bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional and Seasonal Trends in Tropical Ozone From SHADOZ Profiles: Reference for Models and Satellite Products
Authors: Thompson Anne M. , Stauffer Ryan M. , Wargan Krzysztof , Witte Jacquelyn C. , Kollonige Debra E. , Ziemke Jerald R. 
Published: October 2021

AbstractUnderstanding lowermost stratosphere (LMS) ozone variability is an important topic in the trends and climate assessment communities because of feedbacks among changing temperature, dynamics, and ozone. LMS evaluations are usually based on satellite observations. Free tropospheric (FT) ozone assessments typically rely on profiles from commercial aircraft. Ozonesonde measurements constitute an independent data set encompassing both LMS and FT. We used Southern Hemisphere Additional Ozonesondes (SHADOZ) data (5.8°N–14°S) from 1998 to 2019 in the Goddard Multiple Linear Regression model to analyze monthly mean FT and LMS ozone changes across five well‐distributed tropical sites. Our findings: (a) both FT (5–15 km) and LMS (15–20 km) ozone trends show marked seasonal variability. (b) All stations exhibit FT ozone increases in February‐May (up to 15%/decade) when the frequency of convectively driven waves have changed. (c) After May, monthly ozone changes are both positive and negative, leading to mean trends of +(1–4)%/decade, depending on station. (d) LMS ozone losses reach (4–9)%/decade midyear, correlating with an increase in TH as derived from SHADOZ radiosonde data. (e) When the upper FT and LMS are defined by tropopause‐relative coordinates, the LMS ozone trends all become insignificant. Thus, the 20‐year decline in tropical LMS ozone reported in recent satellite‐based studies likely signifies a perturbed tropopause rather than chemical depletion. The SHADOZ‐derived ozone changes highlight regional and seasonal variability across the tropics and define a new reference for evaluating changes derived from models and satellite products over the 1998–2019 period.
Smooth muscle 22 alpha protein inhibits VSMC foam cell formation by supporting normal LXRα signaling, ameliorating atherosclerosis
Authors: Zhang Dan-Dan , Song Yu , Kong Peng , Xu Xin , Gao Ya-Kun , Dou Yong-Qing , Weng Lin , Wang Xiao-Wei , Lin Yan-Ling , Zhang Fan , Zhang Hailin , Han Mei 
Published: October 2021

AbstractVascular smooth muscle cells (VSMCs) are indispensable components in foam cell formation in atherosclerosis. However, the mechanism behind foam cell formation of VSMCs has not been addressed. We found a potential association between deletion of smooth muscle (SM) 22α and deregulated nuclear receptors liver X receptors (LXRs)/retinoid X receptor (RXR) signaling in mice. Here, we investigated the roles of SM22α in LXRα-modulated cholesterol homeostasis, and explore possible mechanisms underlying this process. We identified that the depletion of SM22α was a primary event driving VSMC cholesterol accumulation and the development of atherosclerosis in mice. Proteomic and lipidomic analysis validated that downregulation of SM22α was correlated with reduced expression of LXRα and ATP-binding cassette transporter (ABCA) 1 and increased cholesteryl ester in phenotypically modulated VSMCs induced by platelets-derived growth factor (PDGF)-BB. Notably, LXRα was mainly distributed in the cytoplasm rather than the nucleus in the neointimal andSm22α−/−VSMCs. Loss of SM22α inhibited the nuclear import of LXRα and reduced ABCA1-mediated cholesterol efflux via promoting depolymerization of actin stress fibers. Affinity purification and mass spectrometry (AP-MS) analysis, co-immunoprecipitation and GST pull-down assays, confocal microscopy, and stochastic optical reconstruction microscopy (STORM) revealed that globular-actin (G-actin), monomeric actin, interacted with and retained LXRα in the cytoplasm in PDGF-BB-treated andSm22α−/−VSMCs. This interaction blocked LXRα binding to Importin α, a karyopherin that mediates the trafficking of macromolecules across the nuclear envelope, and the resulting reduction of LXRα transcriptional activity. Increasing SM22α expression restored nuclear localization of LXRα and removed cholesterol accumulation via inducing actin polymerization, ameliorating atherosclerosis. Our findings highlight that LXRα is a mechanosensitive nuclear receptor and that the nuclear import of LXRα maintained by the SM22α-actin axis is a potential target for blockade of VSMC foam cell formation and development of anti-atherosclerosis.
Harmonizing corporate carbon footprints
Authors: Klaaßen Lena , Stoll Christian 
Published: October 2021

AbstractGlobal greenhouse gas emissions need to reach net-zero around mid-century to limit global warming to 1.5 °C. This decarbonization challenge has, inter alia, increased the political and societal pressure on companies to disclose their carbon footprints. As a response, numerous companies announced roadmaps to become carbon neutral or even negative. The first step on the journey towards carbon neutrality, however, is to quantify corporate emissions accurately. Current carbon accounting and reporting practices remain unsystematic and not comparable, particularly for emissions along the value chain (so-called scope 3). Here we present a framework to harmonize scope 3 emissions by accounting for reporting inconsistency, boundary incompleteness, and activity exclusion. In a case study of the tech sector, we find that corporate reports omit half of the total emissions. The framework we present may help companies, investors, and policy makers to identify and close the gaps in corporate carbon footprints.
Globally consistent assessment of coastal eutrophication
Authors: Maúre Elígio de Raús , Terauchi Genki , Ishizaka Joji , Clinton Nicholas , DeWitt Michael 
Published: October 2021

AbstractEutrophication is an emerging global issue associated with increasing anthropogenic nutrient loading. The impacts and extent of eutrophication are often limited to regions with dedicated monitoring programmes. Here we introduce the first global and Google Earth Engine-based interactive assessment tool of coastal eutrophication potential (CEP). The tool evaluates trends in satellite-derived chlorophyll-a (CHL) to devise a global map of CEP. Our analyses suggest that, globally, coastal waters (depth ≤200 m) covering ∼1.15 million km2 are eutrophic potential. Also, waters associated with CHL increasing trends—eutrophication potential—are twofold higher than those showing signs of recovery. The tool effectively identified areas of known eutrophication with severe symptoms, like dead zones, as well as those with limited to no information of the eutrophication. Our tool introduces the prospect for a consistent global assessment of eutrophication trends with major implications for monitoring Sustainable Development Goals (SDGs) and the application of Earth Observations in support of SDGs.
RIPK1 regulates starvation resistance by modulating aspartate catabolism
Authors: Mei Xinyu , Guo Yuan , Xie Zhangdan , Zhong Yedan , Wu Xiaofen , Xu Daichao , Li Ying , Liu Nan , Zhu Zheng-Jiang 
Published: October 2021

AbstractRIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal period without a clear mechanism. Metabolism regulation and autophagy are critical to neonatal survival from severe starvation at birth. However, the mechanism by which RIPK1 regulates starvation resistance and survival remains unclear. Here, we address this question by discovering the metabolic regulatory role of RIPK1. First, metabolomics analysis reveals that Ripk1 deficiency specifically increases aspartate levels in both mouse neonates and mammalian cells under starvation conditions. Increased aspartate in Ripk1−/− cells enhances the TCA flux and ATP production. The energy imbalance causes defective autophagy induction by inhibiting the AMPK/ULK1 pathway. Transcriptional analyses demonstrate that Ripk1−/− deficiency downregulates gene expression in aspartate catabolism by inactivating SP1. To summarize, this study reveals that RIPK1 serves as a metabolic regulator responsible for starvation resistance.
Little evidence for sex or ovarian hormone influences on affective variability
Authors: Weigard Alexander , Loviska Amy M. , Beltz Adriene M. 
Published: October 2021

AbstractWomen were historically excluded from research participation partly due to the assumption that ovarian hormone fluctuations lead to variation, especially in emotion, that could not be experimentally controlled. Although challenged in principle and practice, relevant empirical data are limited by single measurement occasions. The current paper fills this knowledge gap using data from a 75-day intensive longitudinal study. Three indices of daily affective variability—volatility, emotional inertia, and cyclicity—were evaluated using Bayesian inferential methods in 142 men, naturally cycling women, and women using three different oral contraceptive formulations (that “stabilize” hormone fluctuations). Results provided more evidence for similarities between men and women—and between naturally cycling women and oral contraceptive users—than for differences. Even if differences exist, effects are likely small. Thus, there is little indication that ovarian hormones influence affective variability in women to a greater extent than the biopsychosocial factors that influence daily emotion in men.
Anti-cancer efficacy including Rb-deficient tumors and VHL-independent HIF1α proteasomal destabilization by dual targeting of CDK1 or CDK4/6 and HSP90
Authors: Zhao Shuai , Zhou Lanlan , Dicker David T. , Lev Avital , Zhang Shengliang , Ross Eric , El-Deiry Wafik S. 
Published: October 2021

AbstractA prevalent characteristic of solid tumors is intra-tumoral hypoxia. Hypoxia-inducible factor 1α (HIF1α) predominantly mediates the adaptive response to O2 oscillation and is linked to multiple malignant hallmarks. Here we describe a strategy to robustly target HIF1α by dual inhibition of CDK(s) and heat shock protein 90 (HSP90). We show that CDK1 may contribute to HSP90-mediated HIF1α stabilization. CDK1 knockdown enhances the decrease of HIF1α by HSP90 inhibition. Dual inhibition of CDK1 and HSP90 significantly increases apoptosis and synergistically inhibits cancer cell viability. Similarly, targeting CDK4/6 using FDA-approved inhibitors in combination with HSP90 inhibition shows a class effect on HIF1α inhibition and cancer cell viability suppression not only in colorectal but also in various other cancer types, including Rb-deficient cancer cells. Dual inhibition of CDK4/6 and HSP90 suppresses tumor growth in vivo. In summary, combined targeting of CDK(s) (CDK1 or CDK4/6) and HSP90 remarkably inhibits the expression level of HIF1α and shows promising anti-cancer efficacy with therapeutic potential.
Interrelationships between the structural, spectroscopic, and antibacterial properties of nanoscale (< 50 nm) cerium oxides
Authors: Iqbal Neelam , Anastasiou Antonios , Aslam Zabeada , Raif El Mostafa , Do Thuy , Giannoudis Peter V. , Jha Animesh 
Published: October 2021

AbstractBone healing is a complex process, and if not managed successfully, it can lead to non-union, metal-work failure, bacterial infections, physical and psychological patient impairment. Due to the growing urgency to minimise antibiotic dependency, alternative treatment strategies, including the use of nanoparticles, have attracted significant attention. In the present study, cerium oxide nanoparticles (Ce4+, Ce3+) have been selected due to their unique antibacterial redox capability. We found the processing routes affected the agglomeration tendency, particle size distribution, antibacterial potential, and ratio of Ce3+:Ce4+ valence states of the cerium oxide nanoparticles. The antibacterial efficacy of the nanoparticles in the concentration range of 50–200 µg/ml is demonstrated against Escherichia coli, Staphylococcus epidermis, and Pseudomonas aeruginosa by determining the half-maximal inhibitory concentration (IC50). Cerium oxide nanoparticles containing a more significant amount of Ce3+ ions, i.e., FRNP, exhibited 8.5 ± 1.2%, 10.5 ± 4.4%, and 13.8 ± 5.8% increased antibacterial efficacy compared with nanoparticles consisting mainly of Ce4+ ions, i.e., nanoparticles calcined at 815 °C.
NPF activates a specific NPF receptor and regulates food intake in Pacific abalone Haliotis discus hannai
Authors: Kim Kyeong Seop , Kim Mi Ae , Park Keunwan , Sohn Young Chang 
Published: October 2021

AbstractNeuropeptides function through G protein-coupled receptors (GPCRs) with high specificity, implying a significant degree of neuropeptide-GPCR coevolution. However, potential neuropeptide signaling systems in non-chordates are relatively elusive. We determined the specificity of the neuropeptide F (Hdh-NPF) signaling system with a cognate receptor (Hdh-NPFR) in the Pacific abalone, Haliotis discus hannai. Phylogenetic and exon–intron arrangement analyses of bilaterian NPF and the chordate ortholog NPY with their receptor sequences revealed a likely common ancestor, and Hdh-NPFR was similar to the NPYR2 subtype among the NPYR1, NPYR2, and NPYR5 subtypes. Among four Hdh-NPFR-related receptors, Hdh-NPFR specifically responded to Hdh-NPF peptide, supported by the dose–response luciferase reporter curve, intracellular Ca2+ mobilization, and phosphorylation of ERK1/2 and its inhibition with a protein kinase C inhibitor. Peptide fragmentations and shuffling of Hdh-NPF with human NPY could not activate the cellular response of Hdh-NPFR. Three-dimensional in silico modeling suggested that interaction of Hdh-NPF C-terminal amino acids with the extracellular loops of Hdh-NPFR is critical for Hdh-NPFR activation. In vivo injection of Hdh-NPF peptide increased food consumption, and knockdown of Hdh-NPF expression decreased food consumption in Pacific abalone. These findings provide evidence for co-evolution of the NPF/Y ligand-receptor system, enabling further research on mollusk orexigenic neuropeptides.
Quantification of the spatial distribution of primary tumors in the lung to develop new prognostic biomarkers for locally advanced NSCLC
Authors: Vuong Diem , Bogowicz Marta , Wee Leonard , Riesterer Oliver , Vlaskou Badra Eugenia , D’Cruz Louisa Abigail , Balermpas Panagiotis , van Timmeren Janita E. , Burgermeister Simon , Dekker André , De Ruysscher Dirk , Unkelbach Jan , Thierstein Sandra , Eboulet Eric I. , Peters Solange , Pless Miklos , Guckenberger Matthias , Tanadini-Lang Stephanie 
Published: October 2021

AbstractThe anatomical location and extent of primary lung tumors have shown prognostic value for overall survival (OS). However, its manual assessment is prone to interobserver variability. This study aims to use data driven identification of image characteristics for OS in locally advanced non-small cell lung cancer (NSCLC) patients. Five stage IIIA/IIIB NSCLC patient cohorts were retrospectively collected. Patients were treated either with radiochemotherapy (RCT): RCT1* (n = 107), RCT2 (n = 95), RCT3 (n = 37) or with surgery combined with radiotherapy or chemotherapy: S1* (n = 135), S2 (n = 55). Based on a deformable image registration (MIM Vista, 6.9.2.), an in-house developed software transferred each primary tumor to the CT scan of a reference patient while maintaining the original tumor shape. A frequency-weighted cumulative status map was created for both exploratory cohorts (indicated with an asterisk), where the spatial extent of the tumor was uni-labeled with 2 years OS. For the exploratory cohorts, a permutation test with random assignment of patient status was performed to identify regions with statistically significant worse OS, referred to as decreased survival areas (DSA). The minimal Euclidean distance between primary tumor to DSA was extracted from the independent cohorts (negative distance in case of overlap). To account for the tumor volume, the distance was scaled with the radius of the volume-equivalent sphere. For the S1 cohort, DSA were located at the right main bronchus whereas for the RCT1 cohort they further extended in cranio-caudal direction. In the independent cohorts, the model based on distance to DSA achieved performance: AUCRCT2 [95% CI] = 0.67 [0.55–0.78] and AUCRCT3 = 0.59 [0.39–0.79] for RCT patients, but showed bad performance for surgery cohort (AUCS2 = 0.52 [0.30–0.74]). Shorter distance to DSA was associated with worse outcome (p = 0.0074). In conclusion, this explanatory analysis quantifies the value of primary tumor location for OS prediction based on cumulative status maps. Shorter distance of primary tumor to a high-risk region was associated with worse prognosis in the RCT cohort.
Interspecific variation of antennal lobe composition among four hornet species
Authors: Couto Antoine , Arnold Gérard , Ai Hiroyuki , Sandoz Jean-Christophe 
Published: October 2021

AbstractOlfaction is a crucial sensory modality underlying foraging, social and mating behaviors in many insects. Since the olfactory system is at the interface between the animal and its environment, it receives strong evolutionary pressures that promote neuronal adaptations and phenotypic variations across species. Hornets are large eusocial predatory wasps with a highly developed olfactory system, critical for foraging and intra-specific communication. In their natural range, hornet species display contrasting ecologies and olfactory-based behaviors, which might match to adaptive shifts in their olfactory system. The first olfactory processing center of the insect brain, the antennal lobe, is made of morphological and functional units called glomeruli. Using fluorescent staining, confocal microscopy and 3D reconstructions, we compared antennal lobe structure, glomerular numbers and volumes in four hornet species (Vespa crabro, Vespa velutina, Vespa mandarinia and Vespa orientalis) with marked differences in nesting site preferences and predatory behaviors. Despite a conserved organization of their antennal lobe compartments, glomeruli numbers varied strongly between species, including in a subsystem thought to process intraspecific cuticular signals. Moreover, specific adaptations involving enlarged glomeruli appeared in two species, V. crabro and V. mandarinia, but not in the others. We discuss the possible function of these adaptations based on species-specific behavioral differences.
Modeling and analysis of transient lubrication characteristic of the helicopter main transmission spiral bevel gears in point contacts
Authors: Wang Yanzhong , Yang Kai , Chu Xiaomeng , Tang Wen , Huang Changyong 
Published: October 2021

AbstractAn engineering calculation model is introduced for point-contact elastohydrodynamic lubrication analysis of spiral bevel gears. This model can analyze transient lubrication characteristics of spiral bevel gears. The influence of the angle between the lubricant entrainment and the minor axis of the contact ellipse is included in this model. The contact parameters of the spiral bevel gear are calculated, which will change with time during the meshing process. The variation of lubricant film thickness during the meshing process of spiral bevel gears is unraveled. Due to the influence of entrainment velocity, the oil film thickness at the out mesh side is smaller than that at the enter mesh side under the same contact force. It is evident that the higher the pressure is, the larger the contact area will be. Meanwhile, the thickness of the oil film is reduced, and the oil film distribution in the contact area is relatively uniform. Taking helicopter main transmission spiral bevel gears as an example, this study finally calculates the distribution characteristics of the oil film thickness of the spiral bevel gear, and solves the lubrication performance of the spiral bevel gear under different working conditions.
ZSWIM8 is a myogenic protein that partly prevents C2C12 differentiation
Authors: Okumura Fumihiko , Oki Nodoka , Fujiki Yuha , Ikuta Rio , Osaki Kana , Hamada Shun , Nakatsukasa Kunio , Hisamoto Naoki , Hara Taichi , Kamura Takumi 
Published: October 2021

AbstractCell adhesion molecule-related/downregulated by oncogenes (Cdon) is a cell-surface receptor that mediates cell–cell interactions and positively regulates myogenesis. The cytoplasmic region of Cdon interacts with other proteins to form a Cdon/JLP/Bnip-2/CDC42 complex that activates p38 mitogen-activated protein kinase (MAPK) and induces myogenesis. However, Cdon complex may include other proteins during myogenesis. In this study, we found that Cullin 2-interacting protein zinc finger SWIM type containing 8 (ZSWIM8) ubiquitin ligase is induced during C2C12 differentiation and is included in the Cdon complex. We knocked-down Zswim8 in C2C12 cells to determine the effect of ZSWIM8 on differentiation. However, we detected neither ZSWIM8-dependent ubiquitination nor the degradation of Bnip2, Cdon, or JLP. In contrast, ZSWIM8 knockdown accelerated C2C12 differentiation. These results suggest that ZSWIM8 is a Cdon complex-included myogenic protein that prevents C2C12 differentiation without affecting the stability of Bnip2, Cdon, and JLP.
Crizotinib efficacy in advanced non-squamous NSCLC patients with ALK or ROS1 rearrangement
Authors: Krawczyk Paweł , Grenda Anna , Terlecka Paulina , Błach Justyna , Wojas-Krawczyk Kamila , Kucharczyk Tomasz , Chmielewska Izabela , Kieszko Robert , Jarosz Bożena , Gil Michał , Reszka Katarzyna , Milanowski Janusz 
Published: October 2021

AbstractIn patients with advanced non-small cell lung cancer (NSCLC), comprehensive genetic diagnostics is currently carried out in order to qualify for molecularly targeted therapies and immunotherapy. The aim of the study was to assess the usefulness of the reverse transcriptase (RT-PCR) method in the diagnosis of gene rearrangements, the effectiveness of EGFR, ALK, ROS1, and PD-L1 inhibitors in first-line treatment in NSCLC patients. We enrolled 95 non-squamous NSCLC patients with known status of EGFR, ALK, ROS1, MET and RET genes and PD-L1 protein expression. We used the real time PCR, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and RT-PCR techniques for determination of predictive factors. In patients with ALK and ROS1 genes alteration, the median overall survival was 34 months in crizotinib treated patients and 6 months in patients who received chemotherapy (HR = 0.266, p = 0.0056). The risk of death was lower in patients treated with molecularly targeted therapies or immunotherapy compared to patients with predictive factors without personalized treatment (HR = 0.265, 95% CI 0.116–0.606) and to patient without predictive factors who received chemotherapy (HR = 0.42, 95% CI 0.162–1.09). Diagnosis of predictive factors and implementation of personalized treatment are key to prolonging the survival in advanced NSCLC patients.