bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Procedure of Total Organic Carbon Analysis for Water Samples Containing Suspended Solids with Alkaline Extraction and Homogeneity Evaluation by Turbidity
Authors: Lee Han-Saem , Hur Jin , Hwang Yu-Hoon , Shin Hyun-Sang
Published: June 2020

This study was conducted to develop and validate a more reliable total organic carbon (TOC) analytical procedure for water samples containing suspended solids (SS). The effects of the combined ultrasonic and alkaline pretreatment (CULA) on the TOC measurement were studied in water samples containing SS from three origins (algae, sewage particles, and soil) under different analytical conditions (SS concentration, oxidation methods, and sieve size). The applicability of turbidity as a homogeneity index was also evaluated. With CULA, TOC recovery remained high (>80%) for SS concentration ranges up to four times larger than ultrasonic pretreatment alone (UL) due to enhanced particulate organic carbon (POC) solubilization, and did not significantly differ depending on the oxidation methods, at low SS concentrations, or with varying sieve sizes. In particular, the turbidity change rate (i.e., NTU5/NTU0) of the pretreated water sample showed a high correlation with TOC precision (r2 = 0.73, p < 0.01), which suggests that turbidity can be used as an indicator of sample homogeneity. A novel TOC analytical procedure is expected to be useful for more accurate assessments of the impact of particulate pollutants on water quality than current methods, and for the analysis of the carbon cycle, including POCs, in the environment.
Tobacco Dependence Treatment in Oncology: Initial Patient Clinical Characteristics and Outcomes from Roswell Park Comprehensive Cancer Center
Authors: Sheffer Christine E. , Stein Jeffrey S. , Petrucci Cara , Mahoney Martin C. , Johnson Shirley , Giesie Pamela , Carl Ellen , Krupski Laurie , Tegge Allison N. , Reid Mary E. , Bickel Warren K. , Hyland Andrew
Published: June 2020

Despite the importance of smoking cessation to cancer care treatment, historically, few cancer centers have provided treatment for tobacco dependence. To address this gap, the National Cancer Institute (NCI) launched the Cancer Center Cessation Initiative (C3i). As part of this effort, this study examined implementation outcomes in a cohort of cancer survivors (CSs) who smoked cigarettes in the first year of an ongoing process to develop and implement a robust Tobacco Treatment Service at Roswell Park Comprehensive Cancer Center. We provide a comprehensive description of the new tobacco use assessment and referral process, and of the characteristics of cancer survivors who agreed to treatment including traditional tobacco-related psychosocial and cancer treatment-related characteristics and novel characteristics such as delay discounting rates. We also examine characteristic differences among those who agreed to treatment between those who attended and those who did not attend treatment. As the new tobacco assessment was implemented, the number of referrals increased dramatically. The mean number of treatment sessions attended was 4.45 (SD = 2.98) and the six-month point prevalence intention to treat abstinence rate among those who attended was 22.7%. However, only 6.4% agreed to treatment and 4% attended at least one treatment session. A large proportion of cancer survivors who agreed to treatment were women, of older age, of lower socioeconomic status (SES), and who had high levels of depressive symptomology. The findings demonstrate that the implementation of system changes can significantly improve the identification of cancer survivors who use tobacco and are referred to tobacco use treatment. Among those who attend, treatment is effective. However, the findings also suggest that a systematic assessment of barriers to engagement is needed and that cancer survivors may benefit from additional treatment tailoring. We present plans to address these implementation challenges. Systematic electronic medical record (EMR)-sourced referral to tobacco treatment is a powerful tool for reaching cancer survivors who smoke, but more research is needed to determine how to enhance engagement and tailor treatment processes.
Predictors for Sexual Intercourse Experience among Runaway Female At-Risk Adolescents
Authors: Moon So-Hyun , Kim Hyung-Ran , Kim Miok
Published: June 2020

This study attempted to provide basic data for creating a program to help promote safe sexual behavior among runaway female at-risk adolescents by identifying factors related to the sexual experiences. This study conducted a logistic regression analysis using data regarding 182 female at-risk adolescents, which were sourced from the 2016 survey of Korean adolescents’ contact with media usage and harmful environment. This study showed that adolescents’ age, smoking, and harmful environments are associated with the occurrence of sexual activity among at-risk female adolescents. One significant outcome of this study was the identification of harmful environmental factors and their impact on sexual behavior. Since smoking and sex-related problems among adolescents can act as risk factors for adult sexual health in the future, schools should institute direct and indirect channels for assessing sex-related problems among runaway female at-risk adolescents and establishing proactive and preventive measures for promoting their sexual health. In addition, a social cooperation system should be established in order to assess, and mediate within, the environments around schools in order to minimize adolescents’ exposure to harmful environments.
The Association between Utilization of Media Information and Current Health Anxiety Among the Fukushima Daiichi Nuclear Disaster Evacuees
Authors: Orui Masatsugu , Nakayama Chihiro , Kuroda Yujiro , Moriyama Nobuaki , Iwasa Hajime , Horiuchi Teruko , Nakayama Takeo , Sugita Minoru , Yasumura Seiji
Published: June 2020

The 2011 nuclear disaster in Fukushima was not only a health disaster, but also an information disaster. Although media can promote health communication following disasters, studies have revealed associations between media information and negative psychological reactions. To clarify the relationship between media utilization and current health anxiety due to radiation exposure, a cross-sectional questionnaire survey was conducted in Fukushima. We selected 2000 subjects from evacuation (i.e., 500) and non-evacuation (i.e., 1500) areas by two-stage stratified random sampling. As the independent variable, participants were asked about current health anxiety due to radiation exposure at the time of answering the questionnaire. For utilization of media about radiation exposure, local media, national media, Internet media, public broadcasts, and public relations information from local government were set as the dependent variables. Questionnaire data were analyzed by evacuation type (i.e., forced/voluntary). In a multivariate logistic regression analysis, the use of public relations information was significantly associated with lower anxiety for the forced evacuees (odds ratio: 0.72; 95% confidence interval: 0.56–0.93). Our findings highlight the importance of public relations information from local government in terms of it being associated with lower current health anxiety, and this could potentially aid in preparing for future disasters.
How to Estimate Optimal Malaria Readiness Indicators at Health-District Level: Findings from the Burkina Faso Service Availability and Readiness Assessment (SARA) Data
Authors: Rouamba Toussaint , Samadoulougou Sekou , Compaoré Cheick Saïd , Tinto Halidou , Gaudart Jean , Kirakoya-Samadoulougou Fati
Published: June 2020

One of the major contributors of malaria-related deaths in Sub-Saharan African countries is the limited accessibility to quality care. In these countries, malaria control activities are implemented at the health-district level (operational entity of the national health system), while malaria readiness indicators are regionally representative. This study provides an approach for estimating health district-level malaria readiness indicators from survey data designed to provide regionally representative estimates. A binomial-hierarchical Bayesian spatial prediction method was applied to Burkina Faso Service Availability and Readiness Assessment (SARA) survey data to provide estimates of essential equipment availability and readiness for malaria care. Predicted values of each indicator were adjusted by the type of health facility, location, and population density. Then, a health district composite readiness profile was built via hierarchical ascendant classification. All surveyed health-facilities were mandated by the Ministry of Health to manage malaria cases. The spatial distribution of essential equipment and malaria readiness was heterogeneous. Around 62.9% of health districts had a high level of readiness to provide malaria care and prevention during pregnancy. Low-performance scores for managing malaria cases were found in big cities. Health districts with low coverage for both first-line antimalarial drugs and rapid diagnostic tests were Baskuy, Bogodogo, Boulmiougou, Nongr-Massoum, Sig-Nonghin, Dafra, and Do. We provide health district estimates and reveal gaps in basic equipment and malaria management resources in some districts that need to be filled. By providing local-scale estimates, this approach could be replicated for other types of indicators to inform decision makers and health program managers and to identify priority areas.
Underground Pipeline Leakage Risk Assessment in an Urban City
Authors: Chen Shing-Yu , Lin Ming-Sheng , Hsiao Gary Li-Kai , Wang Tzu-Chi , Kao Chen-Shan
Published: June 2020

Underground pipeline safety is a concern among civilians in populated urban cities. Due to the potential for considerable damage from underground pipeline leakages, it is critical to identify potential risk areas. This study developed a simplified risk value using risk assessment software (ALOHA) and geography information systems (SuperGIS and Surfer) to produce potential risk maps for underground pipeline leakage in a major urban city. A risk assessment of areas affected by underground pipeline leakage was performed for vapor diffusion, thermal radiation from combustion, and overpressure from an explosion. The results are applicable to disaster management departments and agencies in highly populated cities.
Relevance of SIRT1-NF-κB Axis as Therapeutic Target to Ameliorate Inflammation in Liver Disease
Authors: de Gregorio Estefanía , Colell Anna , Morales Albert , Marí Montserrat
Published: June 2020

Inflammation is an adaptive response in pursuit of homeostasis reestablishment triggered by harmful conditions or stimuli, such as an infection or tissue damage. Liver diseases cause approximately 2 million deaths per year worldwide and hepatic inflammation is a common factor to all of them, being the main driver of hepatic tissue damage and causing progression from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH), cirrhosis and, ultimately, hepatocellular carcinoma (HCC). The metabolic sensor SIRT1, a class III histone deacetylase with strong expression in metabolic tissues such as the liver, and transcription factor NF-κB, a master regulator of inflammatory response, show an antagonistic relationship in controlling inflammation. For this reason, SIRT1 targeting is emerging as a potential strategy to improve different metabolic and/or inflammatory pathologies. In this review, we explore diverse upstream regulators and some natural/synthetic activators of SIRT1 as possible therapeutic treatment for liver diseases.
Positional Correlation Natural Vector: A Novel Method for Genome Comparison
Authors: He Lily , Dong Rui , He Rong Lucy , Yau Stephen S.-T.
Published: June 2020

Advances in sequencing technology have made large amounts of biological data available. Evolutionary analysis of data such as DNA sequences is highly important in biological studies. As alignment methods are ineffective for analyzing large-scale data due to their inherently high costs, alignment-free methods have recently attracted attention in the field of bioinformatics. In this paper, we introduce a new positional correlation natural vector (PCNV) method that involves converting a DNA sequence into an 18-dimensional numerical feature vector. Using frequency and position correlation to represent the nucleotide distribution, it is possible to obtain a PCNV for a DNA sequence. This new numerical vector design uses six suitable features to characterize the correlation among nucleotide positions in sequences. PCNV is also very easy to compute and can be used for rapid genome comparison. To test our novel method, we performed phylogenetic analysis with several viral and bacterial genome datasets with PCNV. For comparison, an alignment-based method, Bayesian inference, and two alignment-free methods, feature frequency profile and natural vector, were performed using the same datasets. We found that the PCNV technique is fast and accurate when used for phylogenetic analysis and classification of viruses and bacteria.
Design, Synthesis and Characterization of Cyclic NU172 Analogues: A Biophysical and Biological Insight
Authors: Riccardi Claudia , Meyer Albert , Vasseur Jean-Jacques , Cavasso Domenico , Russo Krauss Irene , Paduano Luigi , Morvan François , Montesarchio Daniela
Published: June 2020

NU172—a 26-mer oligonucleotide able to bind exosite I of human thrombin and inhibit its activity—was the first aptamer to reach Phase II clinical studies as an anticoagulant in heart disease treatments. With the aim of favoring its functional duplex-quadruplex conformation and thus improving its enzymatic stability, as well as its thrombin inhibitory activity, herein a focused set of cyclic NU172 analogues—obtained by connecting its 5′- and 3′-extremities with flexible linkers—was synthesized. Two different chemical approaches were exploited in the cyclization procedure, one based on the oxime ligation method and the other on Cu(I)-assisted azide-alkyne cycloaddition (CuAAC), affording NU172 analogues including circularizing linkers with different length and chemical nature. The resulting cyclic NU172 derivatives were characterized using several biophysical techniques (ultraviolet (UV) and circular dichroism (CD) spectroscopies, gel electrophoresis) and then investigated for their serum resistance and anticoagulant activity in vitro. All the cyclic NU172 analogues showed higher thermal stability and nuclease resistance compared to unmodified NU172. These favorable properties were, however, associated with reduced—even though still significant—anticoagulant activity, suggesting that the conformational constraints introduced upon cyclization were somehow detrimental for protein recognition. These results provide useful information for the design of improved analogues of NU172 and related duplex-quadruplex structures.
The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease
Authors: Fujii Hideki , Kawada Norifumi ,   Japan Study Group of NAFLD (JSG-NAFLD)
Published: June 2020

Nonalcoholic fatty liver disease (NAFLD) consists of the entire spectrum of fatty liver disease in patients without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) to cirrhosis, with NASH recently shown as an important cause of hepatocellular carcinoma (HCC). There is a close relationship between insulin resistance (IR) and NAFLD, with a five-fold higher prevalence of NAFLD in patients with type 2 diabetes (T2DM) compared to that in patients without T2DM. IR is involved in the progression of disease conditions such as steatosis and NASH, as well as hepatic fibrosis progression. The mechanisms underlying these processes involve genetic factors, hepatic fat accumulation, alterations in energy metabolism, and inflammatory signals derived from various cell types including immune cells. In NASH-associated fibrosis, the principal cell type responsible for extracellular matrix production is the hepatic stellate cell (HSC). HSC activation by IR involves “direct” and “indirect” pathways. This review will describe the molecular mechanisms of inflammation and hepatic fibrosis in IR, the relationship between T2DM and hepatic fibrosis, and the relationship between T2DM and HCC in patients with NAFLD.
When Good Guys Turn Bad: Bone Marrow’s and Hematopoietic Stem Cells’ Role in the Pathobiology of Diabetic Complications
Authors: Vinci Maria Cristina , Gambini Elisa , Bassetti Beatrice , Genovese Stefano , Pompilio Giulio
Published: June 2020

Diabetes strongly contributes to the development of cardiovascular disease, the leading cause of mortality and morbidity in these patients. It is widely accepted that hyperglycemia impairs hematopoietic stem/progenitor cell (HSPC) mobilization from the bone marrow (BM) by inducing stem cell niche dysfunction. Moreover, a recent study demonstrated that type 2 diabetic patients are characterized by significant depletion of circulating provascular progenitor cells and increased frequency of inflammatory cells. This unbalance, potentially responsible for the reduction of intrinsic vascular homeostatic capacity and for the establishment of a low-grade inflammatory status, suggests that bone BM-derived HSPCs are not only victims but also active perpetrators in diabetic complications. In this review, we will discuss the most recent literature on the molecular mechanisms underpinning hyperglycemia-mediated BM dysfunction and differentiation abnormality of HSPCs. Moreover, a section will be dedicated to the new glucose-lowering therapies that by specifically targeting the culprits may prevent or treat diabetic complications.
Continuum Models of Membrane Fusion: Evolution of the Theory
Authors: Akimov Sergey A. , Molotkovsky Rodion J. , Kuzmin Peter I. , Galimzyanov Timur R. , Batishchev Oleg V.
Published: June 2020

Starting from fertilization, through tissue growth, hormone secretion, synaptic transmission, and sometimes morbid events of carcinogenesis and viral infections, membrane fusion regulates the whole life of high organisms. Despite that, a lot of fusion processes still lack well-established models and even a list of main actors. A merger of membranes requires their topological rearrangements controlled by elastic properties of a lipid bilayer. That is why continuum models based on theories of membrane elasticity are actively applied for the construction of physical models of membrane fusion. Started from the view on the membrane as a structureless film with postulated geometry of fusion intermediates, they developed along with experimental and computational techniques to a powerful tool for prediction of the whole process with molecular accuracy. In the present review, focusing on fusion processes occurring in eukaryotic cells, we scrutinize the history of these models, their evolution and complication, as well as open questions and remaining theoretical problems. We show that modern approaches in this field allow continuum models of membrane fusion to stand shoulder to shoulder with molecular dynamics simulations, and provide the deepest understanding of this process in multiple biological systems.
The Sulphur Response in Wheat Grain and Its Implications for Acrylamide Formation and Food Safety
Authors: Raffan Sarah , Oddy Joseph , Halford Nigel G.
Published: June 2020

Free (soluble, non-protein) asparagine concentration can increase many-fold in wheat grain in response to sulphur deficiency. This exacerbates a major food safety and regulatory compliance problem for the food industry because free asparagine may be converted to the carcinogenic contaminant, acrylamide, during baking and processing. Here, we describe the predominant route for the conversion of asparagine to acrylamide in the Maillard reaction. The effect of sulphur deficiency and its interaction with nitrogen availability is reviewed, and we reiterate our advice that sulphur should be applied to wheat being grown for human consumption at a rate of 20 kg per hectare. We describe the genetic control of free asparagine accumulation, including genes that encode metabolic enzymes (asparagine synthetase, glutamine synthetase, glutamate synthetase, and asparaginase), regulatory protein kinases (sucrose nonfermenting-1 (SNF1)-related protein kinase-1 (SnRK1) and general control nonderepressible-2 (GCN2)), and basic leucine zipper (bZIP) transcription factors, and how this genetic control responds to sulphur, highlighting the importance of asparagine synthetase-2 (ASN2) expression in the embryo. We show that expression of glutamate-cysteine ligase is reduced in response to sulphur deficiency, probably compromising glutathione synthesis. Finally, we describe unexpected effects of sulphur deficiency on carbon metabolism in the endosperm, with large increases in expression of sucrose synthase-2 (SuSy2) and starch synthases.
Omega-3 Fatty Acid-Type Docosahexaenoic Acid Protects against Aβ-Mediated Mitochondrial Deficits and Pathomechanisms in Alzheimer’s Disease-Related Animal Model
Authors: Park Yong Ho , Shin Soo Jung , Kim Hyeon soo , Hong Sang Bum , Kim Sujin , Nam Yunkwon , Kim Jwa-Jin , Lim Kyu , Kim Jong-Seok , Kim Jin-il , Jeon Seong Gak , Moon Minho
Published: June 2020

It has been reported that damage to the mitochondria affects the progression of Alzheimer’s disease (AD), and that mitochondrial dysfunction is improved by omega-3. However, no animal or cell model studies have confirmed whether omega-3 inhibits AD pathology related to mitochondria deficits. In this study, we aimed to (1) identify mitigating effects of endogenous omega-3 on mitochondrial deficits and AD pathology induced by amyloid beta (Aβ) in fat-1 mice, a transgenic omega-3 polyunsaturated fatty acids (PUFAs)-producing animal; (2) identify if docosahexaenoic acid (DHA) improves mitochondrial deficits induced by Aβ in HT22 cells; and (3) verify improvement effects of DHA administration on mitochondrial deficits and AD pathology in B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax (5XFAD), a transgenic Aβ-overexpressing model. We found that omega-3 PUFAs significantly improved Aβ-induced mitochondrial pathology in fat-1 mice. In addition, our in vitro and in vivo findings demonstrate that DHA attenuated AD-associated pathologies, such as mitochondrial impairment, Aβ accumulation, neuroinflammation, neuronal loss, and impairment of adult hippocampal neurogenesis.
Shoot Tip Cryopreservation of Lamprocapnos spectabilis (L.) Fukuhara Using Different Approaches and Evaluation of Stability on the Molecular, Biochemical, and Plant Architecture Levels
Authors: Kulus Dariusz
Published: June 2020

The aim of this study is to optimize and evaluate the effectiveness of vitrification, droplet-vitrification, and encapsulation-vitrification techniques in the cryopreservation of Lamprocapnos spectabilis (L.) Fukuhara ‘Gold Heart’, a popular medicinal and ornamental plant species. In vitro-derived shoot tips were used in the experiments. All three techniques were based on explant dehydration with plant vitrification solution 3 (PVS3; 50% glycerol and 50% sucrose) for 0, 30, 60, 90, 120, 150, or 180 min. The recovered microshoots were subjected to morphometric, biochemical, and molecular analyses (RAPD, ISSR, SCoT). The highest recovery level was reported with the encapsulation-vitrification protocol based on 150 min dehydration (73.1%), while the vitrification technique was the least effective (maximum 25.8% recovery). Explants cryopreserved with the encapsulation-vitrification technique produced the highest mean number of shoots (4.9); moreover, this technique was optimal in terms of rooting efficiency. The highest fresh weight of shoots, on the other hand, was found with the vitrification protocol based on a 30-min PVS3 treatment. The concentrations of chlorophyll a and b were lower in all cryopreservation-derived plants, compared to the untreated control. On the other hand, short dehydration and cryopreservation of non-encapsulated explants stimulated the synthesis of anthocyanins. A small genetic variation in 5% of all samples analyzed was detected by RAPD and ISSR marker systems. Only plants recovered from the encapsulation-vitrification protocol had no DNA sequence alternations.
Albendazole-Induced SIRT3 Upregulation Protects Human Leukemia K562 Cells from the Cytotoxicity of MCL1 Suppression
Authors: Wang Liang-Jun , Liou Li-Ren , Shi Yi-Jun , Chiou Jing-Ting , Lee Yuan-Chin , Huang Chia-Hui , Huang Po-Wei , Chang Long-Sen
Published: June 2020

Previous studies have shown that MCL1 stabilization confers cancer cells resistance to microtubule targeting agents (MTAs) and functionally extends the lifespan of MTA-triggered mitotically arrested cells. Albendazole (ABZ), a benzimidazole anthelmintic, shows microtubule-destabilizing activity and has been repositioned for cancer therapies. To clarify the role of MCL1 in ABZ-induced apoptosis, we investigated the cytotoxicity of ABZ on human leukemia K562 cells. Treatment with ABZ for 24 h did not appreciably induce apoptosis or mitochondrial depolarization in K562 cells, though it caused the mitotic arrest of K562 cells. ABZ-evoked p38 MAPK activation concurrently suppressed Sp1-mediated MCL1 expression and increased SIRT3 mRNA stability and protein expression. ABZ and A-1210477 (an MCL1 inhibitor) enhanced the cytotoxicity of ABT-263 (a BCL2/BCL2L1 inhibitor) to their effect on MCL1 suppression. Unlike ABZ, A-1210477 did not affect SIRT3 expression and reduced the survival of K562 cells. Overexpression of SIRT3 attenuated the A-1210477 cytotoxicity on K562 cells. ABZ treatment elicited marked apoptosis and ΔΨm loss in ABT-263-resistant K562 (K562/R) cells, but did not alter SIRT3 expression. Ectopic expression of SIRT3 alleviated the cytotoxicity of ABZ on K562/R cells. Collectively, our data demonstrate that ABZ-induced SIRT3 upregulation delays the apoptosis-inducing effect of MCL1 suppression on apoptosis induction in K562 cells.
Pilot Scale Study: First Demonstration of Hydrophobic Membranes for the Removal of Ammonia Molecules from Rendering Condensate Wastewater
Authors: Brennan Brian , Briciu-Burghina Ciprian , Hickey Sean , Abadie Thomas , al Ma Awali Sultan M. , Delaure Yan , Durkan John , Holland Linda , Quilty Brid , Tajparast Mohammad , Pulit Casper , Fitzsimons Lorna , Nolan Kieran , Regan Fiona , Lawler Jenny
Published: June 2020

Hydrophobic membrane contactors represent a promising solution to the problem of recycling ammoniacal nitrogen (N-NH4) molecules from waste, water or wastewater resources. The process has been shown to work best with wastewater streams that present high N-NH4 concentrations, low buffering capacities and low total suspended solids. The removal of N-NH4 from rendering condensate, produced during heat treatment of waste animal tissue, was assessed in this research using a hydrophobic membrane contactor. This study investigates how the molecular composition of rendering condensate wastewater undergo changes in its chemistry in order to achieve suitability to be treated using hydrophobic membranes and form a suitable product. The main objective was to test the ammonia stripping technology using two types of hydrophobic membrane materials, polypropylene (PP) and polytetrafluoroethylene (PTFE) at pilot scale and carry out: (i) Process modification for NH3 molecule removal and (ii) product characterization from the process. The results demonstrate that PP membranes are not compatible with the condensate waste as it caused wetting. The PTFE membranes showed potential and had a longer lifetime than the PP membranes and removed up to 64% of NH3 molecules from the condensate waste. The product formed contained a 30% concentrated ammonium sulphate salt which has a potential application as a fertilizer. This is the first demonstration of hydrophobic membrane contactors for treatment of condensate wastewater.
SRC Tyrosine Kinase Inhibitor and X-rays Combined Effect on Glioblastoma Cell Lines
Authors: Torrisi Filippo , Minafra Luigi , Cammarata Francesco P. , Savoca Gaetano , Calvaruso Marco , Vicario Nunzio , Maccari Laura , Pérès Elodie A. , Özçelik Hayriye , Bernaudin Myriam , Botta Lorenzo , Russo Giorgio , Parenti Rosalba , Valable Samuel
Published: June 2020

Glioblastoma (GBM) is one of the most lethal types of tumor due to its high recurrence level in spite of aggressive treatment regimens involving surgery, radiotherapy and chemotherapy. Hypoxia is a feature of GBM, involved in radioresistance, and is known to be at the origin of treatment failure. The aim of this work was to assess the therapeutic potential of a new targeted c-SRC inhibitor molecule, named Si306, in combination with X-rays on the human glioblastoma cell lines, comparing normoxia and hypoxia conditions. For this purpose, the dose modifying factor and oxygen enhancement ratio were calculated to evaluate the Si306 radiosensitizing effect. DNA damage and the repair capability were also studied from the kinetic of γ-H2AX immunodetection. Furthermore, motility processes being supposed to be triggered by hypoxia and irradiation, the role of c-SRC inhibition was also analyzed to evaluate the migration blockage by wound healing assay. Our results showed that inhibition of the c-SRC protein enhances the radiotherapy efficacy both in normoxic and hypoxic conditions. These data open new opportunities for GBM treatment combining radiotherapy with molecularly targeted drugs to overcome radioresistance.
Quantification of Uncoupled Spin Domains in Spin-Abundant Disordered Solids
Authors: Walder Brennan J. , Alam Todd M.
Published: June 2020

Materials often contain minor heterogeneous phases that are difficult to characterize yet nonetheless significantly influence important properties. Here we describe a solid-state NMR strategy for quantifying minor heterogenous sample regions containing dilute, essentially uncoupled nuclei in materials where the remaining nuclei experience heteronuclear dipolar couplings. NMR signals from the coupled nuclei are dephased while NMR signals from the uncoupled nuclei can be amplified by one or two orders of magnitude using Carr-Meiboom-Purcell-Gill (CPMG) acquisition. The signal amplification by CPMG can be estimated allowing the concentration of the uncoupled spin regions to be determined even when direct observation of the uncoupled spin NMR signal in a single pulse experiment would require an impractically long duration of signal averaging. We use this method to quantify residual graphitic carbon using 13 C CPMG NMR in poly(carbon monofluoride) samples synthesized by direct fluorination of carbon from various sources. Our detection limit for graphitic carbon in these materials is better than 0.05 mol%. The accuracy of the method is discussed and comparisons to other methods are drawn.
A Microarray Screening Platform with an Experimental Conditions Gradient Generator for the High-Throughput Synthesis of Micro/Nanosized Calcium Phosphates
Authors: Li Xiaoyu , Shi Zhifeng , Liu Lei , Zhu Guanglin , Zhou Jianhua , Shi Xuetao , Wang Yingjun
Published: June 2020

Calcium phosphates (CaP) represent an impressive kind of biomedical material due to their excellent biocompatibility, bioactivity, and biodegradability. Their morphology and structure highly influence their properties and applications. Whilst great progress has been made in research on biomedical materials, there is still a need to develop a method that can rapidly synthesize and screen micro/nanosized biomedical materials. Here, we utilized a microarray screening platform that could provide the high-throughput synthesis of biomedical materials and screen the vital reaction conditions. With this screening platform, 9 × 9 sets of parallel experiments could be conducted simultaneously with one- or two-dimensions of key reaction condition gradients. We used this platform to establish a one-dimensional gradient of the pH and citrate concentration and a two-dimensional gradient of both the Ca/P ratio and pH to synthesize CaP particles with various morphologies. This screening platform also shows the potential to be extended to other reaction systems for rapid high-throughput screening.
Protein Glycation in Plants—An Under-Researched Field with Much Still to Discover
Authors: Rabbani Naila , Al-Motawa Maryam , Thornalley Paul J.
Published: June 2020

Recent research has identified glycation as a non-enzymatic post-translational modification of proteins in plants with a potential contributory role to the functional impairment of the plant proteome. Reducing sugars with a free aldehyde or ketone group such as glucose, fructose and galactose react with the N-terminal and lysine side chain amino groups of proteins. A common early-stage glycation adduct formed from glucose is Nε-fructosyl-lysine (FL). Saccharide-derived reactive dicarbonyls are arginine residue-directed glycating agents, forming advanced glycation endproducts (AGEs). A dominant dicarbonyl is methylglyoxal—formed mainly by the trace-level degradation of triosephosphates, including through the Calvin cycle of photosynthesis. Methylglyoxal forms the major quantitative AGE, hydroimidazolone MG-H1. Glucose and methylglyoxal concentrations in plants change with the developmental stage, senescence, light and dark cycles and also likely biotic and abiotic stresses. Proteomics analysis indicates that there is an enrichment of the amino acid residue targets of glycation, arginine and lysine residues, in predicted functional sites of the plant proteome, suggesting the susceptibility of proteins to functional inactivation by glycation. In this review, we give a brief introduction to glycation, glycating agents and glycation adducts in plants. We consider dicarbonyl stress, the functional vulnerability of the plant proteome to arginine-directed glycation and the likely role of methylglyoxal-mediated glycation in the activation of the unfolded protein response in plants. The latter is linked to the recent suggestion of protein glycation in sugar signaling in plant metabolism. The overexpression of glyoxalase 1, which suppresses glycation by methylglyoxal and glyoxal, produced plants resistant to high salinity, drought, extreme temperature and other stresses. Further research to decrease protein glycation in plants may lead to improved plant growth and assist the breeding of plant varieties resistant to environmental stress and senescence—including plants of commercial ornamental and crop cultivation value.
Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility
Authors: Sciarra Francesca , Franceschini Edoardo , Campolo Federica , Gianfrilli Daniele , Pallotti Francesco , Paoli Donatella , Isidori Andrea M. , Venneri Mary Anna
Published: June 2020

Infertility represents a growing health problem in industrialized countries. Thus, a greater understanding of the molecular networks involved in this disease could be critical for the development of new therapies. A recent finding revealed that circadian rhythmicity disruption is one of the main causes of poor reproductive outcome. The circadian clock system beats circadian rhythms and modulates several physiological functions such as the sleep-wake cycle, body temperature, heart rate, and hormones secretion, all of which enable the body to function in response to a 24 h cycle. This intricated machinery is driven by specific genes, called “clock genes” that fine-tune body homeostasis. Stress of modern lifestyle can determine changes in hormone secretion, favoring the onset of infertility-related conditions that might reflect disfunctions within the hypothalamic–pituitary–gonadal axis. Consequently, the loss of rhythmicity in the suprachiasmatic nuclei might affect pulsatile sexual hormones release. Herein, we provide an overview of the recent findings, in both animal models and humans, about how fertility is influenced by circadian rhythm. In addition, we explore the complex interaction among hormones, fertility and the circadian clock. A deeper analysis of these interactions might lead to novel insights that could ameliorate the therapeutic management of infertility and related disorders.
The Synergistic Effect of Co-Treatment of Methyl Jasmonate and Cyclodextrins on Pterocarpan Production in Sophora flavescens Cell Cultures
Authors: Kim Soyoung , Jeong Yu Jeong , Park Su Hyun , Park Sung-Chul , Lee Saet Buyl , Lee Jiyoung , Kim Suk Weon , Ha Bo-Keun , Kim Hyun-Soon , Kim HyeRan , Ryu Young Bae , Jeong Jae Cheol , Kim Cha Young
Published: June 2020

Pterocarpans are derivatives of isoflavonoids, found in many species of the family Fabaceae. Sophora flavescens Aiton is a promising traditional Asian medicinal plant. Plant cell suspension cultures represent an excellent source for the production of valuable secondary metabolites. Herein, we found that methyl jasmonate (MJ) elicited the activation of pterocarpan biosynthetic genes in cell suspension cultures of S. flavescens and enhanced the accumulation of pterocarpans, producing mainly trifolirhizin, trifolirhizin malonate, and maackiain. MJ application stimulated the expression of structural genes (PAL, C4H, 4CL, CHS, CHR, CHI, IFS, I3’H, and IFR) of the pterocarpan biosynthetic pathway. In addition, the co-treatment of MJ and methyl-β-cyclodextrin (MeβCD) as a solubilizer exhibited a synergistic effect on the activation of the pterocarpan biosynthetic genes. The maximum level of total pterocarpan production (37.2 mg/g dry weight (DW)) was obtained on day 17 after the application of 50 μM MJ on cells. We also found that the combined treatment of cells for seven days with MJ and MeβCD synergistically induced the pterocarpan production (trifolirhizin, trifolirhizin malonate, and maackiain) in the cells (58 mg/g DW) and culture medium (222.7 mg/L). Noteworthy, the co-treatment only stimulated the elevated extracellular production of maackiain in the culture medium, indicating its extracellular secretion; however, its glycosides (trifolirhizin and trifolirhizin malonate) were not detected in any significant amounts in the culture medium. This work provides new strategies for the pterocarpan production in plant cell suspension cultures, and shows MeβCD to be an effective solubilizer for the extracellular production of maackiain in the cell cultures of S. flavescens.
Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability
Authors: Olejarz Wioletta , Łacheta Dominika , Kubiak-Tomaszewska Grażyna
Published: June 2020

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling and degradation of extracellular matrix (ECM) proteins. MMPs may modulate various cellular and signaling pathways in atherosclerosis responsible for progression and rupture of atherosclerotic plaques. The effect of MMPs polymorphisms and the expression of MMPs in both the atherosclerotic plaque and plasma was shown. They are independent predictors of atherosclerotic plaque instability in stable coronary heart disease (CHD) patients. Increased levels of MMPs in patients with advanced cardiovascular disease (CAD) and acute coronary syndrome (ACS) was associated with future risk of cardiovascular events. These data confirm that MMPs may be biomarkers in plaque instability as they target in potential drug therapies for atherosclerosis. They provide important prognostic information, independent of traditional risk factors, and may turn out to be useful in improving risk stratification.
Low Doses of Arsenic in a Mouse Model of Human Exposure and in Neuronal Culture Lead to S-Nitrosylation of Synaptic Proteins and Apoptosis via Nitric Oxide
Authors: Amal Haitham , Gong Guanyu , Yang Hongmei , Joughin Brian A. , Wang Xin , Knutson Charles G. , Kartawy Maryam , Khaliulin Igor , Wishnok John S. , Tannenbaum Steven R.
Published: June 2020

Background: Accumulating public health and epidemiological literature support the hypothesis that arsenic in drinking water or food affects the brain adversely. Methods: Experiments on the consequences of nitric oxide (NO) formation in neuronal cell culture and mouse brain were conducted to probe the mechanistic pathways of nitrosative damage following arsenic exposure. Results: After exposure of mouse embryonic neuronal cells to low doses of sodium arsenite (SA), we found that Ca2+ was released leading to the formation of large amounts of NO and apoptosis. Inhibition of NO synthase prevented neuronal apoptosis. Further, SA led to concerted S-nitrosylation of proteins significantly associated with synaptic vesicle recycling and acetyl-CoA homeostasis. Our findings show that low-dose chronic exposure (0.1–1 ppm) to SA in the drinking water of mice led to S-nitrosylation of proteomic cysteines. Subsequent removal of arsenic from the drinking water reversed the biochemical alterations. Conclusions: This work develops a mechanistic understanding of the role of NO in arsenic-mediated toxicity in the brain, incorporating Ca2+ release and S-nitrosylation as important modifiers of neuronal protein function.
Fractionation of Enriched Phosphopeptides Using pH/Acetonitrile-Gradient-Reversed-Phase Microcolumn Separation in Combination with LC–MS/MS Analysis
Authors: Ondrej Martin , Rehulka Pavel , Rehulkova Helena , Kupcik Rudolf , Tichy Ales
Published: June 2020

Mass spectrometry (MS) is a powerful and sensitive method often used for the identification of phosphoproteins. However, in phosphoproteomics, there is an identified need to compensate for the low abundance, insufficient ionization, and suppression effects of non-phosphorylated peptides. These may hamper the subsequent liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS) analysis, resulting in incomplete phosphoproteome characterization, even when using high-resolution instruments. To overcome these drawbacks, we present here an effective microgradient chromatographic technique that yields specific fractions of enriched phosphopeptides compatible with LC–MS/MS analysis. The purpose of our study was to increase the number of identified phosphopeptides, and thus, the coverage of the sample phosphoproteome using the reproducible and straightforward fractionation method. This protocol includes a phosphopeptide enrichment step followed by the optimized microgradient fractionation of enriched phosphopeptides and final LC–MS/MS analysis of the obtained fractions. The simple fractionation system consists of a gas-tight microsyringe delivering the optimized gradient mobile phase to reversed-phase microcolumn. Our data indicate that combining the phosphopeptide enrichment with the microgradient separation is a promising technique for in-depth phosphoproteomic analysis due to moderate input material requirements and more than 3-fold enhanced protein identification.
Stage-Specific Effects of Ionizing Radiation during Early Development
Authors: Honjo Yasuko , Ichinohe Tatsuo
Published: June 2020

Early embryonic cells are sensitive to genotoxic stressors such as ionizing radiation. However, sensitivity to these stressors varies depending on the embryonic stage. Recently, the sensitivity and response to ionizing radiation were found to differ during the preimplantation period. The cellular and molecular mechanisms underlying the change during this period are beginning to be elucidated. In this review, we focus on the changes in radio-sensitivity and responses to ionizing radiation during the early developmental stages of the preimplantation (before gastrulation) period in mammals, Xenopus, and fish. Furthermore, we discuss the underlying cellular and molecular mechanisms and the similarities and differences between species.
Syringaresinol Inhibits UVA-Induced MMP-1 Expression by Suppression of MAPK/AP-1 Signaling in HaCaT Keratinocytes and Human Dermal Fibroblasts
Authors: Oh Jung Hwan , Joo Yung Hyup , Karadeniz Fatih , Ko Jaeyoung , Kong Chang-Suk
Published: June 2020

Ultraviolet (UV) irradiation induces detrimental changes in human skin which result in photoaging. UV-induced intracellular changes cause degradation of extracellular matrix (ECM). UV-stimulated cleavage of collagen in ECM occurs via matrix metalloproteinases (MMPs). (±)-syringaresinol (SYR), a phytochemical which belongs to the lignan group of polyphenols, was investigated for its ability to reverse the UVA-induced changes in human HaCaT keratinocytes and dermal fibroblasts (HDFs) in vitro. Effect of SYR on UVA-induced changes was investigated by production and activation of MMPs and its transcriptional upstream effectors; mitogen-activated protein kinases (MAPKs) and pro-inflammatory mediators. Levels of expression were determined using ELISA, RT-PCR and immunoblotting. UVA irradiation stimulated the production of MMP-1 and inhibited collagen production. SYR treatment suppressed MMP-1 and enhanced collagen production in UVA-irradiated HaCaT keratinocytes and HDFs. SYR repressed the UV-induced phosphorylation of p38, ERK and JNK MAPKs in HaCaT keratinocytes while only suppressing JNK phosphorylation in HDFs. In addition, SYR was able to inhibit UVA-induced production of inflammatory cytokines; TNF-α, COX-2, IL-1β and IL-6. Moreover, SYR suppressed the activator protein-1 (AP-1), a heterodimer of phosphorylated transcription factors c-Jun and c-Fos. SYR-treatment decreased nuclear levels of activated c-Fos and c-Jun as a mechanism to inhibit UVA-induced transcriptional activities leading to MMP-1 production. In conclusion, current results demonstrated that SYR could inhibit UVA-induced upregulation of MMP-1 by suppressing MAPK/AP-1 signaling in HaCaT keratinocytes and HDFs. Therefore, SYR was suggested as a potential compound with antiphotoaging properties against UVA-induced skin aging.
Hydrophobic Amino Acids as Universal Elements of Protein-Induced DNA Structure Deformation
Authors: Faltejsková Kateřina , Jakubec David , Vondrášek Jiří
Published: June 2020

Interaction with the DNA minor groove is a significant contributor to specific sequence recognition in selected families of DNA-binding proteins. Based on a statistical analysis of 3D structures of protein–DNA complexes, we propose that distortion of the DNA minor groove resulting from interactions with hydrophobic amino acid residues is a universal element of protein–DNA recognition. We provide evidence to support this by associating each DNA minor groove-binding amino acid residue with the local dimensions of the DNA double helix using a novel algorithm. The widened DNA minor grooves are associated with high GC content. However, some AT-rich sequences contacted by hydrophobic amino acids (e.g., phenylalanine) display extreme values of minor groove width as well. For a number of hydrophobic amino acids, distinct secondary structure preferences could be identified for residues interacting with the widened DNA minor groove. These results hold even after discarding the most populous families of minor groove-binding proteins.
Feature Analysis of Degradation Signal of Rolling Stock Lateral Damper
Authors: Zhao Zhiyan , Wu Bin , Zhou Ting
Published: June 2020

The lateral damper is one of the key components of rolling stock. Establishing the relationship between the degraded signal and the health state of the lateral damper is important in order to perform timely performance detection and fault diagnosis. This paper proposes a wavelet packet cross-correlation method (WPCC) that is based on wavelet packet transform (WPT) and cross-correlation analysis (CCA). First, the vibration signals under different running speeds, different running conditions, and different track excitations were collected and analyzed. Second, the wavelet packet transform was used to select larger energy band signals for reconstruction. Subsequently, the WPCC coefficient was calculated between the reference signal and the signal to be measured. The proposed method was applied to analysis of vibration signals of the lateral damper performance degradation. The lateral damper health condition was divided into four intervals, and the average accuracy calculated under different running speeds, different running conditions, and different track excitation was 95%.