bluuebunny/crossref_metadata_2025 huggingface dataset:
T Cell Receptor Genotype and Ubash3a Determine Susceptibility to Rat Autoimmune Diabetes
Authors: Mordes John P. , Cort Laura , Liu Zhijun , Eberwine Ryan , Blankenhorn Elizabeth P. , Pierce Brian G.
Published: June 2021

Genetic analyses of human type 1 diabetes (T1D) have yet to reveal a complete pathophysiologic mechanism. Inbred rats with a high-risk class II major histocompatibility complex (MHC) haplotype (RT1B/Du) can illuminate such mechanisms. Using T1D-susceptible LEW.1WR1 rats that express RT1B/Du and a susceptible allele of the Ubd promoter, we demonstrate that germline knockout of Tcrb-V13S1A1, which encodes the Vβ13a T cell receptor β chain, completely prevents diabetes. Using the RT1B/Du-identical LEW.1W rat, which does not develop T1D despite also having the same Tcrb-V13S1A1 β chain gene but a different allele at the Ubd locus, we show that knockout of the Ubash3a regulatory gene renders these resistant rats relatively susceptible to diabetes. In silico structural modeling of the susceptible allele of the Vβ13a TCR and its class II RT1u ligand suggests a mechanism by which a germline TCR β chain gene could promote susceptibility to T1D in the absence of downstream immunoregulation like that provided by UBASH3A. Together these data demonstrate the critical contribution of the Vβ13a TCR to the autoimmune synapse in T1D and the regulation of the response by UBASH3A. These experiments dissect the mechanisms by which MHC class II heterodimers, TCR and regulatory element interact to induce autoimmunity.
DNA Methylation of Human Choline Kinase Alpha Promoter-Associated CpG Islands in MCF-7 Cells
Authors: Mohamed Sa’dom Siti Aisyah Faten , Raikundalia Sweta , Shamsuddin Shaharum , See Too Wei Cun , Few Ling Ling
Published: June 2021

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. This study aimed to investigate the regulation of CKα expression by DNA methylation of the CpG islands found on the promoter of this gene in MCF-7 cells. Four CpG islands have been predicted in the 2000 bp promoter region of ckα (chka) gene. Six CpG island deletion mutants were constructed using PCR site-directed mutagenesis method and cloned into pGL4.10 vectors for promoter activity assays. Deletion of CpG4C region located between –225 and –56 significantly increased the promoter activity by 4-fold, indicating the presence of important repressive transcription factor binding site. The promoter activity of methylated full-length promoter was significantly lower than the methylated CpG4C deletion mutant by 16-fold. The results show that DNA methylation of CpG4C promotes the binding of the transcription factor that suppresses the promoter activity. Electrophoretic mobility shift assay analysis showed that cytosine methylation at MZF1 binding site in CpG4C increased the binding of putative MZF1 in nuclear extract. In conclusion, the results suggest that DNA methylation decreased the promoter activity by promoting the binding of putative MZF1 transcription factor at CpG4C region of the ckα gene promoter.
Telerehabilitation of Post-Stroke Patients as a Therapeutic Solution in the Era of the Covid-19 Pandemic
Authors: Ostrowska Paulina Magdalena , Śliwiński Maciej , Studnicki Rafał , Hansdorfer-Korzon Rita
Published: June 2021

(1) Background: Due to the pandemic caused by the SARS-CoV-2 virus, rehabilitation centres have become less available for neurological patients. This is the result of efforts to physically distance society, to try to slow the spread of the pathogen. Health care facilities were mainly restricted to urgent cases, while most physiotherapy treatments, mainly for patients with chronic conditions, were suspended. Some countries have seen a reduction in acute stroke hospital admissions of from 50% to 80%. One solution to the above problem is the use of telerehabilitation in the home environment as an alternative to inpatient rehabilitation. (2) Aim of the study: The purpose of this review is to analyse the benefits and limitations of teletherapy in relation to the functional condition of post-stroke patients. (3) Methods: Selected publications from 2019 to 2021 on the telerehabilitation of stroke patients were reviewed. The review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. (4) Results: Studies have proven that teletherapy significantly improves the functional condition of post-stroke patients, resulting in improved quality of life and faster return to independence (while maintaining maximum possible precautions related to the SARS-CoV-2 virus pandemic). (5) Conclusions: Analysis of the study results showed comparable effectiveness of rehabilitation in the tele system to inpatient therapy. However, it should be emphasised that patients undergoing telerehabilitation must meet strict conditions to be eligible for this type of treatment program. However, the strength of the evidence itself supporting the effectiveness of this method ranks low due to the limited number of randomised control trials (RCT), small number of participants, and heterogeneous trials.
Development and Content Validity of the Physical Activity Questionnaire-Young Children (PAQ-YC) to Assess Physical Activity in Children between 5 and 7 Years
Authors: Amor-Barbosa Marta , Girabent-Farrés Montserrat , Rosés-Noguer Ferran , Ortega-Martínez Anna , Medina-Rincón Almudena , Bagur-Calafat Caritat
Published: June 2021

Childhood is a critical period in the development and consolidation of healthy habits, such as the practice of physical activity (PA). It is essential to have valid instruments to measure PA from an early age. The aim of this study was to design and evaluate the content validity of the Physical Activity Questionnaire-Young Children (PAQ-YC) to measure the PA level in children aged 5–7 years. The first version of the questionnaire was tested by a 2-round Delphi study. It was established as a consensus criterion that the relative interquartile range (RIR) and/or the coefficient of variation (CV) were ≤20%. The most significant discrepancies in the Delphi survey (n = 11–13) were observed for items about hours of Physical Education or similar activities at school (item 7: RIR = 20, CV = 38.73) and for items about participation in Physical Education (item 8: RIR = 25, CV = 15.45). The cognitive interviews (n = 5) confirmed the version agreed by the experts. The results show that the PAQ-YC presents adequate content validity in terms of relevance, comprehensiveness and comprehensibility.
The Impact of Family Care for the Elderly on Women’s Employment from the Perspective of Bargaining Power
Authors: Huang Yujuan , Xu Haoying , Liu Hengyu , Yu Wenguang , Yu Xinliang
Published: June 2021

Due to the wishes of the elderly and the traditional family culture in China, family care is the main way of providing for the aged, and women’s care is the main way. This is not conducive to the protection of women’s employment rights and the realization of self-worth under the background of increasing women’s autonomy. Based on the latest data of the China Health and Nutrition Survey Database (CHNS), this paper uses ordinary least squares (OLS) and the instrumental variable method of control endogeneity to analyze the influence of family care activities on the labor participation rate of married women. The innovation of this paper is to introduce family bargaining power into this kind of model for the first time, and further analyze the heterogeneity from the perspective of bargaining power differences. The empirical results show that the family elderly care activities have an obstacle effect on married women’s participation in employment, and the family members with strong bargaining power will significantly hinder employment, so this paper puts forward policy recommendations in line with the actual situation, hoping to provide theoretical support for the improvement of the social security system for the elderly.
GIS-Based Multi-Criteria Analysis Method for Assessment of Lake Ecosystems Degradation—Case Study in Romania
Authors: Avram Sorin , Cipu Corina , Corpade Ana-Maria , Gheorghe Carmen Adriana , Manta Nicolae , Niculae Mihaita-Iulian , Pascu Ionuţ Silviu , Szép Róbert Eugen , Rodino Steliana
Published: June 2021

In general, the elaboration of the synthesis of water quality in Romania is based on the processing of a large volume of information coming from primary analytical data collected with a constant frequency by the organisms with a specific role in water quality monitoring. This study proposes a novel methodology for multi-criteria analysis aiming to evaluate the degradation state of lake ecosystems. The cornerstone of the newly presented methodology is a geographic information system (GIS) automated tool, involving the assessment of potential degradation sources affecting the watershed that supply the lakes with water. The methodology was tested by performing an analysis on 30 lakes in Romania. The lakes belong to different geographical areas, owing various natural specific conditions and were selected to fit to various types and specific local conditions. The calculation of the WRASTIC-HI (Wastewater–Recreation–Agriculture–Size–Transportation–Industry–Cover–Hazard Index) revealed that, out of 30 lake ecosystems selected as the case study, two lakes were fully degraded, 24 lakes were semi-degraded, and four were in a natural state. The four lakes characterised by a natural state are located in mountainous regions or in the Danube Delta. The results obtained on the selected lakes proved that the proposed index calculation corresponded in all case studies to the real field situation, highlighting thus the accuracy of the assessing process and increased advantages of the assessment’s automation.
Executive Function among Chilean Shellfish Divers: A Cross-Sectional Study Considering Working and Health Conditions in Artisanal Fishing
Authors: Garrido Marie Astrid , Mark Lorenz , Parra Manuel , Nowak Dennis , Radon Katja
Published: June 2021

Knowledge about professional diving-related risk factors for reduced executive function is limited. We therefore evaluated the association between decompression illness and executive functioning among artisanal divers in southern Chile. The cross-sectional study included 104 male divers and 58 male non-diving fishermen from two fishing communities. Divers self-reported frequency and severity of symptoms of decompression illness. Executive function was evaluated by perseverative responses and perseverative errors in the Wisconsin Card Sorting Test. Age, alcohol consumption, and symptoms of depression were a-priori defined as potential confounders and included in linear regression models. Comparing divers and non-divers, no differences in the executive function were found. Among divers, 75% reported a history of at least mild decompression sickness. Higher frequency and severity of symptoms of decompression illness were associated with reduced executive function. Therefore, intervention strategies for artisanal divers should focus on prevention of decompression illness.
Combined Effects of Wildfire and Vegetation Cover Type on Volcanic Soil (Functions and Properties) in a Mediterranean Region: Comparison of Two Soil Quality Indices
Authors: Santorufo Lucia , Memoli Valeria , Panico Speranza Claudia , Santini Giorgia , Barile Rossella , Giarra Antonella , Di Natale Gabriella , Trifuoggi Marco , De Marco Anna , Maisto Giulia
Published: June 2021

Mediterranean regions are the most impacted by fire in Europe. The effects of fire on soil greatly vary according to several factors such as vegetation cover type, but they are scarcely studied. Therefore, this research aimed at evaluating the combined impacts of fire and vegetation on single soil characteristics and on the overall soil quality and functionality through two soil quality indices, simple additive (SQI) and a weighted function (SQIFUNCT). In order to reach the aims, burnt and unburnt soils were collected under different vegetation cover types (herbs and shrubs, black locust, pine and holm oak) within the Vesuvius National Park. The soils were analyzed for the main abiotic (water and organic matter content, total C, N, Ca, K, Cu and Pb concentrations, C/N ratio) and biotic (microbial and fungal biomasses, basal respiration, β-glucosidase activity) characteristics. On the basis of the investigated soil characteristics, several soil functions (water retention, nutrient supply, contamination content, microorganism habitat and activities), and the soil quality indices were calculated. The results showed that the impact of fire on soil quality and functionality was mediated by the vegetation cover type. In fact, fire occurrence led to a decrease in water and C/N ratio under herbs, a decrease in C concentration under holm oak and a decrease in Cu and Pb concentrations under pine. Although the soil characteristics showed significant changes according to vegetation cover types and fire occurrence, both the additive and weighted function soil quality indices did not significantly vary according to both fire occurrence and the vegetation cover type. Among the different vegetation cover types, pine was the most impacted one.
A Qualitative Evaluation of Young People’s, Parents’ and Carers’ Experiences of a National and Specialist CAMHS Dialectical Behaviour Therapy Outpatient Service
Authors: Ratnaweera Namali , Hunt Katrina , Camp Jake
Published: June 2021

(1) Background: Dialectical Behaviour Therapy (DBT) is the recommended treatment for Borderline Personality Disorder (BPD) symptoms in adults, however, research investigating the effectiveness of DBT for adolescents is limited. The present study explores the experiences of young people and their parents/carers of a DBT service using qualitative methodology. (2) Methods: Young people and their parents/carers, who completed DBT within the National and Specialist Child and Adolescent Mental Health DBT Service based at the Maudsley Hospital in London, were asked questions regarding their experience of the service. Data was collected from young people who completed treatment between July 2019 and July 2020 (n = 18) and their parents and carers (n = 7). (3) Results: Amongst young people, the themes identified were: a new way of living, better understanding of self, new skills, person-centred approach, and relationships with others. Parent and carer interviews revealed themes of improved relationships, feeling supported, improved quality of life, and time/timing. (4) Conclusions: Young people reported improvements in emerging BPD symptomology after completing DBT. Parents and carers reported improvements in their young person and families since starting DBT. A longer DBT programme, earlier DBT intervention, and the time-consuming nature of DBT were highlighted as areas for improvement.
Urinary Metabolites of Organophosphate Pesticides among Pregnant Women Participating in the Japan Environment and Children’s Study (JECS)
Authors: Nishihama Yukiko , Nakayama Shoji , Isobe Tomohiko , Jung Chau-Ren , Iwai-Shimada Miyuki , Kobayashi Yayoi , Michikawa Takehiro , Sekiyama Makiko , Taniguchi Yu , Yamazaki Shin ,   on behalf of the Japan Environment and Children’s Study Group
Published: June 2021

Organophosphate pesticides (OPPs) exhibit neurodevelopmental toxicity. To evaluate the effect of prenatal exposure to OPPs in the Japan Environment and Children’s Study, a nationally representative birth cohort study, 4575 maternal urine samples were analysed for six OPP metabolites, i.e., dialkylphosphates (DAPs). This study aimed to investigate predictors of urinary DAPs using machine learning approaches and to assess the cumulative risk based on relative potency factors among Japanese pregnant women. The median creatinine-normalised urinary concentrations (interquartile ranges) of dimethylphosphate, dimethylthiophosphate and diethylphosphate, which had a detection rate of 50% or higher, were 3.53 (1.91–6.78), 4.09 (1.66–10.8) and 3.28 (1.88–5.98) µg/g-creatinine, respectively. Possible predictors of urinary DAP concentrations were the month of urine sampling, consumption of apple and maternal body mass index. When fenitrothion was used as an index chemical for cumulative risk assessment, 0.36% of participants exceeded the lower 95% confidence limit of the benchmark dose10.
Increased Risk of Sjögren’s Syndrome in Patients with Obsessive-Compulsive Disorder: A Nationwide Population-Based Cohort Study
Authors: Chang Yi-Jung , Tseng Jui-Cheng , Leong Pui-Ying , Wang Yu-Hsun , Wei James Cheng-Chung
Published: June 2021

Obsessive-compulsive disorder (OCD) includes a wide range of symptoms and is often associated with comorbidities. Although psychiatric involvement may be an early manifestation of Sjögren’s syndrome (SS), only a few studies have demonstrated the relationship between OCD and SS. This is a nationwide cohort study identifying the risk of SS in OCD patients. We studied a longitudinal health insurance database for the period from 1999 to 2013. The study group was OCD patients with at least three outpatient visits or one hospitalization. The comparison cohort was matched by age and sex, as well as comorbidities. We calculated the risk of Sjögren’s syndrome using Cox proportional hazard regression models. We performed a propensity score match for confounders and effect modifiers between the two groups. The propensity score probability was estimated through logistic regression. Primary outcome was the incidental SS. A total of 1678 patients with OCD (49% women, mean age: 35.6 years) and 3356 controls were followed up, resulting in 13,077 and 25,856 person-years, respectively. The hazard ratio for developing SS was 3.31 (95% C.I.: 1.74–6.28) in patients with OCD, compared to those without OCD after adjusting for age, sex, and comorbidities. Furthermore, the risk of SS significantly increased over the 2-year follow-up period after OCD diagnosis. We concluded that risk of SS is significantly increased in patients with OCD compared to those without OCD. Clinically, Sjögren’s symptoms in OCD patients should be regularly assessed.
Environment Actors Confronting a Post Climate-Related Disaster Scenario: A Feasibility Study of an Action-Based Intervention Aiming to Promote Climate Action
Authors: Areia Neide P. , Tavares Alexandre O. , Mendes José Manuel
Published: June 2021

(1) A climate change awareness-action gap still prevails in our society, with individuals showing significant social inertia regarding environmental issues. The communication on climate change is pointed out as one of the causes of the social inertia; (2) Following an action-oriented transformation research, the main goal of this study was to ascertain the feasibility of an action-based communication intervention, based on the participants’ exposure to a post climate-related disaster scenario. The feasibility of the action-based communication intervention was assessed in a focus group meeting, whose content was qualitatively analysed; (3) The results of this study demonstrate that action-based communication interventions are feasible to trigger an attitude transformation, catalysed by the experiential processing of climate change and by the affect arousal; (4) This study comes to contribute to a transformation of the climate change communication praxis, by highlighting the urgency to shift the for a new paradigm of communicating climate change, in which the affect and the experiential processing should account for conveying environment-related information in order to promote society’s climate action.
Assessing Market Risk in BRICS and Oil Markets: An Application of Markov Switching and Vine Copula
Authors: Muteba Mwamba John Weirstrass , Mwambi Sutene Mwambetania
Published: June 2021

This paper investigates the dynamic tail dependence risk between BRICS economies and the world energy market, in the context of the COVID-19 financial crisis of 2020, in order to determine optimal investment decisions based on risk metrics. For this purpose, we employ a combination of novel statistical techniques, including Vector Autoregressive (VAR), Markov-switching GJR-GARCH, and vine copula methods. Using a data set consisting of daily stock and world crude oil prices, we find evidence of a structure break in the volatility process, consisting of high and low persistence volatility processes, with a high persistence in the probabilities of transition between lower and higher volatility regimes, as well as the presence of leverage effects. Furthermore, our results based on the C-vine copula confirm the existence of two types of tail dependence: symmetric tail dependence between South Africa and China, South Africa and Russia, and South Africa and India, and asymmetric lower tail dependence between South Africa and Brazil, and South Africa and crude oil. For the purpose of diversification in these markets, we formulate an asset allocation problem using raw returns, MS GARCH returns, and C-vine and R-vine copula-based returns, and optimize it using a Particle Swarm optimization algorithm with a rebalancing strategy. The results demonstrate an inverse relationship between the risk contribution and asset allocation of South Africa and the crude oil market, supporting the existence of a lower tail dependence between them. This suggests that, when South African stocks are in distress, investors tend to shift their holdings in the oil market. Similar results are found between Russia and crude oil, as well as Brazil and crude oil. In the symmetric tail, South African asset allocation is found to have a well-diversified relationship with that of China, Russia, and India, suggesting that these three markets might be good investment destinations when things are not good in South Africa, and vice versa.
When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer’s and Huntington’s Disease
Authors: D’Mello Santosh R.
Published: June 2021

Alzheimer’s disease (AD) is a mostly sporadic brain disorder characterized by cognitive decline resulting from selective neurodegeneration in the hippocampus and cerebral cortex whereas Huntington’s disease (HD) is a monogenic inherited disorder characterized by motor abnormalities and psychiatric disturbances resulting from selective neurodegeneration in the striatum. Although there have been numerous clinical trials for these diseases, they have been unsuccessful. Research conducted over the past three decades by a large number of laboratories has demonstrated that abnormal actions of common kinases play a key role in the pathogenesis of both AD and HD as well as several other neurodegenerative diseases. Prominent among these kinases are glycogen synthase kinase (GSK3), p38 mitogen-activated protein kinase (MAPK) and some of the cyclin-dependent kinases (CDKs). After a brief summary of the molecular and cell biology of AD and HD this review covers what is known about the role of these three groups of kinases in the brain and in the pathogenesis of the two neurodegenerative disorders. The potential of targeting GSK3, p38 MAPK and CDKS as effective therapeutics is also discussed as is a brief discussion on the utilization of recently developed drugs that simultaneously target two or all three of these groups of kinases. Multi-kinase inhibitors either by themselves or in combination with strategies currently being used such as immunotherapy or secretase inhibitors for AD and knockdown for HD could represent a more effective therapeutic approach for these fatal neurodegenerative diseases.
Anti-Inflammatory Effect of Auranofin on Palmitic Acid and LPS-Induced Inflammatory Response by Modulating TLR4 and NOX4-Mediated NF-κB Signaling Pathway in RAW264.7 Macrophages
Authors: Hwangbo Hyun , Ji Seon Yeong , Kim Min Yeong , Kim So Young , Lee Hyesook , Kim Gi-Young , Kim Suhkmann , Cheong JaeHun , Choi Yung Hyun
Published: June 2021

Chronic inflammation, which is promoted by the production and secretion of inflammatory mediators and cytokines in activated macrophages, is responsible for the development of many diseases. Auranofin is a Food and Drug Administration-approved gold-based compound for the treatment of rheumatoid arthritis, and evidence suggests that auranofin could be a potential therapeutic agent for inflammation. In this study, to demonstrate the inhibitory effect of auranofin on chronic inflammation, a saturated fatty acid, palmitic acid (PA), and a low concentration of lipopolysaccharide (LPS) were used to activate RAW264.7 macrophages. The results show that PA amplified LPS signals to produce nitric oxide (NO) and various cytokines. However, auranofin significantly inhibited the levels of NO, monocyte chemoattractant protein-1, and pro-inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor-α, and IL-6, which had been increased by co-treatment with PA and LPS. Moreover, the expression of inducible NO synthase, IL-1β, and IL-6 mRNA and protein levels increased by PA and LPS were reduced by auranofin. In particular, the upregulation of NADPH oxidase (NOX) 4 and the translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) induced by PA and LPS were suppressed by auranofin. The binding between the toll-like receptor (TLR) 4 and auranofin was also predicted, and the release of NO and cytokines was reduced more by simultaneous treatment with auranofin and TLR4 inhibitor than by auranofin alone. In conclusion, all these findings suggested that auranofin had anti-inflammatory effects in PA and LPS-induced macrophages by interacting with TLR4 and downregulating the NOX4-mediated NF-κB signaling pathway.
Mining the Biomarker Potential of the Urine Peptidome: From Amino Acids Properties to Proteases
Authors: Trindade Fábio , Barros António S. , Silva Jéssica , Vlahou Antonia , Falcão-Pires Inês , Guedes Sofia , Vitorino Carla , Ferreira Rita , Leite-Moreira Adelino , Amado Francisco , Vitorino Rui
Published: June 2021

Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine.
Comparative TMT Proteomic Analysis Unveils Unique Insights into Helicoverpa armigera (Hübner) Resistance in Cajanus scarabaeoides (L.) Thouars
Authors: Ngugi-Dawit Abigail , Njaci Isaac , Higgins Thomas J. V. , Williams Brett , Ghimire Sita R. , Mundree Sagadevan G. , Hoang Linh Thi My
Published: June 2021

Pigeonpea [Cajanus cajan (L.) Millspaugh] is an economically important legume playing a crucial role in the semi-arid tropics. Pigeonpea is susceptible to Helicoverpa armigera (Hübner), which causes devastating yield losses. This pest is developing resistance to many commercially available insecticides. Therefore, crop wild relatives of pigeonpea, are being considered as potential sources of genes to expand the genetic base of cultivated pigeonpea to improve traits such as host plant resistance to pests and pathogens. Quantitative proteomic analysis was conducted using the tandem mass tag platform to identify differentially abundant proteins between IBS 3471 and ICPL 87 tolerant accession and susceptible variety to H. armigera, respectively. Leaf proteome were analysed at the vegetative and flowering/podding growth stages. H. armigera tolerance in IBS 3471 appeared to be related to enhanced defence responses, such as changes in secondary metabolite precursors, antioxidants, and the phenylpropanoid pathway. The development of larvae fed on an artificial diet with IBS 3471 lyophilised leaves showed similar inhibition with those fed on an artificial diet with quercetin concentrations with 32 mg/25 g of artificial diet. DAB staining (3,3′-diaminobenzidine) revealed a rapid accumulation of reactive oxygen species in IBS 3471. We conclude that IBS 3471 is an ideal candidate for improving the genetic base of cultivated pigeonpea, including traits for host plant resistance.
Serratia symbiotica Enhances Fatty Acid Metabolism of Pea Aphid to Promote Host Development
Authors: Zhou Xiaofei , Ling Xiaoyu , Guo Huijuan , Zhu-Salzman Keyan , Ge Feng , Sun Yucheng
Published: June 2021

Bacterial symbionts associated with insects are often involved in host development and ecological adaptation. Serratia symbiotica, a common facultative endosymbiont harbored in pea aphids, improves host fitness and heat tolerance, but studies concerning the nutritional metabolism and impact on the aphid host associated with carrying Serratia are limited. In the current study, we showed that Serratia-infected aphids had a shorter nymphal developmental time and higher body weight than Serratia-free aphids when fed on detached leaves. Genes connecting to fatty acid biosynthesis and elongation were up-regulated in Serratia-infected aphids. Specifically, elevated expression of fatty acid synthase 1 (FASN1) and diacylglycerol-o-acyltransferase 2 (DGAT2) could result in accumulation of myristic acid, palmitic acid, linoleic acid, and arachidic acid in fat bodies. Impairing fatty acid synthesis in Serratia-infected pea aphids either by a pharmacological inhibitor or through silencing FASN1 and DGAT2 expression prolonged the nymphal growth period and decreased the aphid body weight. Conversely, supplementation of myristic acid (C14:0) to these aphids restored their normal development and weight gain. Our results indicated that Serratia promoted development and growth of its aphid host through enhancing fatty acid biosynthesis. Our discovery has shed more light on nutritional effects underlying the symbiosis between aphids and facultative endosymbionts.
Effects of Tyrosine and Tryptophan Supplements on the Vital Indicators in Mice Differently Prone to Diet-Induced Obesity
Authors: Gmoshinski Ivan V. , Shipelin Vladimir A. , Trusov Nikita V. , Apryatin Sergey A. , Mzhelskaya Kristina V. , Shumakova Antonina A. , Timonin Andrey N. , Riger Nikolay A. , Nikityuk Dmitry B.
Published: June 2021

We studied the effects of the addition of large neutral amino acids, such as tyrosine (Tyr) and tryptophan (Trp), in mice DBA/2J and tetrahybrid mice DBCB receiving a high-fat, high-carbohydrate diet (HFCD) for 65 days. The locomotor activity, anxiety, muscle tone, mass of internal organs, liver morphology, adipokines, cytokines, and biochemical indices of animals were assessed. The Tyr supplementation potentiated increased anxiety in EPM and contributed to a muscle tone increase, a decrease in the AST/ALT ratio, and an increase in protein anabolism in both mice strains. Tyr contributed to a decrease in liver fatty degeneration and ALT reduction only in DBCB that were sensitive to the development of obesity. The addition of Trp caused an increase in muscle tone and potentiated an increase in anxiety with age in animals of both genotypes. Trp had toxic effects on the livers of mice, which was manifested in increased fatty degeneration in DBCB, edema, and the appearance of micronuclei in DBA/2J. The main identified effects of Tyr on mice are considered in the light of its modulating effect on the dopamine neurotransmitter metabolism, while for the Trp supplement, effects were presumably associated with the synthesis of its toxic metabolites by representatives of the intestinal microflora.
Microtubule Dynamics Plays a Vital Role in Plant Adaptation and Tolerance to Salt Stress
Authors: Chun Hyun Jin , Baek Dongwon , Jin Byung Jun , Cho Hyun Min , Park Mi Suk , Lee Su Hyeon , Lim Lack Hyeon , Cha Ye Jin , Bae Dong-Won , Kim Sun Tae , Yun Dae-Jin , Kim Min Chul
Published: June 2021

Although recent studies suggest that the plant cytoskeleton is associated with plant stress responses, such as salt, cold, and drought, the molecular mechanism underlying microtubule function in plant salt stress response remains unclear. We performed a comparative proteomic analysis between control suspension-cultured cells (A0) and salt-adapted cells (A120) established from Arabidopsis root callus to investigate plant adaptation mechanisms to long-term salt stress. We identified 50 differentially expressed proteins (45 up- and 5 down-regulated proteins) in A120 cells compared with A0 cells. Gene ontology enrichment and protein network analyses indicated that differentially expressed proteins in A120 cells were strongly associated with cell structure-associated clusters, including cytoskeleton and cell wall biogenesis. Gene expression analysis revealed that expressions of cytoskeleton-related genes, such as FBA8, TUB3, TUB4, TUB7, TUB9, and ACT7, and a cell wall biogenesis-related gene, CCoAOMT1, were induced in salt-adapted A120 cells. Moreover, the loss-of-function mutant of Arabidopsis TUB9 gene, tub9, showed a hypersensitive phenotype to salt stress. Consistent overexpression of Arabidopsis TUB9 gene in rice transgenic plants enhanced tolerance to salt stress. Our results suggest that microtubules play crucial roles in plant adaptation and tolerance to salt stress. The modulation of microtubule-related gene expression can be an effective strategy for developing salt-tolerant crops.
Nuclear Magnetic Resonance Therapy Modulates the miRNA Profile in Human Primary OA Chondrocytes and Antagonizes Inflammation in Tc28/2a Cells
Authors: Steinecker-Frohnwieser Bibiane , Lohberger Birgit , Eck Nicole , Mann Anda , Kratschmann Cornelia , Leithner Andreas , Kullich Werner , Weigl Lukas
Published: June 2021

Nuclear magnetic resonance therapy (NMRT) is discussed as a participant in repair processes regarding cartilage and as an influence in pain signaling. To substantiate the application of NMRT, the underlying mechanisms at the cellular level were studied. In this study microRNA (miR) was extracted from human primary healthy and osteoarthritis (OA) chondrocytes after NMR treatment and was sequenced by the Ion PI Hi-Q™ Sequencing 200 system. In addition, T/C-28a2 chondrocytes grown under hypoxic conditions were studied for IL-1β induced changes in expression on RNA and protein level. HDAC activity an NAD(+)/NADH was measured by luminescence detection. In OA chondrocytes miR-106a, miR-27a, miR-34b, miR-365a and miR-424 were downregulated. This downregulation was reversed by NMRT. miR-365a-5p is known to directly target HDAC and NF-ĸB, and a decrease in HDAC activity by NMRT was detected. NAD+/NADH was reduced by NMR treatment in OA chondrocytes. Under hypoxic conditions NMRT changed the expression profile of HIF1, HIF2, IGF2, MMP3, MMP13, and RUNX1. We conclude that NMRT changes the miR profile and modulates the HDAC and the NAD(+)/NADH signaling in human chondrocytes. These findings underline once more that NMRT counteracts IL-1β induced changes by reducing catabolic effects, thereby decreasing inflammatory mechanisms under OA by changing NF-ĸB signaling.
Evaluation of Stable LifeAct-mRuby2- and LAMP1-NeonGreen Expressing A549 Cell Lines for Investigation of Aspergillus fumigatus Interaction with Pulmonary Cells
Authors: Schiefermeier-Mach Natalia , Moresco Violetta , Geley Stephan , Heinrich Lea , Lechner Lukas , Oberhauser Heidi , Perkhofer Susanne
Published: June 2021

Inhaled Aspergillus fumigatus spores can be internalized by alveolar type II cells. Cell lines stably expressing fluorescently labeled components of endocytic pathway enable investigations of intracellular organization during conidia internalization and measurement of the process kinetics. The goal of this report was to evaluate the methodological appliance of cell lines for studying fungal conidia internalization. We have generated A549 cell lines stably expressing fluorescently labeled actin (LifeAct-mRuby2) and late endosomal protein (LAMP1-NeonGreen) following an evaluation of cell-pathogen interactions in live and fixed cells. Our data show that the LAMP1-NeonGreen cell line can be used to visualize conidia co-localization with LAMP1 in live and fixed cells. However, caution is necessary when using LifeAct-mRuby2-cell lines as it may affect the conidia internalization dynamics.
Extracellular Vesicles: Versatile Nanomediators, Potential Biomarkers and Therapeutic Agents in Atherosclerosis and COVID-19-Related Thrombosis
Authors: Georgescu Adriana , Simionescu Maya
Published: June 2021

Cells convey information among one another. One instrument employed to transmit data and constituents to specific (target) cells is extracellular vesicles (EVs). They originate from a variety of cells (endothelial, immune cells, platelets, mesenchymal stromal cells, etc.), and consequently, their surface characteristics and cargo vary according to the paternal cell. The cargo could be DNA, mRNA, microRNA, receptors, metabolites, cytoplasmic proteins, or pathological molecules, as a function of which EVs exert different effects upon endocytosis in recipient cells. Recently, EVs have become important participants in a variety of pathologies, including atherogenesis and coronavirus disease 2019 (COVID-19)-associated thrombosis. Herein, we summarize recent advances and some of our own results on the role of EVs in atherosclerotic cardiovascular diseases, and discuss their potential to function as signaling mediators, biomarkers and therapeutic agents. Since COVID-19 patients have a high rate of thrombotic events, a special section of the review is dedicated to the mechanism of thrombosis and the possible therapeutic potential of EVs in COVID-19-related thrombosis. Yet, EV mechanisms and their role in the transfer of information between cells in normal and pathological conditions remain to be explored.
Functional Coupling between the P2X7 Receptor and Pannexin-1 Channel in Rat Trigeminal Ganglion Neurons
Authors: Inoue Hiroyuki , Kuroda Hidetaka , Ofusa Wataru , Oyama Sadao , Kimura Maki , Ichinohe Tatsuya , Shibukawa Yoshiyuki
Published: June 2021

The ionotropic P2X receptor, P2X7, is believed to regulate and/or generate nociceptive pain, and pain in several neuropathological diseases. Although there is a known relationship between P2X7 receptor activity and pain sensing, its detailed functional properties in trigeminal ganglion (TG) neurons remains unclear. We examined the electrophysiological and pharmacological characteristics of the P2X7 receptor and its functional coupling with other P2X receptors and pannexin-1 (PANX1) channels in primary cultured rat TG neurons, using whole-cell patch-clamp recordings. Application of ATP and Bz-ATP induced long-lasting biphasic inward currents that were more sensitive to extracellular Bz-ATP than ATP, indicating that the current was carried by P2X7 receptors. While the biphasic current densities of the first and second components were increased by Bz-ATP in a concentration dependent manner; current duration was only affected in the second component. These currents were significantly inhibited by P2X7 receptor antagonists, while only the second component was inhibited by P2X1, 3, and 4 receptor antagonists, PANX1 channel inhibitors, and extracellular ATPase. Taken together, our data suggests that autocrine or paracrine signaling via the P2X7-PANX1-P2X receptor/channel complex may play important roles in several pain sensing pathways via long-lasting neuronal activity driven by extracellular high-concentration ATP following tissue damage in the orofacial area.
Role of Lateral Hypothalamus in Acupuncture Inhibition of Cocaine Psychomotor Activity
Authors: Ahn DanBi , Jang Han Byeol , Chang Suchan , Kim Hyung Kyu , Ryu Yeonhee , Lee Bong Hyo , Kim Sang Chan , Bills Kyle B. , Steffensen Scott C. , Fan Yu , Kim Hee Young
Published: June 2021

Acupuncture modulates the mesolimbic dopamine (DA) system; an area implicated in drug abuse. However, the mechanism by which peripheral sensory afferents, during acupuncture stimulation, modulate this system needs further investigation. The lateral hypothalamus (LH) has been implicated in reward processing and addictive behaviors. To investigate the role of the LH in mediating acupuncture effects, we evaluated the role of LH and spinohypothalamic neurons on cocaine-induced psychomotor activity and NAc DA release. Systemic injection of cocaine increased locomotor activity and 50 kHz ultrasonic vocalizations (USVs), which were attenuated by mechanical stimulation of needles inserted into HT7 but neither ST36 nor LI5. The acupuncture effects were blocked by chemical lesions of the LH or mimicked by activation of LH neurons. Single-unit extracellular recordings showed excitation of LH and spinohypothalamic neurons following acupuncture. Our results suggest that acupuncture recruits the LH to suppress the mesolimbic DA system and psychomotor responses following cocaine injection.
Regulation of Inflammatory and Proliferative Pathways by Fotemustine and Dexamethasone in Endometriosis
Authors: Genovese Tiziana , Siracusa Rosalba , D’Amico Ramona , Cordaro Marika , Peritore Alessio Filippo , Gugliandolo Enrico , Crupi Rosalia , Trovato Salinaro Angela , Raffone Emanuela , Impellizzeri Daniela , Cuzzocrea Salvatore , Fusco Roberta , Di Paola Rosanna
Published: June 2021

Endometriosis is a common disease. Its pathogenesis still remains uncertain, but it is clear that cell proliferation, apoptosis and chronic inflammation play an important role in its development. This paper aimed to investigate the anti-proliferative and anti-inflammatory effects of a combined therapy with fotemustine and dexamethasone. Endometriosis was induced by intraperitoneal injections of uterine fragments from donor animals to recipient animals. Next, the pathology was allowed to develop for 7 days. On the seventh day, fotemustine was administered once and dexamethasone was administered daily for the next 7 days. On Day 14, the animals were sacrificed, and peritoneal fluids and lesions were explanted. In order to evaluate the gastrointestinal side effects of the drugs, stomachs were harvested as well. The combined therapy of fotemustine and dexamethasone reduced the proinflammatory mediator levels in the peritoneal fluid and reduced the lesions’ area and diameter. In particular, fotemustine and dexamethasone administration reduced the heterogeneous development of endometrial stroma and glands (histological analysis of lesions) and hyperproliferation of endometriotic cells (immunohistochemical analysis of Ki67 and Western blot analysis of PCNA) through the mitogen-activated protein kinase (MAPK) signaling pathway. Combined fotemustine and dexamethasone therapy showed anti-inflammatory effects by inducing the synthesis of anti-inflammatory mediators at the transcriptional and post-transcriptional levels (Western blot analysis of NFκB, COX-2 and PGE2 expression). Fotemustine and dexamethasone administration had anti-apoptotic activity, restoring the impaired mechanism (TUNEL assay and Western blot analysis of Bax and Bcl-2). Moreover, no gastric disfunction was detected (histological analysis of stomachs). Thus, our data showed that the combined therapy of fotemustine and dexamethasone reduced endometriosis-induced inflammation, hyperproliferation and apoptosis resistance.
The Association of Lipoprotein(a) and Circulating Monocyte Subsets with Severe Coronary Atherosclerosis
Authors: Afanasieva Olga I. , Filatova Anastasya Yu. , Arefieva Tatiana I. , Klesareva Elena A. , Tyurina Alexandra V. , Radyukhina Natalia V. , Ezhov Marat V. , Pokrovsky Sergei N.
Published: June 2021

Background and aims: Chronic inflammation associated with the uncontrolled activation of innate and acquired immunity plays a fundamental role in all stages of atherogenesis. Monocytes are a heterogeneous population and each subset contributes differently to the inflammatory process. A high level of lipoprotein(a) (Lp(a)) is a proven cardiovascular risk factor. The aim of the study was to investigate the association between the increased concentration of Lp(a) and monocyte subpopulations in patients with a different severity of coronary atherosclerosis. Methods: 150 patients (124 males) with a median age of 60 years undergoing a coronary angiography were enrolled. Lipids, Lp(a), autoantibodies, blood cell counts and monocyte subpopulations (classical, intermediate, non-classical) were analyzed. Results: The patients were divided into two groups depending on the Lp(a) concentration: normal Lp(a) < 30 mg/dL (n = 82) and hyperLp(a) ≥ 30 mg/dL (n = 68). Patients of both groups were comparable by risk factors, autoantibody levels and blood cell counts. In patients with hyperlipoproteinemia(a) the content (absolute and relative) of non-classical monocytes was higher (71.0 (56.6; 105.7) vs. 62.2 (45.7; 82.4) 103/mL and 17.7 (13.0; 23.3) vs. 15.1 (11.4; 19.4) %, respectively, p < 0.05). The association of the relative content of non-classical monocytes with the Lp(a) concentration retained a statistical significance when adjusted for gender and age (r = 0.18, p = 0.03). The severity of coronary atherosclerosis was associated with the Lp(a) concentration as well as the relative and absolute (p < 0.05) content of classical monocytes. The high content of non-classical monocytes (OR = 3.5, 95% CI 1.2–10.8) as well as intermediate monocytes (OR = 8.7, 2.5–30.6) in patients with hyperlipoproteinemia(a) were associated with triple-vessel coronary disease compared with patients with a normal Lp(a) level and a low content of monocytes. Conclusion: Hyperlipoproteinemia(a) and a decreased quantity of classical monocytes were associated with the severity of coronary atherosclerosis. The expansion of CD16+ monocytes (intermediate and non-classical) in the presence of hyperlipoproteinemia(a) significantly increased the risk of triple-vessel coronary disease.