and the Road to Demonstration
Authors: Folit-Weinberg Benjamin
Published: June 2022

It is widely agreed that Parmenides invented extended deductive argumentation and the practice of demonstration, a transformative event in the history of thought. But how did he manage this seminal accomplishment? In this book, Benjamin Folit-Weinberg finally provides an answer. At the heart of this story is the image of the hodos, the road and the journey. Brilliantly deploying the tools and insights of literary criticism, conceptual history, and archaeology, Folit-Weinberg illuminates how Parmenides adopts and adapts this image from Homer, especially the Odyssey, forging from it his pioneering intellectual approaches. Reinserting Parmenides into the physical world and poetic culture of archaic Greece, Folit-Weinberg reveals both how deeply traditional and how radical was Parmenides' new way of thinking and speaking. By taking this first step toward providing a history of the concept method, this volume uncovers the genealogy of philosophy in poetry and poetic imagery.
P.028 Eye movement biomarkers for early detection of multiple sclerosis disease progression
Authors: Bastien N , Chernock M , De Villers-Sidani E , Voss P , Blanchette F , Arseneau F , Hussein S , Ramos R , Giacomini PS
Published: June 2022

Background: There is growing body of evidence linking abnormal eye movements in people with multiple sclerosis (MS) to disease severity and cognition which could better detect disease progression. The objective of this study is to determine if a novel eye-tracking tool can accurately predict disease severity and cognitive status based on eye movement metrics and characterize how they evolve with progression. Methods: Persons with MS (n=132) will be followed over 4 years with clinical assessments every 6 months. Eye movements are also assessed while performing oculomotor tasks using Innodem Neurosciences’ patented eye-tracking technology. The eye movement metrics will be inputted into machine learning classifying algorithms to identify which metrics can serve as reliable Eye Movement Biomarkers (EMB) for MS progression and cognitive status. Results: There were 16 participants recruited as of January 2022 with mean age 47. 3 (SD 10.4; range 26-67), gender (12F/4M), EDSS 2.59 (SD 1.49; range 1.5-6.5), SDMT 51.4 (SD 14.1, range 24-78). With current enrollment, there is a negative correlation between EDSS and SDMT (r = -0.47) as observed in the literature. Conclusions: This trial will demonstrate the utility of EMBs for monitoring MS progression by improving physicians’ access to a reliable, non-invasive, sensitive and accessible marker of disease progression.
P.100 Early recognition of unique conventional and amplitude-integrated EEG patterns and clinical semiology of neonatal seizures caused by SCN2A and KCNQ3 mutations
Authors: Pijpers JA , Au PY , Weeke L , Vein AA , Smit L , Vilan AI , Jacobs E , de Vries LS , Steggerda SJ , Peeters CM , Appendino J
Published: June 2022

Background: Early recognition of neonatal seizures secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications, but respond well to sodium-channel blockers. We report a unique aEEG pattern in neonatal seizures caused by SCN2A and KCNQ3 pathogenic variants, as well as adding regular EEG description. Methods: International multicentre descriptive study, reporting clinical characteristics, aEEG and conventional EEG findings of 10 newborns with seizures due to pathogenic SCN2A and KCNQ3 gene variants. Results: Seizures started in the first postnatal week. Seizure semiology typically included tonic posturing with apnea and desaturation. The aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral attenuation in the EEG at onset, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. The majority of patients became seizure free upon initiation of a sodium-channel blocker. Conclusions: Neonatal seizures caused by SCN2A and KCNQ3 mutations can be recognized by a characteristic ictal aEEG pattern and clinical semiology. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium-channel blockers even before genetic test results are available.
P.139 Pediatric posterior fossa ependymoma recurrence in a molecularly defined cohort – Clinical, demographic, and surgical factors associated with outcome
Authors: Malhotra AK , Nobre LF , Ibrahim GM , Kulkarni AV , Drake JM , Rutka JT , Bouffet E , Taylor MD , Tsang D , Ramaswamy V , Dewan MC , Dirks PB
Published: June 2022

Background: Pediatric posterior fossa ependymoma contributes to morbidity and mortality in children. Following gross total resection and adjuvant radiotherapy, there is a known risk of local recurrence that portends a dismal prognosis. We sought to characterize survival in a molecularly defined cohort with an emphasis on recurrence patterns that influence outcome. Methods: This study was approved by the Ethics Board of the Hospital for Sick Children. We performed a twenty-year single-center retrospective study to identify clinical, demographic and treatment characteristics of patients with pathologically diagnosed posterior fossa ependymoma. Results: There were 60 patients identified that underwent primary resection. Recurrence rate in the cohort was 48% with 29 cases of recurrent ependymoma occurring at a mean time of 24 months after index surgery. No mortalities were observed among patients undergoing primary resection without recurrent disease. Median cohort survival was 12.3 years in the primary cohort and and 6.32 years among patients recurrent ependymoma. Recurrent disease was significantly associated with worse overall survival after multivariate analysis (HR = 0.024). Conclusions: We highlight overall survival and factors influencing mortality in pediatric posterior fossa ependymoma. Recurrent disease confers a worse prognosis. We describe for the first time survival trends following local and distant recurrences managed through multiple resections.
Sunset similarity solution for a receding hydraulic fracture
Authors: Peirce Anthony , Detournay Emmanuel
Published: June 2022

This paper derives approximate ‘sunset’ similarity solutions for receding plane strain and radially symmetric hydraulic fractures in permeable elastic media close to the point of closure. Local analysis is used to show that a receding hydraulic fracture has a linear aperture asymptote$\hat {w}\sim \hat {s}$in the fracture tip, where$\hat {s}$is the distance from the fracture front. Due to the regularity of the linear asymptote, it is possible to determine similarity solutions in the form of power series expansions, which, for integers$N\ge 2$and values of the radius decay exponent$\gamma =1/N$, can be shown to terminate to yield polynomial solutions for the fracture aperture of degree$N$. Of this countable infinity of polynomial solutions, the final aperture profile as the fracture approaches closure is associated with the second-degree polynomial with$\gamma =1/2$called the sunset solution. For the reverse time$t^{\prime }$measured from closure, the sunset solution is characterized by$w\sim t^{\prime }$and$R\sim t^{\prime 1/2}$. Of all the admissible polynomial similarity solutions, the sunset solution is shown to form an attractor, as$t^{\prime }\rightarrow 0$, for receding hydraulic fractures associated with a wide variety of points in parametric space. Using the sunset solution, it is possible to estimate the duration of recession, assuming that the fracture aperture and radius at the start of recession are given, and determine how it scales with a dimensionless shut-in parameter. As the fracture approaches closure, the term responsible for coupling the elastic force balance and fluid conservation becomes subdominant to the other terms in the lubrication equation, which reduces to a local kinematic relation between the decaying fracture aperture and the leak-off velocity. This fundamental decoupling of dynamics from kinematics results in the sunset solution being dependent on only a single material parameter – namely the leak-off coefficient. This isolation of the leak-off coefficient by the sunset solution opens the possibility to determine this parameter from laboratory or field measurements.
Combined three-dimensional flow field measurements and motion tracking of freely moving spheres in a turbulent boundary layer
Authors: van Hout R. , Hershkovitz A. , Elsinga G.E. , Westerweel J.
Published: June 2022

A combination of time-resolved tomographic particle image velocimetry, refractive index matching technique and machine vision algorithms was used to measure the translational and rotational motion of freely moving, nearly neutrally buoyant spheres in a fully developed turbulent boundary layer (TBL). Located in the buffer and logarithmic layers, the hydrogel spheres (

$\sim$

70 inner wall units in diameter) were refractive index matched with the water and tagged by ‘spokes’. Besides translational motion, the spheres exhibited significant rotation. The spheres were surrounded by typical coherent structures observed in TBLs, among them hairpin packets and transverse and longitudinal vortices that induced ejections and sweeps. While the majority of instantaneous sphere Reynolds numbers did not exceed 100, and vortex shedding was not observed, the results showed that the spheres may affect the evolution of hairpin packets in TBLs due to their finite size. The instantaneous rotation-, wall- and shear-induced lift forces, as well as the drag forces, acting on the spheres were estimated using available correlations for the lift and drag coefficients. Results hinted at negative shear-induced lift due to flow separation at a smaller critical Reynolds number than incorporated in the correlations that do not include the effect of ambient turbulence. The results indicated further that the drag force aided by the rotation-induced lift force was instrumental in keeping one of the spheres aloft. For the wall-ward moving spheres, lift forces opposed sphere motion. As a result, the spheres approached the wall with velocities lower than their quiescent settling velocity.
Biostratigraphy and paleoecology of the trilobite faunas from the Mount Clark and Mount Cap formations (early and middle Cambrian), eastern Mackenzie Mountains, northwestern Canada
Authors: Handkamer Neal M. , Pratt Brian R. , MacNaughton Robert B.
Published: June 2022

Lower and middle Cambrian strata of the eastern Mackenzie Mountains, Northwest Territories, Canada, were deposited in a semi-enclosed basin along the eastern flank of the Mackenzie Arch. The Mount Clark Formation is predominantly composed of nearshore sandstone and is overlain by deeper water siltstone, mudstone, and carbonates of the Mount Cap Formation. The contact between these formations is interpreted as a flooding surface. Trilobite biostratigraphy indicates the presence of the traditional upper Olenellus through Glossopleura zones (Cambrian Series 2, Stage 4–Miaolingian, Wuliuan) and suggests the flooding surface is diachronous, spanning the Dyeran-Delamaran boundary. Above the Olenellus Zone, the Amecephalus arrojosensis-Eokochaspis nodosa Zone, the new Aitkenaspis keelensis Zone, the new Albertelloides mischi Zone, and the Glossopleura walcotti Zone are recognized. Whereas the older zones are comparable to those in other areas of Laurentia, the trilobite faunas in the Albertelloides mischi and Glossopleura walcotti zones show a greater abundance of zacanthoidids and dolichometopids. They also have a lower diversity of ptychoparioids and oryctocephalids, and lack agnostoids, eodiscoids, dorypygids, and ogygopsidids. This suggests that zacanthoidids and dolichometopids were able to tolerate conditions that were unfavorable to the other groups, probably related to semi-restricted conditions in the basin. Four endemic species exhibit characteristics that are considered paedomorphic. This developmental process took place in three separate lineages, suggesting that heterochrony was also environmentally provoked.

New taxonomic names are authored by Handkamer and Pratt. New genera are Eobathyuriscus, Sahtuia, Mexicaspidella Aitkenaspis, Dodoella, and Mackenzieaspis. New species are Bolbolenellus dodoensis, Eobathyuriscus mackenziensis, E. macqueeni, Glossopleura youngi, Sahtuia carcajouensis, Aitkenaspis keelensis, Albertelloides eliasi, Dodoella kobayashii, Mackenzieaspis parallelispinosa, and M. divergens.

UUID: http://zoobank.org/a10a2470-853c-4ce8-bf62-7de1d2c99fab.
Differences in growth patterns and catch-up growth of small for gestational age preterm infants fed on fortified mother’s own milk v. preterm formula
Authors: Hofi Lilach , Flidel-Rimon Orna , Hershkovich–Shporen Calanit , Zaharoni Hilla , Birk Ruth
Published: June 2022

Small for gestational age (SGA) is typically defined as birth weight < 10th percentile for age. Limited data are available regarding the growth of SGA preterm infants in relation to feeding type. We aimed to study SGA preterm infants fed fortified mother’s own milk (MOM) or preterm formula (PF) on growth patterns and catch-up growth at discharge and 2-year corrected age (CA). Our retrospective cohort study included data from medical records and follow-up questionnaires about SGA preterm infants born at < 37 weeks fed on MOM (n 40) and PF (n 40). Weight, length/height and head circumference (HC) were collected at birth, discharge and at 2-year CA, and Δ z-scores were calculated. The MOM group had significantly larger negative change in weight and length z-scores between birth and discharge, and smaller positive change in HC z-score (–0·47 (sd 0·41) v. −0·25 (sd 0·36), P = 0·01; −0·63 (sd 0·75) v. −0·27 (sd 0·75), P = 0·03; 0·13 (sd 0·67) v. 0·41 (sd 0·55), P = 0·04, respectively). Almost half of the MOM-fed infants experienced poor length growth by discharge compared with 22 % of PF-fed infants (P = 0·03). By 2-year CA, both groups had similar positive change in weight and HC z-scores, but MOM-fed infants had a slower increase in height z-score (0·64 (sd 1·30) v. 1·33 (sd 1·33), P = 0·02), and only 40 % had achieved catch-up height compared with 68 % of the PF group (P = 0·02). Our study indicates that fortified MOM-fed SGA preterm infants may need extra nutritional support in the first 2 years of life to achieve height growth potential.
Tectonometamorphic evolution of the Trivandrum and Southern Madurai blocks in the Southern Granulite Terrane, south India: correlation with south-central Madagascar
Authors: Praharaj P , Rekha S
Published: June 2022

Detailed structural investigations across the Achankovil terrane boundary shear zone (AKSZ) system show distinct differences in the geometry of superposed fold structures between the Trivandrum (TB) and Southern Madurai (SMB) blocks separated by the AKSZ. The metamorphic temperatures and pressures estimated from the SMB and TB have a similar range, that is, 600–880°C and 5–8 kbar. The similar clockwiseP-Tpaths retrieved by phase equilibrium modelling from both the blocks represent the last deformation and metamorphism shared between them during their accretion along the AKSZ. The distinct evolutionary history of the SMB and TB prior to their amalgamation is supported by the contrasting structural, metamorphic and chronological patterns, particularly the lack of prominent middle Neoproterozoic ages and the presence of Palaeoproterozoic ages in the TB, and vice versa in the SMB. The prominent 600–500 Ma monazite ages in the TB, SMB and AKSZ attest to their timing of accretion along the AKSZ. The study corroborates the S-directed subduction model proposed for terrane accretion along the AKSZ, and provides further insight into the subduction–accretion–collision tectonics associated with the late Neoproterozoic – Cambrian evolutionary history of this region.

The tectonothermal histories and geochronology of the SMB and TB are compared to the once adjoined crustal domains of Madagascar within Gondwanaland. It is suggested that the TB is equivalent to the Androyan and Anosyan domains of southern Madagascar, the SMB is equivalent to the Antananarivo and Itremo–Ikalamavony blocks of the central Madagascar, and the sinistral AKSZ is contiguous with the Ranotsara Shear Zone in southern Madagascar.
Foodborne trematodes: old foes, new kids on the block and research perspectives for control and understanding host–parasite interactions
Authors: Robinson Mark W. , Sotillo Javier
Published: June 2022

Foodborne trematodes (FBTs) have a worldwide distribution (with particular prevalence in south-east Asia) and are believed to infect almost 75 million people, with millions more living at risk of infection. Although mortality due to trematodiasis is low, these infections cause considerable morbidity and some species are associated with the development of cancer in hyperendemic regions. Despite this, FBTs are often side-lined in terms of research funding and have been dubbed neglected tropical diseases by the World Health Organisation. Thus, the aim of this special issue was to provide an update of our understanding of FBT infections, to shine a light on current work in the field and to highlight some research priorities for the future. With contributions from leading researchers, many from endemic regions, we review the major FBT species. In doing so we revisit some old foes, uncover emerging infections and discover how outbreaks are being dealt with as a result of new approaches to parasite control. We also report advances in our understanding of the interactions of FBTs with their mammalian hosts and uncover new interplay between trematodes and host microbiome components. We hope that this article collection will stimulate discussion and further research on the FBTs and help raise them from their neglected status.
Tree recruitment after native frugivore extinction? A field experiment to test the impact of fruit flesh persistence in a tropical oceanic island
Authors: Albert Sébastien , Flores Olivier , Stahl Mikael , Guilhabert Florian , Strasberg Dominique
Published: June 2022

The loss of large frugivores leads to seed dispersal loss and regeneration failure of numerous large-seeded trees near mother trees. Although Janzen–Connell effects are considered as the primary underlying cause, other factors remain understudied. Here, we used a field experiment to test the impact of flesh persistence on the recruitment of two large-seeded Sapotaceae species that lost their dispersers. In the rainforest of Mare Longue (Réunion), we sowed 3840 seeds in a four-factor design: seed treatment (seed cleaning; flesh persistence), canopy closure (understory; gap), year of sowing (01/2018; 11/2019) and species (Labourdonnaisia calophylloides, Mimusops balata). We also used camera traps to evaluate the impact of extant vertebrates. Seed treatment was by far the most influential factor: flesh persistence led to seedling recruitment divided by 3,2 on average, mainly due to failure of germination or seedling emergence. There were also significant variations in recruitment between species, years and canopy closure levels, notably due to the behaviour of the invasive fauna, especially giant snails that could unexpectedly restore recruitment by feeding on fruit flesh. Together, our results demonstrate strongly depleted recruitment due to flesh persistence and the importance of field experiments to understand the processes at work in complex ecosystems with novel plant–animal interactions.
A value-at-risk approach to futures hedge
Authors: Chiu Wan-Yi
Published: June 2022

This paper examines the value-at-risk (VaR) implications of mean-variance hedging. We derive an equivalence between the VaR-based hedge and the mean-variance hedging. This method transfers the investor's subjective risk-aversion coefficient into the estimated VaR measure. As a result, we characterize the collapse probability bounds under which the VaR-based hedge could be insignificantly different from the minimum-variance hedge in the presence of estimation risk. The results indicate that the squared information ratio of futures returns is the primary factor determining the difference between the minimum-variance and VaR-based hedges.
Influencing the choice of pension distribution at retirement
Authors: Clark Robert L. , Mitchell Olivia S.
Published: June 2022

One of the most important financial decisions that pension participants make concerns how they access their pension assets when they terminate employment with their plan sponsor. Their choices depend both on own preferences and the options offered by their retirement plan. This paper examines both past and future pension withdrawal choices for those with defined benefit (DB) and defined contribution (DC) pensions, separately. Our data are drawn from a set of pension distribution questions we fielded in the Understanding American Study. Results show significant differences in distribution choices based on the type of retirement plan, with individuals covered by DB plans significantly more likely to select annuities compared to similar employees covered by DC plans. We also find differences in how higher annual income affects annuity choices based on coverage by DB plans. Individuals with lower levels of financial literacy and lower annual income have less knowledge of basic pension characteristics.
Volume, Effusion Rate, and Lava Transport During the 2021 Fagradalsfjall Eruption: Results From Near Real‐Time Photogrammetric Monitoring
Authors: Pedersen Gro B. M. , Belart Joaquin M. C. , Óskarsson Birgir Vilhelm , Gudmundsson Magnús Tumi , Gies Nils , Högnadóttir Thórdís , Hjartardóttir Ásta Rut , Pinel Virginie , Berthier Etienne , Dürig Tobias , Reynolds Hannah Iona , Hamilton Christopher W. , Valsson Guðmundur , Einarsson Páll , Ben‐Yehosua Daniel , Gunnarsson Andri , Oddsson Björn
Published: June 2022

The basaltic effusive eruption at Mt. Fagradalsfjall lasted from 19 March to 18 September 2021, ending a 781‐year repose period on Reykjanes Peninsula, Iceland. By late September 2021, 33 near real‐time photogrammetric surveys were completed using satellite and airborne images, usually processed within 3–6 hr. The results provide unprecedented temporal data sets of lava volume, thickness, and effusion rate. This enabled rapid assessment of eruption evolution and hazards to populated areas, important infrastructure, and tourist centers. The lava flow field has a mean lava thickness exceeding 30 m, covers 4.8 km2 and has a bulk volume of 150 ± 3 × 106 m3. The March–September mean bulk effusion rate is 9.5 ± 0.2 m3/s, ranging between 1 and 8 m3/s in March–April and increasing to 9–13 m3/s in May–September. This is uncommon for recent Icelandic eruptions, where the highest discharge usually occurs in the opening phase.
Increasing Inhomogeneity of the Global Oceans
Authors: Ren Qiuping , Kwon Young‐Oh , Yang Jiayan , Huang Rui Xin , Li Yuanlong , Wang Fan
Published: June 2022

The ocean is inhomogeneous in hydrographic properties with diverse water masses. Yet, how this inhomogeneity has evolved in a rapidly changing climate has not been investigated. Using multiple observational and reanalysis datasets, we show that the spatial standard deviation (SSD) of the global ocean has increased by 1.4 ± 0.1% in temperature and 1.5 ± 0.1% in salinity since 1960. A newly defined thermohaline inhomogeneity index, a holistic measure of both temperature and salinity changes, has increased by 2.4 ± 0.1%. Climate model simulations suggest that the observed ocean inhomogeneity increase is dominated by anthropogenic forcing and projected to accelerate by 200%–300% during 2015–2100. Geographically, the rapid upper‐ocean warming at mid‐to‐low latitudes dominates the temperature inhomogeneity increase, while the increasing salinity inhomogeneity is mainly due to the amplified salinity contrast between the subtropical and subpolar latitudes.
Extension of Aseismic Slip Propagation Theory to Slow Earthquake Migration
Authors: Ariyoshi Keisuke
Published: June 2022

Natural faults host various types of migrating slow earthquake phenomena, with migration speeds much lower than seismic wave speeds and different moment‐duration scaling from regular earthquakes. To advance the obtained quantitative understanding of the migration process and long duration of slow earthquakes, I study a chain reaction model in a population of brittle asperities based on a rate‐ and state‐dependent friction on a 3‐D subduction plate boundary. Simulation results show that the migration speed is quantitatively related to frictional properties by an analytical relation derived here. By assuming that local pore water in front of the migration drives rapid tremor reversal and is so local as to hold a constant stress drop, the application of the analytical solution to observational results suggests that (a) the temporal changes of observed migration speeds for the rapid tremor reversal could be explained by about 70% reduction of the effective normal stress; (b) effective normal stress for the deeper extension of seismogenic segment in the western part of Shikoku is about 1.5 times greater than that in the central part. Applying rupture time delay between slow earthquake asperities for the duration longer than regular earthquake, I also conclude that (c) the characteristic slip distance of rate‐and‐state friction for low‐frequency earthquakes is roughly between 30 µm and 30 mm; (d) the stress and strength drops of very low‐frequency earthquakes is much smaller than 1 MPa.
Unlocking the Magmatic Secrets of Antarctica’s Mount Erebus
Authors: Duncombe Jenessa
Published: June 2022

Unprecedented images of Mount Erebus’s inner workings show the unique trappings of a CO2-rich rift volcano.
India (Tethyan Himalaya Series) in Central Myanmar: Implications for the Evolution of the Eastern Himalayan Syntaxis and the Sagaing Transform‐Fault System
Authors: Min Myo , Ratschbacher Lothar , Franz Leander , Hacker Bradley R. , Enkelmann Eva , Toreno Eko Yoan , Härtel Birk , Schurr Bernd , Tichomirowa Marion , Pfänder Jörg A.
Published: June 2022

In the Katha Range of central Myanmar, lithologic tracers and pressure‐temperature‐deformation‐time data identify Cambro‐Ordovician, Indian‐affinity Tethyan Himalaya Series, located ∼700 km from their easternmost outcrop in S‐Tibet, and ∼450 km from Himalayan rocks in the Eastern Himalayan Syntaxis. Metamorphism began at ∼65 Ma, peaked at ∼45 Ma (∼510°C, 0.93 GPa), and exhumation/cooling (∼25°C/Myr) occurred until ∼30 Ma in a subduction‐early collision tectonic setting. When the Burma microplate—part of the intra‐Tethyan Incertus arc—accreted to SE‐Asia, its eastern boundary, the southern continuation of the Indus‐Yarlung suture (IYS), was reactivated as the Sagaing fault (SF), which propagated northward into Indian rocks. In the Katha rocks, this strike‐slip stage is marked by ∼4°C/Myr exhumation/cooling. Restoring the SF system defines a continental collision‐oceanic subduction transition junction, where the IYS bifurcates into the SF at the eastern edge of the Burma microplate and the Jurassic ophiolite‐Jadeite belts that include the Incertus‐arc suture.
Human RIPK3 C-lobe phosphorylation is essential for necroptotic signaling
Authors: Meng Yanxiang , Horne Christopher R. , Samson Andre L. , Dagley Laura F. , Young Samuel N. , Sandow Jarrod J. , Czabotar Peter E. , Murphy James M.
Published: June 2022

Necroptosis is a caspase-independent, pro-inflammatory mode of programmed cell death which relies on the activation of the terminal effector, MLKL, by the upstream protein kinase RIPK3. To mediate necroptosis, RIPK3 must stably interact with, and phosphorylate the pseudokinase domain of MLKL, although the precise molecular cues that provoke RIPK3 necroptotic signaling are incompletely understood. The recent finding that RIPK3 S227 phosphorylation and the occurrence of a stable RIPK3:MLKL complex in human cells prior to exposure to a necroptosis stimulus raises the possibility that additional, as-yet-unidentified phosphorylation events activate RIPK3 upon initiation of necroptosis signaling. Here, we sought to identify phosphorylation sites of RIPK3 and dissect their regulatory functions. Phosphoproteomics identified 21 phosphorylation sites in HT29 cells overexpressing human RIPK3. By comparing cells expressing wild-type and kinase-inactive D142N RIPK3, autophosphorylation sites and substrates of other cellular kinases were distinguished. Of these 21 phosphosites, mutational analyses identified only pT224 and pS227 as crucial, synergistic sites for stable interaction with MLKL to promote necroptosis, while the recently reported activation loop phosphorylation at S164/T165 negatively regulate the kinase activity of RIPK3. Despite being able to phosphorylate MLKL to a similar or higher extent than wild-type RIPK3, mutation of T224, S227, or the RHIM in RIPK3 attenuated necroptosis. This finding highlights the stable recruitment of human MLKL by RIPK3 to the necrosome as an essential checkpoint in necroptosis signaling, which is independent from and precedes the phosphorylation of MLKL.
Asparagine synthetase regulates lung-cancer metastasis by stabilizing the β-catenin complex and modulating mitochondrial response
Authors: Cai Dong-Jing , Zhang Zi-Yu , Bu Yue , Li Li , Deng Yue-Zhen , Sun Lun-Quan , Hu Cheng-Ping , Li Min
Published: June 2022

The availability of asparagine is the limitation of cell growth and metastasis. Asparagine synthetase (ASNS) was an essential enzyme for endogenous asparagine products. In our study, ASNS-induced asparagine products were essential to maintain tumor growth and colony formations in vitro. But mutated ASNS which defected endogenous asparagine products still upregulated cell invasiveness, which indicated that ASNS promoted invasiveness by alternative pathways. Mechanically, ASNS modulated Wnt signal transduction by promoting GSK3β phosphorylation on ser9 and stabilizing the β-catenin complex, as result, ASNS could promote more β-catenin translocation into nucleus independent of endogenous asparagine. At the same time, ASNS modulated mitochondrial response to Wnt stimuli with increased mitochondrial potential and membrane fusion. In summary, ASNS promoted metastasis depending on Wnt pathway and mitochondrial functions even without endogenous asparagine products.
Ecological networks of dissolved organic matter and microorganisms under global change
Authors: Hu Ang , Choi Mira , Tanentzap Andrew J. , Liu Jinfu , Jang Kyoung-Soon , Lennon Jay T. , Liu Yongqin , Soininen Janne , Lu Xiancai , Zhang Yunlin , Shen Ji , Wang Jianjun
Published: June 2022

Microbes regulate the composition and turnover of organic matter. Here we developed a framework called Energy-Diversity-Trait integrative Analysis to quantify how dissolved organic matter and microbes interact along global change drivers of temperature and nutrient enrichment. Negative and positive interactions suggest decomposition and production processes of organic matter, respectively. We applied this framework to manipulative field experiments on mountainsides in subarctic and subtropical climates. In both climates, negative interactions of bipartite networks were more specialized than positive interactions, showing fewer interactions between chemical molecules and bacterial taxa. Nutrient enrichment promoted specialization of positive interactions, but decreased specialization of negative interactions, indicating that organic matter was more vulnerable to decomposition by a greater range of bacteria, particularly at warmer temperatures in the subtropical climate. These two global change drivers influenced specialization of negative interactions most strongly via molecular traits, while molecular traits and bacterial diversity similarly affected specialization of positive interactions.
An intein-split transactivator for intersectional neural imaging and optogenetic manipulation
Authors: Chen Hao-Shan , Zhang Xiao-Long , Yang Rong-Rong , Wang Guang-Ling , Zhu Xin-Yue , Xu Yuan-Fang , Wang Dan-Yang , Zhang Na , Qiu Shou , Zhan Li-Jie , Shen Zhi-Ming , Xu Xiao-Hong , Long Gang , Xu Chun
Published: June 2022

The cell-type-specific recording and manipulation is instrumental to disentangle causal neural mechanisms in physiology and behavior and increasingly requires intersectional control; however, current approaches are largely limited by the number of intersectional features, incompatibility of common effectors and insufficient gene expression. Here, we utilized the protein-splicing technique mediated by intervening sequences (intein) and devised an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in multiple-feature defined cell types in mice. We validated the specificity and sufficiency of IBIST to control fluorophores, optogenetic opsins and Ca2+ indicators in various intersectional conditions. The IBIST-based Ca2+ imaging showed that the IBIST can intersect five features and that hippocampal neurons tune differently to distinct emotional stimuli depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and controls common effectors to effectively regulate gene expression, monitor and manipulate neural activities.
Single molecule demonstration of Debye–Stokes–Einstein breakdown in polystyrene near the glass transition temperature
Authors: Mandel Nicole L. , Lee Soohyun , Kim Kimyung , Paeng Keewook , Kaufman Laura J.
Published: June 2022

Rotational-translational decoupling, in which translational motion is apparently enhanced over rotational motion in violation of Stokes-Einstein (SE) and Debye-Stokes-Einstein (DSE) predictions, has been observed in materials near their glass transition temperatures (Tg). This has been posited to result from ensemble averaging in the context of dynamic heterogeneity. In this work, ensemble and single molecule experiments are performed in parallel on a fluorescent probe in high molecular weight polystyrene near its Tg. Ensemble results show decoupling onset at approximately 1.15Tg, increasing to over three orders of magnitude at Tg. Single molecule measurements also show a high degree of decoupling, with typical molecules at Tg showing translational diffusion coefficients nearly 400 times higher than expected from SE/DSE predictions. At the single molecule level, higher degree of breakdown is associated with particularly mobile molecules and anisotropic trajectories, providing support for anomalous diffusion as a critical driver of rotational-translational decoupling and SE/DSE breakdown.
Peripherally restricted transthyretin-based delivery system for probes and therapeutics avoiding opioid-related side effects
Authors: Tuhin Md Tariqul Haque , Liang Dengpan , Liu Fang , Aldawod Hala , Amin Toufiq Ul , Ho Joshua S. , Emara Rasha , Patel Arjun D. , Felmlee Melanie A. , Park Miki S. , Uchizono James A. , Alhamadsheh Mamoun M.
Published: June 2022

Several investigations into the sites of action of opioid analgesics have utilized peripherally acting mu-opioid receptor antagonists (PAMORAs), which have been incorrectly assumed to possess limited permeability across the blood-brain barrier. Unfortunately, the poor pharmacokinetic properties of current PAMORAs have resulted in misunderstandings of the role of central nervous system and gastrointestinal tract in precipitating side effects such as opioid-induced constipation. Here, we develop a drug delivery approach for restricting the passage of small molecules across the blood-brain barrier. This allows us to develop naloxone- and oxycodone-based conjugates that display superior potency, peripheral selectivity, pharmacokinetics, and efficacy in rats compared to other clinically used PAMORAs. These probes allow us to demonstrate that the mu-opioid receptors in the central nervous system have a fundamental role in precipitating opioid-induced constipation. Therefore, our conjugates have immediate use as pharmacological probes and potential therapeutic agents for treating constipation and other opioid-related side effects.
Exceptional soft-tissue preservation of Jurassic Vampyronassa rhodanica provides new insights on the evolution and palaeoecology of vampyroteuthids
Authors: Rowe Alison J. , Kruta Isabelle , Landman Neil H. , Villier Loïc , Fernandez Vincent , Rouget Isabelle
Published: June 2022

Although soft tissues of coleoid cephalopods record key evolutionary adaptations, they are rarely preserved in the fossil record. This prevents meaningful comparative analyses between extant and fossil forms, as well as the development of a relative timescale for morphological innovations. However, unique 3-D soft tissue preservation ofVampyronassa rhodanica(Vampyromorpha) from the Jurassic Lagerstätte of La Voulte-sur-Rhône (Ardèche, France) provides unparalleled opportunities for the observation of these tissues in the oldest likely relative of extantVampyroteuthis infernalis. Synchrotron X-ray microtomography and reconstruction ofV. rhodanicaallowed, for the first time, a high-resolution re-examination of external and internal morphology, and comparison with other fossil and extant species, includingV. infernalis. The new data obtained demonstrate that some keyV. infernalischaracters, such as its unique type of sucker attachment, were already present in Jurassic taxa. Nonetheless, compared with the extant form, which is considered to be an opportunistic detritivore and zooplanktivore, many characters inV. rhodanicaindicate a pelagic predatory lifestyle. The contrast in trophic niches between the two taxa is consistent with the hypothesis that these forms diversified in continental shelf environments prior to the appearance of adaptations in the Oligocene leading to their modern deep-sea mode of life.
Deep learning for necrosis detection using canine perivascular wall tumour whole slide images
Authors: Rai Taranpreet , Morisi Ambra , Bacci Barbara , Bacon Nicholas J. , Dark Michael J. , Aboellail Tawfik , Thomas Spencer Angus , Bober Miroslaw , La Ragione Roberto , Wells Kevin
Published: June 2022

Necrosis seen in histopathology Whole Slide Images is a major criterion that contributes towards scoring tumour grade which then determines treatment options. However conventional manual assessment suffers from inter-operator reproducibility impacting grading precision. To address this, automatic necrosis detection using AI may be used to assess necrosis for final scoring that contributes towards the final clinical grade. Using deep learning AI, we describe a novel approach for automating necrosis detection in Whole Slide Images, tested on a canine Soft Tissue Sarcoma (cSTS) data set consisting of canine Perivascular Wall Tumours (cPWTs). A patch-based deep learning approach was developed where different variations of training a DenseNet-161 Convolutional Neural Network architecture were investigated as well as a stacking ensemble. An optimised DenseNet-161 with post-processing produced a hold-out test F1-score of 0.708 demonstrating state-of-the-art performance. This represents a novel first-time automated necrosis detection method in the cSTS domain as well specifically in detecting necrosis in cPWTs demonstrating a significant step forward in reproducible and reliable necrosis assessment for improving the precision of tumour grading.
Assessment of solar radiation resource from the NASA-POWER reanalysis products for tropical climates in Ghana towards clean energy application
Authors: Quansah Alfred Dawson , Dogbey Felicia , Asilevi Prince Junior , Boakye Patrick , Darkwah Lawrence , Oduro-Kwarteng Sampson , Sokama-Neuyam Yen Adams , Mensah Patrick
Published: June 2022

In order to expand the output of solar power systems for efficient integration into the national grid, solar energy resource assessment at site is required. A major impediment however, is the widespread scarcity of radiometric measurements, which can be augmented by satellite observation. This paper assessed the suitability of satellite-based solar radiation resource retrieved from the NASA-POWER archives at $$0.5^\circ \times 0.5^\circ$$

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spatial resolution over Ghana–West Africa, to develop a long-term source reference. The assessment is based on the criteria of comparison with estimations from sunshine duration measurement for 22 synoptic stations. Overall, the satellite-based data compared well with ground-based estimations by r = 0.6–0.94 ± 0.1. Spatiotemporally, the agreement is strongest over the northern half Savannah-type climate during March–May, and weakest over the southern half Forest-type climate during June–August. The assessment provides empirical framework to support solar energy utilization in the sub-region.
Associations of body shape phenotypes with sex steroids and their binding proteins in the UK Biobank cohort
Authors: Christakoudi Sofia , Riboli Elio , Evangelou Evangelos , Tsilidis Konstantinos K.
Published: June 2022

Associations of sex steroids and their binding proteins with body shape are unclear, because waist and hip circumference are correlated strongly with body size. We defined body shape using “a body shape index” (ABSI) and hip index (HI), which are independent of weight and height by design, and examined associations in multivariable generalised linear models for the UK Biobank cohort (179,902 men, 207,444 women). Total testosterone was associated inversely with ABSI, especially in men. Free testosterone was lowest for large-ABSI-large-HI (“wide”) and highest for small-ABSI-small-HI (“slim”) in men, but lowest for small-ABSI-large-HI (“pear”) and highest for large-ABSI-small-HI (“apple”) in women. Oestradiol was associated inversely with ABSI in obese pre-menopausal women but positively with HI in obese men and post-menopausal women not using hormone replacement therapy. Sex-hormone binding globulin (SHBG) was associated inversely with ABSI but positively with HI and was lowest for “apple” and highest for “pear” phenotype in both sexes. Albumin was associated inversely with HI in women, but matched the pattern of free testosterone in obese men (lowest for “wide”, highest for “slim” phenotype). In conclusion, sex steroids and their binding proteins are associated with body shape, including hip as well as waist size, independent of body size.