Search results for: expression omnibus (GEO)

Authors: Petra Hypšová, Martin Seitl

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One of the challenges of forensic psychology is to detect deception during a face-to-face interview. In addition to the classical approaches of monitoring the utterance and its components, detection is also sought by observing behavioral and physiological changes that occur as a result of the increased emotional and cognitive load caused by the production of distorted information. Typical are changes in facial temperature, eye movements and their fixation, pupil dilation, emotional micro-expression, heart rate and its variability. Expanding technological capabilities have opened the space to detect these psychophysiological changes and behavioral manifestations through non-contact technologies that do not interfere with face-to-face interaction. Non-contact deception detection methodology is still in development, and there is a lack of studies that combine multiple non-contact technologies to investigate their accuracy, as well as studies that show how different types of lies produced by different interviewers affect physiological and behavioral changes. The main objective of this study is to apply a specific non-contact technology for deception detection. The next objective is to investigate scenarios in which non-contact deception detection is possible. A series of psychophysiological experiments using infrared thermal imaging, eye tracking and behavioral analysis with FaceReader 9.0 software was used to achieve our goals. In the laboratory experiment, 16 adults (12 women, 4 men) between 18 and 35 years of age (SD = 4.42) were instructed to produce alternating prepared and spontaneous truths and lies. The baseline of each proband was also measured, and its results were compared to the experimental conditions. Because the personality of the examiner (particularly gender and facial appearance) to whom the subject is lying can influence physiological and behavioral changes, the experiment included four different interviewers. The interviewer was represented by a photograph of a face that met the required parameters in terms of gender and facial appearance (i.e., interviewer likability/antipathy) to follow standardized procedures. The subject provided all information to the simulated interviewer. During follow-up analyzes, facial temperature (main ROIs: forehead, cheeks, the tip of the nose, chin, and corners of the eyes), heart rate, emotional expression, intensity and fixation of eye movements and pupil dilation were observed. The results showed that the variables studied varied with respect to the production of prepared truths and lies versus the production of spontaneous truths and lies, as well as the variability of the simulated interviewer. The results also supported the assumption of variability in physiological and behavioural values during the subject's resting state, the so-called baseline, and the production of prepared and spontaneous truths and lies. A series of psychophysiological experiments provided evidence of variability in the areas of interest in the production of truths and lies to different interviewers. The combination of technologies used also led to a comprehensive assessment of the physiological and behavioral changes associated with false and true statements. The study presented here opens the space for further research in the field of lie detection with non-contact technologies.

Keywords: emotional expression decoding, eye-tracking, functional infrared thermal imaging, non-contact deception detection, psychophysiological experiment

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Abid Boudiar

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We propose a simple model to obtain an exact expression of Tc/(Tc,max) for the temperature-doping phase diagram of superconducting cuprates. We showed that our model predicted most phase diagram scenario. We found the exact special doping points p(opt), p(qcp) and an accurate E(g,max). Some other properties such as the stripes length 100.1°A and the energy gap in cuprates chain
6meV can also be calculated exactly. Another interesting consequence of this simple picture is the new magic numbers and the ability to express everything using a (Tc,p) diagram via the golden ratio.

Keywords: superconducting cuprates, phase, pseudogap, hole doping, strips, golden ratio, soliton

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Authors: M. A. Tayfun, M. A. Alkhalidi

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The exact theoretical expression describing the probability distribution of nonlinear sea-surface elevations derived from the second-order narrowband model has a cumbersome form that requires numerical computations, not well-disposed to theoretical or practical applications. Here, the same narrowband model is re-examined to develop a simpler closed-form approximation suitable for theoretical and practical applications. The salient features of the approximate form are explored, and its relative validity is verified with comparisons to other readily available approximations, and oceanic data.

Keywords: ocean waves, probability distributions, second-order nonlinearities, skewness coefficient, wave steepness

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Authors: Linda Smail, Zineb Azouz

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Given a Bayesian network relative to a set I of discrete random variables, we are interested in computing the probability distribution P(S) where S is a subset of I. The general idea is to write the expression of P(S) in the form of a product of factors where each factor is easy to compute. More importantly, it will be very useful to give an interpretation of each of the factors in terms of conditional probabilities. This paper considers a semantic interpretation of the factors involved in computing marginal probabilities in Bayesian networks. Establishing such a semantic interpretations is indeed interesting and relevant in the case of large Bayesian networks.

Keywords: Bayesian networks, D-Separation, level two Bayesian networks, factorization of computation

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Authors: Nadia K. Thalji

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In the timeless tapestry of human culture, theater, mythology, and psychology intersect to weave narratives that transcend temporal and spatial boundaries. For millennia, actors have stood as guardians of intuitive wisdom, their craft serving as a conduit for the collective unconscious. This paper embarks on a journey through the realms of creative expression, melding the insights of cross-cultural psychology with the mystical allure of serendipity and synchronicity. At the nexus of these disciplines lies the enigmatic process of active imagination, a gateway to the depths of the psyche elucidated by Jung. Within the hallowed confines of the black box theater at the Department of Performing Arts, UFRGS University in Brazil, this study unfolds. Over the span of four months, a cadre of artists embarked on a voyage of exploration, harnessing the powers of imagery, movement, sound, and dreams to birth a performance that resonated with the echoes of ancient wisdom. Drawing inspiration from the fabled Oracle of Delphi and the priestesses who once dwelled within its sacred precincts, the production delves into the liminal spaces where myth and history intertwine. Through the alchemy of storytelling, participants navigate the labyrinthine corridors of cultural memory, unraveling the threads that bind the past to the present. Central to this endeavor is the phenomenon of synchronicity, wherein seemingly disparate elements coalesce in a dance of cosmic resonance. Serendipity becomes a guiding force, leading actors and audience alike along unexpected pathways of discovery. As the boundaries between performer and spectator blur, the performance becomes a crucible wherein individual narratives merge to form a collective tapestry of shared experience. Yet, beneath the surface of spectacle lies a deeper truth: the exploration of the spiritual dimensions of artistic expression. Through intuitive inquiry and embodied practice, artists tap into reservoirs of insight that transcend rational comprehension. In the communion of minds and bodies, the stage becomes a sacred space wherein the numinous unfolds in all its ineffable glory. In essence, this paper serves as a testament to the transformative power of the creative act. Across cultures and epochs, the theater has served as a crucible wherein humanity grapples with the mysteries of existence. Through the lens of cross-cultural psychology, we glimpse the universal truths that underlie the myriad manifestations of human creativity. As we navigate the turbulent currents of modernity, the wisdom of the ancients beckons us to heed the call of the collective unconscious. In the synthesis of myth and meaning, we find solace amidst the chaos, forging connections that transcend the boundaries of time and space. And in the sacred precincts of the theater, we discover the eternal truth that art is, and always shall be, the soul's journey into the unknown.

Keywords: theater, mythology, cross-cultural, synchronicity, creativity, serendipity, spiritual

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Authors: Asem Bani Amer

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This study handles the linguistic fingerprint in judicial applications described in a law technicality that is recent and developing. It can be adopted to discover criminals by identifying their way of speaking and their special linguistic expressions. This is achieved by understanding the expression "linguistic fingerprint," its concept, and its extended domain, then revealing some of the linguistic fingerprint tools in Western judicial applications and deducing a technical imagination for a linguistic fingerprint in the Arabic language, which is needy for such judicial applications regarding this field, through dictionaries, language rhythm, and language structure.

Keywords: linguistic fingerprint, judicial, application, dictionary, picture, rhythm, structure

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

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

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

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Authors: Roni Naor-Hofri

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This paper shows how self-inflicted pain enabled the expression of love for God among Christian monastic ascetics in medieval central Europe. As scholars have shown, being in a state of pain leads to a change in or destruction of language, an essential feature of the self. The author argues that this transformation allows the self to transcend its boundaries as an object, even if only temporarily and in part. The epistemic achievement of love for God, a non-object, would not otherwise have been possible. To substantiate her argument, the author shows that the self’s transformation into a non-object enables the imitation of God: not solely in the sense of imitatio Christi, of physical and visual representations of God incarnate in the flesh of His son Christ, but also in the sense of the self’s experience of being a non-object, just like God, the target of the self’s love.

Keywords: love for God , pain, philosophy, religion

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Authors: Misty Attwood, Helgi Schioth

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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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Authors: Rohit Kapoor

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In this paper, an attempt is made to formulate 3-echelon repairable parts inventory system under (S-1, S) policy. This analytical model is the extension of an exact formulation of two - echelon repairable parts inventory system, already reported in the established literature. In the present paper, we try to formulate the total cost expression consisting of two components, viz., system investment cost and expected backorder cost.

Keywords: (S-1, S) inventory policy, multi-echelon inventory system, repairable parts

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Authors: J. Adeppa, S. Samanta, O. K. Raina

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Fasciolosis is a widespread economically important parasitic infection throughout the world caused by Fasciola hepatica and F. gigantica. In order to identify novel immunogen conferring significant protection against fasciolosis, currently, research has been focused on the defined antigens viz. glutathione S-transferase, fatty acid binding protein, cathepsin-L, fluke hemoglobin, paramyosin, myosin and F. hepatica- Kunitz Type Molecule. Among various antigens, GST which plays a crucial role in detoxification processes, i.e. phase II defense mechanism of this parasite, has a unique position as a novel vaccine candidate and a drug target in the control of this disease. For producing the antigens in large quantities and their purification to complete homogeneity, the recombinant DNA technology has become an important tool to achieve this milestone. RT- PCR was carried out using F. gigantica total RNA as template, and an amplicon of 657 bp GST gene was obtained. TA cloning vector was used for cloning of this gene, and the presence of insert was confirmed by blue-white selection for recombinant colonies. Sequence analysis of the present isolate showed 99.1% sequence homology with the published sequence of the F. gigantica GST gene of cattle origin (accession no. AF112657), with six nucleotide changes at 72, 74, 423, 513, 549 and 627th bp found in the present isolate, causing an overall change of 4 amino acids. The 657 bp GST gene was cloned at BamH1 and HindIII restriction sites of the prokaryotic expression vector pPROEXHTb in frame with six histidine residues and expressed in E. coli DH5α. Recombinant protein was purified from the bacterial lysate under non-denaturing conditions by the process of sonication after lysozyme treatment and subjecting the soluble fraction of the bacterial lysate to Ni-NTA affinity chromatography. Western blotting with rabbit hyper-immune serum showed immuno-reactivity with 25 kDa recombinant GST. Recombinant protein detected F. gigantica experimental as well as field infection in buffaloes by dot-ELISA. However, cross-reactivity studies on Fasciola gigantica GST antigen are needed to evaluate the utility of this protein in the serodiagnosis of fasciolosis.

Keywords: fasciola gigantic, fasciola hepatica, GST, RT- PCR

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Authors: Bououden Soraya

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This paper aims to study the existence of the change of coordinates which permits to transform a class of nonlinear dynamical systems into the so-called nonlinear observer canonical form (NOCF). Moreover, an algorithm to construct such a change of coordinates is given. Based on this form, we can design an observer with a linear error dynamic. This enables us to estimate the state of a nonlinear dynamical system. A concrete example (biological model) is provided to illustrate the feasibility of the proposed results.

Keywords: nonlinear observer canonical form, observer, design, gene regulation, gene expression

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Authors: Esam Mohammed Al-shaebi

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One of the most crucial approaches for treating human diseases, particularly parasite infections, is nanomedicine. One of the most significant protozoan diseases that impact farm and domestic animals is coccidiosis. While, amprolium is one of the traditional anticoccidial medication, the advent of drug-resistant strains of Eimeria necessitates the development of novel treatments. The goal of the current investigation was to determine whether biosynthesized selenium nanoparticles (Bio-SeNPs) using Azadirachta indica leaves extract might treat mice with Eimeria papillata infection in the jejunal tissue. Five groups of seven mice each were used, as follows: Group 1: Non-infected-non-treated (negative control). Group 2: Non-infected treated group with Bio-SeNPs (0.5 mg/kg of body weight). Groups 3-5 were orally inoculated with 1×103 sporulated oocysts of E. papillata. Group 3: Infected-non-treated (positive control). Group 4: Infected and treated group with Bio-SeNPs (0.5 mg/kg). Group 5: Infected and treated group with the Amprolium. Groups 4 and 5 daily received oral administration (for 5 days) of Bio-SeNPs and anticoccidial medication, respectively, after infection. Bio-SeNPs caused a considerable reduction in oocyst output in mice feces (97.21%). This was also accompanied by a significant reduction in the number of developmental parasitic stages in the jejunal tissues. Glutathione reduced (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels were dramatically reduced by the Eimeria parasite, whereas, nitric oxide (NO) and malonaldehyde (MDA) levels were markedly elevated. The amount of goblet cells and MUC2 gene expression were used as apoptotic indicators, and both were considerably downregulated by infection. However, infection markedly increased the expression of inflammatory cytokines (IL-6 and TNF-α) and the apoptotic genes (Caspase-3 and BCL2). Bio-SeNPs were administrated to mice to drastically lower body weight, oxidative stress, and inflammatory and apoptotic indicators in the jejunal tissue. Our research thus showed the involvement of Bio-SeNPs in protecting mice with E. papillata infections against jejunal damage.

Keywords: coccidiosis, nanoparticles, azadirachta indica, oxidative stress

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Authors: Masahiro Nochi

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This study explores the process in which a Japanese child with congenital blindness deepens understanding of the condition of being “unable to see” and develops the idea of “blind self,” despite having no direct experience of vision. The rehabilitation activities of a child with a congenital visual impairment that were video-recorded from 1 to 6 years old were analyzed qualitatively. The duration of the video was about 80 hours. The recordings were transcribed verbatim, and the episodes in which the child used the words related to the act of “looking” were extracted. Detailed transcripts were constructed referencing the notations of conversation analysis. Characteristics of interactions in those episodes were identified and compared longitudinally. Results showed that the child used the expression "look" under certain interaction patterns and her body expressions and interaction with adults developed in conjunction with the development of language use. Four stages were identified. At the age of 1, interactions involving “look” began to occur. The child said "Look" in the sequence: the child’s “Look,” an adult’s “I’m looking,” certain performances by the child, and the adult’s words of praise. At the age of 3, the child began to behave in accordance with the spatial attributes of the act of "looking," such as turning her face to the adult’s voice before saying, “Look.” She also began to use the expression “Keep looking,” which seemed to reflect her understanding of the temporality of the act of “looking.” At the age of 4, the use of “Look” or “Keep looking” became three times more frequent. She also started to refer to the act of looking in the future, such as “Come and look at my puppy someday.” At the age of 5, she moved her hands toward the adults when she was holding something she wanted to show them. She seemed to understand that people could see the object more clearly when it was in close priximity. About that time, she began to say “I cannot see” to her mother, which suggested a heightened understanding of her own blindness. The findings indicate that as she grew up, the child came to utilize nonverbal behavior before and after the order "Look" to make the progress of the interaction with adults even more certain. As a result, actions that reflect the characteristics of the sighted person's visual experience were incorporated into the interaction chain. The purpose of "Look," with which she intended to attract the adult's attention at first, changed and became something that requests a confirmation she was unable to make herself. It is considered that such a change in the use of the word as well as interaction with sighted adults reflected her heightened self-awareness as someone who could not do what sighted people could do easily. A blind child can gradually deepen their understanding of their own characteristics of blindness among sighted people around them. The child can also develop “blind self” by learning how to interact with others even without direct visual experiences.

Keywords: blindness, child development, conversation analysis, self-concept

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Arash Kosari, Ali Araghi

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A mathematical model for an optical-fiber communication channel is developed which results in an expression that calculates the throughput and loss of the corresponding link. The data are assumed to be transmitted by using of separate photons with different polarizations. The derived model also shows the dependency of data throughput with length of the channel and depolarization factor. It is observed that absorption of photons affects the throughput in a more intensive way in comparison with that of depolarization. Apart from that, the probability of depolarization and the absorption of radiated photons are obtained.

Keywords: absorption, data throughput, depolarization, optical fiber

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Authors: Francesca Lombardi, Francesca Rosaria Augello, Benedetta Cinque, Maria Grazia Cifone, Paola Palumbo

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Glioblastoma multiforme (GBM) is a high-grade primary brain tumor refractory to current forms of treatment. The survival benefits of patients with GBM remain unsatisfactory due to the intrinsic or acquired resistance to temozolomide (TMZ), an alkylating agent, used as the first-line chemotherapeutic drug to treat GBM patients. Its cytotoxic effect is visualized by the induction of O6-methylguanine (O6MeG) within DNA. Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of GBM, its inhibition shows anticancer activities. In the present study, it was verified if the combination of a COX-2 selective inhibitor, NS398, with TMZ could counteract the TMZ resistance. In particular, the effect of NS398 mixed with TMZ was investigated in the GBM TMZ-resistant cell line, T98G. Cells were pretreated with NS398 (100µM, 24 hours) and then exposed to TMZ alone (200µM), NS398 alone, or both for 72 hours, after which cell growth rate and cycle phases, as well as apoptosis level, were evaluated. Coadministration of NS398 and TMZ caused a significant decrease in cell growth and a progressive increase of dead cells detected by trypan blue staining. Moreover, a significant level of apoptotic cell percentage and alteration of cell cycle phases were observed in T98G treated with TMZ-NS398 combination when compared to untreated cells or TMZ-treated cells. TMZ-resistant tumors, as GBM, express elevated levels of DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The mixture drastically reduced MGMT expression in the TMZ-resistant cell line T98G, known to express high levels of MGMT basically. Moreover, while TMZ alone did not influence the COX-2 protein expression, the combination successfully reduced it. In conclusion, these results demonstrated that NS398 enhanced the efficacy of TMZ through cell number reduction, apoptosis induction, and decreased MGMT levels, suggesting the ability of drug combination to reduce the chemoresistance. This drug combination deserves attention and could be considered as a promising therapeutic strategy for GBM patients.

Keywords: COX-2, COX-2 inhibitor, glioblastoma, NS398, T98G, temozolomide

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Authors: Vivian A. Panes, Raymond John S. Rebong, Miel Q. Diaz

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Moringa oleifera Lam. is known mainly for its high nutritional value and medicinal properties contributing to its popular reputation as a 'miracle plant' in the tropical climates where it usually grows. The main objective of this study is to discover the genes and gene products involved in abiotic stress-induced activity that may impact the M. oleifera Lam. mature seeds as well as their corresponding functions. In this study, RNA-sequencing and de novo transcriptome assembly were performed using two assemblers, Trinity and Oases, which produced 177,417 and 120,818 contigs respectively. These transcripts were then subjected to various bioinformatics tools such as Blast2GO, UniProt, KEGG, and COG for gene annotation and the analysis of relevant metabolic pathways. Furthermore, FPKM analysis was performed to identify gene expression levels. The sequences were filtered according to the 'response to stress' GO term since this study dealt with stress response. Clustered Orthologous Groups (COG) showed that the highest frequencies of stress response gene functions were those of cytoskeleton which make up approximately 14% and 23% of stress-related sequences under Trinity and Oases respectively, recombination, repair and replication at 11% and 14% respectively, carbohydrate transport and metabolism at 23% and 9% respectively and defense mechanisms 16% and 12% respectively. KEGG pathway analysis determined the most abundant stress-response genes in the phenylpropanoid biosynthesis at counts of 187 and 166 pathways for Oases and Trinity respectively, purine metabolism at 123 and 230 pathways, and biosynthesis of antibiotics at 105 and 102. Unique and cumulative GO term counts revealed that majority of the stress response genes belonged to the category of cellular response to stress at cumulative counts of 1,487 to 2,187 for Oases and Trinity respectively, defense response at 754 and 1,255, and response to heat at 213 and 208, response to water deprivation at 229 and 228, and oxidative stress at 508 and 488. Lastly, FPKM was used to determine the levels of expression of each stress response gene. The most upregulated gene encodes for thiamine thiazole synthase chloroplastic-like enzyme which plays a significant role in DNA damage tolerance. Data analysis implies that M. oleifera stress response genes are directed towards the effects of climate change more than other stresses indicating the potential of M. oleifera for cultivation in harsh environments because it is resistant to climate change, pathogens, and foreign invaders.

Keywords: stress response, genes, Moringa oleifera, transcriptomics

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Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

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Authors: Silvia Santano Guillén, Luigi Lo Iacono, Christian Meder

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One of the main aims of current social robotic research is to improve the robots’ abilities to interact with humans. In order to achieve an interaction similar to that among humans, robots should be able to communicate in an intuitive and natural way and appropriately interpret human affects during social interactions. Similarly to how humans are able to recognize emotions in other humans, machines are capable of extracting information from the various ways humans convey emotions—including facial expression, speech, gesture or text—and using this information for improved human computer interaction. This can be described as Affective Computing, an interdisciplinary field that expands into otherwise unrelated fields like psychology and cognitive science and involves the research and development of systems that can recognize and interpret human affects. To leverage these emotional capabilities by embedding them in humanoid robots is the foundation of the concept Affective Robots, which has the objective of making robots capable of sensing the user’s current mood and personality traits and adapt their behavior in the most appropriate manner based on that. In this paper, the emotion recognition capabilities of the humanoid robot Pepper are experimentally explored, based on the facial expressions for the so-called basic emotions, as well as how it performs in contrast to other state-of-the-art approaches with both expression databases compiled in academic environments and real subjects showing posed expressions as well as spontaneous emotional reactions. The experiments’ results show that the detection accuracy amongst the evaluated approaches differs substantially. The introduced experiments offer a general structure and approach for conducting such experimental evaluations. The paper further suggests that the most meaningful results are obtained by conducting experiments with real subjects expressing the emotions as spontaneous reactions.

Keywords: affective computing, emotion recognition, humanoid robot, human-robot-interaction (HRI), social robots

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Authors: Sandra Pietri, Helene Dubout, Sabrina Ena, Candice Hoste, Enrico Bastianelli

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Bone Therapeutics is a bone cell therapy company addressing high unmet medical needs in the field of bone fracture repair, more specifically in non-union and delayed-union fractures where the bone repair process is impaired. The company has developed a unique allogeneic osteoblastic cell product (ALLOB®) derived from bone marrow which is currently tested in humans in the indication of delayed-union fractures. The purpose of our study was to directly compare ALLOB® vs. non-differentiated mesenchymal stem cells (MSC) for their in vitro osteogenic characteristics and their in vivo osteogenic potential in order to determine which cellular type would be the most adapted for bone fracture repair. Methods: Healthy volunteers’ bone marrow aspirates (n=6) were expended (i) into BM-MSCs using a complete MSC culture medium or (ii) into ALLOB® cells according to its manufacturing process. Cells were characterized in vitro by morphology, immunophenotype, gene expression and differentiation potential. Additionally, their osteogenic potential was assessed in vivo in the subperiosteal calvaria bone formation model in nude mice. Results: The in vitro side-by-side comparison studies showed that although ALLOB® and BM-MSC shared some common general characteristics such as the 3 minimal MSC criteria, ALLOB® expressed significantly higher levels of chondro/osteoblastic genes such as BMP2 (fold change (FC) > 100), ALPL (FC > 12), CBFA1 (FC > 3) and differentiated significantly earlier than BM-MSC toward the osteogenic lineage. Moreover the bone formation model in nude mice demonstrated that used at the same cellular concentration, ALLOB® was able to induce significantly more (160% vs.107% for control animals) bone formation than BM-MSC (118% vs. 107 % for control animals) two weeks after administration. Conclusion: Our side-by-side comparison studies demonstrated that in vitro and in vivo, ALLOB® displays superior osteogenic capacity to BM-MScs and is therefore a better candidate for the treatment of bone fractures.

Keywords: gene expression, histomorphometry, mesenchymal stem cells, osteogenic differentiation potential, preclinical

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Authors: Trenten Theis, Trevor Daubert, Kennedy Kluthe, Austin Nuxoll

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Staphylococcus aureus is a gram-positive bacterium responsible for an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union annually. Recurring S. aureus bacteremia is associated with biofilm-mediated infections and can occur in 5 - 20% of cases, even with the use of antibiotics. Despite these infections being caused by drug-susceptible pathogens, they are surprisingly difficult to eradicate. One potential explanation for this is the presence of persister cells—a dormant type of cell that shows a high tolerance to antibiotic treatment. Recent studies have shown a connection between low intracellular ATP and persister cell formation. Specifically, this decrease in ATP, and therefore increase in persister cell formation, is due to an interrupted tricarboxylic acid (TCA) cycle. However, S. aureus persister cells’ role in pathogenesis remains unclear. Initial studies have shown that a fumC (TCA cycle gene) knockout survives challenge from aspects of the innate immune system better than wild-type S. aureus. Specifically, challenges from two antimicrobial peptides--LL-37 and hBD-3—show a log increase in survival of the fumC::N∑ strain compared to wild type S. aureus after 18 hours. Furthermore, preliminary studies show that the fumC knockout has a log more survival within a macrophage. These data lead us to hypothesize that the fumC knockout is better suited to other aspects of the innate immune system compared to wild-type S. aureus. To further investigate the mechanism for increased survival of fumC::N∑ within a macrophage, we tested bacterial growth in the presence of reactive oxygen species (ROS), reactive nitrogen species (RNS), and a low pH. Preliminary results suggest that the fumC knockout has increased growth compared to wild-type S. aureus in the presence of all three antimicrobial factors; however, no difference was observed in any single factor alone. To investigate survival within a host, a nine-day biofilm-associated catheter infection was performed on 6–8-week-old male and female C57Bl/6 mice. Although both sexes struggled to clear the infection, female mice were trending toward more frequently clearing the HG003 wild-type infection compared to the fumC::N∑ infection. One possible reason for the inability to reduce the bacterial burden is that biofilms are largely composed of persister cells. To test this hypothesis further, flow cytometry in conjunction with a persister cell marker was used to measure persister cells within a biofilm. Cap5A (a known persister cell marker) expression was found to be increased in a maturing biofilm, with the lowest levels of expression seen in immature biofilms and the highest expression exhibited by the 48-hour biofilm. Additionally, bacterial cells in a biofilm state closely resemble persister cells and exhibit reduced membrane potential compared to cells in planktonic culture, further suggesting biofilms are largely made up of persister cells. These data may provide an explanation as to why infections caused by antibiotic-susceptible strains remain difficult to treat.

Keywords: antibiotic tolerance, Staphylococcus aureus, host-pathogen interactions, microbial pathogenesis

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Authors: Tholaine Matadi

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South Africa is a democratic country with a historical record of racially-motivated marginalisation and exclusion of the majority. During the apartheid era the country was run along pieces of legislation and policies based on racial segregation. The system held a tight clamp on interracial mixing which forced people to remain in segregated areas. For example, a citizen from the Indian community could not own property in an area allocated to white people. In this way, a great majority of people were denied basic human rights. Now, there is a supreme constitution with an entrenched justiciable Bill of Rights founded on democratic values of social justice, human dignity, equality and the advancement of human rights and freedoms. The Constitution also enshrines the values of non-racialism and non-sexism. The Constitutional Court has the power to declare unconstitutional any law or conduct considered to be inconsistent with it. Now, more than two decades down the line, despite the abolition of apartheid, there is evidence that South Africa still experiences hate crimes which violate the entrenched right of vulnerable groups not to be discriminated against on the basis of race, sexual orientation, gender, national origin, occupation, or disability. To remedy this mischief parliament has responded by drafting the Prevention and Combatting of Hate Crimes and Hate Speech Bill. The Bill has been disseminated for public comment and suggestions. It is intended to combat hate crimes and hate speech based on sheer prejudice. The other purpose of the Bill is to bring South Africa in line with international human rights instruments against racism, racial discrimination, xenophobia and related expressions of intolerance identified in several international instruments. It is against this backdrop that this paper intends to analyse the impact of the Bill on the rights to human dignity, equality, and freedom. This study is significant because the Bill was highly contested and creates a huge debate. This study relies on a qualitative evaluative approach based on desktop and library research. The article recurs to primary and secondary sources. For comparative purpose, the paper compares South Africa with countries such as Australia, Canada, Kenya, Cuba, and United Kingdom which have criminalised hate crimes and hate speech. The finding from this study is that despite the Bill’s expressed positive intentions, this draft legislation is problematic for several reasons. The main reason is that it generates considerable controversy mostly because it is considered to infringe the right to freedom of expression. Though the author suggests that the Bill should not be rejected in its entirety, she notes the brutal psychological effect of hate crimes on their direct victims and the writer emphasises that a legislature can succeed to combat hate-crimes only if it provides for them as a separate stand-alone category of offences. In view of these findings, the study recommended that since hate speech clauses have a negative impact on freedom of expression it can be promulgated, subject to the legislature enacting the Prevention and Combatting of Hate-Crimes Bill as a stand-alone law which criminalises hate crimes.

Keywords: freedom of expression, hate crimes, hate speech, human dignity

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Authors: Huijing Wen, Daibao Guo

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Writing is thought to be the most complex facet of language arts. Assessing writing is difficult and subjective, and there are few scientifically validated assessments exist. Research has proposed evaluating writing using a multidimensional approach, including both qualitative and quantitative measures of handwriting, spelling and prose. Given that narrative writing has historically been a staple of literacy instruction in primary grades and is one of the three major genres Common Core State Standards required students to acquire starting in kindergarten, it is essential for teachers to understand how to measure beginning writers writing development and sources of writing difficulties through narrative writing. Guided by the theoretical models of early written expression and using empirical data, this study examines ways teachers can enact a comprehensive approach to understanding beginning writer’s narrative writing through three writing rubrics developed for a Curriculum-based Measurement (CBM). The goal is to help classroom teachers structure a framework for assessing early writing in primary classrooms. Participants in this study included 380 first-grade students from 50 classrooms in 13 schools in three school districts in a Mid-Atlantic state. Three writing tests were used to assess first graders’ writing skills in relation to both transcription (i.e., handwriting fluency and spelling tests) and translational skills (i.e., a narrative prompt). First graders were asked to respond to a narrative prompt in 20 minutes. Grounded in theoretical models of earlier expression and empirical evidence of key contributors to early writing, all written samples to the narrative prompt were coded three ways for different dimensions of writing: length, quality, and genre elements. To measure the quality of the narrative writing, a traditional holistic rating rubric was developed by the researchers based on the CCSS and the general traits of good writing. Students' genre knowledge was measured by using a separate analytic rubric for narrative writing. Findings showed that first-graders had emerging and limited transcriptional and translational skills with a nascent knowledge of genre conventions. The findings of the study provided support for the Not-So-Simple View of Writing in that fluent written expression, measured by length and other important linguistic resources measured by the overall quality and genre knowledge rubrics, are fundamental in early writing development. Our study echoed previous research findings on children's narrative development. The study has practical classroom application as it informs writing instruction and assessment. It offered practical guidelines for classroom instruction by providing teachers with a better understanding of first graders' narrative writing skills and knowledge of genre conventions. Understanding students’ narrative writing provides teachers with more insights into specific strategies students might use during writing and their understanding of good narrative writing. Additionally, it is important for teachers to differentiate writing instruction given the individual differences shown by our multiple writing measures. Overall, the study shed light on beginning writers’ narrative writing, indicating the complexity of early writing development.

Keywords: writing assessment, early writing, beginning writers, transcriptional skills, translational skills, primary grades, simple view of writing, writing rubrics, curriculum-based measurement

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Authors: Fadhl Alakwaa

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One of the sustainable goals of the system biology is understanding gene-gene interactions. Hence, gene regulatory networks (GRN) need to be constructed for understanding the disease ontology and to reduce the cost of drug development. To construct gene regulatory from gene expression we need to overcome many challenges such as data denoising and dimensionality. In this paper, we develop an integrated system to reduce data dimension and remove the noise. The generated network from our system was validated via available interaction databases and was compared to previous methods. The result revealed the performance of our proposed method.

Keywords: gene regulatory network, biclustering, denoising, system biology

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Authors: Monica Karlsson

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The positive effect of a supportive written context on comprehension and retention when faced with a previously unknown idiomatic expression is today an indisputable fact, especially if relevant clues are given in close proximity of the item in question. Also, giving learners a chance of visualizing the meaning of an idiom by offering them its source domain and/or by elaborating etymologically, i.e. providing a mental picture in addition to the spoken/written form (referred to as dual coding), seems to enhance comprehension and retention even further, especially if the idiom is of a more transparent kind. For example, by explaining that walk the plank has a maritime origin and a canary in a coal mine comes from the time when canaries were kept in cages to warn miners if gas was leaking out at which point the canaries succumbed immediately, learners’ comprehension and retention have been shown to increase. The present study aims to investigate whether contextualization of an audiovisual kind could help increase comprehension and retention of L2 idioms. 40 Swedish first-term university students studying English as part of their education to become middle-school teachers participated in the investigation, which tested 24 idioms, all of which were ascertained to be previously unknown to the informants. While half of the learners were subjected to a test in which they were asked to watch scenes from various TV programmes, each scene including one idiomatic expression in a supportive context, the remaining 20 students, as a point of reference, were only offered written contexts, though equally supportive. Immediately after these sessions, both groups were given the same idioms in a decontextualized form and asked to give their meaning. After five weeks, finally, the students were subjected to yet another decontextualized comprehension test. Furthermore, since mastery of idioms in one’s L1 appears to correlate to a great extent with a person’s ability to comprehend idioms in an L2, all the informants were also asked to take a test focusing on idioms in their L1. The result on this test is thus seen to indicate each student’s potential for understanding and memorizing various idiomatic expressions from a more general perspective. Preliminary results clearly show that audiovisual contextualization indeed has a positive effect on learners’ retention. In addition, preliminary results also show that those learners’ who were able to recall most meanings were those who had a propensity for idiom comprehension in their L1.

Keywords: English, L2, idioms, audiovisual context

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Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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Authors: R. L. Ujjwal, Abhishek Jain

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In the field of computer vision, most facial variations such as identity, expression, emotions and gender have been extensively studied. Automatic age estimation has been rarely explored. With age progression of a human, the features of the face changes. This paper is providing a new comparable study of different type of algorithm to feature extraction [Hybrid features using HAAR cascade & HOG features] & classification [KNN & SVM] training dataset. By using these algorithms we are trying to find out one of the best classification algorithms. Same thing we have done on the feature selection part, we extract the feature by using HAAR cascade and HOG. This work will be done in context of age group classification model.

Keywords: computer vision, age group, face detection

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Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich

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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.

Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance

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