Search results for: non proliferation

Authors: Miraji H. Mohamed

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The purpose of this study is to critique ‘radicalisation’ and more particularly ‘youth radicalisation’ by exploring its usage in online newspapers. ‘Radicalisation’ and ‘extremism’ have become the most common terms in terrorism studies since the 9/11 attacks. Regardless of the geographic location, when the word terrorism is used the terms ‘radicalisation’ and ‘extremism’ always follow to attempt to explore the journey of the perpetrators towards violence. These terms have come to represent a discourse of dominantly pejorative traits often used to describe spaces, groups, and processes identified as problematic. Even though ambiguously defined they feature widely in government documents, political statements, news articles, academic research, social media platforms, religious gatherings, and public discussions. Notably, ‘radicalisation’ and ‘extremism’ have been closely conflated with the term youth to form ‘youth radicalisation’ to refer to a discourse of ‘youth at risk’. The three terms largely continue to be used unquestioningly and interchangeably hence the reason why they are placed in single quotation marks to deliberately question their conventional usage. Albeit this comes timely in the Kenyan context where there has been a proliferation of academic and expert research on ‘youth radicalisation’ (used as a neutral label) without considering the political, cultural and socio-historical contexts that inform this label. This study seeks to draw these nuances by employing a genealogical approach that historicises and deconstructs ‘youth radicalisation’; and by applying a Discourse-Historical Approach (DHA) of Critical Discourse Analysis to analyse Kenyan online newspaper - The Daily Nation between 2015 and 2018. By applying the concept of representation to analyse written texts, the study reveals that the use of ‘youth radicalisation’ as a discursive strategy disproportionately affects young people especially those from cultural/ethnic/religious minority groups. Also, the ambiguous use of ‘radicalisation’ and ‘youth radicalisation’ by the media reinforces the discourse of ‘youth at risk’ which has become the major framework underpinning Countering Violent Extremism (CVE) interventions. Similarly, the findings indicate that the uncritical use of ‘youth radicalisation’ has been used to serve political interests; and has become an instrument of policing young people, thus contributing to their cultural shaping. From this, it is evident that the media could thwart rather than assist CVE efforts. By exposing the political nature of the three terms through evidence-based research, this study offers recommendations on how critical reflective reporting by the media could help to make CVE more nuanced.

Keywords: discourse, extremism, radicalisation, terrorism, youth

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Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Christoph Hacker, Zeynep Karahaliloglu, Gunnar Seide, Emir Baki Denkbas, Thomas Gries

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A wound dressing material is designed to facilitate wound healing and minimize scarring. An ideal wound dressing material should protect the wound from any contaminations of exogeneous microorganism. In addition, the dressing material should provide a moist environment through extraction of body fluid from the wound area. Recently, wound dressing electrospun nanofibrous membranes are produced by electrospinning from a polymer solution or a polymer melt. These materials have a great potential as dressing materials for wound healing because of superior properties such as high surface-to-volume ratio, high porosity with excellent pore interconnectivity. Melt electrospinning is an attractive tissue engineering scaffold manufacturing process which eliminated the health risk posed by organic solvents used in electrospinning process and reduced the production costs. In this study, antibacterial wound dressing materials were prepared from TPU (Elastollan 1185A) by a melt-electrospinning technique. The electrospinning parameters for an efficient melt-electrospinning process of TPU were optimized. The surface of the fibers was modified with poly(ethylene glycol) (PEG) by radio-frequency glow discharge plasma deposition method and with silver nanoparticles (nAg) to improve their wettability and antimicrobial properties. TPU melt-electrospun mats were characterized using SEM, DSC, TGA and XPS. The cell viability and proliferation on modified melt-electrospun TPU mats were evaluated using a mouse fibroblast cell line (L929). Antibacterial effects of theirs against both Staphylococcus aureus strain and Escherichia coli were investigated by disk-diffusion method. TPU was successfully processed into a porous, fibrous network of beadless fibers in the micrometer range (4.896±0.94 µm) with a voltage of 50 kV, a working distance of 6 cm, a temperature of the thermocouple and hot coil of 225–230ºC, and a flow rate of 0.1 mL/h. The antibacterial test indicated that PEG-modified nAg-loaded TPU melt-electrospun structure had excellent antibacterial effects and cell study results demonstrated that nAg-loaded TPU mats had no cytotoxic effect on the fibroblast cells. In this work, the surface of a melt-electrospun TPU mats was modified via PEG monomer and then nAg. Results showed melt-electrospun TPU mats modified with PEG and nAg have a great potential for use as an antibacterial wound dressing material and thus, requires further investigation.

Keywords: melt electrospinning, nanofiber, silver nanoparticles, wound dressing

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Authors: Bryan Clark B. Hernandez, Eugene C. Herrera, Kazuo Nadaoka

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Mangrove forests thriving in intertidal zones in tropical and subtropical regions of the world offer a range of ecosystem services including carbon storage and sequestration. They can regulate the detrimental effects of climate change due to carbon releases two to four times greater than that of mature tropical rainforests. Moreover, they are effective natural defenses against storm surges and tsunamis. However, their proliferation depends significantly on the prevailing hydroperiod at the coast. In the Philippines, these coastal ecosystems have been severely threatened with a 50% decline in areal extent observed from 1918 to 2010. The highest decline occurred in 1950 - 1972 when national policies encouraged the development of fisheries and aquaculture. With the intensive land use conversion upstream, changes in the freshwater-saltwater envelope at the coast may considerably impact mangrove growth conditions. This study investigates a developing urban watershed in Kalibo, Aklan province with a 220-hectare mangrove forest replanted for over 30 years from coastal mudflats. Since then, the mangrove forest was sustainably conserved and declared as protected areas. Hybrid land cover classification technique was used to classify Landsat images for years, 1990, 2010, and 2017. Digital elevation model utilized was Interferometric Synthetic Aperture Radar (IFSAR) with a 5-meter resolution to delineate the watersheds. Using numerical modelling techniques, the hydrologic and hydraulic analysis of the influence of land cover change to flow and sediment dynamics was simulated. While significant land cover change occurred upland, thereby increasing runoff and sediment loads, the mangrove forests abundance adjacent to the coasts for the urban watershed, was somehow sustained. However, significant alteration of the coastline was observed in Kalibo through the years, probably due to the massive land-use conversion upstream and significant replanting of mangroves downstream. Understanding the hydrologic-hydraulic response of these watersheds to change land cover is essential to helping local government and stakeholders facilitate better management of these mangrove ecosystems.

Keywords: coastal mangroves, hydrologic model, land cover change, Philippines

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Authors: Diana Islam, Juan Fang, Vito Fanelli, Bing Han, Julie Khang, Jianfeng Wu, Arthur S. Slutsky, Haibo Zhang

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Introduction: MSC delivery in preclinical models of ARDS has demonstrated significant improvements in lung function and recovery from acute injury. However, the role of MSC delivery in ARDS associated pulmonary fibrosis is not well understood. Some animal studies using bleomycin, asbestos, and silica-induced pulmonary fibrosis show that MSC delivery can suppress fibrosis. While other animal studies using radiation induced pulmonary fibrosis, liver, and kidney fibrosis models show that MSC delivery can contribute to fibrosis. Hypothesis: The beneficial and deleterious effects of MSC in ARDS are modulated by the lung microenvironment at the time of MSC delivery. Methods: To induce ARDS a two-hit mouse model of Hydrochloric acid (HCl) aspiration (day 0) and mechanical ventilation (MV) (day 2) was used. HCl and injurious MV generated fibrosis within 14-28 days. 0.5x106 mouse MSCs were delivered (via both intratracheal and intravenous routes) either in the active inflammatory phase (day 2) or during the remodeling phase (day 14) of ARDS (mouse fibroblasts or PBS used as a control). Lung injury accessed using inflammation score and elastance measurement. Pulmonary fibrosis was accessed using histological score, tissue collagen level, and collagen expression. In addition alveolar epithelial (E) and mesenchymal (M) marker expression profile was also measured. All measurements were taken at day 2, 14, and 28. Results: MSC delivery 2 days after HCl exacerbated lung injury and fibrosis compared to HCl alone, while the day 14 delivery showed protective effects. However in the absence of HCl, MSC significantly reduced the injurious MV-induced fibrosis. HCl injury suppressed E markers and up-regulated M markers. MSC delivery 2 days after HCl further amplified M marker expression, indicating their role in myofibroblast proliferation/activation. While with 14-day delivery E marker up-regulation was observed indicating their role in epithelial restoration. Conclusions: Early MSC delivery can be protective of injurious MV. Late MSC delivery during repair phase may also aid in recovery. However, early MSC delivery during the exudative inflammatory phase of HCl-induced ARDS can result in pro-fibrotic profiles. It is critical to understand the interaction between MSC and the lung microenvironment before MSC-based therapies are utilized for ARDS.

Keywords: acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC), hydrochloric acid (HCl), mechanical ventilation (MV)

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Authors: Amira E. Derbalah, Doaa M. Zaghloul

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10 clinically healthy hemal nodes were collected from male bulls aged 2-3 years. Light microscopy revealed a capsule of connective tissue consisted mainly of collagen fiber surrounding hemal node, numerous erythrocytes were found in wide subcapsular sinus under the capsule. The parenchyma of the hemal node was divided into cortex and medulla. Diffused lymphocytes, and lymphoid follicles, having germinal centers were the main components of the cortex, while in the medulla there was wide medullary sinus, diffused lymphocytes and few lymphoid nodules. The area occupied with lymph nodules was larger than that occupied with non-nodular structure of lymphoid cords and blood sinusoids. Electron microscopy revealed the cellular components of hemal node including elements of circulating erythrocytes intermingled with lymphocytes, plasma cells, mast cells, reticular cells, macrophages, megakaryocytes and endothelial cells lining the blood sinuses. The lymphocytes were somewhat triangular in shape with cytoplasmic processes extending between adjacent erythrocytes. Nuclei were triangular to oval in shape, lightly stained with clear nuclear membrane indentation and clear nucleoli. The reticular cells were elongated in shape with cytoplasmic processes extending between adjacent lymphocytes, rough endoplasmic reticulum, ribosomes and few lysosomes were seen in their cytoplasm. Nucleus was elongated in shape with less condensed chromatin. Plasma cells were oval to irregular in shape with numerous dilated rough endoplasmic reticulum containing electron lucent material occupying the whole cytoplasm and few mitochondria were found. Nuclei were centrally located and oval in shape with heterochromatin emarginated and often clumped near the nuclear membrane. Occasionally megakaryocytes and mast cells were seen among lymphocytes. Megakaryocytes had multilobulated nucleus and free ribosomes often appearing as small aggregates in their cytoplasm, while mast cell had their characteristic electron dense granule in the cytoplasm, few electron lucent granules were found also, we conclude that, the main function of the hemal node of cattle is proliferation of lymphocytes. No role for plasma cell in erythrophagocytosis could be suggested.

Keywords: cattle, electron microscopy, hemal node, histology, immune system

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Authors: Sudip Mondal, Biswanath Mondal, Sudit S. Mukhopadhyay, Apurba Dey

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Bioactive materials improve devices for a long lifespan but have mechanical limitations. Mechanical characterization is one of the very important characteristics to evaluate the life span and functionality of the scaffold material. After implantation of scaffold material the primary stage rejection of scaffold occurs due to non biocompatible effect of host body system. The second major problems occur due to the effect of mechanical failure. The mechanical and biocompatibility failure of the scaffold materials can be overcome by the prior evaluation of the scaffold materials. In this study chemically treated Labeo rohita scale is used for synthesizing hydroxyapatite (HAp) biomaterial. Thermo-gravimetric and differential thermal analysis (TG-DTA) is carried out to ensure thermal stability. The chemical composition and bond structures of wet ball-milled calcined HAp powder is characterized by Fourier Transform Infrared spectroscopy (FTIR), X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray (EDX) analysis. Fish scale derived apatite materials consists of nano-sized particles with Ca/P ratio of 1.71. The biocompatibility through cytotoxicity evaluation and MTT assay are carried out in MG63 osteoblast cell lines. In the cell attachment study, the cells are tightly attached with HAp scaffolds developed in the laboratory. The result clearly suggests that HAp material synthesized in this study do not have any cytotoxic effect, as well as it has a natural binding affinity for mammalian cell lines. The synthesized HAp powder further successfully used to develop porous scaffold material with suitable mechanical property of ~0.8GPa compressive stress, ~1.10 GPa a hardness and ~ 30-35% porosity which is acceptable for implantation in trauma region for animal model. The histological analysis also supports the bio-affinity of processed HAp biomaterials in Wistar rat model for investigating the contact reaction and stability at the artificial or natural prosthesis interface for biomedical function. This study suggests the natural sourced fish scale-derived HAp material could be used as a suitable alternative biomaterial for tissue engineering application in near future.

Keywords: biomaterials, hydroxyapatite, scaffold, mechanical property, tissue engineering

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Authors: Azieva A. M., Yastremsky E. V., Kirillova D. A., Patsaev T. D., Sharikov R. V., Kamyshinsky R. A., Lukanina K. I., Sharikova N. A., Grigoriev T. E., Vasiliev A. L.

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Adhesive properties of scaffolds, which predominantly depend on the chemical and structural features of their surface, play the most important role in tissue engineering. The basic requirements for such scaffolds are biocompatibility, biodegradation, high cell adhesion, which promotes cell proliferation and differentiation. In many cases, synthetic polymers scaffolds have proven advantageous because they are easy to shape, they are tough, and they have high tensile properties. The regeneration of nerve tissue still remains a big challenge for medicine, and neural stem cells provide promising therapeutic potential for cell replacement therapy. However, experiments with stem cells have their limitations, such as low level of cell viability and poor control of cell differentiation. Whereas the study of already differentiated neuronal cell culture obtained from newborn mouse brain is limited only to cell adhesion. The growth and implantation of neuronal culture requires proper scaffolds. Moreover, the polymer scaffolds implants with neuronal cells could demand specific morphology. To date, it has been proposed to use numerous synthetic polymers for these purposes, including polystyrene, polylactic acid (PLA), polyglycolic acid, and polylactide-glycolic acid. Tissue regeneration experiments demonstrated good biocompatibility of PLA scaffolds, despite the hydrophobic nature of the compound. Problem with poor wettability of the PLA scaffold surface could be overcome in several ways: the surface can be pre-treated by poly-D-lysine or polyethyleneimine peptides; roughness and hydrophilicity of PLA surface could be increased by plasma treatment, or PLA could be combined with natural fibers, such as collagen or chitosan. This work presents a study of adhesion of both induced pluripotent stem cells (iPSCs) and mouse primary neuronal cell culture on the polylactide scaffolds of various types: oriented and non-oriented fibrous nonwoven materials and sponges – with and without the effect of plasma treatment and composites with collagen and chitosan. To evaluate the effect of different types of PLA scaffolds on the neuronal differentiation of iPSCs, we assess the expression of NeuN in differentiated cells through immunostaining. iPSCs more effectively differentiate into neurons on PLA scaffolds with high adhesive properties for primary neuronal cells.

Keywords: PLA scaffold, neurons, neuronal differentiation, stem cells, polylactid

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Authors: Raghuram Kandimalla, Sanjeeb Kalita, Bhaswati Choudhury, Jibon Kotoky

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The quest for developing an ideal suture material prompted our interest to develop a novel suture with advantageous characteristics to market available ones. We developed novel suture biomaterial from muga silk (Antheraea assama) and ramie (Boehmeria nivea) plant fiber. Field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR) and thermo gravimetric analysis (TGA) results revealed the physicochemical properties of the fibers which supports the suitability of fibers for suture fabrication. Tensile properties of the prepared sutures were comparable with market available sutures and it found to be biocompatible towards human erythrocytes and nontoxic to mammalian cells. The prepared sutures completely healed the superficial deep wound incisions within seven days in adult male wister rats leaving no rash and scar. Histopathology studies supports the wound healing ability of sutures, as rapid synthesis of collagen, connective tissue and other skin adnexal structures were observed within seven days of surgery. Further muga suture surface modified by exposing the suture to oxygen plasma which resulted in formation of nanotopography on suture surface. Broad spectrum antibiotic amoxicillin was functionalized on the suture surface to prepare an advanced antimicrobial muga suture. Surface hydrophilicity induced by oxygen plasma results in an increase in drug-impregnation efficiency of modified muga suture by 16.7%. In vitro drug release profiles showed continuous and prolonged release of amoxicillin from suture up to 336 hours. The advanced muga suture proves to be effective against growth inhibition of Staphylococcus aureus and Escherichia coli, whereas normal muga suture offers no antibacterial activity against both types of bacteria. In vivo histopathology studies and colony-forming unit count data revealed accelerated wound healing activity of advanced suture over normal one through rapid synthesis and proliferation of collagen, hair follicle and connective tissues.

Keywords: sutures, biomaterials, silk, Ramie

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Authors: Abir O. El Sadik

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Introduction: Wound healing involves the interaction of multiple biological processes among different types of cells, intercellular matrix and specific signaling factors producing enhancement of cell proliferation of the epidermis over dermal granulation tissue. Several studies investigated multiple strategies to promote wound healing and to minimize infection and fluid losses. However, burn crisis, and its related morbidity and mortality are still elevated. The aim of the present study was to examine the effects of mesenchymal stem cells (MSCs) in accelerating wound healing and to compare the most efficient route of administration of MSCs, either intradermal or systemic injection, with focusing on the mechanisms producing epidermal and dermal cell regeneration. Material and methods: Forty-two adult male Sprague Dawley albino rats were divided into three equal groups (fourteen rats in each group): control group (group I); full thickness surgical skin wound model, Group II: Wound treated with systemic injection of MSCs and Group III: Wound treated with intradermal injection of MSCs. The healing ulcer was examined on day 2, 6, 10 and 15 for gross morphological evaluation and on day 10 and 15 for fluorescent, histological and immunohistochemical studies. Results: The wounds of the control group did not reach complete closure up to the end of the experiment. In MSCs treated groups, better and faster healing of wounds were detected more than the control group. Moreover, the intradermal route of administration of stem cells increased the rate of healing of the wounds more than the systemic injection. In addition, the wounds were found completely healed by the end of the fifteenth day of the experiment in all rats of the group injected intradermally. Microscopically, the wound areas of group III were hardly distinguished from the adjacent normal skin with complete regeneration of all skin layers; epidermis, dermis, hypodermis and underlying muscle layer. Fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas surrounded by different arrangement of collagen fibers with a significant increase in their area percent were recorded in this group more than in other groups. Conclusion: MSCs accelerate the healing process of wound closure. The route of administration of MSCs has a great influence on wound healing as intradermal injection of MSCs was more effective in enhancement of wound healing than systemic injection.

Keywords: intradermal, mesenchymal stem cells, morphology, skin wound, systemic injection

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Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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Authors: H. Pegram, R. Stevens, L. De Girolamo

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Aligned electrospun nanofibres act as effective neuronal and glial cell scaffolds that can be layered to contain multiple sheets harboring different cell populations. This allows personalised biofunctional prostheses to be manufactured with both acellular and cellularised layers for the treatment of spinal cord injury. Additionally, the manufacturing route may be configured to produce in-vitro 3D cell based model of spinal cord injury to aid drug development and enhance prosthesis performance. The goal of this investigation was to optimise the multi-layer scaffold design parameters for prosthesis manufacture, to enable the development of multi-layer patient specific implant therapies. The work has also focused on the fabricating aligned nanofibre scaffolds that promote in-vitro neuronal and glial cell population growth, cell-to-cell interaction and long-term survival following trauma to mimic an in-vivo spinal cord lesion. The approach has established reproducible lesions and has identified markers of trauma and regeneration marked by effective neuronal migration across the lesion with glial support. The investigation has advanced the development of an in-vitro model of traumatic spinal cord injury and has identified a route to manufacture prostheses which target the repair spinal cord injury. Evidence collated to investigate the multi-layer concept suggests that physical cues provided by nanofibres provide both a natural extra-cellular matrix (ECM) like environment and controls cell proliferation and migration. Specifically, aligned nanofibre layers act as a guidance system for migrating and elongating neurons. On a larger scale, material type in multi-layer systems also has an influence in inter-layer migration as cell types favour different material types. Results have shown that layering nanofibre membranes create a multi-level scaffold system which can enhance or prohibit cell migration between layers. It is hypothesised that modifying nanofibre layer material permits control over neuronal/glial cell migration. Using this concept, layering of neuronal and glial cells has become possible, in the context of tissue engineering and also modelling in-vitro induced lesions.

Keywords: electrospinning, layering, lesion, modeling, nanofibre

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Authors: Neha Dimri, Varsha Gupta

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Purpose: Fast Fashion trend promotes consumption of low cost high fashion garments at a rapid rate. Frequent change in fashion trend results in higher disposability of Fast Fashion products. To cater for the Fast Fashion appetite of the present day consumer, fashion giants have ramped up production of garments, thus imposing a massive strain on the planet’s natural resources. Also, ethical issues related to cheaper methods of production are of concern. India being a large consumer base has a major role to play in proliferation of the Fast Fashion trend. This paper is an attempt to study the effect of fast fashion trends on the Indian consumer’s behaviour. It also attempts to ascertain the awareness of the consumer about the detrimental effect that the fast fashion trends manifest on the environment. Design /methodology/approach: The survey was conducted using a questionnaire targeted at a set of urban Indian consumers of varied age, profession and socio economic backgrounds. Trends regarding frequency of purchase, expenditure on clothing, disposal methods and awareness about environmental issues were analyzed using the obtained data. Findings: The result of the study indicates that urban Indian consumer has a strong affinity towards fast fashion trends, but is largely unaware of its detrimental effect on the environment and strain on natural resources. Research Limitation/implications: The sample size for survey was only of a hundred consumers, and the same could be expanded for a better estimate of trends. Also, the sample consumers were mostly urban. A big chunk of Indian fashion consumers reside in small towns and the same could be included in the survey. Practical implications: As the true cost of Fast Fashion in terms of environmental and ethical aspects is getting realized worldwide, a big market like India cannot remain isolated from this phenomenon. Globally there has been an increase in demand of ethically produced clothing. It is imperative that the Indian consumer be made aware about the unsustainable nature of Fast Fashion so that he can contribute towards conservation of natural resources and ethical production of garments. Originality/value The research attempts to ascertain consumption pattern of the Indian fashion consumer and also his awareness about the true cost and consequences of Fast Fashion. The inferences may be used by fashion giants to use ‘Green Marketing’ and ‘Social Marketing’ techniques to make the Indian consumer more aware about sustainable fashion and to market their own products as ‘Sustainable, Green and Ethical’.

Keywords: consumption, disposable, fast fashion, Indian consumer

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Authors: Inje Cho

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The leading health risks threatening the world today are associated with a modern lifestyle characterized by sedentary behavior, stress, anxiety, and an obesogenic food environment. To counter this alarming trend, the Centers for Disease Control and Prevention have proffered Physical Activity guidelines to bolster physical engagement. Concurrently, the burgeon of smartphones and mobile applications has witnessed a proliferation of fitness applications aimed at invigorating exercise adherence and real-time activity monitoring. Grounded in the Uses and gratification theory, this study delves into the technological affordances of mobile fitness applications, discerning the mediating influences of escapism and social outcome expectations on attitudes and exercise intention. The theory explains how individuals employ distinct communication mediums to satiate their exigencies and desires. Technological affordances manifest as attributes of emerging technologies that galvanize personal engagement in physical activities. Several features of mobile fitness applications include affordances for goal setting, virtual rewards, peer support, and exercise information. Escapism, denoting the inclination to disengage from normal routines, has emerged as a salient motivator for the consumption of new media. This study postulates that individual’s perceptions technological affordances within mobile fitness applications, can affect escapism and social outcome expectations, potentially influencing attitude, and behavior formation. Thus, the integrated model has been developed to empirically examine the interrelationships between technological affordances, escapism, social outcome expectations, and exercise intention. Structural Equation Modelling serves as the methodological tool, and a cohort of 400 Fitbit users shall be enlisted from the Prolific, data collection platform. A sequence of multivariate data analyses will scrutinize both the measurement and hypothesized structural models. By delving into the effects of mobile fitness applications, this study contributes to the growing of new media studies in sport management. Moreover, the novel integration of the uses and gratification theory, technological affordances, via the prism of escapism, illustrates the dynamics that underlies mobile fitness user’s attitudes and behavioral intentions. Therefore, the findings from this study contribute to theoretical understanding and provide pragmatic insights to developers and practitioners in optimizing the impact of mobile fitness applications.

Keywords: technological affordances, uses and gratification, mobile fitness apps, escapism, physical activity

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Authors: Leslie Nobler

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African fabrics based specifically on the Dutch Wax Print, or Ankara, popularized during Africa's colonial era, have had an enormous impact on western fashion (especially in the US and UK), in the last half-decade. The trend has had an effect on the world of visual arts as well, which circuitously, also heavily impacts fashion design. In fashion, and notably in celebrity apparel choices, this is in part due to ‘identity’ and taking pride in one's African roots; in the visual arts, artists such as Yinka Shonibare and Njideka Akunyili Crosby are making statements about identity politics, colonialism up through post-colonialism, and racism. The ‘global village’ brought on by the internet has driven this proliferation, as have improvements in the printing technology with which the Ankara print is made, combining wax-resist with roller printing. The newest patterns can now be designed authentically in western African and easily sent electronically to Europe for printing. Examples of Ankara's new reach across the Atlantic abound. They have taken several paths, which the paper will detail. Briefly, the first is its greater utilization in the fashion world, from authentic textile shops in African American neighborhoods to copied (knocked-off) low-end reproductions in discount chains. Secondly, we are seeing far more uses of these textiles/patterns in important works of fine arts from major museums, in Philadelphia to Palm Beach to the Mass MOCA (in the US), all the way to the Israel Museum in Jerusalem, and everywhere in between. And lastly, but quite significantly, we see this trend throughout social media thanks to Instagram, Pinterest and celebrity photos –even at the recent royal wedding. What shall sustain this major new design direction is that Ankara changes with and adapts to the times. Some of it is now printed in West Africa, often in the Nigeria area. And some may be designed in Europe or even at knock-off apparel studios in NY or Asia. But it stays utterly relevant because the motifs are based on objects and scenes in everyday life. In my design studio and university design classes, this idea is first and foremost, from our big spiritual eye motifs to drawings of our art supplies to the ‘politically-loaded’ chain patterns. This first-hand creativity experience becomes part of the research of this paper, along with historic and contemporary sources of inquiry, both through a literature/image search and anecdotal experience into what is behind this exciting and surprising trend.

Keywords: African wax print, Ankara, identity (politics), textile design, surface design

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Authors: Samashi Munaweera

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Cancer stem cells (CSC) are responsible for the initiation, extensive proliferation and metastasis of cancer. CSCs, including breast cancer stem cells (bCSCs) have a capacity to generate chemo and radiotherapy resistance heterogeneous population of cells. Over-expressed ABCB1 has been reported as a main reason for drug resistance of CSCs via activating drug efflux pumps by creating pores in the cell membrane. The overall efficiency of chemotherapeutic agents might be enhanced by blocking the ABCB protein efflux pump in the CSC membrane. There is an urgent need to search for persuasive natural drugs which can target CSCs. Anti-cancer properties of Hylocereus undatus on cancer CSCs have not yet been studied. In the present study, the anti-cancer effects of the peel and flesh of H. undatus fruit on bCSCs were evaluated with the aim of developing a marketable anti-cancer nutraceutical formulation. The flesh and peel of H. undatus were freeze-dried and sequentially extracted into four different solvents (hexane, chloroform, ethyl acetate and ethanol). All extracts (eight extracts) were dried under reduced pressure, and different concentrations (12.5-400 µg/mL) were treated on bCSCs isolated from a triple-negative chemo-resistant breast cancer phenotype (MDA-MB-231 cells). Anti-proliferative effects of all extracts and paclitaxel (positive control) were determined by a colorimetric assay (WST-1 based). Since peel-chloroform (IC50= 54.8 µg/mL) and flesh-ethyl acetate (IC50= 150.5 µg/mL) extras exerted a potent anti-proliferative effect at 72 h post-incubation, a combinatorial formulation (CF) was developed with the most active peel-chloroform extract and 20 µg/mL of verapamil (a known ABCB1 drug efflux pump blocker) first time in the world. Anti-proliferative effects and pro-apoptotic effects of CF were confirmed by estimating activated caspase3 and caspase7 levels and apoptotic morphological features in the CF-treated bCSCs compared to untreated and only verapamil (20 µg/mL) treated bCSCs, and CF treated normal mammary epithelial cells (MCF-10A). The antiproliferative effects of CF (16.4 µg/mL) are greater than paclitaxel (19.2 µg/mL) and three folds greater than peel-chloroform extract (IC50= 54.8 µg/mL) on bCSCs while exerting less effects on normal cells (> 400 µg/mL). Collectively, CF can be considered as a potential initiative of a nutraceutical formulation that can target CSCs.

Keywords: breast cancer stem cells (bCSCs), Hylocereus undatus, combinatorial formulation (CF), ABCB 1 protein, verapamil

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Authors: Soham Chakraborty

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This article examines the development of start-up culture in India, its development as well as related impact on the Indian society. Another vibrant synonym of start-up in the present century can be starting afresh. Startups have become the new flavor of this decade. A startup ecosystem is formed by mainly the new generation in the making. A startup ecosystem involves a variety of elements without which a startup can never prosper, they are—ideas, inventions, innovations as well as authentic research in the field into which one is interested, mentors, advisors, funding bodies, service provider organizations, angel, venture and so on. The culture of startup is quiet nascent but rampant in India. This is largely due to the widespread of media as a medium through which the newfangled entrepreneurs can spread their word of mouth far and wide. Different kinds of media such as Television, Radio, Internet, Print media and so on, act as the weapon to any startup company in India. The article explores how there is a sudden shift in the growing Indian economy due to the rise of startup ecosystem. There are various reasons, which are the result of the growing success of startup in India, firstly, entrepreneurs are building up startup ideas on the basis of various international startup but giving them a pinch of Indian flavor; secondly, business models are framed based on the current problems that people face in the modern century; thirdly, balance between social and technological entrepreneurs and lastly, quality of mentorship. The Government of India boasts startup as a flagship initiative. Bunch full of benefits and assistance was declared in an event named as 'Start Up India, Stand Up India' on 16th January 2016 by the current Prime Minister of India Mr. Narendra Modi. One of the biggest boon that increasing startups are creating in the society is the proliferation of self-employment. Noted Startups which are thriving in India are like OYO, Where’s The Food (WTF), TVF Pitchers, Flipkart and so on are examples of India is getting covered up by various innovative startups. The deep impact can be felt by each Indian after a few years as various governmental and non-governmental policies and agendas are helping in the sprawling up of startups and have mushroom growth in India. The impact of startup uprising in India is also possible due to increasing globalization which is leading to the eradication of national borders, thereby creating the environment to enlarge one’s business model. To conclude, this article points out on the correlation between rising startup in Indian market and its increasing developmental benefits for the people at large. Internationally, various business portals are tagging India to be the world’s fastest growing startup ecosystem.

Keywords: business, ecosystem, entrepreneurs, media, globalization, startup

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Authors: Sunaina Sunaina

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The emergence of Thailand as a modern nation was amalgamation of several minority groups. Eventually, the nation tried to mitigate these diversities in the name of nationalism in the backdrop of colonial powers presence in neighboring nations. However, the continued imposition of modern nation building processes (which is a western concept) in the post-colonial era deepen the feelings of alienation among the minority groups and leads to separatist conflicts. It is significant that whatever form these conflicts take, will impact the security of nation as well as the region of Southeast Asia. This paper tries to explore the possible factors behind the state policies adopted by the government of Thailand to manage the insurgency in Southern provinces in the south. The protracted insurgency in the South has historical roots as Pattani kingdom had glorious period whether it was trade or commerce or education and its assimilation was never accepted by the leaders of these areas. But after assimilation of southern provinces in the state, it has been the state policy as an important factor in promoting or mitigating the insurgency. Initial protests from the elite class of southern provinces inflated into a more organized and violent uprising after Second World War. It was only the decade of 1990s that a relative peace could prevail for some time. The violence reemerged in 2004 with more intensity and till today this area is suffering with violence. Period of different Prime Ministers dealt this insurgency in different ways sometimes very hard line approach had been adopted especially under Primeminstership of Thaksin Shinawatra. Recently, the peace talks which were started during the period of Yinglunck Shinawatra and were carried forward by Junta government also halted. And again, the region stays in a very volatile state. Violence in these provinces not only questions the capability of government to provide political solution to the problem, but also emerges as a major threat to the internal security of the state. The current era where global terrorism is spreading fast, such vulnerable areas may work as a new ground for its proliferation in Southeast Asia. The paper attempts to understand how Thailand’s historical experience of security determines a different approach to national unity which limits the prospects for autonomy in the South. In conjunction with this experience it is nature of national politics and leadership that influences the nature of policies on the ground in Southern Thailand. The paper also tries to bring out conflict between state sovereignty and self-determination as demanded by many in the southern provinces.

Keywords: insurgency, southern Thailand, security, nation building

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Authors: Yuta Kurashina, Chikahiro Imashiro, Kiyoshi Ohnuma, Kenjiro Takemura

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Research objectives and goals: To realize clinical applications of regenerative medicine, a mass cell culture is highly required. In a conventional cell culture, trypsinization was employed for cell detachment. However, trypsinization causes proliferation decrease due to injury of cell membrane. In order to detach cells using an enzyme-free method, therefore, this study proposes a novel cell detachment method capable of detaching adherent cells using acoustic radiation pressure exposed to the dish by the assistance of serum-free medium with ITS liquid medium supplement. Methods used In order to generate acoustic radiation pressure, a piezoelectric ceramic plate was glued on a glass plate to configure an ultrasonic transducer. The glass plate and a chamber wall compose a chamber in which a culture dish is placed in glycerol. Glycerol transmits acoustic radiation pressure to adhered cells on the culture dish. To excite a resonance vibration of transducer, AC signal with 29-31 kHz (swept) and 150, 300, and 450 V was input to the transducer for 5 min. As a pretreatment to reduce cell adhesivity, serum-free medium with ITS liquid medium supplement was spread to the culture dish before exposed to acoustic radiation pressure. To evaluate the proposed cell detachment method, C2C12 myoblast cells (8.0 × 104 cells) were cultured on a ø35 culture dish for 48 hr, and then the medium was replaced with the serum-free medium with ITS liquid medium supplement for 24 hr. We replaced the medium with phosphate buffered saline and incubated cells for 10 min. After that, cells were exposed to the acoustic radiation pressure for 5 min. We also collected cells by using trypsinization as control. Cells collected by the proposed method and trypsinization were respectively reseeded in ø60 culture dishes and cultured for 24 hr. Then, the number of proliferated cells was counted. Results achieved: By a phase contrast microscope imaging, shrink of lamellipodia was observed before exposed to acoustic radiation pressure, and no cells remained on the culture dish after the exposed of acoustic radiation pressure. This result suggests that serum-free medium with ITS liquid inhibits adhesivity of cells and acoustic radiation pressure detaches cells from the dish. Moreover, the number of proliferated cells 24 hr after collected by the proposed method with 150 and 300 V is the same or more than that by trypsinization, i.e., cells were proliferated 15% higher with the proposed method using acoustic radiation pressure than with the traditional cell collecting method of trypsinization. These results proved that cells were able to be collected by using the appropriate exposure of acoustic radiation pressure. Conclusions: This study proposed a cell detachment method using acoustic radiation pressure by the assistance of serum-free medium. The proposed method provides an enzyme-free cell detachment method so that it may be used in future clinical applications instead of trypsinization.

Keywords: acoustic radiation pressure, cell detachment, enzyme free, ultrasonic transducer

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Authors: Pamela R. Jackson, Andrea Hawkins-Daarud, Cassandra R. Rickertsen, Kamala Clark-Swanson, Scott A. Whitmire, Kristin R. Swanson

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Glioblastoma Multiforme (GBM), the most common primary brain tumor, often presents with hyperintensity on T2-weighted or T2-weighted fluid attenuated inversion recovery (T2/FLAIR) magnetic resonance imaging (MRI). This hyperintensity corresponds with vasogenic edema, however there are likely many infiltrating tumor cells within the hyperintensity as well. While MRIs do not directly indicate tumor cells, MRIs do reflect the microenvironmental water abnormalities caused by the presence of tumor cells and edema. The inherent heterogeneity and resulting MRI features of GBMs complicate assessing disease response. To understand how hyperintensity on T2/FLAIR MRI may correlate with edema in the extracellular space (ECS), a multi-compartmental MRI signal equation which takes into account tissue compartments and their associated volumes with input coming from a mathematical model of glioma growth that incorporates edema formation was explored. The reasonableness of two possible extracellular space schema was evaluated by varying the T2 of the edema compartment and calculating the possible resulting T2s in tumor and peripheral edema. In the mathematical model, gliomas were comprised of vasculature and three tumor cellular phenotypes: normoxic, hypoxic, and necrotic. Edema was characterized as fluid leaking from abnormal tumor vessels. Spatial maps of tumor cell density and edema for virtual tumors were simulated with different rates of proliferation and invasion and various ECS expansion schemes. These spatial maps were then passed into a multi-compartmental MRI signal model for generating simulated T2/FLAIR MR images. Individual compartments’ T2 values in the signal equation were either from literature or estimated and the T2 for edema specifically was varied over a wide range (200 ms – 9200 ms). T2 maps were calculated from simulated images. T2 values based on simulated images were evaluated for regions of interest (ROIs) in normal appearing white matter, tumor, and peripheral edema. The ROI T2 values were compared to T2 values reported in literature. The expanding scheme of extracellular space is had T2 values similar to the literature calculated values. The static scheme of extracellular space had a much lower T2 values and no matter what T2 was associated with edema, the intensities did not come close to literature values. Expanding the extracellular space is necessary to achieve simulated edema intensities commiserate with acquired MRIs.

Keywords: extracellular space, glioblastoma multiforme, magnetic resonance imaging, mathematical modeling

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Elene Zhuravliova, Tamar Barbakadze, Irina Kalandadze, Elnari Zaalishvili, Lali Shanshiashvili, David Mikeladze

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Background: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease, which is accompanied by demyelination and autoimmune response to myelin proteins. Among post-translational modifications, which mediate the modulation of inflammatory pathways during MS, methylation is the main one. The methylation of DNA, also amino acids lysine and arginine, occurs in the cell. It was found that decreased trans-methylation is associated with neuroinflammatory diseases. Therefore, abnormal regulation of the methyl cycle could induce demyelination through the action on PAD (peptidyl-arginine-deiminase) gene promoter. PAD takes part in protein citrullination and targets myelin basic protein (MBP), which is affected during demyelination. To determine whether MBP charge isomers are changing the methyl cycle, we have estimated the concentrations of methyl cycle metabolites in MBP-activated primary astrocytes and oligodendrocytes. For this purpose, the action of the citrullinated MBP- C8 and the most cationic MBP-C1 isomers on the primary cells were investigated. Methods: Primary oligodendrocyte and astrocyte cell cultures were prepared from whole brains of 2-day-old Wistar rats. The methyl cycle metabolites, including homocysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH), were estimated by HPLC analysis using fluorescence detection and prior derivatization. Results: We found that the action of MBP-C8 and MBP-C1 induces a decrease in the concentration of both methyl cycle metabolites, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), in astrocytes compared to the control cells. As for oligodendrocytes, the concentration of SAM was increased by the addition of MBP-C1, while MBP-C8 has no significant effect. As for SAH, its concentration was increased compared to the control cells by the action of both MBP-C1 and MBP-C8. A significant increase in homocysteine concentration was observed by the action of the MBP-C8 isomer in both oligodendrocytes and astrocytes. Conclusion: These data suggest that MBP charge isomers change the concentration of methyl cycle metabolites. MBP-C8 citrullinated isomer causes elevation of homocysteine in astrocytes and oligodendrocytes, which may be the reason for decreased astrocyte proliferation and increased oligodendrocyte cell death which takes place in neurodegenerative processes. Elevated homocysteine levels and subsequent abnormal regulation of methyl cycles in oligodendrocytes possibly change the methylation of DNA that activates PAD gene promoter and induces the synthesis of PAD, which in turn provokes the process of citrullination, which is the accompanying process of demyelination. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, astrocytes, methyl cycle metabolites, homocysteine, oligodendrocytes

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Authors: Wael M. Rabeh, Cesar Carrasco-Lopez, Juliana C. Ferreira, Pance Naumov

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Bioluminescence, the emission of light from a biological process, is found in various living organisms including bacteria, fireflies, beetles, fungus and different marine organisms. Luciferase is an enzyme that catalyzes a two steps oxidation of luciferin in the presence of Mg2+ and ATP to produce oxyluciferin and releases energy in the form of light. The luciferase assay is used in biological research and clinical applications for in vivo imaging, cell proliferation, and protein folding and secretion analysis. The luciferase enzyme consists of two domains, a large N-terminal domain (1-436 residues) that is connected to a small C-terminal domain (440-544) by a flexible loop that functions as a hinge for opening and closing the active site. The two domains are separated by a large cleft housing the active site that closes after binding the substrates, luciferin and ATP. Even though all insect luciferases catalyze the same chemical reaction and share 50% to 90% sequence homology and high structural similarity, they emit light of different colors from green at 560nm to red at 640 nm. Currently, the majority of the structural and biochemical studies have been conducted on green-emitting firefly luciferases. To address the color emission mechanism, we expressed and purified two luciferase enzymes with blue-shifted green and red emission from indigenous Brazilian species Amydetes fanestratus and Phrixothrix, respectively. The two enzymes naturally emit light of different colors and they are an excellent system to study the color-emission mechanism of luciferases, as the current proposed mechanisms are based on mutagenesis studies. Using a vapor-diffusion method and a high-throughput approach, we crystallized and solved the crystal structure of both enzymes, at 1.7 Å and 3.1 Å resolution respectively, using X-ray crystallography. The free enzyme adopted two open conformations in the crystallographic unit cell that are different from the previously characterized firefly luciferase. The blue-shifted green luciferase crystalized as a monomer similar to other luciferases reported in literature, while the red luciferases crystalized as an octamer and was also purified as an octomer in solution. The octomer conformation is the first of its kind for any insect’s luciferase, which might be relate to the red color emission. Structurally designed mutations confirmed the importance of the transition between the open and close conformations in the fine-tuning of the color and the characterization of other interesting mutants is underway.

Keywords: bioluminescence, enzymology, structural biology, x-ray crystallography

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Authors: Leyla A. Sandoval Hamón, Fernando Casani

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Sustainability has been integrated into the cities’ agenda due to the impact that they generate. The dimensions of greater proliferation of sustainability, which are taken as a reference, are economic, social and environmental. Thus, the decisions of management of the sustainable cities search a balance between these dimensions in order to provide environment-friendly alternatives. In this context, urban models (where water consumption, energy consumption, waste production, among others) that have emerged in harmony with the environment, are known as Ecocity. A similar model, but on a smaller scale, is ‘Ecocampus’ that is developed in universities (considered ‘small cities’ due to its complex structure). So, sustainable practices are being implemented in the management of university campus activities, following different relevant lines of work. The universities have a strategic role in society, and their activities can strengthen policies, strategies, and measures of sustainability, both internal and external to the organization. Because of their mission in knowledge creation and transfer, these institutions can promote and disseminate more advanced activities in sustainability. This model replica also implies challenges in the sustainable management of water, energy, waste, transportation, among others, inside the campus. The challenge that this paper focuses on is the water management, taking into account that the universities consume big amounts of this resource. The purpose of this paper is to analyze the sustainability experience, with emphasis on water management, of two different campuses belonging to two different Spanish universities - one urban campus in a historic city and the other a suburban campus in the outskirts of a large city. Both universities are in the top hundred of international rankings of sustainable universities. The methodology adopts a qualitative method based on the technique of in-depth interviews and focus-group discussions with administrative and academic staff of the ‘Ecocampus’ offices, the organizational units for sustainability management, from the two Spanish universities. The hypotheses indicate that sustainable policies in terms of water management are best in campuses without big green spaces and where the buildings are built or rebuilt with modern style. The sustainability efforts of the university are independent of the kind of (urban – suburban) campus but an important aspect to improve is the degree of awareness of the university community about water scarcity. In general, the paper suggests that higher institutions adapt their sustainability policies depending on the location and features of the campus and their engagement with the water conservation. Many Spanish universities have proposed policies, good practices, and measures of sustainability. In fact, some offices or centers of Ecocampus have been founded. The originality of this study is to learn from the different experiences of sustainability policies of universities.

Keywords: ecocampus, ecocity, sustainability, water management

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Authors: Rupali Chaudhary

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Shakespeare has been widely revisited by dramatists, critics, filmmakers and scholars around the globe. Shakespeare's kaleidoscopic work has been borrowed and redesigned into resonant patterns by artists, thus weaving myriad manifestations to pick from. Along with adaptation into wholly verbal medium (e.g., translations) the practice of indigenization through performing arts has played a great role in amplifying the reach of plays. The proliferation of Shakespeare's oeuvre commenced with the spread of colonialism itself. The plays illustrating the core values of Western tradition were introduced in the colonies. Therefore, the colonial domination extended to cultural domination. The plays were translated and adapted by the locals at times as it is and sometimes intermingled with the altered landscape and culture. The present paper discusses the global dimensions of Shakespearean cinema along with the historical cinematic shift from silent era to spoken dialogue in multiple languages. The methodology followed is descriptive in nature, and related information is availed from related literature, i.e., books, research articles and films. America and Europe dominated the silent era Shakespearean film production, thereby giving the term 'global' a less broad meaning. Five nations that dominated silent Shakespearean cinema were the United States, England, Italy, France, and Germany. Gradually the work of the exemplary figure with artistic and literary greatness surpassed the boundaries of the colonies and became a global legacy. Presently apart from English speaking nations Shakespearean films have been shot or produced in many of non-Anglophone locales. The findings indicate that when discussing about global dimensions of Shakespearean cinema various factors can be considered: involvement of actors and directors of foreign origin, transportability and universal comprehensibility of visual imagery across geographical borders, commodification of art or West's use of it as a tool of cultural hegemony or promotion of international amity, propagation of interculturalism through individual director's cultural translations and localization of Western art. Understanding of Shakespeare as a global export also depends on how an individual Shakespearean film works. Shakespeare's global appeal for cinema does not reside alone in his exquisite writings, distinctive characters, the setting, the story and the plots that have nurtured cinema since the medium's formative years. Shakespeare's global cinematic appeal is present in the spirit of cinema itself, i.e., the moving images capturing human behaviour and emotions that the plays invoke in audiences.

Keywords: adaptation, global dimensions, Shakespeare, Shakespearean cinema

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Authors: Piret Pernik

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Based on strategic, operational, and technical analysis of the ongoing armed conflict in Ukraine, this paper will examine the opportunities and risks of using small commercial drones (dual-use unmanned aerial vehicles, UAV) for military purposes. The paper discusses the opportunities and risks in the information domain, encompassing both cyber and electromagnetic interference and attacks. The paper will draw conclusions on a possible strategic impact to the battlefield outcomes in the modern armed conflicts by the widespread use of dual-use UAVs. This article will contribute to filling the gap in the literature by examining based on empirical data cyberattacks and electromagnetic interference. Today, more than one hundred states and non-state actors possess UAVs ranging from low cost commodity models, widely are dual-use, available and affordable to anyone, to high-cost combat UAVs (UCAV) with lethal kinetic strike capabilities, which can be enhanced with Artificial Intelligence (AI) and Machine Learning (ML). Dual-use UAVs have been used by various actors for intelligence, reconnaissance, surveillance, situational awareness, geolocation, and kinetic targeting. Thus they function as force multipliers enabling kinetic and electronic warfare attacks and provide comparative and asymmetric operational and tactical advances. Some go as far as argue that automated (or semi-automated) systems can change the character of warfare, while others observe that the use of small drones has not changed the balance of power or battlefield outcomes. UAVs give considerable opportunities for commanders, for example, because they can be operated without GPS navigation, makes them less vulnerable and dependent on satellite communications. They can and have been used to conduct cyberattacks, electromagnetic interference, and kinetic attacks. However, they are highly vulnerable to those attacks themselves. So far, strategic studies, literature, and expert commentary have overlooked cybersecurity and electronic interference dimension of the use of dual use UAVs. The studies that link technical analysis of opportunities and risks with strategic battlefield outcomes is missing. It is expected that dual use commercial UAV proliferation in armed and hybrid conflicts will continue and accelerate in the future. Therefore, it is important to understand specific opportunities and risks related to the crowdsourced use of dual-use UAVs, which can have kinetic effects. Technical countermeasures to protect UAVs differ depending on a type of UAV (small, midsize, large, stealth combat), and this paper will offer a unique analysis of small UAVs both from the view of opportunities and risks for commanders and other actors in armed conflict.

Keywords: dual-use technology, cyber attacks, electromagnetic warfare, case studies of cyberattacks in armed conflicts

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Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: P. Viduthalai, A. K. Divakar, V. Natarajan

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Media is one of the powerful tools that manipulate the world in numerous aspects especially in the form of a communication process. For instance, the concept of the public sphere, which was earlier represented by landlords and elites has now transformed into a virtual public sphere, which is also represented by marginalized people. Unfortunately, this acquisition is still paradoxical. Though the media proliferation and its effects are humongous, still it has not been the same throughout the world. Inequality in access to media has created a technological divide among people. Finally, globalization and approach by the government towards using media for development communication has significantly changed the way in which the media reaches every nook and corner. Monarchy, oligarchy, republic and democracy together form the basis of most governments of the world. Of which, democracy is the one with the highest involvement and participation of the people. Ideally, the participation of the people is what, that keeps the democracy running. A healthy democracy is possible only when people are able to access information that makes citizens responsible and serves to check the functioning of their elected representatives. On one side the media consumption of people plays a crucial role in the formation of the public sphere, and on the other side, big media conglomerates are a serious threat to community participation, which is a goal that the media should strive for in a country like India. How different people consume these different media, differs greatly from length and breadth of the country. Another aspect of this media consumption is that it isn’t passive. People usage and consumption of media are related with the gratification that they derive from the particular media. This aspect varies from person to person and from society to society according to both internal and external factors. This article sets out from the most underlying belief that Malayali Tribes have adopted television and becomes a part of daily life and a day never passes without it especially after the introduction of Free Television Scheme by the past state government. Though they are living in hilly and socially isolated places, they too have started accessing media for understanding about the people of the plains and their culture, dictated by their interest. Many of these interests appear to have a social and psychological origin. The present research attempts to study how gratification of these needs lead Malayali Tribes to form such a virtual public sphere where they could communicate with people of the plains. Data was collected through survey method, from 300 respondents on “Exposure towards Television and their perception”. Conventional anthropological methods like unstructured interviews were also used to supplement the data collection efforts in the three taluks namely Yercaud, Pethanayankkanpalayam and Panamaraththuppatty in Salem district of TamilNadu. The results highlight the role of Television in gratifying needs of the Malayali Tribes.

Keywords: democracy, gratification, Malayali Tribes and television, virtual public sphere

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Authors: Dosun Shin, Assegid Kidane, Pavan Turaga

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According to the National Institute of Health, living a sedentary lifestyle leads to a number of health issues, including increased risk of cardiovascular dis-ease, type 2 diabetes, obesity, and certain types of cancers. This project brings together experts in multiple disciplines to bring product design, sensor design, algorithms, and health intervention studies to develop a product and system that helps reduce the amount of time sitting at the workplace. This paper illustrates ongoing improvements to prototypes the research team developed in initial research; including working prototypes with a software application, which were developed and demonstrated for users. Additional modifications were made to improve functionality, aesthetics, and ease of use, which will be discussed in this paper. Extending on the foundations created in the initial phase, our approach sought to further improve the product by conducting additional human factor research, studying deficiencies in competitive products, testing various materials/forms, developing working prototypes, and obtaining feedback from additional potential users. The solution consisted of an aesthetically pleasing seat cover cushion that easily attaches to common office chairs found in most workplaces, ensuring a wide variety of people can use the product. The product discreetly contains sensors that track when the user sits on their chair, sending information to a phone app that triggers reminders for users to stand up and move around after sitting for a set amount of time. This paper also presents the analyzed typical office aesthetics and selected materials, colors, and forms that complimented the working environment. Comfort and ease of use remained a high priority as the design team sought to provide a product and system that integrated into the workplace. As the research team continues to test, improve, and implement this solution for the sedentary workplace, the team seeks to create a viable product that acts as an impetus for a more active workday and lifestyle, further decreasing the proliferation of chronic disease and health issues for sedentary working people. This paper illustrates in detail the processes of engineering, product design, methodology, and testing results.

Keywords: anti-sedentary work behavior, new product development, sensor design, health intervention studies

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

Abstract:

As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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