bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Investigation of Mercury's Magma Ocean Viscosity: Implications for the Formation of Mercury's Cumulate Mantle, Its Subsequent Dynamic Evolution, and Crustal Petrogenesis
Authors: Mouser Megan D. , Dygert Nicholas , Anzures Brendan A. , Grambling Nadine L. , Hrubiak Rostislav , Kono Yoshio , Shen Guoyin , Parman Stephen W.
Published: October 2021

Mercury has a compositionally diverse surface that was produced by different periods of igneous activity suggesting heterogeneous mantle sources. Understanding the structure of Mercury's mantle formed during the planet's magma ocean stage could help in developing a petrologic model for Mercury, and thus, understanding its dynamic history in the context of crustal petrogenesis. We present results of falling sphere viscometry experiments on late‐stage Mercurian magma ocean analogue compositions conducted at the Advanced Photon Source, beamline 16‐BM‐B, Argonne National Laboratory. Owing to the presence of sulfur on the surface of Mercury, two compositions were tested, one with sulfur and one without. The liquids have viscosities of 0.6–3.9 (sulfur‐bearing; 2.6–6.2 GPa) and 0.6–10.9 Pa·s (sulfur‐free; 3.2–4.5 GPa) at temperatures of 1600–2000°C. We present new viscosity models that enable extrapolation beyond the experimental conditions and evaluate grain growth and the potential for crystal entrainment in a cooling, convecting magma ocean. We consider scenarios with and without a graphite flotation crust, suggesting endmember outcomes for Mercury's mantle structure. With a graphite flotation crust, crystallization of the mantle would be fractional with negatively buoyant minerals sinking to form a stratified cumulate pile according to the crystallization sequence. Without a flotation crust, crystals may remain entrained in the convecting liquid during solidification, producing a homogeneous mantle. In the context of these endmember models, the surface could result from dynamical stirring or mixing of a mantle that was initially heterogeneous, or potentially from different extents of melting of a homogeneous mantle.
Evaluation of SaRIF High‐Energy Electron Reconstructions and Forecasts
Authors: Glauert S. A. , Horne R. B. , Kirsch P.
Published: October 2021

Increasing numbers of satellites are orbiting through the Earth's radiation belts, and the range of orbits being commonly used is also growing. As a result, there is an increasing need for services to help protect satellites from space weather. The Satellite RIsk prediction and radiation Forecast (SaRIF) system provides reconstructions and forecasts of the high‐energy electron flux throughout the outer radiation belt and translates these predictions into charging currents, dose rates, total ionizing dose and risk indicators. SaRIF both informs satellite operators of current and expected conditions and provides a tool to aid in post‐event analysis. The reconstructions and forecasts are provided by the British Antarctic Survey Radiation Belt Model (BAS‐RBM) running as part of an automatic system using real‐time data to specify the boundary conditions and drive processes within the physics‐based model. If SaRIF is to provide a useful tool, then the accuracy of the reconstructions and forecasts needs to be understood. Here we assess the accuracy of the simulations for geostationary orbit by comparing the model output with measurements made by the GOES 14 spacecraft for the period March–September 2019. No GOES 14 data was used to create the reconstruction or forecasts. We show that, with some improvements to the original system, the reconstructions have a prediction efficiency of 0.82 for >800 keV electrons and 0.87 for >2 MeV electrons, with corresponding prediction efficiencies of 0.59 and 0.78 for the forecasts.
Age-related immune alterations and cerebrovascular inflammation
Authors: Finger Carson E. , Moreno-Gonzalez Ines , Gutierrez Antonia , Moruno-Manchon Jose Felix , McCullough Louise D.
Published: October 2021

Aging is associated with chronic systemic inflammation, which contributes to the development of many age-related diseases, including vascular disease. The world’s population is aging, leading to an increasing prevalence of both stroke and vascular dementia. The inflammatory response to ischemic stroke is critical to both stroke pathophysiology and recovery. Age is a predictor of poor outcomes after stroke. The immune response to stroke is altered in aged individuals, which contributes to the disparate outcomes between young and aged patients. In this review, we describe the current knowledge of the effects of aging on the immune system and the cerebral vasculature and how these changes alter the immune response to stroke and vascular dementia in animal and human studies. Potential implications of these age-related immune alterations on chronic inflammation in vascular disease outcome are highlighted.
Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity
Authors: Cherif Chaïma , Nguyen Dang Tan , Paris Clément , Le Thi Khanh , Sefiane Thibaud , Carbuccia Nadine , Finetti Pascal , Chaffanet Max , kaoutari Abdessamad El , Vernerey Julien , Fazli Ladan , Gleave Martin , Manai Mohamed , Barthélémy Philippe , Birnbaum Daniel , Bertucci François , Taïeb David , Rocchi Palma
Published: October 2021

Disease progression and therapeutic resistance of prostate cancer (PC) are linked to multiple molecular events that promote survival and plasticity. We previously showed that heat shock protein 27 (HSP27) acted as a driver of castration-resistant phenotype (CRPC) and developed an oligonucleotides antisense (ASO) against HSP27 with evidence of anti-cancer activity in men with CRPC. Here, we show that the tumor suppressor Menin (MEN1) is highly regulated by HSP27. Menin is overexpressed in high-grade PC and CRPC. High MEN1 mRNA expression is associated with decreased biochemical relapse-free and overall survival. Silencing Menin with ASO technology inhibits CRPC cell proliferation, tumor growth, and restores chemotherapeutic sensitivity. ChIP-seq analysis revealed differential DNA binding sites of Menin in various prostatic cells, suggesting a switch from tumor suppressor to oncogenic functions in CRPC. These data support the evaluation of ASO against Menin for CRPC.
Platelets in pediatric and neonatal sepsis: novel mediators of the inflammatory cascade
Authors: O’Reilly Daniel , Murphy Claire A. , Drew Richard , El-Khuffash Afif , Maguire Patricia B. , Ainle Fionnuala Ni , Mc Callion Naomi
Published: October 2021

Sepsis, a dysregulated host response to infection, has been difficult to accurately define in children. Despite a higher incidence, especially in neonates, a non-specific clinical presentation alongside a lack of verified biomarkers has prevented a common understanding of this condition. Platelets, traditionally regarded as mediators of haemostasis and thrombosis, are increasingly associated with functions in the immune system with involvement across the spectrum of innate and adaptive immunity. The large number of circulating platelets (approx. 150,000 cells per microlitre) mean they outnumber traditional immune cells and are often the first to encounter a pathogen at a site of injury. There are also well-described physiological differences between platelets in children and adults. The purpose of this review is to place into context the platelet and its role in immunology and examine the evidence where available for its role as an immune cell in childhood sepsis. It will examine how the platelet interacts with both humoral and cellular components of the immune system and finally discuss the role the platelet proteome, releasate and extracellular vesicles may play in childhood sepsis. This review also examines how platelet transfusions may interfere with the complex relationships between immune cells in infection.

Impact

Platelets are increasingly being recognised as important “first responders” to immune threats.

Differences in adult and paediatric platelets may contribute to differing immune response to infections.

Adult platelet transfusions may affect infant immune responses to inflammatory/infectious stimuli.
Regulatory T cells promote cancer immune-escape through integrin αvβ8-mediated TGF-β activation
Authors: Lainé Alexandra , Labiad Ossama , Hernandez-Vargas Hector , This Sébastien , Sanlaville Amélien , Léon Sophie , Dalle Stéphane , Sheppard Dean , Travis Mark A. , Paidassi Helena , Marie Julien C.
Published: October 2021

Presence of TGFβ in the tumor microenvironment is one of the most relevant cancer immune-escape mechanisms. TGFβ is secreted in an inactive form, and its activation within the tumor may depend on different cell types and mechanisms than its production. Here we show in mouse melanoma and breast cancer models that regulatory T (Treg) cells expressing the β8 chain of αvβ8 integrin (Itgβ8) are the main cell type in the tumors that activates TGFβ, produced by the cancer cells and stored in the tumor micro-environment. Itgβ8 ablation in Treg cells impairs TGFβ signalling in intra-tumoral T lymphocytes but not in the tumor draining lymph nodes. Successively, the effector function of tumor infiltrating CD8+ T lymphocytes strengthens, leading to efficient control of tumor growth. In cancer patients, anti-Itgβ8 antibody treatment elicits similar improved cytotoxic T cell activation. Thus, this study reveals that Treg cells work in concert with cancer cells to produce bioactive-TGFβ and to create an immunosuppressive micro-environment.
Microenvironmental IL-6 inhibits anti-cancer immune responses generated by cytotoxic chemotherapy
Authors: Bent Eric H. , Millán-Barea Luis R. , Zhuang Iris , Goulet Daniel R. , Fröse Julia , Hemann Michael T.
Published: October 2021

Cytotoxic chemotherapeutics primarily function through DNA damage-induced tumor cell apoptosis, although the inflammation provoked by these agents can stimulate anti-cancer immune responses. The mechanisms that control these distinct effects and limit immunogenic responses to DNA-damage mediated cell death in vivo are currently unclear. Using a mouse model of BCR-ABL+ B-cell acute lymphoblastic leukemia, we show that chemotherapy-induced anti-cancer immunity is suppressed by the tumor microenvironment through production of the cytokine IL-6. The chemotherapeutic doxorubicin is curative in IL-6-deficient mice through the induction of CD8+ T-cell-mediated anti-cancer responses, while moderately extending lifespan in wild type tumor-bearing mice. We also show that IL-6 suppresses the effectiveness of immune-checkpoint inhibition with anti-PD-L1 blockade. Our results suggest that IL-6 is a key regulator of anti-cancer immune responses induced by genotoxic stress and that its inhibition can switch cancer cell clearance from primarily apoptotic to immunogenic, promoting and maintaining durable anti-tumor immune responses.
BNT162b2 mRNA vaccine elicited antibody response in blood and milk of breastfeeding women
Authors: Rosenberg-Friedman Michal , Kigel Aya , Bahar Yael , Werbner Michal , Alter Joel , Yogev Yariv , Dror Yael , Lubetzky Ronit , Dessau Moshe , Gal-Tanamy Meital , Many Ariel , Wine Yariv
Published: October 2021

The importance of breastmilk in postnatal life lies in the strong association between breastfeeding and the reduction in the risk of infection and infection-related infant mortality. However, data regarding the induction and dynamics of breastmilk antibodies following administration of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine is scarce, as pregnant and lactating women were not included in the initial vaccine clinical trials. Here, we investigate the dynamics of the vaccine-specific antibody response in breastmilk and serum in a prospective cohort of ten lactating women who received two doses of the mRNA vaccine. We show that the antibody response is rapid and highly synchronized between breastmilk and serum, reaching stabilization 14 days after the second dose. The response in breastmilk includes both IgG and IgA with neutralization capacity.
Impact of intensifying nitrogen limitation on ocean net primary production is fingerprinted by nitrogen isotopes
Authors: Buchanan Pearse J. , Aumont Olivier , Bopp Laurent , Mahaffey Claire , Tagliabue Alessandro
Published: October 2021

The open ocean nitrogen cycle is being altered by increases in anthropogenic atmospheric nitrogen deposition and climate change. How the nitrogen cycle responds will determine long-term trends in net primary production (NPP) in the nitrogen-limited low latitude ocean, but is poorly constrained by uncertainty in how the source-sink balance will evolve. Here we show that intensifying nitrogen limitation of phytoplankton, associated with near-term reductions in NPP, causes detectable declines in nitrogen isotopes (δ15N) and constitutes the primary perturbation of the 21stcentury nitrogen cycle. Model experiments show that ~75% of the low latitude twilight zone develops anomalously low δ15N by 2060, predominantly due to the effects of climate change that alter ocean circulation, with implications for the nitrogen source-sink balance. Our results highlight that δ15N changes in the low latitude twilight zone may provide a useful constraint on emerging changes to nitrogen limitation and NPP over the 21stcentury.
Oncogene-mediated metabolic gene signature predicts breast cancer outcome
Authors: Aslan Merve , Hsu En-Chi , Garcia-Marques Fernando J. , Bermudez Abel , Liu Shiqin , Shen Michelle , West Meredith , Zhang Chiyuan Amy , Rice Meghan A. , Brooks James D. , West Robert , Pitteri Sharon J. , Győrffy Balázs , Stoyanova Tanya
Published: October 2021

Breast cancer remains the second most lethal cancer among women in the United States and triple-negative breast cancer is the most aggressive subtype with limited treatment options. Trop2, a cell membrane glycoprotein, is overexpressed in almost all epithelial cancers. In this study, we demonstrate that Trop2 is overexpressed in triple-negative breast cancer (TNBC), and downregulation of Trop2 delays TNBC cell and tumor growth supporting the oncogenic role of Trop2 in breast cancer. Through proteomic profiling, we discovered a metabolic signature comprised of TALDO1, GPI, LDHA, SHMT2, and ADK proteins that were downregulated in Trop2-depleted breast cancer tumors. The identified oncogene-mediated metabolic gene signature is significantly upregulated in TNBC patients across multiple RNA-expression clinical datasets. Our study further reveals that the metabolic gene signature reliably predicts poor survival of breast cancer patients with early stages of the disease. Taken together, our study identified a new five-gene metabolic signature as an accurate predictor of breast cancer outcome.
Mental health in people with Parkinson’s disease during the COVID-19 pandemic: potential for targeted interventions?
Authors: Dommershuijsen L. J. , Van der Heide A. , Van den Berg E. M. , Labrecque J. A. , Ikram M. K. , Ikram M. A. , Bloem B. R. , Helmich R. C. , Darweesh S. K. L.
Published: October 2021

The COVID-19 pandemic has introduced a myriad of challenges to the social life and care of people with Parkinson’s disease (PD), which could potentially worsen mental health problems. We used baseline data of the PRIME-NL study (N = 844) to examine whether the association between COVID-19 stressors and mental health is disproportionately large in specific subgroups of people with PD and to explore effects of hypothetical reductions in COVID-19 stressors on mental health and quality of life. The mean (SD) age of the study population was 70.3 (7.8) years and 321 (38.0%) were women. The linear regression effect estimate of the association of COVID-19 stressors with mental health was most pronounced in women, highly educated people, people with advanced PD and people prone to distancing or seeking social support. Smaller effect estimates were found in people scoring high on confrontive coping or planful problem solving. The parametric G-formula method was used to calculate the effects of hypothetical interventions on COVID-19 stressors. An intervention reducing stressors with 50% in people with above median MDS-UPDRS-II decreased the Beck Depression Inventory in this group from 14.7 to 10.6, the State-Trait Anxiety Inventory from 81.6 to 73.1 and the Parkinson’s Disease Quality of Life Questionnaire from 35.0 to 24.3. Insights from this cross-sectional study help to inform tailored care interventions to subgroups of people with PD most vulnerable to the impact of COVID-19 on mental health and quality of life.
The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial
Authors: Nassif Michael E. , Windsor Sheryl L. , Borlaug Barry A. , Kitzman Dalane W. , Shah Sanjiv J. , Tang Fengming , Khariton Yevgeniy , Malik Ali O. , Khumri Taiyeb , Umpierrez Guillermo , Lamba Sumant , Sharma Kavita , Khan Sadiya S. , Chandra Lokesh , Gordon Robert A. , Ryan John J. , Chaudhry Sunit-Preet , Joseph Susan M. , Chow Chen H. , Kanwar Manreet K. , Pursley Michael , Siraj Elias S. , Lewis Gregory D. , Clemson Barry S. , Fong Michael , Kosiborod Mikhail N.
Published: October 2021

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2,P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6,P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0,P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7,P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8,P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85,P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42,P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.
Downscaling SSP-consistent global spatial urban land projections from 1/8-degree to 1-km resolution 2000–2100
Authors: Gao Jing , Pesaresi Martino
Published: October 2021

Long-term, spatial urban land projections that simultaneously offer global coverage and local-scale empirical accuracy are rare. Recently a set of such projections was produced using data-science-based simulations and the Shared Socioeconomic Pathways (SSPs). These projections update at decadal time intervals from 2000 to 2100 with a spatial resolution of 1/8 degree, while many socio-environmental studies customarily run their analysis and modelling at finer spatial resolutions, e.g. 1-km. Here we develop and validate an algorithm to downscale the 1/8-degree spatial urban land projections to the 1-km resolution. The algorithm uses an iterative process to allocate the decadal amount of urban land expansion originally projected for each 1/8-degree grid to its constituent 1-km grids. The results are a set of global maps showing urban land fractions at the 1-km resolution, updated at decadal intervals from 2000 to 2100, under five different urban land expansion scenarios consistent with the SSPs. The data can support studies of potential interactions between future urbanization and environmental changes across spatial and temporal scales.
Lower-limb kinematics and kinetics during continuously varying human locomotion
Authors: Reznick Emma , Embry Kyle R. , Neuman Ross , Bolívar-Nieto Edgar , Fey Nicholas P. , Gregg Robert D.
Published: October 2021

Human locomotion involves continuously variable activities including walking, running, and stair climbing over a range of speeds and inclinations as well as sit-stand, walk-run, and walk-stairs transitions. Understanding the kinematics and kinetics of the lower limbs during continuously varying locomotion is fundamental to developing robotic prostheses and exoskeletons that assist in community ambulation. However, available datasets on human locomotion neglect transitions between activities and/or continuous variations in speed and inclination during these activities. This data paper reports a new dataset that includes the lower-limb kinematics and kinetics of ten able-bodied participants walking at multiple inclines (±0°; 5° and 10°) and speeds (0.8 m/s; 1 m/s; 1.2 m/s), running at multiple speeds (1.8 m/s; 2 m/s; 2.2 m/s and 2.4 m/s), walking and running with constant acceleration (±0.2; 0.5), and stair ascent/descent with multiple stair inclines (20°; 25°; 30° and 35°). This dataset also includes sit-stand transitions, walk-run transitions, and walk-stairs transitions. Data were recorded by a Vicon motion capture system and, for applicable tasks, a Bertec instrumented treadmill.
In vivo high-resolution structural MRI-based atlas of human thalamic nuclei
Authors: Saranathan Manojkumar , Iglehart Charles , Monti Martin , Tourdias Thomas , Rutt Brian
Published: October 2021

Thalamic nuclei play critical roles in regulation of neurological functions like sleep and wakefulness. They are increasingly implicated in neurodegenerative and neurological diseases such as multiple sclerosis and essential tremor. However, segmentation of thalamic nuclei is difficult due to their poor visibility in conventional MRI scans. Sophisticated methods have been proposed which require specialized MRI acquisitions and complex post processing. There are few high spatial resolution (1 mm3 or higher) in vivo MRI thalamic atlases available currently. The goal of this work is the development of an in vivo MRI-based structural thalamic atlas at 0.7 × 0.7 × 0.5 mm resolution based on manual segmentation of 9 healthy subjects using the Morel atlas as a guide. Using data analysis from healthy subjects as well as patients with multiple-sclerosis and essential tremor and at 3T and 7T MRI, we demonstrate the utility of this atlas to provide fast and accurate segmentation of thalamic nuclei when only conventional T1 weighted images are available.
A unifying view on extended phase graphs and Bloch simulations for quantitative MRI
Authors: Guenthner Christian , Amthor Thomas , Doneva Mariya , Kozerke Sebastian
Published: October 2021

Quantitative MRI methods and learning-based algorithms require exact forward simulations. One critical factor to correctly describe magnetization dynamics is the effect of slice-selective RF pulses. While contemporary simulation techniques correctly capture their influence, they only provide final magnetization distributions, require to be run for each parameter set separately, and make it hard to derive general theoretical conclusions and to generate a fundamental understanding of echo formation in the presence of slice-profile effects. This work aims to provide a mathematically exact framework, which is equally intuitive as extended phase graphs (EPGs), but also considers slice-profiles through their natural spatial representation. We show, through an analytical, hybrid Bloch-EPG formalism, that the spatially-resolved EPG approach allows to exactly predict the signal dependency on off-resonance, spoiling moment, microscopic dephasing, and echo time. We also demonstrate that our formalism allows to use the same phase graph to simulate both gradient-spoiled and balanced SSFP-based MR sequences. We present a derivation of the formalism and identify the connection to existing methods, i.e. slice-selective Bloch, slice-selective EPG, and the partitioned EPG. As a use case, the proposed hybrid Bloch-EPG framework is applied to MR Fingerprinting.
Automated caries detection in vivo using a 3D intraoral scanner
Authors: Michou Stavroula , Lambach Mathias S. , Ntovas Panagiotis , Benetti Ana R. , Bakhshandeh Azam , Rahiotis Christos , Ekstrand Kim R. , Vannahme Christoph
Published: October 2021

The use of 3D intraoral scanners (IOS) and software that can support automated detection and objective monitoring of oral diseases such as caries, tooth wear or periodontal diseases, is increasingly receiving attention from researchers and industry. This study clinically validates an automated caries scoring system for occlusal caries detection and classification, previously defined for an IOS system featuring fluorescence (TRIOS 4, 3Shape TRIOS A/S, Denmark). Four algorithms (ALG1, ALG2, ALG3, ALG4) are assessed for the IOS; the first three are based only on fluorescence information, while ALG4 also takes into account the tooth color information. The diagnostic performance of these automated algorithms is compared with the diagnostic performance of the clinical visual examination, while histological assessment is used as reference. Additionally, possible differences between in vitro and in vivo diagnostic performance of the IOS system are investigated. The algorithms show comparable in vivo diagnostic performance to the visual examination with no significant difference in the area under the ROC curves ($$p>0.05$$

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>
0.05

). Only minor differences between their in vitro and in vivo diagnostic performance are noted but no significant differences in the area under the ROC curves, ($$p>0.05$$

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>
0.05

). This novel IOS system exhibits encouraging performance for clinical application on occlusal caries detection and classification. Different approaches can be investigated for possible optimization of the system.
Twitter as an innovation process with damping effect
Authors: Aletti Giacomo , Crimaldi Irene
Published: October 2021

In the existing literature about innovation processes, the proposed models often satisfy the Heaps’ law, regarding the rate at which novelties appear, and the Zipf’s law, that states a power law behavior for the frequency distribution of the elements. However, there are empirical cases far from showing a pure power law behavior and such a deviation is mostly present for elements with high frequencies. We explain this phenomenon by means of a suitable “damping” effect in the probability of a repetition of an old element. We introduce an extremely general model, whose key element is the update function, that can be suitably chosen in order to reproduce the behaviour exhibited by the empirical data. In particular, we explicit the update function for some Twitter data sets and show great performances with respect to Heaps’ law and, above all, with respect to the fitting of the frequency-rank plots for low and high frequencies. Moreover, we also give other examples of update functions, that are able to reproduce the behaviors empirically observed in other contexts.
Identification of adipocytes as target cells for Leishmania infantum parasites
Authors: Schwing Aurélie , Pisani Didier F. , Pomares Christelle , Majoor Alissa , Lacas-Gervais Sandra , Jager Jennifer , Lemichez Emmanuel , Marty Pierre , Boyer Laurent , Michel Grégory
Published: October 2021

Leishmania infantum is the causative agent of visceral leishmaniasis transmitted by the bite of female sand flies. According to the WHO, the estimated annual incidence of leishmaniasis is one million new cases, resulting in 30,000 deaths per year. The recommended drugs for treating leishmaniasis include Amphotericin B. But over the course of the years, several cases of relapses have been documented. These relapses cast doubt on the efficiency of actual treatments and raise the question of potential persistence sites. Indeed, Leishmania has the ability to persist in humans for long periods of time and even after successful treatment. Several potential persistence sites have already been identified and named as safe targets. As adipose tissue has been proposed as a sanctuary of persistence for several pathogens, we investigated whether Leishmania infantum could be found in this tissue. We demonstrated both in cell cultures and in vivo that Leishmania infantum was able to infect adipocytes. Altogether our results suggest adipocytes as a ‘safe target’ for Leishmania infantum parasites.
Crustal velocity and interseismic strain-rate on possible zones for large earthquakes in the Garhwal–Kumaun Himalaya
Authors: Pappachen John P. , Sathiyaseelan Rajesh , Gautam Param K. , Pal Sanjit Kumar
Published: October 2021

The possibility of a major earthquake like 2015 Gorkha–Nepal or even greater is anticipated in the Garhwal–Kumaun region in the Central Seismic Gap of the NW Himalaya. The interseismic strain-rate from GPS derived crustal velocities show multifaceted strain-rate pattern in the region and are classified into four different strain-rate zones. Besides compressional, we identified two NE–SW orienting low strain rate (~ 20 nstrain/a) zones; namely, the Ramganga-Baijro and the Nainital-Almora, where large earthquakes can occur. These zones have surface locking widths of ~ 72 and ~ 75 km respectively from the Frontal to the Outer Lesser Himalaya, where no significant surface rupture and associated large earthquakes were observed for the last 100 years. However, strain reducing extensional deformation zone that appears sandwiched between the low strain-rate zones pose uncertainties on the occurences of large earthquakes in the locked zone. Nevertheless, such zone acts as a conduit to transfer strain from the compressional zone (> 100 nstrain/a) to the deforming frontal active fault systems. We also observed a curvilinear surface strain-rate pattern in the Chamoli cluster and explained how asymmetric crustal accommodation processes at the northwest and the southeast edges of the Almora Klippe, cause clockwise rotational couple on the upper crust moving over the MHT.
Recognition of post-learning alteration of hippocampal ripples by convolutional neural network differs in the wild-type and AD mice
Authors: Hsu Sheng-Yi , Jura Bartosz , Shih Mau-Hsiang , Meyrand Pierre , Tsai Feng-Sheng , Bem Tiaza
Published: October 2021

Evidence indicates that sharp-wave ripples (SWRs) are primary network events supporting memory processes. However, some studies demonstrate that even after disruption of awake SWRs the animal can still learn spatial task or that SWRs may be not necessary to establish a cognitive map of the environment. Moreover, we have found recently that despite a deficit of sleep SWRs the APP/PS1 mice, a model of Alzheimer’s disease, show undisturbed spatial reference memory. Searching for a learning-related alteration of SWRs that could account for the efficiency of memory in these mice we use convolutional neural networks (CNN) to discriminate pre- and post-learning 256 ms samples of LFP signals, containing individual SWRs. We found that the fraction of samples that were correctly recognized by CNN in majority of discrimination sessions was equal to ~ 50% in the wild-type (WT) and only 14% in APP/PS1 mice. Moreover, removing signals generated in a close vicinity of SWRs significantly diminished the number of such highly recognizable samples in the WT but not in APP/PS1 group. These results indicate that in WT animals a large subset of SWRs and signals generated in their proximity may contain learning-related information whereas such information seem to be limited in the AD mice.
Impact of total splenectomy on peripheral lymphocytes and their subsets in patients with hypersplenism associated with cirrhotic portal hypertension
Authors: Lv Yunfu , Wu Hongfei , Lau Wan Yee , Zheng Jinfang , Wu Jincai , Zeng Min
Published: October 2021

To study the impact of total splenectomy (TS) on peripheral lymphocytes and their subsets in patients with hypersplenism associated with cirrhotic portal hypertension (CPH). We studied 102 consecutive patients who received TS from January 2008 to January 2020 due to CPH-related hypersplenism. A similar number of healthy individuals are used as healthy controls (HC). The total lymphocyte counts and their percentages of B lymphocytes, total T lymphocytes (cluster of differentiation (CD)3+) and their subsets (CD4+, CD8+), and natural killer (NK) cells in preoperative peripheral blood samples in hypersplenism patients were significantly lower than that of the HCs (both P < 0.05). The total lymphocyte counts and percentages of B lymphocytes in peripheral blood were significantly increased 1 week and 1 month after TS when compared with the pre-TS values (P < 0.05). There was no significant difference in the percentages of NK cells before or after surgery (P > 0.05). However, the percentages of CD3+ cells was significantly higher 1 month after than before surgery (P < 0.001). The percentages of CD4+, and CD8+ T lymphocytes were significantly lower 1 week after surgery (P < 0.05), but they were significantly higher 1 month after surgery (P < 0.01). The CD4+:CD8+ ratio was not significantly different from those before surgery, and 1 week or 1 month after surgery (P > 0.05). Patients with hypersplenism associated with CPH were significantly immunosuppressed preoperatively. After TS, the total lymphocyte count and percentages of B lymphocytes, and total T lymphocytes and their subsets increased significantly, resulting in improved immune functions.
Intraspecific variation in thermal tolerance differs between tropical and temperate fishes
Authors: Nati J. J. H. , Svendsen M. B. S. , Marras S. , Killen S. S. , Steffensen J. F. , McKenzie D. J. , Domenici P.
Published: October 2021

How ectothermic animals will cope with global warming is a critical determinant of the ecological impacts of climate change. There has been extensive study of upper thermal tolerance limits among fish species but how intraspecific variation in tolerance may be affected by habitat characteristics and evolutionary history has not been considered. Intraspecific variation is a primary determinant of species vulnerability to climate change, with implications for global patterns of impacts of ongoing warming. Using published critical thermal maximum (CTmax) data on 203 fish species, we found that intraspecific variation in upper thermal tolerance varies according to a species’ latitude and evolutionary history. Overall, tropical species show a lower intraspecific variation in thermal tolerance than temperate species. Notably, freshwater tropical species have a lower variation in tolerance than freshwater temperate species, which implies increased vulnerability to impacts of thermal stress. The extent of variation in CTmax among fish species has a strong phylogenetic signal, which may indicate a constraint on evolvability to rising temperatures in tropical fishes. That is, in addition to living closer to their upper thermal limits, tropical species may have higher sensitivity and lower adaptability to global warming compared to temperate counterparts. This is evidence that freshwater tropical fish communities, worldwide, are especially vulnerable to ongoing climate change.
Directional motion of the foam carrying oils driven by the magnetic field
Authors: Dou Xiaoxiao , Chen Zhewen , Zuo Pingcheng , Cao Xiaojian , Liu Jianlin
Published: October 2021

Foams are substances widely used the foam flooding technology, which aim to greatly improve the residual oil recovery. In the present study, we perform a comprehensive investigation on the oil removal process driven by the foam embedded with magnetic particles, under the action of the magnetic force. The experiment shows that the addition of magnetic particles has little effect on the stability of the foam. During the motion of the foam, its maximum displacement and maximum acceleration are fully explored. Such factors as the volume of the foam, the volume of the oil droplet, the mass concentration of magnetic particles, and the Young’s contact angle of surfactant on solid are surveyed in detail. The function curves of the maximum displacement and the maximum acceleration with respect to these variables are obtained in the experiment, and the selection of some optimal parameters is advised. Moreover, the dimensional analysis has been conducted and several scaling laws are given, which are in agreement with the experimental results. These findings are beneficial to understand the oil displacement with the aid of magnetic field, which also provide some inspirations on drug delivery, robots and micro-fluidics.
Internal morphology of 101 mandibular canines of a Swiss-German population by means of micro-CT: An ex vivo study
Authors: Wolf Thomas Gerhard , Anderegg Andrea Lisa , Haberthür David , Khoma Oleksiy-Zakhar , Schumann Sven , Boemke Nane , Wierichs Richard Johannes , Hlushchuk Ruslan
Published: October 2021

The aim of this study was to investigate the root canal system morphology by means of a root canal configuration (RCC) classification described with a four-digit system, the physiological foramen geometry and accessory canal frequency and morphology, of 101 mandibular canines (MaCa) of a Swiss-German population by means of micro-computed tomography. Micro-CT examination of the MaCa was performed and the obtained images analyzed with a 3D imaging software. In single-rooted MaCas, the most frequently observed RCCs were 1-1-1/1 (74.5%) and 1-1-1/2 (14.3%). Seven other RCCs were less frequently observed with a frequency from 4.1 to 1.0%. One physiological foramen was observed in 80.6% of the MaCas, two in 16.3%, three in 1.0% and four in 2.0%. Accessory and connecting canals were apparent only in the middle and apical root thirds. Two-rooted MaCas occurred less frequently (n = 3). When one physiological foramen was present, the mean size of the narrow and wide diameters were 0.28 mm (± 0.07) and 0.40 mm (± 0.11), while the distance between physiological and anatomical foramen was 0.45 mm (± 0.17). MaCas are predominantly single-rooted teeth with a 1-1-1/1 or 1-1-1/2 RCC. Most MaCas had one physiological foramen with an oval shape.
Effect of vein-bionic surface textures on the tribological behavior of cylindrical roller thrust bearing under starved lubrication
Authors: Long Risheng , Zhao Chao , Zhang Yimin , Wang Yibing , Wang Yueyong
Published: October 2021

To reveal the effect of vein-bionic surface textures on the tribological behavior of cylindrical roller thrust bearings (CRTBs) under starved lubrication, six kinds of leaves (Forsythia, Clausena lansiu, Ash, Purple leaf plum, Pipal and Apricot) were chose and their simplified patterns were fabricated on the shaft washers of CRTBs using laser surface texturing. The coefficients of friction (COFs) of vein-bionic textured bearings were measured using a vertical universal wear test rig. Their mass losses and worn surfaces were also characterized. The results show that: There is important influence of the symmetry of vein-bionic textures and the number of secondary veins on the friction and wear properties of vein-bionic textured CRTBs under starved lubrication. Compared to the smooth group, the COFs and mass losses of vein-bionic textured bearings are all reduced. Among all groups, the tribological performance of bearings with a pattern inspired from Ash is the best. Its wear loss is reduced by 16.23% and its COF is reduced by 15.79%. This work would provide a valuable reference for the raceway design and optimization of roller rolling element bearings.
Intracellular oxygen metabolism during bovine oocyte and preimplantation embryo development
Authors: McKeegan Paul J. , Boardman Selina F. , Wanless Amy A. , Boyd Grace , Warwick Laura J. , Lu Jianping , Gnanaprabha Keerthi , Picton Helen M.
Published: October 2021

We report a novel method to profile intrcellular oxygen concentration (icO2) during in vitro mammalian oocyte and preimplantation embryo development using a commercially available multimodal phosphorescent nanosensor (MM2). Abattoir-derived bovine oocytes and embryos were incubated with MM2 in vitro. A series of inhibitors were applied during live-cell multiphoton imaging to record changes in icO2 associated with mitochondrial processes. The uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) uncouples mitochondrial oxygen consumption to its maximum, while antimycin inhibits complex III to ablate mitochondrial oxygen consumption. Increasing oxygen consumption was expected to reduce icO2 and decreasing oxygen consumption to increase icO2. Use of these inhibitors quantifies how much oxygen is consumed at basal in comparison to the upper and lower limits of mitochondrial function. icO2 measurements were compared to mitochondrial DNA copy number analysed by qPCR. Antimycin treatment increased icO2 for all stages tested, suggesting significant mitochondrial oxygen consumption at basal. icO2 of oocytes and preimplantation embryos were unaffected by FCCP treatment. Inner cell mass icO2 was lower than trophectoderm, perhaps reflecting limitations of diffusion. Mitochondrial DNA copy numbers were similar between stages in the range 0.9–4 × 106 copies and did not correlate with icO2. These results validate the MM2 probe as a sensitive, non-toxic probe of intracellular oxygen concentration in mammalian oocytes and preimplantation embryos.
Loss of hepatic Flcn protects against fibrosis and inflammation by activating autophagy pathways
Authors: Paquette Mathieu , Yan Ming , Ramírez-Reyes Josué M. J. , El-Houjeiri Leeanna , Biondini Marco , Dufour Catherine R. , Jeong Hyeonju , Pacis Alain , Giguère Vincent , Estall Jennifer L. , Siegel Peter M. , Audet-Walsh Étienne , Pause Arnim
Published: October 2021

Non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), which is characterized by triglyceride accumulation, inflammation, and fibrosis. No pharmacological agents are currently approved to treat these conditions, but it is clear now that modulation of lipid synthesis and autophagy are key biological mechanisms that could help reduce or prevent these liver diseases. The folliculin (FLCN) protein has been recently identified as a central regulatory node governing whole body energy homeostasis, and we hypothesized that FLCN regulates highly metabolic tissues like the liver. We thus generated a liver specific Flcn knockout mouse model to study its role in liver disease progression. Using the methionine- and choline-deficient diet to mimic liver fibrosis, we demonstrate that loss of Flcn reduced triglyceride accumulation, fibrosis, and inflammation in mice. In this aggressive liver disease setting, loss of Flcn led to activation of transcription factors TFEB and TFE3 to promote autophagy, promoting the degradation of intracellular lipid stores, ultimately resulting in reduced hepatocellular damage and inflammation. Hence, the activity of FLCN could be a promising target for small molecule drugs to treat liver fibrosis by specifically activating autophagy. Collectively, these results show an unexpected role for Flcn in fatty liver disease progression and highlight new potential treatment strategies.
Recent advances in asymmetric borylation by transition metal catalysis
Authors: Hu Jiefeng , Ferger Matthias , Shi Zhuangzhi , Marder Todd B.
Published: October 2021

We provide a comprehensive overview of transition metal-catalysed asymmetric borylation processes to construct C–B, C–C, and other C–heteroatom bonds with considerable attention devoted to the reaction modes and the mechanisms involved.
Chiral spiro phosphoric acid-catalysed enantioselective reaction of ketenes with N–H pyrroles
Authors: Wang Qian-Yi , Liu Teng-Fei , Chu Li-Feng , Yao Yun , Lu Chong-Dao
Published: October 2021

A chiral spiro phosphoric acid-catalyzed enantioselective reaction of ketenes with N–H pyrroles leads to enantioenriched C-acylated pyrroles bearing α-stereogenic carbon centres.
Atomistic explorations of mechanisms dictating the shear thinning behavior and 3D printability of graphene flake infused epoxy inks
Authors: Chava Bhargav Sai , Thorn Eva K. , Das Siddhartha
Published: October 2021

We employ equilibrium and non-equilibrium molecular dynamics (MD) simulations for respectively predicting the zero-shear viscosity and the mechanisms dictating the shear-thinning behavior of graphene flake infused epoxy ink.
IR spectroscopic characterization of the co-adsorption of CO2 and H2 onto cationic Cun+ clusters
Authors: Lushchikova Olga V. , Szalay Máté , Tahmasbi Hossein , Juurlink Ludo B. F. , Meyer Jörg , Höltzl Tibor , Bakker Joost M.
Published: October 2021

To understand elementary reaction steps in the hydrogenation of CO2 over copper-based catalysts, we experimentally study the adsorption of CO2 and H2 onto cationic Cun+ (n = 4–7) clusters.
Extension of van der Waals theory for supersaturated thin films
Authors: Aslyamov Timur , Akhatov Iskander
Published: October 2021

The vapor/liquid interface properties play an essential role in both fundamental models and practical applications.
First-principles study on multiferroicity in the Cr2Ge2Te6/In2Se3heterostructure influenced by finite strains
Authors: Hur Ji-Hyun
Published: October 2021

Atomic structure of the Cr2Ge2Te6/In2Se3van der Waals heterostructure. Magnetic anisotropic energies per Cr atom under both up- and down-ferroelectric polarization of In2Se3layer for different strain levels.
Bioaccessibility and bioavailability of bioactive compounds from yellow mustard flour and milk whey fermented with lactic acid bacteria
Authors: Escrivá L. , Manyes L. , Vila-Donat P. , Font G. , Meca G. , Lozano M.
Published: October 2021

Lactic acid bacteria fermentation enriched ingredients in bioactive compounds. Yellow mustard flour and milk whey are potential natural preservative ingredients to be used in the baking industry, especially when fermented with lactic acid bacteria.
Rice varieties with a high endosperm lipid content have reduced starch digestibility and increased γ-oryzanol bioaccessibility
Authors: Shen Yi , Wu Dianxing , Fogliano Vincenzo , Pellegrini Nicoletta
Published: October 2021

The amount and distribution of rice endosperm lipids can influence starch digestibility and nutritional properties of white rice.
Plastics to fertilizers: chemical recycling of a bio-based polycarbonate as a fertilizer source
Authors: Abe Takumi , Takashima Rikito , Kamiya Takehiro , Foong Choon Pin , Numata Keiji , Aoki Daisuke , Otsuka Hideyuki
Published: October 2021

A polymer is used as a source of fertilizer. To demonstrate the viability of this concept, the chemical recycling of poly(isosorbide carbonate) (PIC) is presented as a model for the next generation of plastic-recycling systems.
The critical role of anions in the porous biochar structure and potassium release during the potassium-assisted pyrolysis process
Authors: Xia Mingwei , Chen Wei , Wu Jing , Chen Yingquan , Yang Haiping , Chen Xu , Zhu Danchen , Chen Hanping
Published: October 2021

Anions of potassium additives have a great influence on the structure of porous biochar and potassium release during the biomass pyrolysis process.
Cordyline fruticosa(L.) A. Chev. leaves: isolation, HPLC/MS profiling and evaluation of nephroprotective and hepatoprotective activities supported by molecular docking
Authors: Raslan Mona A. , F. Taher Rehab , Al-Karmalawy Ahmed A. , El-Ebeedy Dalia , Metwaly Angham G. , Elkateeb Nourhan M. , Ghanem Aml , Elghaish Reem A. , Abd El Maksoud Ahmed I.
Published: October 2021

The metabolites profile ofC. fruticosa(L.) A. Chev. leaves, 12 isolates, and its nephroprotective and hepatoprotective activities are described.