Search results for: gene expression omnibus

Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari

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Cyperus rotendus rhizomes are used as traditional medicine, including Ayurveda in chronic liver diseases and hepatitis B. We investigated the in vitro hepatoprotective and anti-hepatitis B virus (HBV) potential of Cyperus rotundus rhizome organic and aqueous fractions. Of these, the n-butanol and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-injured HepG2 cells at 48 h. DCFH-toxicated cells were recovered to about 88% and 96%, upon treatment with n-butanol and aqueous fractions (200 g/ml), respectively compared to DCFH-only treated cells. Further, C. rotundus fractions were tested for anti-HBV activities by measuring the expression levels of viral antigens (HBsAg and HBeAg) in the HepG2.2.15 culture supernatants. At 48 h post-treatment, the ethyl acetate, n-butanol and aqueous fractions showed dose-dependent inhibition wherein at a higher dose (100 g/ml), HBsAg production was reduced to 60.27%, 46.87 and 42.76%, respectively. In a time-course study, HBsAg production was inhibited up to 50% and 40% by ethyl acetate and n-butanol fractions (100 g/ml), respectively on day 5. Three three active fractions were further subjected to time-dependent inhibition of HBeAg expression, an indirect measure of HBV active DNA replication. At day 5 post-treatment, ethyl acetate and n-butanol fractions downregulated HBV replication by 44.14% and 24.70%, respectively. In conclusion, our results showed very promising hepatoprotective and anti-HBV potential of C. rotendus tubers fractions in vitro. Our data could, therefore, provide the basis for the claimed traditional use of C. rotendus for jaundice and hepatitis.

Keywords: anti-hepatitis B, cyperus rotundus, hepatitis B virus, hepatoprotection

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Linette van der Merwe

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It is known that visual artists, performing artists, and literary artists have inspired each other since time immemorial. The enduring, symbiotic relationship between the various art genres is evident where words, colours, lines, and sounds act as metaphors, a physical separation of the transcendental reality of art. Simonides of Keos (c. 556-468 BC) confirmed this, stating that a poem is a talking picture, or, in a more modern expression, a picture is worth a thousand words. It can be seen as an ancient relationship, originating from the epigram (tombstone or artefact inscriptions), the carmen figuratum (figure poem), and the ekphrasis (a description in the form of a poem of a work of art). Visual artists, including Michelangelo, Leonardo da Vinci, and Goethe, wrote poems and songs. Goya, Degas, and Picasso are famous for their works of art and for trying their hands at poetry. Afrikaans writers whose fine art is often published together with their writing, as in the case of Andries Bezuidenhout, Breyten Breytenbach, Sheila Cussons, Hennie Meyer, Carina Stander, and Johan van Wyk, among others, are not a strange phenomenon either. Imitating one art form into another art form is a form of translation, transposition, contemplation, and discovery of artistic impressions, showing parallel interpretations rather than physical comparison. It is especially about the harmony that exists between the different art genres, i.e., a poem that describes a painting or a visual text that portrays a poem that becomes a translation, interpretation, and rediscovery of the verbal text, or rather, from the word text to the image text. Poetry-film, as a form of such a translation of the word text into an image text, can be considered a hybrid, transdisciplinary art form that connects poetry and film. Poetry-film is regarded as an intertwined entity of word, sound, and visual image. It is an attempt to transpose and transform a poem into a new artwork that makes the poem more accessible to people who are not necessarily open to the written word and will, in effect, attract a larger audience to a genre that usually has a limited market. Poetry-film is considered a creative expression of an inverted ekphrastic inspiration, a visual description, interpretation, and expression of a poem. Research also emphasises that animated poetry-film is not widely regarded as a genre of anything and is thus severely under-theorized. This paper will focus on Afrikaans animated poetry-films as a multimodal transposition of a poem text to an animated poetry film, with specific reference to animated poetry-films in Filmverse I (2014) and Filmverse II (2016).

Keywords: poetry film, animated poetry film, poetic metaphor, conceptual metaphor, monomodal metaphor, multimodal metaphor, semiotic metaphor, multimodality, metaphor analysis, target domain, source domain

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Authors: Waraporn Thaimit, Yuwadee Insamran, Natchanok Jansawang

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Focusing on Analytical Thinking and Learning Achievement are the critical component of visual thinking that gives one the ability to solve problems quickly and effectively that allows to complex problems into components, and the result had been achieved or acquired form of the subject students of which resulted in changes within the individual as a result of activity in learning. The aims of this study are to administer on comparisons between students’ analytical thinking abilities and their learning achievements sample size consisted of 80 students who sat at the 12th grade level in 2 classes from Chaturaphak Phiman Ratchadaphisek School, the 40-student experimental group with the Problem-Based Learning (PBL) and 40-student controlling group with the Concept Mapping Instructional (CMI) methods were designed. Research instruments composed with the 5-lesson instructional plans to be assessed with the pretest and posttest techniques on each instructional method. Students’ responses of their analytical thinking abilities were assessed with the Analytical Thinking Tests and students’ learning achievements were tested of the Learning Achievement Tests. Statistically significant differences with the paired t-test and F-test (Two-way MANCOVA) between post- and pre-tests of the whole students in two chemistry classes were found. Associations between student learning outcomes in each instructional method and their analytical thinking abilities to their learning achievements also were found (ρ < .05). The use of two instructional methods for this study is revealed that the students perceive their abilities to be highly learning achievement in chemistry classes with the PBL group ought to higher than the CMI group. Suggestions that analytical thinking ability involves the process of gathering relevant information and identifying key issues related to the learning achievement information.

Keywords: comparisons, students learning achievements, analytical thinking abilities, the problem-based learning method, the concept mapping instructional method, gene and chromosome issue, chemistry classes

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV 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 EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs

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Authors: Ashima Sharma, Tapan K. Chaudhuri

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Human Serum Albumin (HSA) is one of the most demanded therapeutic protein with immense biotechnological applications. The current source of HSA is human blood plasma. Blood is a limited and an unsafe source as it possesses the risk of contamination by various blood derived pathogens. This issue led to exploitation of various hosts with the aim to obtain an alternative source for the production of the rHSA. But, till now no host has been proven to be effective commercially for rHSA production because of their respective limitations. Thus, there exists an indispensable need to promote non-animal derived rHSA production. Of all the host systems, Escherichia coli is one of the most convenient hosts which has contributed in the production of more than 30% of the FDA approved recombinant pharmaceuticals. E. coli grows rapidly and its culture reaches high cell density using inexpensive and simple substrates. The fermentation batch turnaround number for E. coli culture is 300 per year, which is far greater than any of the host systems available. Therefore, E. coli derived recombinant products have more economical potential as fermentation processes are cheaper compared to the other expression hosts available. Despite of all the mentioned advantages, E. coli had not been successfully adopted as a host for rHSA production. The major bottleneck in exploiting E. coli as a host for rHSA production was aggregation i.e. majority of the expressed recombinant protein was forming inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA form inclusion body is not preferred because it is tedious, time consuming, laborious and expensive. Because of this limitation, E. coli host system was neglected for rHSA production for last few decades. Considering the advantages of E. coli as a host, the present work has targeted E. coli as an alternate host for rHSA production through resolving the major issue of inclusion body formation associated with it. In the present study, we have developed a novel and innovative method for enhanced soluble and functional production of rHSA in E.coli (~60% of the total expressed rHSA in the soluble fraction) through modulation of the cellular growth, folding and environmental parameters, thereby leading to significantly improved and enhanced -expression levels as well as the functional and soluble proportion of the total expressed rHSA in the cytosolic fraction of the host. Therefore, in the present case we have filled in the gap in the literature, by exploiting the most well studied host system Escherichia coli which is of low cost, fast growing, scalable and ‘yet neglected’, for the enhancement of functional production of HSA- one of the most crucial biomolecule for clinical and biotechnological applications.

Keywords: enhanced functional production of rHSA in E. coli, recombinant human serum albumin, recombinant protein expression, recombinant protein processing

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Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: Emre Bayamlıoğlu

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Apart from being the subject of neighboring rights when broadcasted on TV or of cinematographic work when fixed to a tangible medium including a hard drive, the copyright eligibility of a sports performance, and eventually the sporting event has once again given rise to controversy following the CJEU judgment in the Murphy case. Most of the arguments which deny copyright protection for sports performances focus on the fact that unlike movies, plays, television programs, or operas, athletic events are competitive and have no underlying script. The first part of the paper aims to explain that such rhetoric is rather weak simply for the fact that, several types of performances such as improvised musical or dramatic shows are still protected by copyright despite the fact that they are not based on a script. The second part argues that the core reason for the denial copyright protection was the functionality aiming certain practical results such as winning the game, scoring, eliminating an opponent, obstructing a shot and etc., but no scientific or artistic expression in whatsoever form. The paper further argues that expanding copyright protection to functional performances would give rise to unintended copyright claims by the athletes on tackles, shoots, passes, crosses etc. resulting with further restrictions on reporting and photographing of sporting events. The final part provides a policy analysis of the trend to broaden the scope of copyright to cover sports performances. It is argued that such expansion will clearly undermine the ratio legis of copyright laws since it will give rise to excessive commodification of information beyond the needs of a viable market economy. Therefore, remedies other than copyright protection such as unfair competition and unjust enrichment provides sufficient redress for the damages to be sustained by the investors of sporting events.

Keywords: copyright eligibility, idea-expression dichotomy, sports performance

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Authors: Salma A. Mahmoud

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Epigenetic, or alteration in gene expression influenced by extragenetic factors, has emerged as one of the most promising areas that will address some of the gaps in our current knowledge in understanding patterns of human variation. In the last decade, the research investigating epigenetic mechanisms in many fields has flourished and witnessed significant progress. It paved the way for a new era of integrated research especially between anthropology/archeology and life sciences. Skeletal remains are considered the most significant source of information for studying human variations across history, and by utilizing these valuable remains, we can interpret the past events, cultures and populations. In addition to archeological, historical and anthropological importance, studying bones has great implications in other fields such as medicine and science. Bones also can hold within them the secrets of the future as they can act as predictive tools for health, society characteristics and dietary requirements. Bones in their basic forms are composed of cells (osteocytes) that are affected by both genetic and environmental factors, which can only explain a small part of their variability. The primary objective of this project is to examine the epigenetic landscape/signature within bones of archeological remains as a novel marker that could reveal new ways to conceptualize chronological events, gender differences, social status and ecological variations. We attempted here to address discrepancies in common variants such as methylome as well as novel epigenetic regulators such as chromatin remodelers, which to our best knowledge have not yet been investigated by anthropologists/ paleoepigenetists using plethora of techniques (biological, computational, and statistical). Moreover, extracting epigenetic information from bones will highlight the importance of osseous material as a vector to study human beings in several contexts (social, cultural and environmental), and strengthen their essential role as model systems that can be used to investigate and construct various cultural, political and economic events. We also address all steps required to plan and conduct an epigenetic analysis from bone materials (modern and ancient) as well as discussing the key challenges facing researchers aiming to investigate this field. In conclusion, this project will serve as a primer for bioarcheologists/anthropologists and human biologists interested in incorporating epigenetic data into their research programs. Understanding the roles of epigenetic mechanisms in bone structure and function will be very helpful for a better comprehension of their biology and highlighting their essentiality as interdisciplinary vectors and a key material in archeological research.

Keywords: epigenetics, archeology, bones, chromatin, methylome

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Authors: Mustafa Sertçelik, Turan Çalban, Hacali Necefoğlu, Sabri Çolak

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In this study, Chevreul’s salt solubility and its dissolution kinetics in ammonium chloride solutions were investigated. Chevreul’s salt that we used in the studies was obtained by using the optimum conditions (ammonium sulphide concentration; 0,4 M, copper sulphate concentration; 0,25 M, temperature; 60°C, stirring speed; 600 rev/min, pH; 4 and reaction time; 15 mins) determined by T. Çalban et al. Chevreul’s salt solubility in ammonium chloride solutions and the kinetics of dissolution were investigated. The selected parameters that affect solubility were reaction temperature, concentration of ammonium chloride, stirring speed, and solid/liquid ratio. Correlation of experimental results had been achieved using linear regression implemented in the statistical package program statistica. The effect of parameters on Chevreul’s salt solubility was examined and integrated rate expression of dissolution rate was found using kinetic models in solid-liquid heterogeneous reactions. The results revealed that the dissolution rate of Chevreul’s salt was decreasing while temperature, concentration of ammonium chloride and stirring speed were increasing. On the other hand, dissolution rate was found to be decreasing with the increase of solid/liquid ratio. Based on result of the applications of the obtained experimental results to the kinetic models, we can deduce that Chevreul’s salt dissolution rate is controlled by diffusion through the ash (or product layer). Activation energy of the reaction of dissolution was found as 74.83 kJ/mol. The integrated rate expression along with the effects of parameters on Chevreul's salt solubility was found to be as follows: 1-3(1-X)2/3+2(1-X)= [2,96.1013.(CA)3,08 .(S/L)-038.(W)1,23 e-9001,2/T].t

Keywords: Chevreul's salt, copper, ammonium chloride, ammonium sulphide, dissolution kinetics

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Authors: Dwitya Elvira, Eryati Darwin

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Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.

Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease

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Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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Authors: Chu Wan-Loy, Kok Yih-Yih, Choong Siew-Ling

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The human health risks due to poor air quality caused by a wide array of microorganisms have attracted much interest. Airborne algae have been reported as early as 19th century and they can be found in the air of tropic and warm atmospheres. Airborne algae normally originate from water surfaces, soil, trees, buildings and rock surfaces. It is estimated that at least 2880 algal cells are inhaled per day by human. However, there are relatively little data published on airborne algae and its related adverse health effects except sporadic reports of algae associated clinical allergenicity. A collection of airborne algae cultures has been established following a recent survey on the occurrence of airborne algae in indoor and outdoor environments in Kuala Lumpur. The aim of this study was to investigate the allergenic potential of the isolated airborne green and blue-green algae, namely Scenedesmus sp., Cylindrospermum sp. and Hapalosiphon sp.. The suspensions of freeze-dried airborne algae were adminstered into balb-c mice model through intra-nasal route to determine their allergenic potential. Results showed that Scenedesmus sp. (1 mg/mL) increased the systemic Ig E levels in mice by 3-8 fold compared to pre-treatment. On the other hand, Cylindrospermum sp. and Hapalosiphon sp. at similar concentration caused the Ig E to increase by 2-4 fold. The potential of airborne algae causing Ig E mediated type 1 hypersensitivity was elucidated using other immunological markers such as cytokine interleukin (IL)- 4, 5, 6 and interferon-ɣ. When we compared the amount of interleukins in mouse serum between day 0 and day 53 (day of sacrifice), Hapalosiphon sp. (1mg/mL) increased the expression of IL4 and 6 by 8 fold while the Cylindrospermum sp. (1mg/mL) increased the expression of IL4 and IFɣ by 8 and 2 fold respectively. In conclusion, repeated exposure to the three selected airborne algae may stimulate the immune response and generate Ig E in a mouse model.

Keywords: airborne algae, respiratory, allergenic, immune response, Malaysia

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Authors: Ling-Lang Huang, Yih-Jer Wu

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Empathy is crucial for a patient-physician relationship and medical professionalism. Internet activity, gaming, or even addiction, have been more and more common among medical students. However, there’s been no report showing whether internet behavior has a substantial impact on empathy in medical students to our best knowledge. All year-2 medical students taking the optional course 'Narrative, Comprehension, and Communication' were enrolled. Internet behaviors are divided into two groups, 'internet users without online gaming (IU)' and 'internet users with online gaming (IG)', each group was further divided into 3 groups according to their average online retention time each day (< 2, 2 - 6, > 6 hours). Empathy was evaluated by the scores of the reports and humanities reflection after watching indicated movies, and by self-measured empathy questionnaire. All students taking the year-2 optional course 'Narrative, Comprehension, and Communication' were enrolled. As compared with students in the IU group, those in the IG group had significantly lower scores for the reports (81.3 ± 3.7 vs. 86.4 ± 5.1, P = 0.014). If further dividing the students into 5 groups (IU < 2, IU 2-6, IG < 2, IG 2 - 6, and IG > 6 hours), the scores were significantly and negatively correlated to online gaming with longer hours (r = -0.556, P = 0.006). However, there was no significant difference between IU and IG groups (33.0 ± 5.4 vs. 34.8 ± 3.2, P = n.s.), in terms of scores in the self-measured empathy questionnaire, neither was there any significant trend of scores along with longer online hours across the 5 groups (r = -0.164, P = n.s.). To date, there has been no evidence showing whether different internet behaviors (with or without online gaming) have distinct impacts on empathy. Although all of the medical students had a similarly good self-perception for empathy, our data suggested that online gaming did have a negative impact on their actual expression of empathy. Our observation has brought up an important issue for pondering: May IT- or gaming-assisted medical learning actually harm students’ empathy? In conclusion, this data suggests that long hours of online gaming harms expression of empathy, though all medics think themselves a person of high empathy.

Keywords: empathy. Internet, medical students, online gaming

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Authors: Ishani D. Goonasekara, Erio Camporesi, Timur Bulgakov, Rungtiwa Phookamsak, Kevin D. Hyde

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Phaeosphaeriaceae comprises a large number of species occurring mainly on grasses and cereal crops as endophytes, saprobes and especially pathogens. Parastagonospora is an important genus in Phaeosphaeriaceae that includes pathogens causing leaf and glume blotch on cereal crops. Currently, there are fifteen Parastagonospora species described, including both pathogens and saprobes. In this study, one sexual morph species and an asexual morph species, occurring as saprobes on members of Poaceae are introduced based on morphology and a combined molecular analysis of the LSU, SSU, ITS, and RPB2 gene sequence data. The sexual morph species Parastagonospora elymi was isolated from a Russian sample of Elymus repens, a grass commonly known as couch grass, and important for grazing animals, as a weed and used in traditional Austrian medicine. P. elymi is similar to the sexual morph of P. avenae in having cylindrical asci, bearing 8, overlapping biseriate, fusiform ascospores but can be distinguished by its subglobose to conical shaped, wider ascomata. In addition, no sheath was observed surrounding the ascospores. The asexual morph species was isolated from a specimen from Italy, on Dactylis glomerata, a commonly found grass distributed in temperate regions. It is introduced as Parastagonospora macrouniseptata, a coelomycete, and bears a close resemblance to P. allouniseptata and P. uniseptata in having globose to subglobose, pycnidial conidiomata and hyaline, cylindrical, 1-septate conidia. However, the new species could be distinguished in having much larger conidiomata. In the phylogenetic analysis which consisted of a maximum likelihood and Bayesian analysis P. elymi showed low bootstrap support, but well segregated from other strains within the Parastagonospora clade. P. neoallouniseptata formed a sister clade with P. allouniseptata with high statistical support.

Keywords: dothideomycetes, multi-gene analysis, Poaceae, saprobes, taxonomy

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Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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Authors: Richard G. Carranza, Juan Ospina

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The fin efficiency for a helical fin with a fixed fin tip (or arbitrary) temperature boundary condition is presented. Firstly, the temperature profile throughout the fin is determined via an energy balance around the fin itself. Secondly, the fin efficiency is formulated by integrating across the entire surface of the helical fin. An analytical expression for the fin efficiency is presented and compared with the literature for accuracy.

Keywords: efficiency, fin, heat, helical, transfer

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Authors: Xiaoyuan Suo

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3D object reconstruction is a broad research area within the computer vision field involving many stages and still open problems. One of the existing challenges in this field lies with micromotion, such as the facial expressions on the appearance of the human or animal face. Similar literatures in this field focuses on 3D reconstruction in stable conditions such as an existing image or photos taken in a rather static environment, while the purpose of this work is to discuss a flexible scan system using multiple cameras that can correctly reconstruct 3D stable and moving objects -- human face with expression in particular. Further, a mathematical model is proposed at the end of this literature to automate the 3D object reconstruction process. The reconstruction process takes several stages. Firstly, a set of simple 2D lines would be projected onto the object and hence a set of uneven curvy lines can be obtained, which represents the 3D numerical data of the surface. The lines and their shapes will help to identify object’s 3D construction in pixels. With the two-recorded angles and their distance from the camera, a simple mathematical calculation would give the resulting coordinate of each projected line in an absolute 3D space. This proposed research will benefit many practical areas, including but not limited to biometric identification, authentications, cybersecurity, preservation of cultural heritage, drama acting especially those with rapid and complex facial gestures, and many others. Specifically, this will (I) provide a brief survey of comparable techniques existing in this field. (II) discuss a set of specialized methodologies or algorithms for effective reconstruction of 3D objects. (III)implement, and testing the developed methodologies. (IV) verify findings with data collected from experiments. (V) conclude with lessons learned and final thoughts.

Keywords: 3D photogrammetry, 3D object reconstruction, facial expression recognition, facial recognition

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Authors: Radoslav Stojchevski, Leonid Poretsky, Dimiter Avtanski

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Proinflammatory cytokines play an important role in cancer initiation and progression by mediating the intracellular communication between the cancer cells and tumor microenvironment. Increased tumor growth causing reduced oxygen concentration and oxygen pressure commonly result in hypoxia. Mechanistically, hypoxia is characterized by stabilization and nuclear translocation of hypoxia-inducible factor 1 alpha (HIF-1α) followed by propagation of molecular pathway cascade involving multiple downstream targets. Cobalt(II) chloride (CoCl₂) is commonly used to mimic hypoxia in experimental conditions since it directly induces the expression of HIF-1α. The aim of the present study was to investigate the in vitro effects and the molecular mechanisms by which hypoxia regulates the cytokine secretory profile of breast cancer cells. As a model for this study, we used several breast cancer cell lines bearing various molecular characteristics and metastatic potential (MDA-MB-231 (clauding low, ER-/PR-/HER²⁻), MCF-7 (luminal A, ER⁺/PR⁺/HER²⁻), and BT-474 (liminal B, ER⁺/PR⁺/HER²⁺)). We demonstrated that breast cancer cells secrete numerous cytokines and cytokine ligands, including interleukins, chemokines, and growth factors. Treatment with CoCl₂significantly modulated the breast cancer cells' cytokine expression in a concentration- and time-dependent manner. These effects were mediated via activation of several signaling pathways (JNK/SAPK1, NF-κB, STAT5A/B, and Erk/MAPK1/2). Taken together, the present data define some of the molecular mechanisms by which hypoxia affects the breast cancer cells' cytokine secretory profile, thus contributing to the development of novel therapies for metastatic breast cancer.

Keywords: breast cancer, cytokines, cobalt(II) chloride (CoCl₂), hypoxia

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Authors: Aline Giardin, Maria Rosa Chitolina

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Our research conducted in 8 different schools in the city of Rio Grande do Sul, Brazil, we can clearly see that, even in modern times, where the search for equality between men and women is already over 60 years of struggle in this world where you show Much more than two genres and in this world that is proving that sex is not just biological, are confronted with sexist and phallocentric situations in our Schools, and among our students. The sample consisted of 503 students with a mean age between 13 and 21 years. 107 students identified themselves as gay, lesbian, bisexual or transgender. The remainder was identified as heterosexual or none at all. Compared to LGBT students, transgender students faced the school's more hostile climates, while non-transgender female students were less likely to experience anti-LGBT victimization. In addition, transgender students experienced more negative experiences at school compared to students whose gender expression adhered to traditional gender norms. Transgender students were more likely to feel insecure at school, with 80.0% of transgender students reporting that they felt insecure at school because of their gender identity. Female students in our research reported lower frequencies of victimization based on sexual orientation and gender identity and were less likely to feel insecure at school. In all indicators of discrimination in school, high school students have outperformed elementary school students and have had fewer resources and supports related to LGBT. High school students reported higher rates of victimization on sexual orientation and gender expression than elementary school students. For example, about one-third (35.5%) of high school students suffered regular physical Very often) based on their sexual orientation, compared to less than a quarter (21.4%) of primary school students. The whole premise here is to perceive the phallocentrism and sexism hidden in our schools. Opposition between the sexes is not reflexive or articulates a biological fact, but a social construction.

Keywords: transgender students, school, psychological implications, discrimination

Procedia PDF Downloads 443

Authors: Rita Bagheri, Javed Ahmed, Humayra Bashir, M. Irfan Qureshi

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Agriculture lands suffer from a combination of stresses such as salinity and metal contamination including cadmium at the same time. Under such condition of multiple stresses, plant may exhibit unique responses different from the stress occurring individually. Thus, it would be interesting to investigate that how plant respond to combined stress at level of antioxidants and proteome expression, and identifying the proteins which are involved in imparting stress tolerance. With an approach of comparative proteomics and antioxidant analysis, present study investigates the response of Spinacia oleracea to salt (NaCl), cadmium (Cd), and their combination (NaCl+Cd) stress. Two-dimensional gel electrophoresis was used for resolving leaf proteome, and proteins of interest were identified using PDQuest software. A number of proteins expressed differentially, those indicated towards their roles in imparting stress tolerance, were digested by trypsin and analyzed on mass spectrometer for peptide mass fingerprinting (PMF). Data signals were then matched with protein databases using MASCOT. Results show that NaCl, Cd and both together (NaCl+Cd) induce oxidative stress which was highest in combined stress of Cd+NaCl. Correspondingly, the activities of enzymatic antioxidants viz., SOD, APX, GR and CAT, and non-enzymatic antioxidants had highest changes under combined stress compares to single stress over their respective controls. Among the identified proteins, several interesting proteins were identified that may be have role in Spinacia oleracia tolerance in individual and combinatorial stress of salt and cadmium. The functional classification of identified proteins indicates the importance and necessity of keeping higher ratio of defence and disease responsive proteins.

Keywords: Spinacia oleracea, Cd, salinity, proteomics, antioxidants, combinatorial stress

Procedia PDF Downloads 367

Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Filip Franciszek Karuga, Szymon Turkiewicz, Marta Ditmer, Marcin Sochal, Piotr Białasiewicz, Agata Gabryelska

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Circadian rhythm, an internal coordinator of physiological processes is composed of a set of semi-autonomous clocks. Clocks are regulated through the expression of circadian clock genes which form feedback loops, creating an oscillator. The primary loop consists of activators: CLOCK, BMAL1 and repressors: CRY, PER. CLOCK can be substituted by the Neuronal PAS Domain Protein 2 (NPAS2). Orphan nuclear receptor (REV-ERB-α) is a component of the secondary major loop, modulating the expression of BMAL1. Circadian clocks might be disrupted by the obstructive sleep apnea (OSA), which has also been associated with type II diabetes mellitus (DM2). Interestingly, studies suggest that dysregulation of NPAS2 and REV-ERB-α might contribute to the pathophysiology of DM2 as well. The goal of our study was to examine the role of NPAS2 and REV-ERB-α in DM2 in OSA patients. After examination of the clinical data, all participants underwent polysomnography (PSG) to assess their apnea-hypopnea index (AHI). Based on the acquired data participants were assigned to one of 3 groups: OSA (AHI>30, no DM2; n=17 for NPAS2 and 34 for REV-ERB-α), DM2 (AHI>30 + DM2; n=7 for NPAS2 and 15 for REV-ERB-α) and control group (AHI<5, no DM2; n=16 for NPAS2 and 31 for REV-ERB-α). ELISA immunoassay was performed to assess the serum protein level of REV-ERB-α and NPAS2. The only statistically significant difference between groups was observed in NPAS2 protein level (p=0.037). Post-hoc analysis showed significant differences between the OSA and the control group (p=0.017). AHI and NPAS2 level was significantly correlated (r=-0.478, p=0.002) in all groups. A significant correlation was observed between the REV-ERB-α level and sleep efficiency (r=0.617, p=0.005) as well as sleep maintenance efficiency (r=0.645, p=0.003) in the OSA group. We conclude, that NPAS2 is associated with OSA severity and might contribute to metabolic sequelae of this disease. REV-ERB-α on the other hand can influence sleep continuity and efficiency.

Keywords: OSA, diabetes mellitus, endocrinology, chronobiology

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Authors: Margarida Franca

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The influence of the ‘cultural turn’ movement and the consequent deconstruction of scientific thought allowed geography and other social sciences to open or deepen their studies based on the analysis of multiple identities, on singularities, on what is particular or what marks the difference between individuals. In the context of postmodernity, the geography of religion has gained a favorable scientific, thematic and methodological focus for the qualitative and subjective interpretation of various religious identities, sacred places, territories of belonging, religious communities, among others. In the context of ‘late modernity’ or ‘net modernity’, sacred places and the definition of a network of sacred territories allow believers to attain the ‘ontological security’. The integration on a religious group or a local community, particularly a religious community, allows human beings to achieve a sense of belonging, familiarity or solidarity and to overcome, in part, some of the risks or fears that society has discovered. The importance of sacred places comes not only from their inherent characteristics (eg transcendent, mystical and mythical, respect, intimacy and abnegation), but also from the possibility of adding and integrating members of the same community, creating bonds of belonging, reference and individual and collective memory. In addition, the formation of different networks of sacred places, with multiple scales and dimensions, allows the human being to identify and structure his times and spaces of daily life. Thus, each individual, due to his unique identity and life and religious paths, creates his own network of sacred places. The territorial expression of religious identity allows to draw a variable and unique geography of sacred places. Through the case study of the practicing Catholic population in the diocese of Coimbra (Portugal), the aim is to study the territorial expression of the religious identity of the different local communities of this city. Through a survey of six parishes in the city, we sought to identify which factors, qualitative or not, define the different territorial expressions on a local, national and international scale, with emphasis on the socioeconomic profile of the population, the religious path of the believers, the religious group they belong to and the external interferences, religious or not. The analysis of these factors allows us to categorize the communities of the city of Coimbra and, for each typology or category, to identify the specific elements that unite the believers to the sacred places, the networks and religious territories that structure the religious practice and experience and also the non-representational landscape that unifies and creates memory. We conclude that an apparently homogeneous group, the Catholic community, incorporates multitemporalities and multiterritorialities that are necessary to understand the history and geography of a whole country and of the Catholic communities in particular.

Keywords: geography of religion, sacred places, territoriality, Catholic Church

Procedia PDF Downloads 309

Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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Authors: Stéfani T. A. Dantas, Laura T. S. Takume, Bruna F. Rossi, Érika R. Bonsaglia, Ivana G. Castilho, José C. F. Pantoja, Ary Fernandes Júnior, Juliano L. Gonçalves, Marcos V. Santos, Rinaldo A. Mota, Vera L. M. Rall

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Staphylococcus aureus is one of the main pathogens causing contagious bovine mastitis, being more frequently isolated from subclinical form, although the clinical form also occurs. Clinical mastitis cause visual signs, such as swelling, fever, hardening of the mammary gland, or any change in the characteristics of the milk. Considering the subclinical type, there are no visible signs in the animal nor changes in the milk. S. aureus has many important virulence factors for the establishment of its pathogenicity in animals, such as enterotoxins, which are also responsible for foodborne poisoning. Our objective is to perform a comparative analysis between 103 isolates of S. aureus, obtained from the milk of cows with clinical mastitis and 103 more, from subclinical type, in relation to the presence of these enterotoxins and verify if their presence plays an important role in the signs of illness. We will investigate all enterotoxins described till now, such as sea-see, seg-sez, sel26, sel 27, se01, and se02 (This study was approved by the Sao Paulo State University Animal Use Ethics Committee, No. 0136/2017). For the PCR assay, we used Illustra Bacteria Mini Spin Kit for bacterial DNA. At this moment, we have already tested sea-see, seg-ser, sew, and sex, and the results have already been submitted to Fisher Exact Probability Test or Chi-square Test. Considering the isolates obtained from clinical mastitis, the most frequent enterotoxins were selw (99%), selx (78%) and selh (50.5%), and sec, see, sej, sell, selp,and ser were absent. Among the subclinics, selw (82.5%) selm (15.5%) and selx (14.6%) were the most frequent, and sea-see, seg, sei-sel, sem-ser were absent. We have already observed statistically significant differences for seb, seg, seh, sei, selo, selu, selw and selx. Other interesting results were the low number of genes in each isolate from subclinical mastitis [0 genes: 14 (13.6%); 1 gene: 55 (53.4%); 2 genes: 33 (32%) or 3: 1 (0.97%)] compared to clinical isolates [1 gene: 5 (4.9%); 2 genes: 29 (28.1%); 3 genes: 38 (36.9%); 4 genes: 14 (13.6%); 5 genes: 5 (4.9%); 6 genes: 4 (3.9%); 7 genes: 5 (4.9%); 8 genes: 2 (1.9%) and 9 genes: 1 (1%)]. Based on these results, we can conclude that enterotoxins indeed play an important role in clinical signs in cattle with mastitis.

Keywords: mastitis, S. aureus, PCR, staphylococcal enterotoxin

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Zhala Ahmad, Zainab Lazim, Haider Hamzah

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Bacterial resistance is a pressing global health issue, with multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) strains to pose a serious threat. In this context, researchers are investigating effective, safe, and affordable metabolites to combat these pathogens. This study focuses on gum essential oil (GEO) extracted from Pistacia atlantica and its activity and the mechanism of action against XDR Gram-negative Acinetobacter baumannii. GEO was extracted by hydrodistillation and analyzed using GC-MS. Eleven A. baumannii isolates were collected from the ward environment of Burn and Plastic Surgery Hospital in Al Sulaymaniyah City, Iraq. They were identified using the VITEK 2 system, 16S rRNA gene, and confirmed with the blaₒₓₐ₋₅₁ gene; A. baumannii ATCC 19606 was used as a reference strain. The isolates were identified as resistant to twelve different antibiotics spanning six distinct antibiotic classes while showing susceptibility to tetracycline and trimethoprim. Over 40 chemical constituents were detected in the gum's essential oils, with α-pinene being the most abundant. GEO was found to inhibit the growth of A. baumannii isolates; the minimum inhibitory concentration (MIC) of GEO was 2.5 µl/ml. GEO induced protein leakage, phosphate, and potassium ion efflux, distorted cell morphology, and cell death in the tested bacteria. GEO exhibited bacterial clearance and anti-adhesion activity using Band-Aids. This study's findings suggest that GEO could be used as a potential alternative treatment for infectious diseases caused by XRD pathogens, shedding further light on the importance of GEO in biomedical applications. Future studies must focus on generating clinically feasible sources of GEO for testing in small animal models before proceeding to human trials, ensuring safe and effective translation from the laboratory to the clinic.

Keywords: antibiotic resistance, Acinetobacter baumannii, essential oils, Pistacia atlantica, alpha-pinene

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Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

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Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

Procedia PDF Downloads 276