bluuebunny/crossref_metadata_2025 huggingface dataset:
Instruments to Assess Physical Activity in Primary Education Students with Autism Spectrum Disorder: A Systematic Review
Authors: López-Valverde Paula , Rico-Díaz Javier , Barcala-Furelos Martín , Martí-González Mariacarla , Martín Juan L. , López-García Sergio
Published: May 2021

The scientific evidence supports that physical inactivity in childhood is a reality throughout the world which generates important consequences in the global development of children. Young people with Autism Spectrum Disorder (ASD), due to the characteristics of the disorder they suffer, constitute a group at risk. Therefore, assessing the levels of physical activity (PA) in this group is fundamental for subsequent decision making and implementation of PA promotion programmes. Consequently, the aim of this systematic review was to identify, summarise and analyse the main instruments used to assess the levels of PA (in terms of time and/or intensity) in primary school children diagnosed with ASD. Scientific articles in English and Spanish published in five databases were reviewed: PsycINFO, WOS, SPORTDiscus, Scopus and PubMed, following the guidelines of the PRISMA statement. Out of the 605 articles identified, 12 met the previously established inclusion criteria. The instruments used by the studies analysed were divided into two main groups: accelerometers and questionnaires. Both showed different strengths and limitations but agreed on the low levels registered of PA in children with ASD. For this reason, it is considered necessary that further research be carried out in this field, as well as the development and implementation of sports programmes adjusted and adapted to the needs and characteristics of the ASD group.
Geographic Heterogeneity in Influenza and Pneumonia Mortality in Hispanic Americans
Authors: Diaz-Campbell Annika , Sumon Mahbubur , Mehari Alem , Snead Mackenzie B. , Ramirez Rafael , Arend Elizabeth , Gillum Richard F.
Published: May 2021

(1) Background: Influenza and pneumonia (IP) is a leading cause of death in the US. The hypothesis was tested that the mortality rate differential between Hispanic whites (HW) and non-Hispanic whites (NHW) from IP varied by geographic region in the US. (2) Methods: The CDC database for multiple causes of death between 1999–2018 was used for this study. For ages 25–84, age-adjusted mortality rates per 100,000 (AAMR) for IP were computed by Hispanic ethnicity in whites for 10 Health & Human Services (HHS) regions and for urbanization levels in HHS Region 2. (3) Results: AAMR for IP was 13.76 (13.62–13.9) in HW and 14.91 (14.86–14.95) in NHW (rate ratio 1.08). Among HHS regions, rates were generally lower in HW than in NHW with the major exception of HHS Region 2. The rate there was 21.78 (21.24–22.33) in HW, 36.5% greater (p < 0.05) than that in NHW of 15.71 (15.56–15.86). In large central metro areas of Region 2, the rate was 27.10 (26.36–27.83) in HW compared to 19.78 (19.47–20.09) in NHW. (4) Conclusion: The difference in AAMR from IP between HW and NHW varied by region and urbanization with much higher rates for HW than NHW only in metropolitan areas of New York and New Jersey.
“It’s Just Not Something We Do at School”. Adolescent Boys’ Understanding, Perceptions, and Experiences of Muscular Fitness Activity
Authors: Cox Ashley , Fairclough Stuart J. , Noonan Robert J.
Published: May 2021

Background: English youth typically do not sufficiently engage in the types and intensities of physical activity that develop muscular fitness. The aim of this study was to use a combination of qualitative techniques to explore adolescent boys’ understanding, perceptions, and experiences of physical activity and the role muscular fitness plays within boys’ physically active lifestyles. Methods: Focus group interviews with a write, draw, show, and tell activity were conducted with 32 adolescent boys aged 14–16 years from 3 secondary schools. Three separate sources of data (frequency counts, verbatim transcripts, and visual data) were generated and were pooled together and triangulated. Data were analysed deductively, first using the Youth Physical Activity Promotion model as a thematic framework, and then inductively. Results: Physical activity was frequently associated with organised sport, and most boys were unaware of current UK physical activity guidelines. Co-participation was frequently reported as a reinforcing factor to physical activity. Conclusions: There was a perceived lack of opportunity to participate in muscular fitness activities, particularly in school, and knowledge of how to conduct muscular fitness activities was limited. The contribution of physical education was highlighted as being key to facilitating exposure to muscular fitness activities.
Mental Adjustment as a Predictor of Comprehensive Quality of Life Outcome among Patients with Terminal Cancer
Authors: Chang Li-Fang , Lin Chi-Kang , Wu Li-Fen , Ho Ching-Liang , Lu Yi-Ling , Pan Hsueh-Hsing
Published: May 2021

Using path modeling, this study aimed to explore whether mental adjustment was directly or indirectly related to comprehensive quality of life outcome (CoQoLO) among patients with terminal cancer. We conducted a cross-sectional designed study among patients with terminal cancer who underwent convenience sampling at our northern Taiwan clinic from August 2019 to August 2020. Patient characteristics data were collected via structured questionnaires, namely, the Mini-Mental Adjustment to Cancer Scale and the Comprehensive Quality of Life Outcome Inventory. Descriptive statistics and regression analyses were used to examine the relationship between mental adjustment and CoQoLO. Path analysis described the dependencies among variables. For the 117 enrolled patients analyzed, MAC (β = 1.2, 95% confidence interval (CI) = 0.8–1.6, p < 0.001) and living with others (β = 19.9, 95% CI = 4.1–35.7, p = 0.015) were significant predictors and correlated positively with a CoQoLO score. Path modeling showed that the patients’ mental adjustment, economic status, perceived disease severity, palliative prognostic index, and symptom severity directly affected their CoQoLO. Our results indicate that the higher the mental adjustment, the better the CoQoLO among patients with terminal cancer. Thus, nurses need to assess mental adjustment levels when patients are hospitalized and accordingly develop interventions to improve the terminally ill patients’ mental adjustment to the final stages of cancer, thereby helping them to achieve good CoQoLO.
Copyright Protection Based on Zero Watermarking and Blockchain for Vector Maps
Authors: Ren Na , Zhao Yazhou , Zhu Changqing , Zhou Qifei , Xu Dingjie
Published: May 2021

Zero watermarking does not alter the original information contained in vector map data and provides perfect imperceptibility. The use of zero watermarking for data copyright protection has become a significant trend in digital watermarking research. However, zero watermarking encounters tremendous obstacles to its development and application because of its requirement to store copyright information with a third party and its difficulty in confirming copyright ownership. Aiming at the shortcomings of the existing zero watermarking technology, this paper proposes a new zero watermarking construction method based on the angular features of vector data that store the zero watermarking and copyright information on the blockchain after an XOR operation. When the watermark is being extracted, the copyright information can be extracted with the XOR operation to obtain the information stored on the blockchain. Experimental results show that the combination of zero watermarking and blockchain proposed in this paper gives full play to the advantages of the two technologies and protects the copyright of data in a lossless fashion. Compared with the traditional zero watermarking algorithms, the proposed zero watermarking algorithm exhibits stronger robustness. Moreover, the proposed data copyright protection framework with a combination of zero watermarking and blockchain can also be applied to other data types, such as images, audio, video, and remote sensing images.
The Extension of IFC For Supporting 3D Cadastre LADM Geometry
Authors: Petronijević Marija , Višnjevac Nenad , Praščević Nataša , Bajat Branislav
Published: May 2021

The growth of densely populated urban areas has caused traditional cadastral registration systems to face many difficulties in representing complex and multilevel property situations on 2D maps. These challenges, combined with the rapid development of 3D technologies, have forced the research and progress of 3D cadastre systems. The aim of this study is to investigate how a Building Information Model (BIM) can be used as a data source for the Land Administration Domain Model (LADM) based 3D cadastre system, and how that process can be improved. The Industry Foundation Classes (IFC) format and the LADM-based model were selected because both are international open standards that have a significant impact in their own domain. The data sample for the 3D cadastre system was extracted from a BIM model. The paper proposes an IFC format extension which makes it possible to define 3D geometry according to the LADM standard. In order to demonstrate this extension, the West 65 residential and business complex, Belgrade, was selected as a case study. The IFC format extension presented here is a step towards data harmonization between BIM in the IFC format and 3D cadastre systems; it should provide more suitable data in the current IFC schema and enable easy data flow between BIM projects and 3D cadastral data.
On the Representativeness of OpenStreetMap for the Evaluation of Country Tourism Competitiveness
Authors: Bustamante Alexander , Sebastia Laura , Onaindia Eva
Published: May 2021

Since 2007, the World Economic Forum (WEF) has issued data on the factors and policies that contribute to the development of tourism and competitiveness across countries worldwide. While WEF compiles the yearly report out of data from governmental and private stakeholders, we seek to analyze the representativeness of the open and collaborative platform OpenStreetMap (OSM) to the international tourism scene. For this study, we selected eight parameters indicative of the tourism development of each country, such as the number of beds or cultural sites, and we extracted the OSM objects representative of these indicators. Then, we performed a statistical and regression analysis of the OSM data to compare and model the data emitted by WEF with data from OSM. Our aim is to analyze the tourist representativeness of the OSM data with respect to official reports to better understand when OSM data can be used to complement the official information and, in some cases, when official information is scarce or non-existent, to assess whether the OSM information can be a substitute. Results show that OSM data provide a fairly accurate picture of official tourism statistics for most variables. We also discuss the reasons why OSM data is not so representative for some variables in some specific countries. All in all, this work represents a step towards the exploitation of open and collaborative data for tourism.
p16-3MR: A Novel Model to Study Cellular Senescence in Cigarette Smoke-Induced Lung Injuries
Authors: Kaur Gagandeep , Sundar Isaac K. , Rahman Irfan
Published: May 2021

Cellular senescence and lung aging are associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). COPD progresses with aging, and chronic smoking is the key susceptibility factor in lung pathological changes concurrent with mitochondrial dysfunction and biological aging. However, these processes involving cigarette smoke (CS)-mediated lung cellular senescence are difficult to distinguish. One of the impediments to studying cellular senescence in relation to age-related lung pathologies is the lack of a suitable in vivo model. In view of this, we provide evidence that supports the suitability of p16-3MR mice to studying cellular senescence in CS-mediated and age-related lung pathologies. p16-3MR mice have a trimodal reporter fused to the promoter of the p16INK4a gene that enables detection, isolation, and selective elimination of senescent cells, thus making them a suitable model to study cellular senescence. To determine their suitability in CS-mediated lung pathologies, we exposed young (12–14 months) and old (17–20 months) p16-3MR mice to 30 day CS exposure and studied the expression of senescent genes (p16, p21, and p53) and SASP-associated markers (MMP9, MMP12, PAI-1, and FN-1) in air- and CS-exposed mouse lungs. Our results showed that this model could detect cellular senescence using luminescence and isolate cells undergoing senescence with the help of tissue fluorescence in CS-exposed young and old mice. Our results from the expression of senescence markers and SASP-associated genes in CS-exposed young and old p16-3MR mice were comparable with increased lung cellular senescence and SASP in COPD. We further showed alteration in the; (i) tissue luminescence and fluorescence, (ii) mRNA and protein expressions of senescent markers and SASP genes, and (iii) SA-β-gal activity in CS-exposed young and old p16-3MR mice as compared to their air controls. Overall, we showed that p16-3MR is a competent model for studying the cellular senescence in CS-induced pathologies. Hence, the p16-3MR reporter mouse model may be used as a novel tool for understanding the pathobiology of cellular senescence and other underlying mechanisms involved in COPD and fibrosis.
Endoplasmic Reticulum Subproteome Analysis Reveals Underlying Defense Mechanisms of Wheat Seedling Leaves under Salt Stress
Authors: Zhang Junwei , Liu Dongmiao , Zhu Dong , Liu Nannan , Yan Yueming
Published: May 2021

Salt stress is the second most important abiotic stress factor in the world, which seriously affects crop growth, development and grain production. In this study, we performed the first integrated physiological and endoplasmic reticulum (ER) proteome analysis of wheat seedling leaves under salt stress using a label-free-based quantitative proteomic approach. Salt stress caused significant decrease in seedling height, root length, relative water content and chlorophyll content of wheat seedling leaves, indicating that wheat seedling growth was significantly inhibited under salt stress. The ER proteome analysis identified 233 ER-localized differentially accumulated proteins (DAPs) in response to salt stress, including 202 upregulated and 31 downregulated proteins. The upregulated proteins were mainly involved in the oxidation-reduction process, transmembrane transport, the carboxylic acid metabolic process, stress response, the arbohydrate metabolic process and proteolysis, while the downregulated proteins mainly participated in the metabolic process, biological regulation and the cellular process. In particular, salt stress induced significant upregulation of protein disulfide isomerase-like proteins and heat shock proteins and significant downregulation of ribosomal protein abundance. Further transcript expression analysis revealed that half of the detected DAP genes showed a consistent pattern with their protein levels under salt stress. A putative metabolic pathway of ER subproteome of wheat seedling leaves in response to salt stress was proposed, which reveals the potential roles of wheat ER proteome in salt stress response and defense.
Ribonucleic Acid Export 1 Is a Kinetochore-Associated Protein That Participates in Chromosome Alignment in Mouse Oocytes
Authors: Chen Fan , Jiao Xiao-Fei , Meng Fei , Wang Yong-Sheng , Ding Zhi-Ming , Miao Yi-Liang , Xiong Jia-Jun , Huo Li-Jun
Published: May 2021

Ribonucleic acid export 1 (Rae1) is an important nucleoporin that participates in mRNA export during the interphase of higher eukaryotes and regulates the mitotic cell cycle. In this study, small RNA interference technology was used to knockdown Rae1, and immunofluorescence, immunoblotting, and chromosome spreading were used to study the role of Rae1 in mouse oocyte meiotic maturation. We found that Rae1 is a crucial regulator of meiotic maturation of mouse oocytes. After the resumption of meiosis (GVBD), Rae1 was concentrated on the kinetochore structure. The knockdown of Rae1 by a specific siRNA inhibited GVBD progression at 2 h, finally leading to a decreased 14 h polar body extrusion (PBE) rate. However, a comparable 14 h PBE rate was found in the control, and the Rae1 knockdown groups that had already undergone GVBD. Furthermore, we found elevated PBE after 9.5 h in the Rae1 knockdown oocytes. Further analysis revealed that Rae1 depletion significantly decreased the protein level of securin. In addition, we detected weakened kinetochore–microtubule (K-MT) attachments, misaligned chromosomes, and an increased incidence of aneuploidy in the Rae1 knockdown oocytes. Collectively, we propose that Rae1 modulates securin protein levels, which contribute to chromosome alignment, K-MT attachments, and aneuploidy in meiosis.
Therapeutic Effect and Mechanisms of Essential Oils in Mood Disorders: Interaction between the Nervous and Respiratory Systems
Authors: Fung Timothy K. H. , Lau Benson W. M. , Ngai Shirley P. C. , Tsang Hector W. H.
Published: May 2021

Essential oils (EOs) are extracted from plants and contain active components with therapeutic effects. Evidence shows that various types of EOs have a wide range of health benefits. In our previous studies, the potential of lavender EO for prevention and even treatment of depression and anxiety symptoms was demonstrated. The favourable outcomes may be due to multiple mechanisms, including the regulation of monoamine level, the induction of neurotrophic factor expression, the regulation of the endocrine system and the promotion of neurogenesis. The molecules of EOs may reach the brain and exert an effect through two distinctive pathways, namely, the olfactory system and the respiratory system. After inhalation, the molecules of the EOs would either act directly on the olfactory mucosa or pass into the respiratory tract. These two delivery pathways suggest different underlying mechanisms of action. Different sets of responses would be triggered, such as increased neurogenesis, regulation of hormonal levels, activation of different brain regions, and alteration in blood biochemistry, which would ultimately affect both mood and emotion. In this review, we will discuss the clinical effects of EOs on mood regulation and emotional disturbances as well as the cellular and molecular mechanisms of action. Emphasis will be put on the interaction between the respiratory and central nervous system and the involved potential mechanisms. Further evidence is needed to support the use of EOs in the clinical treatment of mood disturbances. Exploration of the underlying mechanisms may provide insight into the future therapeutic use of EO components treatment of psychiatric and physical symptoms.
Potential of Silver Nanoparticles in Overcoming the Intrinsic Resistance of Pseudomonas aeruginosa to Secondary Metabolites from Carnivorous Plants
Authors: Krychowiak-Maśnicka Marta , Krauze-Baranowska Mirosława , Godlewska Sylwia , Kaczyński Zbigniew , Bielicka-Giełdoń Aleksandra , Grzegorczyk Natalia , Narajczyk Magdalena , Frackowiak Joanna E. , Krolicka Aleksandra
Published: May 2021

Carnivorous plants are exemplary natural sources of secondary metabolites with biological activity. However, the therapeutic antimicrobial potential of these compounds is limited due to intrinsic resistance of selected bacterial pathogens, among which Pseudomonas aeruginosa represents an extreme example. The objective of the study was to overcome the intrinsic resistance of P. aeruginosa by combining silver nanoparticles (AgNPs) with secondary metabolites from selected carnivorous plant species. We employed the broth microdilution method, the checkerboard titration technique and comprehensive phytochemical analyses to define interactions between nanoparticles and active compounds from carnivorous plants. It has been confirmed that P. aeruginosa is resistant to a broad range of secondary metabolites from carnivorous plants, i.e., naphthoquinones, flavonoids, phenolic acids (MBC = 512 µg mL−1) and only weakly sensitive to their mixtures, i.e., extracts and extracts’ fractions. However, it was shown that the antimicrobial activity of extracts and fractions with a significant level of naphthoquinone (plumbagin) was significantly enhanced by AgNPs. Our studies clearly demonstrated a crucial role of naphthoquinones in AgNPs and extract interaction, as well as depicted the potential of AgNPs to restore the bactericidal activity of naphthoquinones towards P. aeruginosa. Our findings indicate the significant potential of nanoparticles to modulate the activity of selected secondary metabolites and revisit their antimicrobial potential towards human pathogenic bacteria.
Exercise-Induced Plasticity in Signaling Pathways Involved in Motor Recovery after Spinal Cord Injury
Authors: Bilchak Jadwiga N. , Caron Guillaume , Côté Marie-Pascale
Published: May 2021

Spinal cord injury (SCI) leads to numerous chronic and debilitating functional deficits that greatly affect quality of life. While many pharmacological interventions have been explored, the current unsurpassed therapy for most SCI sequalae is exercise. Exercise has an expansive influence on peripheral health and function, and by activating the relevant neural pathways, exercise also ameliorates numerous disorders of the central nervous system (CNS). While the exact mechanisms by which this occurs are still being delineated, major strides have been made in the past decade to understand the molecular underpinnings of this essential treatment. Exercise rapidly and prominently affects dendritic sprouting, synaptic connections, neurotransmitter production and regulation, and ionic homeostasis, with recent literature implicating an exercise-induced increase in neurotrophins as the cornerstone that binds many of these effects together. The field encompasses vast complexity, and as the data accumulate, disentangling these molecular pathways and how they interact will facilitate the optimization of intervention strategies and improve quality of life for individuals affected by SCI. This review describes the known molecular effects of exercise and how they alter the CNS to pacify the injury environment, increase neuronal survival and regeneration, restore normal neural excitability, create new functional circuits, and ultimately improve motor function following SCI.
MicroRNAs in Metastasis and the Tumour Microenvironment
Authors: Solé Carla , Lawrie Charles Henderson
Published: May 2021

Metastasis is the process whereby cancer cells migrate from the primary tumour site to colonise the surrounding or distant tissue or organ. Metastasis is the primary cause of cancer-related mortality and approximately half of all cancer patients present at diagnosis with some form of metastasis. Consequently, there is a clear need to better understand metastasis in order to develop new tools to combat this process. MicroRNAs (miRNAs) regulate gene expression and play an important role in cancer development and progression including in the metastatic process. Particularly important are the roles that miRNAs play in the interaction between tumour cells and non-tumoral cells of the tumour microenvironment (TME), a process mediated largely by circulating miRNAs contained primarily in extracellular vesicles (EVs). In this review, we outline the accumulating evidence for the importance of miRNAs in the communication between tumour cells and the cells of the TME in the context of the pre-metastatic and metastatic niche.
Plastid Anionic Lipids Are Essential for the Development of Both Photosynthetic and Non-Photosynthetic Organs in Arabidopsis thaliana
Authors: Yoshihara Akiko , Nagata Noriko , Wada Hajime , Kobayashi Koichi
Published: May 2021

The lipid bilayer matrix of the thylakoid membrane of cyanobacteria and chloroplasts of plants and algae is mainly composed of uncharged galactolipids, but also contains anionic lipids sulfoquinovosyldiacylglycerol (SQDG) and phosphatidylglycerol (PG) as major constituents. The necessity of PG for photosynthesis is evident in all photosynthetic organisms examined to date, whereas the requirement of SQDG varies with species. In plants, although PG and SQDG are also found in non-photosynthetic plastids, their importance for the growth and functions of non-photosynthetic organs remains unclear. In addition, plants synthesize another anionic lipid glucuronosyldiacylglycerol (GlcADG) during phosphorus starvation, but its role in plant cells is not elucidated yet. To understand the functional relationships among PG, SQDG, and GlcADG, we characterized several Arabidopsis thaliana mutants defective in biosynthesis of these lipids. The mutants completely lacking both PG and SQDG biosynthesis in plastids showed developmental defects of roots, hypocotyls, and embryos in addition to leaves, which suggests that these lipids are pleiotropically required for the development of both photosynthetic and non-photosynthetic organs. Furthermore, our analysis revealed that SQDG, but not GlcADG, is essential for complementing the role of PG, particularly in photosynthesis under PG-deficient conditions such as phosphorus starvation.
How an Infection of Sheep Revealed Prion Mechanisms in Alzheimer’s Disease and Other Neurodegenerative Disorders
Authors: Carlson George A. , Prusiner Stanley B.
Published: May 2021

Although it is not yet universally accepted that all neurodegenerative diseases (NDs) are prion disorders, there is little disagreement that Alzheimer’s disease (AD), Parkinson’s disease, frontotemporal dementia (FTD), and other NDs are a consequence of protein misfolding, aggregation, and spread. This widely accepted perspective arose from the prion hypothesis, which resulted from investigations on scrapie, a common transmissible disease of sheep and goats. The prion hypothesis argued that the causative infectious agent of scrapie was a novel proteinaceous pathogen devoid of functional nucleic acids and distinct from viruses, viroids, and bacteria. At the time, it seemed impossible that an infectious agent like the one causing scrapie could replicate and exist as diverse microbiological strains without nucleic acids. However, aggregates of a misfolded host-encoded protein, designated the prion protein (PrP), were shown to be the cause of scrapie as well as Creutzfeldt–Jakob disease (CJD) and Gerstmann–Sträussler–Scheinker syndrome (GSS), which are similar NDs in humans. This review discusses historical research on diseases caused by PrP misfolding, emphasizing principles of pathogenesis that were later found to be core features of other NDs. For example, the discovery that familial prion diseases can be caused by mutations in PrP was important for understanding prion replication and disease susceptibility not only for rare PrP diseases but also for far more common NDs involving other proteins. We compare diseases caused by misfolding and aggregation of APP-derived Aβ peptides, tau, and α-synuclein with PrP prion disorders and argue for the classification of NDs caused by misfolding of these proteins as prion diseases. Deciphering the molecular pathogenesis of NDs as prion-mediated has provided new approaches for finding therapies for these intractable, invariably fatal disorders and has revolutionized the field.
Characterization of Extracellular Vesicle Cargo in Sjögren’s Syndrome through a SWATH-MS Proteomics Approach
Authors: Finamore Francesco , Cecchettini Antonella , Ceccherini Elisa , Signore Giovanni , Ferro Francesco , Rocchiccioli Silvia , Baldini Chiara
Published: May 2021

Primary Sjögren’s syndrome (pSS) is a complex heterogeneous disease characterized by a wide spectrum of glandular and extra-glandular manifestations. In this pilot study, a SWATH-MS approach was used to monitor extracellular vesicles-enriched saliva (EVs) sub-proteome in pSS patients, to compare it with whole saliva (WS) proteome, and assess differential expressed proteins between pSS and healthy control EVs samples. Comparison between EVs and WS led to the characterization of compartment-specific proteins with a moderate degree of overlap. A total of 290 proteins were identified and quantified in EVs from healthy and pSS patients. Among those, 121 proteins were found to be differentially expressed in pSS, 82% were found to be upregulated, and 18% downregulated in pSS samples. The most representative functional pathways associated to the protein networks were related to immune-innate response, including several members of S100 protein family, annexin A2, resistin, serpin peptidase inhibitors, azurocidin, and CD14 monocyte differentiation antigen. Our results highlight the usefulness of EVs for the discovery of novel salivary-omic biomarkers and open novel perspectives in pSS for the identification of proteins of clinical relevance that could be used not only for the disease diagnosis but also to improve patients’ stratification and treatment-monitoring. Data are available via ProteomeXchange with identifier PXD025649.
Identification of miRNAs and Their Targets Involved in Flower and Fruit Development across Domesticated and Wild Capsicum Species
Authors: Lopez-Ortiz Carlos , Peña-Garcia Yadira , Bhandari Menuka , Abburi Venkata Lakshmi , Natarajan Purushothaman , Stommel John , Nimmakayala Padma , Reddy Umesh K.
Published: May 2021

MicroRNAs (miRNAs) are regulators of the post-transcription stage of gene activity documented to play central roles in flower and fruit development in model plant species. However, little is known about their roles and differences in domesticated and wild Capsicum species. In this study, we used high-throughput sequencing to analyze the miRNA content at three developmental stages (flower, small fruit, and middle fruit) from two cultivated (C. baccatum and C. annuum) and two wild (C. chacoense and C. eximium) pepper species. This analysis revealed 22 known and 27 novel miRNAs differentially expressed across species and tissues. A number of stage- and species-specific miRNAs were identified, and Gene Ontology terms were assigned to 138 genes targeted by the miRNAs. Most Gene Ontology terms were for the categories “genetic information processing”, “signaling and cellular processes”, “amino acid metabolism”, and “carbohydrate metabolism”. Enriched KEGG analysis revealed the pathways amino acids, sugar and nucleotide metabolism, starch and sucrose metabolism, and fructose-mannose metabolism among the principal ones regulated by miRNAs during pepper fruit ripening. We predicted miRNA–target gene interactions regulating flowering time and fruit development, including miR156/157 with SPL genes, miR159 with GaMYB proteins, miR160 with ARF genes, miR172 with AP2-like transcription factors, and miR408 with CLAVATA1 gene across the different Capsicum species. In addition, novel miRNAs play an important role in regulating interactions potentially controlling plant pathogen defense and fruit quality via fructokinase, alpha-L-arabinofuranosidase, and aromatic and neutral amino acid transporter. Overall, the small RNA-sequencing results from this study represent valuable information that provides a solid foundation for uncovering the miRNA-mediated mechanisms of flower and fruit development between domesticated and wild Capsicum species.
The Effect of Polybutylcyanoacrylate Nanoparticles as a Protos Delivery Vehicle on Dental Bone Formation
Authors: Chang Li-Ching , Chung Chiu-Yen , Chiu Chun-Hui , Lin Martin Hsiu-Chu , Yang Jen-Tsung
Published: May 2021

Background: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier “polybutylcyanoacrylate” (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. Methodology: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. Results: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of −1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. Conclusion: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.
Single-Walled Carbon Nanotubes Modify Leaf Micromorphology, Chloroplast Ultrastructure and Photosynthetic Activity of Pea Plants
Authors: Velikova Violeta , Petrova Nia , Kovács László , Petrova Asya , Koleva Dimitrina , Tsonev Tsonko , Taneva Stefka , Petrov Petar , Krumova Sashka
Published: May 2021

Single-walled carbon nanotubes (SWCNTs) emerge as promising novel carbon-based nanoparticles for use in biomedicine, pharmacology and precision agriculture. They were shown to penetrate cell walls and membranes and to physically interact and exchange electrons with photosynthetic complexes in vitro. Here, for the first time, we studied the concentration-dependent effect of foliar application of copolymer-grafted SWCNTs on the structural and functional characteristics of intact pea plants. The lowest used concentration of 10 mg L−1 did not cause any harmful effects on the studied leaf characteristics, while abundant epicuticular wax generation on both leaf surfaces was observed after 300 mg L−1 treatment. Swelling of both the granal and the stromal regions of thylakoid membranes was detected after application of 100 mg L−1 and was most pronounced after 300 mg L−1. Higher SWCNT doses lead to impaired photosynthesis in terms of lower proton motive force generation, slower generation of non-photochemical quenching and reduced zeaxanthin content; however, the photosystem II function was largely preserved. Our results clearly indicate that SWCNTs affect the photosynthetic apparatus in a concentration-dependent manner. Low doses (10 mg L−1) of SWCNTs appear to be a safe suitable object for future development of nanocarriers for substances that are beneficial for plant growth.
No Direct Postconditioning Effect of Poloxamer 188 on Mitochondrial Function after Ischemia Reperfusion Injury in Rat Isolated Hearts
Authors: Eskaf Josephine , Cleveland William J. , Riess Matthias L.
Published: May 2021

Myocardial infarction is a leading cause for morbidity and mortality worldwide. The only viable treatment for the ischemic insult is timely reperfusion, which further exacerbates myocardial injury. Maintaining mitochondrial function is crucial in preserving cardiomyocyte function in ischemia reperfusion (IR) injury. Poloxamer (P) 188 has been shown to improve cardiac IR injury by improving cellular and mitochondrial function. The aim of this study was to show if P188 postconditioning has direct protective effects on mitochondrial function in the heart. Langendorff prepared rat hearts were subjected to IR injury ex-vivo and reperfused for 10 min with 1 mM P188 vs. vehicle. Cardiac mitochondria were isolated with 1 mM P188 vs. 1 mM polyethylene glycol (PEG) vs. vehicle by differential centrifugation. Mitochondrial function was assessed by adenosine triphosphate synthesis, oxygen consumption, and calcium retention capacity. Mitochondrial function decreased significantly after ischemia and showed mild improvement with reperfusion. P188 did not improve mitochondrial function in the ex-vivo heart, and neither further P188 nor PEG induced direct mitochondrial protection after IR injury in this model.
Salinity Stress Alters the Secondary Metabolic Profile of M. sativa, M. arborea and Their Hybrid (Alborea)
Authors: Sarri Efi , Termentzi Aikaterini , Abraham Eleni M. , Papadopoulos George K. , Baira Eirini , Machera Kyriaki , Loukas Vassilis , Komaitis Fotios , Tani Eleni
Published: May 2021

Increased soil salinity, and therefore accumulation of ions, is one of the major abiotic stresses of cultivated plants that negatively affect their growth and yield. Among Medicago species, only Medicago truncatula, which is a model plant, has been extensively studied, while research regarding salinity responses of two important forage legumes of Medicago sativa (M. sativa) and Medicago arborea (M. arborea) has been limited. In the present work, differences between M. arborea, M. sativa and their hybrid Alborea were studied regarding growth parameters and metabolomic responses. The entries were subjected to three different treatments: (1) no NaCl application (control plants), (2) continuous application of 100 mM NaCl (acute stress) and (3) gradual application of NaCl at concentrations of 50-75-150 mM by increasing NaCl concentration every 10 days. According to the results, M. arborea maintained steady growth in all three treatments and appeared to be more resistant to salinity. Furthermore, results clearly demonstrated that M. arborea presented a different metabolic profile from that of M. sativa and their hybrid. In general, it was found that under acute and gradual stress, M. sativa overexpressed saponins in the shoots while M. arborea overexpressed saponins in the roots, which is the part of the plant where most of the saponins are produced and overexpressed. Alborea did not perform well, as more metabolites were downregulated than upregulated when subjected to salinity stress. Finally, saponins and hydroxycinnamic acids were key players of increased salinity tolerance.
Age-Dependent Control of Collagen-Dependent Platelet Responses by Thrombospondin-1—Comparative Analysis of Platelets from Neonates, Children, Adolescents, and Adults
Authors: Herken Katrin , Glauner Martin , Robert Stefanie C. , Maas Matthias , Zippel Sonja , Nowak-Göttl Ulrike , Zieger Barbara , Lahav Judith , Fender Anke C. , Jurk Kerstin , Kehrel Beate E.
Published: May 2021

Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood. This critical issue remains challenging for the establishment of age-specific reference ranges. In this study, we evaluated platelet reactivity of five pediatric age categories, ranging from healthy full-term neonates up to adolescents (11–18 years) in comparison to healthy adults (>18 years) by flow cytometry. We confirmed that platelet hypo-reactivity detected by fibrinogen binding, P-selectin, and CD63 surface expression was most pronounced in neonates compared to other pediatric age groups. However, maturation of platelet responsiveness varied with age, agonist, and activation marker. In contrast to TRAP and ADP, collagen-induced platelet activation was nearly absent in neonates. Granule secretion markedly remained impaired at least up to 10 years of age compared to adults. We show for the first time that neonatal platelets are deficient in thrombospondin-1, and exogenous platelet-derived thrombospondin-1 allows platelet responsiveness to collagen. Platelets from all pediatric age groups normally responded to the C-terminal thrombospondin-1 peptide RFYVVMWK. Thus, thrombospondin-1 deficiency of neonatal platelets might contribute to the relatively impaired response to collagen, and platelet-derived thrombospondin-1 may control distinct collagen-induced platelet responses.
MSCs Become Collagen-Type I Producing Cells with Different Phenotype in Allogeneic and Syngeneic Bone Marrow Transplantation
Authors: Rusch Robert Maximilian , Ogawa Yoko , Sato Shinri , Morikawa Satoru , Inagaki Emi , Shimizu Eisuke , Tsubota Kazuo , Shimmura Shigeto
Published: May 2021

Mesenchymal stem cells (MSCs) have been widely used in therapeutic applications for many decades. However, more and more evidence suggests that factors such as the site of origin and pre-implantation treatment have a crucial impact on the result. This study investigates the role of freshly isolated MSCs in the lacrimal gland after allogeneic transplantation. For this purpose, MSCs from transgenic GFP mice were isolated and transplanted into allogeneic and syngeneic recipients. While the syngeneic MSCs maintained a spherical shape, allogeneic MSCs engrafted into the tissue as spindle-shaped cells in the interstitial stroma. Furthermore, the MSCs produced collagen type I in more than 85% to 95% of the detected GFP+ MSCs in the recipients of both models, supposedly contributing to pathogenic fibrosis in allogeneic recipients compared to syngeneic models. These findings indicate that allogeneic MSCs act completely differently from syngeneic MSCs, highlighting the importance of understanding the exact mechanisms behind MSCs.
The Influence of an Adrenergic Antagonist Guanethidine on the Distribution Pattern and Chemical Coding of Caudal Mesenteric Ganglion Perikarya and Their Axons Supplying the Porcine Bladder
Authors: Bossowska Agnieszka , Lepiarczyk Ewa , Janikiewicz Paweł , Wasilewska Barbara , Mazur Urszula , Markiewicz Włodzimierz , Majewski Mariusz
Published: May 2021

This study was aimed at disclosing the influence of intravesically instilled guanethidine (GUA) on the distribution, relative frequency and chemical coding of both the urinary bladder intramural sympathetic nerve fibers and their parent cell bodies in the caudal mesenteric ganglion (CaMG) in juvenile female pigs. GUA instillation led to a profound decrease in the number of perivascular nerve terminals. Furthermore, the chemical profile of the perivascular innervation within the treated bladder also distinctly changed, as most of axons became somatostatin-immunoreactive (SOM-IR), while in the control animals they were found to be neuropeptide Y (NPY)-positive. Intravesical treatment with GUA led not only to a significant decrease in the number of bladder-projecting tyrosine hydroxylase (TH) CaMG somata (94.3 ± 1.8% vs. 73.3 ± 1.4%; control vs. GUA-treated pigs), but simultaneously resulted in the rearrangement of their co-transmitters repertoire, causing a distinct decrease in the number of TH+/NPY+ (89.6 ± 0.7% vs. 27.8 ± 0.9%) cell bodies and an increase in the number of SOM-(3.6 ± 0.4% vs. 68.7 ± 1.9%), calbindin-(CB; 2.06 ± 0.2% vs. 9.1 ± 1.2%) or galanin-containing (GAL; 1.6 ± 0.3% vs. 28.2 ± 1.3%) somata. The present study provides evidence that GUA significantly modifies the sympathetic innervation of the porcine urinary bladder wall, and thus may be considered a potential tool for studying the plasticity of this subdivision of the bladder innervation.
Magnetic Particles with Polymeric Shells Bearing Cholesterol Moieties Sensitize Breast Cancer Cells to Low Doses of Doxorubicin
Authors: Markiewicz Karolina H. , Niemirowicz-Laskowska Katarzyna , Szymczuk Dawid , Makarewicz Kacper , Misztalewska-Turkowicz Iwona , Wielgat Przemysław , Majcher-Fitas Anna M. , Milewska Sylwia , Car Halina , Wilczewska Agnieszka Z.
Published: May 2021

One of the promising strategies for improvement of cancer treatment is application of a combination therapy. The aim of this study was to investigate the anticancer activity of nanoformulations containing doxorubicin and iron oxide particles covered with polymeric shells bearing cholesterol moieties. It was postulated that due to high affinity to cell membranes, particles comprising poly(cholesteryl acrylate) can sensitize cancer cells to doxorubicin chemotherapy. The performed analyses revealed that the developed systems are effective against the human breast cancer cell lines MCF-7 and MDA-MB-231 even at low doses of the active compound applied (0.5 µM). Additionally, high compatibility and lack of toxicity of the tested materials against human red blood cells, immune (monocytic THP-1) cells, and cardiomyocyte H9C2(2-1) cells was demonstrated. Synergistic effects observed upon administration of doxorubicin with polymer–iron oxide hybrids comprising poly(cholesteryl acrylate) may provide an opportunity to limit toxicity of the drug and to improve its therapeutic efficiency at the same time.
Hypergravity Load Modulates Acetaminophen Nephrotoxicity via Endoplasmic Reticulum Stress in Association with Hepatic microRNA-122 Expression
Authors: Wu Hong-Min , Lee Sang-Gil , Oh Choong-Sik , Kim Sang-Geon
Published: May 2021

Hypergravity conditions may subject the kidney to intrinsic stress and lead to hemodynamic kidney dysfunction. However, the mechanisms underlying this phenomenon remain unclear. Accumulation of unfolded proteins in the endoplasmic reticulum (i.e., ER stress) is often observed in kidney diseases. Therefore, this study investigated whether hypergravity stress alters acetaminophen-induced renal toxicity in vivo, as well as the molecular mechanisms involved in this process. C57BL/6 mice were submitted to one or three loads of +9 Gx hypergravity for 1 h with or without acetaminophen (APAP) treatment. The protein levels of cell survival markers, including pAKT and pCREB, were decreased in the kidney after acetaminophen treatment with a single hypergravity load. Additionally, the combined treatment increased kidney injury markers, serum creatinine, and Bax, Bcl2, and Kim-1 transcript levels and enhanced ER stress-related markers were further. Moreover, multiple hypergravity loads enabled mice to overcome kidney injury, as indicated by decreases in serum creatinine content and ER stress marker levels, along with increased cell viability indices. Similarly, multiple hypergravity loads plus APAP elevated miR-122 levels in the kidney, which likely originated from the liver, as the levels of primary miR-122 increased only in the liver and not the kidney. Importantly, this phenomenon may contribute to overcoming hypergravity-induced kidney injury. Taken together, our results demonstrate that APAP-exposed mice submitted to a single load of hypergravity exhibited more pronounced kidney dysfunction due to increased ER stress, which may be overcome by repetitive hypergravity loads presumably due to increased production of miR-122 in the liver. Thus, our study provides novel insights into the mechanisms by which hypergravity stress plus APAP medication induce kidney injury, which may be overcome by repeated hypergravity exposure.