bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetics of Skeletal Muscle-Associated Genes in the ASB, LRRC, TMEM, and OSBPL Gene Families
Authors: Ehrlich Kenneth C. , Lacey Michelle , Ehrlich Melanie
Published: January 2020

Much remains to be discovered about the intersection of tissue-specific transcription control and the epigenetics of skeletal muscle (SkM), a very complex and dynamic organ. From four gene families, Leucine-Rich Repeat Containing (LRRC), Oxysterol Binding Protein Like (OSBPL), Ankyrin Repeat and Socs Box (ASB), and Transmembrane Protein (TMEM), we chose 21 genes that are preferentially expressed in human SkM relative to 52 other tissue types and analyzed relationships between their tissue-specific epigenetics and expression. We also compared their genetics, proteomics, and descriptions in the literature. For this study, we identified genes with little or no previous descriptions of SkM functionality (ASB4, ASB8, ASB10, ASB12, ASB16, LRRC14B, LRRC20, LRRC30, TMEM52, TMEM233, OSBPL6/ORP6, and OSBPL11/ORP11) and included genes whose SkM functions had been previously addressed (ASB2, ASB5, ASB11, ASB15, LRRC2, LRRC38, LRRC39, TMEM38A/TRIC-A, and TMEM38B/TRIC-B). Some of these genes have associations with SkM or heart disease, cancer, bone disease, or other diseases. Among the transcription-related SkM epigenetic features that we identified were: super-enhancers, promoter DNA hypomethylation, lengthening of constitutive low-methylated promoter regions, and SkM-related enhancers for one gene embedded in a neighboring gene (e.g., ASB8-PFKM, LRRC39-DBT, and LRRC14B-PLEKHG4B gene-pairs). In addition, highly or lowly co-expressed long non-coding RNA (lncRNA) genes probably regulate several of these genes. Our findings give insights into tissue-specific epigenetic patterns and functionality of related genes in a gene family and can elucidate normal and disease-related regulation of gene expression in SkM.
Geochemical Referencing of Natural Forest Contamination in Poland
Authors: Rutkowski Paweł , Diatta Jean , Konatowska Monika , Andrzejewska Agnieszka , Tyburski Łukasz , Przybylski Paweł
Published: January 2020

Various studies have established possible threats posed due to pollution using ecological risk indices, but most have focused strictly on anthropogenic areas, so the data from these studies are less comparable with those obtained from natural forest sites, which was the focus of this current study. The main reason for this focus could be attributed to the commonly agreed reference provided by natural forest parks, which are assumed to be uncontaminated. The aim of this research was to determine if the Kampinoski National Park (Poland) could be considered a geochemical referencing ecosystem for Pb, Cd, and Ni levels. The specific purpose was to conduct a soil-background-based evaluation of metal contamination with a focus on geochemical indices as normative tools for assessing similar forest ecosystems at local and international levels. The toxicity response factors indicated some specific metal features that seemed highly magnified for Cd compared with Pb and Ni. The use of geochemical indices when assessing the contamination status of various ecosystems, either natural or strongly anthropogenic, is recommended to enable worldwide comparison, rather than only assessing metal contents. This approach considers the background metal concentrations for local on-site targets as well as pre-industrial reference levels for international referencing.
The Complete Plastid Genome of Rhododendron pulchrum and Comparative Genetic Analysis of Ericaceae Species
Authors: Shen Jianshuang , Li Xueqin , Zhu Xiangtao , Huang Xiaoling , Jin Songheng
Published: January 2020

Background and Objectives: Rhododendron pulchrum Sweet (R. pulchrum) belongs to the genus Rhododendron (Ericaceae), a valuable horticultural and medicinal plant species widely used in Western Europe and the US. Despite its importance, this is the first member to have its cpGenome sequenced. Materials and Methods: In this study, the complete cp genome of R. pulchrum was sequenced with NGS Illumina HiSeq2500, analyzed, and compared to eight species in the Ericaceae family. Results: Our study reveals that the cp genome of R. pulchrum is 136,249 bp in length, with an overall GC content of 35.98% and no inverted repeat regions. The R. pulchrum chloroplast genome encodes 73 genes, including 42 protein-coding genes, 29 tRNA genes, and two rRNA genes. The synonymous (Ks) and nonsynonymous (Ka) substitution rates were estimated and the Ka/Ks ratio of R. pulchrum plastid genes were categorized; the results indicated that most of the genes have undergone purifying selection. A total of 382 forward and 259 inverted long repeats, as well as 221 simple-sequence repeat loci (SSR) were detected in the R. pulchrum cp genome. Comparison between different Ericaceae cp genomes revealed significant differences in genome size, structure, and GC content. Conclusions: The phylogenetic relationships among eight Ericaceae species suggested that R. pulchrum is closely related to Vaccinium oldhamii Miq. and Vaccinium macrocarpon Aiton. This study provides a theoretical basis for species identification and future biological research of Rhododendron resources.
Reasons for the Survival of Tropical Forest Fragments in Xishuangbanna, Southwest China
Authors: Zhang Jia-Qi , Mammides Christos , Corlett Richard T.
Published: January 2020

Research Highlights: The reasons for persistence of forest fragments in human-dominated landscapes have rarely been examined, despite their importance in biodiversity and ecosystem services. We determined these reasons for forest fragments on collective land in Xishuangbanna prefecture, southwest China. Background and Objectives: Reconciling economic development with biodiversity conservation has been a major challenge in China’s small tropical land area, where local realities have often been in conflict with national policies. In Xishuangbanna, much of China’s most biodiverse forest area has been replaced by cash crops in recent decades, but numerous small forest fragments remain on collective land. Our objective was to find out why these fragments have not been cleared. Methods: We used a combination of semi-structured interviews with 600 households in 69 villages representing nine ethnic groups and information from key informants. Results: Overall, 64% of individual households retained forest fragments on the land allocated to them, and 93% of villages retained larger areas managed as a collective forest. Most (71%) interviewees said that fragments on their own land were on sites of low agricultural value and were retained as fuelwood sources. They were also often (33%) underplanted with crops and supplied other forest products. All interviewees attributed the retention of collective forests to policy restrictions on clearance, with most (96%) mentioning cultural and religious uses and many recognizing environmental benefits. Most were also used as sources of wild edible plants (61%) and other forest products. Many said these collective forests had shrunk over time, particularly in areas suitable for profitable cultivation. Conclusions: China’s new ecological redline policy will protect most larger patches of forest in Xishuangbanna, but the smaller fragments on land allocated to individual households are also of conservation value, particularly in areas with no other forest. Some form of compensation scheme is needed to encourage their continued retention.
The Pharmacological Effects and Health Benefits of Platycodon grandiflorus—A Medicine Food Homology Species
Authors: Ji Ming-Yue , Bo Agula , Yang Min , Xu Jin-Fan , Jiang Lin-Lin , Zhou Bao-Chang , Li Min-Hui
Published: January 2020

Platycodon grandiflorus is a widely used edible, traditional Chinese medicinal herb. It is rich in saponins, flavonoids, phenolic acids, and other compounds. It contains a large number of fatty acids such as linoleic acid (up to 63.24%), a variety of amino acids, vitamins, and multiple essential trace elements. P. grandiflorus has several biological applications, such as in hypotension, lipid reduction, atherosclerosis, inflammation, relieving cough and phlegm, promoting cholic acid secretion, and as an antioxidant. Further, P. grandiflorus is often used in the development of cold mixed vegetables, canned vegetables, preserved fruit, salted vegetables, and cosmetics in northeast China, South Korea, Japan, and Korea. In this paper, the active chemical components and the health benefits of P. grandiflorus have been reviewed, providing new ideas for the further development of nutraceutical products to prevent and manage chronic diseases.
Distribution of Medically Relevant Antibiotic Resistance Genes and Mobile Genetic Elements in Soils of Temperate Forests and Grasslands Varying in Land Use
Authors: Willms Inka M. , Yuan Jingyue , Penone Caterina , Goldmann Kezia , Vogt Juliane , Wubet Tesfaye , Schöning Ingo , Schrumpf Marion , Buscot François , Nacke Heiko
Published: January 2020

Antibiotic-resistant pathogens claim the lives of thousands of people each year and are currently considered as one of the most serious threats to public health. Apart from clinical environments, soil ecosystems also represent a major source of antibiotic resistance determinants, which can potentially disseminate across distinct microbial habitats and be acquired by human pathogens via horizontal gene transfer. Therefore, it is of global importance to retrieve comprehensive information on environmental factors, contributing to an accumulation of antibiotic resistance genes and mobile genetic elements in these ecosystems. Here, medically relevant antibiotic resistance genes, class 1 integrons and IncP-1 plasmids were quantified via real time quantitative PCR in soils derived from temperate grasslands and forests, varying in land use over a large spatial scale. The generated dataset allowed an analysis, decoupled from regional influences, and enabled the identification of land use practices and soil characteristics elevating the abundance of antibiotic resistance genes and mobile genetic elements. In grassland soils, the abundance of the macrolide resistance gene mefA as well as the sulfonamide resistance gene sul2 was positively correlated with organic fertilization and the abundance of aac(6′)-lb, conferring resistance to different aminoglycosides, increased with mowing frequency. With respect to forest soils, the beta-lactam resistance gene blaIMP-12 was significantly correlated with fungal diversity which might be due to the fact that different fungal species can produce beta-lactams. Furthermore, except blaIMP-5 and blaIMP-12, the analyzed antibiotic resistance genes as well as IncP-1 plasmids and class-1 integrons were detected less frequently in forest soils than in soils derived from grassland that are commonly in closer proximity to human activities.
Genetic and Genomic Tools in Sunflower Breeding for Broomrape Resistance
Authors: Cvejić Sandra , Radanović Aleksandra , Dedić Boško , Jocković Milan , Jocić Siniša , Miladinović Dragana
Published: January 2020

Broomrape is a root parasitic plant causing yield losses in sunflower production. Since sunflower is an important oil crop, the development of broomrape-resistant hybrids is the prime breeding objective. Using conventional plant breeding methods, breeders have identified resistant genes and developed a number of hybrids resistant to broomrape, adapted to different growing regions worldwide. However, the spread of broomrape into new countries and the development of new and more virulent races have been noted intensively. Recent advances in sunflower genomics provide additional tools for plant breeders to improve resistance and find durable solutions for broomrape spread and virulence. This review describes the structure and distribution of new, virulent physiological broomrape races, sources of resistance for introduction into susceptible cultivated sunflower, qualitative and quantitative resistance genes along with gene pyramiding and marker assisted selection (MAS) strategies applied in the process of increasing sunflower resistance. In addition, it presents an overview of underutilized biotechnological tools, such as phenotyping, -omics, and genome editing techniques, which need to be introduced in the study of sunflower resistance to broomrape in order to achieve durable resistance.
Understanding Historical Demographic Processes to Inform Contemporary Conservation of an Arid Zone Specialist: The Yellow-Footed Rock-Wallaby
Authors: Potter Sally , Neaves Linda E. , Lethbridge Mark , Eldridge Mark D. B.
Published: January 2020

Little genetic research has been undertaken on mammals across the vast expanse of the arid biome in Australia, despite continuing species decline and need for conservation management. Here, we evaluate the contemporary and historical genetic connectivity of the yellow-footed rock-wallaby, Petrogale xanthopus xanthopus, a threatened macropodid which inhabits rocky outcrops across the disconnected mountain range systems of the southern arid biome. We use 17 microsatellite loci together with mitochondrial control region data to determine the genetic diversity of populations and the evolutionary processes shaping contemporary population dynamics on which to base conservation recommendations. Our results indicate the highly fragmented populations have reduced diversity and limited contemporary gene flow, with most populations having been through population bottlenecks. Despite limited contemporary gene flow, the phylogeographic relationships of the mitochondrial control region indicate a lack of structure and suggests greater historical connectivity. This is an emerging outcome for mammals across this arid region. On the basis of our results, we recommend augmentation of populations of P. x. xanthopus, mixing populations from disjunct mountain range systems to reduce the chance of continued diversity loss and inbreeding depression, and therefore maximize the potential for populations to adapt and survive into the future.
A Gamification-Based Intervention Program that Encourages Physical Activity Improves Cardiorespiratory Fitness of College Students: ‘The Matrix rEFvolution Program’
Authors: Mora-Gonzalez Jose , Pérez-López Isaac J. , Esteban-Cornejo Irene , Delgado-Fernández Manuel
Published: January 2020

The aim of the present study was to examine the effects of a gamification-based program on cardiorespiratory fitness (CRF) levels of college students. We divided 112 college students into an intervention group (IG) and a control group (CG). IG college students followed a 15-week gamification-based program, whereas CG followed traditional lectures. CRF was assessed using the 20-meter shuttle-run test. CRF significantly improved after the program in the IG compared to CG (d ≤ 0.94, p < 0.001). Only participants of IG had significant CRF improvements (d ≤ 0.87, p < 0.001) between pre- and post-assessments. In the IG, from the students who attended 100% of lectures, 87.8% met physical activity recommendations for 100% of weeks, whereas from those who attended <100%, only 26.7% met them them for 100% of weeks (p < 0.001). Participants who met recommendations 100% of weeks had a significant CRF improvement (p < 0.001). Motivating college students throughout innovative teaching methods (e.g., gamification) can lead to health improvements.
Analysis of Short-Term Effects of Air Pollution on Cardiovascular Disease Using Bayesian Spatio-Temporal Models
Authors: Liu Yi , Sun Jingjie , Gou Yannong , Sun Xiubin , Zhang Dandan , Xue Fuzhong
Published: January 2020

There has been an increasing number of clinical and epidemiologic research projects providing supporting evidence that short-term exposure to ambient air pollution contributes to the exacerbation of cardiovascular disease. However, few studies consider measurement error and spatial effects in the estimate of underlying air pollution levels, and less is known about the influence of baseline air pollution levels on cardiovascular disease. We used hospital admissions data for cardiovascular diseases (CVD) collected from an inland, heavily polluted city and a coastal city in Shandong Province, China. Bayesian spatio-temporal models were applied to obtain the underlying pollution level in each city, then generalized additive models were adopted to assess the health effects. The total cardiovascular disease hospitalizations were significantly increased in the inland city by 0.401% (0.029, 0.775), 0.316% (0.086, 0.547), 0.903% (0.252, 1.559), and 2.647% (1.607, 3.697) per 10 μg/m3 increase in PM2.5, PM10, SO2, and NO2, respectively. The total cardiovascular diseases hospitalizations were increased by 6.568% (3.636, 9.584) per 10μg/m3 increase in the level of NO2. Although the air pollution overall had a more significant adverse impact on cardiovascular disease hospital admissions in the heavily polluted inland city, the short-term increases in air pollution levels in the less polluted coastal areas led to excessive exacerbations of cardiovascular disease.
Recognition of Trace Element Contamination Using Ficus macrophylla Leaves in Urban Environment
Authors: Alaimo Maria Grazia , Varrica Daniela
Published: January 2020

Urban areas are characterized by numerous pollutants emitted by anthropic sources both in the form of solid and gaseous particulates. Biomonitoring is an easy, economical, and accessible approach for the determination of atmospheric pollutants. In this study, we used the leaves of Ficus macrophylla Desf. ex Pers., collected in the city of Palermo (Italy), to determine major and trace elements. Geogenic elements exhibited the highest concentrations, making up 99% of the weight of the analyzed elements (Ca, K, Mg, P, S, Na, Fe, and Al); they range 21,400 (Ca) to 122 µg g−1 (Al). The remaining elements showed median concentrations in the range 47.5–0.05 µg g−1 in the following order of abundance: Sr > Cu > Mn > Zn > Br > Rb > Ba > Pb > Cr > Sb > As > Mo = Sc. Cluster analysis, with Spearman’s coefficient to measure sample similarity, identified five main groups, namely, three clusters related to the geogenic background and marine spray; one cluster linked to elements essential to plants, and a final group attributed to the influence of traffic emissions. Calculated enrichment factors (EF) showed that the enrichments found for P and K were linked to plant metabolism; Na and Mg confirmed the role of sea spray; Cu and Zn underlined the contribution linked to anthropic processes and the role of micronutrients in plants.. As, Cr, and Mo had EF values ranging from 10 and 20, and Sb had EF > 90. From geochemical distribution maps of As, Cr, Mo, and Sb it was observed that metal and metalloid concentrations were higher in urban areas and immediately decreased as one moved away from these areas. Local pollution sources play a great role in trace element concentrations in airborne particulate matter. The present study confirms that Ficus macrophylla leaves are suitable for screening an urban environment to identify concentrations of inorganic chemicals, since they have high tolerance to pollution.
Relationship of Parental Support on Healthy Habits, School Motivations and Academic Performance in Adolescents
Authors: Moral-García José Enrique , Urchaga-Litago José David , Ramos-Morcillo Antonio Jesús , Maneiro Rubén
Published: January 2020

The objective of the study was to analyze how parental support relates to the physical activity practice, satisfaction with sports, level of physical activity, academic performance and alcohol consumption. Descriptive cross-sectional study, with 1100 adolescents (12–16 years old), where the factors related to parental support, gender and age acted as independent variables, and satisfaction with sport, level of physical activity (PA), academic performance and alcohol consumption acted as dependent variables. A multivariate statistical analysis was conducted. Adolescents with little parental support show (p < 0.001) more boredom, less fun, worse academic performance and higher alcohol consumption. Gender shows differences (p < 0.001) experiencing girls more boredom, less fun, less PA practice and higher academic performance than boys. Age establishes (p < 0.01) that older adolescents (15–16 years old) experience more boredom, less fun, less PA practice, lower academic performance and higher alcohol consumption than young boys and girls (12–14 years old). Parental support towards PA practice improves healthy habits, benefits academic performance and school satisfaction with physical and sports activity.
Spatial Distribution of HIV Prevalence among Young People in Mozambique
Authors: Muleia Rachid , Boothe Makini , Loquiha Osvaldo , Aerts Marc , Faes Christel
Published: January 2020

Mozambique has a high burden of HIV and is currently ranked sixth worldwide for adult prevalence. In Mozambique, HIV prevalence is not uniformly distributed geographically and throughout the population. We investigated the spatial distribution of HIV infection among adolescents and young people in Mozambique using the 2009 AIDS Indicator Survey (AIS). Generalized geoadditive modeling, combining kriging and additive modeling, was used to study the geographical variability of HIV risk among young people. The nonlinear spatial effect was assessed through radial basis splines. The estimation process was done using two-stage iterative penalized quasi-likelihood within the framework of a mixed-effects model. Our estimation procedure is an extension of the approach by Vandendijck et al., estimating the range (spatial decay) parameter in a binary context. The results revealed the presence of spatial patterns of HIV infection. After controlling for important covariates, the results showed a greater burden of HIV/AIDS in the central and northern regions of the country. Several socio-demographic, biological, and behavioral factors were found to be significantly associated with HIV infection among young people. The findings are important, as they can help health officials and policy makers to design targeted interventions for responding to the HIV epidemic.
Body Image and the Double Burden of Nutrition among South Africans from Diverse Sociodemographic Backgrounds: SANHANES-1
Authors: Mchiza Zandile June-Rose , Parker Whadi-ah , Sewpaul Ronel , Onagbiye Sunday Olawale , Labadarios Demetre
Published: January 2020

This study investigated the associations between underweight, obesity and body image (BI) among 15+ year-old South Africans with diverse socio-demographic backgrounds. A cross-sectional survey and the analyses of data for 6411 15+ year-old participants in the first South African National Health and Nutrition Examination Survey was undertaken. Body image was compared to body mass index (BMI) and socio-demography. Data were analyzed using SPSS versions 25. Results are in percentages, means, 95% confidence intervals, p-values, and odds ratios. Overall, participants who were obese of which majority: were females, earned ZAR 9601+, completed grade 6, were non-Black men, were married and resided in urban formal areas, were more likely to underestimate their BMI and desire to be lighter. Participants who were underweight of which majority: were males, had no form of income or education, were black men, were not married, resided in less urban and farm areas, were younger than 25 years, were more likely to overestimate their BMI and desire to be heavier. While underweight and obesity were strong determinants of BI, BI was differentiated by socio-demography. These findings have a public health implication that requires special attention to curb the irrepressible underweight and obesity in South Africa.
Algebraic Operations on Spatiotemporal Data Based on RDF
Authors: Zhu Lin , Li Nan , Bai Luyi
Published: January 2020

In the context of the Semantic Web, the Resource Description Framework (RDF), a language proposed by W3C, has been used for conceptual description, data modeling, and data querying. The algebraic approach has been proven to be an effective way to process queries, and algebraic operations in RDF have been investigated extensively. However, the study of spatiotemporal RDF algebra has just started and still needs further attention. This paper aims to explore an algebraic operational framework to represent the content of spatiotemporal data and support RDF graphs. To accomplish our study, we defined a spatiotemporal data model based on RDF. On this basis, the spatiotemporal semantics and the spatiotemporal algebraic operations were investigated. We defined five types of graph algebras, and, in particular, the filter operation can filter the spatiotemporal graphs using a graph pattern. Besides this, we put forward a spatiotemporal RDF syntax specification to help users browse, query, and reason with spatiotemporal RDF graphs. The syntax specification illustrates the filter rules, which contribute to capturing the spatiotemporal RDF semantics and provide a number of advanced functions for building data queries.
Assessing the Influence of Landmarks and Paths on the Navigational Efficiency and the Cognitive Load of Indoor Maps
Authors: Fang Hao , Xin Shiwei , Zhang Yanlin , Wang Zhong , Zhu Jing
Published: January 2020

The aim of this study was to investigate whether different expressions of landmarks and paths have different influences on the navigational efficiency and the cognitive load of indoor maps. The study tested 80 subjects by indoor path discovery experiments and measured their cognitive loads with the Cooper–Harper scale. According to the results, we extracted some key landmarks from all landmarks of the experimental indoor map and evaluated the saliency degree of each path. Then, the study tested subjects with four different types of experimental indoor maps by path-recognition tasks. The results showed that maps with key landmarks are more effective in terms of navigation than those with full landmarks, but there were no significant differences between their cognitive loads. Maps with highlighted paths are more effective in terms of navigation, and their cognitive loads are much lower than those without highlighted paths. In addition, this study found that women's cognitive loads were more affected by key landmarks compared with men’s, while highlighted paths had no significant differences in terms of navigational efficiency and the cognitive load between males and females. Implications of these results with respect to the optimization strategies of indoor map designs are discussed.
A Unique Regulation Region in the 3′ UTR of HLA-G with a Promising Potential
Authors: Reches Adi , Berhani Orit , Mandelboim Ofer
Published: January 2020

Human leukocyte antigen G (HLA-G) is a non-classical human leukocyte antigen (HLA) class I protein that interacts with inhibitory receptors and is commonly overexpressed in various cancers, thereby establishing itself as an inhibitory checkpoint immune ligand. It is also expressed in trophoblast cells during pregnancy and protects the fetus from immune rejection. Despite its crucial role and its intriguing expression pattern, the regulation of HLA-G’s expression is only partially understood. HLA-G’s mRNA is expressed in many tissues but the protein expression is restricted only to the cells mentioned above. Therefore, we suggest that HLA-G is post-transcriptionally regulated. Here, we reveal a distinctive site present only in the 3′ Untranslated region (UTR) of HLA-G, which might explain its unique expression pattern. Consequently, we attempted to find binding factors such as RNA binding proteins (RBPs) and microRNAS (miRs) that regulate HLA-G expression by interacting with this distinct site present in its 3′ UTR. Our research indicates that this site should be further studied in order to reveal its significance.
Impact and Intricacies of Bone Marrow Microenvironment in B-cell Lymphomas: From Biology to Therapy
Authors: Sircar Anuvrat , Chowdhury Sayan , Hart Amber , Bell William , Singh Satishkumar , Sehgal Lalit , Epperla Narendranath
Published: January 2020

Lymphoma, a group of widely prevalent hematological malignancies of lymphocyte origin, has become the focus of significant clinical research due to their high propensity for refractory/relapsed (R/R) disease, leading to poor prognostic outcomes. The complex molecular circuitry in lymphomas, especially in the aggressive phenotypes, has made it difficult to find a therapeutic option that can salvage R/R disease. Furthermore, the association of lymphomas with the Bone Marrow (BM) microenvironment has been found to portend worse outcomes in terms of heightened chances of relapse and acquired resistance to chemotherapy. This review assesses the current therapy options in three distinct types of lymphomas: diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. It also explores the role of the BM tumor microenvironment as a secure ‘niche’ for lymphoma cells to grow, proliferate and survive. It further evaluates potential mechanisms through which the tumor cells can establish molecular connections with the BM cells to provide pro-tumor benefits, and discusses putative therapeutic strategies for disrupting the BM-lymphoma cell communication.
A Comparison of Osteoblast and Osteoclast In Vitro Co-Culture Models and Their Translation for Preclinical Drug Testing Applications
Authors: Sieberath Alexander , Della Bella Elena , Ferreira Ana Marina , Gentile Piergiorgio , Eglin David , Dalgarno Kenny
Published: January 2020

As the population of western societies on average ages, the number of people affected by bone remodeling-associated diseases such as osteoporosis continues to increase. The development of new therapeutics is hampered by the high failure rates of drug candidates during clinical testing, which is in part due to the poor predictive character of animal models during preclinical drug testing. Co-culture models of osteoblasts and osteoclasts offer an alternative to animal testing and are considered to have the potential to improve drug development processes in the future. However, a robust, scalable, and reproducible 3D model combining osteoblasts and osteoclasts for preclinical drug testing purposes has not been developed to date. Here we review various types of osteoblast–osteoclast co-culture models and outline the remaining obstacles that must be overcome for their successful translation.
CD155: A Multi-Functional Molecule in Tumor Progression
Authors: Molfetta Rosa , Zitti Beatrice , Lecce Mario , Milito Nadia Domenica , Stabile Helena , Fionda Cinzia , Cippitelli Marco , Gismondi Angela , Santoni Angela , Paolini Rossella
Published: January 2020

CD155 is an adhesion molecule belonging to the Nectin/Nectin-like family often overexpressed on tumor cells and involved in many different processes such as cell adhesion, migration and proliferation. In contrast to these pro-tumorigenic functions, CD155 is also a ligand for the activating receptor DNAM-1 expressed on cytotoxic lymphocytes including Natural Killer (NK) cells and involved in anti-tumor immune response. However, during tumor progression inhibitory receptors for CD155 are up-regulated on the surface of effector cells, contributing to an impairment of their cytotoxic capacity. In this review we will focus on the roles of CD155 as a ligand for the activating receptor DNAM-1 regulating immune surveillance against cancer and as pro-oncogenic molecule favoring tumor proliferation, invasion and immune evasion. A deeper understanding of the multiple roles played by CD155 in cancer development contributes to improving anti-tumor strategies aimed to potentiate immune response against cancer.
C-Terminal Domain of the Human Zinc Transporter hZnT8 Is Structurally Indistinguishable from Its Disease Risk Variant (R325W)
Authors: Ullah Raheem , Shehzad Aamir , Shah Majid Ali , March Matteo De , Ismat Fouzia , Iqbal Mazhar , Onesti Silvia , Rahman Moazur , McPherson Michael J.
Published: January 2020

The human zinc transporter 8 (hZnT8) plays important roles in the storage of insulin in the secretory vesicles of pancreatic β cells. hZnT8 consists of a transmembrane domain, with its N- and C-termini protruding into the cytoplasm. Interestingly, the exchange of arginine to tryptophan at position 325 in the C-terminal domain (CTD) increases the risk of developing type 2 diabetes mellitus (T2D). In the present study, the CTDs of hZnT8 (the wild-type (WT) and its disease risk variant (R325W)) were expressed, purified, and characterized in their native forms by biophysical techniques. The data reveal that the CTDs form tetramers which are stabilized by zinc binding, and exhibit negligible differences in their secondary structure content and zinc-binding affinities in solution. These findings provide the basis for conducting further structural studies aimed at unravelling the molecular mechanism underlying the increased susceptibility to develop T2D, which is modulated by the disease risk variant.
Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer
Authors: Sechi Stefano , Frappaolo Anna , Karimpour-Ghahnavieh Angela , Piergentili Roberto , Giansanti Maria Grazia
Published: January 2020

Golgi phosphoprotein 3 (GOLPH3), a Phosphatidylinositol 4-Phosphate [PI(4)P] effector at the Golgi, is required for Golgi ribbon structure maintenance, vesicle trafficking and Golgi glycosylation. GOLPH3 has been validated as an oncoprotein through combining integrative genomics with clinopathological and functional analyses. It is frequently amplified in several solid tumor types including melanoma, lung cancer, breast cancer, glioma, and colorectal cancer. Overexpression of GOLPH3 correlates with poor prognosis in multiple tumor types including 52% of breast cancers and 41% to 53% of glioblastoma. Roles of GOLPH3 in tumorigenesis may correlate with several cellular activities including: (i) regulating Golgi-to-plasma membrane trafficking and contributing to malignant secretory phenotypes; (ii) controlling the internalization and recycling of key signaling molecules or increasing the glycosylation of cancer relevant glycoproteins; and (iii) influencing the DNA damage response and maintenance of genomic stability. Here we summarize current knowledge on the oncogenic pathways involving GOLPH3 in human cancer, GOLPH3 influence on tumor metabolism and surrounding stroma, and its possible role in tumor metastasis formation.
Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer’s Disease
Authors: Ono Kenjiro , Tsuji Mayumi
Published: January 2020

Worldwide, Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease and is characterized by unique pathological hallmarks in the brain, including plaques composed of amyloid β-protein (Aβ) and neurofibrillary tangles of tau protein. Genetic studies, biochemical data, and animal models have suggested that Aβ is responsible for the pathogenesis of AD (i.e., the amyloid hypothesis). Indeed, Aβ molecules tend to aggregate, forming oligomers, protofibrils, and mature fibrils. However, while these Aβ species form amyloid plaques of the type implicated in AD neurodegeneration, recent clinical trials designed to reduce the production of Aβ and/or the plaque burden have not demonstrated clinical efficacy. In addition, recent studies using synthetic Aβ peptides, cell culture models, Arctic transgenic mice, and human samples of AD brain tissues have suggested that the pre-fibrillar forms of Aβ, particularly Aβ protofibrils, may be the most critical species, compared with extracellular fibrillar forms. We recently reported that protofibrils of Aβ1-42 disturbed membrane integrity by inducing reactive oxygen species generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and synaptic toxicity. Therefore, the therapeutic reduction of protofibrils may prevent the progression of AD by ameliorating neuronal damage and cognitive dysfunction through multiple mechanisms.
Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis
Authors: Kataoka Tatsuki R. , Ueshima Chiyuki , Hirata Masahiro , Minamiguchi Sachiko , Haga Hironori
Published: January 2020

Killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) was previously thought to be a human NK cell-specific protein. Mast cells are involved in allergic reactions via their KIT-mediated and FcɛRI-mediated responses. We recently detected the expression of KIR2DL4 in human cultured mast cells established from peripheral blood of healthy volunteers (PB-mast), in the human mast cell line LAD2, and in human tissue mast cells. Agonistic antibodies against KIR2DL4 negatively regulate the KIT-mediated and FcɛRI-mediated responses of PB-mast and LAD2 cells. In addition, agonistic antibodies and human leukocyte antigen (HLA)-G, a natural ligand for KIR2DL4, induce the secretion of leukemia inhibitory factor and serine proteases from human mast cells, which have been implicated in pregnancy establishment and cancer metastasis. Therefore, KIR2DL4 stimulation with agonistic antibodies and recombinant HLA-G protein may enhance both processes, in addition to suppressing mast-cell-mediated allergic reactions.
Low Dose Cyclophosphamide Modulates Tumor Microenvironment by TGF-β Signaling Pathway
Authors: Zhong Hui , Lai Yifan , Zhang Rui , Daoud Abdelkader , Feng Qingyuan , Zhou Jia , Shang Jing
Published: January 2020

The tumor microenvironment has been recently recognized as a critical contributor to cancer progression and anticancer therapy-resistance. Cyclophosphamide (CTX) is a cytotoxic agent commonly used in clinics for the treatment of cancer. Previous reports demonstrated that CTX given at low continuous doses, known as metronomic schedule, mainly targets endothelial cells and circulating Tregs with unknown mechanisms. Here, we investigated the antitumor activity of two different metronomic schedules of CTX along with their corresponding MTD regimen and further explored their effect on immune function and tumor microenvironment. Toxicity evaluation was monitored by overall survival rate, weight loss, and histopathological analysis. A nude mouse model of Lewis lung cancer was established to assess the anti-metastatic effects of CTX in vivo. CD4+, CD8+, and CD4+CD25+FoxP3 T cells were selected by flow cytometry analysis. Low and continuous administration of CTX was able to restore immune function via increase of CD4+/CD8+ T cells and depletion of T regulatory cells, not only in circulatory and splenic compartments, but also at the tumor site. Low-dose CTX also reduced myofibroblasts, accompanied with an increased level of E-cadherin and low N-cadherin, both in the primary tumor and lung through the TGF-β pathway by the downregulated expression of TGF-β receptor 2. Our data may indicate that several other molecular mechanisms of CTX for tumor may be involved in metronomic chemotherapy, besides targeting angiogenesis and regulatory T cells.
The Cannabis Proteome Draft Map Project
Authors: Jenkins Conor , Orsburn Benjamin
Published: January 2020

Recently we have seen a relaxation of the historic restrictions on the use and subsequent research on the Cannabis plants, generally classified as Cannabis sativa and Cannabis indica. What research has been performed to date has centered on chemical analysis of plant flower products, namely cannabinoids and various terpenes that directly contribute to phenotypic characteristics of the female flowers. In addition, we have seen many groups recently completing genetic profiles of various plants of commercial value. To date, no comprehensive attempt has been made to profile the proteomes of these plants. We report herein our progress on constructing a comprehensive draft map of the Cannabis proteome. To date we have identified over 17,000 potential protein sequences. Unfortunately, no annotated genome of Cannabis plants currently exists. We present a method by which “next generation” DNA sequencing output and shotgun proteomics data can be combined to produce annotated FASTA files, bypassing the need for annotated genetic information altogether in traditional proteomics workflows. The resulting material represents the first comprehensive annotated protein FASTA for any Cannabis plant. Using this annotated database as reference we can refine our protein identifications, resulting in the confident identification of 13,000 proteins with putative function. Furthermore, we demonstrate that post-translational modifications play an important role in the proteomes of Cannabis flower, particularly lysine acetylation and protein glycosylation. To facilitate the evolution of analytical investigations into these plant materials, we have created a portal to host resources developed from our proteomic and metabolomic analysis of Cannabis plant material as well as our results integrating these resources.
Synaptotagmin 1 Is Involved in Neuropathic Pain and Electroacupuncture-Mediated Analgesic Effect
Authors: Wan Juan , Nan Sha , Liu Jingjing , Ding Mingxing , Zhu Hongmei , Suo Chuanguang , Wang Zhuole , Hu Manli , Wang Dehai , Ding Yi
Published: January 2020

Numerous studies have verified that electroacupuncture (EA) can relieve neuropathic pain through a variety of mechanisms. Synaptotagmin 1 (Syt-1), a synaptic vesicle protein for regulating exocytosis of neurotransmitters, was found to be affected by EA stimulation. However, the roles of Syt-1 in neuropathic pain and EA-induced analgesic effect remain unclear. Here, the effect of Syt-1 on nociception was assessed through an antibody blockade, siRNA silencing, and lentivirus-mediated overexpression of spinal Syt-1 in rats with spared nerve injury (SNI). EA was used for stimulating bilateral “Sanjinjiao” and “Zusanli” acupoints of the SNI rats to evaluate its effect on nociceptive thresholds and spinal Syt-1 expression. The mechanically and thermally nociceptive behaviors were assessed with paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different temperatures, respectively, at day 0, 7, 8, 14, and 20. Syt-1 mRNA and protein levels were determined with qRT-PCR and Western blot, respectively, and its distribution was observed with the immunohistochemistry method. The results demonstrated Syt-1 antibody blockade and siRNA silencing increased ipsilateral PWTs and PWLs of SNI rats, while Syt-1 overexpression decreased ipsilateral PWTs and PWLs of rats. EA significantly attenuated nociceptive behaviors and down-regulated spinal Syt-1 protein levels (especially in laminae I-II), which were reversed by Syt-1 overexpression. Our findings firstly indicate that Syt-1 is involved in the development of neuropathic pain and that EA attenuates neuropathic pain, probably through suppressing Syt-1 protein expression in the spinal cord.
Deep Reinforcement Learning Based Left-Turn Connected and Automated Vehicle Control at Signalized Intersection in Vehicle-to-Infrastructure Environment
Authors: Chen Juan , Xue Zhengxuan , Fan Daiqian
Published: January 2020

In order to solve the problem of vehicle delay caused by stops at signalized intersections, a micro-control method of a left-turning connected and automated vehicle (CAV) based on an improved deep deterministic policy gradient (DDPG) is designed in this paper. In this paper, the micro-control of the whole process of a left-turn vehicle approaching, entering, and leaving a signalized intersection is considered. In addition, in order to solve the problems of low sampling efficiency and overestimation of the critic network of the DDPG algorithm, a positive and negative reward experience replay buffer sampling mechanism and multi-critic network structure are adopted in the DDPG algorithm in this paper. Finally, the effectiveness of the signal control method, six DDPG-based methods (DDPG, PNRERB-1C-DDPG, PNRERB-3C-DDPG, PNRERB-5C-DDPG, PNRERB-5CNG-DDPG, and PNRERB-7C-DDPG), and four DQN-based methods (DQN, Dueling DQN, Double DQN, and Prioritized Replay DQN) are verified under 0.2, 0.5, and 0.7 saturation degrees of left-turning vehicles at a signalized intersection within a VISSIM simulation environment. The results show that the proposed deep reinforcement learning method can get a number of stops benefits ranging from 5% to 94%, stop time benefits ranging from 1% to 99%, and delay benefits ranging from −17% to 93%, respectively compared with the traditional signal control method.
Contemporary Speech and Oral Language Care for Deaf and Hard-of-Hearing Children Using Hearing Devices
Authors: Bergeron François , Berland Aurore , Demers Dominique , Gobeil Suzie
Published: January 2020

Contemporary speech and language interventions are not limited to disabilities but embrace the pragmatics of communication behaviors from the perspective of functional social participation. Accordingly, current speech and language therapies for deaf and hard-of-hearing children include a broad spectrum of approaches and techniques. This paper explores contemporary approaches and techniques for speech and oral language interventions for deaf and hard-of-hearing children using hearing devices, evidence of efficacy and how they are implemented in diverse clinical practices.
Ensemble Learning to Improve the Prediction of Fetal Macrosomia and Large-for-Gestational Age
Authors: Ye Shangyuan , Zhang Hui , Shi Fuyan , Guo Jing , Wang Suzhen , Zhang Bo
Published: January 2020

Background: The objective of this study was to investigate the use of ensemble methods to improve the prediction of fetal macrosomia and large for gestational age from prenatal ultrasound imaging measurements. Methods: We evaluated and compared the prediction accuracies of nonlinear and quadratic mixed-effects models coupled with 26 different empirical formulas for estimating fetal weights in predicting large fetuses at birth. The data for the investigation were taken from the Successive Small-for-Gestational-Age-Births study. Ensemble methods, a class of machine learning techniques, were used to improve the prediction accuracies by combining the individual models and empirical formulas. Results: The prediction accuracy of individual statistical models and empirical formulas varied considerably in predicting macrosomia but varied less in predicting large for gestational age. Two ensemble methods, voting and stacking, with model selection, can combine the strengths of individual models and formulas and can improve the prediction accuracy. Conclusions: Ensemble learning can improve the prediction of fetal macrosomia and large for gestational age and have the potential to assist obstetricians in clinical decisions.
Matrix Metalloproteinase 13 Activity is Required for Normal and Hypoxia-Induced Precocious Hatching in Zebrafish Embryos
Authors: Small Christopher D. , el-Khoury Megan , Deslongchamps Ghislain , Benfey Tillmann J. , Crawford Bryan D.
Published: January 2020

Hypoxia induces precocious hatching in zebrafish, but we do not have a clear understanding of the molecular mechanisms regulating the activation of the hatching enzyme or how these mechanisms trigger precocious hatching under unfavorable environmental conditions. Using immunohistochemistry, pharmacological inhibition of matrix metalloproteinase 13 (Mmp13), and in vivo zymography, we show that Mmp13a is present in the hatching gland just as embryos become hatching competent and that Mmp13a activity is required for both normal hatching and hypoxia-induced precocious hatching. We conclude that Mmp13a likely functions in activating the hatching enzyme zymogen and that Mmp13a activity is necessary but not sufficient for hatching in zebrafish. This study highlights the broad nature of MMP function in development and provides a non-mammalian example of extra-embryonic processes mediated by MMP activity.