Search results for: metabolic pathways
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1293

Search results for: metabolic pathways

1113 Evaluation of DNA Oxidation and Chemical DNA Damage Using Electrochemiluminescent Enzyme/DNA Microfluidic Array

Authors: Itti Bist, Snehasis Bhakta, Di Jiang, Tia E. Keyes, Aaron Martin, Robert J. Forster, James F. Rusling

Abstract:

DNA damage from metabolites of lipophilic drugs and pollutants, generated by enzymes, represents a major toxicity pathway in humans. These metabolites can react with DNA to form either 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), which is the oxidative product of DNA or covalent DNA adducts, both of which are genotoxic and hence considered important biomarkers to detect cancer in humans. Therefore, detecting reactions of metabolites with DNA is an effective approach for the safety assessment of new chemicals and drugs. Here we describe a novel electrochemiluminescent (ECL) sensor array which can detect DNA oxidation and chemical DNA damage in a single array, facilitating a more accurate diagnostic tool for genotoxicity screening. Layer-by-layer assembly of DNA and enzyme are assembled on the pyrolytic graphite array which is housed in a microfluidic device for sequential detection of two type of the DNA damages. Multiple enzyme reactions are run on test compounds using the array, generating toxic metabolites in situ. These metabolites react with DNA in the films to cause DNA oxidation and chemical DNA damage which are detected by ECL generating osmium compound and ruthenium polymer, respectively. The method is further validated by the formation of 8-oxodG and DNA adduct using similar films of DNA/enzyme on magnetic bead biocolloid reactors, hydrolyzing the DNA, and analyzing by liquid chromatography-mass spectrometry (LC-MS). Hence, this combined DNA/enzyme array/LC-MS approach can efficiently explore metabolic genotoxic pathways for drugs and environmental chemicals.

Keywords: biosensor, electrochemiluminescence, DNA damage, microfluidic array

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1112 Single-Section Fermentation Reactor with Cellular Mixing System

Authors: Marcin Dębowski, Marcin Zieliński, Mirosław Krzemieniewski

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This publication presents a reactor designed for methane fermentation of organic substrates. The design is based on rotating cellular cylinders connected to a biomass feeder and an ultrasonic generator. This allows for simultaneous mixing and partial disintegration of the biomass, as well as stimulating higher metabolic rates within the microorganisms. Such a design allows from 2-fold to 14-fold reduction of power usage when compared to conventional mixing systems. The sludge does not undergo mechanical deformation during the mixing process, which improves substrate biodegradation efficiency by 10-15%. Cavitation occurs near the surface of the rods, partially releasing the biomass and separating it from the destroyed microorganisms. Biogas is released further away from the cellular cylinder rods due to the effect of the ultrasonic waves, in addition to increased biochemical activity of the microorganisms and increased exchange of the nutrient medium with metabolic products, which results in biogas production increase by about 15%.

Keywords: methane fermentation, bioreactors, biomass, mixing system

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1111 Genetic Polymorphism in the Vitamin D Receptor Gene and 25-Hydroxyvitamin D Serum Levels in East Indian Women with Polycystic Ovary Syndrome

Authors: Dipanshu Sur, Ratnabali Chakravorty

Abstract:

Background: Polycystic ovary syndrome (PCOS) is the most common metabolic abnormality such as changes in lipid profile, diabetes, hypertension and metabolic syndrome occurring in young women of reproductive age. Low vitamin D levels were found to be associated with the development of obesity and insulin resistance in women with PCOS. Variants on vitamin D receptor (VDR) gene have also been related to metabolic comorbidities in general population. Aim: The aim of this case-control study was to investigate whether the VDR gene polymorphisms are associated with susceptibility to PCOS. Methods: Women with PCOS and a control group, all aged 16-40 years, were enrolled. Genotyping of VDR Fok-I (rs2228570), VDR Apa-I (rs7975232) as well as GC (rs2282679), DHCR7 (rs12785878) SNPs between groups were determined by using direct sequencing. Serum 25-hydroxyvitamin D [25(OH)] levels were measured by ELISA. Results: Mean serum 25(OH)D in the PCOS and control samples were 19.08±7 and 23.27±6.03 (p=0.048) which were significantly lower in PCOS patients compared with controls. CC genotype of the VDR Apa-I SNP was same frequent in PCOS (25.6%) and controls (25.6%) (OR: 0.9995; 95%CI: 0.528 to 1.8921; p= 0.9987). The CC genotype was also significantly associated with both lower E2 (p=0.031) and Androstenedione levels (p=0.062). We observed a significant association of GC polymorphism with 25(OH)D levels. PCOS women carrying the GG genotype (in GC genes) had significantly higher risk for vitamin D deficiency than women carrying the TT genotype. Conclusions: In conclusion, data from this study indicate that vitamin D levels are lower, and vitamin D deficiency more frequent, in PCOS than in controls. The present findings suggest that the Apa-I, Fok-I polymorphism of the VDR gene is associated with PCOS and seems to modulate ovarian steroid secretion. Further studies are needed to better clarify the biological mechanisms by which the polymorphism influences PCOS risk.

Keywords: vitamin D receptor, polymorphism, vitamin D, polycystic ovary syndrome

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1110 Transgenerational Impact of Intrauterine Hyperglycaemia to F2 Offspring without Pre-Diabetic Exposure on F1 Male Offspring

Authors: Jun Ren, Zhen-Hua Ming, He-Feng Huang, Jian-Zhong Sheng

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Adverse intrauterine stimulus during critical or sensitive periods in early life, may lead to health risk not only in later life span, but also further generations. Intrauterine hyperglycaemia, as a major feature of gestational diabetes mellitus (GDM), is a typical adverse environment for both F1 fetus and F1 gamete cells development. However, there is scare information of phenotypic difference of metabolic memory between somatic cells and germ cells exposed by intrauterine hyperglycaemia. The direct transmission effect of intrauterine hyperglycaemia per se has not been assessed either. In this study, we built a GDM mice model and selected male GDM offspring without pre-diabetic phenotype as our founders, to exclude postnatal diabetic influence on gametes, thereby investigate the direct transmission effect of intrauterine hyperglycaemia exposure on F2 offspring, and we further compared the metabolic difference of affected F1-GDM male offspring and F2 offspring. A GDM mouse model of intrauterine hyperglycemia was established by intraperitoneal injection of streptozotocin after pregnancy. Pups of GDM mother were fostered by normal control mothers. All the mice were fed with standard food. Male GDM offspring without metabolic dysfunction phenotype were crossed with normal female mice to obtain F2 offspring. Body weight, glucose tolerance test, insulin tolerance test and homeostasis model of insulin resistance (HOMA-IR) index were measured in both generations at 8 week of age. Some of F1-GDM male mice showed impaired glucose tolerance (p < 0.001), none of F1-GDM male mice showed impaired insulin sensitivity. Body weight of F1-GDM mice showed no significance with control mice. Some of F2-GDM offspring exhibited impaired glucose tolerance (p < 0.001), all the F2-GDM offspring exhibited higher HOMA-IR index (p < 0.01 of normal glucose tolerance individuals vs. control, p < 0.05 of glucose intolerance individuals vs. control). All the F2-GDM offspring exhibited higher ITT curve than control (p < 0.001 of normal glucose tolerance individuals, p < 0.05 of glucose intolerance individuals, vs. control). F2-GDM offspring had higher body weight than control mice (p < 0.001 of normal glucose tolerance individuals, p < 0.001 of glucose intolerance individuals, vs. control). While glucose intolerance is the only phenotype that F1-GDM male mice may exhibit, F2 male generation of healthy F1-GDM father showed insulin resistance, increased body weight and/or impaired glucose tolerance. These findings imply that intrauterine hyperglycaemia exposure affects germ cells and somatic cells differently, thus F1 and F2 offspring demonstrated distinct metabolic dysfunction phenotypes. And intrauterine hyperglycaemia exposure per se has a strong influence on F2 generation, independent of postnatal metabolic dysfunction exposure.

Keywords: inheritance, insulin resistance, intrauterine hyperglycaemia, offspring

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1109 Compensatory Increased Activities of Mitochondrial Respiratory Chain Complexes from Eyes of Glucose-Immersed Zebrafish

Authors: Jisun Jun, Eun Ko, Sooim Shin, Kitae Kim, Moonsung Choi

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Diabetes is a metabolic disease characterized by hyperglycemia, insulin resistant, mitochondrial dysfunction. Diabetes is associated with the development of diabetic retinopathy resulting in worsening vision and eventual blindness. In this study, eyes were enucleated from glucose-immersed zebrafish which is a good animal model to generate diabetes, and then mitochondria were isolated to evaluate activities of mitochondrial electron transfer complexes. Surprisingly, the amount of isolated mitochondria was increased in eyes from glucose-immersed zebrafish compared to those from non-glucose-immerged zebrafish. Spectrophotometric analysis for measuring activities of mitochondrial complex I, II, III, and IV revealed that mitochondria functions was even enhanced in eyes from glucose-immersed zebrafish. These results indicated that 3 days or 7 days glucose-immersion on zebrafish to induce diabetes might contribute metabolic compensatory mechanism to restore their mitochondrial homeostasis on the early stage of diabetes in eyes.

Keywords: diabetes, glucose immersion, mitochondrial complexes, zebrafish

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1108 The Effects of Acupoint Catgut Embedding for Weight Control in Mice Model

Authors: Chanya Inprasit, Ching-Liang Hsieh, Yi-Wen Lin

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Obesity (OB) is a hazardous global health problem that has been increasing in prevalence, more severely in last decade. It is the mainly resultant from the imbalance between food consumption and energy expenditure, which is concordant with a modern lifestyle, implying an increase in calories with poorer quality of food intake accompanied by a decrease in physical activities. Obesity does not concern the appearance only but is also a major factor contributing to poor physiology, psychology, society and economic issues. Moreover, OB induces low-grade inflammation in the body through the regulatory effect it enacts on the adipocyte function. Various alternative treatments were investigated for body weight control, including Acupoint Catgut Embedding (ACE). ACE is the implantation of absorbable catgut sutures at specific acupoints, displaying durable and potent stimulation and thereby reducing the treatment frequency. Our study utilized a mouse model to exclude any psychological factors of OB and ACE treatment. High-fat diet and body weight were measured once a week before subjects in ACE and Sham group received the ACE treatment or placebo treatment. We hypothesized that ACE can control body weight through the interaction of the TRPV1 pathways, as TRPV1 accordingly responds to inflammatory factors. The results of body weight variation show a significant decrease in body weight in ACE group compared with the baseline of control and Sham group. Meanwhile, converse results were explored in TRPV1 knockout mice, where a significant maintenance of normal body weight throughout the experiment period was observed. There was no significant difference in food consumption of each group. These finding indicated that TRPV1 pathways and its associated pathways may be involved in the maintenance of body weight, which can be controlled by ACE treatment of genetic manipulation.

Keywords: acupoint catgut embedding, obesity, hypothalamus, TRPV1

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1107 Correlation between Vitreoscilla Hemoglobin Gene (Vgb) and Cadmium Uptake in the Heterologous Host Enterobacter Aerogenes in Response to Metabolic Inhibitors

Authors: Khaled Khleifat, Muayyad Abboud, Ahmad Almustafa

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The effect of metabolic inhibitor/uncoupler(s) (CCCP and NaN3) and sulfhydryl reagents (dithiothreitol, 2 mercaptoethanol glutathione) on cadmium uptake was investigated in Enterobacter aerogenes strains. They include a transformed strain bearing the Vitreoscillahemoglobin gene, vgb as well as control strains that lack this transformed gene. The vgb-harboring strains showed better uptake of cadmium than vgb-lacking strains. Under low aeration, there was 2 fold enhancement of Cd+2 uptake in vgb-harboring strains compared with 1.6-fold enhancement under high aeration. The CCCP caused 36, 40 and 58% inhibition in cadmium uptake of parental, pUC9 harboring and VHb expressing cells, respectively. Similarly, the sodium azide exerted 44, 38 and 55% inhibition in Cd+2 uptake of parental, pUC9 harboring and VHb expressing cells, respectively. Less extensive inhibition of Cd+2 uptake in the range of 11 to 39% was observed with sulfhydryl reagents.

Keywords: bacterial hemoglobin, VHb, Cd uptake, biosorption

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1106 Genetically Informed Precision Drug Repurposing for Rheumatoid Arthritis

Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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1105 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma

Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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1104 Collision Induced Dissociation of Transition Metal Fluoride Complexes and the Multiply Charged Anions

Authors: Ruqia Nazir, Robin Perutz

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Collision-induced dissociation (CID) can be used to study the intrinsic properties of ions in the gas phase.1 Decay pathways of transition metal difluoride complexes of titanium, zirconium, hafnium, and ruthenium were studied by CID in an ESI-Ion trap mass spectrometer. Furthermore, the decay pathways of multiply charged anions (MCAs) of titanium and zirconium were also studied. The CID results are illustrated by the behaviour of (Cp*)₂TiF₂, which initially forms the ions [M-F-]⁺, [M+Na]⁺, and [M+K]⁺. The [(Cp*₂)TiF⁺ ion decays on resonant excitation to lose HF forming [Cp*(C₅Me₄CH₂)Ti]⁺ (Figure). The other major ion, [(Cp*)₂TiF₂+Na]⁺, decays on resonant excitation with production of [(Cp*)₂TiF₂]⁺ and [C₅Me₄CH₂]⁺. We also report the behaviour of Cp₂MF₂ (M = Zr, Hf) and Ru(PMe₃)₄F₂. The decay pathway of the multiply charged anions (MCAs), notably TiF₆²⁻ and ZrF₆²⁻ was concluded to be ionic fragmentation with loss of F⁻ rather than electron detachment.

Keywords: collision induced dissociation, transition metal difluoride comolexes, multiply charged anions, mass spectrometry

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1103 Impact of Heavy Metal Toxicity on Metabolic Changes in the Diazotrophic Cyanobacterium Anabaena PCC 7120

Authors: Rishi Saxena

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Cyanobacteria is a photosynthetic prokaryote, and these obtain their energy through photosynthesis. In this paper, we studied the effect of iron on metabolic changes in the diazotrophic cyanobacterium Anabaena PCC 7120. Nowadays, metal contamination due to natural and anthropogenic sources is a global environment concern. Iron induced changes in growth, N2-fixation, CO2 fixation and photosynthetic activity were studied in a diazotrophic cyanobacterium Anabaena PCC 7120. Iron at 50 uM concentration supported the maximum growth, heterocyst frequency, CO2 fixation, photosystem I (PS I), photosystem II (PS II) and nitrogenase activities in the organism. Higher concentration of iron inhibited these processes. Chl a and PS II activities were more sensitive to iron than the protein and PS I activity. Here, it is also mentioned that heavy metal induced altered macromolecules metabolism and changes in the central dogma of life (DNA→ mRNA → Protein). And also recent advances have been made in understanding heavy metal-cyanobacteria interaction and their application for metal detoxification.

Keywords: cyanobacterium anabaena 7120, nitrogen fixation, photosystem I (PS I), photosystem II (PS II)

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1102 Detection of Arterial Stiffness in Diabetes Using Photoplethysmograph

Authors: Neelamshobha Nirala, R. Periyasamy, Awanish Kumar

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Diabetes is a metabolic disorder and with the increase of global prevalence of diabetes, cardiovascular diseases and mortality related to diabetes has also increased. Diabetes causes the increase of arterial stiffness by elusive hormonal and metabolic abnormalities. We used photoplethysmograph (PPG), a simple non-invasive method to study the change in arterial stiffness due to diabetes. Toe PPG signals were taken from 29 diabetic subjects with mean age of (65±8.4) years and 21 non-diabetic subjects of mean age of (49±14) years. Mean duration of diabetes is 12±8 years for diabetic group. Rise-time (RT) and area under rise time (AUR) were calculated from the PPG signal of each subject and Welch’s t-test is used to find the significant difference between two groups. We obtained a significant difference of (p-value) 0.0005 and 0.03 for RT and AUR respectively between diabetic and non-diabetic subjects. Average value of RT and AUR is 0.298±0.003 msec and 14.4±4.2 arbitrary units respectively for diabetic subject compared to 0.277±0.0005 msec and 13.66±2.3 a.u respectively for non-diabetic subjects. In conclusion, this study support that arterial stiffness is increased in diabetes and can be detected early using PPG.

Keywords: area under rise-time, AUR, arterial stiffness, diabetes, photoplethysmograph, PPG, rise-time (RT)

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1101 Structural Protein-Protein Interactions Network of Breast Cancer Lung and Brain Metastasis Corroborates Conformational Changes of Proteins Lead to Different Signaling

Authors: Farideh Halakou, Emel Sen, Attila Gursoy, Ozlem Keskin

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Protein–Protein Interactions (PPIs) mediate major biological processes in living cells. The study of PPIs as networks and analyze the network properties contribute to the identification of genes and proteins associated with diseases. In this study, we have created the sub-networks of brain and lung metastasis from primary tumor in breast cancer. To do so, we used seed genes known to cause metastasis, and produced their interactions through a network-topology based prioritization method named GUILDify. In order to have the experimental support for the sub-networks, we further curated them using STRING database. We proceeded by modeling structures for the interactions lacking complex forms in Protein Data Bank (PDB). The functional enrichment analysis shows that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing are more involved in brain metastasis. The structural analyses of the sub-networks vividly demonstrated their difference in terms of using specific interfaces in lung and brain metastasis. Furthermore, the topological analysis identified genes such as RPL5, MMP2, CCR5 and DPP4, which are already known to be associated with lung or brain metastasis. Additionally, we found 6 and 9 putative genes that are specific for lung and brain metastasis, respectively. Our analysis suggests that variations in genes and pathways contributing to these different breast metastasis types may arise due to change in tissue microenvironment. To show the benefits of using structural PPI networks instead of traditional node and edge presentation, we inspect two case studies showing the mutual exclusiveness of interactions and effects of mutations on protein conformation which lead to different signaling.

Keywords: breast cancer, metastasis, PPI networks, protein conformational changes

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1100 Gene Expression Meta-Analysis of Potential Shared and Unique Pathways Between Autoimmune Diseases Under anti-TNFα Therapy

Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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1099 Energy Options and Environmental Impacts of Carbon Dioxide Utilization Pathways

Authors: Evar C. Umeozor, Experience I. Nduagu, Ian D. Gates

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The energy requirements of carbon dioxide utilization (CDU) technologies/processes are diverse, so also are their environmental footprints. This paper explores the energy and environmental impacts of systems for CO₂ conversion to fuels, chemicals, and materials. Energy needs of the technologies and processes deployable in CO₂ conversion systems are met by one or combinations of hydrogen (chemical), electricity, heat, and light. Likewise, the environmental footprint of any CO₂ utilization pathway depends on the systems involved. So far, evaluation of CDU systems has been constrained to particular energy source/type or a subset of the overall system needed to make CDU possible. This introduces limitations to the general understanding of the energy and environmental implications of CDU, which has led to various pitfalls in past studies. A CDU system has an energy source, CO₂ supply, and conversion units. We apply a holistic approach to consider the impacts of all components in the process, including various sources of energy, CO₂ feedstock, and conversion technologies. The electricity sources include nuclear power, renewables (wind and solar PV), gas turbine, and coal. Heat is supplied from either electricity or natural gas, and hydrogen is produced from either steam methane reforming or electrolysis. The CO₂ capture unit uses either direct air capture or post-combustion capture via amine scrubbing, where applicable, integrated configurations of the CDU system are explored. We demonstrate how the overall energy and environmental impacts of each utilization pathway are obtained by aggregating the values for all components involved. Proper accounting of the energy and emission intensities of CDU must incorporate total balances for the utilization process and differences in timescales between alternative conversion pathways. Our results highlight opportunities for the use of clean energy sources, direct air capture, and a number of promising CO₂ conversion pathways for producing methanol, ethanol, synfuel, urea, and polymer materials.

Keywords: carbon dioxide utilization, processes, energy options, environmental impacts

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1098 Risk of Androgen Deprivation Therapy-Induced Metabolic Syndrome-Related Complications for Prostate Cancer in Taiwan

Authors: Olivia Rachel Hwang, Yu-Hsuan Joni Shao

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Androgen Deprivation Therapy (ADT) has been a primary treatment for patients with advanced prostate cancer. However, it is associated with numerous adverse effects related to Metabolic Syndrome (MetS), including hypertension, diabetes, hyperlipidaemia, heart diseases and ischemic strokes. However, complications associated with ADT for prostate cancer in Taiwan is not well documented. The purpose of this study is to utilize the data from NHIRD (National Health Insurance Research Database) to examine the trajectory changes of MetS-related complications in men receiving ADT. The risks of developing complications after the treatment were analyzed with multivariate Cox regression model. Covariates including in the model were the complications before the diagnosis of prostate cancer, the age, and the year at cancer diagnosis. A total number of 17268 patients from 1997-2013 were included in this study. The exclusion criteria were patients with any other types of cancer or with the existing MetS-related complications. Changes in MetS-related complications were observed among two treatment groups: 1) ADT (n=9042), and 2) non-ADT (n=8226). The ADT group appeared to have an increased risk in hypertension (hazard ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001) and hyperlipidemia (hazard ratio 1.09, 95% confidence interval 1.01-1.17, P = 0.02) when compared with non-ADT group in the multivariate Cox regression analyses. In the risk of diabetes, heart diseases, and ischemic strokes, ADT group appeared to have an increased but not significant hazard ratio. In conclusion, ADT was associated with an increased risk in hypertension and hyperlipidemia in prostate cancer patients in Taiwan. The risk of hypertension and hyperlipidemia should be considered while deciding on ADT, especially those with the known history of hypertension and hyperlipidemia.

Keywords: androgen deprivation therapy, ADT, complications, metabolic syndrome, MetS, prostate cancer

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1097 Multiple Strategies in Prevention of Metabolic Syndrome Result from Vitamin D Deficiency in Children

Authors: Maryam Ghavam Sadri, Maryam Shahrooz

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Background: Nowadays the prevalence of metabolic syndrome (Mets) has taken on a growing trend. Studies have shown the relationship between vitamin D deficiency (VDD) status and Mets in children. Also studies have recorded that exerting strategies for vitamin D status improvement can help prevent Mets in children. This study investigated multiple strategies of prevention of Mets resulting from VDD in children. Methods: This review study has been done by using keywords related to the topic and 54 articles were found (2000-2015) that 25 were selected according to the indicators of Mets, supplementation and fortification of foods with vitamin D and attention to children environment and life style. Results: Studies have suggested the correlation between serum levels of vitamin D with waist circumference (p < 0.0001), systolic blood pressure (p=0.01), HOMA-IR (p=0.001) and HDL cholesterol (p < 0.0001). An inverse correlation between serum 25 (OH) D and HOMA-IR (p = 0.006) and insulin (P = 0.002) has been proved in overweight group. Higher HOMASDS and triglycerides found in vitamin D deficient obese children compared to control group without VDD (p=0.04). After supplementation with vitamin D, serum TG concentration decreases significantly (p=0.04), and improves insulin resistance (p=0.02). The prevalence of VDD is associated with time of watching TV (P < 0.01), hours of physical activity per week (P = 0.01), skipping breakfast (P < 0.001) soda intake (P < 0.001), and milk intake per day (P < 0.01). Conclusion: According to the beneficial role of vitamin D in prevention of Mets and proven relationship between serum levels of vitamin D and Mets indicators, we can prevent childhood Mets through the application of appropriate strategies such as supplementation and food fortification with vitamin D and positive changes in children life style with especial attention to physical activity in exposure of sunlight and their environment condition.

Keywords: children, metabolic syndrome, prevention strategies, vitamin D

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1096 Association of Brain-Derived Neurotrophic Factor (BDNF) Gene with Obesity and Metabolic Traits in Malaysian Adults

Authors: Yamunah Devi Apalasamy, Sanjay Rampal, Tin Tin Su, Foong Ming Moy, Hazreen Abdul Majid, Awang Bulgiba, Zahurin Mohamed

Abstract:

Obesity is a growing global health issue. Obesity results from a combination of environmental and genetics factors. Brain-derived neurotrophic factor (BDNF), a gene encodes the BDNF protein and the BDNF gene have been linked to regulation of body weight and appetite. Genome-wide association studies have identified the BDNF variants to be related to obesity among Caucasians, East Asians, and Filipinos. However, the role of BDNF in other ethnic groups remains inconclusive. This case control study aims to investigate the associations of BDNF gene polymorphisms with obesity and metabolic parameters in Malaysian Malays. BDNF rs4074134, BDNF rs10501087 and BDNF rs6265 were genotyped using Sequenom MassARRAY. Anthropometric, body fat, fasting lipids and glucose levels were measured. A total of 663 subjects (194 obese and 469 non-obese) were included in this study. There were no significant associations association between BDNF SNPs and obesity. The allelic and genotype frequencies of the BDNF SNPs were similar in the obese and non-obese groups. After adjustment for age and sex, the BDNF variants were not associated with obesity, body fat, fasting lipids and glucose levels. Haplotypes at the BDNF gene region, were not significantly associated with obesity. The BDNF rs4074134 was in strong LD with BDNF rs10501087 (D'=0.98) and BDNF rs6265 (D'=0.87). The BDNF rs10501087 was also in strong LD with BDNF rs6265 (D'=0.91). Our findings suggest that the BDNF variants and the haplotypes of BDNF gene were not associated with obesity and metabolic traits in this study population. Further research is needed to explore other BDNF variants with a larger sample size with gene-environment interactions in multi ethnic Malaysian population.

Keywords: genomics of obesity, SNP, BMI, haplotypes

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1095 Effect of Aging on the Second Law Efficiency, Exergy Destruction and Entropy Generation in the Skeletal Muscles during Exercise

Authors: Jale Çatak, Bayram Yılmaz, Mustafa Ozilgen

Abstract:

The second law muscle work efficiency is obtained by multiplying the metabolic and mechanical work efficiencies. Thermodynamic analyses are carried out with 19 sets of arms and legs exercise data which were obtained from the healthy young people. These data are used to simulate the changes occurring during aging. The muscle work efficiency decreases with aging as a result of the reduction of the metabolic energy generation in the mitochondria. The reduction of the mitochondrial energy efficiency makes it difficult to carry out the maintenance of the muscle tissue, which in turn causes a decline of the muscle work efficiency. When the muscle attempts to produce more work, entropy generation and exergy destruction increase. Increasing exergy destruction may be regarded as the result of the deterioration of the muscles. When the exergetic efficiency is 0.42, exergy destruction becomes 1.49 folds of the work performance. This proportionality becomes 2.50 and 5.21 folds when the exergetic efficiency decreases to 0.30 and 0.17 respectively.

Keywords: aging mitochondria, entropy generation, exergy destruction, muscle work performance, second law efficiency

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1094 Comparative Therapeutic Effect of Acalypha indica Linn. Extract and Gemfibrozil on High Fructose and Cholesterol Diet Induced Pancreas Steatosis in Sprague-Dawley Mice

Authors: Adrian Reynaldo Sudirman, Siti Farida, Aisyah Aminy Maulidina, Caren Andika Surbakti

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Sedentary lifestyle and imbalance consumption pattern has made metabolic syndrome as the global time bomb phenomenon in the world. The increasing tendency of people in consuming high amount of fructose and cholesterol food has worsened this issue in the society. Pancreas steatosis become one of the most comorbid when early diagnosis and prompt treatment has not been applied on hyperglycemic and hyperlipidemic condition in metabolic syndrome patient. Gemfibrozil become the drug of choice to prevent this issue, yet the efficacy of this regiment was still questionable. Acalypha indica Linn. is the herb that has protective effect on hyperlipidemic and hyperglycemic condition. This study was aimed to compare therapeutic effect of gemfibrozil (G) and Acalypha indica Linn. (AI) on high fructose and cholesterol diet-induced pancreas steatosis in Sprague-Dawley mice. The post induction mice were divided into four groups: control, gemfibrozil, AI extract, and G+AI combination regiment. Each group received four weeks intervention. The result of statistical analysis using the One-Way ANOVA test and Tukey Post Hoc test showed significant decrease in pancreatic steatosis between the control group and administered Acalypha indica group (p = 0.004, 95% CI: 0.170-0.959) and the group administered with a combination of Gemfibrozil-Acalypha indica (p = 0.023, 95% CI: 0.537-0.813). The protective effect of Acalypha indica Linn. shows that this plant has the potential as therapeutic option in overcoming the condition of pancreas steatosis in metabolic syndrome.

Keywords: Acalypha Indica Linn., Cholesterol, Fructose, Gemfibrozil, Pancreas Steatosis

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1093 Management of Nutritional Strategies in Prevention of Autism Before and During Pregnancy

Authors: Maryam Ghavam Sadri, Kimia Moiniafshari

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Objectives: Autism is a neuro-developmental disorder that has negative effects on verbal, mental and behavioral development. Studies have shown the role of a maternal dietary pattern before and during pregnancy. The relation of exerting of nutritional management programs in prevention of Autism has been approved. This review article has been made to investigate the role of nutritional management strategies before and during pregnancy in the prevention of Autism. Methods: This review study was accomplished by using the keywords related to the topic, 67 articles were found (2000-2015) and finally 20 article with criteria such as including maternal lifestyle, nutritional deficiencies and Autism prevention were selected. Results: Maternal dietary pattern and health before and during pregnancy have important roles in the incidence of Autism. Studies have suggested that high dietary fat intake and obesity can increase the risk of Autism in offspring. Maternal metabolic condition specially gestational diabetes (GDM) (p-value < 0.04) and folate deficiency (p-value = 0.04) is associated with risk of Autism. Studies have shown that folate intake in mothers with autistic children is less than mothers who have typically developing children (TYP) (p-value<0.01). As folate is an essential micronutrient for fetus mental development, consumption of average 600 mcg/day especially in P1 phase of pregnancy results in significant reduction in incidence of Autism (OR:1.53, 95%CI=0.42-0.92, p-value = 0.02). furthermore, essential fatty acid deficiency especially omega-3 fatty acid increases the rate of Autism and consumption of supplements and food sources of omega-3 can decrease the risk of Autism up to 34% (RR=1.53, 95%CI=1-2.32). Conclusion: regards to nutritional deficiency and maternal metabolic condition before and during pregnancy in prevalence of Autism, carrying out the appropriate nutritional strategies such as well-timed folate supplementation before pregnancy and healthy lifestyle adherence for prevention of metabolic syndrome (GDM) seems to help Autism prevention.

Keywords: autism, autism prevention, dietary inadequacy, maternal lifestyle

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1092 Assessment of Hydrogen Demand for Different Technological Pathways to Decarbonise the Aviation Sector in Germany

Authors: Manish Khanra, Shashank Prabhu

Abstract:

The decarbonization of hard-to-abate sectors is currently high on the agenda in the EU and its member states, as these sectors have substantial shares in overall GHG emissions while it is facing serious challenges to decarbonize. In particular, the aviation sector accounts for 2.8% of global anthropogenic CO₂ emissions. These emissions are anticipated to grow dramatically unless immediate mitigating efforts are implemented. Hydrogen and its derivatives based on renewable electricity can have a key role in the transition towards CO₂-neutral flights. The substantial shares of energy carriers in the form of drop-in fuel, direct combustion and Hydrogen-to-Electric are promising in most scenarios towards 2050. For creating appropriate policies to ramp up the production and utilisation of hydrogen commodities in the German aviation sector, a detailed analysis of the spatial distribution of supply-demand sites is essential. The objective of this research work is to assess the demand for hydrogen-based alternative fuels in the German aviation sector to achieve the perceived goal of the ‘Net Zero’ scenario by 2050. Here, the analysis of the technological pathways for the production and utilisation of these fuels in various aircraft options is conducted for reaching mitigation targets. Our method is based on data-driven bottom-up assessment, considering production and demand sites and their spatial distribution. The resulting energy demand and its spatial distribution with consideration of technology diffusion lead to a possible transition pathway of the aviation sector to meet short-term and long-term mitigation targets. Additionally, to achieve mitigation targets in this sector, costs and policy aspects are discussed, which would support decision-makers from airline industries, policymakers and the producers of energy commodities.

Keywords: the aviation sector, hard-to-abate sectors, hydrogen demand, alternative fuels, technological pathways, data-driven approach

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1091 Transcriptional Differences in B cell Subpopulations over the Course of Preclinical Autoimmunity Development

Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

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1090 Effects of Forest Bathing on Cardiovascular and Metabolic Parameters in Middle-Aged Males

Authors: Qing Li, Maiko Kobayashi, Shigeyoshi Kumeda, Hiroko Ochiai, Toshiya Ochiai, Takashi Miura, Takahide Kagawa, Michiko Imai, Toshiaki Otsuka, Tomoyuki Kawada

Abstract:

In the present study, we investigated the effects of a forest bathing program on cardiovascular and metabolic parameters. Nineteen healthy male subjects (mean age: 51.3 ± 8.8 years) were selected after obtaining informed consent. These subjects took day trips to a forest park named Akasawa Shizen Kyuyourin, Agematsu, Nagano Prefecture (situated in central Japan), and to an urban area of Nagano Prefecture as a control in August 2015. On both trips, they walked 2.6 km for 80 min each in the morning and afternoon on Saturdays. Blood and urine were sampled in the morning before and after each trip. Cardiovascular and metabolic parameters were measured. Blood pressure and pulse rate were measured by an ambulatory automatic blood pressure monitor. The Japanese version of the profile of mood states (POMS) test was conducted before, during and after the trips. Ambient temperature and humidity were monitoring during the trips. The forest bathing program significantly reduced pulse rate, and significantly increased the score for vigor and decreased the scores for depression, fatigue, and confusion in the POMS test. The levels of urinary noradrenaline and dopamine after forest bathing were significantly lower than those after urban area walking, suggesting the relaxing effect of the forest bathing program. The level of adiponectin in serum after the forest bathing program was significantly greater than that after urban area walking. There was no significant difference in blood pressure between forest and urban area trips during the trips.

Keywords: ambient temperature, blood pressure, forest bathing, forest therapy, human health, POMS, pulse rate

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1089 Calpains; Insights Into the Pathogenesis of Heart Failure

Authors: Mohammadjavad Sotoudeheian

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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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1088 The Plant Hormone Auxin Impacts the Profile of Aroma Compounds in Tomato Fruits (Solanum lycopersicum)

Authors: Vanessa Caroline De Barros Bonato, Bruna Lima Gomes, Luciano Freschi, Eduardo Purgatto

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The plant hormone ethylene is closely related to the metabolic changes that occur during fruit ripening, including volatile biosynthesis. Although knowledge about the biochemistry pathways that produce flavor compounds and the importance of ethylene to these processes are extensively covered, little is known about the regulation mechanisms. In addition, growing body of evidences indicates that auxin is also involved in controlling ripening. However, there is scarce information about the involvement of auxin in fruit volatile production. This study aimed to assess auxin-ethylene interactions and its influence on tomato fruit volatile profile. Fruits from tomato cultivar Micro-Tom were treated with IAA and ethylene, separately and in combination. The hormonal treatment was performed by injection (IAA) or gas exposure (ethylene) and the volatiles were extracted by Solid Phase Microextraction (SPME) and analyzed by GC-MS. Ethylene levels and color were measured by gas chromatography and colorimetry, respectively. The results indicate that the treatment with IAA (even in the presence of high concentrations of exogenous ethylene), impacted the profile of volatile compounds derived from fatty acids, amino acids, carbohydrates and isoprenoids. Ethylene is a well-known regulator of the transition from green to red color and also is implicated in the biosynthesis of characteristic volatile compounds of tomato fruit. The effects observed suggest the existence of a crosstalk between IAA and ethylene in the aroma volatile formation in the fruit. A possible interference of IAA in the ethylene sensitivity in the fruit flesh is discussed. The data suggest that auxin plays an important role in the volatile synthesis in the tomato fruit and introduce a new level of complexity in the regulation of the fruit aroma formation during ripening.

Keywords: aroma compounds, fruit ripening, fruit quality, phytohormones

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1087 Amelioration of Arsenic and Mercury Induced Vasoconstriction by Eugenol, Linalool and Carvone

Authors: Swati Kundu, Seemi Farhat Basir, Luqman A. Khan

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Acute and chronic exposure to arsenic and mercury is known to produce vasoconstriction. Pathways involved in this hypercontraction and their relative contribution are not understood. In this study, we measure agonist-induced contraction of isolated rat aorta exposed to arsenic and mercury aorta and delineate pathways mediating this effect. PE-induced hypercontraction of 37% and 32% was obtained with 25 µM As(III) and 6 nM Hg(II), respectively. Isometric contraction measurements in the presence of apocynin, verapamil and sodium nitroprusside indicates that the major cause of increased contraction is reactive oxygen species and depletion of nitric oxide. Calcium influx plays a minor role in both arsenic and mercury caused hypercontraction. In the unexposed aorta, eugenol causes relaxation by inhibiting ROS and elevating NO, linalool by blocking voltage dependent calcium channel (VDCC) and elevating NO, and carvone by blocking calcium influx through VDDC. Since arsenic and mercury caused hypercontraction is mediated by increased ROS and depletion of nitric oxide, we hypothesize that molecules which neutralize ROS or elevate NO will be better ameliorators. In line with this argument, we find eugenol to be the best ameliorator of arsenic and mercury hypercontraction followed by linalool and carvone.

Keywords: carvone, eugenol, linalool, mercury

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1086 Increasing Photosynthetic H2 Production by in vivo Expression of Re-Engineered Ferredoxin-Hydrogenase Fusion Protein in the Green Alga Chlamydomonas reinhardtii

Authors: Dake Xiong, Ben Hankamer, Ian Ross

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The most urgent challenge of our time is to replace the depleting resources of fossil fuels by sustainable environmentally friendly alternatives. Hydrogen is a promising CO2-neutral fuel for a more sustainable future especially when produced photo-biologically. Hydrogen can be photosynthetically produced in unicellular green alga like Chlamydomonas reinhardtii, catalysed by the inducible highly active and bidirectional [FeFe]-hydrogenase enzymes (HydA). However, evolutionary and physiological constraints severely restrict the hydrogen yield of algae for industrial scale-up, mainly due to its competition among other metabolic pathways on photosynthetic electrons. Among them, a major challenge to be resolved is the inferior competitiveness of hydrogen production (catalysed by HydA) with NADPH production (catalysed by ferredoxin-NADP+-reductase (FNR)), which is essential for cell growth and takes up ~95% of photosynthetic electrons. In this work, the in vivo hydrogen production efficiency of mutants with ferredoxin-hydrogenase (Fd*-HydA1*) fusion protein construct, where the electron donor ferredoxin (Fd*) is fused to HydA1* and expressed in the model organism C. reinhardtii was investigated. Once Fd*-HydA1* fusion gene is expressed in algal cells, the fusion enzyme is able to draw the redistributed photosynthetic electrons and use them for efficient hydrogen production. From preliminary data, mutants with Fd*-HydA1* transgene showed a ~2-fold increase in the photosynthetic hydrogen production rate compared with its parental strain, which only possesses the native HydA in vivo. Therefore, a solid method of having more efficient hydrogen production in microalgae can be achieved through the expression of the synthetic enzymes.

Keywords: Chlamydomonas reinhardtii, ferredoxin, fusion protein, hydrogen production, hydrogenase

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1085 Health Effect of the Central European Diet in Postmenopausal Women with Increased Waist Circumference: A Preliminary Study

Authors: Joanna Bajerska, Agata Chmurzyńska, Agata Muzsik, Patrycja Krzyżanowska, Klaudia Łochocka, Jarosław Walkowiak

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The Mediterranean diet (MED) is regarded as beneficial in the therapy of central obesity-associated metabolic abnormalities. However, in the traditional diet of the Central European countries, food items with positive nutritional profiles (rye bread, oats, buckwheat, herrings, linseed and rapeseed oil, berries, apples, plums, root vegetables etc.) are also used. We hypothesized that the Central European Diet (CED) may be comparatively effective in reducing symptoms of central obesity as MED. We tested the health effects of the CED, which is an environmentally friendly regional diet and the traditional MED diet in a group of postmenopausal centrally obese women. A total 58 with a mean age of 60 y (50-70y), body mass index (in kg/m(2)) of 33.4 (22.6-47.3), and waist circumference of 105 cm (87.5-137 cm) were randomly assigned to receive either the diet based on food items commonly used in Central Europe (the CED group; n = 29) or the Mediterranean diet (the MED group; n = 29) for 15 weeks. Body mass and body composition were measured with a Bod Pod (Cosmed, Italy). A non-elastic flexible measuring tape was used to measure waist circumference. Additionally, blood pressure, plasma lipid and glucose levels were assessed with the use of a biochemical analyzer. A total of 50 subjects [86% (CED 83%; MED 90%)] completed the intervention. A high dietary compliance for both described diets was achieved. The mean (±SEM) weight and waist circumference changes were -7.4 ± 0.7 kg; -8.3 ± 0.7 cm and -8.1 ± 0.5 kg; -7.1 ± 0.6 cm for the CED and MED groups, respectively. Moreover, there were no differences between the effectiveness of the diets used in terms of the influence on fat mass, blood pressure, and biochemical parameters. The preliminary data suggest that both described diets may be successfully used for improving central obesity-associated metabolic abnormalities. The project was financed by the National Science Centre awarded based on the number of decision DEC-013/09/B/NZ9/02365

Keywords: central european diet, central obesity, Mediterranean diet, metabolic abnormalities

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1084 Effects of Ascophyllum nodosum in Tomato in the Tropical Caribbean Climate: Effects and Molecular Insights into Mechanisms

Authors: Omar Ali, Adesh Ramsubhag, Jayaraj Jayaraman

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Seaweed extracts have been reported as plant biostimulants which could be a safer, organic alternative to harsh pesticides. The incentive to use seaweed-based biostimulants is becoming paramount in sustainable agriculture. The current study, therefore, screened a commercial extract of A. nodosum in tomatoes, cultivated in Trinidad to showcase the multiple beneficial effects. Foliar treatment with an A. nodosum commercial extract led to significant increases in fruit yield and a significant reduction of incidence of bacterial spots and early blight diseases under both greenhouse and field conditions. Investigations were carried out to reveal the possible mechanisms of action of this biostimulant through defense enzyme assays and transcriptome profiling via RNA sequencing of tomato. Studies into disease control mechanisms by A. nodosum showed that the extract stimulated the activity of enzymes such as peroxidase, phenylalanine ammonia-lyase, chitinase, polyphenol oxidase, and β-1,3-glucanase. Additionally, the transcriptome survey revealed the upregulation and enrichment of genes responsible for the biosynthesis of growth hormones, defense enzymes, PR proteins and defense-related secondary metabolites, as well as genes involved in the nutrient mobilization, photosynthesis and primary and secondary metabolic pathways. The results of the transcriptome study also demonstrated the cross-talks between growth and defense responses, confirming the bioelicitor and biostimulant value of seaweed extracts in plants. These effects could potentially implicate the benefits of seaweed extract and validate its usage in sustainable crop production.

Keywords: A. nodosum, biostimulants, elicitor, enzymes, growth responses, seaweeds, tomato, transcriptome analysis

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