bluuebunny/crossref_metadata_2025 huggingface dataset:
A Practical Approach to Using Integrated Knowledge Translation to Inform a Community-Based Exercise Study
Authors: Suderman Kirsten , Dolgoy Naomi , Yurick Janice , Sellar Christopher , Nishimura Kathryn , Culos-Reed S. Nicole , Joy Anil A. , McNeely Margaret L.
Published: June 2020

Background: Our aim was to understand cancer survivor needs prior to, and following the Alberta Cancer Exercise (ACE) pilot randomized trial as a means to inform implementation of a province-wide cancer-specific, community-based exercise program. Methods: Questionnaires and semi-structured stakeholder engagement sessions were conducted with cancer survivors to explore preferences, barriers and facilitators/benefits at two timepoints: (1) pre-ACE: prior to initiation of the ACE pilot trial (n = 13 survivors and n = 5 caregivers); and (2) post-ACE: following participation in the ACE pilot trial (n = 20 survivors). Descriptive statistics were used to summarize quantitative data from questionnaires. Stakeholder engagement data were analyzed using a framework analysis approach. Emergent themes were then mapped to actionable outcomes. Results: Pre-ACE, survivors indicated a preference for exercise programs that were (1) supervised by exercise specialists knowledgeable about cancer, (2) included support from other health care providers, (3) were held in community locations that were easily accessible. Post-ACE, participants identified (1) a lack of exercise counseling from health care providers, (2) the need for earlier introduction of exercise in the care pathway, and (3) supported referral to exercise programming. Conclusions: An integrated knowledge translation approach identified actionable outcomes to address survivor needs related to exercise in clinical cancer and community-based contexts.
Health Indicators of Pregnant Women in Tonkolili District, Rural Sierra Leone
Authors: Bussink-Voorend Daphne , Bussink Anton P. , Falama Abdul M. , Stekelenburg Jelle
Published: June 2020

Despite having reported one of the highest maternal mortality ratios and neonatal mortality rates in the world, surprisingly little is known about the general health status of pregnant women in rural parts of Sierra Leone. Malaria, anaemia and malnutrition are known contributors to adverse pregnancy outcomes. Although their prevalence is known to be high, the burden of these conditions in the rural pregnant population remains unknown. Our study aimed to gain more insight into the health status of pregnant women. An observational retrospective descriptive study was conducted at the Lion Heart Medical Centre using antenatal care (ANC) registers. The study revealed high prevalence of malaria (35.2%), maternal undernutrition (10.4%) and anaemia (65.9%). The proportion of teenage pregnancies in the ANC population was 16.4%. Both malaria and anaemia were more prevalent in this group, with odds ratios of 2.1 and 1.7, respectively. The findings reveal alarming high rates of anaemia, acute undernutrition and malaria among pregnant women and high numbers of pregnancy among adolescents, with increased health risks. These results will be used to advocate for a malnutrition program, specifically for pregnant women. Our study further emphasises the importance of preventing malaria and anaemia in pregnant women.
Risk Factors related to Late Failure of Dental Implant—A Systematic Review of Recent Studies
Authors: Do Thanh An , Le Hoang Son , Shen Yen-Wen , Huang Heng-Li , Fuh Lih-Jyh
Published: June 2020

Resolving late failure of dental implant is difficult and costly; however, only few reviews have addressed the risk factors associated with late failure of dental implant. The aim of this literature review was to summarize the influences of different potential risk factors on the incidence of late dental implant failure. The protocol of this systematic review was prepared and implemented based on the PRISMA (Preferred reporting items for systematic reviews and meta-analyses) guideline. In December 2018, studies published within the previous 10 years on late dental implant failure were selected by fulfilling the eligibility criteria and the risk factors identified in qualified studies were extracted by using a predefined extraction template. Fourteen eligible studies were assessed. The common risk factors for late failure were divided into three groups according to whether they were related to (1) the patient history (radiation therapy, periodontitis, bruxism and early implant failure), (2) clinical parameters (posterior implant location and bone grade 4) or (3) decisions made by the clinician (low initial stability, more than one implant placed during surgery, inflammation at the surgical site during the first year or using an overdenture with conus-type connection). Clinicians should be cautions throughout the treatment process of dental implant—from the initial examination to the treatment planning, surgical operation and prosthesis selection—in order to minimize the risk of late failure of dental implant.
The Relationship between Annual Airborne Pollen Levels and Occurrence of All Cancers, and Lung, Stomach, Colorectal, Pancreatic and Breast Cancers: A Retrospective Study from the National Registry Database of Cancer Incidence in Japan, 1975–2015
Authors: Awaya Akira , Kuroiwa Yoshiyuki
Published: June 2020

Suppression of risk factors including smoking, overdrinking and infections by human papilloma and hepatitis B and C viruses has been recommended for cancer prevention; however, identification of other environmental risk factors has not been enough. Besides the 2003 report that Kawasaki disease may be triggered by pollen exposure, 40 Japanese specific intractable diseases have recently been reported as “pollen diseases”, also potentially triggered by pollen exposure. Various human organs are affected by pollen exposure, leading to systemic vasculitis; autoimmune connective tissue diseases, inflammatory bowel diseases and intractable neuromuscular and bone diseases, suggesting the common effects of pollen exposure on fundamental functions of vital metabolism. In this context, cancer and malignant tumors may be another group of intractable diseases triggered by epigenetic pollen exposure. Thus, this study compared the number of newly registered patients with 24 types of cancer and airborne pollen levels measured from 1975 to 2015. We searched for statistical correlations with Bonferroni correction between the annual number of newly registered patients for all cancers or for each of lung, stomach, colorectal, pancreatic and breast cancers in the patient-registry year “x”, and annual airborne pollen levels measured in the same year as “x”, or 1–7 years prior to the year “x”. The number of newly registered patients for lung, and pancreatic cancers in the patient-registry year “x” was highly correlated with airborne pollen levels measured 2 years prior to “x”. That for breast cancer was correlated with pollen levels measured 2 and 5 years prior to “x”. To our knowledge, this is the first rapid communication of the association between pollen levels and cancer incidence.
An Integrated Approach for Detection and Prediction of Greening Situation in a Typical Desert Area in China and Its Human and Climatic Factors Analysis
Authors: Zhou Lei , Wang Siyu , Du Mingyi , Yang Jianhua , Zhu Yinuo , Wu Jianjun
Published: June 2020

The combined study of vegetation coverage (VC) and land use change provides important scientific guidance for the restoration and protection of arid regions. Taking Hongjian Nur (HJN) Lake in the desert region as a case study, the VC of this area was calculated using a normalized difference vegetation index (NDVI), which is based on a mixed pixel decomposition method. A grey forecasting model (GM) (1, 1) was used to predict future VC. The driving factors of VC and land use change were analyzed. The results indicate that the average VC of the whole watershed showed a gradual increase from 0.29 to 0.49 during 2000–2017. The prediction results of the GM VC showed that the greening trend is projected to continue until 2027. The area of farmland in the watershed increased significantly and its area was mainly converted from unused land, grassland, and forest. The reason for increased VC may be that the combination of the exploitation of unused land and climate change, which is contrary to the country’s sustainable development goals (SDG; goal 15). Therefore, the particularities of the local ecological environment in China’s desert area needs to be considered in the development of ecological engineering projects.
Developing Shopping and Dining Walking Indices Using POIs and Remote Sensing Data
Authors: Deng Yingbin , Yan Yingwei , Xie Yichun , Xu Jianhui , Jiang Hao , Chen Renrong , Tan Runnan
Published: June 2020

Walking is one of the most commonly promoted traveling methods and is garnering increasing attention. Many indices/scores have been developed by scholars to measure the walkability in a local community. However, most existing walking indices/scores involve urban planning-oriented, local service-oriented, regional accessibility-oriented, and physical activity-oriented walkability assessments. Since shopping and dining are two major leisure activities in our daily lives, more attention should be given to the shopping or dining-oriented walking environment. Therefore, we developed two additional walking indices that focus on shopping or dining. The point of interest (POI), vegetation coverage, water coverage, distance to bus/subway station, and land surface temperature were employed to construct walking indices based on 50-m street segments. Then, walking index values were categorized into seven recommendation levels. The field verification illustrates that the proposed walking indices can accurately represent the walking environment for shopping and dining. The results in this study could provide references for citizens seeking to engage in activities of shopping and dining with a good walking environment.
Indoor Positioning Using PnP Problem on Mobile Phone Images
Authors: Kubíčková Hana , Jedlička Karel , Fiala Radek , Beran Daniel
Published: June 2020

As people grow accustomed to effortless outdoor navigation, there is a rising demand for similar possibilities indoors as well. Unfortunately, indoor localization, being one of the requirements for navigation, continues to be a problem without a clear solution. In this article, we are proposing a method for an indoor positioning system using a single image. This is made possible using a small preprocessed database of images with known control points as the only preprocessing needed. Using feature detection with the SIFT (Scale Invariant Feature Transform) algorithm, we can look through the database and find an image that is the most similar to the image taken by a user. Such a pair of images is then used to find coordinates of a database of images using the PnP problem. Furthermore, projection and essential matrices are determined to calculate the user image localization—determining the position of the user in the indoor environment. The benefits of this approach lie in the single image being the only input from a user and the lack of requirements for new onsite infrastructure. Thus, our approach enables a more straightforward realization for building management.
Transglutaminase 2 Has Metabolic and Vascular Regulatory Functions Revealed by In Vivo Activation of Alpha1-Adrenergic Receptor
Authors: Lénárt Kinga , Pap Attila , Pórszász Róbert , V. Oláh Anna , Fésüs László , Mádi András
Published: June 2020

The multifunctional tissue transglutaminase has been demonstrated to act as α1-adrenergic receptor-coupled G protein with GTPase activity in several cell types. To explore further the pathophysiological significance of this function we investigated the in vivo effects of the α1-adrenergic receptor agonist phenylephrine comparing responses in wild type and TG2-/- mice. Injection of phenylephrine, but not a beta3-adrenergic agonist (CL-316,243), resulted in the long-term decline of the respiratory exchange ratio and lower lactate concentration in TG2-/- mice indicating they preferred to utilize fatty acids instead of glucose as fuels. Measurement of tail blood pressure revealed that the vasoconstrictive effect of phenylephrine was milder in TG2-/- mice leading to lower levels of lactate dehydrogenase (LDH) isoenzymes in blood. LDH isoenzyme patterns indicated more damage in lung, liver, kidney, skeletal, and cardiac muscle of wild type mice; the latter was confirmed by a higher level of heart-specific CK-MB. Our data suggest that TG2 as an α1-adrenergic receptor-coupled G protein has important regulatory functions in alpha1-adrenergic receptor-mediated metabolic processes and vascular functions.
Animal Models Used in Hepatitis C Virus Research
Authors: Berggren Keith A. , Suzuki Saori , Ploss Alexander
Published: June 2020

The narrow range of species permissive to infection by hepatitis C virus (HCV) presents a unique challenge to the development of useful animal models for studying HCV, as well as host immune responses and development of chronic infection and disease. Following earlier studies in chimpanzees, several unique approaches have been pursued to develop useful animal models for research while avoiding the important ethical concerns and costs inherent in research with chimpanzees. Genetically related hepatotropic viruses that infect animals are being used as surrogates for HCV in research studies; chimeras of these surrogate viruses harboring specific regions of the HCV genome are being developed to improve their utility for vaccine testing. Concurrently, genetically humanized mice are being developed and continually advanced using human factors known to be involved in virus entry and replication. Further, xenotransplantation of human hepatocytes into mice allows for the direct study of HCV infection in human liver tissue in a small animal model. The current advances in each of these approaches are discussed in the present review.
Time-course Transcriptome of Parageobacillus thermoglucosidasius DSM 6285 Grown in the Presence of Carbon Monoxide and Air
Authors: Aliyu Habibu , Mohr Teresa , Cowan Don , de Maayer Pieter , Neumann Anke
Published: June 2020

Parageobacillus thermoglucosidasius is a metabolically versatile, facultatively anaerobic thermophile belonging to the family Bacillaceae. Previous studies have shown that this bacterium harbours co-localised genes coding for a carbon monoxide (CO) dehydrogenase (CODH) and Ni-Fe hydrogenase (Phc) complex and oxidises CO and produces hydrogen (H2) gas via the water-gas shift (WGS) reaction. To elucidate the genetic events culminating in the WGS reaction, P. thermoglucosidasius DSM 6285 was cultivated under an initial gas atmosphere of 50% CO and 50% air and total RNA was extracted at ~8 (aerobic phase), 20 (anaerobic phase), 27 and 44 (early and late hydrogenogenic phases) hours post inoculation. The rRNA-depleted fraction was sequenced using Illumina NextSeq, v2.5, 1x75bp chemistry. Differential expression revealed that at 8 vs.. 20, 20 vs.. 27 and 27 vs.. 44 h post inoculation, 2190, 2118 and 231 transcripts were differentially (FDR < 0.05) expressed. Cluster analysis revealed 26 distinct gene expression trajectories across the four time points. Of these, two similar clusters, showing overexpression at 20 relative to 8 h and depletion at 27 and 44 h, harboured the CODH and Phc transcripts, suggesting possible regulation by O2. The transition between aerobic respiration and anaerobic growth was marked by initial metabolic deterioration, as reflected by up-regulation of transcripts linked to sporulation and down-regulation of transcripts linked to flagellar assembly and metabolism. However, the transcriptome and growth profiles revealed the reversal of this trend during the hydrogenogenic phase.
Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma
Authors: Katsuta Eriko , Rashid Omar M. , Takabe Kazuaki
Published: June 2020

Achievement of microscopic tumor clearance (R0) after pancreatic ductal adenocarcinoma (PDAC) surgery is determined by cancer biology rather than operative technique. Fibroblasts are known to play pro-cancer roles; however, a small subset was recently found to play anti-cancer roles. Therefore, we hypothesized that intratumor fibroblasts contribute to curative resection and a better survival of PDAC. Utilizing a large, publicly available PDAC cohort, we found that fibroblast composition was associated with R0 curative resection. A high amount of fibroblasts in PDACs was significantly associated with a higher amount of mature vessels, but not with blood angiogenesis. A high amount of fibroblasts was also associated with a higher infiltration of anti-cancer immune cells, such as CD8+ T-cells and dendritic cells, together with higher inflammatory signaling, including IL2/STAT5 and IL6/JAK/STAT3 signaling. Further, the fibroblast composition was inversely associated with cancer cell composition in the bulk tumor, along with an inverse association with proliferative characteristics, such as MYC signaling and glycolysis. The patients with high-fibroblast PDACs showed an improved prognosis. In conclusion, we found that PDACs with high fibroblasts were associated with a higher R0 resection rate, resulting in a better prognosis. These findings may be due to less aggressive biology with a higher vascularity and anti-cancer immunity, and a low cancer cell component.
Consolidated BRCA1/2 Variant Interpretation by MH BRCA Correlates with Predicted PARP Inhibitor Efficacy Association by MH Guide
Authors: Hirotsu Yosuke , Schmidt-Edelkraut Udo , Nakagomi Hiroshi , Sakamoto Ikuko , Hartenfeller Markus , Narang Ram , Soldatos Theodoros G. , Kaduthanam Sajo , Wang Xiaoyue , Hettich Stephan , Brock Stephan , Jackson David B. , Omata Masao
Published: June 2020

BRCA1/2 variants are prognostic biomarkers for hereditary breast and/or ovarian cancer (HBOC) syndrome and predictive biomarkers for PARP inhibition. In this study, we benchmarked the classification of BRCA1/2 variants from patients with HBOC-related cancer using MH BRCA, a novel computational technology that combines the ACMG guidelines with expert-curated variant annotations. Evaluation of BRCA1/2 variants (n = 1040) taken from four HBOC studies showed strong concordance within the pathogenic (98.1%) subset. Comparison of MH BRCA’s ACMG classification to ClinVar submitter content from ENIGMA, the international consortium of investigators on the clinical significance of BRCA1/2 variants, the ARUP laboratories, a clinical testing lab of the University of UTAH, and the German Cancer Consortium showed 99.98% concordance (4975 out of 4976 variants) in the pathogenic subset. In our patient cohort, refinement of patients with variants of unknown significance reduced the uncertainty of cancer-predisposing syndromes by 64.7% and identified three cases with potential family risk to HBOC due to a likely pathogenic variant BRCA1 p.V1653L (NM_007294.3:c.4957G > T; rs80357261). To assess whether classification results predict PARP inhibitor efficacy, contextualization with functional impact information on DNA repair activity were performed, using MH Guide. We found a strong correlation between treatment efficacy association and MH BRCA classifications. Importantly, low efficacy to PARP inhibition was predicted in 3.95% of pathogenic variants from four examined HBOC studies and our patient cohort, indicating the clinical relevance of the consolidated variant interpretation.
Extracellular Matrix Analysis of Human Renal Arteries in Both Quiescent and Active Vascular State
Authors: van Dijk Christian G.M. , Louzao-Martinez Laura , van Mulligen Elise , Boermans Bart , Demmers Jeroen A.A. , van den Bosch Thierry P.P. , Goumans Marie-José , Duncker Dirk J. , Verhaar Marianne C. , Cheng Caroline
Published: June 2020

In vascular tissue engineering strategies, the addition of vascular-specific extracellular matrix (ECM) components may better mimic the in vivo microenvironment and potentially enhance cell–matrix interactions and subsequent tissue growth. For this purpose, the exact composition of the human vascular ECM first needs to be fully characterized. Most research has focused on characterizing ECM components in mature vascular tissue; however, the developing fetal ECM matches the active environment required in vascular tissue engineering more closely. Consequently, we characterized the ECM protein composition of active (fetal) and quiescent (mature) renal arteries using a proteome analysis of decellularized tissue. The obtained human fetal renal artery ECM proteome dataset contains higher levels of 15 ECM proteins versus the mature renal artery ECM proteome, whereas 16 ECM proteins showed higher levels in the mature tissue compared to fetal. Elastic ECM proteins EMILIN1 and FBN1 are significantly enriched in fetal renal arteries and are mainly produced by cells of mesenchymal origin. We functionally tested the role of EMILIN1 and FBN1 by anchoring the ECM secreted by vascular smooth muscle cells (SMCs) to glass coverslips. This ECM layer was depleted from either EMILIN1 or FBN1 by using siRNA targeting of the SMCs. Cultured endothelial cells (ECs) on this modified ECM layer showed alterations on the transcriptome level of multiple pathways, especially the Rho GTPase controlled pathways. However, no significant alterations in adhesion, migration or proliferation were observed when ECs were cultured on EMILIN1- or FNB1-deficient ECM. To conclude, the proteome analysis identified unique ECM proteins involved in the embryonic development of renal arteries. Alterations in transcriptome levels of ECs cultured on EMILIN1- or FBN1-deficient ECM showed that these candidate proteins could affect the endothelial (regenerative) response.
Ubiquitin Carboxyl-Terminal Hydrolases (UCHs): Potential Mediators for Cancer and Neurodegeneration
Authors: Sharma Amit , Liu Hongde , Tobar-Tosse Fabian , Chand Dakal Tikam , Ludwig Michael , Holz Frank G. , Loeffler Karin U. , Wüllner Ullrich , Herwig-Carl Martina C.
Published: June 2020

Emerging evidence suggests an inverse association between cancer and neurodegenerative diseases (NDD). Although phenotypically different, both diseases display a significant imbalance in the ubiquitination/deubiquitination processes. Therefore, we particularly investigated the expression of ubiquitin C-terminal hydrolases (UCHs: UCH-L1, UCH-L3, UCH-L5 and BAP1), a subfamily of deubiquitinating enzymes (DUBs), using publically available datasets (GTEx, TCGA) and observed altered expression of UCH-L1, UCH-L3, UCH-L5 in 17 cancer types. Interestingly, UCH-L1 (known to be enriched in neurons and interacting with the Parkinson’s disease-associated protein α-synuclein) appeared to be a prognostic indicator of unfavorable outcome in endometrial and urothelial cancer, while increased expression of UCH-L3 and UCH-L5 was associated with poor survival in liver and thyroid cancer, respectively. In normal tissues, UCH-L1 was found to be strongly expressed in the cerebral cortex and hypothalamus, while UCH-L3 expression was somewhat higher in the testis. The occurrence of mutation rates in UCHs also suggests that BAP1 and UCH-L5 may play a more dominant role in cancers than UCH-L1 and UCH-L3. We also characterized the functional context and configuration of the repeat elements in the promoter of DUBs genes and found that UCHs are highly discriminatory for catabolic function and are mainly enriched with LINE/CR1 repeats. Regarding the thesis of an inverse association between cancer and NDD, we observed that among all DUBs, UCHs are the one most involved in both entities. Considering a putative therapeutic potential based on presumed common mechanisms, it will be useful to determine whether other DUBs can compensate for the loss of UCH activity under physiological conditions. However, experimental evidence is required to substantiate this argument.
Cerebrovascular and Neurological Dysfunction under the Threat of COVID-19: Is There a Comorbid Role for Smoking and Vaping?
Authors: Archie Sabrina Rahman , Cucullo Luca
Published: June 2020

The recently discovered novel coronavirus, SARS-CoV-2 (COVID-19 virus), has brought the whole world to standstill with critical challenges, affecting both health and economic sectors worldwide. Although initially, this pandemic was associated with causing severe pulmonary and respiratory disorders, recent case studies reported the association of cerebrovascular-neurological dysfunction in COVID-19 patients, which is also life-threatening. Several SARS-CoV-2 positive case studies have been reported where there are mild or no symptoms of this virus. However, a selection of patients are suffering from large artery ischemic strokes. Although the pathophysiology of the SARS-CoV-2 virus affecting the cerebrovascular system has not been elucidated yet, researchers have identified several pathogenic mechanisms, including a role for the ACE2 receptor. Therefore, it is extremely crucial to identify the risk factors related to the progression and adverse outcome of cerebrovascular-neurological dysfunction in COVID-19 patients. Since many articles have reported the effect of smoking (tobacco and cannabis) and vaping in cerebrovascular and neurological systems, and considering that smokers are more prone to viral and bacterial infection compared to non-smokers, it is high time to explore the probable correlation of smoking in COVID-19 patients. Herein, we have reviewed the possible role of smoking and vaping on cerebrovascular and neurological dysfunction in COVID-19 patients, along with potential pathogenic mechanisms associated with it.
Salt Stress Signals on Demand: Cellular Events in the Right Context
Authors: Ismail Ahmed , El-Sharkawy Islam , Sherif Sherif
Published: June 2020

Plant stress is a real dilemma; it puzzles plant biologists and is a global problem that negatively affects people’s daily lives. Of particular interest is salinity, because it represents one of the major water-related stress types. We aimed to determine the signals that guide the cellular-related events where various adaptation mechanisms cross-talk to cope with salinity-related water stress in plants. In an attempt to unravel these mechanisms and introduce cellular events in the right context, we expansively discussed how salt-related signals are sensed, with particular emphasis on aquaporins, nonselective cation channels (NSCCs), and glycosyl inositol phosphorylceramide (GIPC). We also elaborated on the critical role Ca2+, H+, and ROS in mediating signal transduction pathways associated with the response and tolerance to salt stress. In addition, the fragmentary results from the literature were compiled to develop a harmonized, informational, and contemplative model that is intended to improve our perception of these adaptative mechanisms and set a common platform for plant biologists to identify intriguing research questions in this area.
Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: Molecular Docking and DFT Calculations
Authors: Hagar Mohamed , Ahmed Hoda A. , Aljohani Ghadah , Alhaddad Omaima A.
Published: June 2020

The novel coronavirus, COVID-19, caused by SARS-CoV-2, is a global health pandemic that started in December 2019. The effective drug target among coronaviruses is the main protease Mpro, because of its essential role in processing the polyproteins that are translated from the viral RNA. In this study, the bioactivity of some selected heterocyclic drugs named Favipiravir (1), Amodiaquine (2), 2′-Fluoro-2′-deoxycytidine (3), and Ribavirin (4) was evaluated as inhibitors and nucleotide analogues for COVID-19 using computational modeling strategies. The density functional theory (DFT) calculations were performed to estimate the thermal parameters, dipole moment, polarizability, and molecular electrostatic potential of the present drugs; additionally, Mulliken atomic charges of the drugs as well as the chemical reactivity descriptors were investigated. The nominated drugs were docked on SARS-CoV-2 main protease (PDB: 6LU7) to evaluate the binding affinity of these drugs. Besides, the computations data of DFT the docking simulation studies was predicted that the Amodiaquine (2) has the least binding energy (−7.77 Kcal/mol) and might serve as a good inhibitor to SARS-CoV-2 comparable with the approved medicines, hydroxychloroquine, and remdesivir which have binding affinity −6.06 and −4.96 Kcal/mol, respectively. The high binding affinity of 2 was attributed to the presence of three hydrogen bonds along with different hydrophobic interactions between the drug and the critical amino acids residues of the receptor. Finally, the estimated molecular electrostatic potential results by DFT were used to illustrate the molecular docking findings. The DFT calculations showed that drug 2 has the highest of lying HOMO, electrophilicity index, basicity, and dipole moment. All these parameters could share with different extent to significantly affect the binding affinity of these drugs with the active protein sites.
Age Dependent Modification of the Metabolic Profile of the Tibialis Anterior Muscle Fibers in C57BL/6J Mice
Authors: Giacomello Emiliana , Crea Emanuela , Torelli Lucio , Bergamo Alberta , Reggiani Carlo , Sava Gianni , Toniolo Luana
Published: June 2020

Skeletal muscle aging is accompanied by mass reduction and functional decline, as a result of multiple factors, such as protein expression, morphology of organelles, metabolic equilibria, and neural communication. Skeletal muscles are formed by multiple fibers that express different Myosin Heavy Chains (MyHCs) and have different metabolic properties and different blood supply, with the purpose to adapt their contraction to the functional need. The fine interplay between the different fibers composing a muscle and its architectural organization determine its functional properties. Immunohistochemical and histochemical analyses of the skeletal muscle tissue, besides evidencing morphological characteristics, allow for the precise determination of protein expression and metabolic properties, providing essential information at the single-fiber level. Aiming to gain further knowledge on the influence of aging on skeletal muscles, we investigated the expression of the MyHCs, the Succinate Dehydrogenase (SDH) activity, and the presence of capillaries and Tubular Aggregates (TAs) in the tibialis anterior muscles of physiologically aging C57BL/6J mice aged 8 (adult), 18 (middle aged), and 24 months (old). We observed an increase of type-IIB fast-contracting fibers, an increase of the oxidative capacity of type-IIX and -IIA fibers, a general decrease of the capillarization, and the onset of TAs in type-IIB fibers. These data suggest that aging entails a selective modification of the muscle fiber profiles.
Hypersensitivity of Airway Reflexes Induced by Hydrogen Sulfide: Role of TRPA1 Receptors
Authors: Chung Chi-Li , Lin You Shuei , Chan Nai-Ju , Chen Yueh-Yin , Hsu Chun-Chun
Published: June 2020

The activation of capsaicin-sensitive lung vagal (CSLV) afferents can elicit airway reflexes. Hypersensitivity of these afferents is known to contribute to the airway hypersensitivity during airway inflammation. Hydrogen sulfide (H2S) has been suggested as a potential therapeutic agent for airway hypersensitivity diseases, such as asthma, because of its relaxing effect on airway smooth muscle and anti-inflammatory effect. However, it is still unknown whether H2S affects airway reflexes. Our previous study demonstrated that exogenous application of H2S sensitized CSLV afferents and enhanced Ca2+ transients in CSLV neurons. The present study aimed to determine whether the H2S-induced sensitization leads to functional changes in airway reflexes and elevates the electrical excitability of the CSLV neurons. Our results showed that, first and foremost, in anesthetized, spontaneously breathing rats, the inhalation of aerosolized sodium hydrosulfide (NaHS, a donor of H2S; 5 mg/mL, 3 min) caused an enhancement in apneic response evoked by several stimulants of the CSLV afferents. This enhancement effect was found 5 min after NaHS inhalation and returned to control 30 min later. However, NaHS no longer enhanced the apneic response after perineural capsaicin treatment on both cervical vagi that blocked the conduction of CSLV fibers. Furthermore, the enhancing effect of NaHS on apneic response was totally abolished by pretreatment with intravenous HC-030031 (a TRPA1 antagonist; 8 mg/kg), whereas the potentiating effect was not affected by the pretreatment with the vehicle of HC-030031. We also found that intracerebroventricular infusion pretreated with HC-030031 failed to alter the potentiating effect of NaHS on the apneic response. Besides, the cough reflex elicited by capsaicin aerosol was enhanced by inhalation of NaHS in conscious guinea pigs. Nevertheless, this effect was entirely eliminated by pretreatment with HC-030031, not by its vehicle. Last but not least, voltage-clamp electrophysiological analysis of isolated rat CSLV neurons showed a similar pattern of potentiating effects of NaHS on capsaicin-induced inward current, and the involvement of TRPA1 receptors was also distinctly shown. In conclusion, these results suggest that H2S non-specifically enhances the airway reflex responses, at least in part, through action on the TRPA1 receptors expressed on the CSLV afferents. Therefore, H2S should be used with caution when applying for therapeutic purposes in airway hypersensitivity diseases.
Editorial of Special Issue “Frontiers in the Actin Cytoskeleton”
Authors: Rivero Francisco
Published: June 2020

The actin cytoskeleton is of fundamental importance for eukaryotic cell homeostasis [...]
β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration
Authors: Fernandez-Abascal Jesus , Chiaino Elda , Frosini Maria , Davey Gavin P. , Valoti Massimo
Published: June 2020

The 1-methyl-4-phenylpyridinium (MPP+) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP+. The toxic effect of MPP+ in cell viability was rescued with both βNF and EtOH treatments. We also report that this was due to a decrease in reactive oxygen species (ROS) production, restoration of mitochondrial fusion kinetics, and mitochondrial membrane potential. These treatments also protected complex I activity against the inhibitory effects caused by MPP+, suggesting a possible neuroprotective role for CYP inducers. These results bring new insights into the possible role of CYP isoenzymes in xenobiotic clearance and central nervous system homeostasis.
P2X7 Receptor is Involved in Mitochondrial Dysfunction Induced by Extracellular Alpha Synuclein in Neuroblastoma SH-SY5Y Cells
Authors: Wilkaniec Anna , Cieślik Magdalena , Murawska Emilia , Babiec Lidia , Gąssowska-Dobrowolska Magdalena , Pałasz Ewelina , Jęśko Henryk , Adamczyk Agata
Published: June 2020

The purinergic P2X7 receptor (P2X7R) belongs to a family of trimeric ion channels that are gated by extracellular adenosine 5′-triphosphate (ATP). Several studies have pointed to a role of P2X7R-dependent signalling in Parkinson's disease (PD)-related neurodegeneration. The pathology of (PD) is characterized by the formation of insoluble alpha-synuclein (α-Syn) aggregates—Lewy bodies, but the mechanisms underlying α-Syn-induced dopaminergic cell death are still partially unclear. Our previous studies indicate that extracellular α-Syn directly interact with neuronal P2X7R and induces intracellular free calcium mobilization in neuronal cells. The main objective of this study was to examine the involvement of P2X7R receptor in α-Syn-induced mitochondrial dysfunction and cell death. We found that P2X7R stimulation is responsible for α-Syn-induced oxidative stress and activation of the molecular pathways of programmed cell death. Exogenous α-Syn treatment led to P2X7R-dependent decrease in mitochondrial membrane potential as well as elevation of mitochondrial ROS production resulting in breakdown of cellular energy production. Moreover, P2X7R-dependent deregulation of AMP-activated protein kinase as well as decrease in parkin protein level could be responsible for α-Syn-induced mitophagy impairment and accumulation of dysfunctional mitochondria. P2X7R might be putative pharmacological targets in molecular mechanism of extracellular α-Syn toxicity.
Deletion of Thioredoxin-Interacting Protein (TXNIP) Abrogates High Fat Diet-Induced Retinal Leukostasis, Barrier Dysfunction and Microvascular Degeneration in a Mouse Obesity Model
Authors: Mohamed Islam N. , Sheibani Nader , El-Remessy Azza B.
Published: June 2020

We have shown that a high fat diet (HFD) induces the activation of retinal NOD-like receptor protein (NLRP3)-inflammasome that is associated with enhanced expression and interaction with thioredoxin-interacting protein (TXNIP). Here, the specific contribution of TXNIP and the impact of HFD on retinal leukostasis, barrier dysfunction and microvascular degeneration were investigated. Wild-type (WT) and TXNIP knockout (TKO) mice were fed with normal diet or 60% HFD for 8–18 weeks. TXNIP was overexpressed or silenced in human retinal endothelial cells (REC). At 8 weeks, HFD significantly induced retinal leukostasis and breakdown of the blood–retina barrier in WT mice, but not in TKO mice. In parallel, HFD also induced retinal expression of adhesion molecules and cleaved IL-1β in WT mice, which were also abrogated in TKO mice. In culture, TXNIP overexpression induced NLRP3, IL-1β, and adhesion molecules expression, while TXNIP silencing inhibited them. Blocking the IL-1β receptor significantly suppressed TXNIP-induced expression of NLRP3-inflammasome and adhesion molecules in HREC. Ex-vivo assay showed that leukocytes isolated from WT-HFD, but not from TKO-HFD, induced leukostasis and cell death. At 18 weeks, HFD triggered development of degenerated (acellular) capillaries and decreased branching density in WT but not in TKO mice. Together, HFD-induced obesity triggered early retinal leukostasis and microvascular dysfunction at least in part via TXNIP-NLRP3-inflammasome activation.
Acute Kidney Injury: From Diagnosis to Prevention and Treatment Strategies
Authors: Gameiro Joana , Fonseca José Agapito , Outerelo Cristina , Lopes José António
Published: June 2020

Acute kidney injury (AKI) is characterized by an acute decrease in renal function that can be multifactorial in its origin and is associated with complex pathophysiological mechanisms. In the short term, AKI is associated with an increased length of hospital stay, health care costs, and in-hospital mortality, and its impact extends into the long term, with AKI being associated with increased risks of cardiovascular events, progression to chronic kidney disease (CKD), and long-term mortality. Given the impact of the prognosis of AKI, it is important to recognize at-risk patients and improve preventive, diagnostic, and therapy strategies. The authors provide a comprehensive review on available diagnostic, preventive, and treatment strategies for AKI.
Fracture Analysis of Particulate Metal Matrix Composite Using X-ray Tomography and Extended Finite Element Method (XFEM)
Authors: Yuan Rui , Singh Sudhanshu S. , Liao Xiao , Oswald Jay , Chawla Nikhilesh
Published: June 2020

Particle reinforced metal matrix composites (MMCs) offer high strength, low density, and high stiffness, while maintaining reasonable cost. The damage process in these MMCs starts with either the fracture of particles or by the de-cohesion of the particle-matrix interfaces. In this study, the extended finite elements method (XFEM) has been used in conjunction with X-ray synchrotron tomography to study fracture mechanisms in these materials under tensile loading. The initial 3D reconstructed microstructure from X-ray tomography has been used as a basis for the XFEM to simulate the damage in the 20 vol.% SiC particle reinforced 2080 aluminum alloy composite when tensile loading is applied. The effect of mesh sensitivity on the Weibull probability has been studied based on a single sphere and several particles with realistic geometries. Additionally, the effect of shape and volume of particles on the Weibull fracture probability was studied. The evolution of damage with the applied traction has been evaluated using simulation and compared with the experimental results obtained from in situ tensile testing.
In Vitro Study on the Effect of a New Bioactive Desensitizer on Dentin Tubule Sealing and Bonding
Authors: Luong Minh N. , Huang Laurie , Chan Daniel C. N. , Sadr Alireza
Published: June 2020

Bioactive mineral-based dentin desensitizers that can quickly and effectively seal dentinal tubules and promote dentin mineralization are desired. This in vitro study evaluated a novel nanohydroxyapatite-based desensitizer, Predicta (PBD, Parkell), and its effect on bond strength of dental adhesives. Human dentin discs (2-mm thick) were subjected to 0.5 M EDTA to remove the smear layer and expose tubules, treated with PBD, and processed for surface and cross-sectional SEM examination before and after immersion in simulated body fluid (SBF) for four weeks (ISO 23317-2014). The effects of two dental desensitizers on the microshear bond strength of a universal adhesive and a two-step self-etch system were compared. SEM showed coverage and penetration of nanoparticles in wide tubules on the PBD-treated dentin at the baseline. After four weeks in SBF, untreated dentin showed amorphous mineral deposits while PBD-treated dentin disclosed a highly mineralized structure integrated with dentin. Desensitizers significantly reduced microshear bond strength test (MSBS) of adhesives by 15–20% on average, depending on the bonding protocol. In conclusion, PBD demonstrated effective immediate tubules sealing capability and promoted mineral crystal growth over dentin and into the tubules during SBF-storage. For bonding to desensitizer-treated dentin, a two-step self-etching adhesive or universal bond with phosphoric acid pretreatment are recommended.
Field Investigations of Underwater Mounds Formed by Hopper Dredge Discharges in a Coastal Environment
Authors: Dai Wenhong , Ding Wei , Lu Chuanteng , Luo Xiaofeng , Xie Qiancheng
Published: June 2020

In a coastal environment, this paper investigated the formation process and the cumulative shape of subaqueous mounds formed by hopper dredged discharges. Hydrological observations and field tests were performed to examine the flow features and ultimately generated morphology characteristics. A high-precision digital elevation model (DEM) was established by multi-beam depth sweeping (MBDS) in the experiment. Particular attention was paid to the formation of the mounds, the three-dimensional shape and the influence factors. The field measurements showed that the mounds were roughly symmetrical in space, and the tidal current, though of weak strength, played a certain role in shaping the profiles. Cone and volcanic cone mound tops were observed, featuring the main top shapes. The height and covered area of the mounds were proportional to the amount of dumped sediment, and they were also affected a lot by the water depth. The results of superimposed tests showed that the second placement over the existing mound resulted in a similar overall shape, but there was pronounced movement around the mound; additional discharged volumes at the same location mainly increased the mound height. The field tests provided a reference for understanding the sediment dumping in other similar coastal areas.
Chronic Pulmonary Aspergillosis: Notes for a Clinician in a Resource-Limited Setting Where There Is No Mycologist
Authors: Bongomin Felix , Asio Lucy Grace , Baluku Joseph Baruch , Kwizera Richard , Denning David W.
Published: June 2020

Chronic pulmonary aspergillosis (CPA) is a spectrum of several progressive disease manifestations caused by Aspergillus species in patients with underlying structural lung diseases. Duration of symptoms longer than three months distinguishes CPA from acute and subacute invasive pulmonary aspergillosis. CPA affects over 3 million individuals worldwide. Its diagnostic approach requires a thorough Clinical, Radiological, Immunological and Mycological (CRIM) assessment. The diagnosis of CPA requires (1) demonstration of one or more cavities with or without a fungal ball present or nodules on chest imaging, (2) direct evidence of Aspergillus infection or an immunological response to Aspergillus species and (3) exclusion of alternative diagnoses, although CPA and mycobacterial disease can be synchronous. Aspergillus antibody is elevated in over 90% of patients and is the cornerstone for CPA diagnosis. Long-term oral antifungal therapy improves quality of life, arrests haemoptysis and prevents disease progression. Itraconazole and voriconazole are alternative first-line agents; voriconazole is preferred for patients with contra-indications to itraconazole and in those with severe disease (including large aspergilloma). In patients co-infected with tuberculosis (TB), it is not possible to treat TB with rifampicin and concurrently administer azoles, because of profound drug interactions. In those with pan-azole resistance or intolerance or progressive disease while on oral triazoles, short-term courses of intravenous liposomal amphotericin B or micafungin is used. Surgery benefits patients with well-circumscribed simple aspergillomas and should be offered earlier in low-resource settings.
Intercultural Responsiveness: Learning Languages Other Than English and Developing Intercultural Communication Competence
Authors: Yang Ping
Published: June 2020

This paper conceptually discusses why it is essential to foster intercultural responsiveness through learning a language other than English (LOTE) and developing intercultural communication competence at Australian universities. Learning a LOTE is meaningful and helps second language learners develop social skills and cognitive competence, understand the linguistic system of the LOTEs, and sense differences between their home language/culture and target language/culture, and then pave the way to developing intercultural communication competence. However, a LOTE as a compulsory unit has little presence in Australian university curricula. No Australian universities require that students need to learn a LOTE to meet the course requirements. Learning a LOTE is conducive to both bilingual/multilingual and intercultural communication competence development. Furthermore, most current work studies intercultural verbal communication competence more than intercultural nonverbal communication competence. While intercultural verbal communication is audio-oriented, voiced, and externalized with open messages, intercultural nonverbal communication is visually oriented, silent, and internalized with hidden cues. Only when both components are considered can people achieve effective intercultural communication. The implications for learning a LOTE and developing intercultural communication competence are discussed.