bluuebunny/crossref_metadata_2025 huggingface dataset:
Wood Moisture-Induced Swelling at the Cellular Scale—Ab Intra
Authors: Arzola-Villegas Xavier , Lakes Roderic , Plaza Nayomi Z. , Jakes Joseph E.
Published: November 2019

Wood, a complex hierarchical material, continues to be widely used as a resource to meet humankind’s material needs, in addition to providing inspiration for the development of new biomimetic materials. However, for wood to meet its full potential, researchers must overcome the challenge of understanding its fundamental moisture-related properties across its many levels of hierarchy spanning from the molecular scale up to the bulk wood level. In this perspective, a review of recent research on wood moisture-induced swelling and shrinking is presented from the molecular level to the cellular scale. Numerous aspects of swelling and shrinking in wood remain poorly understood, sub-cellular phenomena in particular, because it can be difficult to study them experimentally. Here, we discuss recent research endeavors at each of the relevant length scales, including the molecular, cellulose elementary fibril, secondary cell wall layer nanostructure, cell wall, cell, and cellular levels. At each length scale, we provide a discussion on the current knowledge and suggestions for future research. The potential impacts of moisture-induced swelling pressures on experimental observations of swelling and shrinking in wood at different length scales are also recognized and discussed.
Effects of Lintnerization, Autoclaving, and Freeze-Thaw Treatments on Resistant Starch Formation and Functional Properties of Pathumthani 80 Rice Starch
Authors: Raungrusmee Sujitta , Anal Anil Kumar
Published: November 2019

The objective of this study was to assess the effects of lintnerization, autoclaving, lintnerization followed by autoclaving, and freeze thawing treatments on the production of resistant starch from Pathumthani 80 (RD 31) rice. The produced resistant starch was further evaluated for some important physicochemical properties including pasting properties, swelling behavior, digestibility, water holding capacity, and functional properties including glycemic index and antioxidant properties. The lintnerization treatment and autoclaving significantly (p ˂ 0.05) increased resistant starch content to 64% (w/w) and gave the lowest glycemic index (46.12%). The lintnerization followed by autoclaving treatment significantly increased the solubility and water holding capacity, reduced the swelling power, and disrupted the crystalline structure of the starch granules. The native rice starch with autoclave treatment exhibited the highest swelling power among the samples, while the acid hydrolyzed starch was followed by autoclave treatment showing the lowest swelling power (1 g/g) at 90 °C. Fourier transform infrared analysis revealed the modified structures and bonding of the starch materials with the shifting of C=O stretch. However, the antioxidant properties and pasting properties were observed to decrease with the lintnerization, autoclaving, and freeze-thawing treatment of the native starch. The highly resistant starch content and low glycemic index value of the autoclaved RD 31 starch indicates the potential of the resistant starch’s application for the formulation of functional foods targeting the diabetic population.
Impulsive Fractional-Like Differential Equations: Practical Stability and Boundedness with Respect to h-Manifolds
Authors: Stamov Gani , Martynyuk Anatoliy , Stamova Ivanka
Published: November 2019

In this paper, an impulsive fractional-like system of differential equations is introduced. The notions of practical stability and boundedness with respect to h-manifolds for fractional-like differential equations are generalized to the impulsive case. For the first time in the literature, Lyapunov-like functions and their derivatives with respect to impulsive fractional-like systems are defined. As an application, an impulsive fractional-like system of Lotka–Volterra equations is considered and new criteria for practical exponential stability are proposed. In addition, the uncertain case is also investigated.
MicroRNAs in Vitis vinifera cv. Chardonnay Are Differentially Expressed in Response to Diaporthe Species
Authors: Eichmeier Ales , Kiss Tomas , Penazova Eliska , Pecenka Jakub , Berraf-Tebbal Akila , Baranek Miroslav , Pokluda Robert , Cechova Jana , Gramaje David , Grzebelus Dariusz
Published: November 2019

Diaporthe species are important pathogens, saprobes, and endophytes on grapevines. Several species are known, either as agents of pre- or post-harvest infections, as causal agents of many relevant diseases, including swelling arm, trunk cankers, leaf spots, root and fruit rots, wilts, and cane bleaching. A growing body of evidence exists that a class of small non-coding endogenous RNAs, known as microRNAs (miRNAs), play an important role in post-transcriptional gene regulation, during plant development and responses to biotic and abiotic stresses. In this study, we explored differentially expressed miRNAs in response to Diaporthe eres and Diaporthe bohemiae infection in Vitis vinifera cv. Chardonnay under in vitro conditions. We used computational methods to predict putative miRNA targets in order to explore the involvement of possible pathogen response pathways. We identified 136 known and 41 new miRNA sequence variants, likely generated through post-transcriptional modifications. In the Diaporthe eres treatment, 61 known and 17 new miRNAs were identified while in the Diaporthe bohemiae treatment, 101 known and 21 new miRNAs were revealed. Our results contribute to further understanding the role miRNAs play during plant pathogenesis, which is possibly crucial in understanding disease symptom development in grapevines infected by D. eres and D. bohemiae.
Genetically Determined Physical Activity and Its Association with Circulating Blood Cells
Authors: Prins Femke M. , Said M. Abdullah , van de Vegte Yordi J. , Verweij Niek , Groot Hilde E. , van der Harst Pim
Published: November 2019

Lower levels of physical activity (PA) have been associated with increased risk of cardiovascular disease. Worldwide, there is a shift towards a lifestyle with less PA, posing a serious threat to public health. One of the suggested mechanisms behind the association between PA and disease development is through systemic inflammation, in which circulating blood cells play a pivotal role. In this study we investigated the relationship between genetically determined PA and circulating blood cells. We used 68 single nucleotide polymorphisms associated with objectively measured PA levels to perform a Mendelian randomization analysis on circulating blood cells in 222,645 participants of the UK Biobank. For inverse variance fixed effects Mendelian randomization analyses, p < 1.85 × 10−3 (Bonferroni-adjusted p-value of 0.05/27 tests) was considered statistically significant. Genetically determined increased PA was associated with decreased lymphocytes (β = –0.03, SE = 0.008, p = 1.35 × 10−3) and decreased eosinophils (β = –0.008, SE = 0.002, p = 1.36 × 10−3). Although further mechanistic studies are warranted, these findings suggest increased physical activity is associated with an improved inflammatory state with fewer lymphocytes and eosinophils.
Malignant Transformation in Diabetic Foot Ulcers—Case Reports and Review of the Literature
Authors: Dörr Stefan , Lucke-Paulig Lara , Vollmer Christian , Lobmann Ralf
Published: November 2019

An imbalance of regeneration and destruction of the extracellular matrix due to a plethora of chemo- and cytokines, elevated matrix metalloproteinases, bacterial contamination and repetitive painless tissue damage can lead the chronicity of a wound, especially in diabetic foot ulcers (DFU). Along general lines, wound healing and cancer development are similar. Therefore chronic wounds prepare a breeding ground for cancer development. Several characteristics such as increase in size, verrucous everted margins and contact bleeding are suspicious for malignant growth in a chronic wound. While previously the term Marjolin’s ulcer was attributed to a malignant tumor in (burn) scars, it is nowadays used for every malignant tumor in chronic wounds. Furthermore, chronic ulcers in diabetic feet are susceptible for malignant transformation. We describe two cases of squamous cell carcinoma in patients with DFU—a 71 year-old woman and a 67 year old man. Both received total tumor excision and split-skin grafts with good short-time results.
Development and Validation of an Evaluation Tool to Measure the Effectiveness of a Smoking Cessation Training among Healthcare Providers in Malaysia: The Providers’ Smoking Cessation Training Evaluation (ProSCiTE)
Authors: Hasan Siti Idayu , Mohd Hairi Farizah , Amer Nordin Amer Siddiq , Danaee Mahmoud
Published: November 2019

Background: In line with Article 14 of the Framework Convention for Tobacco Control, we have witnessed vast developments in smoking cessation training for healthcare providers, offering help for smokers. However, there is no specific evaluation tool to monitor and evaluate the effectiveness of these programs for future enhancement and sustainability. Objective: To develop and validate a new tool for evaluating smoking cessation training programs for healthcare providers called the Providers’ Smoking Cessation Training Evaluation (ProSCiTE). Methods: The 74-item ProSCiTE tool was developed based on a review of the literature and an expert panel review. The tool was validated in a sample of 403 healthcare providers using a cross-sectional study design from July to December 2016. Content validity was assessed by the Scale-Content Validity Index (S-CVI). The construct validity of the ProSCiTE was analyzed using exploratory factor analysis (EFA) to confirm psychometric properties. Internal consistency reliability was determined using Cronbach’s alpha. Results: The content validity showed that the S-CVI ranged from 0.82 to 1.00 for consistency, representativeness, relevancy, and the clarity of each construct, resulting in 67 items for the questionnaire. The construct validity of the ProSCiTE (based on eigenvalues and factor loadings to confirm the four-factor structure (attitude, self-efficacy, behavior, and barriers) with 54.74% total variance) was acceptable (Kaiser-Mayer-Olkin = 0.923; Bartlett’s test of sphericity was significant, p < 0.001). The internal consistency reliability of the four-factor structure was very good, with Cronbach’s alpha values at 0.89, 0.94, 0.95, and 0.90, respectively. Conclusions: This study showed that 67 items of the ProSCiTE demonstrated good content and construct validity, as well as a high internal consistency reliability for the measurement of knowledge, attitudes, self-efficacy, behavior, and barriers to smoking cessation interventions among healthcare providers. Therefore, the ProSCiTE is a valid and reliable research tool with which to evaluate the effectiveness of smoking cessation training programs.
sEMG Activation of the Flexor Muscles in the Foot during Balance Tasks by Young and Older Women: A Pilot Study
Authors: Błaszczyszyn Monika , Szczęsna Agnieszka , Piechota Katarzyna
Published: November 2019

Objective: In this publication, we suggest that young adults and seniors use various defense mechanisms to counteract loss of balance. One of the hypotheses is the change in the coordination of antagonistic muscle groups, especially within the ankles. In this study, we tried to determine if there is a relationship between the condition from resilient, to pre-frail, to frail and the ability to maintain balance during free standing and balance tasks. The aim of the study was to define the importance of muscle activity in the ankle joint, dorsal flexor of the foot for the following: tibialis anterior (TA), plantar flexor of the foot gastrocnemius medialis (GM), gastrocnemius lateralis (GL), and peroneus longus (PER), during balance tasks with eyes open (EO) and closed (EC). We hypothesized that there are differences in the activity and co-activation of the tested muscles in young and older women, which may indicate an increased risk of falls and walking disorders. Materials and methods: A group of 20 women qualified for the study. The group was divided into two subgroups, young (G1) and elderly women (G2). The aim of the study was to define the importance of muscle activity in the ankle joint, dorsal flexor of the foot for the following: tibialis anterior (TA), plantar flexor of the foot gastrocnemius medialis (GM), gastrocnemius lateralis (GL), and peroneus longus (PER), during balance tasks with eyes open (EO) and closed (EC). Results: In this study, we observed significant differences between groups in the maximum and mean values of electromyography activity (EMG) activation of the examined muscles on different types of surfaces and with open and closed eyes. Older women generated higher values of EMG activation in all muscles except the gastrocnemius medialis muscle. The results were significant for co-activation at rest for muscles as follows: tibialis anterior and gastrocnemius medialis with eyes closed (p = 0.01) and peroneus and gastrocnemius lateralis at rest with eyes open (p = 0.03), eyes closed (p = 0.04), and on a foam (p = 0.02). The sEMG amplitude of the tested muscles means that agonist muscle activity changed relative to antagonistic muscle activity. Conclusions: Activation of sEMG and coordination of ankle muscles during balance tasks change with age. It can be hypothesized that assessment of balance during free standing and equivalent tasks can predict the state of frailty, after taking into account other physiological variables that are believed to affect balance control.
Development and Evaluation of a Training Program for Community-Based Participatory Research in Breast Cancer
Authors: Plumb Marj , Poole Senaida Fernandez , Sarantis Heather , Braun Susan , Cordeiro Janna , Van Olphen Juliana , Kavanaugh-Lynch Marion
Published: November 2019

This paper describes the development and feasibility of the Community Based Research Infrastructure to Better Science (CRIBS) training. The goal of this training program was to help new or existing community-academic teams to build strong partnerships and successfully develop together fundable research projects focused on breast cancer environmental causes and disparities. A comprehensive mixed-methods participatory approach was utilized to assess the training. Twenty-two community-academic teams applied for the training program; twelve teams were enrolled. All teams completed the training and subsequently submitted research applications for funding. All components of the training received high ratings and positive qualitative comments. Self-rated competency in all of the learning domains increased during the training. Four (33%) of teams were successful in their first attempt to garner research funding, and six (50%) were eventually successful. The evaluation of CRIBS found it to have successfully achieved all four goals of the training: (1) Twelve new CBPR (community-based participatory research) teams, (2) improved knowledge about CBPR and science, (3) twelve submitted grant proposals in the first year, and (4) six (50%) successfully funded research projects.
Cost-Effectiveness of Using Mass Media to Prevent Tobacco Use among Youth and Young Adults: The FinishIt Campaign
Authors: Hair Elizabeth C. , Holtgrave David R. , Romberg Alexa R. , Bennett Morgane , Rath Jessica M. , Diaz Megan C. , Vallone Donna M.
Published: November 2019

Mass media campaigns have been hailed as some of the most effective tobacco prevention interventions. This study examined the cost-effectiveness of the national tobacco prevention campaign, truth® FinishIt, to determine the cost per quality-adjusted life year (QALY) saved and the return on investment (ROI). The cost–utility analysis used four main parameters: program costs, number of smoking careers averted, treatment costs, and number of QALYs saved whenever a smoking career is averted. Parameters were varied to characterize cost-effectiveness under different assumptions (base case, conservative, optimistic, and most optimistic). The ROI estimate compared campaign expenditures to the cost saved due to the campaign implementation. Analyses were conducted in 2019. The base case analysis indicated the campaign results in a societal cost savings of $3.072 billion. Under the most conservative assumptions, estimates indicated the campaign was highly cost-effective at $1076 per QALY saved. The overall ROI estimate was $174 ($144 in costs to smokers, $24 in costs to the smoker’s family, and $7 in costs to society) in cost savings for every $1 spent on the campaign. In all analyses, the FinishIt campaign was found to reach or exceed the threshold levels of cost savings or cost-effectiveness, with a positive ROI. These findings point to the value of this important investment in the health of the younger generation.
The Effect of the Full Coverage of Essential Medicines Policy on Utilization and Accessibility of Primary Healthcare Service for Rural Seniors: A Time Series Study in Qidong, China
Authors: Wang Ying , Zhu Yulei , Shi Hang , Sun Xiaoluan , Chen Na , Li Xin
Published: November 2019

Background: Since 2015, in order to handle the increasing prevalence of age-related diseases and escalating health expenditures arising from the aging population, the full coverage of essential medicines (FCEMs) policy for rural seniors has been implemented in primary healthcare institutions of Qidong County of Jiangsu, China. The purpose of this study is to examine the long-term effects of the introduction of FCEMs’ policy on the utilization and accessibility of primary healthcare service for elderly beneficiaries. Methods: The retrospective study was conducted in Qidong County in the Jiangsu province, China. A 47-month longitudinal dataset involving 91,444 health insurance claims records of inpatients aged 70 and older in primary healthcare institutions was analyzed. Changes in health service utilization (average length of stay), patient copayments (out-of-pocket expenses), New Rural Cooperative Medical System (NRCMS) reimbursement rate and daily hospitalization costs per patient were analyzed using interrupted time series analysis. Augment Dicky-Fuller unit root method was used to test the stationarity of the series alongside the Durbin Watson method to test autocorrelation. Results: Average length of stay increased at 0.372 bed-days per month before the implementation of FCEMs policy, whereas the increasing trend was slowed down at 0.003 bed-days per month after the implementation of FCEMs policy (p < 0.001). The average out-of-pocket expenses increased by 38.035 RMB monthly in pre-implementation of the policy period, but it decreased at the rate of 5.180 RMB per month after the implementation of the FCEMs policy (p = 0.006). The NRCMS reimbursement rate increased at 0.066% per month in pre-implementation of policy and the increasing trend was sharper at 0.349% in post-implementation of policy (p = 0.135). The daily hospitalization costs per patient decreased by 6.263 RMB (p = 0.030) per month, whereas it increased at the rate of 3.119 RMB (p = 0.002) per month afterwards. Conclusions: Based on interrupted time series analyses, we concluded that FCEMs policy was associated with positive changes of average LOS and average OOP expenses. The FCEMs policy has alleviated the financial burden of the rural seniors and slightly improved the efficiency of primary health service utilization. However, it had no positive effect on daily hospitalization costs. Therefore, in the general framework of FCEMs policy, the Chinese health policy-maker should take necessary supporting measures to curb climbing hospitalization expenditures and promote the rational drug use in primary healthcare institutions.
Quick Analysis of Organic Amendments via Portable X-ray Fluorescence Spectrometry
Authors: López-Núñez Rafael , Ajmal-Poley Fátima , González-Pérez José A. , Bello-López Miguel Angel , Burgos-Doménech Pilar
Published: November 2019

The determination of heavy metals in soils and organic amendments, such as compost, manure, biofertilizer, and sludge, generally involves the digestion of samples with aqua regia, and the determination of those in the solution using various techniques. Portable X-ray fluorescence (PXRF) has many advantages in relation to traditional analytical techniques. However, PXRF determines the total elemental content and, until now, its use for the analysis of organic amendments has been limited. The objective of this work is the calibration of a PXRF instrument to determine the aqua regia-soluble elemental contents directly in solid samples of organic amendments. Our proposal will avoid the digestion step and the use of other laboratory techniques. Using a training set of samples, calibration functions were obtained that allow the determination of the aqua regia-soluble contents from the PXRF readings of total contents. The calibration functions (obtained by multiple linear regression) allowed the quantitative determination of the aqua regia-soluble contents of Fe, K, P, S, Zn, Cu, Pb, Sr, Cr, and Mn, as well as the organic matter content and a semi-quantitative assessment of Al, Ca, V, Ba, Ni, and As contents. The readings of Si, Fe, Al, Ca, K, or S were used as correction factors, indicating that the calibrations functions found are truly based on the chemical composition of the sample matrix. This study will allow a fast, cheap, and reliable field analysis of organic amendments and of other biomass-based materials.
Effectiveness of a Psycho-Social Intervention Aimed at Reducing Attrition at Methadone Maintenance Treatment Clinics: A Propensity Score Matching Analysis
Authors: Fan Xiaoyan , Zhang Xiao , Xu Huifang , Yang Fan , Lau Joseph T.F. , Hao Chun , Li Jinghua , Zhao Yuteng , Hao Yuantao , Gu Jing
Published: November 2019

Methadone maintenance treatment (MMT) is an important approach to address opioid dependence. However, MMT clinics usually report high attrition rates. Our previous randomized controlled trial demonstrated additional psycho-social services delivered by social workers could reduce attrition rates compared to MMT alone. This study aimed to evaluate the effectiveness of psycho-social service in a real-world context. A quasi-experimental design and propensity score matching was adopted. 359 clients were recruited from five MMT clinics in Guangzhou from July 2013 to April 2015. One 20-minute counseling session was offered to the control group after enrolment. The intervention group received six sessions of psycho-social services. The baseline characteristics were unbalanced between two arms in the original sample. After propensity score matching, 248 participants remained in the analysis. At month six, the intervention group had a lower attrition rate [intervention (39.5%) versus control (52.4%), P = 0.041], higher monthly income [monthly income of 1000 CNY or higher: intervention (55.9%) versus control (39.0%), P = 0.028)], higher detoxification intention score [full intention score: intervention (51.6%) versus control (32.5%), P = 0.012)], higher family support in MMT participation [intervention (77.9%) versus control (61.4%), P = 0.049)]. This study demonstrated that psycho-social services delivered by social workers can reduce MMT clients’ attrition and improve their well-being in real-world settings.
Influence of Environmental Management on Green Process Innovation: Comparison of Multiple Mediating Effects Based on Routine Replication
Authors: Ma Yuan , Zhang Qiang , Yin Qiyue
Published: November 2019

Although green process technology is vital to sustainable development, few articles focus on how to implement it from the perspective of firms. This article tries to answer this question. Being set as an antecedent of green process innovation, the influence of environmental management is analyzed and the influential path is elaborated. Hypotheses are tested by means of multivariate regression analysis and bootstrap method. The results show that environmental management is conducive to firms’ green process innovation, and the influence is through zero-order routine replication and higher-order routine replication. The mediating effect played by the interaction between the two is stronger than that of the individual. Implications are given to academia and practitioners.
Influenza Vaccination of Pregnant Women and Serious Adverse Events in the Offspring
Authors: Donzelli Alberto
Published: November 2019

Pregnant women are increasingly considered a priority group for influenza vaccination, but the evidence in favor relies mainly on observational studies, subject to the “healthy-vaccinee bias”. Propensity score methods—sometimes applied—reduce but cannot eliminate residual confounding. Meta-analyses of observational studies show relative risks far from the thresholds that would confirm the efficacy of universal vaccination for pregnant women without needing randomized controlled trials (RCTs). Critical articles have shown that in the four RCTs investigating the outcomes of this vaccination, there was a tendency towards higher offspring mortality. In the largest RCT, there was a significant excess of presumed/serious neonatal infections, and also significantly more serious adverse events. Many widely acknowledged observational results (about hormone replacing therapy, vitamin D, omega-3 fatty acids, etc.) were confuted by RCTs. Therefore the international drive to consider this vaccination a “standard of care” is not justified yet. Moreover, there is the risk of precluding further independent RCTs for “ethical considerations”, so as “to not deny the benefits of influenza vaccinations to pregnant women of a control group”. Instead, before promoting national campaigns for universal vaccination in pregnancy, further large, independent, and reassuring RCTs are needed, even braving challenging a current paradigm. Until then, influenza vaccination should be offered to pregnant women only once open information is available about the safety uncertainties, to allow truly informed choices, and promoting also other protective behaviors.
ZmRAD51C Is Essential for Double-Strand Break Repair and Homologous Recombination in Maize Meiosis
Authors: Jing Juli , Zhang Ting , Wang Yazhong , Cui Zhenhai , He Yan
Published: November 2019

Radiation sensitive 51 (RAD51) recombinases play crucial roles in meiotic double-strand break (DSB) repair mediated by homologous recombination (HR) to ensure the correct segregation of homologous chromosomes. In this study, we identified the meiotic functions of ZmRAD51C, the maize homolog of Arabidopsis and rice RAD51C. The Zmrad51c mutants exhibited regular vegetative growth but complete sterility for both male and female inflorescence. However, the mutants showed hypersensitivity to DNA damage by mitomycin C. Cytological analysis indicated that homologous chromosome pairing and synapsis were rigorously inhibited, and meiotic chromosomes were often entangled from diplotene to metaphase I, leading to chromosome fragmentation at anaphase I. Immunofluorescence analysis showed that although the signals of the axial element absence of first division (AFD1) and asynaptic1 (ASY1) were normal, the assembly of the central element zipper1 (ZYP1) was severely disrupted. The DSB formation was normal in Zmrad51c meiocytes, symbolized by the regular occurrence of γH2AX signals. However, RAD51 and disrupted meiotic cDNA 1 (DMC1) signals were never detected at the early stage of prophase I in the mutant. Taken together, our results indicate that ZmRAD51C functions crucially for both meiotic DSB repair and homologous recombination in maize.
Description and Characterization of a Novel Human Mast Cell Line for Scientific Study
Authors: S. Kirshenbaum Arnold , Yin Yuzhi , Sundstrom J. Bruce , Bandara Geethani , D. Metcalfe Dean
Published: November 2019

Background: Laboratory of allergic diseases 2 (LAD2) human mast cells were developed over 15 years ago and have been distributed worldwide for studying mast cell proliferation, receptor expression, mediator release/inhibition, and signaling. LAD2 cells were derived from CD34+ cells following marrow aspiration of a patient with aggressive mastocytosis with no identified mutations in KIT. Another aspiration gave rise to a second cell line which has recently been re-established (LADR). We queried whether LADR had unique properties for the preclinical study of human mast cell biology. Methods: LADR and LAD2 cells were cultured under identical conditions. Experiments examined proliferation, beta-hexosaminidase (β-hex) release, surface receptor and granular protease expression, infectivity with HIV, and gene expression. Results: LADR cells were larger and more granulated as seen with Wright–Giemsa staining and flow cytometry, with cell numbers doubling in 4 weeks, in contrast to LAD2 cells, which doubled every 2 weeks. Both LADR and LAD2 cells released granular contents following aggregation of FcεRI. LADR cells showed log-fold increases in FcεRI/CD117 and expressed CD13, CD33, CD34, CD63, CD117, CD123, CD133, CD184, CD193, and CD195, while LAD2 cells expressed CD33, CD34, CD63, CD117, CD133, CD193 but not CD13, CD123, CD184, or CD195. LADR tryptase expression was one-log-fold increased. LADR cell and LAD2 cell chymase expression were similar. Both cell lines could be infected with T-tropic, M-tropic, and dual tropic HIV. Following monomeric human IgE stimulation, LADR cells showed greater surface receptor and mRNA expression for CD184 and CD195. Expression arrays revealed differences in gene upregulation, especially for the suppressor of cytokine signaling (SOCS) family of genes with their role in JAK2/STAT3 signaling and cellular myelocytomatosis oncogene (c-MYC) in cell growth and regulation. Conclusions: LADR cells are thus unique in that they exhibit a slower proliferation rate, are more advanced in development, have increased FcεRI/CD117 and tryptase expression, have a different profile of gene expression, and show earlier infectivity with HIV-BAL, LAV, and TYBE when compared to LAD2 cells. This new cell line is thus a valuable addition to the few FcεRI+ human mast cell lines previously described and available for scientific inquiry.
A Miniaturized Pump Out Method for Characterizing Molecule Interaction with ABC Transporters
Authors: Sevin Emmanuel , Dehouck Lucie , Versele Romain , Culot Maxime , Gosselet Fabien
Published: November 2019

Characterizing interaction of newly synthetized molecules with efflux pumps remains essential to improve their efficacy and safety. Caco-2 cell line cultivated on inserts is widely used for measuring apparent permeability of drugs across biological barriers, and for estimating their interaction with efflux pumps such as P-gp, BCRP and MRPs. However, this method remains time consuming and expensive. In addition, detection method is required for measuring molecule passage across cell monolayer and false results can be generated if drugs concentrations used are too high as demonstrated with quinidine. For this reason, we developed a new protocol based on the use of Caco-2 cell directly seeded on 96- or 384-well plates and the use of fluorescent substrates for efflux pumps. We clearly observed that the new method reduces costs for molecule screening and leads to higher throughput compared to traditional use of Caco-2 cell model. This accelerated model could provide quick feedback regarding the molecule design during the early stage of drug discovery and therefore reduce the number of compounds to be further evaluated using the traditional Caco-2 insert method.
Effect of Kinase Inhibiting RNase Attenuator (KIRA) Compounds on the Formation of Face-to-Face Dimers of Inositol-Requiring Enzyme 1: Insights from Computational Modeling
Authors: Carlesso Antonio , Chintha Chetan , Gorman Adrienne M. , Samali Afshin , Eriksson Leif A.
Published: November 2019

Inositol-requiring enzyme 1α (IRE1α) is a transmembrane dual kinase/ribonuclease protein involved in propagation of the unfolded protein response (UPR). Inositol-requiring enzyme 1α is currently being explored as a potential drug target due to the growing evidence of its role in variety of disease conditions. Upon activation, IRE1 cleaves X-box binding protein 1 (XBP1) mRNA through its RNase domain. Small molecules targeting the kinase site are known to either increase or decrease RNase activity, but the allosteric relationship between the kinase and RNase domains of IRE1α is poorly understood. Subsets of IRE1 kinase inhibitors (known as “KIRA” compounds) bind to the ATP-binding site and allosterically impede the RNase activity. The KIRA compounds are able to regulate the RNase activity by stabilizing the monomeric form of IRE1α. In the present work, computational analysis, protein–protein and protein–ligand docking studies, and molecular dynamics simulations were applied to different IRE1 dimer systems to provide structural insights into the perturbation of IRE1 dimers by small molecules kinase inhibitors that regulate the RNase activity. By analyzing structural deviations, energetic components, and the number of hydrogen bonds in the interface region, we propose that the KIRA inhibitors act at an early stage of IRE1 activation by interfering with IRE1 face-to-face dimer formation thus disabling the activation of the RNase domain. This work sheds light on the mechanism of action of KIRA compounds and may assist in development of further compounds in, for example, cancer therapeutics. The work also provides information on the sequence of events and protein–protein interactions initiating the unfolded protein response.
Evaluation and Proteomic Analysis of Lead Adsorption by Lactic Acid Bacteria
Authors: Liu Shaoli , Zheng Yi , Ma Yimiao , Sarwar Abid , Zhao Xiao , Luo Tianqi , Yang Zhennai
Published: November 2019

Heavy metals are a growing threat to human health due to the resulting damage to the ecology; the removal of heavy metals by lactic acid bacteria (LAB) has been a focus of many studies. In this study, 10 LAB strains were evaluated for their ability to absorb and tolerate lead. Lactobacillus plantarum YW11 was found to possess the strongest ability of lead absorbing and tolerance, with the rate of absorption as high as 99.9% and the minimum inhibitory concentration of lead on YW11 higher than 1000 mg/L. Based on the isobaric tags for relative and absolute quantitation (iTRAQ) proteomics analysis of YW11, a total of 2009 proteins were identified both in the lead-treated strain and the control without the lead treatment. Among these proteins, 44 different proteins were identified. The abundance of 25 proteins increased significantly, and 19 proteins decreased significantly in the treatment group. These significantly differential abundant proteins are involved in the biological processes of amino acid and lipid metabolism, energy metabolism, cell wall biosynthesis, and substance transport. This study contributed further understanding of the molecular mechanism of L. plantarum in the binding and removal of lead to explore its potential application in counteracting heavy metal pollution of environment, food, and other fields.
A Double Negative Feedback Loop between mTORC1 and AMPK Kinases Guarantees Precise Autophagy Induction upon Cellular Stress
Authors: Holczer Marianna , Hajdú Bence , Lőrincz Tamás , Szarka András , Bánhegyi Gábor , Kapuy Orsolya
Published: November 2019

Cellular homeostasis is controlled by an evolutionary conserved cellular digestive process called autophagy. This mechanism is tightly regulated by the two sensor elements called mTORC1 and AMPK. mTORC1 is one of the master regulators of proteostasis, while AMPK maintains cellular energy homeostasis. AMPK is able to promote autophagy by phosphorylating ULK1, the key inducer of autophagosome formation, while mTORC1 downregulates the self-eating process via ULK1 under nutrient rich conditions. We claim that the feedback loops of the AMPK–mTORC1–ULK1 regulatory triangle guarantee the appropriate response mechanism when nutrient and/or energy supply changes. In our opinion, there is an essential double negative feedback loop between mTORC1 and AMPK. Namely, not only does AMPK downregulate mTORC1, but mTORC1 also inhibits AMPK and this inhibition is required to keep AMPK inactive at physiological conditions. The aim of the present study was to explore the dynamical characteristic of AMPK regulation upon various cellular stress events. We approached our scientific analysis from a systems biology perspective by incorporating both theoretical and molecular biological techniques. In this study, we confirmed that AMPK is essential to promote autophagy, but is not sufficient to maintain it. AMPK activation is followed by ULK1 induction, where protein has a key role in keeping autophagy active. ULK1-controlled autophagy is always preceded by AMPK activation. With both ULK1 depletion and mTORC1 hyper-activation (i.e., TSC1/2 downregulation), we demonstrate that a double negative feedback loop between AMPK and mTORC1 is crucial for the proper dynamic features of the control network. Our computer simulations have further proved the dynamical characteristic of AMPK–mTORC1–ULK1 controlled cellular nutrient sensing.
Angiotensin III Induces JAK2/STAT3 Leading to IL-6 Production in Rat Vascular Smooth Muscle Cells
Authors: Alanazi Ahmed Z. , Clark Michelle A.
Published: November 2019

The Janus kinase-2/ signal transducer and activators of transcription-3 (JAK2/STAT3) pathway and interleukin-6 (IL-6) are pleiotropic signal transduction systems that are responsible for induction of many cytokines and growth factors. It is unknown whether the renin angiotensin aldosterone system (RAAS) peptide, angiotensin (Ang) III induces JAK2/STAT3 and IL-6 in vascular smooth muscle cells (VSMCs). Thus, the purpose of this study was to investigate whether Ang III induces the JAK2/STAT3 pathway leading to IL-6 production in cultured VSMCs isolated from Wistar rats and determine whether differences exist in spontaneously hypertensive rat (SHR) VSMCs. We gauged Ang III’s effects on this pathway by measuring its action on STAT3 as well as IL-6 production. Ang III behaved similarly as Ang II in stimulation of STAT3 phosphorylation in Wistar and SHR VSMCs. Moreover, there were no differences in this Ang III effect in SHR versus Wistar VSMCs. In Wistar VSMCs, Ang II and Ang III significantly induced IL-6 protein secretion and mRNA expression. However, IL-6 protein secretions mediated by these peptides were significantly greater in SHR VSMCs. Ang III induced the JAK2/STAT3 pathway, leading to IL-6 protein secretion and IL-6 mRNA expression via actions on AT1Rs. Moreover, the actions of Ang III to induce IL-6 production was dysregulated in SHR VSMCs. These findings suggest that Ang III acts on AT1Rs to induce JAK2/STAT3, leading to an increase in IL-6 in cultured VSMCs. These findings are important in establishing Ang III as an important physiologically relevant peptide in VSMCs.
RNAase III-Type Enzyme Dicer Regulates Mitochondrial Fatty Acid Oxidative Metabolism in Cardiac Mesenchymal Stem Cells
Authors: Su Xuan , Jin Yue , Shen Yan , Kim Il-man , Weintraub Neal L. , Tang Yaoliang
Published: November 2019

Cardiac mesenchymal stem cells (C-MSC) play a key role in maintaining normal cardiac function under physiological and pathological conditions. Glycolysis and mitochondrial oxidative phosphorylation predominately account for energy production in C-MSC. Dicer, a ribonuclease III endoribonuclease, plays a critical role in the control of microRNA maturation in C-MSC, but its role in regulating C-MSC energy metabolism is largely unknown. In this study, we found that Dicer knockout led to concurrent increase in both cell proliferation and apoptosis in C-MSC compared to Dicer floxed C-MSC. We analyzed mitochondrial oxidative phosphorylation by quantifying cellular oxygen consumption rate (OCR), and glycolysis by quantifying the extracellular acidification rate (ECAR), in C-MSC with/without Dicer gene deletion. Dicer gene deletion significantly reduced mitochondrial oxidative phosphorylation while increasing glycolysis in C-MSC. Additionally, Dicer gene deletion selectively reduced the expression of β-oxidation genes without affecting the expression of genes involved in the tricarboxylic acid (TCA) cycle or electron transport chain (ETC). Finally, Dicer gene deletion reduced the copy number of mitochondrially encoded 1,4-Dihydronicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase core subunit 6 (MT-ND6), a mitochondrial-encoded gene, in C-MSC. In conclusion, Dicer gene deletion induced a metabolic shift from oxidative metabolism to aerobic glycolysis in C-MSC, suggesting that Dicer functions as a metabolic switch in C-MSC, which in turn may regulate proliferation and environmental adaptation.
Prostaglandin E2 Induces Skin Aging via E-Prostanoid 1 in Normal Human Dermal Fibroblasts
Authors: Shim Joong Hyun
Published: November 2019

Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production, and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca2+ concentration in NHDFs. These results indicated that PGE2 is directly associated with EP1 pathway-regulated ERK1/2 and inositol trisphosphate (IP3) signaling in NHDFs.
The Impact of Hypoxia on the Host-Pathogen Interaction between Neutrophils and Staphylococcus aureus
Authors: Hajdamowicz Natalia H , Hull Rebecca C , Foster Simon J , Condliffe Alison M
Published: November 2019

Neutrophils are key to host defence, and impaired neutrophil function predisposes to infection with an array of pathogens, with Staphylococcus aureus a common and sometimes life-threatening problem in this setting. Both infiltrating immune cells and replicating bacteria consume oxygen, contributing to the profound tissue hypoxia that characterises sites of infection. Hypoxia in turn has a dramatic effect on both neutrophil bactericidal function and the properties of S. aureus, including the production of virulence factors. Hypoxia thereby shapes the host–pathogen interaction and the progression of infection, for example promoting intracellular bacterial persistence, enabling local tissue destruction with the formation of an encaging abscess capsule, and facilitating the establishment and propagation of bacterial biofilms which block the access of host immune cells. Elucidating the molecular mechanisms underlying host–pathogen interactions in the setting of hypoxia will enable better understanding of persistent and recalcitrant infections due to S. aureus and may uncover novel therapeutic targets and strategies.
A Smart Energy Harvesting Platform for Wireless Sensor Network Applications
Authors: Filios Gabriel , Katsidimas Ioannis , Nikoletseas Sotiris , Tsenempis Ioannis
Published: November 2019

Advances in micro-electro-mechanical systems (MEMS) as well as the solutions for power scavenging can now provide feasible alternatives in a variety of applications. Wireless sensor networks (WSN), which operate on rechargeable batteries, could be based on a fresh basis which aims both at environmental power collection and wireless charging in various shapes and scales. Consequently, a potential illimitable energy supply can override the hypothesis of the limited energy budget (which can also impact the system’s efficiency). The presented platform is able to efficiently power a low power IoT system with processing, sensing and wireless transmission potentials. It incorporates a cutting-edge energy management IC that enables exceptional energy harvesting, applicable on low power and downsized energy generators. In contrast to other schemes, it supports not only a range of power supply alternatives, but also a compound energy depository system. The objective of this paper is to describe the design of the system, the integrated intelligence and the power autonomy performance.
Modeling Temperature Effects on Population Density of the Dengue Mosquito Aedes aegypti
Authors: El Moustaid Fadoua , Johnson Leah
Published: November 2019

Mosquito density plays an important role in the spread of mosquito-borne diseases such as dengue and Zika. While it remains very challenging to estimate the density of mosquitoes, modelers have tried different methods to represent it in mathematical models. The goal of this paper is to investigate the various ways mosquito density has been quantified, as well as to propose a dynamical system model that includes the details of mosquito life stages leading to the adult population. We first discuss the mosquito traits involved in determining mosquito density, focusing on those that are temperature dependent. We evaluate different forms of models for mosquito densities based on these traits and explore their dynamics as temperature varies. Finally, we compare the predictions of the models to observations of Aedes aegypti abundances over time in Vitòria, Brazil. Our results indicate that the four models exhibit qualitatively and quantitatively different behaviors when forced by temperature, but that all seem reasonably consistent with observed abundance data.
Non-Immersive Virtual Reality for Rehabilitation of the Older People: A Systematic Review into Efficacy and Effectiveness
Authors: Bevilacqua Roberta , Maranesi Elvira , Riccardi Giovanni Renato , Di Donna Valentina , Pelliccioni Paolo , Luzi Riccardo , Lattanzio Fabrizia , Pelliccioni Giuseppe
Published: November 2019

Objective: the objective of this review is to analyze the advances in the field of rehabilitation through virtual reality, while taking into account non-immersive systems, as evidence have them shown to be highly accepted by older people, due to the lowest “cibersikness” symptomatology. Data sources: a systematic review of the literature was conducted in June 2019. The data were collected from Cochrane, Embase, Scopus, and PubMed databases, analyzing manuscripts and articles of the last 10 years. Study selection: we only included randomized controlled trials written in English aimed to study the use of the virtual reality in rehabilitation. We selected 10 studies, which were characterized by clinical heterogeneity. Data extraction: quality evaluation was performed based on the Physioterapy Evidence Database (PEDro) scale, suggested for evidence based review of stroke rehabilitation. Of 10 studies considered, eight were randomized controlled trials and the PEDro score ranged from four to a maximum of nine. Data synthesis: VR (Virtual Reality) creates artificial environments with the possibility of a patient interaction. This kind of experience leads to the development of cognitive and motor abilities, which usually positively affect the emotional state of the patient, increasing collaboration and compliance. Some recent studies have suggested that rehabilitation treatment interventions might be useful and effective in treating motor and cognitive symptoms in different neurological disorders, including traumatic brain injury, multiple sclerosis, and progressive supranuclear palsy. Conclusions: as it is shown by the numerous studies in the field, the application of VR has a positive impact on the rehabilitation of the most predominant geriatric syndromes. The level of realism of the virtual stimuli seems to have a crucial role in the training of cognitive abilities. Future research needs to improve study design by including larger samples, longitudinal designs, long term follow-ups, and different outcome measures, including functional and quality of life indexes, to better evaluate the clinical impact of this promising technology in healthy old subjects and in neurological patients.