bluuebunny/crossref_metadata_2025 huggingface dataset:
Children with Fetal Alcohol Syndrome (FAS): 3D-Analysis of Palatal Depth and 3D-Metric Facial Length
Authors: Blanck-Lubarsch Moritz , Dirksen Dieter , Feldmann Reinhold , Sauerland Cristina , Hohoff Ariane
Published: December 2019

Background: Drinking alcohol during pregnancy can result in severe developmental disorders in the child. Symptoms of the fetal alcohol spectrum disorder (FASD) comprise growth deficiencies, abnormal facial phenotype and damage or dysfunction of the central nervous system. Numerous diagnostic methods for facial phenotyping in FASD exist, but diagnoses are still difficult. Our aim was to find additional and objective methods for the verification of FAS(D). Methods: Three-dimensional dental models of 60 children (30 FAS and 30 controls) were used to metrically determine maximum palatal depths at the median palatine raphe. Three-dimensional facial scans were taken, and vertical distances of the face were measured at five defined facial landmarks (FP1–FP5) for each child. Results: Mean palatal height, total facial length (FP1–FP5) as well as FP4–FP5 did not significantly differ between the FAS group and the control group. Comparing vertical facial subdivisions, however, resulted in significant differences for distances FP1 to FP2 (p = 0.042, FAS > controls), FP2 to FP3 (p < 0.001, FAS < controls), FP3 to FP4 (p < 0.001, FAS > controls) and FP3 to FP5 (p = 0.007, FAS > controls). Conclusions: Metric vertical measurements of the face can be used as additional objective criteria for FAS diagnoses. However, no significant differences were reported for palatal depth evaluation in the specific age range tested in the present study.
Cyclist Injury Severity in Spain: A Bayesian Analysis of Police Road Injury Data Focusing on Involved Vehicles and Route Environment
Authors: Aldred Rachel , García-Herrero Susana , Anaya Esther , Herrera Sixto , Mariscal Miguel Ángel
Published: December 2019

This study analyses factors associated with cyclist injury severity, focusing on vehicle type, route environment, and interactions between them. Data analysed was collected by Spanish police during 2016 and includes records relating to 12,318 drivers and cyclist involving in collisions with at least one injured cyclist, of whom 7230 were injured cyclists. Bayesian methods were used to model relationships between cyclist injury severity and circumstances related to the crash, with the outcome variable being whether a cyclist was killed or seriously injured (KSI) rather than slightly injured. Factors in the model included those relating to the injured cyclist, the route environment, and involved motorists. Injury severity among cyclists was likely to be higher where an Heavy Goods Vehicle (HGV) was involved, and certain route conditions (bicycle infrastructure, 30 kph zones, and urban zones) were associated with lower injury severity. Interactions exist between the two: collisions involving large vehicles in lower-risk environments are less likely to lead to KSIs than collisions involving large vehicles in higher-risk environments. Finally, motorists involved in a collision were more likely than the injured cyclists to have committed an error or infraction. The study supports the creation of infrastructure that separates cyclists from motor traffic. Also, action needs to be taken to address motorist behaviour, given the imbalance between responsibility and risk.
Increased Physical Activity in Preparation for a Women-Only Mass Participation Sport Event: A Framework for Estimating the Health Impact
Authors: Schoemaker Jelle , van Genderen Simon , de Boer Willem I. J.
Published: December 2019

Mass participation sporting events (MPSEs) are increasing in popularity. However, little research exists into the potential value of these events for improving public health by enhancing physical activity (PA). The aim of this study is to estimate the health impact of increased physical activity as a result of preparing for an MPSE. Participants of a mass participation women-only running event were asked if they performed additional PA in preparation of the event, including the length (weeks) and intensity (min per week). Additionally, self-reported change in health status was evaluated. Based on these results, we have developed a framework for estimating the cumulatively gained quality adjusted life years (QALYs) and monetary value thereof. Of the respondents (N = 468; mean age 42.3 ± 11.9 years), 32% performed additional vigorous PA in preparation of the event, with an average of 63 min per week over 8.8 weeks. Performing additional vigorous PA significantly improved the odds of self-rated health. The estimated total health impact of participants preparing for the Marikenloop was 6.6 QALYs gained with a corresponding monetary value between EUR 133,000 and EUR 532,000. We believe our health impact framework helps to understand that MPSEs can be a notable part of the public health domain.
Depressive and Anxiety Symptoms among Pediatric In-Patients with Dengue Fever: A Case-Control Study
Authors: Herbuela Von Ralph Dane M. , de Guzman Ferdinand S. , Sobrepeña Girly D. , Claudio Andrew Benedict F. , Tomas Angelica Cecilia V. , Arriola-delos Reyes Carmina M. , Regalado Rachele A. , Teodoro Mariama M. , Watanabe Kozo
Published: December 2019

Background: Psychiatric symptoms have been reported in adult patients with dengue fever (DF); however, information on pediatric patients remains inadequate. We sought to identify the prevalence and predictors of depressive and anxiety symptoms and identify other psychiatric symptoms among pediatric patients with DF. This case-control study involved pediatric in-patients (n = 225) who had clinical or serologic-confirmed DF and healthy school-based controls (n = 260). Participants completed the Revised Child Anxiety and Depression Scale (RCADS). Results: The prevalence of depressive (13.3%) and anxiety (34.2%) symptoms among pediatric patients with DF was significantly (p < 0.001) higher than that among controls (3.5% and 16.2%, respectively). Multiple linear regression analysis found that age, family history of DF, ≤2 days of hospitalization, myalgia, and arthralgia were predictors of increased depressive and anxiety symptoms among the patients. Further, 26.7% of pediatric patients reported irritability, agitation, visual hallucinations, and aggressiveness. Conclusion: Pediatric patients present depressive and anxiety symptoms whose levels were associated with social and clinical factors. However, whether these symptoms are present only during the infection or may still persist after recovery or are brought by children’s adverse reactions to hospitalization are unknown, and thus, further studies are needed.
Cost-Effective Detection of Perfluoroalkyl Carboxylic Acids with Gas Chromatography: Optimization of Derivatization Approaches and Method Validation
Authors: Li Zhen , Sun Hongwei
Published: December 2019

The reliable quantification of perfluoroalkyl carboxylic acids (PFCAs) in environmental samples like surface water by using gas chromatography (GC) remains challenging because the polar PFCAs call for derivatization before injection and problems involving the integration of sample pretreatment and derivatization procedures. Here we proposed a cost-effective method for the GC based determination of C4–C12 PFCAs in surface water samples by integrating solid phase extraction and PFCAs anilide derivatization. First, we assessed the performance of different PFCAs derivatization methods, namely esterification and amidation. Esterification was unable to derivatize C4–C6 PFCAs. On the contrary, amidation procedures by using 2,4-difluoroaniline (DFA) and N,N′-dicyclohexylcarbodiimide (DCC) could successfully transform all the PFCA analogs to produce anilide derivatives, which could be easily detected by GC. Then the reaction conditions in the amidation approach were further optimized by using orthogonal design experiments. After optimizing the instrumental parameters of GC, the limits of detection (LOD) of this derivatization method were determined to be 1.14–6.32 μg L−1. Finally, in order to establish an intact method for the quantification of PFCAs in surface water samples, solid phase extraction (SPE) was used for extraction and cleanup, which was further integrated with the subsequent amidation process. The SPE-amidation-GC method was validated for application, with good accuracy and precision reflected by the PFCAs recoveries and derivatization of triplicates. The method reported here could provide a promising and cost-effective alternative for the simultaneous determination of C4–C12 PFCAs in environmental water samples.
Environmental Footprints of High-Speed Railway Construction in China: A Case Study of the Beijing–Tianjin Line
Authors: Lin Jianyi , Cheng Shihui , Li Huimei , Yang Dewei , Lin Tao
Published: December 2019

The environmental footprints of China’s high-speed railway (HSR) have attracted much attention nationally and internationally. Although there is some research focusing on CO2 emissions, a comprehensive environmental impacts assessment of HSR construction is still lacking. In this study, the emissions of the Beijing–Tianjin intercity HSR line was calculated using a hybrid input–output life cycle assessment method to quantify the environmental impacts of HSR throughout its construction. The environmental footprints during the construction stage were analyzed in terms of different subsystems and sectors. The results showed that bridges contribute the largest environmental footprints at approximately 60%, followed by rail and electric multiple unit (EMU) systems. The top three sectors that contribute to pollutant emissions are the metal smelting and rolling industry, transport equipment manufacturing, and non-metallic mineral production. CO2 and NOx are the major pollutants directly emitted by site equipment operation. More chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN), and petroleum are emitted in EMU production than in rail construction, while NH3-N is emitted more in rails instead. Cd, Pb, As, and Hg are the significant pollutants in the metal smelting and rolling industry, whereas Cr, Cu, and Zn are the main heavy metal emissions in the transport equipment manufacturing sector. Heavy metals are the main types of environmental footprints in bridges, stations, and electric systems. Water pollutants are the main environmental impacts for rail and EMU systems, and the emissions of air pollutants are significant in subgrades. The production efficiency of upstream materials, desulfurization and denitration in fossil combustion, and the length of the bridge construction should be considered for an HSR under construction, in order to become environmentally friendly and sustainable.
Education First: Promoting LGBT+ Friendly Healthcare with a Competency-Based Course and Game-Based Teaching
Authors: Yang Hsing-Chen
Published: December 2019

How, apart from by conveying professional knowledge, can university medical education nurture and improve the gender competency of medical students and thereby create an LGBT+ friendly healthcare environment? This study explored the use of game-based teaching activities in competency-based teaching from the perspective of competency-based medical education (CBME) and employed a qualitative case-study methodology. We designed an LGBT+ Health and Medical Care course in a medical school. Feedback was collected from two teachers and 19 medical students using in-depth interviews and thematic analysis was used to analyze the collected data. The findings of this study were as follows: (1) Games encouraged student participation and benefited gender knowledge transmission and transformation through competency learning, and (2) games embodied the idea of assessment as learning. The enjoyable feeling of pressure from playing games motivated students to learn. Using games as both a teaching activity and an assessment tool provided the assessment and instant feedback required in the CBME learning process. Game-based teaching successfully guided medical students to learn about gender and achieve the learning goals of integrating knowledge, attitudes, and skills. To fully implement CBME using games as teaching methods, teaching activities, learning tasks, and assessment tools, teachers must improve their teaching competency. This study revealed that leading discussions and designing curricula are key in the implementation of gender competency-based education; in particular, the ability to lead discussions is the core factor. Game-based gender competency education for medical students can be facilitated with discussions that reinforce learning outcomes to achieve the objectives of gender equality education and LGBT+ friendly healthcare. The results of this study indicated that game-based CBME with specific teaching strategies was an effective method of nurturing the gender competency of medical students. The consequent integration of gender competency into medical education could achieve the goal of LGBT+ friendly healthcare.
Family Impacts of Severe Dental Caries among Children in the United Kingdom
Authors: Abed Rawan , Bernabe Eduardo , Sabbah Wael
Published: December 2019

The aim of this study was to evaluate the family impacts of severe dental caries among children. Data from 3859 school-age children (5-, 8-, 12- and 15-year-olds) who participated in the 2013 Children’s Dental Health Survey, a national cross-sectional survey in England, Wales and Northern Ireland, were used. Severe dental caries was defined as having at least one tooth with pulpal involvement, ulceration, fistula, or abscess (PUFA). Family impacts were measured using seven items of the Family Impact Scale (FIS). The association between severe dental caries and family impacts was assessed in logistic regression models, adjusting for child’s age, gender, and country of residence; parent’s marital status, education, and job classification; and area deprivation. Severe dental caries among children showed a significant negative impact on family life (Odds Ratio: 6.00; 95% Confidence Interval: 3.34–10.78). Parents of children with severe dental caries had greater odds of taking time off work (OR: 2.75; 95% CI: 1.16–6.54), reporting the child needed more attention (OR: 4.08; 95% CI: 2.15–7.75), feeling guilty (OR: 6.32; 95% CI: 3.26–12.26), feeling stressed (OR: 7.34; 95% CI: 4.15–12.99), having normal activities disrupted (OR: 5.78; 95% CI: 2.71–12.34), and having sleep disrupted (OR: 4.94; 95% CI: 2.78–8.76). Having severe dental caries was not associated with financial difficulties in the family (OR: 1.64; 95% CI: 0.49–5.51). The observed association between severe dental caries and family impacts was independent of child and family sociodemographic characteristics. The findings underscore the importance of preventive interventions to avoid severe dental caries in children and subsequently reduce negative impacts on their family life.
Exploring Doctors’ Willingness to Provide Online Counseling Services: The Roles of Motivations and Costs
Authors: Chen Jiahe , Lan Yi-Chen , Chang Yu-Wei , Chang Po-Ya
Published: December 2019

With the impetus of information communication technology (ICT), emerging eHealth has attracted increasing number of doctors’ participation in online health platforms, which provide various potential benefits to doctors. However, previous studies on eHealth have seldom distinguished different service modes provided by doctors. In addition, the bulk of the literature has considered doctors’ motivations based solely on online environments. To fill this gap, this study combines expectancy theory and the Bagozzi, Dholakia, and Basuroy (BDB) model to examine the relationships between anticipated outcomes, performance expectations, and effort intentions from online and offline perspectives. Doctors’ behavioral intentions are further divided into two categories: the willingness to offer free services and paid services. Using SmartPLS, this study conducts structural equation modeling (SEM) to analyze 311 sample data. The results show that extrinsic motivations (i.e., extrinsic rewards, expected relationships, and image) and intrinsic motivation (i.e., a sense of self-worth) significantly influence the desire to serve patients well, which in turn positively affects the willingness to offer free services and the willingness to offer paid services. Moreover, counseling time is confirmed as the main cost, which negatively moderates the relationships between desire and behavioral intentions. The findings provide theoretical insights for eHealth and provide practical suggestions to develop marketing strategies for online health platform providers.
Supplier Selection and Order Allocation under a Carbon Emission Trading Scheme: A Case Study from China
Authors: Wang Chen , Yang Qingyan , Dai Shufen
Published: December 2019

In implementing carbon emission trading schemes (ETSs), the cost of carbon embedded in raw materials further complicates supplier selection and order allocation. Firms have to make decisions by comprehensively considering the cost and the important intangible performance of suppliers. This paper uses an analytic network process–integer programming (ANP–IP) model based on a multiple-criteria decision-making (MCDM) approach to solve the above issues by first evaluating and then optimizing them. The carbon embedded in components, which can be used to reflect the carbon competitiveness of a supplier, is integrated into the ANP–IP model. In addition, an international large-scale electronic equipment manufacturer in China is used to validate the model. Different scenarios involving different carbon prices are designed to analyze whether China’s current ETS drives firms to choose more low-carbon suppliers. The results show that current carbon constraints are not stringent enough to drive firms to select low-carbon suppliers. A more stringent ETS with a higher carbon price could facilitate the creation of a low-carbon supply chain. The analysis of the firm’s total cost and of the total cost composition indicates that the impact of a more stringent ETS on the firm results mainly from indirect costs instead of direct costs. The indirect cost is caused by the suppliers’ transfer of part of the low-carbon investment in the product, and arises from buying carbon permits with high carbon prices. Implications revealed by the model analysis are discussed to provide guidance to suppliers regarding the balance between soft competitiveness and low-carbon production capability and to provide guidance to the firm on how to cooperate with suppliers to achieve a mutually beneficial situation.
Interaction Effects of Disruptive Behaviour and Motivation Profiles with Teacher Competence and School Satisfaction in Secondary School Physical Education
Authors: Granero-Gallegos Antonio , Gómez-López Manuel , Baena-Extremera Antonio , Martínez-Molina Marina
Published: December 2019

The objectives of this work were two-fold: Firstly, to identify the profiles of disruptive behaviours and motivation in secondary school physical education students using cluster analysis; and secondly, to analyse the interaction of the profiles with school satisfaction and perceived teaching competence. A group of 758 secondary school students (54.2% female) between the ages of 13 and 18 (M = 15.22, DT = 1.27) participated in the study by responding to the following scales: The Disruptive Behaviours in Physical Education Questionnaire, The School Satisfaction Scale, The Sport Motivation Scale adapted to Physical Education, and the Evaluation of Teaching Competencies Scale in Physical Education. The cluster analysis established two distinct profiles: High levels of disruptive behaviours and low levels of disruptive behaviours. The results showed that the students with the high disruptive behaviours profile were mostly boys, having low levels of intrinsic motivation and high levels of amotivation and misbehaviour in the classroom. In contrast, those students with the low disruptive behaviours profile were mostly girls, having the highest levels of intrinsic motivation and the lowest levels in all the disruptive behaviours. It was shown that students exhibiting the worse classroom behaviours were more bored in school, while those students with better behaviour perceived greater teaching competence.
The Impact of Modern Ultramarathons on Shaping the Social Identity of Runners. The Case Study of Karkonosze Winter Ultramarathon
Authors: Kazimierczak Marek , Dąbrowska Agata , Adamczewska Katarzyna , Malchrowicz-Mośko Ewa
Published: December 2019

Despite the growing interest in extreme sports around the world, researchers have rarely investigated the complex factors that have led to a developed commitment to extreme sports in recent years. Precisely, the social identity of ultramarathoners remains a research niche. The aim of the article is to analyze the impact of a sports event on shaping social identity of ultramarathon runners on the example of Karkonosze Winter Ultramarathon (held in Poland). The qualitative method used in the article—interviews with runners—made it possible to examine the factors that create social identity, among which the motives for participation, sports subculture, and the authenticity of the experience play a key role. The first part of the article describes the theoretical aspects of social identity in sport. The second, empirical part presents the research results supplemented by the statements of the contestants. In this case, the subject of analysis is the motives for participation in a winter ultramarathon and their characteristics. Lastly, the article analyzes the subculture of ultramarathoners and the experience of contestants’ authenticity. The investigated winter ultramarathon created the perfect space for creation, deepening and celebrating the social identity of ultramarathoners assessed as a value in itself. The article enriches the present knowledge about the motivation of ultramarathoners because, unlike the results of quantitative research, it presents in-depth responses of runners who were not always concerned by existing research questionnaires.
Caveolin as a Universal Target in Dermatology
Authors: Kruglikov Ilja L. , Scherer Philipp E.
Published: December 2019

Caveolin-1 is strongly expressed in different dermal and subdermal cells and physically interacts with signaling molecules and receptors, among them with transforming growth factor beta (TGF-β), matrix metalloproteinases, heat shock proteins, toll-like and glucocorticoid receptors. It should therefore be heavily involved in the regulation of cellular signaling in various hyperproliferative and inflammatory skin conditions. We provide an overview of the role of the caveolin-1 expression in different hyperproliferative and inflammatory skin diseases and discuss its possible active involvement in the therapeutic effects of different well-known drugs widely applied in dermatology. We also discuss the possible role of caveolin expression in development of the drug resistance in dermatology. Caveolin-1 is not only an important pathophysiological factor in different hyperproliferative and inflammatory dermatological conditions, but can also serve as a target for their treatment. Targeted regulation of caveolin is likely to serve as a new treatment strategy in dermatology.
The Structure of Sucrose-Soaked Levansucrase Crystals from Erwinia tasmaniensis reveals a Binding Pocket for Levanbiose
Authors: Polsinelli Ivan , Caliandro Rosanna , Demitri Nicola , Benini Stefano
Published: December 2019

Given its potential role in the synthesis of novel prebiotics and applications in the pharmaceutical industry, a strong interest has developed in the enzyme levansucrase (LSC, EC 2.4.1.10). LSC catalyzes both the hydrolysis of sucrose (or sucroselike substrates) and the transfructosylation of a wide range of acceptors. LSC from the Gram-negative bacterium Erwinia tasmaniensis (EtLSC) is an interesting biocatalyst due to its high-yield production of fructooligosaccharides (FOSs). In order to learn more about the process of chain elongation, we obtained the crystal structure of EtLSC in complex with levanbiose (LBS). LBS is an FOS intermediate formed during the synthesis of longer-chain FOSs and levan. Analysis of the LBS binding pocket revealed that its structure was conserved in several related species. The binding pocket discovered in this crystal structure is an ideal target for future mutagenesis studies in order to understand its biological relevance and to engineer LSCs into tailored products.
Clinical and Genetic Analysis of a European Cohort with Pericentral Retinitis Pigmentosa
Authors: Karali Marianthi , Testa Francesco , Brunetti-Pierri Raffaella , Di Iorio Valentina , Pizzo Mariateresa , Melillo Paolo , Barillari Maria Rosaria , Torella Annalaura , Musacchia Francesco , D’Angelo Luigi , Banfi Sandro , Simonelli Francesca
Published: December 2019

Retinitis pigmentosa (RP) is a clinically heterogenous disease that comprises a wide range of phenotypic and genetic subtypes. Pericentral RP is an atypical form of RP characterized by bone-spicule pigmentation and/or atrophy confined in the near mid-periphery of the retina. In contrast to classic RP, the far periphery is better preserved in pericentral RP. The aim of this study was to perform the first detailed clinical and genetic analysis of a cohort of European subjects with pericentral RP to determine the phenotypic features and the genetic bases of the disease. A total of 54 subjects from 48 independent families with pericentral RP, non-syndromic and syndromic, were evaluated through a full ophthalmological examination and underwent clinical exome or retinopathy gene panel sequencing. Disease-causative variants were identified in 22 of the 35 families (63%) in 10 different genes, four of which are also responsible for syndromic RP. Thirteen of the 34 likely pathogenic variants were novel. Intra-familiar variability was also observed. The current study confirms the mild phenotype of pericentral RP and extends the spectrum of genes associated with this condition.
End-to-End Platform for Human Pluripotent Stem Cell Manufacturing
Authors: Pandey Puspa R. , Tomney Amarel , Woon Marites T. , Uth Nicholas , Shafighi Farjad , Ngabo Igor , Vallabhaneni Haritha , Levinson Yonatan , Abraham Eytan , Friedrich Ben-Nun Inbar
Published: December 2019

Industrialization of stem-cell based therapies requires innovative solutions to close the gap between research and commercialization. Scalable cell production platforms are needed to reliably deliver the cell quantities needed during the various stages of development and commercial supply. Human pluripotent stem cells (hPSCs) are a key source material for generating therapeutic cell types. We have developed a closed, automated and scalable stirred tank bioreactor platform, capable of sustaining high fold expansion of hPSCs. Such a platform could facilitate the in-process monitoring and integration of online monitoring systems, leading to significantly reduced labor requirements and contamination risk. hPSCs are expanded in a controlled bioreactor using perfused xeno-free media. Cell harvest and concentration are performed in closed steps. The hPSCs can be cryopreserved to generate a bank of cells, or further processed as needed. Cryopreserved cells can be thawed into a two-dimensional (2D) tissue culture platform or a three-dimensional (3D) bioreactor to initiate a new expansion phase, or be differentiated to the clinically relevant cell type. The expanded hPSCs express hPSC-specific markers, have a normal karyotype and the ability to differentiate to the cells of the three germ layers. This end-to-end platform allows a large scale expansion of high quality hPSCs that can support the required cell demand for various clinical indications.
Pathogenic Puppetry: Manipulation of the Host Actin Cytoskeleton by Chlamydia trachomatis
Authors: Caven Liam , Carabeo Rey A.
Published: December 2019

The actin cytoskeleton is crucially important to maintenance of the cellular structure, cell motility, and endocytosis. Accordingly, bacterial pathogens often co-opt the actin-restructuring machinery of host cells to access or create a favorable environment for their own replication. The obligate intracellular organism Chlamydia trachomatis and related species exemplify this dynamic: by inducing actin polymerization at the site of pathogen-host attachment, Chlamydiae induce their own uptake by the typically non-phagocytic epithelium they infect. The interaction of chlamydial adhesins with host surface receptors has been implicated in this effect, as has the activity of the chlamydial effector TarP (translocated actin recruitment protein). Following invasion, C. trachomatis dynamically assembles and maintains an actin-rich cage around the pathogen’s membrane-bound replicative niche, known as the chlamydial inclusion. Through further induction of actin polymerization and modulation of the actin-crosslinking protein myosin II, C. trachomatis promotes egress from the host via extrusion of the inclusion. In this review, we present the experimental findings that can inform our understanding of actin-dependent chlamydial pathogenesis, discuss lingering questions, and identify potential avenues of future study.
Correction of RNA-Binding Protein CUGBP1 and GSK3β Signaling as Therapeutic Approach for Congenital and Adult Myotonic Dystrophy Type 1
Authors: Timchenko Lubov
Published: December 2019

Myotonic dystrophy type 1 (DM1) is a complex genetic disease affecting many tissues. DM1 is caused by an expansion of CTG repeats in the 3′-UTR of the DMPK gene. The mechanistic studies of DM1 suggested that DMPK mRNA, containing expanded CUG repeats, is a major therapeutic target in DM1. Therefore, the removal of the toxic RNA became a primary focus of the therapeutic development in DM1 during the last decade. However, a cure for this devastating disease has not been found. Whereas the degradation of toxic RNA remains a preferential approach for the reduction of DM1 pathology, other approaches targeting early toxic events downstream of the mutant RNA could be also considered. In this review, we discuss the beneficial role of the restoring of the RNA-binding protein, CUGBP1/CELF1, in the correction of DM1 pathology. It has been recently found that the normalization of CUGBP1 activity with the inhibitors of GSK3 has a positive effect on the reduction of skeletal muscle and CNS pathologies in DM1 mouse models. Surprisingly, the inhibitor of GSK3, tideglusib also reduced the toxic CUG-containing RNA. Thus, the development of the therapeutics, based on the correction of the GSK3β-CUGBP1 pathway, is a promising option for this complex disease.
SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice
Authors: Pahk Kisoo , Joung Chanmin , Song Hwa Young , Kim Sungeun , Kim Won-Ki
Published: December 2019

Interactions between CD147 and cyclophilin A (CypA) promote plaque rupture that causes atherosclerosis-related cardiovascular events, such as myocardial infarction and stroke. Here, we investigated whether SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one), a novel drug, can exert therapeutic effects against plaque progression and instability through disruption of CD147-CypA interactions in apolipoprotein E-deficient (ApoE KO) mice. Immunocytochemistry and immunoprecipitation analyses were performed to assess the effects of SP-8356 on CD147-CypA interactions. Advanced plaques were induced in ApoE KO mice via partial ligation of the right carotid artery coupled with an atherogenic diet, and SP-8356 (50 mg/kg) orally administrated daily one day after carotid artery ligation for three weeks. The anti-atherosclerotic effect of SP-8356 was assessed using histological and molecular approaches. SP-8356 interfered with CD147-CypA interactions and attenuated matrix metalloproteinase-9 activation. Moreover, SP-8356 induced a decreased in atherosclerotic plaque size in ApoE KO mice and stabilized plaque vulnerability by reducing the necrotic lipid core, suppressing macrophage infiltration, and enhancing fibrous cap thickness through increasing the content of vascular smooth muscle cells. SP-8356 exerts remarkable anti-atherosclerotic effects by suppressing plaque development and improving plaque stability through inhibiting CD147-CypA interactions. Our novel findings support the potential utility of SP-8356 as a therapeutic agent for atherosclerotic plaque.
Urinary Peptidomic Biomarkers in Kidney Diseases
Authors: Sirolli Vittorio , Pieroni Luisa , Di Liberato Lorenzo , Urbani Andrea , Bonomini Mario
Published: December 2019

In order to effectively develop personalized medicine for kidney diseases we urgently need to develop highly accurate biomarkers for use in the clinic, since current biomarkers of kidney damage (changes in serum creatinine and/or urine albumin excretion) apply to a later stage of disease, lack accuracy, and are not connected with molecular pathophysiology. Analysis of urine peptide content (urinary peptidomics) has emerged as one of the most attractive areas in disease biomarker discovery. Urinary peptidome analysis allows the detection of short and long-term physiological or pathological changes occurring within the kidney. Urinary peptidomics has been applied extensively for several years now in renal patients, and may greatly improve kidney disease management by supporting earlier and more accurate detection, prognostic assessment, and prediction of response to treatment. It also promises better understanding of kidney disease pathophysiology, and has been proposed as a “liquid biopsy” to discriminate various types of renal disorders. Furthermore, proteins being the major drug targets, peptidome analysis may allow one to evaluate the effects of therapies at the protein signaling pathway level. We here review the most recent findings on urinary peptidomics in the setting of the most common kidney diseases.
Effects of Gangliosides on Spermatozoa, Oocytes, and Preimplantation Embryos
Authors: Kim Bo Hyun , Ju Won Seok , Kim Ji-Su , Kim Sun-Uk , Park Soon Ju , Ward Sean M. , Lyu Ju Hyeong , Choo Young-Kug
Published: December 2019

Gangliosides are sialic acid-containing glycosphingolipids, which are the most abundant family of glycolipids in eukaryotes. Gangliosides have been suggested to be important lipid molecules required for the control of cellular procedures, such as cell differentiation, proliferation, and signaling. GD1a is expressed in interstitial cells during ovarian maturation in mice and exogenous GD1a is important to oocyte maturation, monospermic fertilization, and embryonic development. In this context, GM1 is known to influence signaling pathways in cells and is important in sperm–oocyte interactions and sperm maturation processes, such as capacitation. GM3 is expressed in the vertebrate oocyte cytoplasm, and exogenously added GM3 induces apoptosis and DNA injury during in vitro oocyte maturation and embryogenesis. As a consequence of this, ganglioside GT1b and GM1 decrease DNA fragmentation and act as H2O2 inhibitors on germ cells and preimplantation embryos. This review describes the functional roles of gangliosides in spermatozoa, oocytes, and early embryonic development.
Long-Term Stability and Differentiation Potential of Cryopreserved cGMP-Compliant Human Induced Pluripotent Stem Cells
Authors: Shafa Mehdi , Walsh Tylor , Panchalingam Krishna Morgan , Richardson Thomas , Menendez Laura , Tian Xinghui , Suresh Babu Sahana , Dadgar Saedeh , Beller Justin , Yang Fan , Baghbaderani Behnam Ahmadian
Published: December 2019

The clinical effectiveness of human induced pluripotent stem cells (iPSCs) is highly dependent on a few key quality characteristics including the generation of high quality cell bank, long-term genomic stability, post-thaw viability, plating efficiency, retention of pluripotency, directed differentiation, purity, potency, and sterility. We have already reported the establishment of iPSC master cell banks (MCBs) and working cell banks (WCBs) under current good manufacturing procedure (cGMP)-compliant conditions. In this study, we assessed the cellular and genomic stability of the iPSC lines generated and cryopreserved five years ago under cGMP-compliant conditions. iPSC lines were thawed, characterized, and directly differentiated into cells from three germ layers including cardiomyocytes (CMs), neural stem cells (NSCs), and definitive endoderm (DE). The cells were also expanded in 2D and 3D spinner flasks to evaluate their long-term expansion potential in matrix-dependent and feeder-free culture environment. All three lines successfully thawed and attached to the L7TM matrix, and formed typical iPSC colonies that expressed pluripotency markers over 15 passages. iPSCs maintained their differentiation potential as demonstrated with spontaneous and directed differentiation to the three germ layers and corresponding expression of specific markers, respectfully. Furthermore, post-thaw cells showed normal karyotype, negative mycoplasma, and sterility testing. These cells maintained both their 2D and 3D proliferation potential after five years of cryopreservation without acquiring karyotype abnormality, loss of pluripotency, and telomerase activity. These results illustrate the long-term stability of cGMP iPSC lines, which is an important step in establishing a reliable, long-term source of starting materials for clinical and commercial manufacturing of iPSC-derived cell therapy products.
Identification and Functional Analysis of Tomato CIPK Gene Family
Authors: Zhang Yao , Zhou Xi’nan , Liu Siyuan , Yu Anzhou , Yang Chuanming , Chen Xiuling , Liu Jiayin , Wang Aoxue
Published: December 2019

The calcineurin B-like interacting protein kinase (CIPK) protein family is a critical protein family in plant signaling pathways mediated by Ca2+, playing a pivotal role in plant stress response and growth. However, to the best of our knowledge, no study of the tomato CIPK gene family in response to abiotic stress has been reported. In this study, 22 members of the tomato CIPK gene family were successfully identified by using a combination of bioinformatics techniques and molecular analyses. The expression level of each member of tomato CIPK gene family under abiotic stress (low temperature, high salt, drought treatment) was determined by qRT-PCR. Results indicated that tomato CIPK demonstrated different degrees of responding to various abiotic stresses, and changes in SlCIPK1 and SlCIPK8 expression level were relatively apparent. The results of qRT-PCR showed that expression levels of SlCIPK1 increased significantly in early stages of cold stress, and the expression level of SlCIPK8 increased significantly during the three treatments at different time points, implicating Solanum lycopersicum CIPK1(SlCIPK1) and Solanum lycopersicum CIPK8 (SlCIPK8) involvement in abiotic stress response. SlCIPK1 and SlCIPK8 were silenced using Virus-induced gene silencing (VIGS), and physiological indexes were detected by low temperature, drought, and high salt treatment. The results showed that plants silenced by SlCIPK1 and SlCIPK8 at the later stage of cold stress were significantly less resistant to cold than wild-type plants. SlCIPK1 and SlCIPK8 silenced plants had poor drought resistance, indicating a relationship between SlCIPK1 and SlCIPK8 with response to low temperature and drought resistance. This is the first study to uncover the nucleotide sequence for tomato CIPK family members and systematically study the changes of tomato CIPK family members under abiotic stress. Here, we investigate the CIPK family’s response under abiotic stress providing understanding into the signal transduction pathway. This study provides a theoretical basis for elucidating the function of tomato CIPK at low temperature and its molecular mechanism of regulating low temperatures.
Identification and Functional Characterization of IDS Gene Mutations Underlying Taiwanese Hunter Syndrome (Mucopolysaccharidosis Type II)
Authors: Lin Hsiang-Yu , Tu Ru-Yi , Chern Schu-Rern , Lo Yun-Ting , Fran Sisca , Wei Fang-Jie , Huang Sung-Fa , Tsai Shin-Yu , Chang Ya-Hui , Lee Chung-Lin , Lin Shuan-Pei , Chuang Chih-Kuang
Published: December 2019

Hunter syndrome (mucopolysaccharidosis II; MPS II) is caused by a defect of the iduronate-2-sulfatase (IDS) gene. Few studies have reported integrated mutation data of Taiwanese MPS II phenotypes. In this study, we summarized genotype and phenotype correlations of confirmed MPS II patients and asymptomatic MPS II infants in Taiwan. Regular polymerase chain reaction and DNA sequencing were used to identify genetic abnormalities of 191 cases, including 51 unrelated patients with confirmed MPS II and 140 asymptomatic infants. IDS activity was analyzed in individual novel IDS variants using in vitro expression studies. Nineteen novel mutations were identified, in which the percentages of IDS activity of the novel missense mutations c.137A>C, c.311A>T, c.454A>C, c.797C>G, c.817C>T, c.998C>T, c.1106C>G, c.1400C>T, c.1402C>T, and c.1403G>A were significantly decreased (p < 0.001), c.254C>T and c.1025A>G were moderately decreased (p < 0.01), and c.851C>T was slightly decreased (p < 0.05) comparing with normal enzyme activity. The activities of the other six missense mutations were reduced but were insignificant. The results of genomic studies and their phenotypes were highly correlated. A greater understanding of the positive correlations may help to prevent the irreversible manifestations of Hunter syndrome, particularly in infants suspected of having asymptomatic MPS II. In addition, urinary glycosaminoglycan assay is important to diagnose Hunter syndrome since gene mutations are not definitive (could be non-pathogenic).
Data Compression Approach for Long-Term Monitoring of Pavement Structures
Authors: Manosalvas-Paredes Mario , Lajnef Nizar , Chatti Karim , Aono Kenji , Blanc Juliette , Thom Nick , Airey Gordon , Lo Presti Davide
Published: December 2019

Pavement structures are designed to withstand continuous damage during their design life. Damage starts as soon as the pavement is open to traffic and increases with time. If maintenance activities are not considered in the initial design or considered but not applied during the service life, damage will grow to a point where rehabilitation may be the only and most expensive option left. In order to monitor the evolution of damage and its severity in pavement structures, a novel data compression approach based on cumulative measurements from a piezoelectric sensor is presented in this paper. Specifically, the piezoelectric sensor uses a thin film of polyvinylidene fluoride to sense the energy produced by the micro deformation generated due to the application of traffic loads. Epoxy solution has been used to encapsulate the membrane providing hardness and flexibility to withstand the high-loads and the high-temperatures during construction of the asphalt layer. The piezoelectric sensors have been exposed to three months of loading (approximately 1.0 million loads of 65 kN) at the French Institute of Science and Technology for Transport, Development and Networks (IFSTTAR) fatigue carrousel. Notably, the sensors survived the construction and testing. Reference measurements were made with a commercial conventional strain gauge specifically designed for measurements in hot mix asphalt layers. Results from the carrousel successfully demonstrate that the novel approach can be considered as a good indicator of damage progression, thus alleviating the need to measure strains in pavement for the purpose of damage tracking.
Thermotropic Liquid-Crystalline Materials Based on Supramolecular Coordination Complexes
Authors: Therrien Bruno
Published: December 2019

Liquid crystals are among us, in living organisms and in electronic devices, and they have contributed to the development of our modern society. Traditionally developed by organic chemists, the field of liquid-crystalline materials is now involving chemists and physicists of all domains (computational, physical, inorganic, supramolecular, electro-chemistry, polymers, materials, etc.,). Such diversity in researchers confirms that the field remains highly active and that new applications can be foreseen in the future. In this review, liquid-crystalline materials developed around coordination complexes are presented, focusing on those showing thermotropic behavior, a relatively unexplored family of compounds.
DNA Barcoding Subtropical Aphids and Implications for Population Differentiation
Authors: Li Qiang , Deng Jun , Chen Cui , Zeng Linda , Lin Xiaolan , Cheng Zhentao , Qiao Gexia , Huang Xiaolei
Published: December 2019

DNA barcoding has proven its worth in species identification, discovering cryptic diversity, and inferring genetic divergence. However, reliable DNA barcode reference libraries that these applications depend on are not available for many taxonomic groups and geographical regions. Aphids are a group of plant sap sucking insects, including many notorious pests in agriculture and forestry. The aphid fauna of the subtropical region has been understudied. In this study, based on extensive sampling effort across main subtropical areas, we sequenced 1581 aphid specimens of 143 morphospecies, representing 75 genera, and 13 subfamilies, to build the first comprehensive DNA barcode library for subtropical aphids. We examined the utility of DNA barcodes in identifying aphid species and population differentiation and evaluated the ability of different species delimitation methods (automatic barcode gap discovery (ABGD), generalized mixed Yule-coalescent (GMYC), and Bayesian Poisson tree processes (bPTP)). We found that most aphid species demonstrated barcode gaps and that a threshold value of 2% genetic distance is suitable for distinguishing most species. Our results indicated that ten morphospecies may have species divergence related to factors such as host plant or geography. By using two pest species Aphis spiraecola and A. gossypii as examples, we also discussed the effect of the sampling scale of host plants on the results and reliability of DNA barcoding of phytophagous insects. This DNA barcode library will be valuable for future studies and applications.
Efficient Delivery of dsRNA and DNA in Cultured Silkworm Cells for Gene Function Analysis Using PAMAM Dendrimers System
Authors: Lu Chenchen , Li Zhiqing , Chang Li , Dong Zhaoming , Guo Pengchao , Shen Guanwang , Xia Qingyou , Zhao Ping
Published: December 2019

Polyamidoamine (PAMAM) dendrimers are emerging as intriguing nanovectors for nucleic acid delivery because of their unique well-defined architecture and high binding capacity, which have been broadly applied in DNA- and RNA-based therapeutics. The low-cost and high-efficiency of PAMAM dendrimers relative to traditional liposomal transfection reagents also promote their application in gene function analysis. In this study, we first investigated the potential use of a PAMAM system in the silkworm model insect. We determined the binding property of G5-PAMAM using dsRNA and DNA in vitro, and substantially achieved the delivery of dsRNA and DNA from culture medium to both silkworm BmN and BmE cells, thus leading to efficient knockdown and expression of target genes. Under treatments with different concentrations of G5-PAMAM, we evaluated its cellular cytotoxicity on silkworm cells, and the results show that G5-PAMAM had no obvious toxicity to cells. The presence of serum in the culture medium did not affect the delivery performance of DNA and dsRNA by G5-PAMAM, revealing its convenient use for various purposes. In conclusion, our data demonstrate that the PAMAM system provides a promising strategy for delivering dsRNA and DNA in cultured silkworm cells and promote its further application in individuals.