bluuebunny/crossref_metadata_2025 huggingface dataset:
Interregional Crown Width Models for Individual Trees Growing in Pure and Mixed Stands in Austria
Authors: Buchacher Rafael , Ledermann Thomas
Published: January 2020

Crown width is a functional trait that is commonly used to improve the estimation of above-ground biomass of forests and is often included as a predictor variable in forest growth models. Most of the existing crown width models reflect the relationship between crown width, tree size and competition variables, but do not consider the effect of species mixture. In this study, we developed crown width models for individual-tree of the major tree species growing in Austria. Because these models should be applicable for mixed and pure stands and should also take into account the characteristics of different sites, the relationship between crown width, site variables and species composition was investigated. For that purpose, we used data from a sub-sample of the Austrian National Forest Inventory, which comprises crown width measurements of about 8900 trees from 1508 sample plots. Because of the hierarchical structure of the data set (i.e., trees nested within the plot) which destroys the independencies between observations, linear mixed-effects models were used. The species composition of the stand was included via the species-specific relative proportions of basal area. To describe the interregional variability of crown width, dummy variables were introduced, which account for region-specific differences. Site characteristics were incorporated through the altitude, slope and aspect of the site. For Norway spruce, silver fir, Scots pine, European larch, European beech, oak species and ash/maple species it was possible to develop crown width models, which reflect the effects of site characteristics and species composition of the stand. The crown widths of shade-tolerant species reacted mainly positively to admixture, whereas light-demanding species reacted with decreasing crown widths. Coniferous species were not as strongly affected by mixture as broadleaf species.
Determinants of Non-Timber Forest Product Planting, Development, and Trading: Case Study in Central Vietnam
Authors: Nguyen Thanh Van , Lv Jie Hua , Vu Thi Thanh Huyen , Zhang Bin
Published: January 2020

Non-timber forest products (NTFPs) play an active role in economic development, improving household livelihoods, raising the value of forestry production, and supporting sustainable forest management. This study involved a comprehensive assessment of the growth, development, and trade of NTFPs in Vietnam by combining logistic and tobit methods. Surveys were used to interview 400 households in three regions of Central Vietnam. Results showed that the planting, development, and trading of NTFPs are shaped by forestry production experience, the number of laborers, the percentage of wage earners, agricultural income, timber income, per capita income, the presence of bank deposits, the distance between forest and house, an understanding of forestry economic policies, and participation in technical training. Each factor had a different level of influence. Among the six NTFP groups, the groups generating yarn and medicines produced the highest income and had a strong impact on household reliance on NTFPs. This was followed by NTFPs used to generate food, oil, and plastic. The proportion of people with wages, and the income variable system, negatively impacted NTFP planting and income generation, which reduced household reliance on NTFPs. This means that there is a trade-off between NTFPs and other income generating activities. In the future, the government should develop specific plans, policies, and strategies for developing each type of NTFP suitable to each region’s natural conditions. The policies should include supporting people with low-interest bank loans; expanding the number of training courses to increase their understanding of forestry economic policies; and implementing cultivation techniques and forest care to improve the productivity, quality, and efficiency of NTFP products.
Bacterial Flow Cytometry and Imaging as Potential Process Monitoring Tools for Industrial Biotechnology
Authors: Narayana Sumana Kadamalakunte , Mallick Sanjaya , Siegumfeldt Henrik , van den Berg Frans
Published: January 2020

Minimizing process variations by early identification of deviations is one approach to make industrial production processes robust. Cell morphology is a direct representation of the physiological state and an important factor for the cell’s survival in harsh environments as encountered during industrial processing. The adverse effects of fluctuating process parameters on cells were studied using flow cytometry and imaging. Results showed that altered pH caused a shift in cell size distribution from a heterogeneous mix of elongated and short cells to a homogenous population of short cells. Staining based on membrane integrity revealed a dynamics in the pattern of cluster formation during fermentation. Contradictory findings from forward scatter and imaging highlight the need for use of complementary techniques that provide visual confirmation to interpret changes. An atline flow cytometry or imaging capable of identifying subtle population deviations serves as a powerful monitoring tool for industrial biotechnology.
Tuning the Bivariate Meta-Gaussian Distribution Conditionally in Quantifying Precipitation Prediction Uncertainty
Authors: Wu Limin
Published: January 2020

One of the ways to quantify uncertainty of deterministic forecasts is to construct a joint distribution between the forecast variable and the observed variable; then, the uncertainty of the forecast can be represented by the conditional distribution of the observed given the forecast. The joint distribution of two continuous hydrometeorological variables can often be modeled by the bivariate meta-Gaussian distribution (BMGD). The BMGD can be obtained by transforming each of the two variables to a standard normal variable and the dependence between the transformed variables is provided by the Pearson correlation coefficient of these two variables. The BMGD modeling is exact provided that the transformed joint distribution is standard normal. In real-world applications, however, this normality assumption is hardly fulfilled. This is often the case for the modeling problem we consider in this paper: establish the joint distribution of a forecast variable and its corresponding observed variable for precipitation amounts accumulated over a duration of 24 h. In this case, the BMGD can only serve as an approximate model and the dependence parameter can be estimated in a variety of ways. In this paper, the effect of tuning this parameter is studied. Numerical simulations conducted suggest that, while the parameter tuning results in limited improvements in goodness-of-fit (GOF) for the BMGD as a bivariate distribution model, better results may be achieved by tuning the parameter for the one-dimensional conditional distribution of the observed given the forecast greater than a certain large value.
ATM Serine/Threonine Kinase and its Role in Pancreatic Risk
Authors: Nanda Neha , Roberts Nicholas J.
Published: January 2020

Next-generation sequencing has led to the recent discovery of several novel pancreatic cancer susceptibility genes. These genes include ataxia telangiectasia mutated (ATM), a serine/threonine kinase that is an integral component of DNA repair. Pathogenic germline ATM variants are frequently identified in patients with pancreatic ductal adenocarcinoma (PDAC) with and without a family history of the disease. Loss of ATM is also a frequent somatic event in the development of PDAC. These discoveries have advanced our understanding of the genetic basis of pancreatic cancer risk and will impact patient care through appropriate patient–risk stratification; personalized screening and early detection efforts; and, for some, targeted therapy.
Long-Term Effects of Air Pollutants on Mortality Risk in Patients with End-Stage Renal Disease
Authors: Jung Jiyun , Park Jae Yoon , Kim Yong Chul , Lee Hyewon , Kim Ejin , Kim Yong-Lim , Kim Yon Su , Lee Jung Pyo , Kim Ho ,   Clinical Research Center for End-Stage Renal Disease (CRC for ESRD) Investigators
Published: January 2020

Long-term exposure to air pollutants significantly increases the morbidity and mortality associated with various diseases. However, little is known about the relationship between air pollutants and end-stage renal disease (ESRD)-related mortality. A total of 5041 patients who started dialysis between 2008 and 2015 were prospectively enrolled in the Clinical Research Center for End-Stage Renal Disease (CRC-ESRD) cohort study. We assigned a daily mean concentration of air pollutants (PM10, NO2, and SO2) to each participant. Time-varying Cox models were used to investigate the relationship between air pollutants and mortality in ESRD patients. During the follow-up period (mean 4.18 years), 1475 deaths occurred among 5041 participants. We found a significant long-term relationship between mortality risk and PM10 (HR 1.33, CI 1.13–1.58), NO2 (HR 1.46, CI 1.10–1.95), and SO2 (HR 1.07, CI 1.03–1.11). Elderly patients and patients who lived in metropolitan areas had an increased risk associated with PM10. Elderly patients also had increased risks associated NO2 and SO2. Long-term exposure to air pollutants had negative effects on mortality in ESRD patients. These effects were prominent in elderly patients who lived in metropolitan areas, suggesting that ambient air pollution, in addition to traditional risk factors, is important for the survival of these patients.
Factors Associated with the Psychological Health of Caregiving Older Parents and Support from Their Grown Children: Results from the China Health and Retirement Longitudinal Study
Authors: Fu Liping , Wang Yuhui , He Lanping
Published: January 2020

In China, older parents have become an important source of childcare for their grown children since 2010. However, caring for grandchildren may affect older parents’ psychological health (PH) in both positive and negative ways. Using the method of stepwise decreasing logistic regression, this study aimed to assess the factors associated with PH and support from grown children among caregiving older parents (400 respondents) based on the public panel data of the China Health and Retirement Longitudinal Study (CHARLS). The findings showed that being male (X1, OR = 1.661 (95% CI 1.066–2.590)), being literate (X4, OR = 2.129 (95% CI 1.369–3.309)), and expecting long-term care in the future from their grown children (X6, OR = 2.695 (95% CI 1.736–4.185)) were significant factors associated with PH. Therefore, in such an aging society, we should not regard older parents as a “burden”; we should recognize and appreciate their contribution to caregiving. As family and children, it is important to give older parents the necessary economic and emotional support to maintain their psychological health in the meantime.
Hyperbaric Oxygen Treatment for Carbon Monoxide Poisoning in Italy: Retrospective Validation of a Data Collection Tool for the Italian Registry of Carbon Monoxide Poisonings (IRCOP)
Authors: Maffi Lidio , Paganini Matteo , Vezzani Giuliano , Soumelis Antonios ,   ASPATI Research Group, Camporesi Enrico M , Bosco Gerardo
Published: January 2020

Background: Carbon Monoxide (CO) poisoning is a frequent cause of intoxication. However, CO poisoning incidence is globally underreported, as well as its features, especially in Italy. The aim of this study was to investigate such characteristics of CO intoxication and foster the creation of the Italian Registry of Carbon Monoxide Poisonings. Methods: A data collection tool was developed and organized in five sections: Patient’s characteristics; CO intoxication modality; emergency medical service and emergency department; hyperbaric facility; outcomes. The tool was validated through a retrospective analysis, including CO intoxicated patients treated in 14 Italian hyperbaric facilities between 2015 and 2016. Results: A total of 1383 patients were included. The high completion ratio (85%) of the collection tool suggests its feasibility in practical terms. CO intoxications were mostly accidental (93.64%) and caused by solid fuel (48.59%). There was not a uniform application of hyperbaric oxygen treatment protocols, but most of the patients were adequately treated at least at 2.5 ATA for more than 60 min (44.97%). Conclusion: This analysis provided new information that was previously unavailable in this country. Furthermore, this tool proved to be a valid base for future registry aiming to consolidate the body of knowledge about CO intoxications in Italy.
Domain-Specific and Total Sedentary Behavior Associated with Gait Velocity in Older Adults: The Mediating Role of Physical Fitness
Authors: Kasović Mario , Štefan Lovro , Zvonař Martin
Published: January 2020

Although it has been well-documented that older adults spend a significant amount of time being sedentary and have slower gait velocity, little is known of how physical fitness mediates the association between them. The main purpose of this study was to explore whether objectively measured physical fitness mediates the association between domain-specific and total sedentary behavior and gait velocity. We recruited 120 older adults aged ≥ 60 years. Sedentary behavior was assessed by the Measure of Older Adults’ Sedentary Time questionnaire. We used a Zebris pressure platform to assess gait velocity. To assess the level of overall physical fitness, we summed the z-scores of seven tests: (1) waist circumference, (2) chair stand in 30 s, (3) arm curl in 30 s, (4) 2-min step test, (5) chair sit-and-reach test, (6) back scratch test, and (7) 8-foot up-and-go test. Overall physical fitness was obtained by summing up all physical test z-scores. Gait velocity was significantly associated with all domain-specific and total sedentary behavior (β = −0.04 to −0.35, p < 0.05). Overall physical fitness was significantly associated with all domain-specific and total sedentary behavior (β = −0.21 to −1.24, p < 0.001) and gait velocity (β = 0.23 to 0.24, p < 0.001). When physical fitness was put as the mediator, significant direct effects between sedentary behavior and gait velocity disappeared. Results indicate that physical fitness fully mediates the association between sedentary behavior and gait velocity in older adults.
Associations between Physical Activity and Comorbidities in People with COPD Residing in Spain: A Cross-Sectional Analysis
Authors: Sánchez Castillo Sheila , Smith Lee , Díaz Suárez Arturo , López Sánchez Guillermo Felipe
Published: January 2020

There is a high prevalence of comorbidities among patients with chronic obstructive pulmonary disease (COPD). Comorbidities are likely common in patients with any COPD degree and are associated with increased mortality. The aim of this study was to determine the prevalence of thirty-one different COPD comorbidities and to evaluate the association between physical activity (PA) levels in people with COPD residing in Spain. Cross-sectional data from the Spanish National Health Survey 2017 were analysed. A total of 601 adults (52.2% females) with COPD aged 15 to 69 participated in this study. PA (exposure) was measured with the International Physical Activity Questionnaire (IPAQ) short form and comorbidities (outcomes) were self-reported in response to the question “Have you ever been diagnosed with…?” Multivariable logistic regression, in three different models, was used to assess this association. Results showed a high prevalence of comorbidities (94%), these being chronic lumbar back pain (38.9%), chronic allergy (34.8%), arthrosis (34.1%), chronic cervical back pain (33.3%), asthma (32.9%) and hypertension (32.8%) the most prevalent. Low PA level was significantly associated with urinary incontinence (2.115[1.213–3.689]), chronic constipation (1.970[1.119–3.459]), cataracts (1.840[1.074–3.153]), chronic anxiety (1.508[1.002–2.269]) and chronic lumbar back pain (1.489[1.044–2.125]). Therefore, people with COPD should increase their PA levels in order to reduce their risk of comorbidities and increase their quality of life.
School-Class Co-Ethnic and Immigrant Density and Current Smoking among Immigrant Adolescents
Authors: Kern Matthias Robert , Heinz Andreas , Willems Helmut Erich
Published: January 2020

Although the school-class is known to be an important setting for adolescent risk behavior, little is known about how the ethnic composition of a school-class impacts substance use among pupils with a migration background. Moreover, the few existing studies do not distinguish between co-ethnic density (i.e., the share of immigrants belonging to one’s own ethnic group) and immigrant density (the share of all immigrants). This is all the more surprising since a high co-ethnic density can be expected to protect against substance use by increasing levels of social support and decreasing acculturative stress, whereas a high immigrant density can be expected to do the opposite by facilitating inter-ethnic conflict and identity threat. This study analyses how co-ethnic density and immigrant density are correlated with smoking among pupils of Portuguese origin in Luxembourg. A multi-level analysis is used to analyze data from the Luxembourg Health Behavior in School-Aged Children study (N = 4268 pupils from 283 classes). High levels of co-ethnic density reduced current smoking. In contrast, high levels of immigrant density increased it. Thus, in research on the health of migrants, the distinction between co-ethnic density and immigrant density should be taken into account, as both may have opposite effects.
The Effect of Age on Gait Speed When Texting
Authors: Alapatt Linson J. , Peel Nancye M. , Reid Natasha , Gray Leonard C. , Hubbard Ruth E.
Published: January 2020

Texting while walking exerts a high cognitive load, and may be a sensitive test of the integrity of the cognitive–motor interface. We aimed to investigate the association between chronological age and gait speed while texting. A convenience sample of 308 community-dwellers was recruited: n ≥ 50 in each age group (20–29, 30–39, 40–49, 50–59) and n = 100 aged ≥60 years. Gait speed was measured over 10 metres under two experimental conditions: 1) walking at usual pace; 2) walking at usual pace while texting the message “Good morning Harry” on their smartphone. Both median gait speed with and without texting decreased with increasing age (p < 0.001). The differences between single- and dual-task gait speed were substantial for each age group and increased after the age of 50 years (p < 0.001). Median gait speeds while texting in people aged 50–59 (1.07 m/s) and ≥60 years (1.00 m/s) were below the recommended minimum for safely crossing roads (1.20 m/s). Texting while walking currently exposes people aged 50 and over to considerable environmental hazards. The significant slowing of gait speed while texting from middle age may be a marker of neurodegeneration, a cohort effect, or an appropriate compensatory response to reduce the risk of injury.
Vascular Endothelial Growth Factor A and VEGFR-1 Change during Preimplantation in Heifers
Authors: Chiumia Daniel , Hankele Anna-Katharina , Groebner Anna E. , Schulke Katy , Reichenbach Horst-Dieter , Giller Katrin , Zakhartchenko Valeri , Bauersachs Stefan , Ulbrich Susanne E.
Published: January 2020

Vascular endothelial growth factor A (VEGFA) plays a critical angiogenic role in the endometrium of placentalia during preimplantation. The role of VEGFA and its receptors is not fully characterised in bovine reproduction. We analysed the mRNA expression of VEGFA isoforms 121, 165 and 189, and VEGF receptors 1 and 2 in three experimental settings (A, B and C). We compared intercaruncular endometrium of cyclic to pregnant heifers at Days 12, 15 and 18 post insemination (Day 0), and between Day 15 and Day 18 conceptuses (A). We further compared caruncular versus intercaruncular endometrium at Day 15 (B), and endometrium of heifers carrying embryos originating from somatic cell nuclear transfer (SCNT) versus in vitro fertilisation (IVF) at Day 18 (C). Endometrial VEGFA protein was localised and quantified. Pregnant heifers displayed lower intercaruncular endometrial mRNA expression of VEGFA-121 (p = 0.045) and VEGFA-189 (p = 0.009) as well as lower VEGFA protein abundance (p < 0.001) at Day 15. The VEGFA protein was localised in intercaruncular luminal, glandular epithelium and in tunica muscularis of blood vessels. At Day 15, caruncular endometrium displayed higher VEGFA mRNA expression than intercaruncular endometrium (p < 0.05). Intercaruncular endometrial VEGFA protein at Day 18 was higher in abundance in SCNT than in IVF (p = 0.038). Therefore, during preimplantation in cattle, there may be a need for timely physiological reduction in intercaruncular endometrial VEGFA expression in favour of the caruncular area to facilitate a gradient towards the implantation sites. A higher expression of VEGFA in SCNT may predispose for later placentation abnormalities frequently observed following SCNT.
PreS1 Mutations Alter the Large HBsAg Antigenicity of a Hepatitis B Virus Strain Isolated in Bangladesh
Authors: Hossain Md. Golzar , Mahmud Md. Muket , Nazir K. H. M. Nazmul Hussain , Ueda Keiji
Published: January 2020

Mutations in the hepatitis B virus (HBV) genome can potentially lead to vaccination failure, diagnostic escape, and disease progression. However, there are no reports on viral gene expression and large hepatitis B surface antigen (HBsAg) antigenicity alterations due to mutations in HBV isolated from a Bangladeshi population. Here, we sequenced the full genome of the HBV isolated from a clinically infected patient in Bangladesh. The open reading frames (ORFs) (P, S, C, and X) of the isolated HBV strain were successfully amplified and cloned into a mammalian expression vector. The HBV isolate was identified as genotype C (sub-genotype C2), serotype adr, and evolutionarily related to strains isolated in Indonesia, Malaysia, and China. Clinically significant mutations, such as preS1 C2964A, reverse transcriptase domain I91L, and small HBsAg N3S, were identified. The viral P, S, C, and X genes were expressed in HEK-293T and HepG2 cells by transient transfection with a native subcellular distribution pattern analyzed by immunofluorescence assay. Western blotting of large HBsAg using preS1 antibody showed no staining, and preS1 ELISA showed a significant reduction in reactivity due to amino acid mutations. This mutated preS1 sequence has been identified in several Asian countries. To our knowledge, this is the first report investigating changes in large HBsAg antigenicity due to preS1 mutations.
Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament
Authors: Grotegut Pia , Kuehn Sandra , Dick H. Burkhard , Joachim Stephanie C.
Published: January 2020

Heat shock protein 27 (HSP27) is commonly involved in cellular stress. Increased levels of HSP27 as well as autoantibodies against this protein were previously detected in glaucoma patients. Moreover, systemic immunization with HSP27 induced glaucoma-like damage in rodents. Now, for the first time, the direct effects of an intravitreal HSP27 application were investigated. For this reason, HSP27 or phosphate buffered saline (PBS, controls) was applied intravitreally in rats (n = 12/group). The intraocular pressure (IOP) as well as the electroretinogram recordings were comparable in HSP27 and control eyes 21 days after the injection. However, significantly fewer retinal ganglion cells (RGCs) and amacrine cells were observed in the HSP27 group via immunohistochemistry and western blot analysis. The number of bipolar cells, on the other hand, was similar in both groups. Interestingly, a stronger neurofilament degeneration was observed in HSP27 optic nerves, while no differences were noted regarding the myelination state. In summary, intravitreal HSP27 injection led to an IOP-independent glaucoma-like damage. A degeneration of RGCs as well as their axons and amacrine cells was noted. This suggests that high levels of extracellular HSP27 could have a direct damaging effect on RGCs.
Molecular Profile of Phage Infection: A Novel Approach for the Characterization of Erwinia Phages through qPCR
Authors: Parcey Michael , Gayder Steven , Castle Alan J. , Svircev Antonet M.
Published: January 2020

Due to the emergence of antibiotic resistance, phage-mediated biocontrol has become an attractive alternative for pathogen management in agriculture. While the infection characteristics of many phages can be adequately described using plaque assays and optical density, the results from phages of the apple pathogen Erwinia amylovora have low reproducibility with these techniques. Using quantitative real-time PCR (qPCR), the stage of the lytic cycle was determined through a combination of chloroform-based sampling, centrifugation, and DNase treatment. Monitoring the transition of phage genomes through the lytic cycle generates a molecular profile from which phage infection characteristics such as adsorption rate and burst size can be determined. To our knowledge, this is the first report of qPCR being used to determine these infection parameters. The characteristics of four different genera of Erwinia phages were determined. The phage ΦEa46-1-A1 was able to adsorb at a rate up to 6.6 times faster than ΦEa35-70 and ΦEa9-2. The low enrichment titer of ΦEa9-2 was shown to be due to the absence of lysis. The ΦEa46-1-A1 and ΦEa21-4 phages had the highest productivity, with burst sizes of 57 virions in 38 min and 185 virions in 98 min, respectively, suggesting these genera would make stronger candidates for the phage-mediated biocontrol of E. amylovora.
Riboflavin Plays a Pivotal Role in the UVA-Induced Cytotoxicity of Fibroblasts as a Key Molecule in the Production of H2O2 by UVA Radiation in Collaboration with Amino Acids and Vitamins
Authors: Yoshimoto Satoshi , Kohara Nana , Sato Natsu , Ando Hideya , Ichihashi Masamitsu
Published: January 2020

To investigate environmental factors that contribute to ultraviolet A (UVA)-induced oxidative stress, which accelerates the senescence and toxicity of skin cells, we irradiated human fibroblasts cultured in commonly used essential media with UVA and evaluated their viability and production of reactive oxygen species. The viability of fibroblasts exposed to a single dose of 3.6 J/cm2 UVA was not reduced when cultured in Hanks balanced salt solution, but it was significantly decreased when cultured in Dulbecco’s modified Eagle’s medium (DMEM), which contains various amino acids and vitamins. Furthermore, cell viability was not reduced when fibroblasts were cultured in DMEM and treated with a hydrogen peroxide (H2O2) scavenger such as glutathione or catalase added after UVA irradiation. In addition, we confirmed that the production of H2O2 was dramatically increased by UVA photosensitization when riboflavin (R) coexisted with amino acids such as tryptophan (T), and found that R with folic acid (F) produced high levels of H2O2 after UVA irradiation. Furthermore, we noticed that R and F or R and T have different photosensitization mechanisms since NaN3, which is a singlet oxygen quencher, suppressed only R and T photosensitization. Lastly, we examined the effects of antioxidants (L-ascorbic acid, trolox, L-cysteine, and L-histidine), which are singlet oxygen or superoxide or H2O2 scavengers, on R and F or on R and T photosensitization, and found that 1 mM ascorbic acid, Trolox, and L-histidine were strongly photosensitized with R, and produced significant levels of H2O2 during UVA exposure. However, 1 mM L-cysteine dramatically suppressed H2O2 production by UVA photosensitization. These data suggest that a low concentration of R-derived photosensitization is elicited by different mechanisms depending on the coexisting vitamins and amino acids, and regulates cellular oxidative stress by producing H2O2 during UVA exposure.
Enhanced Efficacy of PEGylated Liposomal Cisplatin: In Vitro and In Vivo Evaluation
Authors: Ghaferi Mohsen , Asadollahzadeh Mohammad Javad , Akbarzadeh Azim , Ebrahimi Shahmabadi Hasan , Alavi Seyed Ebrahim
Published: January 2020

This study aims to evaluate the potency of cisplatin (Cispt)-loaded liposome (LCispt) and PEGylated liposome (PLCispt) as therapeutic nanoformulations in the treatment of bladder cancer (BC). Cispt was loaded into liposomes using reverse-phase evaporation method, and the formulations were characterized using dynamic light scattering, scanning electron microscopy, dialysis membrane, and Fourier-transform infrared spectroscopy (FTIR) methods. The results showed that the particles were formed in spherical monodispersed shapes with a nanoscale size (221–274 nm) and controlled drug release profile. The cytotoxicity effects of LCispt and PLCispt were assessed in an in vitro environment, and the results demonstrated that PLCispt caused a 2.4- and 1.9-fold increase in the cytotoxicity effects of Cispt after 24 and 48 h, respectively. The therapeutic and toxicity effects of the formulations were also assessed on BC-bearing rats. The results showed that PLCispt caused a 4.8-fold increase in the drug efficacy (tumor volume of 11 ± 0.5 and 2.3 ± 0.1 mm3 in Cispt and PLCispt receiver rats, respectively) and a 3.3-fold decrease in the toxicity effects of the drug (bodyweight gains of 3% and 10% in Cispt and PLCispt receiver rats, respectively). The results of toxicity were also confirmed by histopathological studies. Overall, this study suggests that the PEGylation of LCispt is a promising approach to achieve a nanoformulation with enhanced anticancer effects and reduced toxicity compared to Cispt for the treatment of BC.
Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABAA Receptors with a Special Reference to Propofol/Barbiturate
Authors: Kang Youngnam , Saito Mitsuru , Toyoda Hiroki
Published: January 2020

It is known that desensitization of GABAA receptor (GABAAR)-mediated currents is paradoxically correlated with the slowdown of their deactivation, i.e., resensitization. It has been shown that an upregulation of calcineurin enhances the desensitization of GABAAR-mediated currents but paradoxically prolongs the decay phase of inhibitory postsynaptic currents/potentials without appreciable diminution of their amplitudes. The paradoxical correlation between desensitization and resensitization of GABAAR-mediated currents can be more clearly seen in response to a prolonged application of GABA to allow more desensitization, instead of brief pulse used in previous studies. Indeed, hump-like GABAAR currents were produced after a strong desensitization at the offset of a prolonged puff application of GABA in pyramidal cells of the barrel cortex, in which calcineurin activity was enhanced by deleting phospholipase C-related catalytically inactive proteins to enhance the desensitization/resensitization of GABAAR-mediated currents. Hump-like GABAAR currents were also evoked at the offset of propofol or barbiturate applications in hippocampal or sensory neurons, but not GABA applications. Propofol and barbiturate are useful to treat benzodiazepine/alcohol withdrawal syndrome, suggesting that regulatory mechanisms of desensitization/resensitization of GABAAR-mediated currents are important in understanding benzodiazepine/alcohol withdrawal syndrome. In this review, we will discuss the molecular and regulatory mechanisms underlying the desensitization and resensitization of GABAAR-mediated currents and their functional significances.
Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases
Authors: Méchin Marie-Claire , Takahara Hidenari , Simon Michel
Published: January 2020

Deimination, also known as citrullination, corresponds to the conversion of the amino acid arginine, within a peptide sequence, into the non-standard amino acid citrulline. This post-translational modification is catalyzed by a family of calcium-dependent enzymes called peptidylarginine deiminases (PADs). Deimination is implicated in a growing number of physiological processes (innate and adaptive immunity, gene regulation, embryonic development, etc.) and concerns several human diseases (rheumatoid arthritis, neurodegenerative diseases, female infertility, cancer, etc.). Here, we update the involvement of PADs in both the homeostasis of skin and skin diseases. We particularly focus on keratinocyte differentiation and the epidermal barrier function, and on hair follicles. Indeed, alteration of PAD activity in the hair shaft is responsible for two hair disorders, the uncombable hair syndrome and a particular form of inflammatory scarring alopecia, mainly affecting women of African ancestry.
Does Protein Glycation Impact on the Drought-Related Changes in Metabolism and Nutritional Properties of Mature Pea (Pisum sativum L.) Seeds?
Authors: Leonova Tatiana , Popova Veronika , Tsarev Alexander , Henning Christian , Antonova Kristina , Rogovskaya Nadezhda , Vikhnina Maria , Baldensperger Tim , Soboleva Alena , Dinastia Ekaterina , Dorn Mandy , Shiroglasova Olga , Grishina Tatiana , Balcke Gerd U. , Ihling Christian , Smolikova Galina , Medvedev Sergei , Zhukov Vladimir A. , Babakov Vladimir , Tikhonovich Igor A. , Glomb Marcus A. , Bilova Tatiana , Frolov Andrej
Published: January 2020

Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications formed by reducing sugars and carbonyl products of their degradation. The resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied with respect to glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in the dramatic suppression of primary seed metabolism, although the secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.
Phytochemicals for the Prevention and Treatment of Gastric Cancer: Effects and Mechanisms
Authors: Mao Qian-Qian , Xu Xiao-Yu , Shang Ao , Gan Ren-You , Wu Ding-Tao , Atanasov Atanas G. , Li Hua-Bin
Published: January 2020

Gastric cancer is the fifth most common cancer, and the third most prevalent cause of cancer-related deaths in the world. Voluminous evidence has demonstrated that phytochemicals play a critical role in the prevention and management of gastric cancer. Most epidemiological investigations indicate that the increased intake of phytochemicals could reduce the risk of gastric cancer. Experimental studies have elucidated the mechanisms of action, including inhibiting cancer cell proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis as well as cancer cell metastasis. These mechanisms have also been related to the inhibition of Helicobacter pylori and the modulation of gut microbiota. In addition, the intake of phytochemicals could enhance the efficacy of anticancer chemotherapeutics. Moreover, clinical studies have illustrated that phytochemicals have the potential for the prevention and the management of gastric cancer in humans. To provide an updated understanding of relationships between phytochemicals and gastric cancer, this review summarizes the effects of phytochemicals on gastric cancer, highlighting the underlying mechanisms. This review could be helpful for guiding the public in preventing gastric cancer through phytochemicals, as well as in developing functional food and drugs for the prevention and treatment of gastric cancer.
iTRAQ-Based Quantitative Proteomic Analysis of the Arabidopsis Mutant opr3-1 in Response to Exogenous MeJA
Authors: Qi Jiayu , Zhao Xiaoyun , Li Zhen
Published: January 2020

Jasmonates (JAs) regulate the defense of biotic and abiotic stresses, growth, development, and many other important biological processes in plants. The comprehensive proteomic profiling of plants under JAs treatment provides insights into the regulation mechanism of JAs. Isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis was performed on the Arabidopsis wild type (Ws) and JA synthesis deficiency mutant opr3-1. The effects of exogenous MeJA treatment on the proteome of opr3-1, which lacks endogenous JAs, were investigated. A total of 3683 proteins were identified and 126 proteins were differentially regulated between different genotypes and treatment groups. The functional classification of these differentially regulated proteins showed that they were involved in metabolic processes, responses to abiotic stress or biotic stress, the defense against pathogens and wounds, photosynthesis, protein synthesis, and developmental processes. Exogenous MeJA treatment induced the up-regulation of a large number of defense-related proteins and photosynthesis-related proteins, it also induced the down-regulation of many ribosomal proteins in opr3-1. These results were further verified by a quantitative real-time PCR (qRT-PCR) analysis of 15 selected genes. Our research provides the basis for further understanding the molecular mechanism of JAs’ regulation of plant defense, photosynthesis, protein synthesis, and development.
Stereoselective Synthesis of Carbon-Sulfur-Bridged Glycomimetics by Photoinitiated Thiol-Ene Coupling Reactions
Authors: Csávás Magdolna , Eszenyi Dániel , Mező Erika , Lázár László , Debreczeni Nóra , Tóth Marietta , Somsák László , Borbás Anikó
Published: January 2020

Oligosaccharides and glycoconjugates are abundant in all living organisms, taking part in a multitude of biological processes. The application of natural O-glycosides in biological studies and drug development is limited by their sensitivity to enzymatic hydrolysis. This issue made it necessary to design hydrolytically stable carbohydrate mimetics, where sulfur, carbon, or longer interglycosidic connections comprising two or three atoms replace the glycosidic oxygen. However, the formation of the interglycosidic linkages between the sugar residues in high diastereoslectivity poses a major challenge. Here, we report on stereoselective synthesis of carbon-sulfur-bridged disaccharide mimetics by the free radical addition of carbohydrate thiols onto the exo-cyclic double bond of unsaturated sugars. A systematic study on UV-light initiated radical mediated hydrothiolation reactions of enoses bearing an exocyclic double bond at C1, C2, C3, C4, C5, and C6 positions of the pyranosyl ring with various sugar thiols was performed. The effect of temperature and structural variations of the alkenes and thiols on the efficacy and stereoselectivity of the reactions was systematically studied and optimized. The reactions proceeded with high efficacy and, in most cases, with complete diastereoselectivity producing a broad array of disaccharide mimetics coupling through an equatorially oriented methylensulfide bridge.
The Impact of IPTG Induction on Plasmid Stability and Heterologous Protein Expression by Escherichia coli Biofilms
Authors: Gomes Luciana , Monteiro Gabriel , Mergulhão Filipe
Published: January 2020

This work assesses the effect of chemical induction with isopropyl β-D-1-thiogalactopyranoside (IPTG) on the expression of enhanced green fluorescent protein (eGFP) by planktonic and biofilm cells of Escherichia coli JM109(DE3) transformed with a plasmid containing a T7 promoter. It was shown that induction negatively affected the growth and viability of planktonic cultures, and eGFP production did not increase. Heterologous protein production was not limited by gene dosage or by transcriptional activity. Results suggest that plasmid maintenance at high copy number imposes a metabolic burden that precludes high level expression of the heterologous protein. In biofilm cells, the inducer avoided the overall decrease in the amount of expressed eGFP, although this was not correlated with the gene dosage. Higher specific production levels were always attained with biofilm cells and it seems that while induction of biofilm cells shifts their metabolism towards the maintenance of heterologous protein concentration, in planktonic cells the cellular resources are directed towards plasmid replication and growth.
Platelet-Rich Fibrin Facilitates One-Stage Cartilage Repair by Promoting Chondrocytes Viability, Migration, and Matrix Synthesis
Authors: Wong Chin-Chean , Ou Keng-Liang , Lin Yun-Ho , Lin Ming-Fang , Yang Tsung-Lin , Chen Chih-Hwa , Chan Wing P.
Published: January 2020

The main aim of this study is to develop a one-stage method to combine platelet-rich fibrin (PRF) and autologous cartilage autografts for porcine articular cartilage repair. The porcine chondrocytes were treated with different concentrations of PRF-conditioned media and were evaluated for their cell viability and extracellular glycosaminoglycan (GAG) synthesis during six day cultivation. The chemotactic effects of PRF on chondrocytes on undigested cartilage autografts were revealed in explant cultures. For the in vivo part, porcine chondral defects were created at the medial femoral condyles of which were (1) left untreated, (2) implanted with PRF combined with hand-diced cartilage grafts, or (3) implanted with PRF combined with device-diced cartilage grafts. After six months, gross grades, histological, and immunohistochemical analyses were compared. The results showed that PRF promotes the viability and GAG expression of the cultured chondrocytes. Additionally, the PRF-conditioned media induce significant cellular migration and outgrowth of chondrocytes from undigested cartilage grafts. In the in vivo study, gross grading and histological scores showed significantly better outcomes in the treatment groups as compared with controls. Moreover, both treatment groups showed significantly more type II collagen staining and minimal type I collagen staining as compared with controls, indicating more hyaline-like cartilage and less fibrous tissue. In conclusion, PRF enhances the viability, differentiation, and migration of chondrocytes, thus, showing an appealing capacity for cartilage repair. The data altogether provide evidences to confirm the feasibility of a one-stage, culture-free method of combining PRF and cartilage autografts for repairing articular cartilage defects. From translational standpoints, these advantages benefit clinical applications by simplifying and potentiating the efficacy of cartilage autograft transplants.
In Vitro Fabrication of Hybrid Bone/Cartilage Complex Using Mouse Induced Pluripotent Stem Cells
Authors: Limraksasin Phoonsuk , Kondo Takeru , Zhang Maolin , Okawa Hiroko , Osathanon Thanaphum , Pavasant Prasit , Egusa Hiroshi
Published: January 2020

Cell condensation and mechanical stimuli play roles in osteogenesis and chondrogenesis; thus, they are promising for facilitating self-organizing bone/cartilage tissue formation in vitro from induced pluripotent stem cells (iPSCs). Here, single mouse iPSCs were first seeded in micro-space culture plates to form 3-dimensional spheres. At day 12, iPSC spheres were subjected to shaking culture and maintained in osteogenic induction medium for 31 days (Os induction). In another condition, the osteogenic induction medium was replaced by chondrogenic induction medium at day 22 and maintained for a further 21 days (Os-Chon induction). Os induction produced robust mineralization and some cartilage-like tissue, which promoted expression of osteogenic and chondrogenic marker genes. In contrast, Os-Chon induction resulted in partial mineralization and a large area of cartilage tissue, with greatly increased expression of chondrogenic marker genes along with osterix and collagen 1a1. Os-Chon induction enhanced mesodermal lineage commitment with brachyury expression followed by high expression of lateral plate and paraxial mesoderm marker genes. These results suggest that combined use of micro-space culture and mechanical stimuli facilitates hybrid bone/cartilage tissue formation from iPSCs, and that the bone/cartilage tissue ratio in iPSC constructs could be manipulated through the induction protocol.
Mechanical Model for Catch-Bond-Mediated Cell Adhesion in Shear Flow
Authors: Li Long , Kang Wei , Wang Jizeng
Published: January 2020

Catch bond, whose lifetime increases with applied tensile force, can often mediate rolling adhesion of cells in a hydrodynamic environment. However, the mechanical mechanism governing the kinetics of rolling adhesion of cells through catch-bond under shear flow is not yet clear. In this study, a mechanical model is proposed for catch-bond-mediated cell adhesion in shear flow. The stochastic reaction of bond formation and dissociation is described as a Markovian process, whereas the dynamic motion of cells follows classical analytical mechanics. The steady state of cells significantly depends on the shear rate of flow. The upper and lower critical shear rates required for cell detachment and attachment are extracted, respectively. When the shear rate increases from the lower threshold to the upper threshold, cell rolling became slower and more regular, implying the flow-enhanced adhesion phenomenon. Our results suggest that this flow-enhanced stability of rolling adhesion is attributed to the competition between stochastic reactions of bonds and dynamics of cell rolling, instead of force lengthening the lifetime of catch bonds, thereby challenging the current view in understanding the mechanism behind this flow-enhanced adhesion phenomenon. Moreover, the loading history of flow defining bistability of cell adhesion in shear flow is predicted. These theoretical predictions are verified by Monte Carlo simulations and are related to the experimental observations reported in literature.
Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges
Authors: Kunimasa Kei , Goto Taichiro
Published: January 2020

The immune system plays a dual role in tumor evolution—it can identify and control nascent tumor cells in a process called immunosurveillance and can promote tumor progression through immunosuppression via various mechanisms. Thus, bilateral host-protective and tumor-promoting actions of immunity are integrated as cancer immunoediting. In this decade, immune checkpoint inhibitors, specifically programmed cell death 1 (PD-1) pathway inhibitors, have changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). These agents are approved for the treatment of patients with NSCLC and demonstrate impressive clinical activity and durable responses in some patients. However, for many NSCLC patients, the efficacy of immune checkpoint inhibitors is limited. To optimize the full utility of the immune system for eradicating cancer, a broader understanding of cancer immunosurveillance and immunoediting is essential. In this review, we discuss the fundamental knowledge of the phenomena and provide an overview of the next-generation immunotherapies in the pipeline.