bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular Aluminium in Inflammatory and Glial Cells in Cerebral Amyloid Angiopathy: A Case Report
Authors: Mold Matthew , Cottle Jason , King Andrew , Exley Christopher
Published: April 2019

(1) Introduction: In 2006, we reported on very high levels of aluminium in brain tissue in an unusual case of cerebral amyloid angiopathy (CAA). The individual concerned had been exposed to extremely high levels of aluminium in their potable water due to a notorious pollution incident in Camelford, Cornwall, in the United Kingdom. The recent development of aluminium-specific fluorescence microscopy has now allowed for the location of aluminium in this brain to be identified. (2) Case Summary: We used aluminium-specific fluorescence microscopy in parallel with Congo red staining and polarised light to identify the location of aluminium and amyloid in brain tissue from an individual who had died from a rare and unusual case of CAA. Aluminium was almost exclusively intracellular and predominantly in inflammatory and glial cells including microglia, astrocytes, lymphocytes and cells lining the choroid plexus. Complementary staining with Congo red demonstrated that aluminium and amyloid were not co-located in these tissues. (3) Discussion: The observation of predominantly intracellular aluminium in these tissues was novel and something similar has only previously been observed in cases of autism. The results suggest a strong inflammatory component in this case and support a role for aluminium in this rare and unusual case of CAA.
Recent Status and Methodological Quality of Return-to-Work Rates of Cancer Patients Reported in Japan: A Systematic Review
Authors: Ota Atsuhiko , Fujisawa Akiko , Kawada Kenji , Yatsuya Hiroshi
Published: April 2019

Cancer patients’ return-to-work rates in Japan and their methodological quality have been little reported. We conducted a systematic review to explore the recent return-to-work rates and to assess the methodological quality of the existing literature. We selected 13 papers (2 in English and 11 in Japanese) published between 2005 and 2017. The return-to-work rates ranged from 53.8% to 95.2%. Of the selected papers, 12 papers employed a cross-sectional design, possessing high risk of selection bias due to participant selection. A total of 8 papers did not fully report the subjects’ sex, age, employment status at cancer diagnosis, cancer site, stage, and treatment, suggesting high risk of selection bias due to confounding variables. High or unclear risk of attrition bias due to incomplete outcome data was detected in 12 papers in which data on return to work were not collected from all participants. High risk of reporting bias due to selective outcome reporting was pointed out in 6 studies in which the subjects’ employment status at return to work or the duration between cancer diagnosis and assessment of return to work was unclear. Future studies must reduce the risk of selection, attrition, and reporting biases for specifying accurate return-to-work rates.
Health-Related Quality of Life Profiles among Patients with Different Road Traffic Injuries in an Urban Setting of Vietnam
Authors: Vu Hai Minh , Dang Anh Kim , Tran Tung Thanh , Vu Giang Thu , Truong Nu Thi , Nguyen Cuong Tat , Doan Anh Van , Pham Kiet Tuan Huy , Tran Tung Hoang , Tran Bach Xuan , Latkin Carl A. , Ho Cyrus S.H. , Ho Roger C.M.
Published: April 2019

Road traffic injuries (RTIs) cause a substantial disease burden in Vietnam. Evaluating health-related quality of life (HRQOL) among patients having a diversity of RTIs informs an integral part of treatment effectiveness. This study aims to examine HRQOL of patients suffering different RTIs in Vietnam’s urban areas. A cross-sectional study was conducted on 408 patients from October to December 2018 in six hospitals in Thai Binh. The EuroQol-5 dimensions-5 levels (EQ-5D-5L) and visual analog scale (VAS) were used to assess the HRQOL of patients. Multivariable Tobit regression was applied to measure the difference of HRQOL among different kinds of injuries. The mean EQ-5D-5L and VAS score was 0.40–0.66, respectively. Mean EQ-5D-5L index was lowest in patients with oral and facial injuries (0.22) and fracture injuries (0.23), while patients having hand injuries had the highest EQ-5D-5L index (0.54). EQ-5D-5L index had a negative association with oral, facial, and fracture injuries. Meanwhile, patients with brain, fracture, and multiple injuries tended to have lower VAS score. Poor HRQOL among patients injured in road traffic were observed. Pain management, early rehabilitation, and mental health counseling services should be considered during treatment time, especially among those having the brain, oral and facial trauma, fracture, and multiple injuries.
Hybrid Resiliency-Stressor Conceptual Framework for Informing Decision Support Tools and Addressing Environmental Injustice and Health Inequities
Authors: Burwell-Naney Kristen , Wilson Sacoby M. , Whitlock Siobhan T. , Puett Robin
Published: April 2019

While structural factors may drive health inequities, certain health-promoting attributes of one’s “place” known as salutogens may further moderate the cumulative impacts of exposures to socio-environmental stressors that behave as pathogens. Understanding the synergistic relationship between socio-environmental stressors and resilience factors is a critical component in reducing health inequities; however, the catalyst for this concept relies on community-engaged research approaches to ultimately strengthen resiliency and promote health. Furthermore, this concept has not been fully integrated into environmental justice and cumulative risk assessment screening tools designed to identify geospatial variability in environmental factors that may be associated with health inequities. As a result, we propose a hybrid resiliency-stressor conceptual framework to inform the development of environmental justice and cumulative risk assessment screening tools that can detect environmental inequities and opportunities for resilience in vulnerable populations. We explore the relationship between actual exposures to socio-environmental stressors, perceptions of stressors, and one’s physiological and psychological stress response to environmental stimuli, which collectively may perpetuate health inequities by increasing allostatic load and initiating disease onset. This comprehensive framework expands the scope of existing screening tools to inform action-based solutions that rely on community-engaged research efforts to increase resiliency and promote positive health outcomes.
Burnout Syndrome in Middle and Senior Management in the Industrial Manufacturing Sector of Mexico
Authors: Macias-Velasquez Sharon , Baez-Lopez Yolanda , Maldonado-Macías Aidé Aracely , Limon-Romero Jorge , Tlapa Diego
Published: April 2019

Due to globalization and the accelerated growth of technology, ever more employees of companies are affected by burnout syndrome, the psychological nature of which requires a prolonged response to chronic interpersonal stressors in work environments. The present research aims to validate the operability of the Maslach Burnout Inventory-General Survey (MBI-GS) using a sample of 378 professionals belonging to middle and senior management working in companies within the IMMEX sector (comprising the industrial-manufacturing, maquiladora and export services) located in the state of Baja California, Mexico. Firstly, an exploratory factor analysis using the principal components method and Varimax rotation was performed and the results revealed the existence of three factors representing more than 67 percent of the total variance. Secondly, a confirmatory factorial analysis was carried out performing appropriate results for the indices Chi-square goodness-of-fit model, Root Mean Square Error of Approximation (RMSEA), Normed Fit Index (NFI), Comparative Fit Index (CFI), Relative Fit Index (RFI), Parsimony Ratio (PRATIO) and Parsimony Normed Fit Index (PNFI), which are highly recommended by literature in these types of studies. Additionally, construct validity was satisfactorily verified. The factorial solution coincided with the Maslach Burnout Inventory original proposal so that this instrument can be considered a valid and reliable option to analyze the burnout levels in people pertaining to middle and senior management in these types of industries.
Perceived Stress among Caregivers of Children with Autism Spectrum Disorder: A State-Wide Study
Authors: Nik Adib Nik Aida , Ibrahim Mohd Ismail , Ab Rahman Azriani , Bakar Raishan Shafini , Yahaya Nor Azni , Hussin Suria , Wan Mansor Wan Nor Arifin
Published: April 2019

Background: Caregivers of children with autism spectrum disorder (ASD) experience increased stress and more significant negative caregiving consequences than those with typically developing children. There is a lack of studies specifically focusing on stress among caregivers with ASD children in Asian countries. The current study examines levels of perceived stress and factors associated with it among caregivers in Kelantan, Malaysia. Methods: In a cross-sectional study, the Malay version of the Perceived Stress Scale (PSS) was administered to 227 caregivers of children with ASD. The caregivers were recruited from ASD databases in four tertiary hospitals in Kelantan and a meeting was set up during the child’s follow-up in the clinic. Multiple linear regression analyses were applied to determine the predictors of perceived stress. Results: The mean total perceived stress score was 20.84 (4.72). This was considered higher than average. Higher perceived stress was significantly predicted among caregivers who live far from the health institution, caregivers who do not own transportation to bring the child to the treatment center, and caregivers who have an ASD child with a learning disability. Conclusion: Caregivers of an ASD child perceived significant stress while taking care of their children. Institutions should alleviate the factors that were predicted to increase the caregivers’ perceived stress to improve the quality of the lives of children and ASD families as a whole.
Changes in Major Global River Discharges Directed into the Ocean
Authors: Shi Xiaoqing , Qin Tianling , Nie Hanjiang , Weng Baisha , He Shan
Published: April 2019

Under the influence of global climate change, the discharges of major global rivers directed into the ocean have undergone significant changes. To study the trends and causes in discharge variation, we selected 40 large rivers and analyzed their annual discharges near their estuaries from 1960 to 2010. The method of runoff variation attribution analysis based on the Budyko hypothesis for large-scale basins was developed, in which influencing factors of human activities and glacial melting factors were added to the formula. The contribution rate of climate factors and human activities to changes in discharge were quantitatively identified. Climatic factors include precipitation, evapotranspiration and glacial melting. Human activity factors include underlying surface and artificial water transfer. The contribution rate is determined by the elastic coefficient, which is obtained by the ratio of change rate of each factor and the change rate of runoff. The results indicated that the discharges predominantly showed downward trends with a few upward trends. Rivers in North America and Africa showed downward trends, and those in Europe principally showed upward trends. Climate was the main influencing factor of discharges changes, and only approximately 25% of river discharges were greatly affected by human activities. River discharges in 75% of the basins which mainly contains subtropical monsoon humid climate and savanna climate zones showed upward trends. In the four basins which are mainly contains tropical rainforest climate and tropical monsoon climate, they all showed downward trends. The trend of discharges in the temperate monsoon climate, temperate continental climate, and temperate maritime climate cannot be accurately judged because of irregular variation. The discharges in the mid-high latitudinal zones predominantly showed upward trends, while those in the mid-low latitudinal zones with the influence of human activities showed downward trends.
Evaluating the Relationship between Well-Being and Living with a Dog for People with Chronic Low Back Pain: A Feasibility Study
Authors: Carr Eloise C.J. , Wallace Jean E. , Pater Rianne , Gross Douglas P.
Published: April 2019

Chronic low back pain is a significant societal and personal burden that negatively impacts quality of life. Dog ownership has been associated with health benefits. This study evaluated the feasibility of surveying people with chronic low back pain to assess the relationship between dog ownership and well-being. A mail-out survey was sent to 210 adult patients with chronic low back pain. Measures of quality of life, pain, physical activity, emotional health, social ties and dog ownership were included. Feasibility was assessed by examining survey response rate, responses to established and newly developed measures, and the potential relationships between dog ownership and a number of key well-being variables in this patient population. There were 56 completed surveys returned (n = 36 non-dog owners and n = 20 dog owners). Established, adapted and newly developed scales revealed promising results. Dog owners reported fewer depression and anxiety symptoms, and more social ties than non-dog owners. Living with a dog may be associated with improved well-being for people with chronic pain. The findings from this feasibility study will inform a general population survey, to be conducted with a larger, more representative sample of people living with chronic pain.
Modelling a Supplementary Vaccination Program of Rubella Using the 2012–2013 Epidemic Data in Japan
Authors: Kayano Taishi , Lee Hyojung , Nishiura Hiroshi
Published: April 2019

From 2012–2013, Japan experienced a major epidemic of rubella, involving a total of 12,614 rubella cases and 45 confirmed cases of congenital rubella syndrome (CRS). One of the contributory factors in this outbreak may have been that the majority of adult males remained unvaccinated. To plan for a supplementary immunization program (SIP) to elevate the herd immunity level, it is critical to determine the required amount of vaccine and identify the target age groups among males for the SIP. The present study aimed to answer these policy questions, employing a mathematical model and analyzing epidemiological datasets from 2012–2013. Our model allowed us to reconstruct the age- and sex-dependent transmission patterns, and the effective reproduction number during the exponential growth phase in 2013 was estimated to be 1.5. The computed next-generation matrix indicated that vaccinating adult males aged from 20–49 years in 2013, using at least 17 million doses, was considered essential to prevent a major epidemic in the future. The proposed model also indicated that, even with smaller doses of vaccine, the SIP in adult males could lead to a substantial reduction in the incidence of rubella, as well as CRS. Importantly, the present study endorses a substantial background risk of observing another major epidemic from 2018–2019, in which cases may be dominated by adult males aged from 25–54 years, that is, our identified age groups plus a five-year time lag from 2013 to 2018.
Rational Design of Modified Oxobacteriochlorins as Potential Photodynamic Therapy Photosensitizers
Authors: Alberto Marta Erminia , De Simone Bruna Clara , Sicilia Emilia , Toscano Marirosa , Russo Nino
Published: April 2019

The modulation of the photophysical properties of a series of recently synthetized oxobacteriochlorins with the introduction of heavy atoms in the macrocycles, was investigated at density functional level of theory and by means of the time-dependent TDDFT formulation. Absorption frequencies, singlet-triplet energy gaps and spin-orbit coupling (SOC) constants values were computed for all the investigated compounds. Results show how the sulfur- selenium- and iodine-substituted compounds possess improved properties that make them suitable for application in photodynamic therapy (PDT).
Nitrergic Enteric Neurons in Health and Disease—Focus on Animal Models
Authors: Bódi Nikolett , Szalai Zita , Bagyánszki Mária
Published: April 2019

Nitrergic enteric neurons are key players of the descending inhibitory reflex of intestinal peristalsis, therefore loss or damage of these neurons can contribute to developing gastrointestinal motility disturbances suffered by patients worldwide. There is accumulating evidence that the vulnerability of nitrergic enteric neurons to neuropathy is strictly region-specific and that the two main enteric plexuses display different nitrergic neuronal damage. Alterations both in the proportion of the nitrergic subpopulation and in the total number of enteric neurons suggest that modification of the neurochemical character or neuronal death occurs in the investigated gut segments. This review aims to summarize the gastrointestinal region and/or plexus-dependent pathological changes in the number of nitric oxide synthase (NOS)-containing neurons, the NO release and the cellular and subcellular expression of different NOS isoforms. Additionally, some of the underlying mechanisms associated with the nitrergic pathway in the background of different diseases, e.g., type 1 diabetes, chronic alcoholism, intestinal inflammation or ischaemia, will be discussed.
Structural Identification of Antibacterial Lipids from Amazonian Palm Tree Endophytes through the Molecular Network Approach
Authors: Barthélemy Morgane , Elie Nicolas , Pellissier Léonie , Wolfender Jean-Luc , Stien Didier , Touboul David , Eparvier Véronique
Published: April 2019

A library of 197 endophytic fungi and bacteria isolated from the Amazonian palm tree Astrocaryum sciophilum was extracted and screened for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Four out of five antibacterial ethyl acetate extracts were also cytotoxic for the MRC-5 cells line. Liquid chromatography coupled to tandem mass spectrometry (UPHLC-HRMS/MS) analyses combined with molecular networking data processing were carried out to allow the identification of depsipeptides and cyclopeptides responsible for the cytotoxicity in the dataset. Specific ion clusters from the active Luteibacter sp. extract were also highlighted using an MRSA activity filter. A chemical study of Luteibacter sp. was conducted leading to the structural characterization of eight fatty acid exhibiting antimicrobial activity against MRSA in the tens of µg/mL range.
Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
Authors: Glazunova Olga A. , Moiseenko Konstantin V. , Kamenihina Inna A. , Isaykina Tatyana U. , Yaropolov Alexander I. , Fedorova Tatyana V.
Published: April 2019

Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications. It is known that laccases from different fungal strains may vary in properties; however, the reason of this remains unclear. In the current study we have isolated and characterized seven laccases from different strains of Steccherinum ochraceum obtained from regions of central Russia. Although all seven laccases had the same primary sequences, there was a little variation in their molecular weights and thermostabilities. Moreover, statistically significant differences in laccases’ catalytic parameters of oxidation of phenolic substrates and ABTS were observed. After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
Modified Carboxyl-Terminated PAMAM Dendrimers as Great Cytocompatible Nano-Based Drug Delivery System
Authors: Vu Minh Thanh , Bach Long Giang , Nguyen Duy Chinh , Ho Minh Nhat , Nguyen Ngoc Hoi , Tran Ngoc Quyen , Nguyen Dai Hai , Nguyen Cuu Khoa , Hoang Thi Thai Thanh
Published: April 2019

Polyamidoamine (PAMAM) dendrimers are extensively researched as potential drug delivery system thanks to their desirable features such as controlled and stable structures, and ease of functionalization onto their surface active groups. However, there have been concerns about the toxicity of full generation dendrimers and risks of premature clearance from circulation, along with other physical drawbacks presented in previous formulations, including large particle sizes and low drug loading efficiency. In our study, carboxyl-terminated PAMAM dendrimer G3.5 was grafted with poly (ethylene glycol) methyl ether (mPEG) to be employed as a nano-based drug delivery system with great cytocompatibility for the delivery of carboplatin (CPT), a widely prescribed anticancer drug with strong side effects so that the drug will be effectively entrapped and not exhibit uncontrolled outflow from the open structure of unmodified PAMAM G3.5. The particles formed were spherical in shape and had the optimal size range (around 36 nm) that accommodates high drug entrapment efficiency. Surface charge was also determined to be almost neutral and the system was cytocompatible. In vitro release patterns over 24 h showed a prolonged CPT release compared to free drug, which correlated to the cytotoxicity assay on malignant cell lines showing the lack of anticancer effect of CPT/mPEG-G3.5 compared with CPT.
Improvement of l-Leucine Production in Corynebacterium glutamicum by Altering the Redox Flux
Authors: Wang Ying-Yu , Zhang Feng , Xu Jian-Zhong , Zhang Wei-Guo , Chen Xiu-Lai , Liu Li-Ming
Published: April 2019

The production of l-leucine was improved by the disruption of ltbR encoding transcriptional regulator and overexpression of the key genes (leuAilvBNCE) of the l-leucine biosynthesis pathway in Corynebacterium glutamicum XQ-9. In order to improve l-leucine production, we rationally engineered C. glutamicum to enhance l-leucine production, by improving the redox flux. On the basis of this, we manipulated the redox state of the cells by mutating the coenzyme-binding domains of acetohydroxyacid isomeroreductase encoded by ilvC, inserting NAD-specific leucine dehydrogenase, encoded by leuDH from Lysinibacillus sphaericus, and glutamate dehydrogenase encoded by rocG from Bacillus subtilis, instead of endogenous branched-chain amino acid transaminase and glutamate dehydrogenase, respectively. The yield of l-leucine reached 22.62 ± 0.17 g·L−1 by strain ΔLtbR-acetohydroxyacid isomeroreductase (AHAIR)M/ABNCME, and the concentrations of the by-products (l-valine and l-alanine) increased, compared to the strain ΔLtbR/ABNCE. Strain ΔLtbR-AHAIRMLeuDH/ABNCMLDH accumulated 22.87±0.31 g·L−1 l-leucine, but showed a drastically low l-valine accumulation (from 8.06 ± 0.35 g·L−1 to 2.72 ± 0.11 g·L−1), in comparison to strain ΔLtbR-AHAIRM/ABNCME, which indicated that LeuDH has much specificity for l-leucine synthesis but not for l-valine synthesis. Subsequently, the resultant strain ΔLtbR-AHAIRMLeuDHRocG/ABNCMLDH accumulated 23.31 ± 0.24 g·L−1 l-leucine with a glucose conversion efficiency of 0.191 g·g−1.
FKBP5 rs4713916: A Potential Genetic Predictor of Interindividual Different Response to Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease in a Real-Life Setting
Authors: Russo Patrizia , Tomino Carlo , Santoro Alessia , Prinzi Giulia , Proietti Stefania , Kisialiou Aliaksei , Cardaci Vittorio , Fini Massimo , Magnani Mauro , Collacchi Francesco , Provinciali Mauro , Giacconi Robertina , Bonassi Stefano , Malavolta Marco
Published: April 2019

Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient’s response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.
Phosphoinositide 3 Kinase Signaling in Human Stem Cells from Reprogramming to Differentiation: A Tale in Cytoplasmic and Nuclear Compartments
Authors: Ramazzotti Giulia , Ratti Stefano , Fiume Roberta , Follo Matilde Yung , Billi Anna Maria , Rusciano Isabella , Owusu Obeng Eric , Manzoli Lucia , Cocco Lucio , Faenza Irene
Published: April 2019

Stem cells are undifferentiated cells that can give rise to several different cell types and can self-renew. Given their ability to differentiate into different lineages, stem cells retain huge therapeutic potential for regenerative medicine. Therefore, the understanding of the signaling pathways involved in stem cell pluripotency maintenance and differentiation has a paramount importance in order to understand these biological processes and to develop therapeutic strategies. In this review, we focus on phosphoinositide 3 kinase (PI3K) since its signaling pathway regulates many cellular processes, such as cell growth, proliferation, survival, and cellular transformation. Precisely, in human stem cells, the PI3K cascade is involved in different processes from pluripotency and induced pluripotent stem cell (iPSC) reprogramming to mesenchymal and oral mesenchymal differentiation, through different and interconnected mechanisms.
Acyl-CoA-Binding Domain-Containing 3 (ACBD3; PAP7; GCP60): A Multi-Functional Membrane Domain Organizer
Authors: Yue Xihua , Qian Yi , Gim Bopil , Lee Intaek
Published: April 2019

Acyl-CoA-binding domain-containing 3 (ACBD3) is a multi-functional scaffolding protein, which has been associated with a diverse array of cellular functions, including steroidogenesis, embryogenesis, neurogenesis, Huntington’s disease (HD), membrane trafficking, and viral/bacterial proliferation in infected host cells. In this review, we aim to give a timely overview of recent findings on this protein, including its emerging role in membrane domain organization at the Golgi and the mitochondria. We hope that this review provides readers with useful insights on how ACBD3 may contribute to membrane domain organization along the secretory pathway and on the cytoplasmic surface of intracellular organelles, which influence many important physiological and pathophysiological processes in mammalian cells.
Real-Time 3D High-Resolution Microscopy of Human Cells on the International Space Station
Authors: Thiel Cora Sandra , Tauber Svantje , Seebacher Christian , Schropp Martin , Uhl Rainer , Lauber Beatrice , Polzer Jennifer , Neelam Srujana , Zhang Ye , Ullrich Oliver
Published: April 2019

Here we report the successful first operation of FLUMIAS-DEA, a miniaturized high-resolution 3D fluorescence microscope on the International Space Station (ISS) by imaging two scientific samples in a temperature-constant system, one sample with fixed cells and one sample with living human cells. The FLUMIAS-DEA microscope combines features of a high-resolution 3D fluorescence microscope based on structured illumination microscope (SIM) technology with hardware designs to meet the requirements of a space instrument. We successfully demonstrated that the FLUMIAS technology was able to acquire, transmit, and store high-resolution 3D fluorescence images from fixed and living cells, allowing quantitative and dynamic analysis of subcellular structures, e.g., the cytoskeleton. The capability of real-time analysis methods on ISS will dramatically extend our knowledge about the dynamics of cellular reactions and adaptations to the space environment, which is not only an option, but a requirement of evidence-based medical risk assessment, monitoring and countermeasure development for exploration class missions.
Theaflavin-Enriched Fraction Stimulates Adipogenesis in Human Subcutaneous Fat Cells
Authors: Park Phil June , Rha Chan-Su , Kim Sung Tae
Published: April 2019

Skin provides the first defense line against the environment while preserving physiological homeostasis. Subcutaneous tissues including fat depots that are important for maintaining skin structure and alleviating senescence are altered during aging. This study investigated whether theaflavin (TF) in green tea (GT) has skin rejuvenation effects. Specifically, we examined whether high ratio of TF contents can induce the subcutaneous adipogenesis supporting skin structure by modulating lipid metabolism. The co-fermented GT (CoF-GT) fraction containing a high level of TF was obtained by co-fermentation with garland chrysanthemum (Chrysanthemum coronarium) and the conventionally fermented GT (F-GT) fraction was also obtained. The effects of the CoF- or F-GT fractions on adipogenesis were assessed using primary human subcutaneous fat cells (hSCF). Adipogenesis was evaluated based on lipid droplet (LD) formation, as visualized by Oil Red O staining; by analyzing of adipogenesis-related factors by real-time quantitative polyperase chain reaction (RT-qPCR); and by measuring the concentration of adiponectin released into the culture medium by enzyme-linked immunosorbent assay. TF-enriched CoF-GT fraction did not adversely affect hSCF cell viability but induced their adipogenic differentiation, as evidenced by LD formation, upregulation of adipogenesis-related genes, and adiponectin secretion. TF and TF-enriched CoF-GT fraction promoted differentiation of hSCFs and can therefore be used as an ingredient in rejuvenating agents.
Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer
Authors: Moncho-Amor Verónica , Pintado-Berninches Laura , Ibañez de Cáceres Inmaculada , Martín-Villar Ester , Quintanilla Miguel , Chakravarty Probir , Cortes-Sempere María , Fernández-Varas Beatriz , Rodriguez-Antolín Carlos , de Castro Javier , Sastre Leandro , Perona Rosario
Published: April 2019

DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor prognosis in those Non-small cell lung cancer (NSCLC) patients with low expression levels of DUSP6. In agreement with these data, here we show that DUSP6 plays a major role in the regulation of cell migration, motility and tumor growth. We have found upregulation in the expression of several genes involved in epithelial to mesenchymal transition (EMT) in NSCLC-DUSP6 depleted cells. Data obtained in RNA-seq studies carried out in DUSP6 depleted cells identified EGFR, TGF-β and WNT signaling pathways and several genes such as VAV3, RUNXR2, LEF1, FGFR2 whose expression is upregulated in these cells and therefore affecting cellular functions such as integrin mediated cell adhesion, focal adhesion and motility. Furthermore, EGF signaling pathway is activated via ERK5 and not ERK1/2 and TGF-β via SMAD2/3 in DUSP6 depleted cells. In summary DUSP6 is a tumor suppressor in NSCLC and re-establishment of its expression may be a potential strategy to revert poor outcome in NSCLC patients.
Mast Cells in Early Rheumatoid Arthritis
Authors: Rivellese Felice , Rossi Francesca Wanda , Galdiero Maria Rosaria , Pitzalis Costantino , de Paulis Amato
Published: April 2019

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation of the synovial membrane, with thickening of the synovial layer, cellular hyperplasia, and infiltration of immune cells. Mast cells (MCs) are cells of the innate immunity present in healthy synovia and part of the cellular hyperplasia characterizing RA synovitis. Although their presence in synovia has been well described, the exact functions and the correlation of MCs with disease development and progression have been debated, particularly because of contradictory data obtained in animal models and from patients with longstanding disease. Here, we present a revision of the literature on MCs in RA, including the most recent observations obtained from patients with early RA, indicating MCs as relevant markers of disease severity in early RA.
Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance
Authors: Goffart Steffi , Hangas Anu , Pohjoismäki Jaakko L. O.
Published: April 2019

Like any genome, mitochondrial DNA (mtDNA) also requires the action of topoisomerases to resolve topological problems in its maintenance, but for a long time, little was known about mitochondrial topoisomerases. The last years have brought a closer insight into the function of these fascinating enzymes in mtDNA topology regulation, replication, transcription, and segregation. Here, we summarize the current knowledge about mitochondrial topoisomerases, paying special attention to mammalian mitochondrial genome maintenance. We also discuss the open gaps in the existing knowledge of mtDNA topology control and the potential involvement of mitochondrial topoisomerases in human pathologies. While Top1mt, the only exclusively mitochondrial topoisomerase in mammals, has been studied intensively for nearly a decade, only recent studies have shed some light onto the mitochondrial function of Top2β and Top3α, enzymes that are shared between nucleus and mitochondria. Top3α mediates the segregation of freshly replicated mtDNA molecules, and its dysfunction leads to mtDNA aggregation and copy number depletion in patients. Top2β, in contrast, regulates mitochondrial DNA replication and transcription through the alteration of mtDNA topology, a fact that should be acknowledged due to the frequent use of Topoisomerase 2 inhibitors in medical therapy.
AHK3-Mediated Cytokinin Signaling Is Required for the Delayed Leaf Senescence Induced by SSPP
Authors: Wang Yanan , Zhang Xiyu , Cui Yanjiao , Li Lei , Wang Dan , Mei Yuanyuan , Wang Ning Ning
Published: April 2019

Leaf senescence is a highly-programmed developmental process regulated by an array of multiple signaling pathways. Our group previously reported that overexpression of the protein phosphatase-encoding gene SSPP led to delayed leaf senescence and significantly enhanced cytokinin responses. However, it is still unclear how the delayed leaf senescence phenotype is associated with the enhanced cytokinin responses. In this study, we introduced a cytokinin receptor AHK3 knockout into the 35S:SSPP background. The phenotypic analysis of double mutant revealed that AHK3 loss-of-function reversed the delayed leaf senescence induced by SSPP. Moreover, we found the hypersensitivity of 35S:SSPP to exogenous cytokinin treatment disappeared due to the introduction of AHK3 knockout. Collectively, our results demonstrated that AHK3-mediated cytokinin signaling is required for the delayed leaf senescence caused by SSPP overexpression and the detailed mechanism remains to be further elucidated.
Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production
Authors: Liao Hung-Wei , Huang Tsang-Hai , Chang Yi-Han , Liou Hung-Hsiang , Chou Yu-Hsien , Sue Yuh-Mou , Hung Peir-Haur , Chang Yu-Tzu , Ho Pei-Chuan , Tsai Kuen-Jer
Published: April 2019

Chronic kidney disease–mineral bone disorder (CKD–MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/β-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial β-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.
High Efficient Expression and Purification of Human Epidermal Growth Factor in Arachis Hypogaea L.
Authors: Yao Qingshou , Yu Zipeng , Liu Pu , Zheng Hao , Xu Yang , Sai Sixiang , Wu Yuyong , Zheng Chengchao
Published: April 2019

Background: Human epidermal growth factor (hEGF) has drawn intense research attention due to its potential ability to promote healing of serious injuries, such as cuts, burns, and diabetic ulcers. Although hEGF displays prospective clinical value, the growth factor is restricted to the treatment of chronic diabetic ulcers because of its high production cost. Methods: Leguminous plant peanut (Arachis hypogaea L.) hairy roots contain relatively few toxic and harmful substances, and tested as an excellent production system for hEGF in our study. To explore the possibility of hEGF expression in peanut, hEGF overexpression hairy roots were obtained by infecting leaves with Agrobacterium rhizogenes R1601. Results: The maximum transgenic hairy roots inducing rate was 82%. Protein purification and mass spectrometry assays showed that the protein expressed in peanut hairy roots was identified as hEGF. Furthermore, Methylthiazolyldiphenyl-tetrazolium bromide assay showed that hEGF promoted HL-7702 liver cells proliferation, which indicate that hEGF has biological activity and non-toxic on human cells. Conclusion: Our results demonstrate the capacity of peanut hairy root cultures as a controlled, sustainable, and scalable production system that can be induced to produce valued human proteins, such as hEGF.
Exercise Rescues Gene Pathways Involved in Vascular Expansion and Promotes Functional Angiogenesis in Subcutaneous White Adipose Tissue
Authors: Min So Yun , Learnard Heather , Kant Shashi , Gealikman Olga , Rojas-Rodriguez Raziel , DeSouza Tiffany , Desai Anand , Keaney John F. , Corvera Silvia , Craige Siobhan M.
Published: April 2019

Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose tissue (scWAT). Using transcriptomic profiling, scWAT was analyzed for HFD gene expression changes that were rescued by exercise. Gene networks involved in vascularization were identified as prominent targets of exercise, which led us to investigate the vasculature architecture and endothelial phenotype. Vascular density in scWAT was found to be compromised in HFD, and exercise rescued this defect. Similarly, angiogenic capacity as measured by ex vivo capillary sprouting was significantly promoted with exercise. Together, these data demonstrate that exercise enhances scWAT vascularization and functional capacity for angiogenesis, and can prevent the detrimental effects of HFD. The improvement in these indices correlates with improvement of whole-body metabolism, suggesting that scWAT vascularization may be a potential therapeutic target for metabolic disease.
A High Throughput Hardware Architecture for Parallel Recursive Systematic Convolutional Encoders
Authors: Meoni Gabriele , Giuffrida Gianluca , Fanucci Luca
Published: April 2019

During the last years, recursive systematic convolutional (RSC) encoders have found application in modern telecommunication systems to reduce the bit error rate (BER). In view of the necessity of increasing the throughput of such applications, several approaches using hardware implementations of RSC encoders were explored. In this paper, we propose a hardware intellectual property (IP) for high throughput RSC encoders. The IP core exploits a methodology based on the ABCD matrices model which permits to increase the number of inputs bits processed in parallel. Through an analysis of the proposed network topology and by exploiting data relative to the implementation on Zynq 7000 xc7z010clg400-1 field programmable gate array (FPGA), an estimation of the dependency of the input data rate and of the source occupation on the parallelism degree is performed. Such analysis, together with the BER curves, provides a description of the principal merit parameters of a RSC encoder.
The Effect of Evidence Transfer on Latent Feature Relevance for Clustering
Authors: Davvetas Athanasios , Klampanos Iraklis A. , Skiadopoulos Spiros , Karkaletsis Vangelis
Published: April 2019

Evidence transfer for clustering is a deep learning method that manipulates the latent representations of an autoencoder according to external categorical evidence with the effect of improving a clustering outcome. Evidence transfer’s application on clustering is designed to be robust when introduced with a low quality of evidence, while increasing the effectiveness of the clustering accuracy during relevant corresponding evidence. We interpret the effects of evidence transfer on the latent representation of an autoencoder by comparing our method to the information bottleneck method. Information bottleneck is an optimisation problem of finding the best tradeoff between maximising the mutual information of data representations and a task outcome while at the same time being effective in compressing the original data source. We posit that the evidence transfer method has essentially the same objective regarding the latent representations produced by an autoencoder. We verify our hypothesis using information theoretic metrics from feature selection in order to perform an empirical analysis over the information that is carried through the bottleneck of the latent space. We use the relevance metric to compare the overall mutual information between the latent representations and the ground truth labels before and after their incremental manipulation, as well as, to study the effects of evidence transfer regarding the significance of each latent feature.
Maintenance Negative Pressure Ventilation Improves Survival in COPD Patients with Exercise Desaturation
Authors: Huang Hung-Yu , Lo Chun-Yu , Yang Lan-Yan , Chung Fu-Tsai , Sheng Te-Fang , Lin Horng-Chyuan , Lin Chang-Wei , Huang Yu-Chen , Chang Chee-Jen , Chung Kian Fan , Wang Chun-Hua
Published: April 2019

Negative pressure ventilation (NPV), when used as an adjuvant to pulmonary rehabilitation, improves lung function, increases exercise capacity, and reduces exacerbations. The aim of this study was to determine whether maintenance NPV improves long-term clinical outcomes and reduces mortality in patients with chronic obstructive pulmonary disease (COPD). Between 2003 and 2009, 341 patients were treated for COPD either with or without hospital-based NPV. We measured forced expiratory volume in one second (FEV1), 6-min walking distance (6MWD), and oxygen saturation by pulse oximetry (SpO2) during a 6-min walk test (6MWT) every 3–6 months. Desaturation (D) during the 6MWT was defined as a reduction in SpO2 of ≥10% from baseline. The NPV group had a better survival outcome than the Non-NPV group. The 8-year survival probabilities for the NPV and Non-NPV groups were 60% and 20%, respectively (p < 0.01). Baseline desaturation was a significant risk factor for death, and the risk of death increased with desaturation severity (SpO2 80~89: hazard ratios (HR) 2.7, 95% confidence interval (CI) 1.4–5.3; SpO2 < 80: HR 3.1, 95% CI 1.3–7.4). The NPV group had a slower decline in lung function and 6MWD. The NPV + D and Non-NPV+D had a threefold and fourfold increase in the risks of all-cause mortality compared with the NPV-ND, respectively. Maintenance non-invasive NPV reduced long-term mortality in COPD patients. The desaturating COPD patients had an increased mortality risk compared with non-desaturating COPD patients.
Modeling the Impact of the Implementation of a Submerged Structure on Surf Zone Sandbar Dynamics
Authors: Bouvier Clément , Castelle Bruno , Balouin Yann
Published: April 2019

Coastal defense strategies based on structures are increasingly unpopular as they are costly, leave lasting scars on the landscape, and sometimes have limited effectiveness or even adverse impacts. While a clear improvement concerning aesthetic considerations using soft submerged breakwater is undeniable, their design has often focused on wave transmission processes across the crest of the structure, overlooking short- to medium-term morphodynamic responses. In this study, we used a time- and depth-averaged morphodynamic model to investigate the impact of the implementation of a submerged breakwater on surf zone sandbar dynamics at the beach of Sète, SE France. The hydrodynamic module was calibrated with data collected during a field experiment using three current profilers deployed to capture rip-cell circulation at the edge of the structure. The model showed good agreement with measurements, particularly for the longshore component of the flow (RMSE = 0.07 m/s). Results showed that alongshore differential wave breaking at the edge of the submerged breakwater drove an intense (0.4 m/s) two-dimensional circulation for low- to moderate-energy waves. Simulations indicated that inner-bar rip channel development, which was observed prior to the submerged reef implementation, was inhibited in the lee of the structure as rip-cell circulation across the inner bar disappeared owing to persistently low-energy breaking waves. The cross-shore sandbar dynamics in the lee of the structure were also impacted due to the drastic decrease of the offshore-directed flow over the inner-bar during energetic events. This paper highlights that implementation of a submerged breakwater results in larges changes in nearshore hydrodynamics that, in turn, can affect overall surf zone sandbar behavior.