Search results for: immune tolerance

Authors: Mandana Hoseini

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During last decades, intensive selection for higher growth rate in broiler chickens has accelerated daily body weight gain, which this has changed/increased the trends and amounts of nutrient requirements in the diet. As a result, considerable studies have been focused on the better determination of protein/amino acids requirements in modern broiler diets. One approach to minimize dietary crude protein inclusion levels is substitution of some of the dietary crude protein with synthetic amino acids. In addition, using synthetic forms of limiting essential amino acids in the diet could help better coincidence of dietary protein with ideal protein concept, which this in turn, minimizes nitrogen dissipation and environmental pollution. Threonine is usually considered as the third limiting amino acid in broiler diets. Recent studies have been demonstrated that dietary supplemental threonine would optimize growth performance, immune system, intestinal morphology, as well as oxidative defense in broiler chickens. In this review, threonine metabolism and its effects in relation with different aspects of broiler performance have been discussed.

Keywords: immune system, intestine, performance, requirement, threonine

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Authors: Cajethan U. Ugwuoke

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Agriculture is taught in secondary schools to develop skills in students which will empower them to contribute to national economic development. Unfortunately, our educational system emphasizes the application of conventional teaching methods in delivering instructions, which fails to produce students competent enough to carry out agricultural production. This study was therefore aimed at examining the application of digital technologies as tools for transformative instructional delivery. Four specific purposes, research questions and hypotheses guided the study. The study adopted a descriptive survey research design where 80 subjects representing 64 teachers of agriculture and 16 principals in the Udenu local government area of Enugu State, Nigeria, participated in the study. A structured questionnaire was used to collect data. The assumption of normality was ascertained by subjecting the data collected to a normality test. Data collected were later subjected to mean, Pearson product-moment correlation, ANOVA and t-test to answer the research questions and test the hypotheses at a 5% significant level. The result shows that the application of digital technologies helps to reduce learners’ boredom (3.52.75), improves learners’ performance (3.63.51), and is used as a visual aid for learners (3.56.61), among others. There was a positive, strong and significant relationship between the application of digital technologies and effective instructional delivery (+.895, p=.001<.05, F=17.73), competency of teachers to the application of digital technologies and effective instructional delivery (+998, p=.001<0.5, F=16263.45), and frequency of the application of digital technologies and effective instructional delivery (+.999, p=.001<.05, F=31436.14). There was no evidence of autocorrelation and multicollinearity in the regression models between the application of digital technologies and effective instructional delivery (2.03, Tolerance=1.00, VIF=1.00), competency of teachers in the application of digital technologies and effective instructional delivery (2.38, Tolerance=1.00, VIF=1.00) and frequency of the application of digital technologies and effective instructional delivery (2.00, Tolerance=1.00, VIF=1.00). Digital technologies should be therefore applied in teaching to facilitate effective instructional delivery in agriculture.

Keywords: agricultural science, digital technologies, instructional delivery, learning

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Authors: Zhao Tianxu, Cui Shumei

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This paper proposes a novel multiphase motor structure. The armature winding consists of several independent multiphase windings that have different rating rotate speed and power. Compared to conventional motor, the novel motor structure has more operation mode and fault tolerance mode, which makes it adapt to high-reliability requirement situation such as electric vehicle, aircraft and ship. Performance of novel motor structure varies with winding match. In order to find optimum control strategy, motor torque character, efficiency performance and fault tolerance ability under different operation mode are analyzed in this paper, and torque distribution strategy for efficiency optimization is proposed. Simulation analyze is taken and the result shows that proposed structure has the same efficiency on heavy load and higher efficiency on light load operation points, which expands high efficiency area of motor and cruise range of vehicle. The proposed structure can improve motor highest speed.

Keywords: multiphase motor, armature winding match, torque distribution strategy, efficiency

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Authors: Elmira Davasaz Tabrizi, Müşteba Sevil, Ercan Arican

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In recent decades, there has been a sharp increase in the prevalence of several unrelated chronic diseases. The use of long-term antibiotics for chronic illnesses is increasing. The antibiotic resistance occurrence and its relationship with host microbiomes are still unclear. Properties of the identifying antibodies have been the focus of chronic disease research, such as prostatitis or autoimmune. The immune system is made up of a complicated but well-organized network of cell types that constantly monitor and maintain their surroundings. The regulated homeostatic interaction between immune system cells and their surrounding environment shapes the microbial flora. Researchers believe that the disappearance of special bacterial species from our ancestral microbiota might have altered the body flora that can cause a rise in disease during the human life span. This unpleasant pattern demonstrates the importance of focusing on discovering and revealing the root causes behind the disappearance or alteration of our microbiota. In this review, we gathered the results of some studies that reveal changes in the diversity and quantity of microorganisms that may affect chronic and autoimmune diseases. Additionally, a Ph.D. thesis that is still in process as Metagenomic studies in chronic prostatitis samples is mentioned.

Keywords: metagenomic, autoimmune, prostatitis, microbiome

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Authors: Leander Van Neste, Kirk Wojno

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The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

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Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

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Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

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Authors: Narendra Akhadkar, Philippe Delcambre

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In power protection and control products, assembly process variations due to the individual parts manufactured from single or multi-cavity tooling is a major problem. The dimensional and geometrical variations on the individual parts, in the form of manufacturing tolerances and assembly tolerances, are sources of clearance in the kinematic joints, polarization effect in the joints, and tolerance stack-up. All these variations adversely affect the quality of product, functionality, cost, and time-to-market. Variation simulation analysis may be used in the early product design stage to predict such uncertainties. Usually, variations exist in both manufacturing processes and materials. In the tolerance analysis, the effect of the dimensional and geometrical variations of the individual parts on the functional characteristics (conditions) of the final assembled products are studied. A functional characteristic of the product may be affected by a set of interrelated dimensions (functional parameters) that usually form a geometrical closure in a 3D chain. In power protection and control products, the prerequisite is: when a fault occurs in the electrical network, the product must respond quickly to react and break the circuit to clear the fault. Usually, the response time is in milliseconds. Any failure in clearing the fault may result in severe damage to the equipment or network, and human safety is at stake. In this article, we have investigated two important functional characteristics that are associated with the robust performance of the product. It is demonstrated that the experimental data obtained at the Schneider Electric Laboratory prove the very good prediction capabilities of the variation simulation performed using CETOL (tolerance analysis software) in an industrial context. Especially, this study allows design engineers to better understand the critical parts in the product that needs to be manufactured with good, capable tolerances. On the contrary, some parts are not critical for the functional characteristics (conditions) of the product and may lead to some reduction of the manufacturing cost, ensuring robust performance. The capable tolerancing is one of the most important aspects in product and manufacturing process design. In the case of miniature circuit breaker (MCB), the product's quality and its robustness are mainly impacted by two aspects: (1) allocation of design tolerances between the components of a mechanical assembly and (2) manufacturing tolerances in the intermediate machining steps of component fabrication.

Keywords: geometrical variation, product robustness, tolerance analysis, variation simulation

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Authors: Mmapula Petunia Tsweleng

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This qualitative study presents an exploration and findings thereof the quality of primary caregiving relationships between adolescents orphaned through Acquired Immune Deficiency Syndrome (AIDS) and their grandmothers. This exploration was based on in-depth narratives of 6 stakeholders who provided community-based psychosocial support services to children and families affected by AIDS. The narratives show that grandmothers provided high-quality parental care and support to the orphans. Furthermore, stakeholders categorised grandmother caregiving as genuine. Findings also show that the orphans thrived emotionally, socially, and cognitively and performed well academically. However, it was also identified that grandmothers’ caregiving had elements of overprotectiveness as well as susceptibility to manipulation -which appeared to be a threat to the positive development of the orphans. Relevant interventions, with a special focus on strengthening grandmother caregiving, are needed. Special attention should be on equipping grandmothers with a better understanding of adolescent behaviours and abilities to provide appropriate monitoring and supervision.

Keywords: adolescent orphans, AIDS, caregiving relationships, grandmothers

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Authors: Alaaeddeen M. Seufi

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Many have been published on therapeutic derivatives from living organisms including insects. In addition to traditional maggot therapy, more than 900 therapeutic products were isolated from insects. Most people look at insects as enemies and others believe that insects are friends. Many beneficial insects rather than Honey Bees, Silk Worms and Shellac insect could insure human-insect friendship. In addition, insects could be MicroFactories, Biosensors or Bioreactors. InsectFarm is an amazing example of the applied research that transfers insects from laboratory to market by Prof Mircea Ciuhrii and co-workers. They worked for 18 years to derive therapeutics from insects. Their research resulted in production of more than 30 commercial medications derived from insects (e.g. Imunomax, Noblesse, etc.). Two general approaches were followed to discover drugs from living organisms. Some laboratories preferred biochemical approach to purify components of the innate immune system of insects and insect metabolites as well. Then the purified components could be tested for many therapeutic trials. Other researchers preferred molecular approach based on proteomic studies. Components of the innate immune system of insects were then tested for their medical activities. Our Laboratory team preferred to induce insect immune system (using oral, topical and injection routes of administration), then a transcriptomic study was done to discover the induced genes and to identify specific biomarkers that can help in drug discovery. Biomarkers play an important role in medicine and in drug discovery and development as well. Optimum biomarker development and application will require a team approach because of the multifaceted nature of biomarker selection, validation, and application. This team uses several techniques such as pharmacoepidemiology, pharmacogenomics, and functional proteomics; bioanalytical development and validation; modeling and simulation to improve and refine drug development. Our Achievements included the discovery of four components of the innate immune system of Spodoptera littoralis and Musca domestica. These components were designated as SpliDef (defesin), SpliLec (lectin), SpliCec (cecropin) and MdAtt (attacin). SpliDef, SpliLec and MdAtt were confirmed as antimicrobial peptides, while SpliCec was additionally confirmed as anticancer peptide. Our current research is going on to achieve something in antioxidants and anticoagulants from insects. Our perspective is to achieve something in the mass production of prototypes of our products and to reach it to the commercial level. These achievements are the integrated contributions of everybody in our team staff.

Keywords: AMPs, insect, innate immunitty, therappeutics

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Authors: N. Benhabyles, K. Arab, O. Bouchenak, A. Baz

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The hypoglycemic and antihyperglycemic effects of flavonoids rich extract obtained from leaves of Olea europaea L. was analyzed in normal and alloxan induced diabetic rats. The extraction was performed by confrontation with organic solvents method, which yielded four extracts: Di ethyl Ether, Ethyl Acetate, Butanolic, and Aqueous extract. A single oral dose of 100 mg/kg of the different extract was evaluated for hypoglycemic activity in a glucose tolerance test in normal rats and 200 mg/kg, 400 mg/kg, 600 mg/kg of AE for anti-hyperglycemic activity in alloxan-induced (125 mg/kg) diabetic rats. Dosage of 100 mg/kg of the extract significantly decreased (p<0.05) blood glucose levels in the glucose tolerance test after 120 min. However, a better activity is obtained with the AE. For the anti-hyperglycemic study, the results showed a substantial decrease in blood glucose during the 2 h of treatment for all groups treated with different doses of flavonoids. From the results it can be concluded that flavonoids of O. europaea can be a potential candidate in treating the hyperglycemic conditions.

Keywords: alloxan, antihyperglycemic effect, diabetes mellitus, flavonoids, hypoglycemic effect, Olea europaea L.

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Authors: Supanan Chansap, Werachon Cheukamud, Pornanan Kueakhai, Narin Changklungmoa

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Fasciola species (Fasciola spp.) is caused fasciolosis in ruminants such as cattle, sheep, and buffalo. Fasciola gigantica (F.gigantica) commonly infects tropical regions. Fasciola hepatica (F.hepatica) in temperate regions. Liver fluke infection affects livestock economically, for example, reduced milk and meat production, weight loss, sterile animals. Currently, Triclabendazole is used to treat liver flukes. However, liver flukes have also been found to be resistant to drugs in countries. Therefore, vaccination is an attractive alternative to prevent liver fluke infection. Peptide vaccines are new vaccine technologies that mimic epitope antigens that trigger an immune response. An interesting antigen used in vaccine production is catepsin L, a family of proteins that play an important role in the life of the parasite in the host. This study aims to identify immunogenic regions of protein and construct a multi-epidetope vaccine using an immunoinformatic tool. Fasciola gigantica Cathepsin L1 (FgCatL1), Fasciola gigantica Cathepsin L1G (FgCatL1G), and Fasciola gigantica Cathepsin L1H (FgCatL1H) were predicted B-cell and Helper T lymphocytes (HTL) by Immune Epitope and Analysis Resource (IEDB) servers. Both B-cell and HTL epitopes aligned with cathepsin L of the host and Fasciola hepatica (F. hepatica). Epitope groups were selected from non-conserved regions and overlapping sequences with F. hepatica. All overlapping epitopes were linked with the GPGPG and KK linker. GPGPG linker was linked between B-cell epitope. KK linker was linked between HTL epitope and B-cell and HTL epitope. The antigenic scores of multi-epitope peptide vaccine was 0.7824. multi-epitope peptide vaccine was non-allergen, non-toxic, and good soluble. Multi-epitope peptide vaccine was predicted tertiary structure and refinement model by I-Tasser and GalaxyRefine server, respectively. The result of refine structure model was good quality that was generated by Ramachandran plot analysis. Discontinuous and linear B-cell epitopes were predicted by ElliPro server. Multi-epitope peptide vaccine model was two and seven of discontinuous and linear B-cell epitopes, respectively. Furthermore, multi-epitope peptide vaccine was docked with Toll-like receptor 2 (TLR-2). The lowest energy ranged from -901.3 kJ/mol. In summary, multi-epitope peptide vaccine was antigenicity and probably immune response. Therefore, multi-epitope peptide vaccine could be used to prevent F. gigantica infections in the future.

Keywords: fasciola gigantica, Immunoinformatic tools, multi-epitope, Vaccine

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Authors: Kun Chun, Jin-Chun Heo, Sang-Han Lee

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Asthma is a chronic airway inflammatory disease characterized by the infiltration of inflammatory cells and tissue remodeling. In this study, we examined the anti-asthmatic activity of a derivative of L-allo threonine by in vitro and in vivo anti-asthmatic assays. Ovalbumin (OVA)-induced C57BL/6 mice were used to analyze lung inflammation and cytokine expressions for exhibiting anti-atopic activity of the derivative. LX519290, a derivative of L-allo threonine, induced an increased IFN-γ and a decreased IL-10 mRNA level. This compound exhibited potent anti-asthmatic activity by decreasing immune cell infiltration in the lung, and IL-4 and IL-13 cytokine levels in the serum of OVA-induced mice. These results indicated that chronic airway injury was decreased by LX519290. We also assessed that LX519290 inhibits infiltration of immune cell, mucus release and cytokine expression in an in vivo model. Our results collectively suggest that the L-allo threonine is effective in alleviating asthmatic symptoms by treating inflammatory factors in the lung.

Keywords: asthma, L -allo threonine, LX519290, mice

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Authors: Kuei-Ling Sun, Emily Chia-Yu Su

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Allergy is a hypersensitive overreaction of the immune system to environmental stimuli, and a major health problem. These overreactions include rashes, sneezing, fever, food allergies, anaphylaxis, asthmatic, shock, or other abnormal conditions. Allergies can be caused by food, insect stings, pollen, animal wool, and other allergens. Their development of allergies is due to both genetic and environmental factors. Allergies involve immunoglobulin E antibodies, a part of the body’s immune system. Immunoglobulin E antibodies will bind to an allergen and then transfer to a receptor on mast cells or basophils triggering the release of inflammatory chemicals such as histamine. Based on the increasingly serious problem of environmental change, changes in lifestyle, air pollution problem, and other factors, in this study, we both collect allergens and non-allergens from several databases and use several machine learning methods for classification, including logistic regression (LR), stepwise regression, decision tree (DT) and neural networks (NN) to do the model comparison and determine the permutations of allergen amino acid’s sequence.

Keywords: allergy, classification, decision tree, logistic regression, machine learning

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Authors: Matjaž Šraml, Marko Renčelj, Tomaž Tollazzi, Chiara Gruden

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Road safety is a worldwide issue with numerous and heterogeneous factors influencing it. On the side, driver state – comprising distraction/inattention, fatigue, drowsiness, extreme emotions, and socio-cultural factors highly affect road safety. On the other side, the vehicle state has an important role in mitigating (or not) the road risk. Finally, the road environment is still one of the main determinants of road safety, defining driving task complexity. At the same time, thanks to technological development, a lot of detailed data is easily available, creating opportunities for the detection of driver state, vehicle characteristics and road conditions and, consequently, for the design of ad hoc interventions aimed at improving driver performance, increase awareness and mitigate road risks. This is the challenge faced by the i-DREAMS project. i-DREAMS, which stands for a smart Driver and Road Environment Assessment and Monitoring System, is a 3-year project funded by the European Union’s Horizon 2020 research and innovation program. It aims to set up a platform to define, develop, test and validate a ‘Safety Tolerance Zone’ to prevent drivers from getting too close to the boundaries of unsafe operation by mitigating risks in real-time and after the trip. After the definition and development of the Safety Tolerance Zone concept and the concretization of the same in an Advanced driver-assistance system (ADAS) platform, the system was tested firstly for 2 months in a driving simulator environment in 5 different countries. After that, naturalistic driving studies started for a 10-month period (comprising a 1-month pilot study, 3-month baseline study and 6 months study implementing interventions). Currently, the project team has approved a common evaluation approach, and it is developing the assessment of the usage and outcomes of the i-DREAMS system, which is turning positive insights. The i-DREAMS consortium consists of 13 partners, 7 engineering universities and research groups, 4 industry partners and 2 partners (European Transport Safety Council - ETSC - and POLIS cities and regions for transport innovation) closely linked to transport safety stakeholders, covering 8 different countries altogether.

Keywords: advanced driver assistant systems, driving simulator, safety tolerance zone, traffic safety

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Authors: Muhammad Asif Rasheed

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Newcastle disease virus (NDV), an avian orthoavulavirus, is a causative agent of Newcastle disease named (NDV) and can cause even the epidemics when the disease is not treated. Previously several vaccines based on attenuated and inactivated viruses have been reported, which are rendered useless with the passage of time due to versatile changes in viral genome. Therefore, we aimed to develop an effective multi-epitope vaccine against the haemagglutinin neuraminidase (HN) protein of 26 NDV strains from Pakistan through a modern immunoinformatic approaches. As a result, a vaccine chimaera was constructed by combining T-cell and B-cell epitopes with the appropriate linkers and adjuvant. The designed vaccine was highly immunogenic, non-allergen, and antigenic; therefore, the potential 3D-structureof multi epitope vaccine was constructed, refined, and validated. A molecular docking study of a multiepitope vaccine candidate with the chicken Toll-like receptor-4 indicated successful binding. An In silico immunological simulation was used to evaluate the candidate vaccine's ability to elicit an effective immune response. According to the computational studies, the proposed multiepitope vaccine is physically stable and may induce immune responses, whichsuggested it a strong candidate against 26 Newcastle disease virus strains from Pakistan. A wet lab study is under process to confirm the results.

Keywords: epitopes, newcastle disease virus, paramyxovirus virus, vaccine

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Authors: Iñaki Iturria, Pasquale Russo, Montserrat Nacher-Vázquez, Giuseppe Spano, Paloma López, Miguel Angel Pardo

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Introduction: It is known that some Lactic Acid Bacteria (LAB) present an interesting probiotic effect. Probiotic bacteria stimulate host resistance to microbial pathogens and thereby aid in immune response, and modulate the host's immune responses to antigens with a potential to down-regulate hypersensitivity reactions. Therefore, probiotic therapy is valuable against intestinal infections and may be beneficial in the treatment of Inflammatory Bowel Disease (IBD). Several in vitro tests are available to evaluate the probiotic potential of a LAB strain. However, an in vivo model is required to understand the interaction between the host immune system and the bacteria. During the last few years, zebrafish (Danio rerio) has gained interest as a promising vertebrate model in this field. This organism has been extensively used to study the interaction between the host and the microbiota, as well as the host immune response under several microbial infections. In this work, we report on the use of the zebrafish model to investigate in vivo the colonizing ability and the immunomodulatory effect of probiotic LAB. Methods: Lactobacillus strains belonging to different LAB species were fluorescently tagged and used to colonize germ-free zebrafish larvae gastrointestinal tract (GIT). Some of the strains had a well-documented probiotic effect (L. acidophilus LA5); while others presented an exopolysaccharide (EPS) producing phenotype, thus allowing evaluating the influence of EPS in the colonization and immunomodulatory effect. Bacteria colonization was monitored for 72 h by direct observation in real time using fluorescent microscopy. CFU count per larva was also evaluated at different times. The immunomodulatory effect was assessed analysing the differential expression of several innate immune system genes (MyD88, NF-κB, Tlr4, Il1β and Il10) by qRT- PCR. The anti-inflammatory effect was evaluated using a chemical enterocolitis zebrafish model. The protective effect against a pathogen was also studied. To that end, a challenge test was developed using a fluorescently tagged pathogen (Vibrio anguillarum-GFP+). The progression of the infection was monitored up to 3 days using a fluorescent stereomicroscope. Mortality rates and CFU counts were also registered. Results and conclusions: Larvae exposed to EPS-producing bacteria showed a higher fluorescence and CFU count than those colonized with no-EPS phenotype LAB. In the same way, qRT-PCR results revealed an immunomodulatory effect on the host after the administration of the strains with probiotic activity. A downregulation of proinflammatory cytoquines as well as other cellular mediators of inflammation was observed. The anti-inflammatory effect was found to be particularly marked following exposure to LA% strain, as well as EPS producing strains. Furthermore, the challenge test revealed a protective effect of probiotic administration. As a matter of fact, larvae fed with probiotics showed a decrease in the mortality rate ranging from 20 to 35%. Discussion: In this work, we developed a promising model, based on the use of gnotobiotic zebrafish coupled with a bacterial fluorescent tagging in order to evaluate the probiotic potential of different LAB strains. We have successfully used this system to monitor in real time the colonization and persistence of exogenous LAB within the gut of zebrafish larvae, to evaluate their immunomodulatory effect and for in vivo competition assays. This approach could bring further insights into the complex microbial-host interactions at intestinal level.

Keywords: gnotobiotic, immune system, lactic acid bacteria, probiotics, zebrafish

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Authors: Hasan Basri Jumin, Henni Rosneti, Agusnimar

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Crude palm oil liquid sludge sewage was treated to maize with 400 cc/plant could be increased mean relative growth rates, net assimilation rate, leaf area and dry weight of seed. There are indicated that 400 cc / plant treated to maize significantly increase the average of mean relative growth rates into 0.32 g.day-1. Net assimilation rates increase from 13.5 mg.m-2.day-1 into 34.5 mg.m-2.day-1, leaf area at 50 days after planting increase from 1419 cm-2 into 2458 cm-2 and dry weight of seed from 38 g per plant into 43 g per plant. Crude palm oil liquid sludge waste chemical analysis indicated that, there are no exceed threshold content of dangerous metals and biology effects. Cadmium content as heavy metal is lower than threshold of human healthy tolerance. Therefore, it has no syndrome effect to human health. Biological oxygen demands and chemical oxygen demands as indicators for micro-organism activities, there are under the threshold of human healthy tolerance.

Keywords: crude-palm-oil, fertilizer, liquid-sludge, maize, pollutant, waste

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Authors: Rona Hanani Simamora, Bahagia Loebis, M. Surya Husada

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Background: The exact cause of schizophrenia is not known, although several etiology theories have been proposed for the disease, including immune dysfunction or autoimmune mechanisms. Cytokines including Tnf-α has an important role in the pathophysiology of schizophrenia and the effects of pharmacological treatment with antipsychotics. Nicotine is widespread effects on the brain, immune system and cytokine levels. Smoking among schizophrenic patients could play a role in the altered cytokine profiles of schizophrenia such as Tnf-α. Aims: To determine differences of serum Tnf-α levels between schizophrenic patients with smoking in male and healthy control. Methods: This study was a comparative analytic study, divided into two groups: 1) group of male schizophrenic patients with smoking (n1=30) with inclusion criteria were patients who have been diagnosed schizophrenic based PPDGJ-III, 20-60 years old, male, smoking, chronic schizophrenic patients in the stable phase and willing to participate this study. Exclusion criteria were having other mental disorders and comorbidity with other medical illnesses. 2) healthy control group (n2=30) with inclusion criteria were 20-60 years old, male, smoking, willing to participate this study. Exclusion criteria were having mental disorder, a family history of psychiatric disorders, the other medical illnesses, a history of alcohol and other substances abuse (except caffeine and nicotine). Serum Tnf-α were analyzed using the Quantikine HS Human Tnf –α Immunoassay. Results: Serum Tnf-α level measure in patient schizophrenia male with smoking and compared with the healthy control subjects. Tnf-α levels were significantly higher in patients schizophrenic male with smoking (25,79±27,96) to healthy control subjects (2,74±2,19), by using the Mann Whitney U test showed a statistically significant difference was observed for serum Tnf-α level (p < 0,001). Conclusions: Schizophrenia is a highly heterogeneous disorder, and this study shows an increase Tnf-α as pro-inflammation cytokines in schizophrenics. These results suggest an immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia.

Keywords: male, schizophrenic, smoking, Tnf Alpha

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Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

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Authors: Gamze Uslu, Sebnem Baydere, Alper K. Demir

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In this study, data loss tolerance of Support Vector Machines (SVM) based activity recognition model and multi activity classification performance when data are received over a lossy wireless sensor network is examined. Initially, the classification algorithm we use is evaluated in terms of resilience to random data loss with 3D acceleration sensor data for sitting, lying, walking and standing actions. The results show that the proposed classification method can recognize these activities successfully despite high data loss. Secondly, the effect of differentiated quality of service performance on activity recognition success is measured with activity data acquired from a multi hop wireless sensor network, which introduces high data loss. The effect of number of nodes on the reliability and multi activity classification success is demonstrated in simulation environment. To the best of our knowledge, the effect of data loss in a wireless sensor network on activity detection success rate of an SVM based classification algorithm has not been studied before.

Keywords: activity recognition, support vector machines, acceleration sensor, wireless sensor networks, packet loss

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Authors: Maryam Nazari

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COVID-19 is a respiratory disease triggered by the novel coronavirus, SARS-CoV-2, that has reached pandemic status today. Acute inflammation and immune cells infiltration into lung injuries result in multi-organ failure. The presence of other non-communicable diseases (NCDs) with systemic inflammation derived from COVID-19 may exacerbate the patient's situation and increase the risk for adverse effects and mortality. This pandemic is a novel situation and the scientific community at this time is looking for vaccines or drugs to treat the pathology. One of the biggest challenges is focused on reducing inflammation without compromising the correct immune response of the patient. In this regard, addressing the nutritional factors should not be overlooked not only as a matter of avoiding the presence of NCDs with severe infections but also as an adjunctive way to modulate the inflammatory status of the patients. Despite the pivotal role of nutrition in modifying immune response, due to the novelty of the COVID-19 disease, information about the effects of specific dietary agents is limited in this area. From the macronutrients point of view, protein deficiency (quantity or quality) has negative effects on the number of functional immunoglobulins and gut-associated lymphoid tissue (GALT). High biological value proteins or some amino acids like arginine and glutamine are well known for their ability to augment the immune system. Among lipids, fish oil has the ability to inactivate enveloped viruses, suppress pro-inflammatory prostaglandin production and block platelet-activating factors and their receptors. In addition, protectin D1, which is an Omega-3 PUFAs derivation, is a novel antiviral drug. So it seems that these fatty acids can reduce the severity and/or improve recovery of patients with COVID-19. Carbohydrates with lower glycemic index and fibers are associated with lower levels of inflammatory cytokines (CRP, TNF-α, and IL-6). Short-Chain Fatty acids not only exert a direct anti-inflammatory effect but also provide appropriate gut microbial, which is important in gastrointestinal issues related to COVID-19. From the micronutrients point of view, Vitamins A, C, D, E, iron, magnesium, zinc, selenium and copper play a vital role in the maintenance of immune function. Inadequate status in these nutrients may result in decreased resistance against COVID-19 infection. There are specific bioactive compounds in the diet that interact with the ACE2 receptor, which is the gateway for SARS and SARS-CoV-2, and thus controls the viral infection. Regarding this, the potential benefits of probiotics, resveratrol (a polyphenol found in grape), oleoylethanolamide (derived from oleic acid), and natural peroxisome proliferator-activated receptor γ agonists in foodstuffs (like curcumin, pomegranate, hot pepper) are suggested. Yet, it should be pointed out that most of these results have been reported in animal models and further human studies are needed to be verified.

Keywords: Covid-19, inflammation, nutrition, dietary agents

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Authors: Hameed Alsamadany, Nader Aryamanesh, Guijun Yan

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Heat is one of the major abiotic stresses limiting wheat production worldwide. To identify heat tolerant genotypes, a newly designed system involving a large plastic box holding many layers of filter papers positioned vertically with wheat seeds sown in between for the ease of screening large number of wheat geno types was developed and used to study heat tolerance. A collection of 499 wheat geno types were screened under heat stress (35ºC) and non-stress (25ºC) conditions using the new method. Compared with those under non-stress conditions, a substantial and very significant reduction in seedling length (SL) under heat stress was observed with an average reduction of 11.7 cm (P<0.01). A damage index (DI) of each geno type based on SL under the two temperatures was calculated and used to rank the genotypes. Three hexaploid geno types of Triticum aestivum [Perenjori (DI= -0.09), Pakistan W 20B (-0.18) and SST16 (-0.28)], all growing better at 35ºC than at 25ºC were identified as extremely heat tolerant (EHT). Two hexaploid genotypes of T. aestivum [Synthetic wheat (0.93) and Stiletto (0.92)] and two tetraploid genotypes of T. turgidum ssp dicoccoides [G3211 (0.98) and G3100 (0.93)] were identified as extremely heat susceptible (EHS). Another 14 geno types were classified as heat tolerant (HT) and 478 as heat susceptible (HS). Extremely heat tolerant and heat susceptible geno types were used to develop re combinant inbreeding line populations for genetic studies. Four major QTLs, HTI4D, HTI3B.1, HTI3B.2 and HTI3A located on wheat chromosomes 4D, 3B (x2) and 3A, explaining up to 34.67 %, 28.93 %, 13.46% % and 11.34% phenotypic variation, respectively, were detected. The four QTLs together accounted for 88.40% of the total phenotypic variation. Random wheat geno types possessing the four heat tolerant alleles performed significantly better under the heat condition than those lacking the heat tolerant alleles indicating the importance of the four QTLs in conferring heat tolerance in wheat. Molecular markers are being developed for marker assisted breeding of heat tolerant wheat.

Keywords: bread wheat, heat tolerance, screening, RILs, QTL mapping, association analysis

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Authors: Vladimir Berezin, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Aizhan Turmagambetova, Irina Zaitseva, Nadezhda Sokolova, Elmira Omirtaeva

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Introduction: Triterpene saponins of plant origin are one of the most promising candidates for elaboration of novel adjuvants. Due to the combination of immunostimulating activity and the capacity interact with amphipathic molecules with formation of highly immunogenic nanocomplexes, triterpene saponins could serve as a good adjuvant/delivery system for vaccine use. In the research presented adjuvants on the base of nanocomplexes contained triterpene saponins isolated from Glycyrrhiza glabra and Saponaria officinalis plants indigenous to Kazakhstan were elaborated for influenza vaccine use. Methods: Purified triterpene saponins 'Glabilox' and 'SO1' with low toxicity and high immunostimulatory activity were isolated from plants Glycyrrhiza glabra L. and Saponaria officinalis L. by high-performance liquid chromatography (HPLC) and identified using electrospray ionization mass spectrometry (ESI-MS). Influenza virus A/St-Petersburg/5/09 (H1N1) propagated in 9-days old chicken embryos was concentrated and purified by centrifugation in sucrose gradient. Nanocomplexes contained lipids, and triterpene saponins Glabilox or SO1 were prepared by dialysis technique. Immunostimulating activity of experimental vaccine preparations was studied in vaccination/challenge experiments in mice. Results: Humoral and cellular immune responses and protection against influenza virus infection were examined after single subcutaneous and intranasal immunization. Mice were immunized subunit influenza vaccine (HA+NA) or whole virus inactivated influenza vaccine in doses 3.0/5.0/10.0 µg antigen/animal mixed with adjuvant in dose 15.0 µg/animal. Sera were taken 14-21 days following single immunization and mice challenged by A/St-Petersburg/5/09 influenza virus in dose 100 EID₅₀. Study of experimental influenza vaccine preparations in animal immunization experiments has shown that subcutaneous and intranasal immunization with subunit influenza vaccine mixed with nanocomplexes contained Glabilox or SO1 saponins stimulated high levels of humoral immune response (IgM, IgA, IgG1, IgG2a, and IgG2b antibody) and cellular immune response (IL-2, IL-4, IL-10, and IFN-γ cytokines) and resulted 80-90% protection against lethal influenza infection. Also, single intranasal and single subcutaneous immunization with whole virus inactivated influenza vaccine mixed with nanoparticulated adjuvants stimulated high levels of humoral and cellular immune responses and provided 100% protection against lethal influenza infection. Conclusion: The results of study have shown that nanocomplexes contained purified triterpene saponins Glabilox and SO1 isolated from plants indigenous to Kazakhstan can stimulate a broad spectrum of humoral and cellular immune responses and induce protection against lethal influenza infection. Both elaborated adjuvants are promising for incorporation to influenza vaccine intended for subcutaneous and intranasal routes of immunization.

Keywords: influenza vaccine, adjuvants, triterpene saponins, immunostimulating activity

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Authors: Farhad Ahmadi, Mehran Mohammadi Khah, Fariba Rahimi, N. Vejdani Far

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The aim of present research was to investigate the effect of different levels of protexin (PRT) and Curcuma longa (CUR) on performance, serum lipid and indices of immune system in broiler chickens at the starter stage. A total of 300, one-day-old male broiler (Ross-308) were allotted, in a 2×2+1 factorial design contain 2 levels of protexin (10 and 40 mg/kg diet) and 2 levels of Curcuma longa (200 and 400 mg/kg diet) with four replicate and 15 birds per pens. Experimental diets were: T1 control (basal diet); T2 (2g/kg CUR+0.1g PRT/kg diet), T3 (2g CUR/kg+0.2g PRT/kg diet), T4 (4g CUR/kg+0.1g PRT/kg) and T5 (4g CUR/kg+0.2g PRT/kg). Results indicated that body weight gain and feed conversion ratio had significantly improved (P < 0.05) in birds that fed diet inclusion any levels of additive. The highest BWG and lowest FCR observed in T5 birds group as compared to control (P < 0.05). Relative bursa of Fabricius and spleen weight in T5 and T3 birds groups were higher than control (P > 0.05). The serum of cholesterol, TG, LDL had significantly decreased (P < 0.05). As well, HDL was higher (P < 0.05) in T5 birds group compared to control. In conclusion, results of present trial indicated that blend of mention additive was better than using individual of those and improved performance traits.

Keywords: broiler, Curcuma longa, performance, protexin, serum

Procedia PDF Downloads 335

Authors: Libo Jiang, Huan Li, Rongling Wu

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Ordinary differentiation equations (ODE) have proven to be powerful for reconstructing precise and informative gene regulatory networks (GRNs) from dynamic gene expression data. However, joint modeling and analysis of all genes, essential for the systematical characterization of genetic interactions, are challenging due to high dimensionality and a complex pattern of genetic regulation including activation, repression, and antitermination. Here, we address these challenges by unifying variable selection and game theory through ODE. Each gene within a GRN is co-expressed with its partner genes in a way like a game of multiple players, each of which tends to choose an optimal strategy to maximize its “fitness” across the whole network. Based on this unifying theory, we designed and conducted a real experiment to infer salt tolerance-related GRNs for Euphrates poplar, a hero tree that can grow in the saline desert. The pattern and magnitude of interactions between several hub genes within these GRNs were found to determine the capacity of Euphrates poplar to resist to saline stress.

Keywords: gene regulatory network, ordinary differential equation, game theory, LASSO, saline resistance

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Authors: Sonal Budhiraja, Biswabrata Pradhan

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This work considers statistical inference based on progressive Type-I interval censored data with random removal. The scheme of progressive Type-I interval censoring with random removal can be described as follows. Suppose n identical items are placed on a test at time T0 = 0 under k pre-fixed inspection times at pre-specified times T1 < T2 < . . . < Tk, where Tk is the scheduled termination time of the experiment. At inspection time Ti, Ri of the remaining surviving units Si, are randomly removed from the experiment. The removal follows a binomial distribution with parameters Si and pi for i = 1, . . . , k, with pk = 1. In this censoring scheme, the number of failures in different inspection intervals and the number of randomly removed items at pre-specified inspection times are observed. Asymptotic properties of the maximum likelihood estimators (MLEs) are established under some regularity conditions. A β-content γ-level tolerance interval (TI) is determined for two parameters Weibull lifetime model using the asymptotic properties of MLEs. The minimum sample size required to achieve the desired β-content γ-level TI is determined. The performance of the MLEs and TI is studied via simulation.

Keywords: asymptotic normality, consistency, regularity conditions, simulation study, tolerance interval

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Authors: Ramesh K. Sunkaria, Puneeta Marwaha

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Nonlinear methods of heart rate variability (HRV) analysis are becoming more popular. It has been observed that complexity measures quantify the regularity and uncertainty of cardiovascular RR-interval time series. In the present work, SampEn has been evaluated in healthy Normal Sinus Rhythm (NSR) male and female subjects for different data lengths and tolerance level r. It is demonstrated that SampEn is small for higher values of tolerance r. Also SampEn value of healthy female group is higher than that of healthy male group for short data length and with increase in data length both groups overlap each other and it is difficult to distinguish them. The SampEn gives inaccurate results by assigning higher value to female group, because male subject have more complex HRV pattern than that of female subjects. Therefore, this traditional algorithm exhibits higher complexity for healthy female subjects than for healthy male subjects, which is misleading observation. This may be due to the fact that SampEn do not account for multiple time scales inherent in the physiologic time series and the hidden spatial and temporal fluctuations remains unexplored.

Keywords: heart rate variability, normal sinus rhythm group, RR interval time series, sample entropy

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Authors: A. Bouaouiche, M. S. Boulakoud

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The functioning of the pineal gland, the transducer body of environmental information to the neuroendocrine system is subject to a circadian rhythm. Melatonin is the main neuro-hormone expressing this operation. It is synthesized in the pinealocytes after conversion serotonin via N-acetyl-transferase enzyme, itself subject to a photoperiodic modulation (activation dark inhibition by light). Some authors have suggested that melatonin is involved in diabetic disease and found that it could have a diabetogenic effect. To this study the effect of this hormone on glucose metabolism has long been subject to controversy. Agreeing in effect and hyperinsulinemic hypoglycemic effect. In order to illustrate the level of interaction of melatonin with neuro-immune- corticotropin axis and its impact on carbohydrate metabolism, we studied the impact homeostatic (glucose) through the solicitation of two control systems (gland pineal and corticotropin axis). We then found that melatonin could have an indirect influence on insulin control (glucose metabolism) to the levels of the growth hormone axis (somatostatin) and adrenocorticotropic (corticotropin). In addition, we have suggested that melatonin might limit the hyperglycemic action of corticosteroids by direct action at peripheral level.

Keywords: pinéal gland, melatonin, neuro-immuno-corticotrop, metabolism

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Authors: John Lyndon C. Lunnay

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This study discerns to evaluate the antidiabetic efficacy of pig bile on alloxan-induced BALB/c mice. The experimental animals were divided and selected using RCBD into 5 groups (n= 4): T1 (negative control), T2 (1ml/kg), T3 (2ml/kg), T4 (3ml/kg) and T5 (Glibenclamide). Hyperglycemia was induced by injecting 1% alloxan monohydrate intraperitoneally. A glucose tolerance test was performed using a 2g/kg glucose solution, and blood glucose levels were measured at different time intervals. 14 days of monitoring was also done to ensure effectivity and efficacy of the different treatments. Bodyweight was also determined. Results show that administration of treatments on test animals significantly reverted the blood glucose levels of mice in 60 minutes and 120 minutes using an oral glucose tolerance test. After 14 days of monitoring, normal blood glucose levels were seen significantly on T2 (1ml/kg), T3 (2ml/kg), T4 (3ml/kg), and T5 (Glibenclamide), which only suggests the efficacy of pig bile on lowering glucose levels on alloxan-induced diabetic mice. Bodyweight analysis shows no significant difference. Duncan’s multiple range test (DMRT) shows comparable efficacy and effectivity between T4 (3ml/kg) and T5 (Glibenclamide) on lowering BGL at different day and time intervals.

Keywords: pig bile, BALB/c mice, blood glucose, Gllibenclamide

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Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

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