bluuebunny/crossref_metadata_2025 huggingface dataset:
Feeling Weary? Feeling Insecure? Are All Workplace Changes Bad News?
Authors: Nikolova Irina , van Dam Karen , Van Ruysseveldt Joris , De Witte Hans
Published: May 2019

Prior research indicates that workplace changes can have both positive and negative consequences for employees. To explore the mechanisms that trigger these different outcomes, we propose and test a mediation model, which builds on the premises of the challenge–hindrance model of work stress. Specifically, we suggest that whereas workplace changes can engender positive outcomes (e.g., learning outcomes) through an increase in learning demands, they can also enhance negative outcomes (e.g., emotional exhaustion) through increased perceptions of qualitative job insecurity. While we made these specific assumptions, we also analyzed the reversed causation relationships. Two-wave data obtained from 1366 Dutch employees were used to test the study hypotheses. The results showed that the reciprocal causation model had the best fit for the data. However, whereas emotional exhaustion was only mediated by qualitative job insecurity, no mediation was found by learning demands. In addition to the hypothesized effects, several reversed causation effects emerged from the analyses, indicating that the relationships between workplace changes and employee learning and strain are not unidirectional. This underscores the need for a broader view on the causes and effects of workplace changes, as the traditional causation relationships (i.e., perceptions of workplace changes impacting employee learning and strain experiences) are insufficient to explain the complex dynamics between the studied phenomena.
The Influence of Audio-Visual Interactions on Psychological Responses of Young People in Urban Green Areas: A Case Study in Two Parks in China
Authors: Zhang Shilun , Zhao Xiaolong , Zeng Zixi , Qiu Xuan
Published: May 2019

Audio-visual interactions in green spaces are important for mental health and wellbeing. However, the influence of audio-visual interactions on psychological responses is still less clear. This study introduced a new method, namely the audio-visual walk (AV-walk), to obtain data on the audio-visual context, audio-visual experiences, and psychological responses in two typical parks, namely Cloves Park and Music Park in Harbin, China. Some interesting results are as follows: First, based on Pearson’s correlation analysis, sound pressure level and roughness were significantly correlated with psychological responses in Cloves Park (p < 0.05). Second, the results of stepwise regression models showed the impact intensity of acoustic comfort was 1.64–1.68 times higher than that of visual comfort on psychological responses of emotion dimension, while visual comfort was 1.35–1.37 times higher than acoustic comfort on psychological responses of cognition dimension in Music Park. In addition, an orthogonal analysis diagram explained the influence of audio-visual interactions on psychological responses of young people. The audio-visual context located beside the waterscape with a relatively higher level of acoustic and visual comfort was the most cheerful (2.60), relaxed (2.45), and energetic (2.05), while the audio-visual context close to an urban built environment tended to be both acoustically and visually uncomfortable, and the psychological state was decreased to the most depressed (−0.25), anxious (−0.75), fatigued (−1.13) and distracted (−1.13).
Qualitative Job Insecurity and Informal Learning: A Longitudinal Test of Occupational Self-Efficacy and Psychological Contract Breach as Mediators
Authors: Van Hootegem Anahí , De Witte Hans
Published: May 2019

Current work life has become increasingly turbulent, which has sparked employees’ concern about the loss of valued job features, coined as qualitative job insecurity. No prior research has investigated the relationship between this type of job insecurity and informal learning. However, informal learning might be particularly relevant for qualitatively job-insecure employees, as it might aid them to deal with the incessant changes in their work environment. This study examined whether qualitative job insecurity is associated with lower levels of three types of informal learning activities: information-seeking, feedback-seeking, and help-seeking behavior, and whether these relationships are mediated by a decline in occupational self-efficacy and an increase in psychological contract breach. We employed a three-wave panel design to survey 1433 Belgian employees. Results, by means of cross-lagged structural equation modelling, demonstrated that occupational self-efficacy mediates the relationship between qualitative job insecurity and information-seeking, feedback-seeking from colleagues, and feedback-seeking from one’s supervisor, while psychological contract breach only mediated the relationship between qualitative job insecurity and feedback-seeking from one’s supervisor. Both mediators were not significantly related to help-seeking behavior. This study demonstrates that qualitatively job-insecure employees are less likely to engage in informal learning via a decrease in occupational self-efficacy and an increase in psychological contract breach, thereby becoming even more vulnerable in an increasingly volatile work environment.
Comparative Analysis of Calcium-Dependent Protein Kinase in Cucurbitaceae and Expression Studies in Watermelon
Authors: Wei Chunhua , Zhang Ruimin , Yang Xiaozhen , Zhu Chunyu , Li Hao , Zhang Yong , Ma Jianxiang , Yang Jianqiang , Zhang Xian
Published: May 2019

Both the calcium-dependent protein kinases (CDPKs) and CDPK-related kinases (CRKs) play numerous roles in plant growth, development, and stress response. Despite genome-wide identification of both families in Cucumis, comparative evolutionary and functional analysis of both CDPKs and CRKs in Cucurbitaceae remain unclear. In this study, we identified 128 CDPK and 56 CRK genes in total in six Cucurbitaceae species (C. lanatus, C. sativus, C. moschata, C. maxima, C. pepo, and L. siceraria). Dot plot analysis indicated that self-duplication of conserved domains contributed to the structural variations of two CDPKs (CpCDPK19 and CpCDPK27) in C. pepo. Using watermelon genome as reference, an integrated map containing 25 loci (16 CDPK and nine CRK loci) was obtained, 16 of which (12 CDPK and four CRK) were shared by all seven Cucurbitaceae species. Combined with exon-intron organizations, topological analyses indicated an ancient origination of groups CDPK IV and CRK. Moreover, the evolutionary scenario of seven modern Cucurbitaceae species could also be reflected on the phylogenetic trees. Expression patterns of ClCDPKs and ClCRKs were studied under different abiotic stresses. Some valuable genes were uncovered for future gene function exploration. For instance, both ClCDPK6 and its ortholog CsCDPK14 in cucumber could be induced by salinity, while ClCDPK6 and ClCDPK16, as well as their orthologs in Cucumis, maintained high expression levels in male flowers. Collectively, these results provide insights into the evolutionary history of two gene families in Cucurbitaceae, and indicate a subset of candidate genes for functional characterizations in the future.
Transcriptome Analysis to Shed Light on the Molecular Mechanisms of Early Responses to Cadmium in Roots and Leaves of King Grass (Pennisetum americanum × P. purpureum)
Authors: Zhao Junming , Xia Bo , Meng Yu , Yang Zhongfu , Pan Ling , Zhou Man , Zhang Xinquan
Published: May 2019

King grass, a hybrid grass between pearl millet and elephant grass, has many excellent characteristics such as high biomass yield, great stress tolerance, and enormous economic and ecological value, which makes it ideal for development of phytoremediation. At present, the physiological and molecular response of king grass to cadmium (Cd) stress is poorly understood. Transcriptome analysis of early response (3 h and 24 h) of king grass leaves and roots to high level Cd (100 µM) has been investigated and has shed light on the molecular mechanism underlying Cd stress response in this hybrid grass. Our comparative transcriptome analysis demonstrated that in combat with Cd stress, king grass roots have activated the glutathione metabolism pathway by up-regulating glutathione S-transferases (GSTs) which are a multifunctional family of phase II enzymes that detoxify a variety of environmental chemicals, reactive intermediates, and secondary products of oxidative damages. In roots, early inductions of phenylpropanoid biosynthesis and phenylalanine metabolism pathways were observed to be enriched in differentially expressed genes (DEGs). Meanwhile, oxidoreductase activities were significantly enriched in the first 3 h to bestow the plant cells with resistance to oxidative stress. We also found that transporter activities and jasmonic acid (JA)-signaling might be activated by Cd in king grass. Our study provided the first-hand information on genome-wide transcriptome profiling of king grass and novel insights on phytoremediation.
Review of the Effect of Natural Compounds and Extracts on Neurodegeneration in Animal Models of Diabetes Mellitus
Authors: Infante-Garcia Carmen , Garcia-Alloza Monica
Published: May 2019

Diabetes mellitus is a chronic metabolic disease with a high prevalence in the Western population. It is characterized by pancreas failure to produce insulin, which involves high blood glucose levels. The two main forms of diabetes are type 1 and type 2 diabetes, which correspond with >85% of the cases. Diabetes shows several associated alterations including vascular dysfunction, neuropathies as well as central complications. Brain alterations in diabetes are widely studied; however, the mechanisms implicated have not been completely elucidated. Diabetic brain shows a wide profile of micro and macrostructural changes, such as neurovascular deterioration or neuroinflammation leading to neurodegeneration and progressive cognition dysfunction. Natural compounds (single isolated compounds and/or natural extracts) have been widely assessed in metabolic disorders and many of them have also shown antioxidant, antiinflamatory and neuroprotective properties at central level. This work reviews natural compounds with brain neuroprotective activities, taking into account several therapeutic targets: Inflammation and oxidative stress, vascular damage, neuronal loss or cognitive impairment. Altogether, a wide range of natural extracts and compounds contribute to limit neurodegeneration and cognitive dysfunction under diabetic state. Therefore, they could broaden therapeutic alternatives to reduce or slow down complications associated with diabetes at central level.
GI inflammation Increases Sodium-Glucose Cotransporter Sglt1
Authors: Park Jiyoung , Lee In-Seung , Kim Kang-Hoon , Kim Yumi , An Eun-Jin , Jang Hyeung-Jin
Published: May 2019

A correlation between gastrointestinal (GI) inflammation and gut hormones has reported that inflammatory stimuli including bacterial endotoxins, lipopolysaccharides (LPS), TNFα, IL-1β, and IL-6 induces high levels of incretin hormone leading to glucose dysregulation. Although incretin hormones are immediately secreted in response to environmental stimuli, such as nutrients, cytokines, and LPS, but studies of glucose-induced incretin secretion in an inflamed state are limited. We hypothesized that GI inflammatory conditions induce over-stimulated incretin secretion via an increase of glucose-sensing receptors. To confirm our hypothesis, we observed the alteration of glucose-induced incretin secretion and glucose-sensing receptors in a GI inflammatory mouse model, and we treated a conditioned media (Mϕ 30%) containing inflammatory cytokines in intestinal epithelium cells and enteroendocrine L-like NCI-H716 cells. In GI-inflamed mice, we observed that over-stimulated incretin secretion and insulin release in response to glucose and sodium glucose cotransporter (Sglt1) was increased. Incubation with Mϕ 30% increases Sglt1 and induces glucose-induced GLP-1 secretion with increasing intracellular calcium influx. Phloridzin, an sglt1 inhibitor, inhibits glucose-induced GLP-1 secretion, ERK activation, and calcium influx. These findings suggest that the abnormalities of incretin secretion leading to metabolic disturbances in GI inflammatory disease by an increase of Sglt1.
Quantitative Proteomic Analysis Reveals Novel Insights into Intracellular Silicate Stress-Responsive Mechanisms in the Diatom Skeletonema dohrnii
Authors: Thangaraj Satheeswaran , Shang Xiaomei , Sun Jun , Liu Haijiao
Published: May 2019

Diatoms are a successful group of marine phytoplankton that often thrives under adverse environmental stress conditions. Members of the Skeletonema genus are ecologically important which may subsist during silicate stress and form a dense bloom following higher silicate concentration. However, our understanding of diatoms’ underlying molecular mechanism involved in these intracellular silicate stress-responses are limited. Here an iTRAQ-based proteomic method was coupled with multiple physiological techniques to explore distinct cellular responses associated with oxidative stress in the diatom Skeletonema dohrnii to the silicate limitation. In total, 1768 proteins were detected; 594 proteins were identified as differentially expressed (greater than a two-fold change; p < 0.05). In Si-limited cells, downregulated proteins were mainly related to photosynthesis metabolism, light-harvesting complex, and oxidative phosphorylation, corresponding to inducing oxidative stress, and ROS accumulation. None of these responses were identified in Si-limited cells; in comparing with other literature, Si-stress cells showed that ATP-limited diatoms are unable to rely on photosynthesis, which will break down and reshuffle carbon metabolism to compensate for photosynthetic carbon fixation losses. Our findings have a good correlation with earlier reports and provides a new molecular level insight into the systematic intracellular responses employed by diatoms in response to silicate stress in the marine environment.
Pathophysiology of Fibrosis in the Vocal Fold: Current Research, Future Treatment Strategies, and Obstacles to Restoring Vocal Fold Pliability
Authors: Kumai Yoshihiko
Published: May 2019

Communication by voice depends on symmetrical vibrations within the vocal folds (VFs) and is indispensable for various occupations. VF scarring is one of the main reasons for permanent dysphonia and results from injury to the unique layered structure of the VFs. The increased collagen and decreased hyaluronic acid within VF scars lead to a loss of pliability of the VFs and significantly decreases their capacity to vibrate. As there is currently no definitive treatment for VF scarring, regenerative medicine and tissue engineering have become increasingly important research areas within otolaryngology. Several recent reviews have described the problem of VF scarring and various possible solutions, including tissue engineered cells and tissues, biomaterial implants, stem cells, growth factors, anti-inflammatory cytokines antifibrotic agents. Despite considerable research progress, these technical advances have not been established as routine clinical procedures. This review focuses on emerging techniques for restoring VF pliability using various approaches. We discuss our studies on interactions among adipose-derived stem/stromal cells, antifibrotic agents, and VF fibroblasts using an in vitro model. We also identify some obstacles to advances in research.
Chemokine CXCL13 as a New Systemic Biomarker for B-Cell Involvement in Acute T Cell-Mediated Kidney Allograft Rejection
Authors: Schiffer Lena , Wiehler Flavia , Bräsen Jan Hinrich , Gwinner Wilfried , Greite Robert , Kreimann Kirill , Thorenz Anja , Derlin Katja , Teng Beina , Rong Song , von Vietinghoff Sibylle , Haller Hermann , Mengel Michael , Pape Lars , Lerch Christian , Schiffer Mario , Gueler Faikah
Published: May 2019

The presence of B-cell clusters in allogenic T cell-mediated rejection (TCMR) of kidney allografts is linked to more severe disease entities. In this study we characterized B-cell infiltrates in patients with TCMR and examined the role of serum CXCL-13 in these patients and experimentally. CXCL-13 serum levels were analyzed in 73 kidney allograft recipients at the time of allograft biopsy. In addition, four patients were evaluated for CXCL13 levels during the first week after transplantation. ELISA was done to measure CXCL-13 serum levels. For further mechanistic understanding, a translational allogenic kidney transplant (ktx) mouse model for TCMR was studied in BalbC recipients of fully mismatched transplants with C57BL/6 donor kidneys. CXCL-13 serum levels were measured longitudinally, CD20 and CD3 composition and CXCL13 mRNA in tissue were examined by flow cytometry and kidneys were examined by histology and immunohistochemistry. We found significantly higher serum levels of the B-cell chemoattractant CXCL13 in patients with TCMR compared to controls and patients with borderline TCMR. Moreover, in patients with acute rejection within the first week after ktx, a >5-fold CXCL13 increase was measured and correlated with B-cell infiltrates in the biopsies. In line with the clinical findings, TCMR in mice correlated with increased systemic serum-CXCL13 levels. Moreover, renal allografts had significantly higher CXCL13 mRNA expression than isogenic controls and showed interstitial CD20+ B-cell clusters and CD3+ cell infiltrates accumulating in the vicinity of renal vessels. CXCL13 blood levels correlate with B-cell involvement in TCMR and might help to identify patients at risk of a more severe clinical course of rejection.
Fighting Thyroid Cancer with Microgravity Research
Authors: Krüger Marcus , Melnik Daniela , Kopp Sascha , Buken Christoph , Sahana Jayashree , Bauer Johann , Wehland Markus , Hemmersbach Ruth , Corydon Thomas J. , Infanger Manfred , Grimm Daniela
Published: May 2019

Microgravity in space or simulated by special ground-based devices provides an unusual but unique environment to study and influence tumour cell processes. By investigating thyroid cancer cells in microgravity for nearly 20 years, researchers got insights into tumour biology that had not been possible under normal laboratory conditions: adherently growing cancer cells detach from their surface and form three-dimensional structures. The cells included in these multicellular spheroids (MCS) were not only altered but behave also differently to those grown in flat sheets in normal gravity, more closely mimicking the conditions in the human body. Therefore, MCS became an invaluable model for studying metastasis and developing new cancer treatment strategies via drug targeting. Microgravity intervenes deeply in processes such as apoptosis and in structural changes involving the cytoskeleton and the extracellular matrix, which influence cell growth. Most interestingly, follicular thyroid cancer cells grown under microgravity conditions were shifted towards a less-malignant phenotype. Results from microgravity research can be used to rethink conventional cancer research and may help to pinpoint the cellular changes that cause cancer. This in turn could lead to novel therapies that will enhance the quality of life for patients or potentially develop new preventive countermeasures.
Effect of Bilastine on Diabetic Nephropathy in DBA2/J Mice
Authors: Verta Roberta , Grange Cristina , Gurrieri Maura , Borga Sara , Nardini Patrizia , Argenziano Monica , Ghè Corrado , Cavalli Roberta , Benetti Elisa , Miglio Gianluca , Bussolati Benedetta , Pini Alessandro , Rosa Arianna Carolina
Published: May 2019

Diabetic nephropathy is an unmet therapeutic need, and the search for new therapeutic strategies is warranted. Previous data point to histamine H1 receptor as a possible target for glomerular dysfunction associated with long term hyperglycaemia. Therefore, this study investigated the effects of the H1 receptor antagonist bilastine on renal morphology and function in a murine model of streptozotocin-induced diabetes. Diabetes was induced in DBA2/J male mice and, from diabetes onset (glycaemia ≥200 mg/dL), mice received bilastine (1–30 mg/kg/day) by oral gavage for 14 consecutive weeks. At the end of the experimental protocol, diabetic mice showed polyuria (+195.5%), increase in Albumin-to-Creatine Ratio (ACR, +284.7%), and a significant drop in creatinine clearance (p < 0.05). Bilastine prevented ACR increase and restored creatinine clearance in a dose-dependent manner, suggesting a positive effect on glomerular filtration. The ultrastructural analysis showed a preserved junctional integrity. Preservation of the basal nephrin, P-cadherin, and synaptopodin expression could explain this effect. In conclusion, the H1 receptor could contribute to the glomerular damage occurring in diabetic nephropathy. Bilastine preserved the glomerular junctional integrity, leading to the hypothesis of anti-H1 antihistamines as a possible add-on therapy for diabetic nephropathy.
Molecular-Based Treatment Strategies for Osteoporosis: A Literature Review
Authors: Ukon Yuichiro , Makino Takahiro , Kodama Joe , Tsukazaki Hiroyuki , Tateiwa Daisuke , Yoshikawa Hideki , Kaito Takashi
Published: May 2019

Osteoporosis is an unavoidable public health problem in an aging or aged society. Anti-resorptive agents (calcitonin, estrogen, and selective estrogen-receptor modulators, bisphosphonates, anti-receptor activator of nuclear factor κB ligand antibody along with calcium and vitamin D supplementations) and anabolic agents (parathyroid hormone and related peptide analogs, sclerostin inhibitors) have major roles in current treatment regimens and are used alone or in combination based on the pathological condition. Recent advancements in the molecular understanding of bone metabolism and in bioengineering will open the door to future treatment paradigms for osteoporosis, including antibody agents, stem cells, and gene therapies. This review provides an overview of the molecular mechanisms, clinical evidence, and potential adverse effects of drugs that are currently used or under development for the treatment of osteoporosis to aid clinicians in deciding how to select the best treatment option.
Adipokinome Signatures in Obese Mouse Models Reflect Adipose Tissue Health and Are Associated with Serum Lipid Composition
Authors: Knebel Birgit , Fahlbusch Pia , Poschmann Gereon , Dille Matthias , Wahlers Natalie , Stühler Kai , Hartwig Sonja , Lehr Stefan , Schiller Martina , Jacob Sylvia , Kettel Ulrike , Müller-Wieland Dirk , Kotzka Jörg
Published: May 2019

Adipocyte and hepatic lipid metabolism govern whole-body metabolic homeostasis, whereas a disbalance of de novo lipogenesis (DNL) in fat and liver might lead to obesity, with severe co-morbidities. Nevertheless, some obese people are metabolically healthy, but the “protective” mechanisms are not yet known in detail. Especially, the adipocyte-derived molecular mediators that indicate adipose functionality are poorly understood. We studied transgenic mice (alb-SREBP-1c) with a “healthy” obese phenotype, and obob mice with hyperphagia-induced “sick” obesity to analyze the impact of the tissue-specific DNL on the secreted proteins, i.e., the adipokinome, of the primary adipose cells by label-free proteomics. Compared to the control mice, adipose DNL is reduced in both obese mouse models. In contrast, the hepatic DNL is reduced in obob but elevated in alb-SREBP-1c mice. To investigate the relationship between lipid metabolism and adipokinomes, we formulated the “liver-to-adipose-tissue DNL” ratio. Knowledge-based analyses of these results revealed adipocyte functionality with proteins, which was involved in tissue remodeling or metabolism in the alb-SREBP-1c mice and in the control mice, but mainly in fibrosis in the obob mice. The adipokinome in “healthy” obesity is similar to that in a normal condition, but it differs from that in “sick” obesity, whereas the serum lipid patterns reflect the “liver-to-adipose-tissue DNL” ratio and are associated with the adipokinome signature.
Information Usage Behavior and Importance: Korean Scientist and Engineer Users of a Personalized Recommendation Service
Authors: Park Jung-Hoon , Park Seong Eun , Choi Hee-Seok , Hwang Yun-Young
Published: May 2019

Background: We conducted research on the newly developed personalized recommendation service (PRS) of the global network of Korean scientists and engineers (KOSEN) in order to explore the information usage behavior and importance of the PRS used by Korean scientists and engineers. Methods: In order to understand information usage behavior, we gathered data from 513 survey results and analyzed them in terms of information usage behavior and the corresponding importance in each of the service quality areas. Results: We analyzed the 321 outcomes that indicated non-use of the PRS in order to understand the underlying reason(s); we employed 192 results that demonstrated the use of functionality to examine information usage behavior and importance. They found that the predominant motive for non-use of the service resulted from the respondents not knowing how to use it. According to demographic characteristics, the usage behavior of the PRS showed a difference regarding the purpose of using the service in the categories of gender and major field of study. Furthermore, users were concerned with various components of the PRS such as ease of use, design, relevance of content, user support, and interactivity. Conclusions: We suggest reinforcing user education degree and promotion to enhance the PRS. Since users were concerned with ease of use, design, relevance, user support, and interactivity, we recommend these as major points for improvement.
Perioperative Factors for Predicting the Need for Postoperative Intensive Care after Major Lung Resection
Authors: Kim Seung Hyun , Na Sungwon , Park Seong Yong , Lee Jinae , Kang Yhen-Seung , Jung Hwan-ho , Kim Jeongmin
Published: May 2019

Postoperative management after major lung surgery is critical. This study evaluates risk factors for predicting mandatory intensive care unit (ICU) admission immediately after major lung resection. We retrospectively reviewed patients for whom the surgeon requested an ICU bed before major lung resection surgery. Patients were classified into three groups. Univariable and multivariable logistic regression analyses were performed, and a clinical nomogram was constructed. Among 340 patients, 269, 50, and 21 were classified into the no need for ICU, mandatory ICU admission, and late-onset complication groups, respectively. Predictive postoperative diffusion capacity of the lung for carbon monoxide (47.2 (interquartile range (IQR) 43.3–65.7)% versus vs. 67.8 (57.1–79.7)%; p = 0.003, odds ratio (OR) 0.969, 95% confidence interval (CI) 0.95–0.99), intraoperative blood loss (400.00 (250.00–775.00) mL vs. 100.00 (50.00–250.00) mL; p = 0.040, OR 1.001, 95% CI 1.000–1.002), and open thoracotomy (p = 0.030, OR 2.794, 95% CI 1.11–7.07) were significant predictors for mandatory ICU admission. The risk estimation nomogram demonstrated good accuracy in estimating the risk of mandatory ICU admission (concordance index 83.53%). In order to predict the need for intensive care after major lung resection, preoperative and intraoperative factors need to be considered.
Computational Simulations Identify Pyrrolidine-2,3-Dione Derivatives as Novel Inhibitors of Cdk5/p25 Complex to Attenuate Alzheimer’s Pathology
Authors: Zeb Amir , Kim Donghwan , Alam Sayed , Son Minky , Kumar Raj , Rampogu Shailima , Parameswaran Saravanan , Shelake Rahul , Rana Rabia , Parate Shraddha , Kim Jae-Yean , Lee Keun
Published: May 2019

Mechanistically, neurotoxic insults provoke Ca2+-mediated calpain activation, which cleaves the cytoplasmic region of membrane-embedded p35 and produces its truncated form p25. Upon physical interaction, cyclin-dependent kinase 5 (Cdk5) and p25 forms hyperactivated Cdk5/p25 complex and causes severe neuropathological aberrations including hyperphosphorylated tau-mediated neurofibrillary tangles formation, Alzheimer’s symptoms, and neuronal death. Therefore, the inhibition of Cdk5/p25 complex may relieve p-tau-mediated Alzheimer’s pathology. Herein, computational simulations have identified pyrrolidine-2,3-dione derivatives as novel inhibitors of Cdk5/p25 complex. A ligand-based pharmacophore was designed and employed as 3D query to retrieve drug-like molecules from chemical databases. By molecular docking, drug-like molecules obtaining dock score > 67.67 (Goldcore of the reference compound) were identified. Molecular dynamics simulation and binding free energy calculation retrieved four pyrrolidine-2,3-dione derivatives as novel candidate inhibitors of Cdk5/p25. The root means square deviation of Cdk5/p25 in complex with candidate inhibitors obtained an average value of ~2.15 Å during the 30 ns simulation period. Molecular interactions analysis suggested that each inhibitor occupied the ATP-binding site of Cdk5/p25 and formed stable interactions. Finally, the binding free energy estimation suggested that each inhibitor had lowest binding energy than the reference compound (−113.10 kJ/mol) to recapitulate their strong binding with Cdk5/p25. Overall, these inhibitors could mitigate tau-mediated Alzheimer’s phenotype.
Retinoids in Stellate Cells: Development, Repair, and Regeneration
Authors: Carmona Rita , Barrena Silvia , Muñoz-Chápuli Ramón
Published: May 2019

Stellate cells, either hepatic (HSCs) or pancreatic (PSCs), are a type of interstitial cells characterized by their ability to store retinoids in lipid vesicles. In pathological conditions both HSCs and PSCs lose their retinoid content and transform into fibroblast-like cells, contributing to the fibrogenic response. HSCs also participate in other functions including vasoregulation, drug detoxification, immunotolerance, and maintenance of the hepatocyte population. PSCs maintain pancreatic tissue architecture and regulate pancreatic exocrine function. Recently, PSCs have attracted the attention of researchers due to their interactions with pancreatic ductal adenocarcinoma cells. PSCs promote tumour growth and angiogenesis, and their fibrotic activity increases the resistance of pancreatic cancer to chemotherapy and radiation. We are reviewing the current literature concerning the role played by retinoids in the physiology and pathophysiology of the stellate cells, paying attention to their developmental aspects as well as the function of stellate cells in tissue repair and organ regeneration.
Influence of a Specific Aquatic Program on Social and Gross Motor Skills in Adolescents with Autism Spectrum Disorders: Three Case Reports
Authors: Battaglia Giuseppe , Agrò Gianna , Cataldo Pietro , Palma Antonio , Alesi Marianna
Published: May 2019

Swimming pool activities revealed to be efficacious to train psychomotor skills and increase adaptive behaviors in children with Autism Spectrum Disorders (ASD). Therefore, the purpose of this study was to investigate the efficacy of a specific multi-systemic aquatic therapy (CI-MAT) on gross motor and social skills in three adolescents with Autism Spectrum Disorders (ASD). Methods: three adolescents with ASD of which two boys (M1 with a chronological age of 10.3 years and a mental age of 4.7 years; M2 with a chronological age of 14.6 and a mental age inferior to 4 years) and one girl (chronological age of 14.0 and a mental age inferior to 4 years). The study was divided into three phases: baseline, 12-week CI-MAT program and Post-Test. Participants were administered a battery of tests incorporating anthropometric measurements, gross motor development test and a social skills questionnaire before and after a 12-week MAT-CI program. Results: Subjects improved locomotors and object control skills following the CI-MAT program in a different way. Concerning social behaviors, the higher proportion of gains was observed in the sensitivity of other’s presence and eye contact, for the contact domain, and in the comply turn for the relationship domain. Conclusions: The results of this study showed that the CI-MAT program was effective for the development of gross-motor skills and social behaviors in subjects with ASD. Moreover there is an urge to carry out a whole psychological assessment targeting both motor and adaptive development suitable to provide educational and vocational plans of exercises for people with ASD.
Primary Care Physicians’ Knowledge, Attitudes, and Experience with Personal Genetic Testing
Authors: Haga Susanne B. , Kim Esther , Myers Rachel A. , Ginsburg Geoffrey S.
Published: May 2019

Primary care providers (PCPs) will play an important role in precision medicine. However, their lack of training and knowledge about genetics and genomics may limit their ability to advise patients or interpret or utilize test results. We evaluated PCPs’ awareness of the role of genetics/genomics in health, knowledge about key concepts in genomic medicine, perception/attitudes towards direct-to-consumer (DTC) genetic testing, and their level of confidence/comfort in discussing testing with patients prior to and after undergoing DTC testing through the 23andMe Health + Ancestry Service. A total of 130 PCPs completed the study. Sixty-three percent were board-certified in family practice, 32% graduated between 1991 and 2000, and 88% had heard of 23andMe prior to the study. Seventy-two percent decided to participate in the study to gain a better understanding about testing. At baseline, 23% of respondents indicated comfort discussing genetics as a risk factor for common diseases, increasing to 59% after undergoing personal genetic testing (PGT) (p < 0.01). In summary, we find that undergoing PGT augments physicians’ confidence, comfort, and interest in DTC testing.
Effect of Heat Treatment on Microstructures and Mechanical Properties of a Novel β-Solidifying TiAl Alloy
Authors: Cui Ning , Wu Qianqian , Bi Kexiao , Xu Tiewei , Kong Fantao
Published: May 2019

The effect of heat treatment on the microstructures and mechanical properties of a novel β-solidifying Ti–43Al–2Cr–2Mn–0.2Y alloy was investigated. A fully lamellar (FL) microstructure with a colony size of about 100 μm was obtained by heat treatment at 1320 °C/10 min/furnace cooling (FC). A duplex (DP) microstructure with globular γ grains and γ/α2 lamellae was obtained by heat treatment at 1250 °C/4 h/FC. The residual hard–brittle β0 phase was also eliminated after heat treatment. The mechanical properties of the β-solidifying TiAl alloy depended closely on the heat treatment. The FL alloy had better fracture toughness, and the fracture toughness (KIC) value was 24.15 MPa·m1/2. The DP alloy exhibited better ductility, and the room temperature (RT) elongation of the alloy could reach 1%. The elongation of the alloy with different microstructures sharply increased when the temperature increased from 700 to 750 °C, indicating that the microstructure had no effect on the ductile–brittle transition temperature of the β-solidifying TiAl alloy. The fracture morphologies of different tensile specimens were observed. Interlamellar and translamellar fractures were the main fracture features of the FL alloy. Intergranular, translamellar, and interlamellar fractures were the main fracture features of the DP alloy.
Microwave-assisted Synthesis of Hexagonal Gold Nanoparticles Reduced by Organosilane (3-Mercaptopropyl)trimethoxysilane
Authors: Shah Kwok Wei , Zheng Long
Published: May 2019

A novel synthesis of hexagonal gold nanoparticles (Au NPs) via hydrolyzed organosilane (3-mercaptopropyl)trimethoxysilane (MPTMS) using an ultrafast and environmentally friendly method is presented in this study. For the first time, organosilane MPTMS is used for chemical reduction of auric acid under ultrafast microwave irradiation. To the best of our knowledge, the use of organosilane for the synthesis of Au NPs has not been reported. The entire one-step process is convenient, rapid and cost-effective, as well as eco-friendly under alcohol-free aqueous media. Different characterization methods were carried out to investigate the properties of synthesized gold nanoparticles. transmission electron microscopy and scanning electron microscopy were used to investigate the morphology of as-synthesized Au NPs, while X-ray powder diffraction was applied to obtain the crystalline nature. Nuclear magnetic resonance was used to track the hydrolysis of organosilane MPTMS, which is employed for the first time as a reducing agent for the synthesis of Au NPs. The impact from microwave irradiation time and power, as well as the catalytic property of as-synthesized Au NPs, was investigated via ultraviolet–visible spectroscopy. The as-synthesized products include gold nanohexagon and two-dimensional hexagonal gold nanoplatelets, both of which are single-crystal with (1 1 1) planes as basal surfaces. From UV-vis spectra, it is found that the facile water-based fabrication of hexagonal Au NPs began within seconds of microwave irradiation and the size growth increased with the microwave power and time. Moreover, the efficient reduction of 4-nitrophenol to 4-aminophenol in the presence of as-synthesized Au NPs was observed, exhibiting a remarkable catalytic activity. The present simple, rapid and convenient one-step microwave process possess high scalability and useful for future applications such as catalysis, medical, biological, plasmonic sensors and electronics.
Preparation and Characterization of New Environmentally Friendly Starch-Cellulose Materials Modified with Casein or Gelatin for Agricultural Applications
Authors: Prochoń Mirosława , Marzec Anna , Szadkowski Bolesław
Published: May 2019

The purpose of this work was to prepare new biodegradable starch-cellulose composites, with starch, using casein and gelatin as natural nutrients. The physico-chemical properties of the starch films and cellulose fabrics with starch coatings were studied by Fourier transformation infrared analysis, laser confocal scanning microscopy (LCSM), scanning electron microscopy (SEM), UV-Vis spectroscopy, swelling tests, mechanical tests, thermal analysis thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The susceptibility of the starch films to biodegradation was investigated, together with their resistance to thermo-oxidative aging. As a result of the formation of the starch films, both the casein and gelatin macromolecules were able to interact directly with the starch matrix and the fractions of unbranched amylose and branched amylopectin it contained. This interaction was visible as changes in the absorption bands of the polar groups, as revealed by infrared analysis. Spectral analysis of the cellulose fabrics coated with starch films suggests that hydrogen bridges formed between the micelles of long cellulose filaments and the micro and macro-fibers of the starch pectins. An applicative test revealed that when used as a covering for bean cultivation the cellulose-starch composites act as a fertilizing component, contributing to significantly improved growth of Phaseolus vulgaris in comparison to the use of unmodified cellulose.
Sensitivity and Uncertainty Analysis of One-Dimensional Tanaka and Liang-Rogers Shape Memory Alloy Constitutive Models
Authors: Islam A. B. M. Rezaul , Karadoğan Ernur
Published: May 2019

A shape memory alloy (SMA) can remember its original shape and recover from strain due to loading once it is exposed to heat (shape memory effect). SMAs also exhibit elastic response to applied stress above the characteristic temperature at which transformation to austenite is completed (pseudoelasticity or superelasticity). Shape memory effect and pseudoelasticity of SMAs have been addressed by several microscopic thermodynamic and macroscopic phenomenological models using different modeling approaches. The Tanaka and Liang-Rogers models are two of the most widely used macroscopic phenomenological constitutive models for describing SMA behavior. In this paper, we performed sensitivity and uncertainty analysis using Sobol and extended Fourier Amplitude Sensitivity Testing (eFAST) methods for the Tanaka and Liang-Rogers models at different operating temperatures and loading conditions. The stress-dependent and average sensitivity indices have been analyzed and are presented for determining the most influential parameters for these models. The results show that variability is primarily caused by a change in operating temperature and loading conditions. Both models appear to be influenced by the uncertainty in elastic modulus of the material significantly. The analyses presented in this paper aim to provide a better insight for designing applications using SMAs by increasing the understanding of these models’ sensitivity to the input parameters and the cause of output variability due to uncertainty in the same input parameters.
Unified First Order Inertial Element Based Model of Magnetostrictive Hysteresis and Lift-Off Phenomenon
Authors: Szewczyk Roman
Published: May 2019

The present paper presents a new model of magnetostrictive hysteresis loop. A unified approach of both the hysteresis of λ(B) relation, as well as the lift-off phenomenon is proposed, which are explained together on the base of the response of the first order inertial element. Considering previously presented reports, the Maxwell–Boltzmann distribution based model of magnetostrictive characteristics with local maxima, enables modeling magnetostrictive loops. The model was validated on the results of measurements of magnetostrictive hysteresis loops of Mn0.70Zn0.24Fe2.06O4 ferrite for power applications. Good agreement was confirmed for major magnetostrictive loop, especially for smaller values of flux density. As a result, the proposed model may be used for modeling the magnetostrictive response of inductive components of electrical machines, power conversion devices or magnetostrictive actuators.
The Proof-of-the-Concept of Application of Pelletization for Mitigation of Volatile Organic Compounds Emissions from Carbonized Refuse-Derived Fuel
Authors: Białowiec Andrzej , Micuda Monika , Szumny Antoni , Łyczko Jacek , Koziel Jacek
Published: May 2019

Waste can be effectively reused through the production of carbonized refuse-derived fuel (CRDF) that enables further energy recovery. Developing cleaner production of CRDF requires consideration of practical issues of storage and handling. Thus, it needs to be ensured that CRDF does not pose an excessive risk to humans and the ecosystem. Very few studies indicate a wide variety of volatile organic compounds (VOCs) are present in CRDF, some of which are toxic. During handling, storage, transportation, and use of VOC-rich CRDF, workers and end-users could be exposed to emissions that could pose a health and safety hazard. Our recent study shows that CRDF densification via pelletization can increase the efficiency of storage and transportation. Thus, the following research question was identified: can pelletization mitigate VOCs emissions from CRDF during storage? Preliminary research aiming at the determination of the influence of CRDF pelletization on VOCs emission during storage was completed to address this question. The VOCs emissions from two types of CRDF: ground (loose, torrefied refuse-derived fuel (RDF)) and pelletized, were measured. Pelletization reduced the VOCs emissions potential during the four-day storage by ~86%, in comparison with ground CRDF. Mitigation of VOCs emissions from densified CRDF is feasible, and research is warranted to understand the influence of structural modification on VOCs emission kinetics, and possibilities of scaling up this solution into the practice of cleaner storage and transportation of CRDF.
On Subtrees of Fan Graphs, Wheel Graphs, and “Partitions” of Wheel Graphs under Dynamic Evolution
Authors: Yang Yu , Wang An , Wang Hua , Zhao Wei-Ting , Sun Dao-Qiang
Published: May 2019

The number of subtrees, or simply the subtree number, is one of the most studied counting-based graph invariants that has applications in many interdisciplinary fields such as phylogenetic reconstruction. Motivated from the study of graph surgeries on evolutionary dynamics, we consider the subtree problems of fan graphs, wheel graphs, and the class of graphs obtained from “partitioning” wheel graphs under dynamic evolution. The enumeration of these subtree numbers is done through the so-called subtree generation functions of graphs. With the enumerative result, we briefly explore the extremal problems in the corresponding class of graphs. Some interesting observations on the behavior of the subtree number are also presented.
On the Approximation of a Nonlinear Biological Population Model Using Localized Radial Basis Function Method
Authors: Uddin Marjan , Ali Hazrat , Taufiq Muhammad
Published: May 2019

A localized radial basis function meshless method is applied to approximate a nonlinear biological population model with highly satisfactory results. The method approximates the derivatives at every point corresponding to their local support domain. The method is well suited for arbitrary domains. Compared to the finite element and element free Galerkin methods, no integration tool is required. Four examples are demonstrated to check the efficiency and accuracy of the method. The results are compared with an exact solution and other methods available in literature.
Synthetic Pinnatoxins A and G Reversibly Block Mouse Skeletal Neuromuscular Transmission In Vivo and In Vitro
Authors: Benoit Evelyne , Couesnon Aurélie , Lindovsky Jiri , Iorga Bogdan I. , Aráoz Rómulo , Servent Denis , Zakarian Armen , Molgó Jordi
Published: May 2019

Pinnatoxins (PnTXs) A-H constitute an emerging family belonging to the cyclic imine group of phycotoxins. Interest has been focused on these fast-acting and highly-potent toxins because they are widely found in contaminated shellfish. Despite their highly complex molecular structure, PnTXs have been chemically synthetized and demonstrated to act on various nicotinic acetylcholine receptor (nAChR) subtypes. In the present work, PnTX-A, PnTX-G and analogue, obtained by chemical synthesis with a high degree of purity (>98%), have been studied in vivo and in vitro on adult mouse and isolated nerve-muscle preparations expressing the mature muscle-type (α1)2β1δε nAChR. The results show that PnTX-A and G acted on the neuromuscular system of anesthetized mice and blocked the compound muscle action potential (CMAP) in a dose- and time-dependent manner, using a minimally invasive electrophysiological method. The CMAP block produced by both toxins in vivo was reversible within 6–8 h. PnTX-A and G, applied to isolated extensor digitorum longus nerve-muscle preparations, blocked reversibly isometric twitches evoked by nerve stimulation. The action of PnTX-A was reversed by 3,4-diaminopyridine. Both toxins exerted no direct action on muscle fibers, as revealed by direct muscle stimulation. PnTX-A and G blocked synaptic transmission at mouse neuromuscular junctions and PnTX-A amino ketone analogue (containing an open form of the imine ring) had no effect on neuromuscular transmission. These results indicate the importance of the cyclic imine for interacting with the adult mammalian muscle-type nAChR. Modeling and docking studies revealed molecular determinants responsible for the interaction of PnTXs with the muscle-type nAChR.