Search results for: wnt1 inducible signaling pathway protein-1

Authors: Andleeb Zahra, Itrat Rubab, Sumaira Malik, Amina Khan, Muhammad Jawad Khan, M. Qaiser Fatmi

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Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use in an early diagnostic tool. miRNAs are small, double stranded, non-coding RNAs that regulate gene expression by deregulating mRNAs. miRNAs play important roles in modifying various cellular processes such as cell growth, differentiation, apoptosis, and immune response. Dis-regulated expression of miRNAs is known to affect the cell growth, and this may function as tumor suppressors or oncogenes in various cancers. Objectives: The main objectives of this study were to characterize the extracellular miRNAs involved in oral cancer (OC) to assist early detection of cancer as well as to propose a list of genes that can potentially be used as biomarkers of OC. We used gene expression data by microarrays already available in literature. Materials and Methods: In the first step, a total of 318 miRNAs involved in oral carcinoma were shortlisted followed by the prediction of their target genes. Simultaneously, the differentially expressed genes (DEGs) of oral carcinoma from all experiments were identified. The common genes between lists of DEGs of OC based on experimentally proven data and target genes of each miRNA were identified. These common genes are the targets of specific miRNA, which is involved in OC. Finally, a list of genes was generated which may be used as biomarker of OC. Results and Conclusion: In results, we included some of pathways in cancer to show the change in gene expression under the control of specific miRNA. Ingenuity pathway analysis (IPA) provided a list of major biomarkers like CDH2, CDK7 and functional enrichment analysis identified the role of miRNA in major pathways like cell adhesion molecules pathway affected by cancer. We observed that at least 25 genes are regulated by maximum number of miRNAs, and thereby, they can be used as biomarkers of OC. To better understand the role of miRNA with respect to their target genes further experiments are required, and our study provides a platform to better understand the miRNA-OC relationship at genomics level.

Keywords: biomarkers, gene expression, miRNA, oral carcinoma

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Authors: Manabu Sasajima, Takao Yamaguchi, Yoshio Koike, Mitsuharu Watanabe

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This paper discusses the propagation of sound waves in air, specifically in narrow rectangular pathways of an occluded-ear simulator for acoustic measurements. In narrow pathways, both the speed of sound and the phase of the sound waves are affected by the damping of the air viscosity. Herein, we propose a new finite-element method (FEM) that considers the effects of the air viscosity. The method was developed as an extension of existing FEMs for porous, sound-absorbing materials. The results of a numerical calculation for a three-dimensional ear-simulator model using the proposed FEM were validated by comparing with theoretical lumped-parameter modeling analysis and standard values.

Keywords: ear simulator, FEM, simulation, viscosity

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Authors: Indu Bhushan Sharma, Rashmi Saraswat

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The thermotolerant, solvent stable and alkalophilic lipase producing bacterial strain was isolated from the water sample of the foothills of Trikuta Mountain in Kakryal (Reasi district) in Jammu and Kashmir, India. The lipase-producing microorganisms were screened using tributyrin agar plates. The selected microbe was optimized for maximum lipase production by subjecting to various carbon and nitrogen sources, incubation period and inoculum size. The selected strain was identified as Bacillus subtilis strain kakrayal_1 (BSK_1) using 16S rRNA sequence analysis. Effect of pH, temperature, metal ions, detergents and organic solvents were studied on lipase activity. Lipase was found to be stable over a pH range of 6.0 to 9.0 and exhibited maximum activity at pH 8. Lipolytic activity was highest at 37°C and the enzyme activity remained at 60°C for 24hrs, hence, established as thermo-tolerant. Production of lipase was significantly induced by vegetable oil and the best nitrogen source was found to be peptone. The isolated Bacillus lipase was stimulated by pre-treatment with Mn2+, Ca2+, K+, Zn2+, and Fe2+. Lipase was stable in detergents such as triton X 100, tween 20 and Tween 80. The 100% ethyl acetate enhanced lipase activity whereas, lipase activity were found to be stable in Hexane. The optimization resulted in 4 fold increase in lipase production. Bacillus lipases are ‘generally recognized as safe’ (GRAS) and are industrially interesting. The inducible alkaline, thermo-tolerant lipase exhibited the ability to be stable in detergents and organic solvents. This could be further researched as a potential biocatalyst for industrial applications such as biotransformation, detergent formulation, bioremediation and organic synthesis.

Keywords: bacillus, lipase, thermotolerant, alkalophilic

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Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

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Authors: Khiem M. Nguyen, Ming C. Yang

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Chloroplast pigments are extremely important during photosynthesis since they play essential roles in light absorption and energy transfer. Therefore, understanding the efficiency of chlorophyll (Chl) biosynthesis could facilitate enhancement in photo-assimilates accumulation, and ultimately, in crop yield. The Chl-deficient mutants have been used extensively to study the Chl biosynthetic pathways and the biogenesis of the photosynthetic apparatus. Rice (Oryza sativa L.) is one of the most leading food crops, serving as staple food for many parts of the world. To author’s best knowledge, Chl b–lacking rice has been found; however the molecular mechanism of Chl biosynthesis still remains unclear compared to wild-type rice. In this study, the ultrastructure analysis, photosynthetic properties, and transcriptome profile of wild-type rice (Norin No.8, N8) and its Chl b-lacking mutant (Chlorina 1, C1) were examined. The finding concluded that total Chl content and Chl b content in the C1 leaves were strongly reduced compared to N8 leaves, suggesting that reduction in the total Chl content contributes to leaf color variation at the physiological level. Plastid ultrastructure of C1 possessed abnormal thylakoid membranes with loss of starch granule, large number of vesicles, and numerous plastoglobuli. The C1 rice also exhibited thinner stacked grana, which was caused by a reduction in the number of thylakoid membranes per granum. Thus, the different Chl a/b ratio of C1 may reflect the abnormal plastid development and function. Transcriptional analysis identified 23 differentially expressed genes (DEGs) and 671 transcription factors (TFs) that were involved in Chl metabolism, chloroplast development, cell division, and photosynthesis. The transcriptome profile and DEGs revealed that the gene encoding PsbR (PSII core protein) was down-regulated, therefore suggesting that the lower in light-harvesting complex proteins are responsible for the lower photosynthetic capacity in C1. In addition, expression level of cell division protein (FtsZ) genes were significantly reduced in C1, causing chloroplast division defect. A total of 19 DEGs were identified based on KEGG pathway assignment involving Chl biosynthesis pathway. Among these DEGs, the GluTR gene was down-regulated, whereas the UROD, CPOX, and MgCH genes were up-regulated. Observation through qPCR suggested that later stages of Chl biosynthesis were enhanced in C1, whereas the early stages were inhibited. Plastid structure analysis together with transcriptomic analysis suggested that the Chl a/b ratio was amplified both by the reduction in Chl contents accumulation, owning to abnormal chloroplast development, and by the enhanced conversion of Chl b to Chl a. Moreover, the results indicated the same Chl-cycle pattern in the wild-type and C1 rice, indicating another Chl b degradation pathway. Furthermore, the results demonstrated that normal grana stacking, along with the absence of Chl b and greatly reduced levels of Chl a in C1, provide evidence to support the conclusion that other factors along with LHCII proteins are involved in grana stacking. The findings of this study provide insight into the molecular mechanisms that underlie different Chl a/b ratios in rice.

Keywords: Chl-deficient mutant, grana stacked, photosynthesis, RNA-Seq, transcriptomic analysis

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Authors: Moon Hee Jung, Dae Seung Kim, Sang-Myung Jung, Gwang Heum Yoon, Hoo Cheol Lee, Hwa Sung Shin

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Scaffolds are an important part to support growth and differentiation of osteoblast for regeneration of injured bone in bone tissue engineering. We utilized tunicate cellulose nanowhisker (CNW) as scaffold and developed complex system that can enhance differentiation of osteoblast by applying mechanical stimulation. CNW, a crystal form of cellulose, has high stiffness with a large surface area and is useful as a biomedical material due to its biodegradability and biocompatibility. In this study, CNW was obtained from tunicate extraction and was confirmed for its adhesion, differentiation, growth of osteoblast without cytotoxicity. In addition, osteoblast was successfully differentiated under mechanical stimulation, followed by calcium dependent signaling. In conclusion, we verified suitability of CNW as scaffold and possibility of bone substitutes.

Keywords: osteoblast, cellulose nanowhisker, CNW, mechanical stimulation, bone tissue engineering, bone substitute

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Authors: Sa’ed Abed, Mohammad H. Al Shayeji, Ovais Ahmed, Sahel Alouneh

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Session Initiation Protocol (SIP) is a signaling layer protocol for building, adjusting and ending sessions among participants including Internet conferences, telephone calls and multimedia distribution. SIP facilitates user movement by proxying and forwarding requests to the present location of the user. In this paper, we provide a formal Specification and Description Language (SDL) and Message Sequence Chart (MSC) to model and define the Internet Engineering Task Force (IETF) SIP protocol and its sample services resulted from informal SIP specification. We create an “Abstract User Interface” using case analysis so that can be applied to identify SIP services more explicitly. The issued sample SIP features are then used as case scenarios; they are revised in MSCs format and validated to their corresponding SDL models.

Keywords: modeling, MSC, SDL, SIP, validating

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Yuriko Takayama, Norihiro Kato

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Quorum sensing (QS) is a cell-to-cell communication system in bacteria to regulate expression of target genes. In gram-negative bacteria, activation on QS is controlled by a concentration increase of N-acylhomoserine lactone (AHL), which can diffuse in and out of the cell. Effective control of QS is expected to avoid virulence factor production in infectious pathogens, biofilm formation, and antibiotic production because various cell functions in gram-negative bacteria are controlled by AHL-mediated QS. In this research, we applied cyclodextrins (CDs) as artificial hosts for the AHL signal to reduce the AHL concentration in the culture broth below its threshold for QS activation. The AHL-receptor complex induced under the high AHL concentration activates transcription of the QS-target gene. Accordingly, artificial reduction of the AHL concentration is one of the effective strategies to inhibit the QS. A hydrophobic cavity of the CD can interact with the acyl-chain of the AHL due to hydrophobic interaction in aqueous media. We studied N-hexanoylhomoserine lactone (C6HSL)-mediated QS in Serratia marcescens; accumulation of C6HSL is responsible for regulation of the expression of pig cluster. Inhibitory effects of added CDs on QS were demonstrated by determination of prodigiosin amount inside cells after reaching stationary phase, because production of prodigiosin depends on the C6HSL-mediated QS. By adding approximately 6 wt% hydroxypropyl-β-CD (HP-β-CD) in Luria-Bertani (LB) medium prior to inoculation of S. maecescens AS-1, the intracellularly accumulated prodigiosin was drastically reduced to 7-10%, which was determined after the extraction of prodigiosin in acidified ethanol. The AHL retention ability of HP-β-CD was also demonstrated by Chromobacterium violacuem CV026 bioassay. The CV026 strain is an AHL-synthase defective mutant that activates QS solely by adding AHLs from outside of cells. A purple pigment violacein is induced by activation of the AHL-mediated QS. We demonstrated that the violacein production was effectively suppressed when the C6HSL standard solution was spotted on a LB agar plate dispersing CV026 cells and HP-β-CD. Physico-chemical analysis was performed to study the affinity between the immobilized CD and added C6HSL using a quartz crystal microbalance (QCM) sensor. The COOH-terminated self-assembled monolayer was prepared on a gold electrode of 27-MHz AT-cut quartz crystal. Mono(6-deoxy-6-N, N-diethylamino)-β-CD was immobilized on the electrode using water-soluble carbodiimide. The C6HSL interaction with the β-CD cavity was studied by injecting the C6HSL solution to a cup-type sensor cell filled with buffer solution. A decrement of resonant frequency (ΔFs) clearly showed the effective C6HSL complexation with immobilized β-CD and its stability constant for MBP-SpnR-C6HSL complex was on the order of 102 M-1. The CD has high potential for engineered control of QS because it is safe for human use.

Keywords: acylhomoserine lactone, cyclodextrin, intracellular signaling, quorum sensing

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Authors: Seul Ki Min, Gwang Heum Yoon, Jung Hyun Joo, Hwa Sung Shin

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Cellular membrane distortion is known as a factor to change intracellular signaling. However, progress of relevant studies is difficult because there are no facilities that can control membrane distortion finely. In this study, we developed microfluidic device which can inflict mechanical stress on cell membrane of Chlamydomonas reinhardtii using regular height of the channels. And cellular physiological changes were analyzed from cells cultured in the device. Excessive calcium ion influx through into cytoplasm was induced from mechanical stress. The results revealed that compressed cells had up-regulated Mat3 mRNA which regulates cell size and cell cycle from a prolonged G1 phase. Additionally, TAG used for the production of biodiesel was raised rapidly from 4 h after compression. Taken together, membrane distortion can be considered as an attractive inducer for biofuel production.

Keywords: mechanical stress, membrane distortion, Chlamydomonas reinhardtii, deflagellation, cell cycle, lipid metabolism

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Authors: Vinaya Kambappa, Chinnadurai Mani, Komaraiah Palle

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Non-small cell-lung cancer (NSCLC) cells have increased expression of EGFR, which makes them a potential target for cancer therapy. Based on molecular docking and previous reports, we designed and synthesized quinazoline derivatives as potent EGFR inhibitors. Among the derivatives, three compounds showed good antiproliferative activity against A-549 and H-1299 cells. Furthermore, these compounds inhibited EGFR signaling exhibiting diminishing p-EGFR and its downstream proteins like p-Akt, p-Erk1/2, and p-mTOR; however, it did not alter the levels of EGFR, Akt, Erk1/2 and mTOR proteins. Flow cytometric analysis indicated the accumulation of cells at G1 phase suggesting induction of apoptosis, which was further confirmed by annexin V/propidium iodide staining. Our study suggested that quinazoline scaffold can be developed as novel EGFR kinase inhibitors for cancer therapy.

Keywords: apoptosis, non-small cell-lung cancer cells, EGFR, quinazoline

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Dake Xiong, Ben Hankamer, Ian Ross

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The most urgent challenge of our time is to replace the depleting resources of fossil fuels by sustainable environmentally friendly alternatives. Hydrogen is a promising CO2-neutral fuel for a more sustainable future especially when produced photo-biologically. Hydrogen can be photosynthetically produced in unicellular green alga like Chlamydomonas reinhardtii, catalysed by the inducible highly active and bidirectional [FeFe]-hydrogenase enzymes (HydA). However, evolutionary and physiological constraints severely restrict the hydrogen yield of algae for industrial scale-up, mainly due to its competition among other metabolic pathways on photosynthetic electrons. Among them, a major challenge to be resolved is the inferior competitiveness of hydrogen production (catalysed by HydA) with NADPH production (catalysed by ferredoxin-NADP+-reductase (FNR)), which is essential for cell growth and takes up ~95% of photosynthetic electrons. In this work, the in vivo hydrogen production efficiency of mutants with ferredoxin-hydrogenase (Fd*-HydA1*) fusion protein construct, where the electron donor ferredoxin (Fd*) is fused to HydA1* and expressed in the model organism C. reinhardtii was investigated. Once Fd*-HydA1* fusion gene is expressed in algal cells, the fusion enzyme is able to draw the redistributed photosynthetic electrons and use them for efficient hydrogen production. From preliminary data, mutants with Fd*-HydA1* transgene showed a ~2-fold increase in the photosynthetic hydrogen production rate compared with its parental strain, which only possesses the native HydA in vivo. Therefore, a solid method of having more efficient hydrogen production in microalgae can be achieved through the expression of the synthetic enzymes.

Keywords: Chlamydomonas reinhardtii, ferredoxin, fusion protein, hydrogen production, hydrogenase

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Authors: Hyun Ji Hyun, Hyo Sun Suh, Min Kook Kim, Yong Chan Kwon, Byung-Mu Lee

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Scope: This study is focused on the effect of myristic acid on LPS-induced inflammation in RAW 264.7 macrophage cells. Methods and results: For the experiment, RAW 264.7 mouse macrophage cell line was used. Results showed that treatment with myristic acid can attenuate LPS-induced inflammation. Moreover, myristic acid significantly suppressed expression of inflammatory mediators and down-regulating UVB-induced intracellular ROS generation. Furthermore, myristic acid reduced the expression of NF-κB by inhibiting degradation of IκB-α and ERK, JNK, and p38 pathways by inhibiting phosphorylation in RAW 264.7 macrophage cells. Conclusion: Overall, these data suggest that the myristic acid could reduce LPS-induced inflammation. Acknowledgment: This research was supported by the Ministry of Trade, Industry & Energy(MOTIE), Korea Institute for Advancement of Technology(KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region

Keywords: anti-inflammation, myristic acid, ROS, ultraviolet light

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Authors: Sourita Ghosh, Falguni Pati, Suhanya Duraiswamy

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Spheroid, a simple three-dimensional cellular aggregate, allows us to simulate the in-vivo complexity of cellular signaling and interactions in greater detail than traditional 2D cell culture. It can be used as an in-vitro model for drug toxicity testing, tumor modeling and many other such applications specifically for cancer. Our work is focused on the development of an affordable, user-friendly, robust, reproducible, high throughput microfluidic device for water in oil droplet production, which can, in turn, be used for spheroids manufacturing. Here, we have investigated the droplet breakup between two non-Newtonian fluids, viz. silicone oil and decellularized liver matrix, which acts as our extra cellular matrix (ECM) for spheroids formation. We performed some biochemical assays to characterize the liver ECM, as well as rheological studies on our two fluids and observed a critical dependence of capillary number (Ca) on droplet breakup and homogeneous drop formation

Keywords: chip less, droplets, extracellular matrix, liver spheroid

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

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

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

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Authors: Hechmi Saidi, Noureddine Hamdi

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The performance of decode and forward (DF) multihop free space optical (FSO) scheme deploying multiple input multiple output (MIMO) configuration under gamma-gamma (GG) statistical distribution, that adopts M-ary pulse position modulation (MPPM) coding, is investigated. We have extracted exact and estimated values of symbol-error rates (SERs) respectively. The probability density function (PDF)’s closed-form formula is expressed for our designed system. Thanks to the use of DF multihop MIMO FSO configuration and MPPM signaling, atmospheric turbulence is combatted; hence the transmitted signal quality is improved.

Keywords: free space optical, gamma gamma channel, radio frequency, decode and forward, multiple-input multiple-output, M-ary pulse position modulation, symbol error rate

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Authors: K. Thiel, P. Patrikainen, C. Nagy, D. Fitzpatrick, E.-M. Aro, P. Kallio

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Photosynthetic cyanobacteria have been recognized as potential future biotechnological hosts for the direct conversion of CO₂ into chemicals of interest using sunlight as the solar energy source. However, in order to develop commercially viable systems, the flux of electrons from the photosynthetic light reactions towards specified target chemicals must be significantly improved. The objective of the study was to investigate whether the autotrophic production efficiency of specified end-metabolites can be improved in engineered cyanobacterial cells by rescuing excited electrons that are normally lost to molecular oxygen due to the cyanobacterial flavodiiron protein Flv1/3. Natively Flv1/3 dissipates excess electrons in the photosynthetic electron transfer chain by directing them to molecular oxygen in Mehler-like reaction to protect photosystem I. To evaluate the effect of flavodiiron inactivation on autotrophic production efficiency in the cyanobacterial host Synechocystis sp. PCC 6803 (Synechocystis), sucrose was selected as the quantitative reporter and a representative of a potential end-product of interest. The concept is based on the native property of Synechocystis to produce sucrose as an intracellular osmoprotectant when exposed to high external ion concentrations, in combination with the introduction of a heterologous sucrose permease (CscB from Escherichia coli), which transports the sucrose out from the cell. In addition, cell growth, photosynthetic gas fluxes using membrane inlet mass spectrometry and endogenous storage compounds were analysed to illustrate the consequent effects of flv deletion on pathway flux distributions. The results indicate that a significant proportion of the electrons can be lost to molecular oxygen via Flv1/3 even when the cells are grown under high CO₂ and that the inactivation of flavodiiron activity can enhance the photosynthetic electron flux towards optionally available sinks. The flux distribution is dependent on the light conditions and the genetic context of the Δflv mutants, and favors the production of either sucrose or one of the two storage compounds, glycogen or polyhydroxybutyrate. As a conclusion, elimination of the native Flv1/3 reaction and concomitant introduction of an engineered product pathway as an alternative sink for excited electrons could enhance the photosynthetic electron flux towards the target endproduct without compromising the fitness of the host.

Keywords: cyanobacterial engineering, flavodiiron proteins, redirecting electron flux, sucrose

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Authors: Sergio Saponara, Luca Fanucci, Riccardo Cassettari, Ruggero Piernicola, Marco Righetto

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The paper presents an innovative networked radar system for detection of obstacles in a railway level crossing scenario. This Monitoring System (MS) is able to detect moving or still obstacles within the railway level crossing area automatically, avoiding the need of human presence for surveillance. The MS is also connected to the National Railway Information and Signaling System to communicate in real-time the level crossing status. The architecture is compliant with the highest Safety Integrity Level (SIL4) of the CENELEC standard. The number of radar sensors used is configurable at set-up time and depends on how large the level crossing area can be. At least two sensors are expected and up four can be used for larger areas. The whole processing chain that elaborates the output sensor signals, as well as the communication interface, is fully-digital, was designed in VHDL code and implemented onto a Xilinx Virtex 6.

Keywords: radar for safe mobility, railroad crossing, railway, transport safety

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Authors: Dhruvit S. Berawala, Jann R. Ursin, Obrad Slijepcevic

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Shale gas is one of the most rapidly growing forms of natural gas. Unconventional natural gas deposits are difficult to characterize overall, but in general are often lower in resource concentration and dispersed over large areas. Moreover, gas is densely packed into the matrix through adsorption which accounts for large volume of gas reserves. Gas production from tight shale deposits are made possible by extensive and deep well fracturing which contacts large fractions of the formation. The conventional reservoir modelling and production forecasting methods, which rely on fluid-flow processes dominated by viscous forces, have proved to be very pessimistic and inaccurate. This paper presents a new approach to forecast shale gas production by detailed modeling of gas desorption, diffusion and non-linear flow mechanisms in combination with statistical representation of these processes. The representation of the model involves a cube as a porous media where free gas is present and a sphere (SiC: Sphere in Cube model) inside it where gas is adsorbed on to the kerogen or organic matter. Further, the sphere is considered consisting of many layers of adsorbed gas in an onion-like structure. With pressure decline, the gas desorbs first from the outer most layer of sphere causing decrease in its molecular concentration. The new available surface area and change in concentration triggers the diffusion of gas from kerogen. The process continues until all the gas present internally diffuses out of the kerogen, gets adsorbs onto available surface area and then desorbs into the nanopores and micro-fractures in the cube. Each SiC idealizes a gas pathway and is characterized by sphere diameter and length of the cube. The diameter allows to model gas storage, diffusion and desorption; the cube length takes into account the pathway for flow in nanopores and micro-fractures. Many of these representative but general cells of the reservoir are put together and linked to a well or hydraulic fracture. The paper quantitatively describes these processes as well as clarifies the geological conditions under which a successful shale gas production could be expected. A numerical model has been derived which is then compiled on FORTRAN to develop a simulator for the production of shale gas by considering the spheres as a source term in each of the grid blocks. By applying SiC to field data, we demonstrate that the model provides an effective way to quickly access gas production rates from shale formations. We also examine the effect of model input properties on gas production.

Keywords: adsorption, diffusion, non-linear flow, shale gas production

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Authors: Monty Vacura

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Hamilton’s Rule is a universal law of biology expressed in protists, plants and animals. When applied to human populations, this model explains: 1) Origin of religion in society as a biopsychological need selected to increase population size; 2) Instincts of racism expressed through intergroup competition; 3) Simultaneous selection for human cooperation and conflict, love and hate; 4) Connection between sporting events and instinctive social messaging for stimulating offensive and defensive responses; 5) Pathway to reduce human sacrifice. This chapter discusses the deep psychological influences of Hamilton’s Rule. Suggestions are provided to reduce human deaths via our instinctive sacrificial behavior, by consciously monitoring Hamilton’s Rule variables highlighted throughout our media outlets.

Keywords: psychology, Hamilton’s rule, evolution, human instincts

Procedia PDF Downloads 35

Authors: Iman Kamranfar, Gang-Ping Xue, Salma Balazadeh, Bernd Mueller-Roeber

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Adverse environmental conditions such as salinity stress, high temperature and drought limit plant growth and typically lead to precocious tissue degeneration and leaf senescence, a process by which nutrients from photosynthetic organs are recycled for the formation of flowers and seeds to secure reaching the next generation under such harmful conditions. In addition, abiotic stress affects developmental patterns that help the plant to withstand unfavourable environmental conditions. We discovered an NAC (for NAM, ATAF1, 2, and CUC2) transcription factor (TF), called RAF in the following, which plays a central role in abiotic drought stress-triggered senescence and the control of developmental adaptations to stressful environments. RAF is an ABA-responsive TF; RAF overexpressors are hypersensitive to abscisic acid (ABA) and exhibit precocious senescence while knock-out mutants show delayed senescence. To explore the RAF gene regulatory network (GRN), we determined its preferred DNA binding sites by binding site selection assay (BSSA) and performed microarray-based expression profiling using inducible RAF overexpression lines and chromatin immunoprecipitation (ChIP)-PCR. Our studies identified several direct target genes, including those encoding for catabolic enzymes acting during stress-induced senescence. Furthermore, we identified various genes controlling drought stress-related developmental changes. Based on our results, we conclude that RAF functions as a central transcriptional regulator that coordinates developmental programs with stress-related inputs from the environment. To explore the potential agricultural applications of our findings, we are currently extending our studies towards crop species.

Keywords: abiotic stress, Arabidopsis, development, transcription factor

Procedia PDF Downloads 173

Authors: Jeongyeob Hong, Myeonghoon Park, Taeson Yoon

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After the advent of Achaeans which utilize different metabolism pathway and contain conspicuously different cellular structure, they have been recognized as possible materials for developing quality of human beings. Among diverse Achaeans, in this paper, we compared 16s RNA Sequences of four different species of Thermococcus: Achaeans genus specialized in sulfur-dealing metabolism. Four Species, Barophilus, Kodakarensis, Hydrothermalis, and Onnurineus, live near the hydrothermal vent that emits extreme amount of sulfur and heat. By comparing ribosomal sequences of aforementioned four species, we found similarities in their sequences and expressed protein, enabling us to expect that certain ribosomal sequence or proteins are vital for their survival. Apriori algorithms and Decision Tree were used. for comparison.

Keywords: Achaeans, Thermococcus, apriori algorithm, decision tree

Procedia PDF Downloads 271

Authors: Mohammed Benlemlih

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Using a sample of 22,839 US firm-year observations over the 1991-2012 period, we find that high CSR firms pay more dividends than low CSR firms. The analysis of individual components of CSR provides strong support for this main finding: five of the six individual dimensions are also associated with high dividend payout. When analyzing the stability of dividend payout, our results show that socially irresponsible firms adjust dividends more rapidly than socially responsible firms do: dividend payout is more stable in high CSR firms. Additional results suggest that firms involved in two controversial activities -the military and alcohol - are associated with low dividend payouts. These findings are robust to alternative assumptions and model specifications, alternative measures of dividend, additional control, and several approaches to address endogeneity. Overall, our results are consistent with the expectation that high CSR firms may use dividend policy to manage the agency problems related to overinvestment in CSR.

Keywords: corporate social responsibility, dividend policy, Lintner model, agency theory, signaling theory, dividend stability

Procedia PDF Downloads 239

Authors: Sayor Ajfar Aaron, Ashif Newaz, Sajjat Hossain Abir, Mushfiqur Rahman

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This paper examines the transformative potential of quantum computing in the field of cybersecurity, with a focus on advanced penetration testing and forensics. It explores how quantum technologies can be leveraged to identify and exploit vulnerabilities more efficiently than traditional methods and how they can enhance the forensic analysis of cyber-attacks. Through theoretical analysis and practical simulations, this study highlights the enhanced capabilities of quantum algorithms in detecting and responding to sophisticated cyber threats, providing a pathway for developing more resilient cybersecurity infrastructures.

Keywords: cybersecurity, cyber forensics, penetration testing, quantum computing

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: Arjmand Khaliq, Pemra Sohaib

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There is increasing trend of use of smart devices in the present age. The growth of computing techniques and advancement in hardware has also brought the use of sensors and smart devices to a high degree during the course of time. So use of smart devices for control, management communication and optimization has become very popular. This paper gives proposed methodology which involves sensing and switching unite for load, two way communications between utility company and smart phones of consumers using cellular techniques and price signaling resulting active participation of user in energy management .The goal of this proposed control methodology is active participation of user in energy management with accommodation of renewable energy resource. This will provide load adjustment according to consumer’s choice, increased security and reliability for consumer, switching of load according to consumer need and monitoring and management of energy.

Keywords: cellular networks, energy management, renewable energy source, smart grid technology

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Authors: Khayriniso Bakhtiyarovna Ganiyeva

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The article explores the significance of punctuation in achieving communicative competence. It underscores that effective communication goes beyond simply using punctuation correctly. In the successful completion of a communicative activity, it is important not that the writer correctly uses punctuation marks but that he was able to achieve a goal aimed at expressing a certain meaning. The unanimity of the writer and the reader in the mutual understanding of the text is of primary importance. It should also be taken into account that situational communication provides special informative content and expressiveness of speech. Also, the norms of the situation are determined by the nature of the information in the text, and the punctuation marks expressed in accordance with the norm perform logical-semantic, highlighting expressive-emotional and signaling functions. It is a mistake to classify the signs subject to the norm of the situation as created by the author because they functionally reflect the general stylistic features of different texts. Such signs are among the common signs that are codified only by the semantics and structure of the created text.

Keywords: communicative-pragmatic approach, expressiveness of speech, stylistic features, comparative analysis

Procedia PDF Downloads 38

Authors: Serena Gomez, Raeesa Tanseen, Netra Shaligram, Nithin Francis, Sandesh B. J.

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The human gut consists of a community of microbes which has a lot of effects on human health disease. Metabolic modeling can help to predict relative populations of stable microbes and their effect on health disease. In order to study and visualize microbes in the human gut, we developed a tool that offers the following modules: Build a tool that can be used to perform Flux Balance Analysis for microbes in the human gut using the Artificial Bee Colony optimization algorithm. Run simulations for an individual microbe in different conditions, such as aerobic and anaerobic and visualize the results of these simulations.

Keywords: microbes, metabolic modeling, flux balance analysis, artificial bee colony

Procedia PDF Downloads 77

Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan

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The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.

Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide

Procedia PDF Downloads 80