bluuebunny/crossref_metadata_2025 huggingface dataset:
Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility
Authors: Wassarman Paul M. , Litscher Eveline S.
Published: August 2021

All mammalian oocytes and eggs are surrounded by a relatively thick extracellular matrix (ECM), the zona pellucida (ZP), that plays vital roles during oogenesis, fertilization, and preimplantation development. Unlike ECM surrounding somatic cells, the ZP is composed of only a few glycosylated proteins, ZP1–4, that are unique to oocytes and eggs. ZP1–4 have a large region of polypeptide, the ZP domain (ZPD), consisting of two subdomains, ZP-N and ZP-C, separated by a short linker region, that plays an essential role in polymerization of nascent ZP proteins into crosslinked fibrils. Both subdomains adopt immunoglobulin (Ig)-like folds for their 3-dimensional structure. Mouse and human ZP genes are encoded by single-copy genes located on different chromosomes and are highly expressed in the ovary by growing oocytes during late stages of oogenesis. Genes encoding ZP proteins are conserved among mammals, and their expression is regulated by cis-acting sequences located close to the transcription start-site and by the same/similar trans-acting factors. Nascent ZP proteins are synthesized, packaged into vesicles, secreted into the extracellular space, and assembled into long, crosslinked fibrils that have a structural repeat, a ZP2-ZP3 dimer, and constitute the ZP matrix. Fibrils are oriented differently with respect to the oolemma in the inner and outer layers of the ZP. Sequence elements in the ZPD and the carboxy-terminal propeptide of ZP1–4 regulate secretion and assembly of nascent ZP proteins. The presence of both ZP2 and ZP3 is required to assemble ZP fibrils and ZP1 and ZP4 are used to crosslink the fibrils. Inactivation of mouse ZP genes by gene targeting has a detrimental effect on ZP formation around growing oocytes and female fertility. Gene sequence variations in human ZP genes due to point, missense, or frameshift mutations also have a detrimental effect on ZP formation and female fertility. The latter mutations provide additional support for the role of ZPD subdomains and other regions of ZP polypeptide in polymerization of human ZP proteins into fibrils and matrix.
Development and Usability Validation of a Social Robot Platform for Physical and Cognitive Stimulation in Elder Care Facilities
Authors: Cobo Hurtado Luis , Viñas Pablo Francisco , Zalama Eduardo , Gómez-García-Bermejo Jaime , Delgado José María , Vielba García Beatriz
Published: August 2021

This article shows our work for developing an elder care platform for social interaction and physical and cognitive stimulation using the Pepper robot and Android OS as clients, based on the knowledge acquired on our long-term social robotics research experience. The first results of the user’s acceptance of the solution are presented in this article. The platform is able to provide different services to the user, such as information, news, games, exercises or music. The games, which have a bi-modal way of interacting (speech and a touch screen interface), have been designed for cognitive stimulation based on the items of the mini-mental state examination. The results of the user’s performance are stored in a cloud database and can be reviewed by therapists through a web interface that also allows them to establish customized therapy plans for each user. The platform has been tested and validated, first using adult people and then deployed to an elder care facility where the robot has been interacting with users for a long period of time. The results and feedback received have shown that the robot can help to keep the users physically and mentally active as well as establish an emotional link between the user and the robot.
Objective Behavioral Measures in Children before, during, and after the COVID-19 Lockdown in Israel
Authors: Shneor Einat , Doron Ravid , Levine Jonathan , Zimmerman Deena Rachel , Benoit Julia S. , Ostrin Lisa A. , Gordon-Shaag Ariela
Published: August 2021

Studies using questionnaires report that COVID-19 restrictions resulted in children spending significantly less time outdoors. This study used objective measures to assess the impact of pandemic-related restrictions on children’s behavior. A total of 19 healthy 8–12-year-old boys were observed before and during social restriction periods. Of these, 11 boys were reassessed after restrictions were lifted. For each session, Actiwatches were dispensed for measures of time outdoors, activity, and sleep. Changes overall and by school status were assessed using signed-rank test and Wilcoxon rank sum tests. During restrictions, children spent significantly less time outdoors (p = 0.001), were less active (p = 0.001), and spent less time engaged in moderate-to-vigorous physical activity (p = 0.004). Sleep duration was not significantly different between sessions (p > 0.99), but bedtime and wake time shifted to a later time during restrictions (p < 0.05 for both). Time outdoors and activity returned close to pre-pandemic levels after restrictions were lifted (p > 0.05 for both). Children’s behaviors significantly changed during the COVID-19 pandemic. The reduction in outdoor light exposure is of importance due to the role of light in the etiology of myopia and vitamin D production. The reduction in physical activity may have negative health effects in terms of obesity and depression, although further research is required to ascertain the long-term effects.
The Relationship of Tobacco, Alcohol, and Betel Quid with the Formation of Oral Potentially Malignant Disorders: A Community-Based Study from Northeastern Thailand
Authors: Worakhajit Prangtip , Fuangtharnthip Pornpoj , Khovidhunkit Siribang-on Piboonniyom , Chiewwit Pim , Klongnoi Boworn
Published: August 2021

This study’s objective was to describe the relationship between the main risk factors for oral cancer, including tobacco (in the form of cigarettes, smokeless tobacco (SLT), secondhand smoking (SS)), alcohol, and betel quid (BQ), and the occurrence of oral potentially malignant disorders (OPMDs). A community-based case-control study was conducted with a population of 1448 adults aged 40 years or above in northeastern Thailand. Patients aged 60 years or above (OR 1.79, p < 0.001) and female patients (OR 2.17, p < 0.001) had a significant chance of having OPMDs. Our multivariate analysis showed that the most potent risk factor for OPMDs occurrence was betel quid (BQ) (adjusted OR 4.65, p < 0.001), followed by alcohol (OR 3.40, p < 0.001). Even former users were at risk of developing OPMDs. The synergistic effect between these main risk factors was significantly shown in the group exposed to SLT, SS, BQ, and alcohol. The most potent synergistic effect was found in the group exposed to SLT, BQ and alcohol with the OR = 20.96.
Trail Conditions and Community Use: Utilizing Geospatial Video to Guide the Adoption of a Spatial-Temporal Trail Audit Tool (STAT)
Authors: Smock Carissa , Carlson Naomi , Kirkland Chelsey
Published: August 2021

Physical activity (PA), associated with all-cause mortality, morbidity, and healthcare costs, improves vitamin D absorption, immune response, and stress when completed outdoors. Rural communities, which experience PA inequities, rely on trails to meet PA guidelines. However, current trail audit methods could be more efficient and accurate, which geospatial video may support. Therefore, the study purpose was (1) to identify and adopt validated instruments for trail audit evaluations using geospatial video and a composite score and (2) to determine if geospatial video and a composite score motivate (influence the decision to use) specific trail selection among current trail users. Phase 1 used a mixed-method exploratory sequential core design using qualitative data, then quantitative data for the development of the Spatial-temporal Trail Audit Tool (STAT). Geospatial videos of two Northeast Ohio trails were collected using a bicycle-mounted spatial video camera and video analysis software. The creation of STAT was integrated from Neighborhood Environment Walkability Scale (NEWS), Walk Score, and Path Environment Audit Tool (PEAT) audit tools based on four constructs: trail accessibility, conditions, amenities, and safety. Scoring was determined by three independent reviewers. Phase 2 included a mixed-method convergent core design to test the applicability of STAT for trail participant motivation. STAT has 20 items in 4 content areas computing a composite score and was found to increase trail quality and motivation for use. STAT can evaluate trails for PA using geospatial video and a composite score which may spur PA through increased motivation to select and use trails.
Cost-Utility Analysis of Oxybutynin vs. OnabotulinumtoxinA (Botox) in the Treatment of Overactive Bladder Syndrome
Authors: Shabir Habiba , Hashemi Sana , Al-Rufayie Moussa , Adelowo Tayo , Riaz Umar , Ullah Umayair , Alam Benyamin , Anwar Mehreen , de Preux Laure
Published: August 2021

Background: The UK National Health Service (NHS) propose the use of oxybutynin prior to onabotulinumtoxinA (Botox) in the management of overactive bladder syndrome (OAB). Oxybutynin is costly and associated with poor adherence, which may not occur with Botox. We conducted a cost-utility analysis (CUA) to compare the medications. Methods: we compared the two treatments in quality-adjusted life years (QALYS), through the NHS’s perspective. Costs were obtained from UK-based sources and were discounted. Total costs were determined by adding the treatment cost and management cost for complications on each branch. A 12-month time frame was used to model the data into a decision tree. Results: Our results found that using Botox first-line had greater cost utility than oxybutynin. The health net benefit calculation showed an increase in 0.22 QALYs when Botox was used first-line. Botox also had greater cost-effectiveness, with the exception of pediatric patients with an ICER of £42,272.14, which is above the NICE threshold of £30,000. Conclusion: Botox was found to be more cost-effective than antimuscarinics in the management of OAB in adults, however less cost-effective in younger patients. This predicates the need for further research to ascertain the age at which Botox becomes cost-effective in the management of OAB.
Changes in Adolescents’ Psychosocial Functioning and Well-Being as a Consequence of Long-Term COVID-19 Restrictions
Authors: Kerekes Nóra , Bador Kourosh , Sfendla Anis , Belaatar Mohjat , Mzadi Abdennour , Jovic Vladimir , Damjanovic Rade , Erlandsson Maria , Nguyen Hang , Nguyen Nguyet , Ulberg Scott , Kuch-Cecconi Rachael , Szombathyne Meszaros Zsuzsa , Stevanovic Dejan , Senhaji Meftaha , Hedman Ahlström Britt , Zouini Btissame
Published: August 2021

This work studied self-reports from adolescents on how the COVID-19 pandemic has changed their behaviors, relationships, mood, and victimization. Data collection was conducted between September 2020 and February 2021 in five countries (Sweden, the USA, Serbia, Morocco, and Vietnam). In total, 5114 high school students (aged 15 to 19 years, 61.8% females) responded to our electronic survey. A substantial proportion of students reported decreased time being outside (41.7%), meeting friends in real life (59.4%), and school performance (30.7%), while reporting increased time to do things they did not have time for before (49.3%) and using social media to stay connected (44.9%). One third of the adolescents increased exercise and felt that they have more control over their life. Only a small proportion of adolescents reported substance use, norm-breaking behaviors, or victimization. The overall COVID-19 impact on adolescent life was gender-specific: we found a stronger negative impact on female students. The results indicated that the majority of adolescents could adapt to the dramatic changes in their environment. However, healthcare institutions, municipalities, schools, and social services could benefit from the findings of this study in their work to meet the needs of those young people who signaled worsened psychosocial functioning, increased stress, and victimization.
Risk Characterization and Benefit–Risk Assessment of Brominated Flame Retardant in Commercially Exploited Freshwater Fishes and Crayfish of Lake Trasimeno, Italy
Authors: Roila Rossana , Branciari Raffaella , Ranucci David , Stramenga Arianna , Tavoloni Tamara , Stecconi Tommaso , Franceschini Raffaella , Piersanti Arianna
Published: August 2021

Among brominated flame retardants (BFRs), polybrominateddiphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) were the most widely used in past decades. BFRs not being chemically bonded to polymers means they can easily leach from the products into the environment and bioaccumulate. Humans are exposed to flame retardants mainly through food consumption, especially fish and fish products. In the present study, the occurrence of PBDEs and HBCDs in freshwater fishes and crayfish from Lake Trasimeno (Umbria region, central Italy) was assessed according to monitoring plans recommended by European competent authorities. The dietary exposure of the central Italian population to such molecules was calculated, and the risk characterization and the benefit–risk evaluation were also assessed. A total of 90 samples were analyzed by means of gas and liquid chromatography associated with triple quadrupole mass spectroscopy. A total of 51% of samples were found positive for at least one of the congeners; the most frequently found molecule was BDE-47. The data on dietary exposure ranged from 0.138 to 1.113 pg/kg body weight/day for ∑PBDE and from 0.805 to 0.868 pg/kg body weight/day for ∑HBCD. The data show no health risks for the central Italian population consuming freshwater fish products from Lake Trasimeno in relation to exposure to PBDE and HBCD.
Assessment of Radioactivity Level in the Terrestrial and Marine Organisms in Yangjiang and Its Adjacent Areas (China)
Authors: Li Dongmei , Jiang Zhongchen , Zhao Li , Zhao Feng , Zhou Peng
Published: August 2021

In order to assess the radioactive level in the terrestrial and marine organisms in Yangjiang and the adjacent areas, 90Sr, gross beta and gamma-emitting radionuclides (238U, 226Ra, 228Th, 226Ra, 40K, 137Cs, 51Cr, 55Fe, 54Mn, 58Co, 60Co and 65Zn) were analyzed from 2011 to 2012. The annual effective doses were estimated in the high natural radioactive background areas in Yangjiang (HBRAYJ). The specific activities of 238U, 228Th, 226Ra, 40K and 137Cs in all organisms were <0.05–5.20, 0.30–14.50, 0.11–3.58, 11.1–148.0 and <0.003–0.088 Bq/kg, whilst 51Cr, 55Fe, 54Mn, 58Co, 60Co, 65Zn and 110mAg were below the minimum detectable activity. 90Sr and gross beta specific activities were 20.0–143.0 and 0.021–0.316 Bq/kg. Results show that 228Th was significantly higher than 238U and 226Ra of natural U series in organisms due to the rich-Th soils in the HBRAYJ; 228Th, 226Ra, 40K, 137Cs and 90Sr were greatly lower than the limited concentrations in Chinese foods. The internal dose mainly contributes to natural 40K, 226Ra and 228Th. It is useful to provide some basic data and assess the radiological risk from the HBRAYJ and Yangjiang nuclear power plants in future.
Genome-Wide Characterization and Expression Analysis of the SBP-Box Gene Family in Sweet Orange (Citrus sinensis)
Authors: Song Na , Cheng Yulin , Peng Weiye , Peng ErPing , Zhao Zengling , Liu Tiantian , Yi Tuyong , Dai Liangying , Wang Bing , Hong Yanyun
Published: August 2021

SBP-box is an important plant-specific transcription factor family and is involved in diverse biological processes. Here, we identified a total of 15 SBP-BOX genes in the important fruit crop sweet orange (Citrus sinensis) and characterized their gene structures, conserved domain and motif, chromosomal location, and cis-acting regulatory elements. SBP genes were classified into four subfamilies based on the amino acid sequence homology, and the classification is equally strongly supported by the gene and protein structures. Our analysis revealed that segmental duplication events were the main driving force in the evolution of CsSBP genes, and gene pairs might undergo extensive purifying selection. Further synteny analysis of the SBP members among sweet orange and other plant species provides valuable information for clarifying the CsSBP family evolutionary relationship. According to publicly available RNA-seq data and qRT-PCR analysis from various sweet orange tissues, CsSBP genes may be expressed in different tissues and developmental stages. Gene expression analysis showed variable expression profiles of CsSBP genes under various abiotic stresses, such as high and low-temperature, salt, and wound treatments, demonstrating the potential role of SBP members in sweet orange response to abiotic stress. Noticeably, all CsSBP genes were also downregulated in sweet orange upon the infection of an important fungal pathogen Diaporthe citri. Our results provide valuable information for exploring the role of SBP-Box in sweet orange.
Neuroprotective and Symptomatic Effects of Cannabidiol in an Animal Model of Parkinson’s Disease
Authors: Giuliano Claudio , Francavilla Miriam , Ongari Gerardo , Petese Alessandro , Ghezzi Cristina , Rossini Nora , Blandini Fabio , Cerri Silvia
Published: August 2021

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta, leading to classical PD motor symptoms. Current therapies are purely symptomatic and do not modify disease progression. Cannabidiol (CBD), one of the main phytocannabinoids identified in Cannabis Sativa, which exhibits a large spectrum of therapeutic properties, including anti-inflammatory and antioxidant effects, suggesting its potential as disease-modifying agent for PD. The aim of this study was to evaluate the effects of chronic treatment with CBD (10 mg/kg, i.p.) on PD-associated neurodegenerative and neuroinflammatory processes, and motor deficits in the 6-hydroxydopamine model. Moreover, we investigated the potential mechanisms by which CBD exerted its effects in this model. CBD-treated animals showed a reduction of nigrostriatal degeneration accompanied by a damping of the neuroinflammatory response and an improvement of motor performance. In particular, CBD exhibits a preferential action on astrocytes and activates the astrocytic transient receptor potential vanilloid 1 (TRPV1), thus, enhancing the endogenous neuroprotective response of ciliary neurotrophic factor (CNTF). These results overall support the potential therapeutic utility of CBD in PD, as both neuroprotective and symptomatic agent.
Hippocampal and Reticulo-Thalamic Parvalbumin Interneurons and Synaptic Re-Organization during Sleep Disorders in the Rat Models of Parkinson’s Disease Neuropathology
Authors: Radovanovic Ljiljana , Petrovic Jelena , Saponjic Jasna
Published: August 2021

We investigated the alterations of hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV) interneurons and their synaptic re-organizations underlying the prodromal local sleep disorders in the distinct rat models of Parkinson’s disease (PD). We demonstrated for the first time that REM sleep is a predisposing state for the high-voltage sleep spindles (HVS) induction in all experimental models of PD, particularly during hippocampal REM sleep in the hemiparkinsonian models. There were the opposite underlying alterations of the hippocampal and RT GABAergic PV+ interneurons along with the distinct MAP2 and PSD-95 expressions. Whereas the PD cholinopathy enhanced the number of PV+ interneurons and suppressed the MAP2/PSD-95 expression, the hemiparkinsonism with PD cholinopathy reduced the number of PV+ interneurons and enhanced the MAP2/PSD-95 expression in the hippocampus. Whereas the PD cholinopathy did not alter PV+ interneurons but partially enhanced MAP2 and suppressed PSD-95 expression remotely in the RT, the hemiparkinsonism with PD cholinopathy reduced the PV+ interneurons, enhanced MAP2, and did not change PSD-95 expression remotely in the RT. Our study demonstrates for the first time an important regulatory role of the hippocampal and RT GABAergic PV+ interneurons and the synaptic protein dynamic alterations in the distinct rat models of PD neuropathology.
Dissecting the Purinergic Signaling Puzzle
Authors: Pérez-Sen Raquel , Delicado Esmerilda G.
Published: August 2021

Purinergic signaling regulates a plethora of physiological processes and is an expanding research field [...]
17,20S(OH)2pD Can Prevent the Development of Skin Fibrosis in the Bleomycin-Induced Scleroderma Mouse Model
Authors: Brown Lobbins Monica L. , Scott Imara-Safi O. , Slominski Andrzej T. , Hasty Karen A. , Zhang Sicheng , Miller Duane D. , Li Wei , Kim Tae-Kang , Janjetovic Zorica , Patel Tejesh S. , Myers Linda K. , Postlethwaite Arnold E.
Published: August 2021

Systemic sclerosis (SSc; scleroderma) is a chronic fibrotic disease involving TGF-β1. Low serum vitamin D (vit D) correlates with the degree of fibrosis and expression of TGF-β1. This study was designed to determine whether the noncalcemic vit D analog, 17,20S(OH)2pD, suppresses fibrosis and mediators of the TGF-β1 pathway in the bleomycin (BLM) model of fibrosis. Fibrosis was induced into the skin of female C57BL/6 mice by repeated injections of BLM (50 μg/100 μL) subcutaneously. Mice received daily oral gavage with either vehicle (propylene glycol) or 17,20S(OH)2pD using 5, 15, or 30 μg/kg for 21 days. The injected skin was biopsied; analyzed histologically; examined for total collagen by Sircol; and examined for mRNA expression of MMP-13, BMP-7, MCP-1, Gli1, and Gli2 by TR-PCR. Spleen was analyzed for lymphocytes using flow cytometry. Serum was analyzed for cytokines using a multiplexed ELISA. Results showed that all three doses of 17,20S(OH)2pD suppressed net total collagen production, dermal thickness, and total collagen content in the BLM fibrosis model. 17,20S(OH)2pD also increased MMP-13 expression, decreased MCP-1 and Gli-2 expression in vivo, and suppressed serum levels of IL-13, TNF-α, IL-6, IL-10, IL-17, and IL-12p70. In summary, 17,20S(OH)2pD modulates the mediators of fibrosis in vivo and suppresses total collagen production and dermal thickness. This antifibrotic property of 17,20S(OH)2pD offers new therapeutic approaches for fibrotic disorders.
Targeting Drug Delivery in the Elderly: Are Nanoparticles an Option for Treating Osteoporosis?
Authors: Thurner Gudrun C. , Haybaeck Johannes , Debbage Paul
Published: August 2021

Nanoparticles bearing specific targeting groups can, in principle, accumulate exclusively at lesion sites bearing target molecules, and release therapeutic agents there. However, practical application of targeted nanoparticles in the living organism presents challenges. In particular, intravasally applied nanoparticles encounter physical and physiological barriers located in blood vessel walls, blocking passage from the blood into tissue compartments. Whereas small molecules can pass out of the blood, nanoparticles are too large and need to utilize physiological carriers enabling passage across endothelial walls. The issues associated with crossing blood-tissue barriers have limited the usefulness of nanoparticles in clinical applications. However, nanoparticles do not encounter blood-tissue barriers if their targets are directly accessible from the blood. This review focuses on osteoporosis, a disabling and common disease for which therapeutic strategies are limited. The target sites for therapeutic agents in osteoporosis are located in bone resorption pits, and these are in immediate contact with the blood. There are specific targetable biomarkers within bone resorption pits. These present nanomedicine with the opportunity to treat a major disease by use of simple nanoparticles loaded with any of several available effective therapeutics that, at present, cannot be used due to their associated side effects.
Pathogenic Mechanisms of Hypertrophic Cardiomyopathy beyond Sarcomere Dysfunction
Authors: Chou Chun , Chin Michael T.
Published: August 2021

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 people in the general population. Although characterized by asymmetric left ventricular hypertrophy, cardiomyocyte disarray, and cardiac fibrosis, HCM is in fact a highly complex disease with heterogenous clinical presentation, onset, and complications. While HCM is generally accepted as a disease of the sarcomere, variable penetrance in families with identical genetic mutations challenges the monogenic origin of HCM and instead implies a multifactorial cause. Furthermore, large-scale genome sequencing studies revealed that many genes previously reported as causative of HCM in fact have little or no evidence of disease association. These findings thus call for a re-evaluation of the sarcomere-centered view of HCM pathogenesis. Here, we summarize our current understanding of sarcomere-independent mechanisms of cardiomyocyte hypertrophy, highlight the role of extracellular signals in cardiac fibrosis, and propose an alternative but integrated model of HCM pathogenesis.
Effects of 4-Hexylresorcinol on Craniofacial Growth in Rats
Authors: Lee In-Song , Kim Dae-Won , Oh Ji-Hyeon , Lee Suk Keun , Choi Je-Yong , Kim Seong-Gon , Kim Tae-Woo
Published: August 2021

4-Hexylresorcinol (4HR) has been used as a food additive, however, it has been recently demonstrated as a Class I histone deacetylase inhibitor (HDACi). Unlike other HDACi, 4HR can be taken through foods. Unfortunately, some HDACi have an influence on craniofacial growth, therefore, the purpose of this study was to evaluate the effects of 4HR on craniofacial growth. Saos-2 cells (osteoblast-like cells) were used for the evaluation of HDACi and its associated activities after 4HR administration. For the evaluation of craniofacial growth, 12.8 mg/kg of 4HR was administered weekly to 4 week old rats (male: 10, female: 10) for 12 weeks. Ten rats were used for untreated control (males: 5, females: 5). Body weight was recorded every week. Serum and head samples were collected at 12 weeks after initial administration. Craniofacial growth was evaluated by micro-computerized tomography. Serum was used for ELISA (testosterone and estrogen) and immunoprecipitation high-performance liquid chromatography (IP-HPLC). The administration of 4HR (1–100 μM) showed significant HDACi activity (p < 0.05). Body weight was significantly different in male rats (p < 0.05), and mandibular size was significantly smaller in 4HR-treated male rats with reduced testosterone levels. However, the mandibular size was significantly higher in 4HR treated female rats with increased growth hormone levels. In conclusion, 4HR had HDACi activity in Saos-2 cells. The administration of 4HR on growing rats showed different responses in body weight and mandibular size between sexes.
Novel Insight into the Effects of CpxR on Salmonella enteritidis Cells during the Chlorhexidine Treatment and Non-Stressful Growing Conditions
Authors: Liu Xiaoying , Omar Misara , Nagaraja Kakambi V. , Goyal Sagar M. , Vidovic Sinisa
Published: August 2021

The development and spread of antibiotics and biocides resistance is a significant global challenge. To find a solution for this emerging problem, the discovery of novel bacterial cellular targets and the critical pathways associated with antimicrobial resistance is needed. In the present study, we investigated the role of the two most critical envelope stress response regulators, RpoE and CpxR, on the physiology and susceptibility of growing Salmonella enterica serovar enteritidis cells using the polycationic antimicrobial agent, chlorhexidine (CHX). It was shown that deletion of the cpxR gene significantly increased the susceptibility of this organism, whereas deletion of the rpoE gene had no effect on the pathogen’s susceptibility to this antiseptic. It has been shown that a lack of the CpxR regulator induces multifaceted stress responses not only in the envelope but also in the cytosol, further affecting the key biomolecules, including DNA, RNA, and proteins. We showed that alterations in cellular trafficking and most of the stress responses are associated with a dysfunctional CpxR regulator during exponential growth phase, indicating that these physiological changes are intrinsically associated with the lack of the CpxR regulator. In contrast, induction of type II toxin-antitoxin systems and decrease of abundances of enzymes and proteins associated with the recycling of muropeptides and resistance to polymixin and cationic antimicrobial peptides were specific responses of the ∆cpxR mutant to the CHX treatment. Overall, our study provides insight into the effects of CpxR on the physiology of S. Enteritidis cells during the exponential growth phase and CHX treatment, which may point to potential cellular targets for the development of an effective antimicrobial agent.
ExpressHeart: Web Portal to Visualize Transcriptome Profiles of Non-Cardiomyocyte Cells
Authors: Li Gang , Luan Changfei , Dong Yanhan , Xie Yifang , Zentz Scott C. , Zelt Rob , Roach Jeff , Liu Jiandong , Qian Li , Li Yun , Yang Yuchen
Published: August 2021

Unveiling the molecular features in the heart is essential for the study of heart diseases. Non-cardiomyocytes (nonCMs) play critical roles in providing structural and mechanical support to the working myocardium. There is an increasing amount of single-cell RNA-sequencing (scRNA-seq) data characterizing the transcriptomic profiles of nonCM cells. However, no tool allows researchers to easily access the information. Thus, in this study, we develop an open-access web portal, ExpressHeart, to visualize scRNA-seq data of nonCMs from five laboratories encompassing three species. ExpressHeart enables comprehensive visualization of major cell types and subtypes in each study; visualizes gene expression in each cell type/subtype in various ways; and facilitates identifying cell-type-specific and species-specific marker genes. ExpressHeart also provides an interface to directly combine information across datasets, for example, generating lists of high confidence DEGs by taking the intersection across different datasets. Moreover, ExpressHeart performs comparisons across datasets. We show that some homolog genes (e.g., Mmp14 in mice and mmp14b in zebrafish) are expressed in different cell types between mice and zebrafish, suggesting different functions across species. We expect ExpressHeart to serve as a valuable portal for investigators, shedding light on the roles of genes on heart development in nonCM cells.
Biodiversity in a Cool-Climate Vineyard: A Case Study from Quebec
Authors: Vincent Charles , Lasnier Jacques , de Coussergues Charles-Henri , Baril Alain
Published: August 2021

In Quebec (Canada), viticulture has experienced steady growth in the last 35 years in terms of surfaces cultivated and value, although it is practiced in climatic conditions at the edge of what is considered a cool-climate area. This case study documents biodiversity studies conducted at the l’Orpailleur vineyard (Dunham, QC, Canada) from 1997 to 2021. In a first phase starting in 1997, the biodiversity of insecticide-free and insecticide-treated plots was determined for the taxa Scarabaeidae, Curculionidae, Chrysomelidae, Cicadellidae, Acari and Aranae. This step provided a baseline allowing to identify key arthropods. In a second phase starting in 2004, entomological issues were addressed on an ad hoc basis. In 2014, a third phase began with a perspective of sustainability and management of plant diversity in the vineyard to conserve natural enemies. Because of increased Japanese beetle (Popillia japonica-Scarabaeidae) populations and threats to vineyards, a biocontrol program based on the parasitoid Istocheta aldrichi (Tachinidae) was initiated. The unusually fast development of grapevines during the growing season, selection of flowering species, as well as selected arthropods associated with these flowering species, will be illustrated. Periodic update of protection programs will be required to address future challenges associated with climate change scenarios and world trade.
Microfluidic Systems for Isolation of Spermatozoa from Testicular Specimens of Non-Obstructive Azoospermic Men: Does/Can It Improve Sperm Yield?
Authors: Smith Gary D. , Cantatore Clementina , Ohl Dana A.
Published: August 2021

Intracytoplasmic sperm injection (ICSI) has allowed reproduction options through assisted reproductive technologies (ARTs) for men with no spermatozoa within the ejaculate (azoospermia). In men with non-obstructive azoospermia (NOA), the options for spermatozoa retrieval are testicular sperm extraction (TESE), testicular sperm aspiration (TESA), or micro-surgical sperm extraction (microTESE). At the initial time of spermatozoa removal from the testis, spermatozoa are immobile. Independent of the means of spermatozoa retrieval, the subsequent steps of removing spermatozoa from seminiferous tubules, determining spermatozoa viability, identifying enough spermatozoa for oocyte injections, and isolating viable spermatozoa for injection are currently performed manually by laboratory microscopic dissection and collection. These laboratory techniques are highly labor-intensive, with yield unknown, have an unpredictable efficiency and/or success rate, and are subject to inter-laboratory personnel and intra-laboratory variability. Here, we consider the potential utility, benefits, and shortcomings of developing technologies such as motility induction/stimulants, microfluidics, dielectrophoresis, and cell sorting as andrological laboratory add-ons to reduce the technical burdens and variabilities in viable spermatozoa isolation from testicular samples in men with NOA.
Association of Echocardiographic Diastolic Dysfunction with Discordance of Invasive Intracoronary Pressure Indices
Authors: Tahir Hassan , Livesay James , Fogelson Benjamin , Baljepally Raj
Published: August 2021

Instantaneous wave-free ratio (iFR)-guided coronary revascularization has similar clinical outcomes compared to fractional flow reserve (FFR)-guided revascularization strategy. However, some studies have shown a discordance of around 20% between iFR and FFR. Although various factors have been reported in the literature to affect pressure indices and lead to such discordance, there is a paucity of data regarding the effect of diastolic dysfunction on functional assessment of coronary arteries. Our study aimed to investigate whether there was an association between echocardiographic left ventricular diastolic dysfunction and iFR/FFR discordance. This retrospective observational study evaluated 100 patients with angiographically intermediate coronary stenosis (50–70%) who underwent physiological testing with iFR and FFR. Transthoracic echocardiograms were reviewed to assess echocardiographic indices of diastolic function. The study population was divided into two groups based on diastolic function. iFR and FFR discordance was measured in each group and compared to evaluate the statistical difference. The mean age of the study population was 66.22 ± 10.02 years. Discordance between iFR and FFR was seen in 45.16% of patients with diastolic dysfunction compared to 24.64% of patients with normal diastolic function (p = 0.04). Multivariable logistic regression analysis indicated that echocardiographic E/e′ was independently associated with iFR/FFR discordance (p = 0.02). Left ventricular diastolic dysfunction is a significant factor that can lead to discordance between iFR and FFR and should be taken into account during coronary physiological testing.
Urine Phenylacetylglutamine Determination in Patients with Hyperphenylalaninemia
Authors: Andrade Fernando , Cano Ainara , Unceta Suarez María , Arza Arantza , Vinuesa Ana , Ceberio Leticia , López-Oslé Nuria , de Frutos Gorka , López-Oceja Raquel , Aznal Elena , González-Lamuño Domingo , de las Heras Javier
Published: August 2021

Phenylketonuria (PKU), an autosomal-recessive inborn error of phenylalanine (Phe) metabolism is the most prevalent disorder of amino acid metabolism. Currently, clinical follow-up relies on frequent monitoring of Phe levels in blood. We hypothesize that the urine level of phenylacetylglutamine (PAG), a phenyl-group marker, could be used as a non-invasive biomarker. In this cross-sectional study, a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS) method was used for urinary PAG quantification in 35 participants with hyperphenylalaninemia (HPA) and 33 age- and sex-matched healthy controls. We have found that (a) PKU patients present higher urine PAG levels than healthy control subjects, and that (b) there is a significant correlation between urine PAG and circulating Phe levels in patients with HPA. In addition, we show a significant strong correlation between Phe levels from venous blood samples and from capillary finger-prick dried blood spot (DBS) samples collected at the same time in patients with HPA. Further research in order to assess the potential role of urine PAG as a non-invasive biomarker in PKU is warranted.
Hospital Dentistry for Intensive Care Unit Patients: A Comprehensive Review
Authors: Jun Mi-Kyoung , Ku Jeong-Kui , Kim Il-hyung , Park Sang-Yoon , Hong Jinson , Kim Jae-Young , Lee Jeong-Keun
Published: August 2021

This study aimed to review the oral hygiene status, oral care guidelines, and outcomes of oral care in intensive care unit (ICU) patients from a dental perspective for effective oral care. A literature search using the keywords “Hospital dentistry” OR “Oral care” OR “Intensive care unit” OR “Hospital inpatient” OR “Hospitalization” OR “Emergency service” AND “Oral health” OR “Oral hygiene” OR “Dental plaque” was conducted in PubMed, Medline, and Google Scholar to identify publications reporting on the oral care of the patients admitted to ICUs. A total of 17,400 articles were initially identified. Of these, 58 were selected and classified into three categories for critical review. Seven of these studies evaluated the oral status of ICU patients, and most of the studies indicated that ICU patients had poor oral hygiene or required active dental treatment. Thirty-three of these studies evaluated oral care methods for ICU patients, and in general, oral care methods using chlorhexidine as adjuncts along with tooth brushing were recommended. However, there were insufficient studies to evaluate oral hygiene through effective assessment tools from a dental perspective. In 36 studies on the outcomes of oral care in ICU patients, interventions by dental professionals showed effective results in preventing hospital-acquired infection. This review highlights the importance of establishing guidelines for the evaluation of oral status in ICU patients and summarizes data that may be useful for future studies. Further studies on maintaining good oral hygiene among ICU patients are needed.
Enhanced Expression but Decreased Specific Activity of Matrix Metalloproteinase 10 (MMP-10) in Comparison with Matrix Metalloproteinase 3 (MMP-3) in Human Urinary Bladder Carcinoma
Authors: Kudelski Jacek , Młynarczyk Grzegorz , Gudowska-Sawczuk Monika , Mroczko Barbara , Darewicz Barbara , Bruczko-Goralewska Marta , Sobolewski Krzysztof , Romanowicz Lech
Published: August 2021

Human urinary bladder cancer is a huge worldwide oncological problem causing many deaths every year. The degradation of extracellular matrix (ECM) induced by molecules such as matrix metalloproteinases (MMPs) is one of the main factors influencing the process of metastasis origination. The MMP expression is tied to tumor aggressiveness, stage, and patient prognosis. The cleavage of constituent proteins is initiated and prolonged by matrix metalloproteinases, such as MMP-3 and MMP-10. The aim of this study was to evaluate the expression and activity of both MMPs in human urinary bladder cancer occurring at various stages of the disease. Tissue samples from patients with urinary bladder cancer were analyzed. Samples were collected from patients with a low- and high-grade cancer. Control tissue was collected from the site opposite to the tumor. DNA content, MMPs content, and activity of MMP-3 and MMP-10 were measured using ELISA and Western blot techniques. MMP-3 and MMP-10 occur in high molecular complexes in human urinary bladder in healthy and cancerous tissues. Particularly, in high-grade tumors, the content of MMP-10 prevails over MMP-3. The actual and specific activities vary in both grades of urinary bladder cancer; however, the highest activity for MMP-3 and MMP-10 was found in low-grade tissues. In conclusion, MMP-10 had a higher content, but a lower activity in all investigated tissues compared to MMP-3. Generally, obtained results demonstrated a contrary participation of MMP-3 and MMP-10 in ECM remodeling what may be crucial in the pathogenesis of human urinary bladder carcinoma.
Exploring Critical Success Factors of Competence-Based Synergy in Strategic Alliances: The Renault–Nissan–Mitsubishi Strategic Alliance
Authors: Čirjevskis Andrejs
Published: August 2021

This paper aims to unbundle the antecedents of competence-based synergy in the strategic alliance formation process by employing the ARCTIC framework. The current research provides a new empirical application of the ARCTIC framework to reveal the success factors of reciprocal synergies of the Renault–Nissan–Mitsubishi strategic alliance in the automotive industry. By taking a resource-based view on the sources of competitive advantage, the current paper contributes to theoretical and practical issues of global strategic alliances as part of the existing literature on strategic management, international business, and corporate finance. By bridging qualitative and quantitative research methods, the paper provides validity to the ARCTIC framework with an application of the real option valuation. A conceptual model of research helps practitioners and scholars to explore critical success factors of alliance formation and to predict a competence-based synergy of strategic alliances. Future research may explore the institutional context of strategic alliances, specifically, exploring the impact of the French and Japanese governments on the Renault–Nissan–Mitsubishi alliance’s synergies.
The Association between Low Muscle Mass and Hepatic Steatosis in Asymptomatic Population in Korea
Authors: Chung Goh-Eun , Park Hyo-Eun , Kim Min-Joo , Kwak Min-Sun , Yang Jong-In , Chung Su-Jin , Yim Jeong-Yoon , Yoon Ji-Won
Published: August 2021

Background: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). Methods: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. Results: Among 960 subjects (58.1 years; 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38–2.78; class II, OR: 3.33, 95% CI: 1.77–6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, <302; OR: 2.19, in CAP ≥ 302; class II, OR: 2.33, for CAP ≥ 248, <302; OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31–2.95; class II, OR: 2.96, 95% CI: 1.51–5.78). Conclusion: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.
Effects of a Sodium Phosphate Electrolyte Additive on Elevated Temperature Performance of Spinel Lithium Manganese Oxide Cathodes
Authors: Jo Minsang , Park Seong-Hyo , Lee Hochun
Published: August 2021

LiMn2O4 (LMO) spinel cathode materials suffer from severe degradation at elevated temperatures because of Mn dissolution. In this research, monobasic sodium phosphate (NaH2PO4, P2) is examined as an electrolyte additive to mitigate Mn dissolution; thus, the thermal stability of the LMO cathode material is improved. The P2 additive considerably improves the cyclability and storage performances of LMO/graphite and LMO/LMO symmetric cells at 60 °C. We explain that P2 suppresses the hydrofluoric acid content in the electrolyte and forms a protective cathode electrolyte interphase layer, which mitigates the Mn dissolution behavior of the LMO cathode material. Considering its beneficial role, the P2 additive is a useful additive for spinel LMO cathodes that suffer from severe Mn dissolution.
Development and Characterization of High Efficacy Cell-Penetrating Peptide via Modulation of the Histidine and Arginine Ratio for Gene Therapy
Authors: Liu Yu , Wan Huan-Huan , Tian Duo-Mei , Xu Xiao-Jun , Bi Chang-Long , Zhan Xiao-Yong , Huang Bi-Hui , Xu Yun-Sheng , Yan Le-Ping
Published: August 2021

Cell-penetrating peptides (CPPs), as non-viral gene delivery vectors, are considered with lower immunogenic response, and safer and higher gene capacity than viral systems. In our previous study, a CPP peptide called RALA (arginine rich) presented desirable transfection efficacy and owns a potential clinic use. It is believed that histidine could enhance the endosome escaping ability of CPPs, yet RALA peptide contains only one histidine in each chain. In order to develop novel superior CPPs, by using RALA as a model, we designed a series of peptides named HALA (increased histidine ratio). Both plasmid DNA (pDNA) and siRNA transfection results on three cell lines revealed that the transfection efficacy is better when histidine replacements were on the C-terminal instead of on the N-terminal, and two histidine replacements are superior to three. By investigating the mechanism of endocytosis of the pDNA nanocomplexes, we discovered that there were multiple pathways that led to the process and caveolae played the main role. During the screening, we discovered a novel peptide-HALA2 of high cellular transfection efficacy, which may act as an exciting gene delivery vector for gene therapy. Our findings also bring new insights on the development of novel robust CPPs.
Simulated and Experimental Investigation of Mechanical Properties for Improving Isotropic Fracture Strength of 3D-Printed Capsules
Authors: Lim Taeuk , Cheng Hao , Song Wonil , Lee Jasung , Kim Sunghoon , Jung Wonsuk
Published: August 2021

Three-dimensional (3D) printer-based self-healing capsules, embedded in cement composites, were proposed to heal cracks, as they allow for various structural designs of capsules, repeatable fabrication, and strength analysis. Out of many 3D printing methods, such as fusion deposition modeling (FDM), powder layer fusion, and PolyJet printing, FDM was used to design, analyze, and produce new self-healing capsules, which are widely used due to their high-speed, low-cost, and precise manufacturing. However, the PLA extruded in the FDM had low adhesion energy between stacked layers, which caused a degradation of the performance of the self-healing capsule, because it had different strengths depending on the angle between the stacked layers and the applied load within the concrete structure. Therefore, in this paper, specimens were produced, in accordance with ASTM specifications, using the FDM PLA method, and mechanical properties were obtained through tensile, shear, and compression tests. Additionally, the isotropic fracture characteristics of the four types of capsules were analyzed through finite element method analysis. Subsequently, the 3D-printed capsules were produced, and the fracture strength was analyzed in the x, y and z directions of the applied load through a compression test. As a result, the newly proposed capsule design was verified to have an isotropic fracture strength value of 1400% in all directions compared to conventional spherical thin film capsules