bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed Cell Death Protein 1 Blockade Reduces Glycogen Synthase Kinase 3β Activity and Tau Hyperphosphorylation in Alzheimer’s Disease Mouse Models
Authors: Zou Yulian , Gan Chen-Ling , Xin Zhiming , Zhang Hai-Tao , Zhang Qi , Lee Tae Ho , Pan Xiaodong , Chen Zhou
Published: December 2021

Alzheimer’s disease (AD) is a central nervous system degenerative disease, with no effective treatment to date. Administration of immune checkpoint inhibitors significantly reduces neuronal damage and tau hyperphosphorylation in AD, but the specific mechanism is unclear. Here, we found that programmed cell death-receptor 1 (PD1) and its ligand PDL1 were induced by an intracerebroventricular injection of amyloid-β; they were significantly upregulated in the brains of APP/PS1, 5×FAD mice and in SH-SY5Y-APP cell line compared with control. The PD1 and PDL1 levels positively correlated with the glycogen synthase kinase 3 beta (GSK3β) activity in various AD mouse models, and the PDL1-GSK3β immune complex was found in the brain. The application of PD1-blocking antibody reduced tau hyperphosphorylation and GSK3β activity and prevented memory impairments. Mechanistically, we identified PD1 as a critical regulator of GSK3β activity. These results suggest that the immune regulation of the PD1/PDL1 axis is closely involved in AD.
The Synergistic Effects of SHR6390 Combined With Pyrotinib on HER2+/HR+ Breast Cancer
Authors: Wang Yukun , Yuan Xiang , Li Jing , Liu Zhiwei , Li Xinyang , Wang Ziming , Wei Limin , Li Yuanpei , Wang Xinshuai
Published: December 2021

HER2+/HR+ breast cancer is a special molecular type of breast cancer. Existing treatment methods are prone to resistance; “precision treatment” is necessary. Pyrotinib is a pan-her kinase inhibitor that can be used in HER2-positive tumors, while SHR6390 is a CDK4/6 inhibitor that can inhibit ER+ breast cancer cell cycle progression and cancer cell proliferation. In cancer cells, HER2 and CDK4/6 signaling pathways could be nonredundant; co-inhibition of both pathways by combination of SHR6390 and pyrotinib may have synergistic anticancer activity on HER2+/HR+ breast cancer. In this study, we determined the synergy of the two-drug combination and underlying molecular mechanisms. We showed that the combination of SHR6390 and pyrotinib synergistically inhibited the proliferation, migration, and invasion of HER2+/HR+ breast cancer cells in vitro. The combination of two drugs induced G1/S phase arrest and apoptosis in HER2+/HR+ breast cancer cell lines. The combination of two drugs prolonged the time to tumor recurrence in the xenograft model system. By second-generation RNA sequencing technology and enrichment analysis of the pyrotinib-resistant cell line, we found that FOXM1 was associated with induced resistance to HER2-targeted therapy. In HER2+/HR+ breast cancer cell lines, the combination of the two drugs could further reduce FOXM1 phosphorylation, thereby enhancing the antitumor effect to a certain extent. These findings suggest that SHR6390 combination with pyrotinib suppresses the proliferation, migration, and invasion of HER2+/HR+ breast cancers through regulation of FOXM1.
The Tongue Squamous Carcinoma Cell Line Cal27 Primarily Employs Integrin α6β4-Containing Type II Hemidesmosomes for Adhesion Which Contribute to Anticancer Drug Sensitivity
Authors: Tadijan Ana , Humphries Jonathan D. , Samaržija Ivana , Stojanović Nikolina , Zha Junzhe , Čuljak Kristina , Tomić Marija , Paradžik Mladen , Nestić Davor , Kang Heemin , Humphries Martin J. , Ambriović-Ristov Andreja
Published: December 2021

Integrins are heterodimeric cell surface glycoproteins used by cells to bind to the extracellular matrix (ECM) and regulate tumor cell proliferation, migration and survival. A causative relationship between integrin expression and resistance to anticancer drugs has been demonstrated in different tumors, including head and neck squamous cell carcinoma. Using a Cal27 tongue squamous cell carcinoma model, we have previously demonstrated that de novo expression of integrin αVβ3 confers resistance to several anticancer drugs (cisplatin, mitomycin C and doxorubicin) through a mechanism involving downregulation of active Src, increased cell migration and invasion. In the integrin αVβ3 expressing Cal27-derived cell clone 2B1, αVβ5 expression was also increased, but unrelated to drug resistance. To identify the integrin adhesion complex (IAC) components that contribute to the changes in Cal27 and 2B1 cell adhesion and anticancer drug resistance, we isolated IACs from both cell lines. Mass spectrometry (MS)-based proteomics analysis indicated that both cell lines preferentially, but not exclusively, use integrin α6β4, which is classically found in hemidesmosomes. The anticancer drug resistant cell clone 2B1 demonstrated an increased level of α6β4 accompanied with increased deposition of a laminin-332-containing ECM. Immunofluorescence and electron microscopy demonstrated the formation of type II hemidesmosomes by both cell types. Furthermore, suppression of α6β4 expression in both lines conferred resistance to anticancer drugs through a mechanism independent of αVβ3, which implies that the cell clone 2B1 would have been even more resistant had the upregulation of α6β4 not occurred. Taken together, our results identify a key role for α6β4-containing type II hemidesmosomes in regulating anticancer drug sensitivity.
Long Noncoding RNA H19: A Novel Therapeutic Target Emerging in Oncology Via Regulating Oncogenic Signaling Pathways
Authors: Wu Baokang , Zhang Yizhou , Yu Yang , Zhong Chongli , Lang Qi , Liang Zhiyun , Lv Chao , Xu Feng , Tian Yu
Published: December 2021

Long noncoding RNA H19 (H19) is an imprinting gene with only maternal expression that is involved in regulating different processes in various types of cells. Previous studies have shown that abnormal H19 expression is involved in many pathological processes, such as cancer, mainly through sponging miRNAs, interacting with proteins, or regulating epigenetic modifications. Accumulating evidence has shown that several oncogenic signaling pathways lead to carcinogenesis. Recently, the regulatory relationship between H19 and oncogenic signaling pathways in various types of cancer has been of great interest to many researchers. In this review, we discussed the key roles of H19 in cancer development and progression via its regulatory function in several oncogenic signaling pathways, such as PI3K/Akt, canonical Wnt/β-catenin, canonical NF-κB, MAPK, JAK/STAT and apoptosis. These oncogenic signaling pathways regulated by H19 are involved in cell proliferation, proliferation, migration and invasion, angiogenesis, and apoptosis of various cancer cells. This review suggests that H19 may be a novel therapeutic target for cancers treatment by regulating oncogenic signaling pathways.
Gene-Based Testing of Interactions Using XGBoost in Genome-Wide Association Studies
Authors: Guo Yingjie , Wu Chenxi , Yuan Zhian , Wang Yansu , Liang Zhen , Wang Yang , Zhang Yi , Xu Lei
Published: December 2021

Among the myriad of statistical methods that identify gene–gene interactions in the realm of qualitative genome-wide association studies, gene-based interactions are not only powerful statistically, but also they are interpretable biologically. However, they have limited statistical detection by making assumptions on the association between traits and single nucleotide polymorphisms. Thus, a gene-based method (GGInt-XGBoost) originated from XGBoost is proposed in this article. Assuming that log odds ratio of disease traits satisfies the additive relationship if the pair of genes had no interactions, the difference in error between the XGBoost model with and without additive constraint could indicate gene–gene interaction; we then used a permutation-based statistical test to assess this difference and to provide a statistical p-value to represent the significance of the interaction. Experimental results on both simulation and real data showed that our approach had superior performance than previous experiments to detect gene–gene interactions.
The RUNX1b Isoform Defines Hemogenic Competency in Developing Human Endothelial Cells
Authors: Menegatti Sara , Potts Bethany , Garcia-Alegria Eva , Paredes Roberto , Lie-A-Ling Michael , Lacaud Georges , Kouskoff Valerie
Published: December 2021

The transcription factor RUNX1 is a master regulator of blood cell specification. During embryogenesis, hematopoietic progenitors are initially generated from hemogenic endothelium through an endothelium-to-hematopoietic transition controlled by RUNX1. Several studies have dissected the expression pattern and role of RUNX1 isoforms at the onset of mouse hematopoiesis, however the precise pattern of RUNX1 isoform expression and biological output of RUNX1-expressing cells at the onset of human hematopoiesis is still not fully understood. Here, we investigated these questions using a RUNX1b:VENUS RUNX1c:TOMATO human embryonic stem cell line which allows multi-parameter single cell resolution via flow cytometry and isolation of RUNX1b-expressing cells for further analysis. Our data reveal the sequential expression of the two RUNX1 isoforms with RUNX1b expressed first in a subset of endothelial cells and during the endothelial to hematopoietic transition while RUNX1c only becomes expressed in fully specified blood cells. Furthermore, our data show that RUNX1b marks endothelial cells endowed with hemogenic potential and that RUNX1b expression level determines hemogenic competency in a dose-dependent manner. Together our data reveal the dynamic of RUNX1 isoforms expression at the onset of human blood specification and establish RUNX1b isoform as the earliest known marker for hemogenic competency.
Weibel Palade Bodies: Unique Secretory Organelles of Endothelial Cells that Control Blood Vessel Homeostasis
Authors: Naß Johannes , Terglane Julian , Gerke Volker
Published: December 2021

Vascular endothelial cells produce and release compounds regulating vascular tone, blood vessel growth and differentiation, plasma composition, coagulation and fibrinolysis, and also engage in interactions with blood cells thereby controlling hemostasis and acute inflammatory reactions. These interactions have to be tightly regulated to guarantee smooth blood flow in normal physiology, but also allow specific and often local responses to blood vessel injury and infectious or inflammatory insults. To cope with these challenges, endothelial cells have the remarkable capability of rapidly changing their surface properties from non-adhesive (supporting unrestricted blood flow) to adhesive (capturing circulating blood cells). This is brought about by the evoked secretion of major adhesion receptors for platelets (von-Willebrand factor, VWF) and leukocytes (P-selectin) which are stored in a ready-to-be-used form in specialized secretory granules, the Weibel-Palade bodies (WPB). WPB are unique, lysosome related organelles that form at the trans-Golgi network and further mature by receiving material from the endolysosomal system. Failure to produce correctly matured VWF and release it through regulated WPB exocytosis results in pathologies, most importantly von-Willebrand disease, the most common inherited blood clotting disorder. The biogenesis of WPB, their intracellular motility and their fusion with the plasma membrane are regulated by a complex interplay of proteins and lipids, involving Rab proteins and their effectors, cytoskeletal components as well as membrane tethering and fusion machineries. This review will discuss aspects of WPB biogenesis, trafficking and exocytosis focussing on recent findings describing factors contributing to WPB maturation, WPB-actin interactions and WPB-plasma membrane tethering and fusion.
The Peroxisome-Autophagy Redox Connection: A Double-Edged Sword?
Authors: Li Hongli , Lismont Celien , Revenco Iulia , Hussein Mohamed A. F. , Costa Cláudio F. , Fransen Marc
Published: December 2021

Peroxisomes harbor numerous enzymes that can produce or degrade hydrogen peroxide (H2O2). Depending on its local concentration and environment, this oxidant can function as a redox signaling molecule or cause stochastic oxidative damage. Currently, it is well-accepted that dysfunctional peroxisomes are selectively removed by the autophagy-lysosome pathway. This process, known as “pexophagy,” may serve a protective role in curbing peroxisome-derived oxidative stress. Peroxisomes also have the intrinsic ability to mediate and modulate H2O2-driven processes, including (selective) autophagy. However, the molecular mechanisms underlying these phenomena are multifaceted and have only recently begun to receive the attention they deserve. This review provides a comprehensive overview of what is known about the bidirectional relationship between peroxisomal H2O2 metabolism and (selective) autophagy. After introducing the general concepts of (selective) autophagy, we critically examine the emerging roles of H2O2 as one of the key modulators of the lysosome-dependent catabolic program. In addition, we explore possible relationships among peroxisome functioning, cellular H2O2 levels, and autophagic signaling in health and disease. Finally, we highlight the most important challenges that need to be tackled to understand how alterations in peroxisomal H2O2 metabolism contribute to autophagy-related disorders.
Synthesis of Hierarchically Porous Metal Oxide Monoliths via Sol–Gel Process Accompanied by Phase Separation From Divalent Metal Salts: A Short Review
Authors: Lu Xuanming , Nakanishi Kazuki
Published: December 2021

The sol–gel process accompanied by phase separation is one of the methods to prepare hierarchically porous monoliths, hierarchically porous monolith, which is applicable not only to oxides but also to various materials compositions such as metal phosphates, organic-polymers/carbons, metal-organic frameworks. It is not until recently, however, that progress has been made in the preparation of low-valence metal oxide HPMs, such as those of magnesium, manganese, cobalt, nickel, etc. Due to the difficulty of divalent metal precursors to form homogeneous gels, different approaches from those established for trivalent and tetravalent counterparts have been attempted. This short review introduces the methods and trials in the preparation of metal oxide HPMs from divalent metal salts.
Vitreoscilla filiformis Extract for Topical Skin Care: A Review
Authors: Gueniche Audrey , Liboutet Muriel , Cheilian Stephanie , Fagot Dominique , Juchaux Franck , Breton Lionel
Published: December 2021

The term probiotic has been defined by experts as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host. Probiotics are, thus, by definition, live microorganisms, and the viability of probiotics is a prerequisite for certain benefits, such as the release of metabolites at the site or adhesion properties, for example. However, some semi-active or non-replicative bacterial preparations may retain a similar activity to the live forms. On cosmetic, lysates or fractions are generally used. Topically applied Vitreoscilla filiformis extract has shown to have some similar biological activity of probiotics in the gut, for example, regulating immunity by optimisation of regulatory cell function, protecting against infection, and helping skin barrier function for better recovery and resistance. Due to their mode of action and efficacy, V. filiformis extract (lysate including membrane and cytosol) may be considered as non-replicative probiotic fractions, and this review article presents all its properties.
Co-Speech Movement in Conversational Turn-Taking
Authors: Danner Samantha Gordon , Krivokapić Jelena , Byrd Dani
Published: December 2021

This study investigates co-speech movements as a function of the conversational turn exchange type, the type of speech material at a turn exchange, and the interlocutor’s role as speaker or listener. A novel interactive protocol that mixes conversation and (non-read) nursery rhymes works to elicit many speech turns and co-speech movements within dyadic speech interaction. To evaluate a large amount of data, we use the density of co-speech movement as a quantitative measure. Results indicate that both turn exchange type and participant role are associated with variation in movement density for head and brow co-speech movement. Brow and head movement becomes denser as speakers approach overlapping speech exchanges, indicating that speakers increase their movement density as an interruptive exchange is approached. Similarly, head movement generally increases after such overlapping exchanges. Lastly, listeners display a higher rate of co-speech movement than speakers, both at speech turns and remote from them. Brow and head movements generally behave similarly across speech material types, conversational roles, and turn exchange types. On the whole, the study demonstrates that the quantitative co-speech movement density measure advanced here is useful in the study of co-speech movement and turn-taking.
Wild Predators, Livestock, and Free Ranging Dogs: Patterns of Livestock Mortality and Attitudes of People Toward Predators in an Urbanizing Trans-Himalayan Landscape
Authors: Pahuja Meenal , Sharma Rishi Kumar
Published: December 2021

Livestock depredation by large carnivores is a significant source of conflicts over predators and an important conservation and economic concern. Preventing livestock loss to wild predators is a substantial focus of human-carnivore conflict mitigation programs. A key assumption of the preventive strategy is reduction in the livestock losses leading to a positive shift in the attitudes toward predators. Therefore, it is important to quantify the true extent of livestock mortality caused by wild predators and its influence on attitudes of the affected communities. We examined seasonal and spatial patterns of livestock mortality and factors influencing people's attitudes toward wild predators i.e., snow leopards (Panthera uncia) and wolves (Canis lupuschanco) and free-ranging dogs (Canis lupusfamiliaris) in a Trans-Himalayan urbanizing landscape in India. We used systematic sampling to select the survey households and implemented a semi-structured questionnaire to respondents. The sampled villages (n= 16) represent a mosaic of urban and agricultural ecosystems within a radius of 40 km of Leh town. In 2016–2017, 93% of the sampled households lost livestock to predators, accounting for 0.93 animals per household per year. However, of the total events of livestock mortality, 33% were because of weather/natural events, 24% by snow leopards, 20% because of disease, 15% because of free-ranging dogs and 9% because of wolves. The annual economic loss per household because of livestock mortality was USD 371, a substantial loss given the average per capita income of USD 270 in the region. Of the total loss, weather/natural events caused highest loss of USD 131 (35%), followed by snow leopards USD 91 (25%), disease USD 87 (24%), free ranging dogs USD 48 (13%), and wolves USD 14 (4%). Despite losing a considerable proportion of livestock (33 %) to wild predators, respondents showed a positive attitude toward them but exhibited neutral attitudes toward free-ranging dogs. Gender emerged as the most important determinant of attitudes toward wild predators, with men showing higher positive attitude score toward wild predators than women. Our findings highlight the context specific variation in human-wildlife interactions and emphasize that generalizations must be avoided in the absence of site specific evidence.
Public Perceptions of Deer Management in Scotland
Authors: Hare Darragh , Daniels Mike , Blossey Bernd
Published: December 2021

In Scotland, large deer populations are associated with negative ecological and socioeconomic impacts, such as damage to peatlands and forests, agricultural and commercial forestry losses, Lyme disease transmission, and road accidents. Increasing the annual deer cull might help address these negative impacts, but could be ethically controversial. A stratified sample of adults living in Scotland (n = 1,002) responded to our online questionnaire measuring perceptions of deer management, including the acceptability of increasing the deer cull if doing so would help achieve a variety of ecological and social objectives. Overall, respondents indicated that it would be acceptable to increase the deer cull if doing so would serve public interests by reducing negative impacts of deer, with deer welfare, environmental conservation, and public health and safety being the most relevant ethical considerations. Although rural and urban respondents reported significantly different experiences and perceptions of deer, their values (i.e., attitudes, beliefs, and policy preferences) regarding deer management were very similar. Understanding values of the general public, beyond vocal interest groups, can help inform decisions on contentious wildlife management issues.
Molecular Mechanisms and Epigenetic Regulation in Diabetic Cardiomyopathy
Authors: Mittal Anupam , Garg Rajni , Bahl Ajay , Khullar Madhu
Published: December 2021

Diabetes mellitus (DM) is an important lifestyle disease. Type 2 diabetes is one of the prime contributors to cardiovascular diseases (CVD) and diabetic cardiomyopathy (DbCM) and leads to increased morbidity and mortality in patients with DM. DbCM is a typical cardiac disease, characterized by cardiac remodeling in the presence of DM and in the absence of other comorbidities such as hypertension, valvular diseases, and coronary artery disease. DbCM is associated with defective cardiac metabolism, altered mitochondrial structure and function, and other physiological and pathophysiological signaling mechanisms such as oxidative stress, inflammation, myocardial apoptosis, and autophagy. Epigenetic modifiers are crucial players in the pathogenesis of DbCM. Thus, it is important to explore the role of epigenetic modifiers or modifications in regulating molecular pathways associated with DbCM. In this review, we have discussed the role of various epigenetic mechanisms such as histone modifications (acetylation and methylation), DNA methylation and non-coding RNAs in modulating molecular pathways involved in the pathophysiology of the DbCM.
Relationship Between Heart Rate Variability and Pulse Rate Variability Measures in Patients After Coronary Artery Bypass Graft Surgery
Authors: Chen Yung-Sheng , Lin Yi-Ying , Shih Chun-Che , Kuo Cheng-Deng
Published: December 2021

Background: Heart rate variability (HRV) and pulse rate variability (PRV) measures are two kinds of physiological indices that can be used to evaluate the autonomic nervous function of healthy subjects and patients with various kinds of illness.

Purpose: In this study, we compared the agreement and linear relationship between electrocardiographic signals (ECG)-derived HRV and photoplethysmographic signals (PPG)-derived right hand PRV (R-PRV) and left hand PRV (L-PRV) measures in 14 patients over 1 year after coronary artery bypass graft (CABG) surgery.

Method: The ECG and PPG signals of the patient were recorded simultaneously for 10 min in a supine position. The last 512 stationary RR intervals (RRI) and peak-to peak intervals (PPI) of pulse wave were derived for data analysis. Bland-Altman plot was used to assess the agreement among HRV and both hand PRV measures, while linear regression analysis was used to examine the relationship among corresponding measures of HRV, R-PRV, and L-PRV.

Result: The results revealed significant differences in total power (TP), very low-frequency power (VLF), low-frequency power (LF), high-frequency power (HF), and normalized VLF (VLFnorm) among HRV, R-PRV, and L-PRV. Bland-Altman plot analysis showed good agreements in almost all measures between R-PRV and L-PRV, except insufficient agreement was found in LF/HF. Insufficient agreements were found in root mean square successive difference (RMSSD), normalized HF (HFnorm), and LF/HF indices between HRV and L-PRV, and in VLFnorm, HFnorm, and LF/HF indices between HRV and R-PRV. Linear regression analysis showed that the HRV, R-PRV, and L-PRV measures were all highly correlated with one another (r = 0.94 ~ 1; p < 0.001).

Conclusion: Though PRV measures of either hand are not surrogates of HRV measures, they might still be used to evaluate the autonomic nervous functions of CABG patients due to the moderate to good agreements in most time-domain and frequency-domain HRV measures and the strong and positive correlations among HRV and both hands PRV measures in CABG patients.
Nutritional Risk Index Improves the GRACE Score Prediction of Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Ma Xiao-Teng , Shao Qiao-Yu , Li Qiu-Xuan , Yang Zhi-Qiang , Han Kang-Ning , Liang Jing , Shen Hua , Liu Xiao-Li , Zhou Yu-Jie , Wang Zhi-Jian
Published: December 2021

Background: Malnutrition has been shown to be associated with adverse cardiovascular outcomes in many patient populations.

Aims: To investigate the prognostic significance of malnutrition as defined by nutritional risk index (NRI) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and whether NRI could improve the GRACE score based prognostic models.

Methods: This study applied NRI among 1,718 patients with ACS undergoing PCI. Patients were divided into three nutritional risk groups according to their baseline NRI: no nutritional risk (NRI ≥ 100), mild nutritional risk (97.5 ≤ NRI <100), and moderate-to-severe nutritional risk (NRI <97.5). The primary endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, non-fatal stroke, non-fatal myocardial infarction, or unplanned repeat revascularization.

Results: During a median follow-up of 927 days, 354 patients developed MACE. In the overall population, compared with normal nutritional status, malnutrition was associated with increased risk for MACE [adjusted HR for mild and moderate-to-severe nutritional risk, respectively: 1.368 (95%CI 1.004–1.871) and 1.473 (95%CI 1.064–2.041)], and NRI significantly improved the predictive ability of the GRACE score for MACE (cNRI: 0.070, P = 0.010; IDI: 0.005, P < 0.001). In the diabetes subgroup, malnutrition was associated with nearly 2-fold high adjusted risk of MACE, and the GRACE score combined with NRI appeared to have better predictive ability than that in the overall population.

Conclusion: Malnutrition as defined by NRI was independently associated with MACE in ACS patients who underwent PCI, especially in individuals with diabetes, and improved the predictive ability of the GRACE score based prognostic models.
Recent Progress in Cardiovascular Research Involving Single-Cell Omics Approaches
Authors: Dai Zhehao , Nomura Seitaro
Published: December 2021

Cardiovascular diseases are among the leading causes of morbidity and mortality worldwide. Although the spectrum of the heart from development to disease has long been studied, it remains largely enigmatic. The emergence of single-cell omics technologies has provided a powerful toolbox for defining cell heterogeneity, unraveling previously unknown pathways, and revealing intercellular communications, thereby boosting biomedical research and obtaining numerous novel findings over the last 7 years. Not only cell atlases of normal and developing hearts that provided substantial research resources, but also some important findings regarding cell-type-specific disease gene program, could never have been established without single-cell omics technologies. Herein, we briefly describe the latest technological advances in single-cell omics and summarize the major findings achieved by such approaches, with a focus on development and homeostasis of the heart, myocardial infarction, and heart failure.
Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights
Authors: Gander Joséphine , Carrard Justin , Gallart-Ayala Hector , Borreggine Rébecca , Teav Tony , Infanger Denis , Colledge Flora , Streese Lukas , Wagner Jonathan , Klenk Christopher , Nève Gilles , Knaier Raphael , Hanssen Henner , Schmidt-Trucksäss Arno , Ivanisevic Julijana
Published: December 2021

Coronary artery disease (CAD) remains the leading cause of death worldwide. Expanding patients' metabolic phenotyping beyond clinical chemistry investigations could lead to earlier recognition of disease onset and better prevention strategies. Additionally, metabolic phenotyping, at the molecular species level, contributes to unravel the roles of metabolites in disease development. In this cross-sectional study, we investigated clinically healthy individuals (n = 116, 65% male, 70.8 ± 8.7 years) and patients with CAD (n = 54, 91% male, 67.0 ± 11.5 years) of the COmPLETE study. We applied a high-coverage quantitative liquid chromatography-mass spectrometry approach to acquire a comprehensive profile of serum acylcarnitines, free carnitine and branched-chain amino acids (BCAAs), as markers of mitochondrial health and energy homeostasis. Multivariable linear regression analyses, adjusted for confounders, were conducted to assess associations between metabolites and CAD phenotype. In total, 20 short-, medium- and long-chain acylcarnitine species, along with L-carnitine, valine and isoleucine were found to be significantly (adjusted p ≤ 0.05) and positively associated with CAD. For 17 acylcarnitine species, associations became stronger as the number of affected coronary arteries increased. This implies that circulating acylcarnitine levels reflect CAD severity and might play a role in future patients' stratification strategies. Altogether, CAD is characterized by elevated serum acylcarnitine and BCAA levels, which indicates mitochondrial imbalance between fatty acid and glucose oxidation.
Progressive Microstructural Deterioration Dictates Evolving Biomechanical Dysfunction in the Marfan Aorta
Authors: Cavinato Cristina , Chen Minghao , Weiss Dar , Ruiz-Rodríguez Maria Jesús , Schwartz Martin A. , Humphrey Jay D.
Published: December 2021

Medial deterioration leading to thoracic aortic aneurysms arises from multiple causes, chief among them mutations to the gene that encodes fibrillin-1 and leads to Marfan syndrome. Fibrillin-1 microfibrils associate with elastin to form elastic fibers, which are essential structural, functional, and instructional components of the normal aortic wall. Compromised elastic fibers adversely impact overall structural integrity and alter smooth muscle cell phenotype. Despite significant progress in characterizing clinical, histopathological, and mechanical aspects of fibrillin-1 related aortopathies, a direct correlation between the progression of microstructural defects and the associated mechanical properties that dictate aortic functionality remains wanting. In this paper, age-matched wild-type, Fbn1C1041G/+, and Fbn1mgR/mgR mouse models were selected to represent three stages of increasing severity of the Marfan aortic phenotype. Ex vivo multiphoton imaging and biaxial mechanical testing of the ascending and descending thoracic aorta under physiological loading conditions demonstrated that elastic fiber defects, collagen fiber remodeling, and cell reorganization increase with increasing dilatation. Three-dimensional microstructural characterization further revealed radial patterns of medial degeneration that become more uniform with increasing dilatation while correlating strongly with increased circumferential material stiffness and decreased elastic energy storage, both of which comprise aortic functionality.
Influence of Supraglacial Debris Thickness on Thermal Resistance of the Glaciers of Chandra Basin, Western Himalaya
Authors: Patel Lavkush Kumar , Sharma Parmanand , Singh Ajit , Oulkar Sunil , Pratap Bhanu , Thamban Meloth
Published: December 2021

A large number of glaciers in the Hindu-Kush Himalaya are covered with debris in the lower part of the ablation zone, which is continuously expanding due to enhanced glacier mass loss. The supraglacial debris transported over the melting glacier surface acts as an insulating barrier between the ice and atmospheric conditions and has a strong influence on the spatial distribution of surface ice melt. We conducted in-situ field measurements of point-wise ablation rate, supraglacial debris thickness, and debris temperature to examine the thermal resistivity of the debris pack and its influence on ablation over three glaciers (Bara Shigri, Batal, and Kunzam) in Chandra Basin of Western Himalaya during 2016–2017. Satellite-based supraglacial debris cover assessment shows an overall debris covered area of 15% for Chandra basin. The field data revealed that the debris thickness varied between 0.5 and 326 cm, following a spatially distributed pattern in the Chandra basin. The studied glaciers have up to 90% debris cover within the ablation area, and together represent ∼33.5% of the total debris-covered area in the basin. The supraglacial debris surface temperature and near-surface air temperature shows a significant correlation (r = > 0.88, p = < 0.05), which reflects the effective control of energy balance over the debris surface. The thermal resistivity measurements revealed low resistance (0.009 ± 0.01 m2°C W−1) under thin debris pack and high resistance (0.55 ± 0.09 m2°C W−1) under thick debris. Our study revealed that the increased thickness of supraglacial debris significantly retards the glacier ablation due to its high thermal resistivity.
Ovarian Aging: Role of Pituitary-Ovarian Axis Hormones and ncRNAs in Regulating Ovarian Mitochondrial Activity
Authors: Colella Marco , Cuomo Danila , Peluso Teresa , Falanga Ilaria , Mallardo Massimo , De Felice Mario , Ambrosino Concetta
Published: December 2021

The number of mitochondria in the oocyte along with their functions (e.g., energy production, scavenger activity) decline with age progression. Such multifaceted functions support several processes during oocyte maturation, ranging from energy supply to synthesis of the steroid hormones. Hence, it is hardly surprising that their impairment has been reported in both physiological and premature ovarian aging, wherein they are crucial players in the apoptotic processes that arise in aged ovaries. In any form, ovarian aging implies the progressive damage of the mitochondrial structure and activities as regards to ovarian germ and somatic cells. The imbalance in the circulating hormones and peptides (e.g., gonadotropins, estrogens, AMH, activins, and inhibins), active along the pituitary-ovarian axis, represents the biochemical sign of ovarian aging. Despite the progress accomplished in determining the key role of the mitochondria in preserving ovarian follicular number and health, their modulation by the hormonal signalling pathways involved in ovarian aging has been poorly and randomly explored. Yet characterizing this mechanism is pivotal to molecularly define the implication of mitochondrial dysfunction in physiological and premature ovarian aging, respectively. However, it is fairly difficult considering that the pathways associated with ovarian aging might affect mitochondria directly or by altering the activity, stability and localization of proteins controlling mitochondrial dynamics and functions, either unbalancing other cellular mediators, released by the mitochondria, such as non-coding RNAs (ncRNAs). We will focus on the mitochondrial ncRNAs (i.e., mitomiRs and mtlncRNAs), that retranslocate from the mitochondria to the nucleus, as active players in aging and describe their role in the nuclear-mitochondrial crosstalk and its modulation by the pituitary-ovarian hormone dependent pathways. In this review, we will illustrate mitochondria as targets of the signaling pathways dependent on hormones and peptides active along the pituitary/ovarian axis and as transducers, with a particular focus on the molecules retrieved in the mitochondria, mainly ncRNAs. Given their regulatory function in cellular activities we propose them as potential diagnostic markers and/or therapeutic targets.
Green Energy Sources Assessment Using Sentinel-1 Satellite Remote Sensing
Authors: Majidi Nezhad Meysam , Nastasi Benedetto , Groppi Daniele , Lamagna Mario , Piras Giuseppe , Astiaso Garcia Davide
Published: December 2021

Due to the growing use of Green Energy Sources (GESs), the activities of mapping, monitoring, measurement, and detection of various GESs have become crucial. Assessing and measuring GESs are very complex since different environmental conditions occur. This importance is even greater when researchers face a shortage of measuring instruments and tools in many parts of the world. GES assessment is a challenging task that requires accurate and continuous measurement methods. Currently, traditional methods are very time-consuming and require spending money and human sources. So, the use of accurate and fast measurement methods and tools assessing measuring GESs potential are seriously recommended, which can greatly help the growth of the use of GESs, especially to cover and focus large areas. Satellite remote sensing is used to observe the environment in many fields and new and fast applications. Satellites remote sensing technologies and techniques for GESs assessing are fast, accurate, and can help to reduce costs and decision-making risks of GESs converters installations projects and provide suitable products to the public end-users. These could also be used to identify regions of interest for energy converter installations and to accurately identify new areas with interesting potentials. In this case, researchers can dramatically reduce the possibility of significant error in assessment methods. There is a lack of in-situ measuring tools mainly due to their high economic costs in the interested areas; an accurate analysis was carried out to assess the GESs energy potential. Since there are only limited options for further expanding the measurement over large areas, the use of satellites makes it easier to overcome in-situ limitations. Actually, to use and develop it as much as possible, a correct interdisciplinary understanding is needed. Satellite remote sensing technology for identifying suitable areas for GESs power plants could be a powerful tool that is constantly increasing in its new and fast applications but requires good planning to apply it in various GESs converters installations projects. In this article, a comprehensive review on wind, wave, biomass, geothermal sources assessment using Sentinel-1 (S-1) Synthetic Aperture Radar (SAR) satellite estimation has been summarized along with the different techniques available to measure GESs using satellites. In the paper, several of the successful estimation techniques were introduced in each section and compared for the understanding of limitations and strengths of different methods of GESs availability evaluation.
Experimental Investigation on Hydraulic Fracture Morphology of Inter-Salt Shale Formation
Authors: Zhang Xiaoyu , Bi Zhenhui , Chang Xin , Wang Lei , Yang Hanzhi
Published: December 2021

The inter-salt shale in the Qianjiang formation of Jianghan Basin in China is characterized by multiple salt-shale bedding planes, various rock strength, and high heterogeneity of rock mechanics. In this paper fracturing experiments under different conditions were carried out to study the effects of the injection velocity, type of fracturing fluid and interface strength on the propagation law of hydraulic fracture in the salt sedimentary rhythm there. In the meantime, Acoustic emission system and radial strain sensor were applied to monitor experimental process. The result indicates that 1) compared with the shale, there are four fracture propagation modes mainly being observed: passivating type (Mode I), “I”-type (Mode II), penetration type (Mode III) and mixed type ((Mode IV)), among which the mixed type is the relatively complex crack propagation mode. 2) With the increase of injection rate and viscosity of fracturing fluid, the hydraulic fracture will penetrate cementation surface more easily. 3) The increase of flow rate and viscosity will increase the breakdown pressure. The breakdown pressure of high strength cementation surface is 16.70% higher than that of low strength.
Experimental Study on the Relationship Between Cavitation and Lift Fluctuations of S-Shaped Hydrofoil
Authors: Liu Haiyu , Lin Pengcheng , Tang Fangping , Chen Ye , Zhang Wenpeng , Yan Shikai
Published: December 2021

In order to study the energy loss of bi-directional hydraulic machinery under cavitation conditions, this paper uses high-speed photography combined with six-axis force and torque sensors to collect cavitating flow images and lift signals of S-shaped hydrofoils simultaneously in a cavitation tunnel. The experimental results show that the stall angle of attack of the S-shaped hydrofoil is at ±12° and that the lift characteristics are almost symmetrical about +1°. Choosingα= +6° andα= −4° with almost equal average lift for comparison, it was found that both cavitation inception and cloud cavitation inception were earlier atα= −4° than atα= +6°, and that the cavitation length atα= −4° grew significantly faster than atα= +6°. Whenα= +6°, the cavity around the S-shaped hydrofoil undergoes a typical cavitation stage as the cavitation number decreases: from incipient cavitation to sheet cavitation to cloud cavitation. However, whenα= −4°, as the cavitation number decreases, the cavitation phase goes through a developmental process from incipient cavitation to sheet cavitation to cloud cavitation to sheet cavitation to cloud cavitation, mainly because the shape of the S-shaped hydrofoil at the negative angle of attack affects the flow of the cavity tails, which is not sufficient to form re-entrant jets that cuts off the sheet cavitation. The formation mechanism of cloud cavitation at the two different angles of attack (α = +6°、−4°) is the same, both being due to the movement of the re-entrant jet leading to the unstable shedding of sheet cavity. The fast Fourier analysis reveals that the fluctuations of the lift signals under cloud cavitation are significantly higher than those under non-cavitation, and the main frequencies of the lift signals under cloud cavitation were all twice the frequency of the cloud cavitation shedding.
Identifying Edaphic Factors and Normalized Difference Vegetation Index Metrics Driving Wildlife Mortality From Anthrax in Kenya’s Wildlife Areas
Authors: Obanda Vincent , Otieno Viola A. , Kingori Edward M. , Ndeereh David , Lwande Olivia W. , Chiyo Patrick I.
Published: December 2021

Anthrax, an acute disease of homeotherms caused by soil-borne Bacillus anthracis is implicated in dramatic declines in wildlife mainly in sub-Saharan Africa. Anthrax outbreaks are often localized in space and time. Therefore, understanding predictors of the spatial and temporal occurrence of anthrax in wildlife areas is useful in supporting early warning and improved response and targeting measures to reduce the impact of epizootic risk on populations. Spatial localization of anthrax is hypothesized to be driven by edaphic factors, while the temporal outbreaks are thought to be driven by extreme weather events including temperature, humidity, rainfall, and drought. Here, we test the role of select edaphic factors and normalized difference vegetation index (NDVI) metrics driven by vegetation structure and climate variability on the spatial and temporal patterns of wildlife mortality from anthrax in key wildlife areas in Kenya over a 20-year period, from 2000 to 2019. There was a positive association between the number of anthrax outbreaks and the total number of months anthrax was reported during the study period and the nitrogen and organic carbon content of the soil in each wildlife area. The monthly occurrence (timing) of anthrax in Lake Nakuru (with the most intense outbreaks) was positively related to the previous month’s spatial heterogeneity in NDVI and monthly NDVI deviation from 20-year monthly means. Generalized linear models revealed that the number of months anthrax was reported in a year (intensity) was positively related to spatial heterogeneity in NDVI, total organic carbon and cation exchange capacity of the soil. These results, examined in the light of experimental studies on anthrax persistence and amplification in the soil enlighten on mechanisms by which these factors are driving anthrax outbreaks and spatial localization.
Heterothermy in a Small Passerine: Eastern Yellow Robins Use Nocturnal Torpor in Winter
Authors: Aharon-Rotman Yaara , McEvoy John F. , Beckmann Christa , Geiser Fritz
Published: December 2021

Torpor is a controlled reduction of metabolism and body temperature, and its appropriate use allows small birds to adapt to and survive challenging conditions. However, despite its great energy conservation potential, torpor use by passerine birds is understudied although they are small and comprise over half of extant bird species. Here, we first determined whether a free-living, small ∼20 g Australian passerine, the eastern yellow robin (Eopsaltria australis), expresses torpor by measuring skin temperature (Ts) as a proxy for body temperature. Second, we tested if skin temperature fluctuated in relation to ambient temperature (Ta). We found that the Ts of eastern yellow robins fluctuated during winter by 9.1 ± 3.9°C on average (average minimum Ts 30.1 ± 2.3°C), providing the first evidence of torpor expression in this species. Daily minimum Ts decreased with Ta, reducing the estimated metabolic rate by as much as 32%. We hope that our results will encourage further studies to expand our knowledge on the use of torpor in wild passerines. The implications of such studies are important because species with highly flexible energy requirements may have an advantage over strict homeotherms during the current increasing frequency of extreme and unpredictable weather events, driven by changing climate.
Threshold Response to Extreme Drought Shifts Inter-Tree Growth Dominance in Pinus sylvestris
Authors: Ovenden Thomas S. , Perks Mike P. , Clarke Toni-Kim , Mencuccini Maurizio , Jump Alistair S.
Published: December 2021

Many studies quantify short-term drought impact on tree growth relative to pre-drought growth averages. However, fewer studies examine the extent to which droughts of differing severity differentially impact tree growth or shape stand dynamics. Focusing on three droughts in high and low density stands of Pinus sylvestris in Scotland, we calculated pre-drought growth averages using climatically standardized antecedent growth years to assess tree level drought and post-drought growth performance as percentage growth change (PGC). We then used mixed-effects models to understand how droughts of differing severity impact tree growth and calculated indices of growth dominance (Gd), size inequality (Si), and size asymmetry (Sa) to detect changes in stand structure. Mixed-effects model results indicate that the magnitude and duration of the growth reduction during and following the more extreme drought was significantly larger compared to less severe droughts, for which we found limited evidence of drought impact. While no changes in Si or Sa were noted following any drought, we found evidence of a difference in Gd after the most extreme drought in both stand densities indicative of a threshold response, with smaller trees contributing proportionally more to stand growth relative to their size. Under less severe droughts, inter-tree variability may have partially buffered against stand-level growth change, however, a small increase in drought severity was associated with a significant reduction in average tree growth, an increase in the number of trees growing at >2SD below pre-drought levels and a shift in Gd toward smaller trees, indicating that a drought severity threshold in P. sylvestris may have been exceeded.