Search results for: gene expression data analysis

Authors: Yanyue Yuan

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In this paper, the author shares the findings of a pilot study that examines students’ creative expressions and their perceptions of creativity when engaged in project-based learning. The study is based on an elective course that the author co-designed and co-taught with a colleague to sixteen grade six and seven students over the spring semester in 2019. Using the Little Prince story as the main prompt, they facilitated students’ original creation of a storytelling concert that integrated script writing, music production, lyrics, songs, and visual design as a result of both individual and collaborative work. The author will share the specific challenges we met during the project, including learning cultures of the school, class management, teachers' and parents’ attitude, process-oriented versus product-oriented mindset, and facilities and logistical resources. The findings of this pilot study will inform the ongoing research initiative of exploring how we can foster creative learning in public schools in the Chinese context. While K-12 schools of China’s public education system are still dominated by exam-oriented and teacher-centered approaches, the author proposes that expression-based learning can be a starting point for promoting students’ creativity and can serve as experimental efforts to initiate incremental changes within the current education framework. The paper will also touch upon insights gained from collaborations between university and K-12 schools.

Keywords: creativity, expression-based learning, K-12, incremental changes

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Authors: Lydia Tan, Philippe Lemey, Lieselot Houspie, Marco Viveen, Darren Martin, Frank Coenjaerts

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Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of severe respiratory tract infections in infants under the age of two. Genomic substitutions and related evolutionary dynamics of hRSV are of great influence on virus transmission behavior. The evolutionary patterns formed are due to a precarious interplay between the host immune response and RSV, thereby selecting the most viable and less immunogenic strains. Studying genomic profiles can teach us which genes and consequent proteins play an important role in RSV survival and transmission dynamics. Study design: In this study, genetic diversity and evolutionary rate analysis were conducted on 36 RSV subgroup B whole genome sequences and 37 subgroup A genome sequences. Clinical RSV isolates were obtained from nasopharyngeal aspirates and swabs of children between 2 weeks and 5 years old of age. These strains, collected during epidemic seasons from 2001 to 2011 in the Netherlands and Belgium by either conventional or 454-sequencing. Sequences were analyzed for genetic diversity, recombination events, synonymous/non-synonymous substitution ratios, epistasis, and translational consequences of mutations were mapped to known 3D protein structures. We used Bayesian statistical inference to estimate the rate of RSV genome evolution and the rate of variability across the genome. Results: The A and B profiles were described in detail and compared to each other. Overall, the majority of the whole RSV genome is highly conserved among all strains. The attachment protein G was the most variable protein and its gene had, similar to the non-coding regions in RSV, more elevated (two-fold) substitution rates than other genes. In addition, the G gene has been identified as the major target for diversifying selection. Overall, less gene and protein variability was found within RSV-B compared to RSV-A and most protein variation between the subgroups was found in the F, G, SH and M2-2 proteins. For the F protein mutations and correlated amino acid changes are largely located in the F2 ligand-binding domain. The small hydrophobic phosphoprotein and nucleoprotein are the most conserved proteins. The evolutionary rates were similar in both subgroups (A: 6.47E-04, B: 7.76E-04 substitution/site/yr), but estimates of the time to the most recent common ancestor were much lower for RSV-B (B: 19, A: 46.8 yrs), indicating that there is more turnover in this subgroup. Conclusion: This study provides a detailed description of whole RSV genome mutations, the effect on translation products and the first estimate of the RSV genome evolution tempo. The immunogenic G protein seems to require high substitution rates in order to select less immunogenic strains and other conserved proteins are most likely essential to preserve RSV viability. The resulting G gene variability makes its protein a less interesting target for RSV intervention methods. The more conserved RSV F protein with less antigenic epitope shedding is, therefore, more suitable for developing therapeutic strategies or vaccines.

Keywords: drug target selection, epidemiology, respiratory syncytial virus, RSV

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Authors: B. Atika, S. Lehmann, E. Wimmer

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The defense strategy is very common in the insect world. Defensive substances play a wide variety of functions for beetles, such as repellents, toxicants, insecticides, and antimicrobics. Beetles react to predators, invaders, and parasitic microbes with the release of toxic and repellent substances. Defensive substances are directed against a large array of potential target organisms or may function for boiling bombardment or as surfactants. Usually, Coleoptera biosynthesize and store their defensive compounds in a complex secretory organ, known as odoriferous defensive stink glands. The red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae), uses these glands to produce antimicrobial p-benzoquinones and 1-alkenes. In the past, the morphology of stink gland has been studied in detail in tenebrionid beetles; however, very little is known about the genes that are involved in the production of gland secretion. In this study, we studied a subset of genes that are essential for the benzoquinone production in red flour beetle. In the first phase, we selected 74 potential candidate genes from a genome-wide RNA interference (RNAi) knockdown screen named 'iBeetle.' All these 74 candidate genes were functionally characterized by RNAi-mediated gene knockdown. Therefore, they were selected for a subsequent gas chromatography-mass spectrometry (GC-MS) analysis of secretion volatiles in respective RNAi knockdown glands. 33 of them were observed to alter the phenotype of stink gland. In the GC-MS analysis, 7 candidate genes were noted to display a strongly altered gland, in terms of secretion color and chemical composition, upon knockdown, showing their key role in the biosynthesis of gland secretion. Morphologically altered stink glands were found for odorant receptor and protein kinase superfamily. Subsequent GC-MS analysis of secretion volatiles revealed reduced benzoquinone levels in LIM domain, PDZ domain, PBP/GOBP family knockdowns and a complete lack of benzoquinones in the knockdown of sulfatase-modifying factor enzyme 1, sulfate transporter family. Based on stink gland transcriptome data, we analyzed the function of sulfatase-modifying factor enzyme 1 and sulfate transporter family via RNAi-mediated gene knockdowns, GC-MS, in situ hybridization, and enzymatic activity assays. Morphologically altered stink glands were noted in knockdown of both these genes. Furthermore, GC-MS analysis of secretion volatiles showed a complete lack of benzoquinones in the knockdown of these two genes. In situ hybridization showed that these two genes are expressed around the vesicle of certain subgroup of secretory stink gland cells. Enzymatic activity assays on stink gland tissue showed that these genes are involved in p-benzoquinone biosynthesis. These results suggest that sulfatase-modifying factor enzyme 1 and sulfate transporter family play a role specifically in benzoquinone biosynthesis in red flour beetles.

Keywords: Red Flour Beetle, defensive stink gland, benzoquinones, sulfate transporter, sulfatase-modifying factor enzyme 1

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Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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Authors: Yuyun Wabula, B. J. Dewancker

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In the past decade, the social networking app has been growing very rapidly. Geolocation data is one of the important features of social media that can attach the user's location coordinate in the real world. This paper proposes the use of geolocation data from the Twitter social media application to gain knowledge about urban dynamics, especially on human mobility behavior. This paper aims to explore the relation between geolocation Twitter with the existence of people in the urban area. Firstly, the study will analyze the spread of people in the particular area, within the city using Twitter social media data. Secondly, we then match and categorize the existing place based on the same individuals visiting. Then, we combine the Twitter data from the tracking result and the questionnaire data to catch the Twitter user profile. To do that, we used the distribution frequency analysis to learn the visitors’ percentage. To validate the hypothesis, we compare it with the local population statistic data and land use mapping released by the city planning department of Makassar local government. The results show that there is the correlation between Twitter geolocation and questionnaire data. Thus, integration the Twitter data and survey data can reveal the profile of the social media users.

Keywords: geolocation, Twitter, distribution analysis, human mobility

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Authors: Tri Wijayanti Septiarini, Agus Maman Abadi, Muhammad Rifki Taufik

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The exchange rate of IDR/USD can be the indicator to analysis Indonesian economy. The exchange rate as a important factor because it has big effect in Indonesian economy overall. So, it needs the analysis data of exchange rate. There is decomposition data of exchange rate of IDR/USD to be frequency and time. It can help the government to monitor the Indonesian economy. This method is very effective to identify the case, have high accurate result and have simple structure. In this paper, data of exchange rate that used is weekly data from December 17, 2010 until November 11, 2014.

Keywords: the exchange rate, fuzzy mamdani, discrete wavelet transforms, fuzzy wavelet

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Authors: Takahiro Nishigaki, Takashi Onoda

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In recent years, the number of document data has been increasing since the spread of the Internet. Many methods have been studied for extracting topics from large document data. We proposed Independent Topic Analysis (ITA) to extract topics independent of each other from large document data such as newspaper data. ITA is a method for extracting the independent topics from the document data by using the Independent Component Analysis. The topic represented by ITA is represented by a set of words. However, the set of words is quite different from the topics the user imagines. For example, the top five words with high independence of a topic are as follows. Topic1 = {"scor", "game", "lead", "quarter", "rebound"}. This Topic 1 is considered to represent the topic of "SPORTS". This topic name "SPORTS" has to be attached by the user. ITA cannot name topics. Therefore, in this research, we propose a method to obtain topics easy for people to understand by using the web search engine, topics given by the set of words given by independent topic analysis. In particular, we search a set of topical words, and the title of the homepage of the search result is taken as the topic name. And we also use the proposed method for some data and verify its effectiveness.

Keywords: independent topic analysis, topic extraction, topic naming, web search engine

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Authors: Reza Salehi, Peter L. Dold, Yves Comeau

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The aim of the present study was to investigate the effect of a total of 6 operating parameters including pH (X1), temperature (X2), stirring speed (X3), chemical oxygen demand (COD) (X4), volatile suspended solids (VSS) (X5) and time (X6) on anaerobic orthophosphate release from enhanced biological phosphorus removal (EBPR) sludge. An 8-run Plackett Burman design was applied and the statistical analysis of the experimental data was performed using Minitab16.2.4 software package. The Analysis of variance (ANOVA) results revealed that temperature, COD, VSS and time had a significant effect with p-values of less than 0.05 whereas pH and stirring speed were identified as non-significant parameters, but influenced orthophosphate release from the EBPR sludge. The mathematic expression obtained by the first-order multiple linear regression model between orthophosphate release from the EBPR sludge (Y) and the operating parameters (X1-X6) was Y=18.59+1.16X1-3.11X2-0.81X3+3.79X4+9.89X5+4.01X6. The model p-value and coefficient of determination (R2) value were 0.026 and of 99.87%, respectively, which indicates the model is significant and the predicted values of orthophosphate release from the EBPR sludge have been excellently correlated with the observed values.

Keywords: anaerobic, operating parameters, orthophosphate release, Plackett-Burman design

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Authors: Ayse Ozge Demir, Nihat Mert

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In this research, Kilis and Honamli goats are used, which are specific local genetic resources of Turkey. The herds were independent, but they had similar care and nutrition circumstances. From each breed 30 samples were taken, in all 120 samples were collected. Erytrocyte, all blood and serum samples were used for hemoglobine (Hb), glutathione (GSH) and Tf with Cp analysis, respectively. In the analysis of this samples, Hb and Tf bands were determined by electrophoresis. However, Cp and GSH levels were analyzed by the spectrophotometer. Three Hb phenotypes (AA, BB, AB) and Six Tf phenotypes (AA, AB, AC, BB, BC, CC) were determined in this study. In addition, both the observed and the expected values of polymorphic characteristic for 2 characters were presented according to the Hardy-Weinberg Equilibrium (HWE). Cp levels were detected as 0.822 ± 0.055 mg/dl and 1.793 ± 0.109 mg/dl in Kilis and Honamli herds, respectively. GSH levels were detected as, 42,486 ± 1,034 mg/dl and 33.515 ± 0.345 mg/dl in these breeds, respectively,. On the other hand, the high and low GSH levels (GSHH and GSHh) of herds were presented.

Keywords: electrophoresis, gene resource, goat, spectrophotometer

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Authors: Sadia Arshad, Yifa Tang, Dumitru Baleanu

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A fractional order mathematical model is proposed that incorporate CD8+ cells, natural killer cells, cytokines and tumor cells. The tumor cells growth in the absence of an immune response is modeled by logistic law as it was the simplest form for which predictions also agreed with the experimental data. Natural Killer Cells are our first line of defense. NK cells directly kill tumor cells through several mechanisms, including the release of cytoplasmic granules containing perforin and granzyme, expression of tumor necrosis factor (TNF) family members. The effect of the NK cells on the tumor cell population is expressed with the product term. Rational form is used to describe interaction between CD8+ cells and tumor cells. A number of cytokines are produced by NKs, including tumor necrosis factor TNF, IFN, and interleukin (IL-10). Source term for cytokines is modeled by Michaelis-Menten form to indicate the saturated effects of the immune response. Stability of the equilibrium points is discussed for biologically significant values of bifurcation parameters. We studied the treatment of fractional order system by investigating analytical conditions of tumor eradication. Numerical simulations are presented to illustrate the analytical results.

Keywords: cancer model, fractional calculus, numerical simulations, stability analysis

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Authors: Mrunmayee Das

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This study aims to explore the film 'Pyasa' directed by actor-director Guru Dutt, filmed during the 1950’s golden age of Hindi cinema. 'Pyasa' was filmed after a decade of India being a new nation and narrates the world-view of a poet dressed in western ideals, tasting modernity, uprooted from his familial and social moorings causing friction of being between survival and self- expression. The research is based on literature review to study the attitudes, particularly the post-colonial, informing the film. In terms of the structure, the relational study of the film and the historical background of that time came first. Further explorations deal with the use of image making, dialogue, and poetry in the form of songs facilitating the central theme of the human plight of poverty, not of material but of thought. The literature review establishes Dutt’s style of expressing melodic melodrama through a dance between light and shadow majorly in the form of song sequences signifying the greys of the society. It was found in this research that melodrama is created by the changing contrasts and use of close-ups. The song sequences convey the tensions of being a contemporary liberal educated youth and having to deal with the societal-ills of this world, which highlights the theme of compulsion towards self-destruction. It is concluded that Dutt’s 'Pyasa' is a autobiographical commentary on the state of a nation doing away with a borrowed identity and refashioning its own.

Keywords: cinema, Guru Dutt, post-colonial India, self-expression

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Authors: Ibrahim Ilker Ozyigit, Ertugrul Filiz, Seda Birbilener, Semsettin Kulac, Zeki Severoglu

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In this study, we have performed genetic diversity analysis of Tilia tomentosa genotypes by using randomly amplified polymorphic DNA (RAPD) primers. A total of 28 genotypes, including 25 members from the urban ecosystem and 3 genotypes from forest ecosystem as outgroup were used. 8 RAPD primers produced a total of 53 bands, of which 48 (90.6 %) were polymorphic. Percentage of polymorphic loci (P), observed number of alleles (Na), effective number of alleles (Ne), Nei's (1973) gene diversity (h), and Shannon's information index (I) were found as 94.29 %, 1.94, 1.60, 0.34, and 0.50, respectively. The unweighted pair-group method with arithmetic average (UPGMA) cluster analysis revealed that two major groups were observed. The genotypes of urban and forest ecosystems showed a high genetic similarity between 28% and 92% and these genotypes did not separate from each other in UPGMA tree. Also, urban and forest genotypes clustered together in principal component analysis (PCA).

Keywords: Tilia tomentosa, genetic diversity, urban ecosystem, RAPD, UPGMA

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Authors: Yaya Gao, Jifeng Liu, Yafeng Liu

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Objectives: This study aimed to improve clinicians' understanding and diagnosis of the Mammary analogue secretory carcinoma of the salivary gland（MASC）. Methods: The clinical features of a MASC patient who was admitted to WestChina Hospital of Sichuan University in July 2020 were reviewed and analyzed. A 49-year-old woman with left upper neck pain for three months was admitted to the hospital. She underwent adenoma resection of the left submandibular gland 14 years ago and mucoepidermoid carcinoma resection surgery five years ago. Three months before admission, the patient developed pain in the left mandibular angle after "fatigue" and gradually developed radiation pain in the left ear, which could be relieved after rest. A mass of 1cm could be touched at the mandibular, with tenderness, poor mobility, and hard texture. No swelling, heat, pain, rupture, or pus was found on the surrounding skin. Color doppler ultrasonography of the salivary gland indicated a weak echo mass of 23*14*17mm in the left parotid gland. Results: Surgical excision was completed. Immunohistochemistry of the tumor samples after operation showed that P63（a few，+）, CK7（+）, S100（+）, DOG1（-）, Ki67（MIB-1）（+，5%），pan-TRK（+）, PAS(+) . ETV-6 gene translocation was detected in FISH in postoperative pathology, which indicated MASC. After this diagnosis, the patient sent the postoperative specimen of the second submandibular tumor to our hospital for consultation. The morphology of the two was similar. FISH detected ETV-6 gene translocation, so the second pathological diagnosis was revised to MASC. Conclusion: MASC of the salivary gland is a rare salivary gland tumor whose diagnosis depends on the result of the ETV6-NTRK3 fusion gene.

Keywords: mammary analogue secretory carcinoma, ETV6-NTRK3, salivary gland, misdiagnosed

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Authors: Surbhi Surbhi, Andrea Erni, Gunter Meister, Harold Cremer, Christophe Beclin

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MicroRNAs (miRNAs) are short 20-23 nucleotide long non-coding RNAs; there are 2605 miRNA in humans and 1936 miRNA in mouse in total (miRBase). The nervous system expresses the most abundant miRNA and most diverse. MiRNAs play a role in many steps during neurogenesis, like cell proliferation, differentiation, neural patterning, axon pathfinding, etc. Moreover, in vitro studies suggested a role in the regulation of local translation at the synapse, thus controlling neuronal plasticity. However, due to the specific structure of miRNA molecules, an in-vivo confirmation of the general role of miRNAs in the control of neuronal plasticity is still pending. For example, their small size and their high level of sequence homology make difficult the analysis of their cellular and sub-cellular localization in-vivo by in-situ hybridization. Moreover, it was found that only 40% of the expressed miRNA molecules in a cell are included in RNA-Induced Silencing Complexes (RISC) and, therefore, involved in inhibitory interactions while the rest is silent. Definitively, the development of new tools is needed to have a better understanding of the cellular function of miRNAs, in particular their role in neuronal plasticity. Here we describe a new technique called in-vivo AGO-APP designed to investigate miRNA expression and function in-vivo. This technique is based on the expression of a small peptide derived from the human RISC-complex protein TNRC6B, called T6B, which binds all known Argonaute (Ago) proteins with high affinity allowing the efficient immunoprecipitation of AGO-bound miRNAs. We have generated two transgenic mouse lines conditionally expressing T6B either ubiquitously in the cell or targeted at the synapse. A comparison of the repertoire of miRNAs immuno-precipitated from mature neurons of both mouse lines will provide us with a list of miRNAs showing a specific activity at the synapse. The physiological role of these miRNAs will be subsequently addressed through gain and loss of function experiments.

Keywords: RNA-induced silencing complexes, TNRC6B, miRNA, argonaute, synapse, neuronal plasticity, neurogenesis

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Authors: K. Roushanger, A. Soleymanzadeh

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Weirs are structures often used in irrigation techniques, sewer networks and flood protection. However, the hydraulic behavior of this type of weir is complex and difficult to predict accurately. An accurate flow prediction over a weir mainly depends on the proper estimation of discharge coefficient. In this study, the Genetic Expression Programming (GEP) approach was used for predicting trapezoidal and rectangular sharp-crested side weirs discharge coefficient. Three different performance indexes are used as comparing criteria for the evaluation of the model’s performances. The obtained results approved capability of GEP in prediction of trapezoidal and rectangular side weirs discharge coefficient. The results also revealed the influence of downstream Froude number for trapezoidal weir and upstream Froude number for rectangular weir in prediction of the discharge coefficient for both of side weirs.

Keywords: discharge coefficient, genetic expression programming, trapezoidal weir

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Authors: Nazish Badar

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In early 2009, Pandemic type A (H1N1) Influenza virus emerged globally. Since then, it has continued circulation causing considerable morbidity and mortality. The purpose of this study was to evaluate the evolutionary changes in Influenza A (H1N1) pdm09 viruses from 2009-15 and their relevance with the current vaccine viruses. Methods: Respiratory specimens were collected with influenza-like illness and Severe Acute Respiratory Illness. Samples were processed according to CDC protocol. Sequencing and phylogenetic analysis of Haemagglutinin (HA) and neuraminidase (NA) genes was carried out comparing representative isolates from Pakistan viruses. Results: Between Jan2009 - Feb 2016, 1870 (13.2%) samples were positive for influenza A out of 14086. During the pandemic period (2009–10), Influenza A/ H1N1pdm 09 was the dominant strain with 366 (45%) of total influenza positives. In the post-pandemic period (2011–2016), a total of 1066 (59.6%) cases were positive Influenza A/ H1N1pdm 09 with co-circulation of different Influenza A subtypes. Overall, the Pakistan A(H1N1) pdm09 viruses grouped in two genetic clades. Influenza A(H1N1)pdm09 viruses only ascribed to Clade 7 during the pandemic period whereas viruses belong to clade 7 (2011) and clade 6B (2015) during the post-pandemic years. Amino acid analysis of the HA gene revealed mutations at positions S220T, I338V and P100S specially associated with outbreaks in all the analyzed strains. Sequence analyses of post-pandemic A(H1N1)pdm09 viruses showed additional substitutions at antigenic sites; S179N,K180Q (SA), D185N, D239G (CA), S202A (SB) and at receptor binding sites; A13T, S200P when compared with pandemic period. Substitution at Genetic markers; A273T (69%), S200P/T (15%) and D239G (7.6%) associated with severity and E391K (69%) associated with virulence was identified in viruses isolated during 2015. Analysis of NA gene revealed outbreak markers; V106I (23%) among pandemic and N248D (100%) during post-pandemic Pakistan viruses. Additional N-Glycosylation site; HA S179N (23%), NA I23T(7.6%) and N44S (77%) in place of N386K(77%) were only found in post-pandemic viruses. All isolates showed histidine (H) at position 275 in NA indicating sensitivity to neuraminidase inhibitors. Conclusion: This study shows that the Influenza A(H1N1)pdm09 viruses from Pakistan clustered into two genetic clades, with co-circulation of some variants. Certain key substitutions in the receptor binding site and few changes indicative of virulence were also detected in post-pandemic strains. Therefore, it is imperative to continue monitoring of the viruses for early identification of potential variants of high virulence or emergence of drug-resistant variants.

Keywords: Influenza A (H1N1) pdm09, evolutionary analysis, post pandemic period, Pakistan

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Authors: Junaid Jibran Jawed, Prasanta Saini, Subrata Majumdar

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Background: Leishmania donovani infection causes severe host immune-suppression through the modulation of pathogen recognition receptors. Apart from TLRs (Toll Like Receptor), recent studies focus on the important contribution of NLR (NOD-Like Receptor) family member NOD1 and NOD2 as these receptors are capable of triggering host innate immunity. The aim of this study was to decipher the role of NOD1/NOD2 receptors during experimental visceral leishmaniasis (VL) and the important link between host failure and parasite evasion strategy. Method: The status of NOD1 and NOD2 receptors were analysed in uninfected and infected cells through western blotting and RT-PCR. The active contributions of these receptors in reducing parasite burden were confirmed by siRNA mediated silencing, and over-expression studies and the parasite numbers were calculated through microscopic examination of the Giemsa-stained slides. In-vivo studies were done by using non-toxic dose of Mw (Mycobacterium indicus pranii), Ara-LAM(Arabinoasylated lipoarabinomannan) along with MDP (Muramyl dipeptide) administration. Result: Leishmania donovani infection of the macrophages reduced the expression of NOD2 receptors whereas NOD1 remain unaffected. MDP, a NOD2-ligand, treatment during over-expression of NOD2, reduced the parasite burden effectively which was associated with increased pro-inflammatory cytokine generation and NO production. In experimental mouse model, Ara-LAM treatment increased the expression of NOD2 and in combination with MDP it showed active therapeutic potential against VL and found to be more effective than Mw which was already reported to be involved in NOD2 modulation. Conclusion: This work explores the essential contribution of NOD2 during experimental VL and mechanistic understanding of Ara-LAM + MDP combination therapy to work against this disease and highlighted NOD2 as an essential therapeutic target.

Keywords: Ara-LAM (Arabinoacylated Lipoarabinomannan), NOD2 (nucleotide binding oligomerization receptor 2), MDP (muramyl di peptide), visceral Leishmaniasis

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Authors: S. D. N. K. Bathige, G. I. Godahewa, Navaneethaiyer Umasuthan, Jehee Lee

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Kunitz-type serine protease inhibitors (KTIs) are identified in various organisms including animals, plants and microbes. These proteins shared single or multiple Kunitz inhibitory domains link together or associated with other types of domains. Characteristic Kunitz type domain composed of around 60 amino acid residues with six conserved cysteine residues to stabilize by three disulfide bridges. KTIs are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis and inflammation. In this study, two Kunitz-type domain containing protein was identified from rock bream database and designated as RbKunitz. The coding sequence of RbKunitz encoded for 507 amino acids with 56.2 kDa theoretical molecular mass and 5.7 isoelectric point (pI). There are several functional domains including MANEC superfamily domain, PKD superfamily domain, and LDLa domain were predicted in addition to the two characteristic Kunitz domain. Moreover, trypsin interaction sites were also identified in Kunitz domain. Homology analysis revealed that RbKunitz shared highest identity (77.6%) with Takifugu rubripes. Completely conserved 28 cysteine residues were recognized, when comparison of RbKunitz with other orthologs from different taxonomical groups. These structural evidences indicate the rigidity of RbKunitz folding structure to achieve the proper function. The phylogenetic tree was constructed using neighbor-joining method and exhibited that the KTIs from fish and non-fish has been evolved in separately. Rock bream was clustered with Takifugu rubripes. The SYBR Green qPCR was performed to quantify the RbKunitz transcripts in different tissues and challenged tissues. The mRNA transcripts of RbKunitz were detected in all tissues (muscle, spleen, head kidney, blood, heart, skin, liver, intestine, kidney and gills) analyzed and highest transcripts level was detected in gill tissues. Temporal transcription profile of RbKunitz in rock bream blood tissues was analyzed upon LPS (lipopolysaccharide), Poly I:C (Polyinosinic:polycytidylic acid) and Edwardsiella tarda challenge to understand the immune responses of this gene. Compare to the unchallenged control RbKunitz exhibited strong up-regulation at 24 h post injection (p.i.) after LPS and E. tarda injection. Comparatively robust expression of RbKunits was observed at 3 h p.i. upon Poly I:C challenge. Taken together all these data indicate that RbKunitz may involve into to immune responses upon pathogenic stress, in order to protect the rock bream.

Keywords: Kunitz-type, rock bream, immune response, serine protease inhibitor

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Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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Authors: Xinge Liao, Francesc Xavier Roige Ventura, Dolores Sanchez Aguilera

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With the development of the Internet, the study of tourism behavior has rapidly expanded from the traditional physical market to the online market. Data on the Internet is characterized by dynamic changes, and new data appear all the time. In recent years the generation of a large volume of data was characterized, such as forums, blogs, and other sources, which have expanded over time and space, together they constitute large-scale Internet data, known as Big Data. This data of technological origin that derives from the use of devices and the activity of multiple users is becoming a source of great importance for the study of geography and the behavior of tourists. The study will focus on cultural heritage tourist practices in the context of Big Data. The research will focus on exploring the characteristics and behavior of Chinese tourists in relation to the cultural heritage of Catalonia. Geographical information, target image, perceptions in user-generated content will be studied through data analysis from Weibo -the largest social networks of blogs in China. Through the analysis of the behavior of heritage tourists in the Big Data environment, this study will understand the practices (activities, motivations, perceptions) of cultural tourists and then understand the needs and preferences of tourists in order to better guide the sustainable development of tourism in heritage sites.

Keywords: Barcelona, Big Data, Catalonia, cultural heritage, Chinese tourism market, tourists’ behavior

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Authors: A. Alexandru, C. A. Alexandru, D. Coardos, E. Tudora

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Big Data (BD) is associated with a new generation of technologies and architectures which can harness the value of extremely large volumes of very varied data through real time processing and analysis. It involves changes in (1) data types, (2) accumulation speed, and (3) data volume. This paper presents the main concepts related to the BD paradigm, and introduces architectures and technologies for BD and BD sets. The integration of BD with the Hadoop Framework is also underlined. BD has attracted a lot of attention in the public sector due to the newly emerging technologies that allow the availability of network access. The volume of different types of data has exponentially increased. Some applications of BD in the public sector in Romania are briefly presented.

Keywords: big data, big data analytics, Hadoop, cloud

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Authors: Rozeena Shaikh, Syed M Shahid, Jamil Ahmad, Qaisar Mansoor, Muhammad Ismail, Abid Azhar

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Introduction: Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. In most high-income countries as well as middle-income and low- income countries. DM is among the top causes of deaths. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy, and foot. Diabetic nephropathy (DN) characterized by persistent albuminuria is a leading cause of end stage renal failure (ESRF). Pathogenesis of diabetic nephropathy is implicated by the polymorphisms in genes encoding the components of reninangiotensin- aldosteron system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and particularly angiotensin converting enzyme (ACE) gene. Method: Study subjects include 110 control, 110 patients with DM without hypertension, 110 patients with DM with hypertension and 110 patients with DN. Blood samples were collected for Biochemical analysis and PCR and sequencing for the specific region of both genes. Results: The frequency of DD genotype and D allele of ACE (I/D) was significantly (p<0.05) high in DM normotensive, DM hypertensive and DN patients when compared to control. The ACE G2350A genotypes and allele frequencies were significantly different (p<0.05) in DM hypertensive patients as compared to control and DN, while no difference was observed between DM normotensive and DN when compared to control. The genotypes and alleles of AGT (M268T) polymorphism were significantly different (p<0.05) in DM normotensive, DM hypertensive and DN when compared to control. Conclusion: The DD genotype and D allele of ACE (I/D), GG genotype and G allele of ACE (G2350A) and the TT genotype and T allele of AGT (M268T) polymorphism have shown a significant difference in genotype and allele frequencies between controls and patients.

Keywords: genetic variations, ACE, AGT, diabetes mellitus, diabetic nephropathy, Pakistan

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Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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Authors: Hung-Chieh Chen, Kuo-Hui Wang, Tsu-Lin Yeh

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Proteomics represent the performance of genomic complement proteins and the protein level on functional genomics. This study adopted proteomic strategies for comparing serum proteins among three groups: elite sprinter (sprint runner group, SR), long-distance runners (long-distance runner group, LDR), and the untrained control group (control group, CON). Purposes: This study aims to identify elite sprinters and long-distance runners’ serum protein and to provide a comparison of their serum proteome’ composition. Methods: Serum protein fractionations that separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by a quantitative nano-LC-MS/MS-based proteomic profiling. The one-way analysis of variance (ANOVA) and Scheffe post hoc comparison (α= 0.05) was used to determine whether there is any significant difference in each protein level among the three groups. Results: (1) After analyzing the 307 identified proteins, there were 26 unique proteins in the SR group, and 18 unique proteins in the LDR group. (2) For the LDR group, 7 coagulation function-associated proteins’ expression levels were investigated: vitronectin, serum paraoxonase/arylesterase 1, fibulin-1, complement C3, vitamin K-dependent protein, inter-alpha-trypsin inhibitor heavy chain H3 and von Willebrand factor, and the findings show the seven coagulation function-associated proteins were significantly lower than the group of SR. (3) Comparing to the group of SR, this study found that the LDR group’s expression levels of the 2 antioxidant proteins (afamin and glutathione peroxidase 3) were also significantly lower. (4) The LDR group’s expression levels of seven immune function-related proteins (Ig gamma-3 chain C region, Ig lambda-like polypeptide 5, clusterin, complement C1s subcomponent, complement factor B, complement C4-A, complement C1q subcomponent subunit A) were also significantly lower than the group of SR. Conclusion: This study identified the potential serum protein markers for elite sprinters and long-distance runners. The changes in the regulation of coagulation, antioxidant, or immune function-specific proteins may also provide further clinical applications for these two different track athletes.

Keywords: biomarkers, coagulation, immune response, oxidative stress

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Authors: Eryati Darwin, Arina Widya Murni, Adnil Edwin Nurdin

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Background: Functional dyspepsia (FD) is a highly prevalent and heterogeneous disorder. Most patients with FD complain of symptoms related to the intake of meals. Psychological stress may promote peptic ulcer and had an effect on ulcers associated Hp, and may also trigger worsen symptoms in inflammatory disorders of the gastrointestinal. Cells in mucosal gastric stimulate the production of several cytokines, which might associated with Helicobacter pylori infection. The cascade of biological events leading to stress-induced FD remains poorly understood. Aim of Study: To determine the prion-flammatory cytokine IL-6, and Helicobacter pylori activity on mucosal gastric of FD and their association with psychological stress. Methods: The subjects of this study were dyspeptic patients who visited M. Djamil General Hospital and in two Community Health Centers in Padang. On the basis of the stress index scale to identify psychological stress by using Depression Anxiety and Stress Scale (DASS 42), subjects were divided into two groups of 20 each, stress groups and non-stress groups. All diagnoses were confirmed by review of cortisol and esophagogastroduodenoscopy reports. Gastric biopsy samples and peripheral blood were taken during diagnostic procedures. Immunohistochemistry methods were used to determine the expression of IL-6 and Hp in gastric mucosal. The data were statistically analyzed by univariate and bivariate analysis. All procedures of this study were approved by Research Ethics Committee of Medical Faculty Andalas University. Results: In this study, we enrolled 40 FD patients (26 woman and 14 men) in range between 35-56 years old. Cortisol level of blood FD patients as parameter of stress hormone which taken in the morning was significantly higher in stress group than non-stress group. The expression of IL-6 in gastric mucosa was significantly higher in stress group in compared to non-stress group (p<0,05). Helicobacter pylori activity in gastric mucosal in stress group were significantly higher than non-stress group. Conclusion: The present study showed that psychological stress can induce gastric mucosal inflammation and increase of Helicobacter pylori activity.

Keywords: functional dyspepsia, Helicobacter pylori, interleukin-6, psychological stress

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Authors: Grzegorz Kubinski

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In the proposed paper, we would like to present the phenomenon of disease and disability as an element of discourse redefining the contemporary canons of beauty and the category of normativity. In widely understood media, and above all in social media and fashion industry, the use of the disease as an aesthetic category has long been observed. There is an interesting case of promoting and maintaining a certain, ideal pattern of physical beauty, while at the same time very clear exploitation of various types of illnesses. The categories of disease and disabled body are shown as an element of the expression of the individuality and originality of one's own identity, while at the same time the disabled person is still experiencing social exclusion. Illness or body abnormality as an aesthetic category also functions as an ethical-political category. The analysis of the interrelations of these discourses will be presented on the example of selected projects present in social media, like Instagram or Facebook. We would like to present how old forms of 'curiosities' or 'abnormalities' turned into mainstream forms of a new aesthetic. For marginalized disabled people, there is a new form of expression and built their identity. But, there is an interesting point: are this contemporary forms of using disability and illness really new? Or maybe this is just another form of Wunderkammer or even cabinets of curiosities? We propose to analyze contemporary cultural and social context in order to clarify this issue. On the other hand, we would like to present some examples from personal interviews with disabled internet influencers and statements disabled persons concerning the role of the different body in society (e.g. #bodypositive, #perfeclyflawed).

Keywords: disability, new media, defect, fashion

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Kkochorong Park, Keun Cheon Kim, Hyoban Lee, Eun Ju Lee, Bongsoo Kim

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Introduction of biomaterials such as DNA, RNA, proteins is important for many research areas. There are many methods to introduce biomaterials into living organisms like tissue and cells. To introduce biomaterials, several indirect methods including virus‐mediated delivery, chemical reagent (i.e., lipofectamine), electrophoresis have been used. Such methods are passive delivery using an endocytosis process of cell, reducing an efficiency of delivery. Unlike the indirect delivery method, it has been reported that a direct delivery of exogenous biomolecules into nucleus have been more efficient to expression or integration of biomolecules. Nano-sized material is beneficial for detect signal from cell or deliver stimuli/materials into the cell at cellular and molecular levels, due to its similar physical scale. Especially, because 1 dimensional (1D) nanomaterials such as nanotube, nanorod and nanowire with high‐aspect ratio have nanoscale geometry and excellent mechanical, electrical, and chemical properties, they could play an important role in molecular and cellular biology. In this study, by using single crystalline 1D noble metal nanowire, we fabricated nano-sized 1D injector which can successfully interface with living cells and directly deliver biomolecules into several types of cell line (i.e., stem cell, mammalian embryo) without inducing detrimental damages on living cell. This nano-bio technology could be a promising and robust tool for introducing exogenous biomaterials into living organism.

Keywords: DNA, gene delivery, nanoinjector, nanowire

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Authors: Sina Mahdavi

Abstract:

Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human immunodeficiency virus (HIV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on human HIV infection in MS disease progression. In this study, the keywords "Multiple sclerosis", "Human immunodeficiency virus ", and "Central nervous system" in the databases PubMed, and Google Scholar between 2017 and 2022 were searched and 15 articles were chosen, studied, and analyzed. Revealed histologic signs of "MS-like illness" in the setting of HIV, which comprised widespread demyelination with reactive astrocytes, foamy macrophages, and perivascular infiltration with inflammatory cells, all of which are compatible with MS lesions. Human immunodeficiency virus causes dysfunction of the immune system, especially characterized by hypergammaglobulinemia and chronic activation of B cells. Activation of B cells leads to increased synthesis of immunoglobulin and finally to an excess of free light chains. Free light chains may be involved in autoimmune responses against neurons. There is a high expression of HIV during the course of MS, which indicates the relationship between HIV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HIV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human immunodeficiency virus, central nervous system, autoimmunity

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Authors: Thomais Tsoulia, Arvind Y. M. Sundaram, Stine Braaen, Øyvind Haugland, Espen Rimstad, Øystein Wessel, Maria K. Dahle

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Fish red blood cells (RBC) are nucleated, and in addition to their function in gas exchange, they have been characterized as mediators of immune responses. Salmonid RBC are the major target cells of Piscineorthoreovirus (PRV), a virus associated with heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. The activation of antiviral response genesin RBChas previously been described in ex vivo and in vivo PRV-infection models, but not explored in the initial virus encounter phase. In the present study, mRNA transcriptome responses were explored in erythrocytes from individual fish, kept ex vivo, and exposed to purified PRV for 24 hours. The responses were compared to responses in macrophage-like salmon head kidney (SHK-1) and endothelial-like Atlantic salmon kidney (ASK) cells, none of which support PRV replication. The comparative analysis showed that the antiviral response to PRV was strongest in the SHK-1 cells, with a set of 80 significantly induced genes (≥ 2-fold upregulation). In RBC, 46 genes were significantly upregulated, while ASK cells were not significantly responsive. In particular, the transcriptome analysis of RBC revealed that PRV significantly induced interferon regulatory factor 1 (IRF1) and interferon-induced protein with tetratricopeptide repeats 5-like (IFIT9). However, several interferon-regulated antiviral genes which have previously been reported upregulated in PRV infected RBC in vivo (myxovirus resistance (Mx), interferon-stimulated gene 15 (ISG15), toll-like receptor 3 (TLR3)), were not significantly induced after 24h of virus stimulation. In contrast to RBC, these antiviral response genes were significantly upregulated in SHK-1. These results confirm that RBC are involved in the innate immune response to viruses, but with a delayed antiviral response compared to SHK-1. A notable difference is that interferon regulatory factor 1 (IRF-1) is the most strongly induced gene in RBC, but not among the significantly induced genes in SHK-1. Putative differences in the binding, recognition, and response to PRV, and any link to effects on the ability of PRV to replicate remains to be explored.

Keywords: antiviral responses, atlantic salmon, piscine orthoreovirus-1, red blood cells, RNA-seq

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