bluuebunny/crossref_metadata_2025 huggingface dataset:
Cathepsin D Variants Associated With Neurodegenerative Diseases Show Dysregulated Functionality and Modified α-Synuclein Degradation Properties
Authors: Bunk Josina , Prieto Huarcaya Susy , Drobny Alice , Dobert Jan Philipp , Walther Lina , Rose-John Stefan , Arnold Philipp , Zunke Friederike
Published: February 2021

Cathepsin D (CTSD) is a lysosomal protease important for the degradation of various substrates, including disease-associated proteins like α-synuclein (a-syn), amyloid precursor protein (APP) and tau, all of which tend to aggregate if not efficiently degraded. Hence, it is not surprising that genetic variants within the CTSD gene have been linked to neurodegenerative diseases, like Parkinson’s and Alzheimer’s disease (PD, AD), as well as the lysosomal storage disorder neuronal ceroid lipofuscinosis type-10 (NCL10). Although recent studies have shown the molecular dependence of substrate degradation via CTSD within autophagic pathways, only little is known about the precise role of lysosomal CTSD function in disease development. We here performed biochemical, cellular and structural analyses of eleven disease-causing CTSD point mutations found in genomic sequencing data of patients to understand their role in neurodegeneration. These CTSD variants were analyzed for cellular localization, maturation and enzymatic activity in overexpression analyses. Moreover, for PD-associated mutants, intracellular degradation of a-syn was monitored. In summary, our results suggest that NCL10-associated CTSD variants are significantly impaired in lysosomal maturation and enzymatic activity, whereas the AD- and PD-associated variants seemed rather unaffected, indicating normal maturation, and lysosomal presence. Interestingly, a PD-associated CTSD variant (A239V) exhibited increased enzymatic activity accompanied by enhanced a-syn degradation. By structural analyses of this mutant utilizing molecular dynamics simulation (MDS), we identified a structural change within a loop adjacent to the catalytic center leading to a higher flexibility and potentially accelerated substrate exchange rates. Our data sheds light onto the role of CTSD in disease development and helps to understand the structural regulation of enzymatic function, which could be utilized for targeted CTSD activation. Because of the degradative function of CTSD, this enzyme is especially interesting for therapeutic strategies tackling protein aggregates in neurodegenerative disorders.
AQP1 Is Up-Regulated by Hypoxia and Leads to Increased Cell Water Permeability, Motility, and Migration in Neuroblastoma
Authors: Huo Zihe , Lomora Mihai , Kym Urs , Palivan Cornelia , Holland-Cunz Stefan G. , Gros Stephanie J.
Published: February 2021

The water channel aquaporin 1 (AQP1) has been implicated in tumor progression and metastasis. It is hypothesized that AQP1 expression can facilitate the transmembrane water transport leading to changes in cell structure that promote migration. Its impact in neuroblastoma has not been addressed so far. The objectives of this study have been to determine whether AQP1 expression in neuroblastoma is dependent on hypoxia, to demonstrate whether AQP1 is functionally relevant for migration, and to further define AQP1-dependent properties of the migrating cells. This was determined by investigating the reaction of neuroblastoma cell lines, particularly SH-SY5Y, Kelly, SH-EP Tet-21/N and SK-N-BE(2)-M17 to hypoxia, quantitating the AQP1-related water permeability by stopped-flow spectroscopy, and studying the migration-related properties of the cells in a modified transwell assay. We find that AQP1 expression in neuroblastoma cells is up-regulated by hypoxic conditions, and that increased AQP1 expression enabled the cells to form a phenotype which is associated with migratory properties and increased cell agility. This suggests that the hypoxic tumor microenvironment is the trigger for some tumor cells to transition to a migratory phenotype. We demonstrate that migrating tumor cell express elevated AQP1 levels and a hypoxic biochemical phenotype. Our experiments strongly suggest that elevated AQP1 might be a key driver in transitioning stable tumor cells to migrating tumor cells in a hypoxic microenvironment.
A Mechanism Leading to Changes in Copy Number Variations Affected by Transcriptional Level Might Be Involved in Evolution, Embryonic Development, Senescence, and Oncogenesis Mediated by Retrotransposons
Authors: Sui Yunpeng , Peng Shuanghong
Published: February 2021

In recent years, more and more evidence has emerged showing that changes in copy number variations (CNVs) correlated with the transcriptional level can be found during evolution, embryonic development, and oncogenesis. However, the underlying mechanisms remain largely unknown. The success of the induced pluripotent stem cell suggests that genome changes could bring about transformations in protein expression and cell status; conversely, genome alterations generated during embryonic development and senescence might also be the result of genome changes. With rapid developments in science and technology, evidence of changes in the genome affected by transcriptional level has gradually been revealed, and a rational and concrete explanation is needed. Given the preference of the HIV-1 genome to insert into transposons of genes with high transcriptional levels, we propose a mechanism based on retrotransposons facilitated by specific pre-mRNA splicing style and homologous recombination (HR) to explain changes in CNVs in the genome. This mechanism is similar to that of the group II intron that originated much earlier. Under this proposed mechanism, CNVs on genome are dynamically and spontaneously extended in a manner that is positively correlated with transcriptional level or contract as the cell divides during evolution, embryonic development, senescence, and oncogenesis, propelling alterations in them. Besides, this mechanism explains several critical puzzles in these processes. From evidence collected to date, it can be deduced that the message contained in genome is not just three-dimensional but will become four-dimensional, carrying more genetic information.
Long Non-coding RNA Expression Patterns in Stomach Adenocarcinoma Serve as an Indicator of Tumor Mutation Burden and Are Associated With Tumor-Infiltrating Lymphocytes and Microsatellite Instability
Authors: Yang Dongdong , Yu Jinling , Han Bing , Sun Yue , Mo Steven , Hu Jing
Published: February 2021

Long non-coding RNAs (lncRNAs) are crucial in controlling important aspects of tumor immunity. However, whether the expression pattern of lncRNAs in stomach adenocarcinoma (STAD) reflects tumor immunity is not fully understood. We screened differentially expressed lncRNAs (DElncRNAs) between high and low tumor mutation burden (TMB) STAD samples. Using the least absolute shrinkage and selection operator method, 33 DElncRNAs were chosen to establish a lncRNA-based signature classifier for predicting TMB levels. The accuracy of the 33-lncRNA-based signature classifier was 0.970 in the training set and 0.950 in the test set, suggesting the expression patterns of the 33 lncRNAs may be an indicator of TMB in STAD. Survival analysis showed that a lower classifier index reflected better prognosis for STAD patients, and the index showed correlation with expression of immune checkpoint molecules (PD1, PDL1, and CTLA4), tumor-infiltrating lymphocytes, and microsatellite instability. In conclusion, STAD samples with different tumor mutation burdens have different lncRNA expression patterns. The 33-lncRNA-based signature classifier index may be an indicator of TMB and is associated expression of immune checkpoints, tumor-infiltrating lymphocytes, and microsatellite instability.
Cisplatin-Resistant Gastric Cancer Cells Promote the Chemoresistance of Cisplatin-Sensitive Cells via the Exosomal RPS3-Mediated PI3K-Akt-Cofilin-1 Signaling Axis
Authors: Sun Meng-Yao , Xu Bo , Wu Qiu-Xue , Chen Wen-Lian , Cai Si , Zhang Hui , Tang Qing-Feng
Published: February 2021

Cisplatin is an important agent in first-line chemotherapy against gastric cancer (GC). However, consequential drug resistance limits its effectiveness for the treatment of GC. In this study, a cisplatin resistant gastric cancer cell line SGC7901R was determined by LC-MS/MS with increased exosomal levels of RPS3 protein. SGC7901R cell-derived exosomes were readily taken up by cisplatin-sensitive SGC7901S cells, thus triggering off a phenotype of chemoresistance in the receptor cells. Subsequently, it was demonstrated that exosomal RPS3 was essential for inducing chemoresistance of receptor cells as shown by the acquisition of this phenotype in SGC7901S cells with enforced expression of RPS3. Further mechanism study demonstrated that cisplatin-resistant gastric cancer cell-derived exosomal RPS3 enhanced the chemoresistance of cisplatin-sensitive gastric cancer cells through the PI3K-Akt-cofilin-1 signaling pathway. All these findings demonstrated that cisplatin-resistant gastric cancer cells communicate with sensitive cells through the intercellular delivery of exosomal RPS3 and activation of the PI3K-Akt-cofilin-1 signaling pathway. Targeting exosomal RPS3 protein in cisplatin-resistant gastric cancer cells may thus be a promising strategy to overcome cisplatin resistance in gastric cancer.
A Tale of 20 Alphaviruses; Inter-species Diversity and Conserved Interactions Between Viral Non-structural Protein 3 and Stress Granule Proteins
Authors: Nowee Gwen , Bakker Julian W. , Geertsema Corinne , Ros Vera I. D. , Göertz Giel P. , Fros Jelke J. , Pijlman Gorben P.
Published: February 2021

Alphaviruses infect a diverse range of host organisms including mosquitoes, mammals, and birds. The enigmatic alphavirus non-structural protein 3 (nsP3) has an intrinsically disordered, C-terminal hypervariable domain (HVD) that can interact with a variety of host proteins associated with stress granules (SGs). The HVD displays the highest variability across the more than 30 known alphaviruses, yet it also contains several motifs that are conserved amongst different subgroups of alphaviruses. For some alphaviruses, specific nsP3–SG protein interactions are essential for virus replication. However, it remains difficult to attribute general roles to these virus-host interactions, as multiple amino acid motifs in the HDV display a degree of redundancy and previous studies were performed with a limited number of alphaviruses. To better understand nsP3-host protein interactions we conducted comprehensive co-localization experiments with the nsP3s of 20 diverse alphaviruses: chikungunya, Semliki Forest, Sindbis, Bebaru, Barmah Forest, Getah, Mayaro, Middelburg, O'nyong-nyong, Ross River QML and T48, Una, Whataroa, Southern Elephant Seal, Eilat, Tai Forest (TAFV), Venezuelan/Eastern/Western equine encephalitis (V/E/WEEV) and the aquatic Salmonid alphavirus (SAV), with three different SG proteins (G3BP and its insect homolog Rasputin, FMRP) and BIN1 in mammalian and mosquito cell lines. Despite that all terrestrial alphavirus nsP3s contained at least one BIN1-binding motif (PxPxPR), not all nsP3s co-localized with BIN1. Further, all alphaviruses except SAV, TAFV and VEEV displayed co-localization with G3BP. Although viruses lacking FGxF-like motifs contained Agenet-like domain binding motifs to facilitate interaction with FMRP, cytoplasmic nsP3 granules of all tested alphaviruses co-localized with FMRP. Crispr-Cas9 knockout of G3BP in mammalian cells abolished nsP3-FMRP co-localization for all alphaviruses except V/E/WEEV nsP3s that bind FMRP directly. G3BP knockout also changed nsP3 subcellular localization of Bebaru, Barmah Forest, Getah, and Sindbis viruses. Taken together this study paints a more detailed picture of the diverse interactions between alphavirus nsP3 and SG-associated host proteins. The interaction between nsP3 and G3BP clearly plays a central role and results in recruitment of additional host proteins such as FMRP. However, direct binding of FMRP can make the interaction with G3BP redundant which exemplifies the alternate evolutionary paths of alphavirus subgroups.
The P2X7 Receptor in Osteoarthritis
Authors: Li Zihao , Huang Ziyu , Bai Lunhao
Published: February 2021

Osteoarthritis (OA) is the most common joint disease. With the increasing aging population, the associated socio-economic costs are also increasing. Analgesia and surgery are the primary treatment options in late-stage OA, with drug treatment only possible in early prevention to improve patients’ quality of life. The most important structural component of the joint is cartilage, consisting solely of chondrocytes. Instability in chondrocyte balance results in phenotypic changes and cell death. Therefore, cartilage degradation is a direct consequence of chondrocyte imbalance, resulting in the degradation of the extracellular matrix and the release of pro-inflammatory factors. These factors affect the occurrence and development of OA. The P2X7 receptor (P2X7R) belongs to the purinergic receptor family and is a non-selective cation channel gated by adenosine triphosphate. It mediates Na+, Ca2+influx, and K+efflux, participates in several inflammatory reactions, and plays an important role in the different mechanisms of cell death. However, the relationship between P2X7R-mediated cell death and the progression of OA requires investigation. In this review, we correlate potential links between P2X7R, cartilage degradation, and inflammatory factor release in OA. We specifically focus on inflammation, apoptosis, pyroptosis, and autophagy. Lastly, we discuss the therapeutic potential of P2X7R as a potential drug target for OA.
Flavin-Containing Monooxygenases Are Conserved Regulators of Stress Resistance and Metabolism
Authors: Huang Shijiao , Howington Marshall B. , Dobry Craig J. , Evans Charles R. , Leiser Scott F.
Published: February 2021

Flavin-Containing Monooxygenases are conserved xenobiotic-detoxifying enzymes. Recent studies have revealed endogenous functions of FMOs in regulating longevity in Caenorhabditis elegans and in regulating aspects of metabolism in mice. To explore the cellular mechanisms of FMO’s endogenous function, here we demonstrate that all five functional mammalian FMOs may play similar endogenous roles to improve resistance to a wide range of toxic stresses in both kidney and liver cells. We further find that stress-activated c-Jun N-terminal kinase activity is enhanced in FMO-overexpressing cells, which may lead to increased survival under stress. Furthermore, FMO expression modulates cellular metabolic activity as measured by mitochondrial respiration, glycolysis, and metabolomics analyses. FMO expression augments mitochondrial respiration and significantly changes central carbon metabolism, including amino acid and energy metabolism pathways. Together, our findings demonstrate an important endogenous role for the FMO family in regulation of cellular stress resistance and major cellular metabolic activities including central carbon metabolism.
Single-Cell Sequencing Applications in the Inner Ear
Authors: Wu Mingxuan , Xia Mingyu , Li Wenyan , Li Huawei
Published: February 2021

Genomics studies face specific challenges in the inner ear due to the multiple types and limited amounts of inner ear cells that are arranged in a very delicate structure. However, advances in single-cell sequencing (SCS) technology have made it possible to analyze gene expression variations across different cell types as well as within specific cell groups that were previously considered to be homogeneous. In this review, we summarize recent advances in inner ear research brought about by the use of SCS that have delineated tissue heterogeneity, identified unknown cell subtypes, discovered novel cell markers, and revealed dynamic signaling pathways during development. SCS opens up new avenues for inner ear research, and the potential of the technology is only beginning to be explored.
Depletion of Toll-Like Receptor-9 Attenuates Renal Tubulointerstitial Fibrosis After Ischemia-Reperfusion Injury
Authors: Zheng Haofeng , Zhang Yannan , Li Lei , Zhang Rui , Luo Zihuan , Yang Zhe , Ye Yongrong , He Jiannan , Sun Qiquan
Published: February 2021

Toll-like receptor-9 (TLR-9) is a potent proinflammatory receptor that mediates renal injury. However, the reported effects of TLR-9 are contradictory. Here, using a traditional mouse AKI→CKD transition model, the roles of TLR-9 during the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) were further explored. Using a TLR-9–/– mouse, the effects and mechanisms of TLR-9 were investigated. Loss of TLR-9 elicited no obvious effects as regards renal function or histology during AKI in the early phases (24–48 h), while TLR-9 KO attenuated renal fibrosis (as shown using fibronectin and collagen III) and epithelial-to-mesenchymal transition (EMT) [E-cadherin (E-Cad) and α-smooth muscle actin (α-SMA)] on the long-term after AKI through the inhibition of macrophages infiltration, especially M2 macrophages. The roles of TLR-9 on macrophages were also explored using Raw264.7 macrophage cell line, and results indicated that the inhibition of TLR-9 on Raw 264.7 macrophages decreased the induction of M2 type macrophage in a dose-dependent manner. The roles of TLR-9 on renal tubular epithelial (RTE) cells were also explored. Conversely, TLR-9 depletion did not contribute to the improvement of fibrosis and EMT in vitro. Therefore, TLR-9 plays a critical role in the AKI→CKD transition. Attenuation of CKD post-AKI in the TLR-9 KO group mainly relies on the effects of TLR-9 on macrophages. These results also suggest that TLR-9 could be a therapeutic target for CKD.
Increased Environment-Related Metabolism and Genetic Expression in the In Vitro Matured Mouse Oocytes by Transcriptome Analysis
Authors: Zhang Hao-Lin , Xu Yi , Ju Jia-Qian , Pan Zhen-Nan , Liu Jing-Cai , Sun Shao-Chen
Published: February 2021

Infertility in humans at their reproductive age is a world-wide problem. Oocyte in vitro maturation (IVM) is generally used in such cases to acquire the embryo in assisted reproductive technology (ART). However, the differences between an in vivo (IVO) and IVM culture environment in the RNA expression profile in oocytes, remains unclear. In this study, we compared the global RNA transcription pattern of oocytes from in vitro and in vivo maturation. Our results showed that 1,864 genes differentially expressed between the IVO and IVM oocytes. Among these, 1,638 genes were up-regulated, and 226 genes were down-regulated, and these changes were mainly divided into environmental adaption, metabolism, and genetic expression. Our detailed analysis showed that the expression of genes that belonged to metabolism-related processes such as energy metabolism, nucleotide metabolism, and carbohydrate metabolism was changed; and these genes also belonged to organismal systems including environmental adaptation and the circulatory system; moreover, we also found that the relative gene expression of genetic expression processes, such as protein synthesis, modification, and DNA replication and repair were also altered. In conclusion, our data suggests that in vitro maturation of mouse oocyte resulted in metabolism and genetic expression changes due to environmental changes compared with in vivo matured oocytes.
“Biomechanical Signaling in Oocytes and Parthenogenetic Cells”
Authors: Pennarossa Georgia , Gandolfi Fulvio , Brevini Tiziana A. L.
Published: February 2021

Oocyte-specific competence remains one of the major targets of current research in the field of reproduction. Several mechanisms are involved in meiotic maturation and the molecular signature of an oocyte is considered to reflect its quality and to predict its subsequent developmental and functional capabilities. In the present minireview, we focus on the possible role of mechanotransduction and mechanosensor signaling pathways, namely the Hippo and the RhoGTPase, in the maturing oocyte. Due to the limited access to female gametes, we propose the use of cells isolated from parthenogenetic embryos as a promising model to characterize and dissect the oocyte distinctive molecular signatures, given their exclusive maternal origin. The brief overview here reported suggests a role of the mechanosensing related pathways in oocyte quality and developmental competence and supports the use of uniparental cells as a useful tool for oocyte molecular signature characterization.
Differential Imprints of Distinct ENSO Flavors in Global Patterns of Very Low and High Seasonal Precipitation
Authors: Wiedermann Marc , Siegmund Jonatan F. , Donges Jonathan F. , Donner Reik V.
Published: February 2021

The effects of El Niño's two distinct flavors, East Pacific (EP) and Central Pacific (CP)/Modoki El Niño, on global climate variability have been studied intensively in recent years. Most of these studies have made use of linear multivariate statistics or composite analysis. Especially the former assumes the same type of linear statistical dependency to apply across different phases of the El Niño–Southern Oscillation (ENSO), which appears not necessarily a justified assumption. Here, we statistically evaluate the likelihood of co-occurrences between very high or very low seasonal precipitation sums over vast parts of the global land surface and the presence of the respective EP and CP types of both, El Niño and La Niña. By employing event coincidence analysis, we uncover differential imprints of both flavors on very low and very high seasonal precipitation patterns over distinct regions across the globe, which may severely affect, among others, agricultural and biomass production or public health. We particularly find that EP periods exhibit statistically significant event coincidence rates with hydrometeorological anomalies at larger spatial scales, whereas sparser patterns emerge along with CP periods. Our statistical analysis confirms previously reported interrelations for EP periods and uncovers additional distinct regional patterns of very high/low seasonal precipitation, such as increased rainfall over Central Asia alongside CP periods that have to our knowledge not been reported so far. Our results demonstrate that a thorough distinction of El Niño and La Niña into their two respective flavors could be crucial for understanding the emergence of strong regional hydrometeorological anomalies and anticipating their associated ecological and socioeconomic impacts.
Addressing Challenges in Humanistic Communication During COVID-19 Through Medical Education
Authors: Amin Shefali , Chin Justin , Terrell Mark A. , Lomiguen Christine M.
Published: February 2021

The current global pandemic due to COVID-19 has resulted in widespread lockdowns, social distancing, and other protective guidelines; these infectious control and mitigation measures challenge the medical system and create anxiety among all populations. In hospitals and healthcare facilities, patient interaction and shared decision making are sacrificed for fear of COVID-19 nosocomial spread. The intangible effects of human interaction with COVID-19 patients, whether of a physician or a patient’s family, are replaced with isolation amid ventilators. Medical professionals must find a way to practice life-saving medical care while maintaining humanistic and professional interactions. This article provides insight into the necessity and challenges of humanistic communication during COVID-19 across various institutions and offers both short- and long-term solutions and reforms through medical education.
Right Atrial Pressure Is Associated With Outcomes in Patient With Cardiogenic Shock Receiving Acute Mechanical Circulatory Support
Authors: Davila Carlos D. , Esposito Michele , Hirst Colin S. , Morine Kevin , Jorde Lena , Newman Sarah , Paruchuri Vikram , Whitehead Evan , Thayer Katherine L. , Kapur Navin K.
Published: February 2021

Background: We describe the association between longitudinal hemodynamic changes and clinical outcomes in patients with cardiogenic shock (CS) receiving acute mechanical circulatory support devices (AMCS) at a single center. We hypothesized that improved right atrial pressure is associated with better survival in CS.

Methods: Retrospective analysis of patients from Tufts Medical Center that received AMCS for CS. Baseline characteristics and invasive hemodynamics were collected, analyzed, and correlated against outcomes. Hemodynamics were recorded at different time intervals during index admission [pre-AMCS, 24 h after AMCS (post AMCS), and last available set of hemodynamics (final-AMCS)]. Logistic regression was performed to determine variables associated with in-hospital mortality.

Results: A total of 76 patients had longitudinal hemodynamics available. In hospital mortality occurred in 46% of the cohort. Mean baseline right atrial pressure (RAP) was significantly higher among non-survivors vs. survivors (19.5+6.6 vs. 16.4+5.3 mmHg). Change in right atrial pressure from baseline to before device removal (ΔRA:final AMCS—pre AMCS) was significantly different between survivors and non survivors (−6.5 ± 6.9 mmHg vs. −2.5 ± 6.2 mmHg p = 0.03). Unadjusted logistic regression revealed baseline RAP (OR: 1.1 95% CI: 1.0–1.2), 24 h post device implant RAP (OR: 1.3 95% CI: 1.1–1.4), and final RAP (OR: 1.3 95% CI: 1.1–1.5) to be significant predictors of in-hospital mortality. In a multivariate logistic regression baseline RAP was no longer significantly associated with mortality in the overall cohort, while 24 h (OR: 1.26 95% CI: 1.1–1.5) and final RAP (OR: 1.3 95% CI: 1.1–1.6) remained statistically significant.

Conclusion: We report a novel retrospective analysis of hemodynamic changes in patients with CS receiving AMCS. Our findings identify the potential importance of venous congestion as a prognostic marker of mortality. Furthermore, early decongestion or reduced RA pressure is associated with better survival in these critically ill CS patients. These observations suggest the need for further study in larger retrospective and prospective cohorts of patients with varying degrees of CS severity.
Endurance Training Improves Oxygen Uptake and Endurance Capacity in Patients With Moderate to Severe Valvular Disease
Authors: Vonbank Karin , Haubenberger Daniel , Rosenhek Raphael , Schneider Matthias , Aschauer Stefan , Idzko Marco , Gabriel Harald
Published: February 2021

Aim: Peak oxygen uptake (peakVO2) is one of the strongest predictors of survival in patients with valvular heart disease. The purpose of this study was to determine whether endurance training improves peakVO2 and endurance capacity in patients with moderate-severe aortic and mitral valve disease.

Methods: 30 patients with moderate-severe valvular heart disease were randomly assigned to 12 weeks of endurance training (TG) (n = 16) or standard care (SC) (n = 14). PeakVO2 and maximum working capacity (Wattmax) were assessed by cardiopulmonary exercise testing, as well as submaximal endurance test at 80% of peakVO2 at baseline and after 12 weeks.

Results: There was a significant improvement in peakVO2 from 27.2 ± 5.9 ml/kg to 30.4 ± 6.3 ml/kg (P < 0.001) in TG compared to the SC (peakVO2 from 24.6 ± 4.4 to 24.7 ± 3.8) and in the Wattmax from 151.8 ± 41.0 Watt to 171.2 ± 49.7 Watt in the TG compared to the SC (152.9 ± 35.6 Watt to 149.2 ± 28.4 Watt). The endurance capacity increased significantly from 17.0 ± 9.4 min to 32.8 ± 16.8 min (p = 0.003) in the TG compared to the SC (11.7 ± 6.2 min to 11.2 ± 7.6 min). The heart rate during the endurance test decreased in the TG from 154 ± 14 b/min to 142 ± 20 b/min for the same workload. No changes could be seen in the SC.

Conclusion: Endurance training in patients with moderate to severe valvular heart disease increased significantly the peakVO2 as well as the endurance capacity.
Myocardial Disease and Long-Distance Space Travel: Solving the Radiation Problem
Authors: Meerman Manon , Bracco Gartner Tom C. L. , Buikema Jan Willem , Wu Sean M. , Siddiqi Sailay , Bouten Carlijn V. C. , Grande-Allen K. Jane , Suyker Willem J. L. , Hjortnaes Jesper
Published: February 2021

Radiation-induced cardiovascular disease is a well-known complication of radiation exposure. Over the last few years, planning for deep space missions has increased interest in the effects of space radiation on the cardiovascular system, as an increasing number of astronauts will be exposed to space radiation for longer periods of time. Research has shown that exposure to different types of particles found in space radiation can lead to the development of diverse cardiovascular disease via fibrotic myocardial remodeling, accelerated atherosclerosis and microvascular damage. Several underlying mechanisms for radiation-induced cardiovascular disease have been identified, but many aspects of the pathophysiology remain unclear. Existing pharmacological compounds have been evaluated to protect the cardiovascular system from space radiation-induced damage, but currently no radioprotective compounds have been approved. This review critically analyzes the effects of space radiation on the cardiovascular system, the underlying mechanisms and potential countermeasures to space radiation-induced cardiovascular disease.
Sex–Gender Disparities in Cardiovascular Diseases: The Effects of Estrogen on eNOS, Lipid Profile, and NFATs During Catecholamine Stress
Authors: Ndzie Noah Marie Louise , Adzika Gabriel Komla , Mprah Richard , Adekunle Adebayo Oluwafemi , Adu-Amankwaah Joseph , Sun Hong
Published: February 2021

Cardiovascular diseases (CVDs) characterized by sex–gender differences remain a leading cause of death globally. Hence, it is imperative to understand the underlying mechanisms of CVDs pathogenesis and the possible factors influencing the sex–gender disparities in clinical demographics. Attempts to elucidate the underlying mechanisms over the recent decades have suggested the mechanistic roles of estrogen in modulating cardioprotective and immunoregulatory effect as a factor for the observed differences in the incidence of CVDs among premenopausal and post-menopausal women and men. This review from a pathomechanical perspective aims at illustrating the roles of estrogen (E2) in the modulation of stimuli signaling in the heart during chronic catecholamine stress (CCS). The probable mechanism employed by E2 to decrease the incidence of hypertension, coronary heart disease, and pathological cardiac hypertrophy in premenopausal women are discussed. Initially, signaling via estrogen receptors and β-adrenergic receptors (βARs) during physiological state and CCS were summarized. By reconciling the impact of estrogen deficiency and hyperstimulation of βARs, the discussions were centered on their implications in disruption of nitric oxide synthesis, dysregulation of lipid profiles, and upregulation of nuclear factor of activated T cells, which induces the aforementioned CVDs, respectively. Finally, updates on E2 therapies for maintaining cardiac health during menopause and suggestions for the advancement treatments were highlighted.
Quantifying Downstream, Vertical and Lateral Variation in Fluvial Deposits: Implications From the Huesca Distributive Fluvial System
Authors: Martin Ben , Owen Amanda , Nichols Gary J. , Hartley Adrian J. , Williams Richard D.
Published: February 2021

Quantifying sedimentary deposits is crucial to fully test generic trends cited within facies models. To date, few studies have quantified downstream trends alongside vertical and lateral variations within distributive fluvial systems (DFS), with most studies reporting qualitative trends. This study reports on the generation of a quantitative dataset on the Huesca DFS, Ebro Basin, Spain, in which downstream, vertical and lateral trends in channel characteristics are analyzed using a fusion of field data and virtual outcrop model derived data (VOM). Vertical trend analysis reveals that the exposed portion of the Huesca DFS does not show any systematic changes through time, which suggests autogenic-driven local variability. Proximal-to-distal trends from field data display a downstream decrease in average channel body thicknesses (13.1–0.7 m), channel deposit percentage (70–4%), and average storey thicknesses (5.2–0.7 m) and confirm trends observed on other DFS. The VOM dataset shows a similar downstream trend in all characteristics. The range in values are, however, larger due to the increase in amount of data that can be collected, and trends are thus less clear. This study therefore highlights that standard field techniques do not capture the variability that can be present in outcrops. Channel percentage was found to be most variable (37% variation) in the medial setting, whereas channel body thickness is most variable (∼15 m range) in the proximal setting. Storey thickness varied in both the proximal and medial settings (range of 9 and 11 m for field and VOM data respectively) becoming more consistent downstream. Downstream shifts in architecture are also noted from massive, highly amalgamated channel-body sandstones in proximal regions to isolated or offset-stacked channel-bodies dominating the distal region. Trends are explained by spatial variability in DFS processes and preservation potential. The overlap present indicates that no single value is representative of position within a DFS, which has important implications for interpreting the location that a data point sits within a DFS when using limited (i.e., single log) datasets. These comparative results contribute to improving the accuracy of system-scale downstream predictions for channel characteristic variability within subsurface deposits.
Biomarker and Isotopic Composition of Seep Carbonates Record Environmental Conditions in Two Arctic Methane Seeps
Authors: Yao Haoyi , Panieri Giuliana , Lehmann Moritz F. , Himmler Tobias , Niemann Helge
Published: February 2021

Present-day activity of cold seeps in the ocean is evident from direct observations of methane emanating from the seafloor, the presence of chemosynthetic organisms, or the quantification of high gas concentrations in sediment pore waters and the water column. Verifying past cold seep activity and biogeochemical characteristics is more challenging but may be reconstructed from proxy records of authigenic seep carbonates. Here, we investigated the lipid-biomarker inventory, carbonate mineralogy, and stable carbon and oxygen isotope compositions of seep-associated carbonates from two active Arctic methane seeps, located to the northwest (Vestnesa Ridge; ∼1,200 m water depth) and south (Storfjordrenna; ∼380 m water depth) offshore Svalbard. The aragonite-dominated mineralogy of all but one carbonate sample indicate precipitation close to the seafloor in an environment characterized by high rates of sulfate-dependent anaerobic oxidation of methane (AOM). In contrast, Mg-calcite rich nodules sampled in sediments of Storfjordrenna appear to have formed at the sulfate-methane-transition zone deeper within the sediment at lower rates of AOM. AOM activity at the time of carbonate precipitation is indicated by the 13C-depleted isotope signature of the carbonates [−20 to −30‰ Vienna Pee Dee Belemnite (VPDB)], as well as high concentrations of 13C-depleted lipid biomarkers diagnostic for anaerobic methanotrophic archaea (archaeol and sn2-hydroxyarchaeol) and sulfate-reducing bacteria (iso and anteiso-C15:0 fatty acids) in the carbonates. We also found 13C-depleted lipid biomarkers (diploptene and a 4α-methyl sterol) that are diagnostic for bacteria mediating aerobic oxidation of methane (MOx). This suggests that the spatial separation between AOM and MOx zones was relatively narrow at the time of carbonate formation, as is typical for high methane-flux regimes. The seep-associated carbonates also displayed relatively high δ18O values (4.5–5‰ VPDB), indicating the presence of 18O-enriched fluids during precipitation, possibly derived from destabilized methane gas hydrates. Based on the combined isotopic evidence, we suggest that all the seep carbonates resulted from the anaerobic oxidation of methane during intense methane seepage. The seepage likely was associated to gas hydrates destabilization, which led to the methane ebullition from the seafloor into the water column.
Modelling the Effect of Electrification on Volcanic Ash Aggregation
Authors: Pollastri Stefano , Rossi Eduardo , Bonadonna Costanza , Merrison Jonathan P.
Published: February 2021

The fine ash released into the atmosphere (particles <63 μm) during explosive volcanic eruptions represents a significant threat for both the ecosystem and many sectors of society. In order to mitigate the associated impact, ash dispersal models need to accurately estimate ash concentration through time and space. Since most fine ash sediments in the form of aggregates, ash dispersal models require a quantitative description of ash aggregation. The physical and chemical processes involved in the collision and sticking of volcanic ash have been extensively studied in the last few decades. Among the different factors affecting volcanic particle aggregation (e.g., turbulence, particle-particle adhesion, presence of liquid and solid water), the charge carried by volcanic particles has been found to play a crucial role. However, Coulomb interactions are not yet taken into account in existing models. In order to fill this gap, we propose a strategy to take charge into account. In particular, we introduce a quantitative model for aggregation of oppositely charged micron—to millimetre-sized objects settling in still air. Our results show that the presence of charge considerably enhances the collision efficiency when one of the colliding objects is very small (<20 µm), and that the sticking efficiency is not affected by particle charge if colliding objects are either small enough (<20 µm) or large enough (>200 µm). Besides providing a theoretical framework to quantify the effect of charge, our findings demonstrate that aggregation models that do not account for electrification significantly underestimate the amount of fine ash that sediments in the form of aggregates, leading to an overestimation of the residence time of fine ash in the atmosphere after explosive volcanic eruptions.
A Review of the Microstructural Location of Impurities in Polar Ice and Their Impacts on Deformation
Authors: Stoll Nicolas , Eichler Jan , Hörhold Maria , Shigeyama Wataru , Weikusat Ilka
Published: February 2021

Insoluble and soluble impurities, enclosed in polar ice sheets, have a major impact on the deformation behaviour of the ice. Macro- and Micro-scale deformation observed in ice sheets and ice cores has been retraced to chemical loads in the ice, even though the absolute concentration is negligible. And therefore the exact location of the impurities matters: Allocating impurities to specific locations inside the ice microstructure inherently determines the physical explanation of the observed interaction between chemical load and the deformational behaviour. Both, soluble and non-soluble impurities were located in grain boundaries, triple junctions or in the grain interior, using different methods, samples and theoretical approaches. While each of the observations is adding to the growing understanding of the effect of impurities in polar ice, the growing number of ambiguous results calls for a dedicated and holistic approach in assessing the findings. Thus, we here aim to give a state of the art overview of the development in microstructural impurity research over the last 20 years. We evaluate the used methods, discuss proposed deformation mechanisms and identify two main reasons for the observed ambiguity: 1) limitations and biases of measurement techniques and 2) the physical state of the analysed impurity. To overcome these obstacles we suggest possible approaches, such as the continuous analysis of impurities in deep ice cores with complementary methods, the implementation of these analyses into established in-situ ice core processing routines, a more holistic analysis of the microstructural location of impurities, and an enhanced knowledge-transfer via an open access data base.
A Knowledge-Based Smart Trainer System for Transferring Knowledge From Coaches to Long Jump Students
Authors: Kamnardsiri Teerawat , Khuwuthyakorn Pattaraporn , Boripuntakul Sirinun , Janchai Worawit
Published: February 2021

Background:The constructive and specific feedback in guiding long jump athletes to improve their performance in each phase is part of the critical process for achieving desired long jump distance. However, to date, the potential approach for assisting a coach in capturing long jump movement and transferring their knowledge to long jump students is not well-established.

Objectives:To investigate the performance of long jump students and evaluate transferring knowledge from coaches to long jump students using a Knowledge-Based Smart Trainer (KBST) System.

Methods:Twenty-two participants (fifteen males, mean age = 15.33 ± 1.95 years; seven females, mean age = 14.57 ± 2.07 years) participated in the study. All participants were recruited from eleven sports schools in Thailand. Each participant was instructed to perform the long jump movement, including running, take-off, and landing, for three attempts (Test 1,Test 2,andTest 3).Test 1was the conventional approach (coaches provided the feedback based on their experience).Test 2andTest 3were the KBST system approach (coaches provided the feedback based on the results from KBST system). Two cameras were used to record the participant movement from the starting position to the landing position. The capture data were analyzed by KBST system program. The outcome measures were starting position, maximum velocity, maximum velocity position, and take-off angle. Repeated-Measures ANOVA was conducted to compare the long jump performance across the three trials. The statistical significance was set atp-value < 0.05.

Results:There was a statistically significant difference betweenTest 1andTest 3for long jump distance (mean difference = 0.292; Std. Error = 0.129; Sig. = 0.34). However, the mean of take-off angle was similar across the three trials (Test 1 =12.16°,Test 2= 12.71°, andTest 3= 12.95°, respectively).

Conclusion:TheKBSTsystem was effective in improving long jump students’ performance and also transferring knowledge from the coach to long jump students.
The Ablation of Thyroid Nodule’s Afferent Arteries Before Radiofrequency Ablation: Preliminary Data
Authors: Offi Chiara , Garberoglio Sara , Antonelli Giovanni , Esposito Maria Grazia , Brancaccio Umberto , Misso Claudia , D’Ambrosio Edoardo , Pace Daniela , Spiezia Stefano
Published: February 2021

Induced radiofrequency thermal ablation is the cytoreductive treatment of symptomatic benign thyroid nodules, metastatic and recurrent thyroid tumors and papillary thyroid microcarcinomas. It is a safe and effective alternative to surgery and it allows to obtain satisfactory results in terms of volumetric reduction of the nodule with significant improvement in the quality of life. The trans-isthmic approach and the moving shot technique are the two basic techniques; however, an advanced technique, artery-first feeding radiofrequency ablation, has been developed and validated. We have prospectively included 29 consecutive patients who have undergone radiofrequency ablation (Group A) or artery- first vRFA (Group B). All included patients had a diagnosis of benign nodular goiter and they underwent a single session of radiofrequency ablation. All patients followed a follow-up program at 1 month, 3 months, and 6 months. Continuous variables (age, TSH value, basal volume of nodule, used Joule, time in second of the procedure, nodules’ volume at 1-, 3-, and 6- months of follow-up and percentage of volume reduction at 1-, 3-, and 6- months of follow-up) were described as mean, standard deviation and range, while categorical variables (gender, nodule structure and nodule vascularization) were described as number of cases and percentage. Independent samples t-test were performed to compare the continuous variables. A Test of Proportions was applied to the categorical variables. The Fisher’s exact test was used to analyze the gender. Statistical significance was considered in case of p-value <0.05. Solid structure and spongiform structure showed statistic differences with p-values of 0.022 and 0.023 respectively between two groups. The percentage of reduction at 1 month did not show a significant difference between two groups; instead, the percentage of volume reduction was decreased mostly in the Group B at 3 months and 6 months of follow-up with a p-value of 0.003 and 0.013, respectively. The Joules/energy used showed a statistically significant difference (p-value=0.05), more energy must be used in vascular radiofrequency ablation. These data allow us to hypothesize that vRFA may improve the effectiveness of the procedure, allowing for a reduction in volume more quickly. They were preliminary but promising results, clearly a larger series of cases and prolonged follow-up are needed to clarify and confirm our observations.
Modeling the Effects of Agricultural Innovation and Biocapacity on Carbon Dioxide Emissions in an Agrarian-Based Economy: Evidence From the Dynamic ARDL Simulations
Authors: Ali Aminu , Usman Monday , Usman Ojonugwa , Sarkodie Samuel Asumadu
Published: February 2021

In this paper, we modeled the effects of income, agricultural innovation, energy utilization, and biocapacity on Carbon dioxide (CO2) emissions. We tested the validity of the environmental Kuznets curve (EKC) hypothesis for Nigeria from 1981 to 2014. We applied the novel dynamic autoregressive distributed lag (ARDL) simulations to develop conceptual tools for policy formulation. The empirical results confirmed the EKC hypothesis and found that agricultural innovation and energy utilization have an escalation effect on CO2 emissions whereas income and biocapacity have long-run emission-reduction effects. The causality results found agricultural innovation attributable to CO2 emissions and observed that income drives energy demand. Income, biocapacity, and energy utilization are found to predict changes in CO2 emissions. These results are validated by the innovation accounting techniques—wherein 22.79% of agricultural innovation corresponds to 49.43% CO2 emissions—5.95% of biocapacity has 35.78% attributable CO2 emissions—and 1.61% of energy spurs CO2 emissions by 16.27%. The policy implication for this study is that energy efficiency, clean energy utilization and sustainable ecosystem recovery and management are the surest ways to combat climate change and its impacts.
Preparation and Electrochemical Performance of V2O5 @N-CNT/S Composite Cathode Materials
Authors: Liu Cheng , Xiang Meng , Zhang Haiyang , Feng Shuaiqiang , Xiao Jianrong , Ma Songshan , Li Xinyu
Published: February 2021

Lithium–sulfur battery hasreceived widespread attention because of its high energy density, low cost, environmental friendliness, and nontoxicity. However, the insulating properties of elemental sulfur, huge volume changes, and dissolution of polysulfides in electrolytes that result in the shuttle effect, low sulfur utilization, and low rate performance seriously hinder the commercialization of lithium–sulfur batteries. In this work, a composite material of nitrogen-doped multiwalled carbon nanotubes and V2O5 was designed and fabricated to serve as the positive electrode of lithium–sulfur battery via the hydrothermal method. The positive electrode of the V2O5@N-CNTs composite material could reach an initial discharge specific capacity of 1,453 mAh g−1at a rate of 0.1C. Moreover, the composite material could maintain a discharge ratio of 538 mAh g−1 at a rate of 0.5C even after 200 charge and discharge cycles. After 400 cycles, the composite had a specific discharge capacity of 439 mAh g−1 at a rate of 1.0C. The excellent electrochemical performance of the V2O5@N-CNT/S composite cathode material was due to the fact that V2O5 contains oxygen ions and has a strong polarized surface. Furthermore, nitrogen doping changed the hybrid structure of carbon atoms and provided additional active sites, thereby improving the conductivity of the material itself and effectively inhibiting the dissolution and diffusion of polysulfides.