Search results for: gene diversity

Authors: Sunidhi Syal, Rasangi Tennakoon, Patrick O'Donoghue

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Polyglutamine (polyQ) diseases are a group of diseases related to neurodegeneration caused by repeats of the amino acid glutamine (Q) in the DNA, which translates into an elongated polyQ tract in the protein. The pathological explanation is that the polyQ tract forms cytotoxic aggregates in the neurons, leading to their degeneration. There are no cures or preventative efforts established for these diseases as of today, although the symptoms of these diseases can be relieved. This study specifically focuses on Huntington's disease, which is a type of polyQ disease in which aggregation is caused by the extended cytosine, adenine, guanine (CUG) codon repeats in the huntingtin (HTT) gene, which encodes for the huntingtin protein. Using this principle, we attempted to create six models, which included mutating wildtype tRNA alanine variant tRNA-AGC-8-1 to have glutamine anticodons CUG and UUG so serine is incorporated at glutamine sites in poly Q tracts. In the process, we were successful in obtaining tAla-8-1 CUG mutant clones in the HTTexon1 plasmids with a polyQ tract of 23Q (non-pathogenic model) and 74Q (disease model). These plasmids were transfected into mouse neuroblastoma cells to characterize protein synthesis and aggregation in normal and mistranslating cells and to investigate the effects of glutamines replaced with alanines on the disease phenotype. Notably, we observed no noteworthy differences in mean fluorescence between the CUG mutants for 23Q or 74Q; however, the Triton X-100 assay revealed a significant reduction in insoluble 74Q aggregates. We were unable to create a tAla-8-1 UUG mutant clone, and determining the difference in the effects of the two glutamine anticodons may enrich our understanding of the disease phenotype. In conclusion, by generating structural disruption with the amino acid alanine, it may be possible to find ways to minimize the toxicity of Huntington's disease caused by these polyQ aggregates. Further research is needed to advance knowledge in this field by identifying the cellular and biochemical impact of specific tRNA variants found naturally in human genomes.

Keywords: Huntington's disease, polyQ, tRNA, anticodon, clone, overlap PCR

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Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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Authors: Hafiz Arbab Sakandar

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Time-restricted intermittent fasting (TRIF) impacts host’s physiology and health. Plenty of health benefits have been reported for TRIF in animal models. However, limited studies have been conducted on humans especially in underdeveloped economies. Here, we designed a study to investigate the impact of TRIF/Ramadan fasting (16:8) on the modulation of gut-microbiome structure, metabolic pathways, and predicted metabolites and explored the correlation among them at different time points (during and after the month of Ramadan) in Pakistani Expats living in China. We observed different trends of Shannon-Wiener index in different subjects; however, all subjects showed substantial change in bacterial diversity with the progression of TRIF. Moreover, the changes in gut microbial structure by the end of TRIF were higher vis-a-vis in the beginning, significant difference was observed among individuals. Additionally, metabolic pathways analysis revealed that amino acid, carbohydrate and energy metabolism, glycan biosynthesis metabolism of cofactors and vitamins were significantly affected by TRIF. Pyridoxamine, glutamate, citrulline, arachidonic acid, and short chain fatty acid showed substantial difference at different time points based on the predicted metabolism. In conclusion, these results contribute to further our understanding about the key relationship among, dietary intervention (TRIF), gut microbiome structure and function. The preliminary results from study demonstrate significant potential for elucidating the mechanisms underlying gut microbiome stability and enhancing the effectiveness of microbiome-tailored interventions among the Pakistani populace. Nonetheless, extensive, and rigorous large-scale research on the Pakistani population is necessary to expound on the association between diet, gut microbiome, and overall health.

Keywords: gut microbiome, health, fasting, functionality

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Authors: Maria Ukolova

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Social and cultural processes over the past decades have largely affected the understanding of conventional female beauty all over the world. Fine arts and design tendencies could not remain unchanged and show a dynamic interplay with female rights, gender equality, and other social processes. As of now, the area lacks comprehensive academic research on the tendencies of understanding female beauty in contemporary art. This article makes an attempt to outline and analyse the main tendencies of contemporary works of art that turn to the image of a woman, including photography, digital art, and various forms of design. The research bases itself on paintings, performing arts, photography, digital art, and various forms of design, mainly on the principle of the most broadly resonated in society, as an empirical basis, and on existing researches in the sphere. The results of the research show a general trend that the concept of female beauty in art is either challenged as such or its understanding has shifted to individuality, diversity, and the state of mental health. However, some categories of art, such as digital art in the gaming industry, remain resistant to change and retain the appearance-based understanding of beauty. Specific tendencies are, firstly, aestheticization of all types of appearances; secondly, a ubiquitous interest in mental health issues and understanding the state of mental health as a part of beauty; thirdly, a certain infantilization of the image of the woman is observed as compared to previous decades. The significance of the findings of the research is to contribute to a scientific understanding of the concept of beauty in contemporary art and to give ground for prospective further related research in sociology, phycology, etc. The findings might be perceived not only by academics but also by artists and practitioners in the spheres of art and society.

Keywords: fine arts, history of art, contemporary art, concept of beauty

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Authors: Hossam Hegazi

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Global culture museums play a pivotal role in fostering cross-cultural connections, enhancing mutual understanding, and safeguarding the rich tapestry of cultural heritage. These institutions serve as dynamic bridges, facilitating the exchange of ideas and values among diverse societies. One of the primary functions of global culture museums is to connect people from different backgrounds. By showcasing the artistic expressions, traditions, and historical artifacts of various civilizations, these museums create a shared space for dialogue. Visitors are afforded the opportunity to explore and appreciate the nuances of cultures different from their own, promoting a sense of global interconnectedness. Moreover, these museums contribute significantly to mutual understanding. Through interactive exhibits, innovative technologies, and educational programs, they offer immersive experiences that transcend linguistic and geographical barriers. Visitors gain insights into the customs, beliefs, and lifestyles of others, fostering empathy and appreciation for cultural diversity. Preserving cultural heritage stands as another key objective of global culture museums. By housing and curating artifacts, artworks, and historical items, these institutions play a crucial role in safeguarding the collective memory of humanity. This preservation effort ensures that future generations have access to the cultural legacies that have shaped societies across the globe. In conclusion, global culture museums serve as dynamic hubs that bring people together, promote understanding, and safeguard the wealth of human cultural heritage. Their impact extends beyond the walls of exhibition halls, contributing to a more interconnected and culturally enriched world.

Keywords: global culture museums, cross-cultural connections, mutual understanding, societal dialogue

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Authors: Jordan Chamarande, Lisiane Cunat, Corentine Alauzet, Catherine Cailliez-Grimal

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Gut microbiota (GM) is now considered a new organ mainly due to the microorganism’s specific biochemical interaction with its host. Although mechanisms underlying host-microbiota interactions are not fully described, it is now well-defined that cell surface molecules and structures of the GM play a key role in such relation. The study of surface structures of GM members is also fundamental for their role in the establishment of species in the versatile and competitive environment of the digestive tract and as a potential virulence factor. Among these structures are capsular polysaccharides (CPS), fimbriae, pili and lipopolysaccharides (LPS), all well-described for their central role in microorganism colonization and communication with host epithelium. The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and as a new potential biotherapeutic product. However, to the best of the authors’ knowledge, the cell surface molecules and structures of P. distasonis that allow its maintain within the GM are not identified. Moreover, although P. distasonis is strongly recognized as intestinal commensal species with benefits for its host, it has also been recognized as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of the capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-Typing classification in order to better understand and characterize the beneficial/pathogenic behaviour related to P. distasonis strains. In context, 2 different types of fimbriae, 3 of pilus and up to 14 capsular polysaccharide loci, have been identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-Type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed in P. distasonis adhesion capacities and its potential pathogenicity.

Keywords: gut microbiota, Parabacteroides distasonis, capsular polysaccharide, fimbriae, pilus, O-antigen, pathogenicity, probiotic, comparative genomics

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Authors: Diane M. Bender

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In design education, professional education is delivered in a studio, where students learn and understand their discipline. This learning methodology culminates in a final review, where students present their work before instructors and invited reviewers, known as jurors. These jurors are recognized experts who add a wide diversity of opinions in their feedback to students. This feedback can be provided in multiple formats, mainly a verbal critique of the work. To better understand how these expert reviewers prepare for a studio review, a survey was distributed to reviewers at a multi-disciplinary design school within the United States. Five design disciplines are involved in this case study: architecture, graphic design, industrial design, interior design, and landscape architecture. Respondents (n=122) provided information about if and how they received training on how to critique and participate in a final review. Common forms of training included mentorship, modeled behavior from other designers/past professors, workshops on critique from the instructing faculty prior to the crit session, and by being a practicing design professional. Respondents also gave feedback about how much the instructor provided course materials prior to the review in order to better prepare for student interaction. Finally, respondents indicated if they had interaction, and in what format, with students prior to the final review. Typical responses included participation in studio desk crits, a midterm jury member, meetings with students, and email or social media correspondence. While the focus of this study is the studio review, the findings are equally applicable to other disciplines. Suggestions will be provided on how to improve the preparation of guests in the learning process and how their interaction can positively influence student engagement.

Keywords: critique, design, education, evaluation, juror

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Authors: Justin D. Olmanson, Fitsum Abebe, Valerie Jones, Eric Kyle, Xianquan Liu, Katherine Robbins, Guieswende Rouamba

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The history of education technology--and designing, adapting, and adopting technologies for use in educational spaces--is nuanced, complex, and dynamic. Yet, despite a range of continually emerging technologies, the design and development process often yields results that appear quite similar in terms of affordances and interactions. Through this study we (1) verify the extent to which designs have been constrained, (2) consider what might account for it, and (3) offer a way forward in terms of how we might identify and strategically sidestep these influences--thereby increasing the diversity of our designs with a given technology or within a particular learning domain. We begin our inquiry from the perspective that a host of co-influencing elements, fields, and meta narratives converge on the education technology design process to exert a tangible, often homogenizing effect on the resultant designs. We identify several elements that influence design in often implicit or unquestioned ways (e.g. curriculum, learning theory, economics, learning context, pedagogy), we describe our methodology for identifying the elemental positionality embedded in a design, we direct our analysis to a particular subset of technologies in the field of literacy, and unpack our findings. Our early analysis suggests that the majority of education technologies designed for use/used in US public schools are heavily influenced by a handful of mainstream theories and meta narratives. These findings have implications for how we approach the education technology design process--which we use to suggest alternative methods for designing/ developing with emerging technologies. Our analytical process and re conceptualized design process hold the potential to diversify the ways emerging and established technologies get incorporated into our designs.

Keywords: curriculum, design, innovation, meta narratives

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Authors: Bella Japoshvili, Zhanetta Shubitidze, Ani Bikashvili, Sophio Gabelashvili, Marina Gioshvili, Levan Mumladze

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Paravani and Saghamo Lakes are oligotrophic lentic systems located in Javakheti plateau (South Georgia) at 2073 m and 1996 m a.s.l. respectively. Javakheti plateau is known as a lakes region as there are located almost 60 small and medium size lakes. Paravani Lake is the biggest lake by its surface area in Georgia, 37 km 2. The Saghamo Lake is smaller and its surface area consists 4.58 km2. These two lakes are connected with Paravani River, because of this the main hydrobiological and ichthyological features are the same. More than 15-30 years were not studied macroinvertebrates of these lakes. Even the existing information is lack and very limited. The aim of our study was to identify main macroinvertebrate groups inhabiting both lakes and to compare obtaining results to existing information. Our investigation was carried out during 2014 and 2015, in 3 seasons of the year, in winter because of severe condition samples were not taken. Kick-net and Petersen grab were used for material collecting, 4 sites from Paravani Lake and 3–from Saghamo Lake were sampled. Collected invertebrates were fixed in ethanol and late taken to the laboratory, where organisms were identified to the lowest taxon possible, usually family. By our results identified 14 taxa for Paravani Lake and 12 taxa for Saghamo Lake. Our results differ from previous information; for Saghamo Lake previously 13 taxa and for Paravani Lake 12 taxa were described. The percentage of the groups also differ from existing information. Our investigation showed that in Paravani Lake most abundant are Apmhipoda, Hydrachnidae, and Hemiptera, in our samples the number of individuals for those 3 taxa was more than thousand, in each. For Saghamo Lake numerous taxon was Amphipoda-36.3%, following by Ephemeroptera-11.37%, Chironomidae-10.5% and Hydrachnidae-7.03% respectively. We also identified the dominant taxon for all studied seasons. Autumn is the period when the diversity of macroinvertebrates are higher in both lakes.

Keywords: Georgia, lakes, macroinvertebrates, monitoring

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Authors: Li Yang, Yang Song, Martin Y. M. Chiang

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Objective: To experimentally substantiate the micromechanical compatibility between cell and scaffold, in the regenerative medicine approach for restoring bone volume, is essential for phenotypic transitions Methods: Through nanotechnology and electrospinning process, nanofibrous scaffolds were fabricated to host dental follicle stem cells (DFSCs). Blends (50:50) of polycaprolactone (PCL) and silk fibroin (SF), mixed with various content of cellulose nanocrystals (CNC, up to 5% in weight), were electrospun to prepare nanofibrous scaffolds with heterogeneous microstructure in terms of fiber size. Colloidal probe atomic force microscopy (AFM) and conventional uniaxial tensile tests measured the scaffold stiffness at the micro-and macro-scale, respectively. The cell elastic modulus and cell-scaffold adhesive interaction (i.e., a chemical function) were examined through single-cell force spectroscopy using AFM. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine if the mechanotransduction signal (i.e., Yap1, Wwr2, Rac1, MAPK8, Ptk2 and Wnt5a) is upregulated by the scaffold stiffness at the micro-scale (cellular scale). Results: The presence of CNC produces fibrous scaffolds with a bimodal distribution of fiber diameter. This structural heterogeneity, which is CNC-composition dependent, remarkably modulates the mechanical functionality of scaffolds at microscale and macroscale simultaneously, but not the chemical functionality (i.e., only a single material property is varied). In in vitro tests, the osteogenic differentiation and gene expression associated with mechano-sensitive cell markers correlate to the degree of micromechanical compatibility between DFSCs and the scaffold. Conclusion: Cells require compliant scaffolds to encourage energetically favorable interactions for mechanotransduction, which are converted into changes in cellular biochemistry to direct the phenotypic evolution. The micromechanical compatibility is indeed important to the efficacy of regenerative medicine.

Keywords: phenotype transition, scaffold stiffness, electrospinning, cellulose nanocrystals, single-cell force spectroscopy

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Authors: Sepideh Mohammadi

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Iran is a country that boasts of ethnic diversity, comprising various groups such as Turks, Lors, Arabs, Baluchs, Persians, Kurds, Gliks, Azaris, and Tabaris. The majority of people in Iran are Persians and as such, the Persian language is the official language of the country. However, it is also a common language among different ethnic groups. It is worth noting that there is a longstanding history of coexistence and cultural relations between the Turkic and Lor ethnic groups. The purpose of this article is to study the range of intercultural sensitivities of Turks and Lor peoples to identify the state of intercultural competence and reduce conflicts in the direction of cultural policy. It is important to gain insight into the mutual perceptions of Lor and Turkic people towards each other. Understanding these perceptions can greatly aid in fostering stronger relationships and promoting effective communication between the two ethnic groups. The study employed a qualitative content analysis approach to gather data using a semi-structured interview tool. The participants consisted of ten individuals from the Lor ethnic and ten individuals from the Turk ethnic. According to Milton Bennett's six-stage model, our findings reveal that the Turkish and Lor ethnic groups tend to exhibit higher intercultural sensitivity in the second stage, which consists of defense against differences. Both groups tend to emphasize the differences between them, and the notion of "us and the other" holds significant importance for them. It is important to acknowledge that both the Turk and Lor ethnicities consist of various clans, which significantly shape intercultural relations between them. A common stereotype in this regard is that the Turks of Tabriz province often do not recognize the Turks of other provinces of the country as their own. Moreover, our study indicates that an increase in interaction and communication between the Lor and Turk ethnic groups may lead to a reduction in cultural sensitivities between them.

Keywords: intercultural communication, intercultural sensitivity, Iran, Lor, Turk

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Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou

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The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.

Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms

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Authors: C. Flynn, Q. Yuan, C. Reinhardt

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting broad areas of the cerebral cortex and hippocampus. More than 95% of AD cases are representative of sporadic AD, where both genetic and environmental risk factors play a role. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tau tangles in the brain. The earliest brain pathology related to AD has been defined as hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons, characterized by Braak. However, the cause of this pathology and the ultimate progression of AD is not understood. Increasing research points to a connection between the gut microbiota and the brain, and mounting evidence has shown that there is a bidirectional interaction between the two, known as the gut-brain axis. This axis can allow for bidirectional movement of neuroinflammatory cytokines and pathogenic misfolded proteins, as seen in AD. Prebiotics and probiotics have been shown to have a beneficial effect on gut health and can strengthen the gut-barrier as well as the blood-brain barrier, preventing the spread of these pathogens across the gut-brain axis. Our laboratory has recently established a pretangle tau rat model, in which we selectively express pseudo-phosphorylated human tau (htauE14) in the LC neurons of TH-Cre rats. LC htauE14 produced pathological changes in rats resembling those of the preclinical AD pathology (reduced olfactory discrimination and LC degeneration). In this work, we will investigate the effects of pre/probiotic ingestion on AD behavioral deficits, blood inflammation/cytokines, and various brain markers in our experimental rat model of AD. Rats will be infused with an adeno-associated viral vector containing a human tau gene pseudophosphorylated at 14 sites (common in LC pretangles) into 2-3 month TH-Cre rats. Fecal and blood samples will be taken at pre-surgery, and various post-surgery time points. A collection of behavioral tests will be performed, and immunohistochemistry/western blotting techniques will be used to observe various biomarkers. This work aims to elucidate the relationship between gut health and AD progression by strengthening gut-brain relationship and aims to observe the overall effect on tau formation and tau pathology in AD brains.

Keywords: alzheimer’s disease, aging, gut microbiome, neurodegeneration

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Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: Eka Darbaidze

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Due to its important geopolitical location and strategic economic situation, the South Caucasus has been a region that has been a crossroads of interests between different states and empires since ancient times. Over the centuries, the forms of international relations with regard to the South Caucasus region have been constantly changing, however, the national interests of the Caucasian nations as well as the interests of the regional hegemonic powers in relation to the countries of the South Caucasus have remained almost unchanged. The conflict-ridden South Caucasus's attempt to create a new format of regional cooperation has a rather rich history, dating back to the collapse of the Soviet Union. However, despite the diversity of initiatives, they do not deviate from the format of political statements and it is natural that the case was never settled before their implementation, as none of the previous cooperation initiatives was able to reach all members of the region. The current regional co-operation platform is linked to the name of Turkish President Recep Tayyip Erdogan, who spoke out about the initiative during a visit to Azerbaijan. The so-called 3 + 3 platform for regional cooperation involves cooperation between three countries in the South Caucasus (Armenia, Azerbaijan and Georgia) and three "big neighbors" - Russia, Turkey and Iran. Very soon, the initiative received a positive response from the authorities of Azerbaijan, Iran and Armenia. According to them, this cooperation platform will strengthen cooperation between the countries involved in the regional platform and will focus on security, economic and transport issues. Our goal is to determine the interests of the main regional actors involved in the South Caucasus Cooperation Platform (3 + 3): Iran, Russia and Turkey. Our goal is also to determine what threats, risks or benefits may be associated with the involvement of the three countries of the South Caucasus: Azerbaijan, Armenia and Georgia in this platform and what will be the consequences for Georgia, whose 20% of its internationally recognized borders are still occupied by Russia and whose territory is still under creeping occupation.

Keywords: South Caucasus, Georgia's interest, the interests of Iran, the interests of Turkey, Russian interests, Georgia's occupation

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Authors: Lydia Foucan, Laurent Larifla, Emmanuelle Durand, Christine Rambhojan, Veronique Dhennin, Jean-Marc Lacorte, Philippe Froguel, Amelie Bonnefond

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In the population of Guadeloupe Island (472,124 inhabitants and 80% of subjects of African descent), overweight and obesity were estimated at 23% and 9% respectively among children. High prevalence of diabetes has been reported (~10%) in the adult population. Nevertheless, no study has investigated the contribution of gene mutations to childhood obesity in this population. We aimed to investigate rare genetic mutations in genes involved in monogenic obesity or diabetes in obese Afro-Caribbean children from Guadeloupe Island using next-generation sequencing. The present investigation included unrelated obese children, from a previous study on overweight conducted in Guadeloupe Island in 2013. We sequenced coding regions of 59 genes involved in monogenic obesity or diabetes. A total of 25 obese schoolchildren (with Z-score of body mass index [BMI]: 2.0 to 2.8) were screened for rare mutations (non-synonymous, splice-site, or insertion/deletion) in 59 genes. Mean age of the study population was 12.4 ± 1.1 years. Seventeen children (68%) had insulin-resistance (HOMA-IR > 3.16). A family history of obesity (mother or father) was observed in eight children and three of the accompanying parent presented with type 2 diabetes. None of the children had gonadotrophic abnormality or mental retardation. We detected five rare heterozygous mutations, in four genes involved in monogenic obesity, in five different obese children: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations which were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations which were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutation in ABCC8 or KCNJ11 (involved in monogenic diabetes), which were of uncertain significance (KCNJ11 p.Val13Met, KCNJ11 p.Val151Met, ABCC8 p.Lys1521Asn and ABCC8 p.Ala625Val). Rare pathogenic or likely pathogenic mutations, linked to severe obesity were detected in more than 15% of this Afro-Caribbean population at high risk of obesity and type 2 diabetes.

Keywords: childhood obesity, MC4R, monogenic obesity, SIM1

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Authors: Nouzha Yasmina Soulimane-Benhabib

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Language is a medium of communication and a means of expression that is why today the learning of foreign languages especially the English language has become a basic necessity for every student who is ambitious. It is known that culture and language are inseparable and complementary, however, in the process of teaching a foreign language, teachers used to focus mainly on preparing adequate syllabi for ESP students, yet, some parameters should be considered. For instance; the culture of the target language may play an important role since students attitudes towards a foreign language enhance their learning or vice versa. The aim of this study is to analyse how culture could influence the teaching of a foreign language, we have taken the example of the English language as it is considered as the second foreign language in Algeria after French. The study is conducted at the Preparatory School of Sciences and Techniques, Tlemcen where twenty-five students participated in this research. The reasons behind learning the English language are various, and since English is the most widely-spoken language in the world, it is the language of research and education and it is used in many other fields, we have to take into consideration one important factor which is the social distance between the culture of the Algerian learner and the culture of the target language, this gap may lead to a culture shock. Two steps are followed in this research: The first one is to collect data from those students who are studying at the Preparatory School under the form of questionnaire and an interview is submitted to six of them in order to reinforce our research and get effective and precise results, and the second step is to analyse these data taking into consideration the diversity of the learners within this institution. The results obtained show that learners’ attitudes towards the English community and culture are mixed and it may influence their curiosity and attention to learn. Despite of big variance between Algerian and European cultures, some of the students focused mainly on the benefits of the English language since they need it in their studies, research and a future carrier, however, the others manifest their reluctance towards this language and this is mainly due to the profound impact of the English culture which is different from the Algerian one.

Keywords: Algeria, culture, English, impact

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Authors: Thobela Conco, Sheena Kumari, Chika Nnadozie, Mahmoud Nasr, Thor A. Stenström, Mushal Ali, Arshad Ismail, Faizal Bux

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The discharge of antibiotics and its residues into the wastewater treatment plants (WWTP’s) create a conducive environment for the development of antibiotic resistant pathogens. This presents a risk of potential dissemination of antibiotic resistant pathogens and antibiotic resistance genes into the environment. It is, therefore, necessary to study the level of antibiotic resistance genes (ARG’s) among bacterial pathogens that proliferate in biological wastewater treatment systems. In the current study, metagenomic and meta-transcriptomic sequences of samples collected from the influents, secondary effluents and post chlorinated effluents of three wastewater treatment plants treating domestic and hospital effluents in Durban, South Africa, were analyzed for profiling of ARG’s among bacterial pathogens. Results show that a variety of ARG’s, mostly, aminoglycoside, β-lactamases, tetracycline and sulfonamide resistance genes were harbored by diverse bacterial genera found at different stages of treatment. A significant variation in diversity of pathogen and ARGs between the treatment plant was observed; however, treated final effluent samples from all three plants showed a significant reduction in bacterial pathogens and detected ARG’s. Both pre- and post-chlorinated samples showed the presence of mobile genetic elements (MGE’s), indicating the inefficiency of chlorination to remove of ARG’s integrated with MGE’s. In conclusion, the study showed the wastewater treatment plant efficiently caused the reduction and removal of certain ARG’s, even though the initial focus was the removal of biological nutrients.

Keywords: antibiotic resistance, mobile genetic elements, wastewater, wastewater treatment plants

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Authors: P. S. Dhananjaya Swamy, B. Chinnappa, G. B. Ramesh, Naveen P. Kumar

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Kodagu district is one of the most densely forested districts in the India as around sixty five per cent of geographical areas under tree cover. Nearly 53 per cent of the flora of Kodagu is endemic. The district is also a hotspot of endemic orchids found mainly in the Thadiandamol. Shade grown, eco-friendly coffee farms are perhaps a selected few places on this planet where nature runs wild. The Kodagu accounts for more than 8.8 per cent of floral diversity of Karnataka state. Estimation of unit cost of cultivation plays a vital role in determining the governmental program their market intervention policies. On an average, planters incurred around Rs. 17041 per acre. The extent of production risk was highest among small category of planters (66 %) compared to other two exhibiting production instability. The result shows that, the coffee productivity in medium plantations was 1051.2 kg per acre as against 758.5 and 789.2 kg in the case of small and large plantations. An annual net return per acre was highest in the case of medium planters (Rs. 26109.3) as against Rs. 20566.7 and Rs. 18572.7 in the case of small and large planters. Cost of production was lowest in the case of small planters (Rs. 18.9 per kg of output) followed by medium planters (Rs. 21.2 per kg of output) and large planters (Rs. 22.5 per kg of output). The productivity of coffee is less whenever it is grown under high shade and native tree cover; it is around 6 quintals per acre when compared with low shade conditions, which is around 8.9 quintals per acre, without a significant difference in the amount invested for growing coffee. Net gain was lower by Rs. 15.5 per kg for the planters growing under high shade and native trees cover when compared with low shade and exotic trees cover.

Keywords: coffee, cultivation, economics, Kodagu

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Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn

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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.

Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins

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Authors: Mark Bezner, Shani Deri, Tom Trigano, Kfir Ben-Harush

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Intermediate filament (IF) proteins-based fibers are among the toughest fibers in nature, as was shown by native hagfish slime threads and by synthetic fibers that are based on type V IF-proteins, the nuclear lamins. It is assumed that their mechanical performance stems from two major factors: (1) the transition from elastic -helices to stiff-sheets during tensile load; and (2) the specific organization of the coiled-coil proteins into a hierarchical network of nano-filaments. Here, we investigated the interrelationship between these two factors by using wet-spun fibers based on C. elegans (Ce) lamin. We found that Ce-lamin fibers, whether assembled in aqueous or alcoholic solutions, had the same nonlinear mechanical behavior, with the elastic region ending at ~5%. The pattern of the transition was, however, different: the ratio between -helices and -sheets/random coils was relatively constant until a 20% strain for fibers assembled in an aqueous solution, whereas for fibers assembled in 70% ethanol, the transition ended at a 6% strain. This structural phenomenon in alcoholic solution probably occurred through the transition between compacted and extended conformation of the random coil, and not between -helix and -sheets, as cycle analyses had suggested. The different transition pattern can also be explained by the different higher order organization of Ce-lamins in aqueous or alcoholic solutions, as demonstrated by introducing a point mutation in conserved residue in Ce-lamin gene that alter the structure of the Ce-lamins’ nano-fibrils. In addition, biomimicking the layered structure of silk and hair fibers by coating the Ce-lamin fiber with a hydrophobic layer enhanced fiber toughness and lead to a reversible transition between -helix and the extended conformation. This work suggests that different hierarchical structures, which are formed by specific assembly conditions, lead to diverse secondary structure transitions patterns, which in turn affect the fibers’ mechanical properties.

Keywords: protein-based fibers, intermediate filaments (IF) assembly, toughness, structure-property relationships

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Authors: Fouzia Ajmal

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Global Citizenship Education (GCED) could prove to be the best solution to prevent violent extremism as it will sustain a respect for all and build up a feeling of having a place with humankind. To meet the target 4.7 of sustainable development goals, it is important to focus on global citizenship education at all levels of education in general and in pre-service teacher education in particular so that the message and practices reach the young masses. The pre-service education is imperative to develop knowledge, skills and disposition of prospective teachers. The current study was conducted to investigate the integration of GCED in pre-service teacher education curriculum of Pakistan. The study was delimited to B.Ed (hons) Elementary Education programme. The curriculum of B.Ed Elementary developed by Higher Education Commission was analyzed through Curriculum Alignment Matrix. 31 course outlines were analyzed, and percentage was used to analyze the level of integration of GCED in courses. The analyses depicted that the concepts of civic sense, tolerance, duties and rights of citizens and fundamental rights of humans are partially aligned in a few of the courses. The tolerance, active citizenship, and respect for cultural diversity and religious harmony are evident in Pakistan Studies and teaching of social studies courses. The relevant books are also mentioned as resources in these courses. The intercultural understanding is not very evident while globalization is mentioned in a few courses. It is recommended that a deliberate effort may be made to integrate concepts of Global Citizenship Education so as to enable the prospective teachers in developing necessary skills to play their active role in promoting peace and building resilience to extremism in elementary school students.

Keywords: curriculum analysis, global citizenship education, preservice teacher education, resilience building

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Authors: Pelin Balcik Ercin

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Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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Authors: Vibhore Bakshi

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This research paper is a step towards understanding the role of governance in the plan preparation process. It addresses the complexities of the peri-urban, historical constructions, politics and policies of sustainability, and legislative frameworks. The paper reflects on the Delhi NCT as one of the classical cases that have happened to witness different structural changes in the master plan around 1981, 2001, 2021, and Proposed Draft 2041. The Delhi Landsat imageries for 1989 and 2018 show an increase in the built-up areas around the periphery of NCT. The peri-urbanization has been a result of increasing in-migration to peri–urban areas of Delhi. The built-up extraction for years 1981, 1991, 2001, 2011, and 2018 highlights the growing peri-urbanization on scarce land therefore, it becomes equally important to research the history of the land and its legislative measures. It is interesting to understand the streaks of changes that have occurred in the land of Delhi in accordance with the different master plans and land legislative policies. The process of masterplan process in Delhi has experienced a lot of complexities in juxtaposition to other metropolitan regions of the world. The paper identifies the shortcomings in the current master planning process approach in regard to the stage of the planning process, traditional planning approach, and lagging ICT-based interventions. The metropolitan governance systems across the globe and India depict diversity in the organizational setup and varied dissemination of functions. It addresses the complexity of the peri-urban, historical constructions, politics and policies of sustainability, and legislative frameworks.

Keywords: governance, land provisions, built-up areas, in migration, built up extraction, master planning process, legislative policies, metropolitan governance systems

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Authors: Asma Inge-Hanif, Ayyub Ansari Hanif

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The impact of conflicts, the subsequent refugee migration to America and their attempted use of societal resources implicate the lack of further humanitarian aid as a consequence of the abrupt decrease in services and policy changes stemming from new governmental mandates and Executive Orders. Statistical research data indicates a substantial decline in access to standardized health services by refugee women creating a significant alteration in the management of their maternal health care in America, previously shown to result in decreased mortality and morbidity. Studying nursing at Howard University in Washington, D.C., observed doctors were not always sensitive to the needs and modesty concerns of immigrant Muslim women - often unintentionally. Among health care professionals, the prevailing belief should be that every man, woman and child has the right to quality care in a dignified manner and the achievement of optimal health and well-being, regardless of race, creed, socio-economic level or status. In 1987 Muslimat Al Nisaa Health and Social Services Center was established to care for underserved and uninsured women and children. This Center, plus the subsequent shelter, provided direct access to those homeless, refugees, human trafficking and women victims of domestic violence was established and provides the data for this study. Understanding specific culture, social, economic and religious nuances respects their diversity and addressing their basic human needs that they achieve optimal success. The ultimate goal being to facilitate the rescue and housing of those whom escaped from a country/communities where girls are devalued, brought, sold and abused.

Keywords: women, refugee, domestic violence, health care

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Authors: Shreya Borthakur, Adhar Sharma

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The North-east states of India are well known for their age-old practice of preparing alcoholic beer from rice and millet. They do so in a traditional way by sprinkling starter cake (inoculum) on cooked rice or millet after which the fermentation starts and eventually, forms the beer. This starter cake has a rich composition of different microbes and medicinal herbs along with the powdered rice dough or maize dough with rice bran. The starter cake microbial composition has an important role in determining the microbial succession and metabolic secretions as the fermentation proceeds from the early to its late stage, thus, giving the beer a unique aroma, taste, and other sensory properties of traditionally prepared beer. Here, We have worked on identifying and characterizing the microbial community in the starter cakes prepared by the Monpa and Galo tribes of Arunachal Pradesh. A total of 18 microbial strains have been isolated from the starter cake of Monpa tribe, while 10 microbial isolates in that of Galo tribe. A metagenomic approach was applied to enumerate the cultural and non-cultural microbes present in the starter cakes prepared by the Monpa and Galo tribes of Arunachal Pradesh. The findings of the mini-project lays foundation to understand the role of microbes present in the starter cake in the beer’s fermentation process and will aide in future research on re-formulating the starter cakes to prevent the early spoilage of the ready to consume beer as the traditional rice beer has a short shelf-life. The paper concludes with the way forward being controlled CRISPR-Cas9.

Keywords: fermentation, traditional beer, microbial succession, preservation, CRISPR-Cas, food microbiology

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Authors: Easa Almustanyir

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This study investigates the linguistic and thematic approach of translator Abdullah Khrief in the context of video translations on the X platform. The sample comprises 15 videos from Khrief's account, covering diverse content categories like science, religion, social issues, personal experiences, lifestyle, and culture. The analysis focuses on two aspects: language usage and thematic representation. Regarding language, the study examines the prevalence of English while considering the inclusion of French and German content, highlighting Khrief's multilingual versatility and ability to navigate cultural nuances. Thematically, the study explores the diverse range of topics covered, encompassing scientific, religious, social, and personal narratives, underscoring Khrief's broad subject matter expertise and commitment to knowledge dissemination. The study employs a mixed-methods approach, combining quantitative data analysis with qualitative content analysis. Statistical data on video languages, presenter genders, and content categories are analyzed, and a thorough content analysis assesses translation accuracy, cultural appropriateness, and overall quality. Preliminary findings indicate a high level of professionalism and expertise in Khrief's translations. The absence of errors across the diverse range of videos establishes his credibility and trustworthiness. Furthermore, the accurate representation of cultural nuances and sensitive topics highlights Khrief's cultural sensitivity and commitment to preserving intended meanings and emotional resonance.

Keywords: audiovisual translation, linguistic versatility, thematic diversity, cultural sensitivity, content analysis, mixed-methods approach

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Authors: Dimakatso B. Gumede, Nicolette N. Houreld

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Diabetic foot ulcers (DFUs) are a complication of diabetes mellitus (DM), a metabolic disease caused by insulin resistance or insufficiency, resulting in hyperglycaemia and low-grade chronic inflammation. Current therapies for treating DFUs include wound debridement, glycaemic control, and wound dressing. However, these therapies are moderately effective as there is a recurrence of these ulcers and an increased risk of lower limb amputations. Photobiomodulation (PBM), which is the application of non-invasive low-level light for wound healing at the spectrum of 660-1000 nm, has shown great promise in accelerating the healing of chronic wounds. However, its underlying mechanisms are not clearly defined. Studies have indicated that PBM induces wound healing via the activation of signaling pathways that are involved in tissue repair, such as the transforming growth factor-β (TGF-β). However, other signaling pathways, such as the WNT/β-catenin pathway, which is also critical for wound repair, have not been investigated. This study aimed to elucidate if PBM at 660 nm and a fluence of 5 J/cm² activates the WNT/β-catenin signaling pathway for wound healing in a diabetic cellular model. Human dermal fibroblasts (WS1) were continuously cultured high-glucose (26.5 mM D-glucose) environment to create a diabetic cellular model. A central scratch was created in the diabetic model to ‘wound’ the cells. The diabetic wounded (DW) cells were thereafter irradiated at 660 nm and a fluence of 5 J/cm². Cell migration, gene expression and protein assays were conducted at 24- and 48-h post-PBM. The results showed that PBM at 660 nm and a fluence of 5 J/cm² significantly increased cell migration in diabetic wounded cells at 24-h post-PBM. The expression of CTNNB1, ACTA2, COL1A1 and COL3A1 genes was also increased in DW cells post-PBM. Furthermore, there was increased cytoplasmic accumulation and nuclear localization of β-catenin at 24 h post-PBM. The findings in this study demonstrate that PBM activates the WNT/β-catenin signaling pathway by inducing the accumulation of β-catenin in diabetic wounded cells, leading to increased cell migration and expression of wound repair markers. These results thus indicate that PBM has the potential to improve wound healing in diabetic ulcers via activation of the WNT/β-catenin signaling pathway.

Keywords: wound healing, diabetic ulcers, photobiomodulation, WNT/β-catenin, signalling pathway

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Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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