bluuebunny/crossref_metadata_2025 huggingface dataset:
The Internal Structure and Dynamics of Jupiter Unveiled by a High‐Resolution Magnetic Field and Secular Variation Model
Authors: Sharan S. , Langlais B. , Amit H. , Thébault E. , Pinceloup M. , Verhoeven O.
Published: August 2022

Unique information about the dynamo process acting at Jupiter can be inferred by modeling and interpreting its magnetic field. Using the fluxgate magnetometer measurements acquired during the 4 years of the Juno mission, we derive a magnetic field model which describes simultaneously the main field and the secular variation (SV) up to spherical harmonic degrees 16 and 8, respectively. Apart from the Earth's, this is the first time another planetary magnetic field along with its time variation is described to such a high degree. We use properties of the power spectrum of the static field to infer the upper boundary of the dynamo convective region at 0.830 ± 0.022 Jupiter radius. The SV and correlation times are relatively comparable to the Earth's and indicate that the field is dominated by advection. The field and SV morphologies suggest zonal as well as non‐zonal deep fluid motions.
Numerical Modeling of Tsunami‐Generated Acoustic‐Gravity Waves in Mesopause Airglow
Authors: Inchin P. A. , Heale C. J. , Snively J. B. , Zettergren M. D.
Published: August 2022

Numerical simulations of mesopause airglow (MA) fluctuations induced by tsunami‐generated acoustic and gravity waves (TAGWs) are performed. Simulated tsunamis over realistic bathymetry are used to excite atmospheric waves at the surface level of a three‐dimensional nonlinear and compressible neutral atmospheric model. The model incorporates the dynamics and chemistry of hydroxyl OH(3,1) MA under nighttime assumptions. We report case study results of eight recent large tsunami events and demonstrate that TAGW‐induced MA fluctuations are readily detectable with modern ground‐ and space‐based imagers, and may provide quantitative insight. The amplitudes of MA fluctuations reflect the evolution of ocean surface displacements, enhancing or decreasing accordingly, and revealing the tsunami's lobes and local wave focusing. The results suggest that MA observations have potential to supplement early‐warning systems, providing information on spatial and temporal evolution of tsunami waves of ∼10 cm and higher for the cases shown. They may find applications in tsunami tracking over large open ocean areas, as well as in the investigation or reconstruction of tsunami source characteristics.
Rotational Extension Promotes Coeval Upper Crustal Brittle Faulting and Deep‐Seated Rift‐Axis Parallel Flow: Dynamic Coupling Processes Inferred From Analog Model Experiments
Authors: Schmid Timothy Chris , Schreurs Guido , Adam Jürgen
Published: August 2022

The lower parts of warm, thick continental crust can flow in a ductile fashion to accommodate thinning of the upper brittle crust during extension. Naturally occurring continental rifts with a rift‐axis parallel deformation gradient imply an underlying rotational component. In such settings, rift‐parallel crustal flow transports material perpendicular to the direction of rifting. We use analog experiments to investigate rotational rifting and coeval crustal flow. To test the effect of rift‐axis parallel flow on rift evolution, we use different gravitational loads resulting in a range of horizontal pressure gradient magnitudes which drive horizontal lower‐crustal flow. The use of (three dimensional) 3D Digital Volume Correlation techniques on X‐ray CT data combined with 3D Digital Image Correlation techniques applied to topographic stereo images provides detailed insights on the contemporaneous evolution of ductile flow patterns and brittle rift structures, respectively. Our results depict a complex flow field in the ductile lower crust during rotational rifting with: (a) extension‐parallel horizontal inward flow and vertical upward flow that compensates thinning of the brittle upper crustal layer; (b) rift‐axis parallel lateral flow, that compensates greater amounts of thinning further away from the rotation axis; and (c) different degrees of mechanical coupling between the brittle and viscous layers that change during rift propagation. Our analog experiments provide insights into ductile lower crustal flow patterns during rift evolution. The results emphasize the three dimensionality of rifting, which is an important effect that should be considered when estimating the amount of crustal extension from two dimensional (2D) cross sections.
Application of Machine Learning to Characterizing Magma Fertility in Porphyry Cu Deposits
Authors: Zou Shaohao , Chen Xilian , Brzozowski Matthew J. , Leng Cheng‐Biao , Xu Deru
Published: August 2022

Large and easily accessible porphyry Cu deposits have already been identified, exploited, and gradually exhausted. Novel strategies, therefore, are required to identify new, deeply buried deposits. Previous studies have proposed several lithogeochemical and mineralogical approaches for identifying porphyry Cu systems. Most of these methods, however, require significant a priori knowledge of the exploration region and are, generally, of low effectiveness. In this study, machine learning models using Random Forest and Deep Neural Network algorithms are utilized to characterize magma fertility. The two models have first been trained using a large trace‐element data set of magmatic zircon and then validated on unseen data set during the training process. The performance of both models was evaluated using a fivefold cross‐validation technique, which demonstrates that the models provide consistent results and yield good classification accuracy (∼90% on average) with low false positive rates. Feature importance analysis of the models suggests that Eu/Eu*, Eu/Eu*/Y, Ce/Nd, Ce/Ce*, Dy, Hf, and Ti are the important parameters that distinguish fertile and barren zircons. The real‐world applicability of the validated models was evaluated using two well‐characterized porphyry Cu deposits in subduction and postcollisional settings—the Highland Valley porphyry Cu district (south‐central British Columbia, Canada) and the southern Gangdese belt (Tibet, China), respectively. The results demonstrate that our generalized models can discriminate zircon from igneous rocks associated with porphyry Cu deposits from those in nonmineralized systems with high accuracy and independent of geological setting, suggesting that this new approach can be used effectively in greenfield and brownfield exploration.
Vapor Bubbles and Velocity Control on the Cooling Rates of Lava and Pyroclasts During Submarine Eruptions
Authors: Moitra Pranabendu , Sonder Ingo
Published: August 2022

Investigating the conditions behind the formation of pyroclast textures and lava flow morphologies is important to understand the dynamics of submarine volcanic eruptions, which are hard to observe. The development of clast textures and lava morphologies depends on the competing effects of their eruption rates and the rates of solidification. While eruption rates are governed by subsurface magmatic processes, the solidification timescales depend on the rate of heat loss from lava to the external water. However, the effect of the speed of lava flow or clast on their solidification timescales under two‐phase (liquid water and vapor bubbles) water boiling conditions is poorly constrained. Using laboratory experiments with remelted igneous rocks, we investigate the effect of the relative motion between lava and external water on its cooling timescale. We use a range of water speed (0–12.5 cm s−1) in our experiments while keeping our sample stationary to simulate a range of relative speed between lava and ambient water. Using transient heat transfer modeling, we find that heat flux from the surface of the sample to the external water overall increases with increasing water speed. We find heat transfer coefficients of up to ∼1.72 × 103 W m−2 K−1. The implications of high heat flux on the formation of solid lava crust under submarine conditions are discussed.
Scientists get a closer look at mechanism of Deep Bolivian Quake
Authors: Wakefield Julie
Published: August 2022

While big earthquakes typically wreack havoc for humankind, the biggest deep earthquake ever recorded—the magnitude 8.3 event that occurred 637 km beneath the surface of Bolivia on June 9, 1994—has brought enlightenment—of sorts.

Instead of bringing death and destruction, the recent Bolivian quake, the largest quake of any type in recent decades, has given scientists one of the best probes yet of the Earth's interior. Within several minutes of the deep rupture, the quake benignly shook the ground from Argentina to Canada. But more important, the quake shook the Earth like a bell for months thereafter, giving scientists a raw data set of the planet's free oscillations—like none other.
Macrophages in obesity are characterised by increased IL-1β response to calcium-sensing receptor signals
Authors: Thrum Stephan , Sommer Miriam , Raulien Nora , Gericke Martin , Massier Lucas , Kovacs Peter , Krasselt Marco , Landgraf Kathrin , Körner Antje , Dietrich Arne , Blüher Matthias , Rossol Manuela , Wagner Ulf
Published: August 2022

Objective

Obesity is complicated by inflammatory activation of the innate immune system. Stimulation of the calcium-sensing receptor (CaSR) by extra-cellular calcium ions ([Ca2+]ex) can trigger NLRP3 inflammasome activation and inflammation. We hypothesised, that this mechanism might contribute to the activation of adipose tissue (AT) in obesity, and investigated [Ca2+]ex-induced, CaSR mediated IL-1β release by macrophages in obesity.

Methods

[Ca2+]ex-induced IL-1β release was investigated in monocyte-derived macrophages (MDM) generated from peripheral blood of patients with obesity and from normal-weight controls. Visceral and subcutaneous AT biosamples were stimulated with [Ca2+]ex, and IL-1β release, as well as expression of NLRP3 inflammasome and cytokine genes, was determined.

Results

Both MDM and AT readily responded with concentration-dependent IL-1β release already at low, near physiological concentrations to addition of [Ca2+]ex, which was more than 80 fold higher than the LPS-induced effect. IL-1β levels induced by [Ca2+]ex were significantly higher not only in MDM from patients with obesity compared to controls, but also in visceral versus subcutaneous AT. This fat-depot difference was also reflected by mRNA expression levels of inflammasome and cytokine genes.

Conclusions

Obesity renders macrophages more susceptible to [Ca2+]ex-induced IL-1β release and pyroptosis. Increased susceptibility was independent of the response to LPS and circulating CRP arguing against mere pro-inflammatory pre-activation of monocytes. Instead, we propose that CaSR mediated signalling is relevant for the deleterious innate immune activation in obesity.
Liquid crystal-based structural color actuators
Authors: Zhang Pei , de Haan Laurens T. , Debije Michael G. , Schenning Albert P. H. J.
Published: August 2022

Animals can modify their body shape and/or color for protection, camouflage and communication. This adaptability has inspired fabrication of actuators with structural color changes to endow soft robots with additional functionalities. Using liquid crystal-based materials for actuators with structural color changes is a promising approach. In this review, we discuss the current state of liquid crystal-based actuators with structural color changes and the potential applications of these structural color actuators in soft robotic devices.
Association between ADHD and vision problems. A systematic review and meta-analysis
Authors: Bellato Alessio , Perna John , Ganapathy Preethi S. , Solmi Marco , Zampieri Andrea , Cortese Samuele , Faraone Stephen V.
Published: August 2022

Aim

To conduct the first systematic review and meta-analysis assessing whether attention-deficit/hyperactivity disorder (ADHD) is associated with disorders of the eye, and/or altered measures of visual function.

Method

Based on a pre-registered protocol (PROSPERO: CRD42021256352), we searched PubMed, Web of Knowledge/Science, Ovid Medline, Embase and APA PsycINFO up to 16th November 2021, with no language/type of document restrictions. We included observational studies reporting at least one measure of vision in people of any age meeting DSM/ICD criteria for ADHD and in people without ADHD; or the prevalence of ADHD in people with and without vision disorders. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Random effects meta-analyses were used for data synthesis.

Results

We included 42 studies in the narrative synthesis and 35 studies in the meta-analyses (3,250,905 participants). We found meta-analytic evidence of increased risk of astigmatism (OR = 1.79 [CI: 1.50, 2.14]), hyperopia and hypermetropia (OR = 1.79 [CI: 1.66, 1.94]), strabismus (OR = 1.93 [CI: 1.75, 2.12]), unspecified vision problems (OR = 1.94 [CI: 1.38, 2.73]) and reduced near point of convergence (OR = 5.02 [CI: 1.78, 14.11]); increased lag (Hedge’s g = 0.63 [CI: 0.30, 0.96]) and variability (Hedge’s g = 0.40 [CI: 0.17, 0.64]) of the accommodative response; and increased self-reported vision problems (Hedge’s g = 0.63 [CI: 0.44, 0.82]) in people with ADHD compared to those without ADHD (with no significant heterogeneity). We also found meta-analytic evidence of no differences between people with and without ADHD on retinal nerve fiber layer thickness (Hedge’s g = −0.19 [CI: −0.41, 0.02]) and refractive error (Hedge’s g = 0.08 [CI: −0.26, 0.42]) (with no significant heterogeneity).

Discussion

ADHD is associated with some self-reported and objectively ascertained functional vision problems, but not with structural alterations of the eye. Further studies should clarify the causal relationship, if any, between ADHD and problems of vision.

Trial registration

PROSPERO registration: CRD42021256352.
Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances BCAA metabolism in type 2 diabetes
Authors: Vanweert Froukje , Schrauwen Patrick , Phielix Esther
Published: August 2022

Branched-chain amino acid (BCAA) catabolism has been considered to have an emerging role in the pathogenesis of metabolic disturbances in obesity and type 2 diabetes (T2D). Several studies showed elevated plasma BCAA levels in humans with insulin resistance and patients with T2D, although the underlying reason is unknown. Dysfunctional BCAA catabolism could theoretically be an underlying factor. In vitro and animal work collectively show that modulation of the BCAA catabolic pathway alters key metabolic processes affecting glucose homeostasis, although an integrated understanding of tissue-specific BCAA catabolism remains largely unknown, especially in humans. Proof-of-concept studies in rodents -and to a lesser extent in humans – strongly suggest that enhancing BCAA catabolism improves glucose homeostasis in metabolic disorders, such as obesity and T2D. In this review, we discuss several hypothesized mechanistic links between BCAA catabolism and insulin resistance and overview current available tools to modulate BCAA catabolism in vivo. Furthermore, this review considers whether enhancing BCAA catabolism forms a potential future treatment strategy to promote metabolic health in insulin resistance and T2D.
Interpretable machine learning-derived nomogram model for early detection of diabetic retinopathy in type 2 diabetes mellitus: a widely targeted metabolomics study
Authors: Li Jushuang , Guo Chengnan , Wang Tao , Xu Yixi , Peng Fang , Zhao Shuzhen , Li Huihui , Jin Dongzhen , Xia Zhezheng , Che Mingzhu , Zuo Jingjing , Zheng Chao , Hu Honglin , Mao Guangyun
Published: August 2022

Objective

Early identification of diabetic retinopathy (DR) is key to prioritizing therapy and preventing permanent blindness. This study aims to propose a machine learning model for DR early diagnosis using metabolomics and clinical indicators.

Methods

From 2017 to 2018, 950 participants were enrolled from two affiliated hospitals of Wenzhou Medical University and Anhui Medical University. A total of 69 matched blocks including healthy volunteers, type 2 diabetes, and DR patients were obtained from a propensity score matching-based metabolomics study. UPLC-ESI-MS/MS system was utilized for serum metabolic fingerprint data. CART decision trees (DT) were used to identify the potential biomarkers. Finally, the nomogram model was developed using the multivariable conditional logistic regression models. The calibration curve, Hosmer–Lemeshow test, receiver operating characteristic curve, and decision curve analysis were applied to evaluate the performance of this predictive model.

Results

The mean age of enrolled subjects was 56.7 years with a standard deviation of 9.2, and 61.4% were males. Based on the DT model, 2-pyrrolidone completely separated healthy controls from diabetic patients, and thiamine triphosphate (ThTP) might be a principal metabolite for DR detection. The developed nomogram model (including diabetes duration, systolic blood pressure and ThTP) shows an excellent quality of classification, with AUCs (95% CI) of 0.99 (0.97–1.00) and 0.99 (0.95–1.00) in training and testing sets, respectively. Furthermore, the predictive model also has a reasonable degree of calibration.

Conclusions

The nomogram presents an accurate and favorable prediction for DR detection. Further research with larger study populations is needed to confirm our findings.
CYP2C19 expression modulates affective functioning and hippocampal subiculum volume—a large single-center community-dwelling cohort study
Authors: Grosu Claire , Trofimova Olga , Gholam-Rezaee Mehdi , Strippoli Marie-Pierre F. , Kherif Ferath , Lutti Antoine , Preisig Martin , Draganski Bogdan , Eap Chin B.
Published: August 2022

Given controversial findings of reduced depressive symptom severity and increased hippocampus volume in CYP2C19 poor metabolizers, we sought to provide empirical evidence from a large-scale single-center longitudinal cohort in the community-dwelling adult population—Colaus|PsyCoLaus in Lausanne, Switzerland (n = 4152). We looked forCYP2C19genotype-related behavioral and brain anatomy patterns using a comprehensive set of psychometry, water diffusion- and relaxometry-based magnetic resonance imaging (MRI) data (BrainLaus,n = 1187). Our statistical models tested for differential associations between poor metabolizer and other metabolizer status with imaging-derived indices of brain volume and tissue properties that explain individuals’ current and lifetime mood characteristics. The observed association betweenCYP2C19genotype and lifetime affective status showing higher functioning scores in poor metabolizers, was mainly driven by female participants (ß = 3.9,p = 0.010). There was no difference in total hippocampus volume between poor metabolizer and other metabolizer, though there was higher subiculum volume in the right hippocampus of poor metabolizers (ß = 0.03,pFDRcorrected = 0.036). Our study supports the notion of association between mood phenotype andCYP2C19genotype, however, finds no evidence for concomitant hippocampus volume differences, with the exception of the right subiculum.
Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression
Authors: Varela-Eirín Marta , Carpintero-Fernández Paula , Guitián-Caamaño Amanda , Varela-Vázquez Adrián , García-Yuste Alejandro , Sánchez-Temprano Agustín , Bravo-López Susana B. , Yañez-Cabanas José , Fonseca Eduardo , Largo Raquel , Mobasheri Ali , Caeiro José Ramón , Mayán María D.
Published: August 2022

The accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related diseases such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin 43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage. OA has been reclassified as a musculoskeletal disease characterized by the breakdown of the articular cartilage affecting the whole joint, subchondral bone, synovium, ligaments, tendons and muscles. However, the mechanisms that contribute to the spread of pathogenic factors throughout the joint tissues are still unknown. Here, we show for the first time that small extracellular vesicles (sEVs) released by human OA-derived chondrocytes contain high levels of Cx43 and induce a senescent phenotype in targeted chondrocytes, synovial and bone cells contributing to the formation of an inflammatory and degenerative joint environment by the secretion of senescence-associated secretory associated phenotype (SASP) molecules, including IL-1ß and IL-6 and MMPs. The enrichment of Cx43 changes the protein profile and activity of the secreted sEVs. Our results indicate a dual role for sEVs containing Cx43 inducing senescence and activating cellular plasticity in target cells mediated by NF-kß and the extracellular signal-regulated kinase 1/2 (ERK1/2), inducing epithelial-to-mesenchymal transition (EMT) signalling programme and contributing to the loss of the fully differentiated phenotype. Our results demonstrated that Cx43-sEVs released by OA-derived chondrocytes spread senescence, inflammation and reprogramming factors involved in wound healing failure to neighbouring tissues, contributing to the progression of the disease among cartilage, synovium, and bone and probably from one joint to another. These results highlight the importance for future studies to consider sEVs positive for Cx43 as a new biomarker of disease progression and new target to treat OA.
The deubiquitinase USP7 promotes HNSCC progression via deubiquitinating and stabilizing TAZ
Authors: Li Jin , Dai Yibin , Ge Han , Guo Songsong , Zhang Wei , Wang Yanling , Liu Laikui , Cheng Jie , Jiang Hongbing
Published: August 2022

Dysregulated abundance, location and transcriptional output of Hippo signaling effector TAZ have been increasingly linked to human cancers including head neck squamous cell carcinoma (HNSCC). TAZ is subjected to ubiquitination and degradation mediated by E3 ligase β-TRCP. However, the deubiquitinating enzymes and mechanisms responsible for its protein stability remain underexplored. Here, we exploited customized deubiquitinases siRNA and cDNA library screen strategies and identified USP7 as a bona fide TAZ deubiquitinase in HNSCC. USP7 promoted cell proliferation, migration, invasion in vitro and tumor growth by stabilizing TAZ. Mechanistically, USP7 interacted with, deubiquitinated and stabilized TAZ by selectively removing its K48-linked ubiquitination chain independent of canonical Hippo kinase cascade. USP7 potently antagonized β-TRCP-mediated ubiquitin-proteasomal degradation of TAZ and enhanced its nuclear retention and transcriptional output. Importantly, overexpression of USP7 correlated with TAZ upregulation, tumor aggressiveness and unfavorable prognosis in HNSCC patients. Pharmacological inhibition of USP7 significantly suppressed tumor growth in both xenograft and PDX models. Collectively, these findings identify USP7 as an essential regulator of TAZ and define USP7-TAZ signaling axis as a novel biomarker and potential therapeutic target for HNSCC.
Regulatory T cells in skeletal muscle repair and regeneration: recent insights
Authors: Wu Jianhui , Ren Bowen , Wang Daochao , Lin Hui
Published: August 2022

Skeletal muscle repair and regeneration after injury is a multi-stage process, involving a dynamic inflammatory microenvironment consisting of a complex network formed by the interaction of immune cells and their secreted cytokines. The homeostasis of the inflammatory microenvironment determines whether skeletal muscle repair tissues will ultimately form scar tissue or regenerative tissue. Regulatory T cells (Tregs) regulate homeostasis within the immune system and self-immune tolerance, and play a crucial role in skeletal muscle repair and regeneration. Dysregulated Tregs function leads to abnormal repair. In this review, we discuss the role and mechanisms of Tregs in skeletal muscle repair and regeneration after injury and provide new strategies for Treg immunotherapy in skeletal muscle diseases.
Sign-tunable anisotropic magnetoresistance and electrically detectable dual magnetic phases in a helical antiferromagnet
Authors: Kim Jong Hyuk , Shin Hyun Jun , Kim Mi Kyung , Hong Jae Min , Jeong Ki Won , Kim Jin Seok , Moon Kyungsun , Lee Nara , Choi Young Jai
Published: August 2022

Emerging from competing exchange interactions, the helimagnetic order describes a noncollinear spin texture of antiferromagnets. Although collinear antiferromagnets act as the elemental building blocks of antiferromagnetic (AFM) spintronics, until now, the potential of implementing spintronic functionality in noncollinear antiferromagnets has not been clarified. Here, we propose an AFM helimagnet of EuCo2As2 as a novel single-phase spintronic material that exhibits a remarkable sign reversal of anisotropic magnetoresistance (AMR). The contrast in the AMR arises from two electrically distinctive magnetic phases with spin reorientation that is driven by the magnetic field prevailing in the easy plane, which converts the AMR from positive to negative. Furthermore, based on an easy-plane anisotropic spin model, we theoretically identified various AFM memory states associated with the evolution of the spin structure under magnetic fields. The results revealed the potential of noncollinear antiferromagnets for application in the development of spintronic devices.
Structure of SARS-CoV-2 membrane protein essential for virus assembly
Authors: Zhang Zhikuan , Nomura Norimichi , Muramoto Yukiko , Ekimoto Toru , Uemura Tomoko , Liu Kehong , Yui Moeko , Kono Nozomu , Aoki Junken , Ikeguchi Mitsunori , Noda Takeshi , Iwata So , Ohto Umeharu , Shimizu Toshiyuki
Published: August 2022

The coronavirus membrane protein (M) is the most abundant viral structural protein and plays a central role in virus assembly and morphogenesis. However, the process of M protein-driven virus assembly are largely unknown. Here, we report the cryo-electron microscopy structure of the SARS-CoV-2 M protein in two different conformations. M protein forms a mushroom-shaped dimer, composed of two transmembrane domain-swapped three-helix bundles and two intravirion domains. M protein further assembles into higher-order oligomers. A highly conserved hinge region is key for conformational changes. The M protein dimer is unexpectedly similar to SARS-CoV-2 ORF3a, a viral ion channel. Moreover, the interaction analyses of M protein with nucleocapsid protein (N) and RNA suggest that the M protein mediates the concerted recruitment of these components through the positively charged intravirion domain. Our data shed light on the M protein-driven virus assembly mechanism and provide a structural basis for therapeutic intervention targeting M protein.
Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells
Authors: Tan Yuying , Li Junjie , Zhao Guangyuan , Huang Kai-Chih , Cardenas Horacio , Wang Yinu , Matei Daniela , Cheng Ji-Xin
Published: August 2022

Increased glycolysis is considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during therapeutic resistance development is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we find that cisplatin-resistant cells exhibit increased fatty acids (FA) uptake, accompanied by decreased glucose uptake and lipogenesis, indicating reprogramming from glucose to FA dependent anabolic and energy metabolism. A metabolic index incorporating glucose derived anabolism and FA uptake correlates linearly to the level of cisplatin resistance in ovarian cancer (OC) cell lines and primary cells. The increased FA uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing beta-oxidation. Consequently, blocking beta-oxidation by a small molecule inhibitor combined with cisplatin or carboplatin synergistically suppresses OC proliferation in vitro and growth of patient-derived xenografts in vivo. Collectively, these findings support a rapid detection method of cisplatin-resistance at single cell level and a strategy for treating cisplatin-resistant tumors.
Multistep orthophosphate release tunes actomyosin energy transduction
Authors: Moretto Luisa , Ušaj Marko , Matusovsky Oleg , Rassier Dilson E. , Friedman Ran , Månsson Alf
Published: August 2022

Muscle contraction and a range of critical cellular functions rely on force-producing interactions between myosin motors and actin filaments, powered by turnover of adenosine triphosphate (ATP). The relationship between release of the ATP hydrolysis product ortophosphate (Pi) from the myosin active site and the force-generating structural change, the power-stroke, remains enigmatic despite its central role in energy transduction. Here, we present a model with multistep Pi-release that unifies current conflicting views while also revealing additional complexities of potential functional importance. The model is based on our evidence from kinetics, molecular modelling and single molecule fluorescence studies of Pi binding outside the active site. It is also consistent with high-speed atomic force microscopy movies of single myosin II molecules without Pi at the active site, showing consecutive snapshots of pre- and post-power stroke conformations. In addition to revealing critical features of energy transduction by actomyosin, the results suggest enzymatic mechanisms of potentially general relevance.
Superelastic graphene aerogel-based metamaterials
Authors: Wu Mingmao , Geng Hongya , Hu Yajie , Ma Hongyun , Yang Ce , Chen Hongwu , Wen Yeye , Cheng Huhu , Li Chun , Liu Feng , Jiang Lan , Qu Liangti
Published: August 2022

Ultralight, ultrastrong, and supertough graphene aerogel metamaterials combining with multi-functionalities are promising for future military and domestic applications. However, the unsatisfactory mechanical performances and lack of the multiscale structural regulation still impede the development of graphene aerogels. Herein, we demonstrate a laser-engraving strategy toward graphene meta-aerogels (GmAs) with unusual characters. As the prerequisite, the nanofiber-reinforced networks convert the graphene walls’ deformation from the microscopic buckling to the bulk deformation during the compression process, ensuring the highly elastic, robust, and stiff nature. Accordingly, laser-engraving enables arbitrary regulation on the macro-configurations of GmAs with rich geometries and appealing characteristics such as large stretchability of 5400% reversible elongation, ultralight specific weight as small as 0.1 mg cm−3, and ultrawide Poisson’s ratio range from −0.95 to 1.64. Additionally, incorporating specific components into the pre-designed meta-structures could further achieve diversified functionalities.
Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers
Authors: Van Nyen Tom , Planque Mélanie , van Wagensveld Lilian , Duarte Joao A. G. , Zaal Esther A. , Talebi Ali , Rossi Matteo , Körner Pierre-René , Rizzotto Lara , Moens Stijn , De Wispelaere Wout , Baiden-Amissah Regina E. M. , Sonke Gabe S. , Horlings Hugo M. , Eelen Guy , Berardi Emanuele , Swinnen Johannes V. , Berkers Celia R. , Carmeliet Peter , Lambrechts Diether , Davidson Ben , Agami Reuven , Fendt Sarah-Maria , Annibali Daniela , Amant Frédéric
Published: August 2022

Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12–15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the lack of clinical applicability limits exploitation of many potential targets, leaving patients with limited options. Serine biosynthesis has been linked to cancer growth and poor prognosis in various cancer types, however its role in platinum-resistant ovarian cancer is not known. Here, we show that a subgroup of resistant tumors decreases phosphoglycerate dehydrogenase (PHGDH) expression at relapse after platinum-based chemotherapy. Mechanistically, we observe that this phenomenon is accompanied by a specific oxidized nicotinamide adenine dinucleotide (NAD+) regenerating phenotype, which helps tumor cells in sustaining Poly (ADP-ribose) polymerase (PARP) activity under platinum treatment. Our findings reveal metabolic vulnerabilities with clinical implications for a subset of platinum resistant ovarian cancers.
Fractional neural sampling as a theory of spatiotemporal probabilistic computations in neural circuits
Authors: Qi Yang , Gong Pulin
Published: August 2022

A range of perceptual and cognitive processes have been characterized from the perspective of probabilistic representations and inference. To understand the neural circuit mechanism underlying these probabilistic computations, we develop a theory based on complex spatiotemporal dynamics of neural population activity. We first implement and explore this theory in a biophysically realistic, spiking neural circuit. Population activity patterns emerging from the circuit capture realistic variability or fluctuations of neural dynamics both in time and in space. These activity patterns implement a type of probabilistic computations that we name fractional neural sampling (FNS). We further develop a mathematical model to reveal the algorithmic nature of FNS and its computational advantages for representing multimodal distributions, a major challenge faced by existing theories. We demonstrate that FNS provides a unified account of a diversity of experimental observations of neural spatiotemporal dynamics and perceptual processes such as visual perception inference, and that FNS makes experimentally testable predictions.
3D printing colloidal crystal microstructures via sacrificial-scaffold-mediated two-photon lithography
Authors: Liu Keliang , Ding Haibo , Li Sen , Niu Yanfang , Zeng Yi , Zhang Junning , Du Xin , Gu Zhongze
Published: August 2022

The orderly arrangement of nanomaterials’ tiny units at the nanometer-scale accounts for a substantial part of their remarkable properties. Maintaining this orderness and meanwhile endowing the nanomaterials with highly precise and free-designed 3D micro architectures will open an exciting prospect for various novel applications. In this paper, we developed a sacrificial-scaffold-mediated two-photon lithography (TPL) strategy that enables the fabrication of complex 3D colloidal crystal microstructures with orderly-arranged nanoparticles inside. We show that, with the help of a degradable hydrogel scaffold, the disturbance effect of the femtosecond laser to the nanoparticle self-assembling could be overcome. Therefore, hydrogel-state and solid-state colloidal crystal microstructures with diverse compositions, free-designed geometries and variable structural colors could be easily fabricated. This enables the possibility to create novel colloidal crystal microsensing systems that have not been achieved before.
A deep learning approach to fight illicit trafficking of antiquities using artefact instance classification
Authors: Winterbottom Thomas , Leone Anna , Al Moubayed Noura
Published: August 2022

We approach the task of detecting the illicit movement of cultural heritage from a machine learning perspective by presenting a framework for detecting a known artefact in a new and unseen image. To this end, we explore the machine learning problem of instance classification for large archaeological images datasets, i.e. where each individual object (instance) is itself a class that all of the multiple images of that object belongs. We focus on a wide variety of objects in the Durham Oriental Museum with which we build a dataset with over 24,502 images of 4332 unique object instances. We experiment with state-of-the-art convolutional neural network models, the smaller variations of which are suitable for deployment on mobile applications. We find the exact object instance of a given image can be predicted from among 4332 others with ~ 72% accuracy, showing how effectively machine learning can detect a known object from a new image. We demonstrate that accuracy significantly improves as the number of images-per-object instance increases (up to ~ 83%), with an ensemble of classifiers scoring as high as 84%. We find that the correct instance is found in the top 3, 5, or 10 predictions of our best models ~ 91%, ~ 93%, or ~ 95% of the time respectively. Our findings contribute to the emerging overlap of machine learning and cultural heritage, and highlights the potential available to future applications and research.
Bioherbicidal potential of plant species with allelopathic effects on the weed Bidens bipinnata L.
Authors: Lopes Robson Willian Nunes , Marques Morais Estefenson , Lacerda Julian Junio de Jesus , Araújo Francisca Diana da Silva
Published: August 2022

Plant species with allelopathic effects against weeds have emerged as a potential strategy for the development of ecologically friendly bioherbicides. In this study, the allelopathic effects of the plant species Dipteryx lacunifera Ducke, Ricinus communis L., Piper tuberculatum Jacq., and Jatropha gossypiifolia L. on the weed Bidens bipinnata L. were investigated. In vitro bioassays revealed that aqueous extracts of selected plant species were able to inhibit seed germination and seedling growth of B. bipinnata, highlighting the strongest allelopathic effect evidenced by R. communis. The phytotoxicity of the aqueous extracts was evaluated in pot experiments, which indicated that the foliar application of R. communis and P. tuberculatum extracts on B. bipinnata plants caused yellowing of leaves, affecting the chlorophyll content and reducing growth. The discrimination of the plant extracts by attenuated total reflectance Fourier transform mid-infrared (ATR FT-MIR) spectroscopy combined with principal component analysis (PCA) indicated the presence of allelochemical compounds, such as phenolics and terpenoids, which may be associated with allelopathic activity. Overall, this study provides valuable information about the substantial allelopathic inhibitory effects of the plant species R. communis and P. tuberculatum on the weed B. bipinnata, which may be used for the development of eco-friendly bioherbicides.
Prevalence and associated factors of tuberculosis among isoniazid users and non-users of HIV patients in Dessie, Ethiopia
Authors: Mebratu Wondwosen , Wedajo Shambel , Mohammed Semira , Endawkie Abel , Damtew Yeshiwork
Published: August 2022

Tuberculosis (TB) is major public health concern and Isoniazid Preventive Therapy (IPT) helps to prevent TB development among patients living with human immune deficiency virus (PLWHIV). However, the evidence is limited especially in the study area. Therefore, this study aimed to determine the prevalence and factors associated with TB among IPT users and non-IPT users of PLWHIV in Dessie, Ethiopia. A comparative cross-sectional study was employed for1 month in Dessie. A total of 326 respondents were selected using systematic random sampling. Bivariable and multivariable logistic regression analyses were computed to identify factors associated with Tuberculosis. In multivariable analysis, AOR with 95% CI was used to declare statistically significant variables with TB. The prevalence of TB among non-IPT users was 48.5%, (95% CI 40.8–56.2%), and among IPT users was 8%, (95% CI 5–13%). Cotrimoxazole prophylaxis therapy (CPT) (AOR = 5.835, 95% CI 2.565–13.274), IPT (AOR = 10.359, 95% CI 4.054–26.472), ART adherence (AOR = 30.542, 95% CI 12.871–72.475), and believing that IPT use prevents TB (AOR = 0.093, 95% CI 0.018–0.484) were statistically significant factors. The prevalence of TB was higher among non-IPT users than among IPT users. Therefore, efforts should be strengthened to implement widespread use of IPT among adult PLWHIV.
A systems immunology approach to investigate cytokine responses to viruses and bacteria and their association with disease
Authors: Lin Lijing , Curtin John A. , Regis Eteri , Hirsman Aurica , Howard Rebecca , Tutino Mauro , Edwards Michael R. , Prosperi Mattia , Simpson Angela , Rattray Magnus , Custovic Adnan , Johnston Sebastian L.
Published: August 2022

Patterns of human immune responses to viruses and bacteria and how this impacts risk of infections or onset/exacerbation of chronic respiratory diseases are poorly understood. In a population-based birth cohort, we measured peripheral blood mononuclear cell responses (28 cytokines) to respiratory viruses and bacteria, Toll-like receptor ligands and phytohemagglutinin, in 307 children. Cytokine responses were highly variable with > 1000-fold differences between children. Machine learning revealed clear distinction between virus-associated and bacteria-associated stimuli. Cytokines clustered into three functional groups (anti-viral, pro-inflammatory and T-cell derived). To investigate mechanisms potentially explaining such variable responses, we investigated cytokine Quantitative Trait Loci (cQTLs) of IL-6 responses to bacteria and identified nine (eight novel) loci. Our integrative approach describing stimuli, cytokines and children as variables revealed robust immunologically and microbiologically plausible clustering, providing a framework for a greater understanding of host-responses to infection, including novel genetic associations with respiratory disease.
Convolutional neural networks for the automatic segmentation of lumbar paraspinal muscles in people with low back pain
Authors: Wesselink E. O. , Elliott J. M. , Coppieters M. W. , Hancock M. J. , Cronin B. , Pool-Goudzwaard A. , Weber II K. A.
Published: August 2022

The size, shape, and composition of paraspinal muscles have been widely reported in disorders of the cervical and lumbar spine. Measures of size, shape, and composition have required time-consuming and rater-dependent manual segmentation techniques. Convolutional neural networks (CNNs) provide alternate timesaving, state-of-the-art performance measures, which could realise clinical translation. Here we trained a CNN for the automatic segmentation of lumbar paraspinal muscles and determined the impact of CNN architecture and training choices on segmentation performance. T2-weighted MRI axial images from 76 participants (46 female; age (SD): 45.6 (12.8) years) with low back pain were used to train CNN models to segment the multifidus, erector spinae, and psoas major muscles (left and right segmented separately). Using cross-validation, we compared 2D and 3D CNNs with and without data augmentation. Segmentation accuracy was compared between the models using the Sørensen-Dice index as the primary outcome measure. The effect of increasing network depth on segmentation accuracy was also investigated. Each model showed high segmentation accuracy (Sørensen-Dice index ≥ 0.885) and excellent reliability (ICC2,1 ≥ 0.941). Overall, across all muscles, 2D models performed better than 3D models (p = 0.012), and training without data augmentation outperformed training with data augmentation (p < 0.001). The 2D model trained without data augmentation demonstrated the highest average segmentation accuracy. Increasing network depth did not improve accuracy (p = 0.771). All trained CNN models demonstrated high accuracy and excellent reliability for segmenting lumbar paraspinal muscles. CNNs can be used to efficiently and accurately extract measures of paraspinal muscle health from MRI.
Ancient mitochondrial diversity reveals population homogeneity in Neolithic Greece and identifies population dynamics along the Danubian expansion axis
Authors: Silva Nuno M. , Kreutzer Susanne , Souleles Angelos , Triantaphyllou Sevasti , Kotsakis Kostas , Urem-Kotsou Dushka , Halstead Paul , Efstratiou Nikos , Kotsos Stavros , Karamitrou-Mentessidi Georgia , Adaktylou Fotini , Chondroyianni-Metoki Areti , Pappa Maria , Ziota Christina , Sampson Adamantios , Papathanasiou Anastasia , Vitelli Karen , Cullen Tracey , Kyparissi-Apostolika Nina , Lanz Andrea Zeeb , Peters Joris , Rio Jérémy , Wegmann Daniel , Burger Joachim , Currat Mathias , Papageorgopoulou Christina
Published: August 2022

The aim of the study is to investigate mitochondrial diversity in Neolithic Greece and its relation to hunter-gatherers and farmers who populated the Danubian Neolithic expansion axis. We sequenced 42 mitochondrial palaeogenomes from Greece and analysed them together with European set of 328 mtDNA sequences dating from the Early to the Final Neolithic and 319 modern sequences. To test for population continuity through time in Greece, we use an original structured population continuity test that simulates DNA from different periods by explicitly considering the spatial and temporal dynamics of populations. We explore specific scenarios of the mode and tempo of the European Neolithic expansion along the Danubian axis applying spatially explicit simulations coupled with Approximate Bayesian Computation. We observe a striking genetic homogeneity for the maternal line throughout the Neolithic in Greece whereas population continuity is rejected between the Neolithic and present-day Greeks. Along the Danubian expansion axis, our best-fitting scenario supports a substantial decrease in mobility and an increasing local hunter-gatherer contribution to the gene-pool of farmers following the initial rapid Neolithic expansion. Οur original simulation approach models key demographic parameters rather than inferring them from fragmentary data leading to a better understanding of this important process in European prehistory.
Dilemma breaking in quantum games by joint probabilities approach
Authors: Legón Alexis R. , Medina Ernesto
Published: August 2022

Classical games get fundamentally modified in the quantum realm because of non-locality and entanglement, that bypass some of the crucial features of the classical problem that define a dilemma. We will analyze how the dilemma can be shunted and even completely eliminated by the players using quantum strategies from the viewpoint of joint probabilities. In this approach, the game information (entropy) needs to be incorporated into the game strategies. We also connect the potential of the formalism of quantum games with the transmission of quantum information in quantum noisy channels and recent considerations of the connection between thermalization mechanisms in statistical mechanics, the many body problem and cooperative games considered here in the quantum regime.
Association of compliance with COVID-19 public health measures with depression
Authors: Byun Ju An , Sim Tae Jun , Lim Tae Yoon , Jang Sung-In , Kim Seung Hoon
Published: August 2022

Although previous studies have demonstrated increased depression related to COVID-19, the reasons for this are not well-understood. We investigated the association of compliance with COVID-19 public health measures with depression. Data from the 2020 Korea Community Health Survey were analyzed. The main independent variable was compliance with rules based on three performance variables (social distancing, wearing a mask in indoor facilities, and outdoors). Depression was assessed using Patient Health Questionnaire-9 scores. Of 195,243 participants, 5,101 participants had depression. Bad and moderate performance scores for compliance were associated with depression (Bad score, men: adjusted odds ratio [aOR] = 2.24, 95% confidence interval [CI] = 1.29–3.87; women: aOR = 2.42, 95% CI = 1.42–4.13; moderate score, men: aOR = 1.31, 95% CI = 1.02–1.68; women: aOR = 1.28, 95% CI = 1.07–1.53). In the subgroup analysis, among the quarantine rules, not wearing a mask indoors was the most prominently associated with depression. In participants with a high level of education, non-compliance with quarantine rules was significantly associated with depression. People who do not comply with public health measures are more likely to be depressed. The preparation and observance of scientific quarantine rules can help mental health in the ongoing COVID-19 pandemic and another infectious disease pandemic that may come.