Search results for: neuronal differentiation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 616

Search results for: neuronal differentiation

256 Computational Approach for Grp78–Nf-ΚB Binding Interactions in the Context of Neuroprotective Pathway in Brain Injuries

Authors: Janneth Gonzalez, Marco Avila, George Barreto

Abstract:

GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

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255 Stimulation of NCAM1-14.3.3.ζδ-derived Peptide Interaction Fuels Angiogenesis and Osteogenesis in Ageing

Authors: Taha Kadir Yesin, Hanyu Liu, Zhangfan Ding, Amit Singh, Qi Tian, Yuheng Zhang, Biswajyoti Borah, Junyu Chen, Anjali P. Kusumbe

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The skeletal structure and bone marrow endothelium collectively form a critical functional unit essential for bone development, health, and aging. At the core of osteogenesis and bone formation lies the dynamic process of angiogenesis. In this study, we reveal a potent endogenous anabolic NCAM1-14.3.3. ζδ-derived- Peptide interaction, which stimulates bone angiogenesis and osteogenesis during homeostasis, aging, and age-related bone diseases. Employing high-resolution imaging and inducible cell-specific mouse genetics, our results elucidate the pivotal role of the NCAM1-14.3.3.ζδ-derived-Peptide interaction in driving the expansion of Clec14a+ angiogenic endothelial cells. Notably, Clec14a+ endothelial cells express key osteogenic factors. The NCAM1-14.3.3.ζδ-derived-Peptide interaction in osteoblasts drives osteoblast differentiation, ultimately contributing to the genesis of bone. Moreover, the NCAM1-14.3.3.ζδ-derived-Peptide interaction leads to a reduction in bone resorption. In age-associated vascular and bone loss diseases, stimulating the NCAM1-14.3.3.ζδ-derived-Peptide interaction not only promotes angiogenesis but also reverses bone loss. Consequently, harnessing the endogenous anabolic potential of the NCAM1-14.3.3.ζδ-derived-Peptide interaction emerges as a promising therapeutic modality for managing age-related bone diseases.

Keywords: endothelial cell, NCAM1, Clec14a, 14.3.3.ζδ

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254 Psychopedagogical Service for the Promotion of Cognitive Abilities in Competitive Athletes

Authors: T. Esteves, S. Mesquita, A. Santos, A. Campina, C. Costa-Lobo

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The theme regarding the differentiation of high-performance athletes has always aroused curiosity and fascination, becoming a target for study, especially in the social and human sciences. It was from the 60's and 70's that the concern for the study of the excellence of athletes that showed indices of high performance in sports began to arise. From the 1990s, it became possible to specify the mental competencies and psychological characteristics associated with Olympic athletes with high levels of success. Several studies considered that well-structured pre-competitive and competitive routines and plans were predictors of sports success. Likewise, the high levels of motivation, commitment and concentration; the high levels of self-confidence and optimism; the presence of effective coping strategies to deal with distractions and unexpected situations or events; adequate regulation of activation and anxiety; the establishment and formulation of objectives; and mental visualization and practice were determinants in the manifestation of excellence in these athletes. As such, the promotion of these cognitive abilities has been emphasized in the good performance of the athletes. With the objective of implementing cognitive stimulation programs to meet the specific needs of talented athletes, together with pedagogical activities to promote educational strategies and promote interpersonal relationships, this communication systematizes a proposal for a psychopedagogical service to promote cognitive abilities in competitive athletes, SPAC, to implement in a Portuguese soccer team. This service will be based on a holistic vision in order to promote talent.

Keywords: athletes, cognitive abilities, high competition, psycho-pedagogical service

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253 Acoustic Characteristics of Ultrasonic Vocalizations in Rat Pups Prenatally Exposed to Ethanol

Authors: Mohd. Ashik Shahrier, Hiromi Wada

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Prenatal ethanol exposure has potential to induce difficulties in the social behavior of rats and can alter pup-dam communication suggesting that deficits in pups could result in altered dam behavior, which in turn could result in more aberrant behavior in the pup. Ultrasonic vocalization (USV) is a sensitive tool for investigating social behavior between rat pups and their dam. Rat pups produce USVs on separation from their dam. This signals the dam to locate her pups and retrieve them back to the nest. In this study, it was predicted that prenatal ethanol exposure cause alterations on the acoustic characteristics of USVs in rat pups. Thirteen pregnant rats were purchased and randomly assigned into three groups: high-ethanol (n = 4), low-ethanol (n = 5), and control (n = 4) groups. Laboratory ethanol (purity = 99.5%) was dissolved in tap water and administered to the high- and low-ethanol groups as drinking water from gestational days (GD) 8-20. Ethanol-containing water was administered to the animals in three stages by gradually increasing the concentration between GDs 8–20. From GDs 8–10, 10% and 5%, from GDs 11–13, 20% and 10%, and from GDs 14–20, 30% and 15% ethanol-containing water (v/v) was administered to the high- and low-ethanol groups, respectively. Tap water without ethanol was given to the control group throughout the experiment. The day of birth of the pups was designated as postnatal day (PND) 0. On PND 4, each litter was culled to four male and four female pups. For the present study, two male and two female pups were randomly sampled from each litter as subjects. Thus, eight male and eight female pups from the high-ethanol and control groups and another 10 male and 10 female pups from the low-ethanol group, were sampled. An ultrasonic microphone and the Sonotrack system version 2.4.0 (Metris, Hoofddorp, The Netherlands) were used to record and analyze USVs of the pups. On postnatal days 4, 8, 12 and 16, the resultant pups were individually isolated from their dams and littermates, and USVs were recorded for 5 min in a sound-proof box. Pups in the high-ethanol group produced greater number of USVs compared with that in both low-ethanol and control groups on PND 12. Rat pups in the high-ethanol group also produced higher mean, minimum, and maximum fundamental frequencies of USVs compared with that in both low-ethanol and control groups. Male pups in the high-ethanol group had higher USV amplitudes than in those in low-ethanol and control groups on PND 12. These results suggest that pups in the high-ethanol group relatively experienced more negative emotionality due to the ethanol-induced neuronal activation in the core limbic system and tegmental structures and accordingly, produced altered USVs as distress calls.

Keywords: emotionality, ethanol, maternal separation, ultrasonic vocalization

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252 Tussle of Intellectual Property Rights and Privacy Laws with Reference to Artificial Intelligence

Authors: Lipsa Dash, Gyanendra Sahu

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Intelligence is the cornerstone of humans, and now they have created a counterpart of themselves artificially. Our understanding of the word intelligence is a very perspective based and mostly superior understanding of what we read, write, perceive and understand the adversities around better. A wide range of industrial sectors have also started involving the technology to perceive, reason and act. Similarly, intellectual property is the product of human intelligence and creativity. The World Intellectual Property Organisation is currently working on technology trends across the globe, and AI tops the list in the digital frontier that will have a profound impact on the world, transforming the way we live and work. Coming to Intellectual Property, patents and creations of the AI’s itself have constantly been in question. This paper explores whether AI’s can fit in the flexibilities of Trade Related Intellectual Property Studies and gaps in the existing IP laws or rthere is a need of amendment to include them in the ambit. The researcher also explores the right of AI’s who create things out of their intelligence and whether they could qualify to be legal persons making the other laws applicable on them. Differentiation between AI creations and human creations are explored in the paper, and the need of amendments to determine authorship, ownership, inventorship, protection, and identification of beneficiary for remuneration or even for determining liability. The humans and humanoids are all indulged in matters related to Privacy, and that attracts another constitutional legal issue to be addressed. The authors will be focusing on the legal conundrums of AI, transhumanism, and the Internet of things.

Keywords: artificial intelligence, humanoids, healthcare, privacy, legal conundrums, transhumanism

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251 Neuro-Preservation Potential of Resveratrol Against High Fat High Fructose-Induced Metabolic Syndrome

Authors: Rania F. Ahmed, Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O. Saleh, Omar A. H. Ahmed-Farid

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The metabolic syndrome is an important public health concern often related to obesity, improper diet, and sedentary lifestyles and can predispose individuals to the development of many dangerous health conditions, disability and early death. This research aimed to investigate the efficacy of resveratrol (RSV) to reverse the neuro-complications associated with metabolic syndrome experimentally-induced in rats using an eight weeks high fat, high fructose diet (HFHF) model. The corresponding drug treatments were administered orally during the last 10 days of the diet. Behavioural tests namely the open field test (OFT) and the forced swimming test (FST) were conducted. Brain levels of monoamines viz. serotonin, norepinephrine and dopamine as well as their metabolites were assessed. 8-hydroxyguanosine (8-OHDG) as an indicative of DNA-fragmentation, nitric oxide (NOx) and tumor necrosis factor-α (TNF- α) were estimated. Finally, brain antioxidant parameters namely malondialdehyde (MDA), reduced and oxidized glutathione (GSH, GSSG) were evaluated. HFHF-induced metabolic syndrome resulted in decreased activity in the OFT and increased immobility duration in the FST. Furthermore, HFHF-induced metabolic syndrome lead to a significant increase in brain monoamines turn over as well as elevation in 8-OHDG, NOx, TNF- α, MDA and GSSG; and reduction in GSH. Ten days daily treatment with RSV (20 and 40 mg/kg p.o) dose dependently increased activity in the OFT and decreased immobility duration in the FST. Moreover, RSV normalized brain monoamines contents, reduced 8-OHDG, NOx, TNF- α, MDA and GSSG; and elevated GSH. In conclusion, we can say that RSV showed neuro-protective properties against HFHF-induced metabolic syndrome represented by monoamines preservation, prevention of neurodegeneration, anti-inflammatory and antioxidant potentials and could be recommended as a beneficial daily dietary supplement to treat the neuronal side effects associated with HFHF-induced metabolic syndrome.

Keywords: antioxidants, DNA-fragmentation, forced swimming test, HFHF-induced metabolic syndrome, monoamines, nitric oxide (NOx), open field, resveratrol, tumor necrosis factor-α (TNF- α), 8-hydroxyguanosine (8-OHDG)

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250 A Review On Traditional Agroforestry Systems In Europe Revisited: Biodiversity, Ecosystem Services, And Future Perspectives

Authors: Thuy Hang Le

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Traditional agroforestry systems are land-use practices still widespread in tropical and subtropical countries, while in Europe have significantly decreased due to land-use intensification, land abandonment, and urbanization. Nevertheless, scientific evidence reveals that traditional agroforestry systems significantly support biodiversity and ecosystem services and may positively contribute to socioeconomic rural regional development. We worked out a review that follows the PRISMA approach and compiled comprehensive information on traditional agroforestry systems in Europe. Based on the differentiation of different land-use systems, also considering the agricultural as well as forestry components, we compiled information regarding current distribution, management (agrodiversity), biodiversity and agrobiodiversity, ecosystem and landscape services, threats, and restoration initiatives. From a total of 3,304 studies that dealt with agroforestry systems in Europe, both “modern” (e.g., buffer strip) and “traditional” (e.g., meadow orchards), we filtered out 158 studies from 35 European countries which represent the basis for in-depth investigation. We found, for example, that the traditional pastoral agroforestry system in the Mediterranean region, the so-called Dehesa, can harbor up to 300 plant species as well as 238 bird species, of which 134 are breeding birds. With regard to carbon storage, the traditional orchard agroforestry system in Germany stocks ranged between 6.5 and 9.8 Mg C ha−1, showing significantly higher values compared to an intensively used grassland with around 3.4 to 6.7 Mg C ha−1. With the remarkably high benefit for biodiversity and ecosystem services provided, the important role and multifunctionality of traditional agroforestry systems in Europe should be acknowledged and promoted.

Keywords: biodiversity, ecosystem services, landscape services, traditional agroforestry systems

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249 Population Structure Analysis of Pakistani Indigenous Cattle Population by Using High Density SNP Array

Authors: Hamid Mustafa, Huson J. Heather, Kim Eiusoo, McClure Matt, Khalid Javed, Talat Nasser Pasha, Afzal Ali1, Adeela Ajmal, Tad Sonstegard

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Genetic differences associated with speciation, breed formation or local adaptation can help to preserve and effective utilization of animals in selection programs. Analyses of population structure and breed diversity have provided insight into the origin and evolution of cattle. In this study, we used a high-density panel of SNP markers to examine population structure and diversity among ten Pakistani indigenous cattle breeds. In total, 25 individuals from three cattle populations, including Achi (n=08), Bhagnari (n=04) and Cholistani (n=13) were genotyped for 777, 962 single nucleotide polymorphism (SNP) markers. Population structure was examined using the linkage model in the program STRUCTURE. After characterizing SNP polymorphism in the different populations, we performed a detailed analysis of genetic structure at both the individual and population levels. The whole-genome SNP panel identified several levels of population substructure in the set of examined cattle breeds. We further searched for spatial patterns of genetic diversity among these breeds under the recently developed spatial principal component analysis framework. Overall, such high throughput genotyping data confirmed a clear partitioning of the cattle genetic diversity into distinct breeds. The resulting complex historical origins associated with both natural and artificial selection have led to the differentiation of numerous different cattle breeds displaying a broad phenotypic variety over a short period of time.

Keywords: Pakistan, cattle, genetic diversity, population structure

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248 Preventive Impact of Regional Analgesia on Chronic Neuropathic Pain After General Surgery

Authors: Beloulou Mohamed Lamine, Fedili Benamar, Meliani Walid, Chaid Dalila, Lamara Abdelhak

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Introduction: Post-surgical chronic pain (PSCP) is a pathological condition with a rather complex etiopathogenesis that extensively involves sensitization processes and neuronal damage. The neuropathic component of these pains is almost always present, with variable expression depending on the type of surgery. Objective: To assess the presumed beneficial effect of Regional Anesthesia-Analgesia Techniques (RAAT) on the development of post-surgical chronic neuropathic pain (PSCNP) in various surgical procedures. Patients and Methods: A comparative study involving 510 patients distributed across five surgical models (mastectomy, thoracotomy, hernioplasty, cholecystectomy, and major abdominal-pelvic surgery) and randomized into two groups: Group A (240) receiving conventional postoperative analgesia and Group B (270) receiving balanced analgesia, including the implementation of a Regional Anesthesia-Analgesia Technique (RAAT). These patients were longitudinally followed over a 6-month period, with postsurgical chronic neuropathic pain (PSCNP) defined by a Neuropathic Pain Score DN2≥ 3. Comparative measurements through univariate and multivariable analyses were performed to identify associations between the development of PSCNP and certain predictive factors, including the presumed preventive impact (protective effect) of RAAT. Results: At the 6th month post-surgery, 419 patients were analyzed (Group A= 196 and Group B= 223). The incidence of PSCNP was 32.2% (n=135). Among these patients with chronic pain, the prevalence of neuropathic pain was 37.8% (95% CI: [29.6; 46.5]), with n=51/135. It was significantly lower in Group B compared to Group A, with respective percentages of 31.4% vs. 48.8% (p-value = 0.035). The most significant differences were observed in breast and thoracopulmonary surgeries. In a multiple regression analysis, two predictors of PSCNP were identified: the presence of preoperative pain at the surgical site as a risk factor (OR: 3.198; 95% CI [1.326; 7.714]) and RAAT as a protective factor (OR: 0.408; 95% CI [0.173; 0.961]). Conclusion: The neuropathic component of PSCNP can be observed in different types of surgeries. Regional analgesia included in a multimodal approach to postoperative pain management has proven to be effective for acute pain and seems to have a preventive impact on the development of PSCNP and its neuropathic nature, particularly in surgeries that are more prone to chronicization.

Keywords: post-surgical chronic pain, post-surgical chronic neuropathic pain, regional anesthesia-analgesia techniques, neuropathic pain score DN2, preventive impact

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247 Morphological and Molecular Studies (ITS1) of Hydatid Cysts in Slaughtered Sheep in Mashhad Area

Authors: G. R. Hashemi Tabar, G. R. Razmi, F. Mirshekar

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Echinococcus granulosus have ten strains from G1 to G9. Each strain is related to special intermediated host. The morphology, epidemiology, treatment and control in these strains are different. There are many morphological and molecular methods to differentiate of Echinococcus strains. However, using both methods were provided better information about identification of each strain. The aim of study was to identify Echinococcus granulosus strain of hydrated cysts in slaughtered sheep using morphological and molecular methods in Mashhad area. In the present study, the infected liver and lung with hydatid cysts were collected and transferred to laboratory. The hydatid cyst liquid was extracted and morphological characters of rostellar hook protosclocies were measured using micrometer ocular. The total length of large blade length of large hooks, total length of small and blade length of small hooks, and number of hooks per protoscolex were 23± 0.3μm, 11.7±0.5 μm, 19.3±1.1 μm,8±1.1 and 33.7±0.7 μm, respectively. In molecular section of the study, DNA each samples was extracted with MBST Kit and development of PCR using special primers (EgF, EgR) which amplify fragment of ITS1 gen. The PCR product was digested with Bsh1236I enzyme. Based on pattern of PCR-RLFP results (four band forming), G1, G2 and G3 strain of Echinococcus granulosus were obtained. Differentiation of three strains was done using sequencing analysis and G1 strain was diagnosed. The agreement between the molecular results with morphometric characters of rosetellar hook was confirmed the presence of G1 strain of Echinococcus in the slaughtered sheep of Mashhad area.

Keywords: Echinococcus granulosus, Hydatid cyst, PCR, sheep

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246 Intercultural Trainings for Future Global Managers: Evaluating the Effect on the Global Mind-Set

Authors: Nina Dziatzko, Christopher Stehr, Franziska Struve

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Intercultural competence as an explicit required skill nearly never appears in job advertisements in international or even global contexts. But especially those who have to deal with different nationalities and cultures in their everyday business need to have several intercultural competencies and further a global mind-set. This way the question arises how potential future global managers can be trained to learn these competencies. In this regard, it might be helpful to see if different types of intercultural trainings have different effects on those skills. This paper outlines lessons learned based on the evaluation of two different intercultural trainings for management students. The main differences between the observed intercultural trainings are the amount of theoretical input in relation to hands-on experiences, the number of trainers as well as the used methods to teach implicit cultural rules. Both groups contain management students with the willingness and perspective to work abroad or to work in international context. The research is carried out with a pre-training-survey and a post-training-survey which consists of questions referring the international context of the students and a self-estimation of 19 identified intercultural and global mind-set skills, such as: cosmopolitanism, empathy, differentiation and adaptability. Whereas there is no clear result which training gets overall a significant higher increase of skills, there is a clear difference between the focus of competencies trained by each of the intercultural trainings. This way this research provides a guideline for both academicals institutions as well as companies for the decision between different types of intercultural trainings, if the to be trained required skills are defined. Therefore the efficiency and the accuracy of fit of the education of future global managers get optimized.

Keywords: global mind-set, intercultural competencies, intercultural training, learning experiences

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245 A Case of Osteopetrosis Diagnosed with Nystagmus

Authors: Zerrin Orbak, Busra Demir

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Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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244 Pricing Strategy in Marketing: Balancing Value and Profitability

Authors: Mohsen Akhlaghi, Tahereh Ebrahimi

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Pricing strategy is a vital component in achieving the balance between customer value and business profitability. The aim of this study is to provide insights into the factors, techniques, and approaches involved in pricing decisions. The study utilizes a descriptive approach to discuss various aspects of pricing strategy in marketing, drawing on concepts from market research, consumer psychology, competitive analysis, and adaptability. This approach presents a comprehensive view of pricing decisions. The result of this exploration is a framework that highlights key factors influencing pricing decisions. The study examines how factors such as market positioning, product differentiation, and brand image shape pricing strategies. Additionally, it emphasizes the role of consumer psychology in understanding price elasticity, perceived value, and price-quality associations that influence consumer behavior. Various pricing techniques, including charm pricing, prestige pricing, and bundle pricing, are mentioned as methods to enhance sales by influencing consumer perceptions. The study also underscores the importance of adaptability in responding to market dynamics through regular price monitoring, dynamic pricing, and promotional strategies. It recognizes the role of digital platforms in enabling personalized pricing and dynamic pricing models. In conclusion, the study emphasizes that effective pricing strategies strike a balance between customer value and business profitability, ultimately driving sales, enhancing brand perception, and fostering lasting customer relationships.

Keywords: business, customer benefits, marketing, pricing

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243 Effect of Varying Scaffold Architecture and Porosity of Calcium Alkali Orthophosphate Based-Scaffolds for Bone Tissue Engineering

Authors: D. Adel, F. Giacomini, R. Gildenhaar, G. Berger, C. Gomes, U. Linow, M. Hardt, B. Peleskae, J. Günster, A. Houshmand, M. Stiller, A. Rack, K. Ghaffar, A. Gamal, M. El Mofty, C. Knabe

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The goal of this study was to develop 3D scaffolds from a silica containing calcium alkali orthophosphate utilizing two different fabrication processes, first a replica technique namely the Schwartzwalder Somers method (SSM), and second 3D printing, i.e. Rapid prototyping (RP). First, the mechanical and physical properties of the scaffolds (porosity, compressive strength, and solubility) was assessed and second their potential to facilitate homogenous colonization with osteogenic cells and extracellular bone matrix formation throughout the porous scaffold architecture. To this end murine and rat calavarie osteoblastic cells were dynamically seeded on both scaffold types under perfusion with concentrations of 3 million cells. The amount of cells and extracellular matrix as well as osteogenic marker expression was evaluated using hard tissue histology, immunohistochemistry, and histomorphometric analysis. Total porosities of both scaffolds were 86.9 % and 50% for SSM and RP respectively, Compressive strength values were 0.46 ± 0.2 MPa for SSM and 6.6± 0.8 MPa for RP. Regarding the cellular behavior, RP scaffolds displayed a higher cell and matrix percentage of 24.45%. Immunoscoring yielded strong osteocalcin expression of cells and matrix in RP scaffolds and a moderate expression in SSM scaffolds. 3D printed RP scaffolds displayed superior mechanical and biological properties compared to SSM. 3D printed scaffolds represent excellent candidates for bone tissue engineering.

Keywords: calcium alkali orthophosphate, extracellular matrix mineralization, osteoblast differentiation, rapid prototyping, scaffold

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242 Language Inequalities in the Algerian Public Space: A Semiotic Landscape Analysis

Authors: Sarah Smail

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Algeria has been subject to countless conquests and invasions that resulted in having a diverse linguistic repertoire. The sociolinguistic situation of the country made linguistic landscape analysis pertinent. This in fact, has led to the growth of diverse linguistic landscape studies that mainly focused on identifying the sociolinguistic situation of the country through shop names analysis. The present research adds to the existing literature by offering another perspective to the analysis of signs by combining the physical and digital semiotic landscape. The powerful oil, gas and agri-food industries in Algeria make it interesting to focus on the commodification of natural resources for the sake of identifying the language and semiotic resources deployed in the Algerian public scene in addition to the identification of the visibility of linguistic inequalities and minorities in the business domain. The study discusses the semiotic landscape of three trade cities: Bejaia, Setif and Hassi-Messaoud. In addition to interviews conducted with business owners and graphic designers and questionnaires with business employees. Withal, the study relies on Gorter’s multilingual inequalities in public space (MIPS) model (2021) and Irvine and Gal’s language ideology and linguistic differentiation (2000). The preliminary results demonstrate the sociolinguistic injustice existing in the business domain, e.g., the exclusion of the official languages, the dominance of foreign languages, and the excessive use of the roman script.

Keywords: semiotic landscaping, digital scapes, language commodification, linguistic inequalities, business signage

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241 Exploring the Impact of Dual Brand Image on Continuous Smartphone Usage Intention

Authors: Chiao-Chen Chang, Yang-Chieh Chin

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The mobile phone has no longer confined to communication, from the aspect of smartphones, consumers are only willing to pay for the product which the added value has corresponded with their appetites, such as multiple application, upgrade of the camera, and the appearance of the phone and so on. Moreover, as the maturity stage of smartphone industry today, the strategy which manufactures used to gain competitive advantages through hardware as well as software differentiation, is no longer valid. Thus, this research aims to initiate from brand image, to examine exactly whether consumers’ buying intention focus on smartphone brand or operating system, at the same time, perceived value and customer satisfaction will be added between brand image and continuous usage intention to investigate the impact of these two facets toward continuous usage intention. This study verifies the correlation, fitness, and relationship between the variables that lies within the conceptual framework. The result of using structural equation modeling shows that brand image has a positive impact on continuous usage intention. Firms can affect consumer perceived value and customer satisfaction through the creation of the brand image. It also shows that the brand image of smartphone and brand image of the operating system have a positive impact on customer perceived value and customer satisfaction. Furthermore, perceived value also has a positive impact on satisfaction, and so is the relation within satisfaction and perceived value to the continuous usage intention. Last but not least, the brand image of the smartphone has a more remarkable impact on customers than the brand image of the operating system. In addition, this study extends the results to management practice and suggests manufactures to provide fine product design and hardware.

Keywords: smartphone, brand image, perceived value, continuous usage intention

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240 Zoning and Planning Response to Low-Carbon Development Transition in the Chengdu-Chongqing City Clusters, China

Authors: Hanyu Wang, Guangdong Wang

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County-level areas serve as vital spatial units for advancing new urbanization and implementing the principles of low-carbon development, representing critical regions where conflicts between the two are pronounced. Using the 142 county-level units in the Chengdu-Chongqing city clusters as a case study, a coupled coordination model is employed to investigate the coupled coordination relationship and its spatiotemporal evolution between county-level new urbanization and low-carbon development levels. Results indicate that (1) from 2005 to 2020, the overall levels of new urbanization and low-carbon development in the Chengdu-Chongqing city clusters showed an upward trend but with significant regional disparities. The new urbanization level exhibited a spatial differentiation pattern of "high in the suburban areas, low in the distant suburbs, and some counties standing out." The temporal change in low-carbon development levels was not pronounced, yet spatial disparities were notable. (2) The overall coupling coordination degree between new urbanization and low-carbon development is transitioning from barely coordinated to moderately coordinated. The lag in new urbanization levels serves as a primary factor constraining the coordinated development of most counties. (3) Based on the temporal evolution of development states, all county units can be categorized into four types: coordinated demonstration areas, synergistic improvement areas, low-carbon transformation areas, and development lag areas. The research findings offer crucial reference points for spatial planning and the formulation of low-carbon development policies.

Keywords: county units, coupling coordination, low-carbon development, new urbanization

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239 Experiences of Marital Relationship of Middle-Aged Couples in Hong Kong: Implications for Services Interventions

Authors: Wai M. Shum

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There was evidence that the change of marital quality satisfaction was related to the different stages of the family life cycle. Research studies have been largely based on western contexts, which found a curvilinear U-shaped trend in changes of marital satisfaction over the course of a marriage, but little is known about the marital experiences of Hong Kong couples. Through in-depth interviews, this qualitative study explored the marital relationship of middle-aged couples in a satisfying marriage and to identify how couples maintain a satisfying relationship in the local context. Findings from this study suggested twelve themes with some showing consistency with previous literature, such as communication, companionship, trust, and fidelity. The affective aspects of empathetic understanding and perceived empathy were found to have an enormous effect on couples’ bondedness. The high level of differentiation and security served as a basis for unconditional contribution, acceptance, and adjustment to unsolvable issues such that negative emotion would not be escalated. The manifestations of intimacy and commitment in the triangular theory of love were more frequently addressed than passion in striving for marital longevity in the local context. This study challenged the curvilinear trend of marital satisfaction throughout marriage, with couples showing different pathways of marital satisfaction. The study gave insights on martial enrichment, such as facilitating couples to disclose their vulnerabilities, desire for physical intimacy, and passion in the pursuit of enduring marriage instead of an emphasis on skills training on communication and conflict resolution.

Keywords: intimacy, marital relationship, marital satisfaction, middle-aged

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238 An Experimental Study of Self-Regulated Learning with High School Gifted Pupils

Authors: Prakash Singh

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Research studies affirm the view that gifted pupils are endowed with unique personality traits, enabling them to study at higher levels of thinking, at a faster pace, and with a greater degree of autonomy than their average counterparts. The focus of this study was whether high school gifted pupils are capable of studying an advanced level curriculum on their own by employing self-regulated learning (SRL) strategies. To be self-regulated, pupils are required to be metacognitively, motivationally, and behaviourally active participants in their own learning processes so that they are able to initiate and direct their personal curriculum efforts to acquire cognitive skills and knowledge, instead of being solely reliant on their teachers. Researchers working with gifted populations concede that limited studies have been conducted thus far to examine gifted pupils’ expertise in using SRL strategies to assume ownership of their learning. In order to conduct this investigation, an enriched module in Accounting for specifically gifted grade eleven pupils was developed, incorporating advanced level content, and use was made of the Post-test-Only Control Group Design to accomplish this research objective. The results emanating from this empirical study strongly suggest that SRL strategies can be employed to overcome a narrow, rigid approach that limits the education of gifted pupils in the regular classroom of the high school. SRL can meaningfully offer an alternative way to implement an advanced level curriculum for the gifted in the mainstream of education. This can be achieved despite the limitations of differentiation in the regular classroom.

Keywords: advanced level curriculum, high school gifted pupils, self-regulated learning, teachers’ professional competencies

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237 Neural Networks Underlying the Generation of Neural Sequences in the HVC

Authors: Zeina Bou Diab, Arij Daou

Abstract:

The neural mechanisms of sequential behaviors are intensively studied, with songbirds a focus for learned vocal production. We are studying the premotor nucleus HVC at a nexus of multiple pathways contributing to song learning and production. The HVC consists of multiple classes of neuronal populations, each has its own cellular, electrophysiological and functional properties. During singing, a large subset of motor cortex analog-projecting HVCRA neurons emit a single 6-10 ms burst of spikes at the same time during each rendition of song, a large subset of basal ganglia-projecting HVCX neurons fire 1 to 4 bursts that are similarly time locked to vocalizations, while HVCINT neurons fire tonically at average high frequency throughout song with prominent modulations whose timing in relation to song remains unresolved. This opens the opportunity to define models relating explicit HVC circuitry to how these neurons work cooperatively to control learning and singing. We developed conductance-based Hodgkin-Huxley models for the three classes of HVC neurons (based on the ion channels previously identified from in vitro recordings) and connected them in several physiologically realistic networks (based on the known synaptic connectivity and specific glutaminergic and gabaergic pharmacology) via different architecture patterning scenarios with the aim to replicate the in vivo firing patterning behaviors. We are able, through these networks, to reproduce the in vivo behavior of each class of HVC neurons, as shown by the experimental recordings. The different network architectures developed highlight different mechanisms that might be contributing to the propagation of sequential neural activity (continuous or punctate) in the HVC and to the distinctive firing patterns that each class exhibits during singing. Examples of such possible mechanisms include: 1) post-inhibitory rebound in HVCX and their population patterns during singing, 2) different subclasses of HVCINT interacting via inhibitory-inhibitory loops, 3) mono-synaptic HVCX to HVCRA excitatory connectivity, and 4) structured many-to-one inhibitory synapses from interneurons to projection neurons, and others. Replication is only a preliminary step that must be followed by model prediction and testing.

Keywords: computational modeling, neural networks, temporal neural sequences, ionic currents, songbird

Procedia PDF Downloads 42
236 A 3D Bioprinting System for Engineering Cell-Embedded Hydrogels by Digital Light Processing

Authors: Jimmy Jiun-Ming Su, Yuan-Min Lin

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Bioprinting has been applied to produce 3D cellular constructs for tissue engineering. Microextrusion printing is the most common used method. However, printing low viscosity bioink is a challenge for this method. Herein, we developed a new 3D printing system to fabricate cell-laden hydrogels via a DLP-based projector. The bioprinter is assembled from affordable equipment including a stepper motor, screw, LED-based DLP projector, open source computer hardware and software. The system can use low viscosity and photo-polymerized bioink to fabricate 3D tissue mimics in a layer-by-layer manner. In this study, we used gelatin methylacrylate (GelMA) as bioink for stem cell encapsulation. In order to reinforce the printed construct, surface modified hydroxyapatite has been added in the bioink. We demonstrated the silanization of hydroxyapatite could improve the crosslinking between the interface of hydroxyapatite and GelMA. The results showed that the incorporation of silanized hydroxyapatite into the bioink had an enhancing effect on the mechanical properties of printed hydrogel, in addition, the hydrogel had low cytotoxicity and promoted the differentiation of embedded human bone marrow stem cells (hBMSCs) and retinal pigment epithelium (RPE) cells. Moreover, this bioprinting system has the ability to generate microchannels inside the engineered tissues to facilitate diffusion of nutrients. We believe this 3D bioprinting system has potential to fabricate various tissues for clinical applications and regenerative medicine in the future.

Keywords: bioprinting, cell encapsulation, digital light processing, GelMA hydrogel

Procedia PDF Downloads 152
235 The Maps of Meaning (MoM) Consciousness Theory

Authors: Scott Andersen

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Perhaps simply and rather unadornedly, consciousness is having multiple goals for action and the continuously adjudication of such goals to implement action, referred to as the Maps of Meaning (MoM) Consciousness Theory. The MoM theory triangulates through three parallel corollaries, action (behavior), mechanism (morphology/pathophysiology), and goals (teleology). (1) An organism’s consciousness contains a fluid, nested goals. These goals are not intentionality, but intersectionality, embodiment meeting the world. i.e., Darwinian inclusive fitness or randomization, then survival of the fittest. These goals form via gradual descent under inclusive fitness, the goals being the abstraction of a ‘match’ between the evolutionary environment and organism. Human consciousness implements the brain efficiency hypothesis, genetics, epigenetics, and experience crystallize efficiencies, not necessitating best or objective but fitness, i.e., perceived efficiency based on one’s adaptive environment. These efficiencies are objectively arbitrary, but determine the operation and level of one’s consciousness, termed extreme thrownness. Since inclusive fitness drives efficiencies in physiologic mechanism, morphology and behavior (action) and originates one’s goals, embodiment is necessarily entangled to human consciousness as its the intersection of mechanism or action (both necessitating embodiment) occurring in the world that determines fitness. Perception is the operant process of consciousness and is the consciousness’ de facto goal adjudication process. Goal operationalization is fundamentally efficiency-based via one’s unique neuronal mapping as a byproduct of genetics, epigenetics, and experience. Perception involves information intake and information discrimination, equally underpinned by efficiencies of inclusive fitness via extreme thrownness. Perception isn’t a ‘frame rate,’ but Bayesian priors of efficiency based on one’s extreme thrownness. Consciousness and human consciousness is a modular (i.e., a scalar level of richness, which builds up like building blocks) and dimensionalized (i.e., cognitive abilities become possibilities as emergent phenomena at various modularities, like stratified factors in factor analysis). The meta dimensions of human consciousness seemingly include intelligence quotient, personality (five-factor model), richness of perception intake, and richness of perception discrimination, among other potentialities. Future consciousness research should utilize factor analysis to parse modularities and dimensions of human consciousness and animal models.

Keywords: consciousness, perception, prospection, embodiment

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234 Role of Mismatch Repair Protein Expression in Colorectal Cancer: A Study from North India

Authors: Alka Yadav, Mayank Jain, Rajan Saxena, Niraj Kumari, Narendra Krishnani, Ashok Kumar

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Purpose: To study the mismatch repair (MMR) protein expression and its clinicopathological correlation in colorectal cancer patients in North India. Methods: A prospective study was conducted on histologically proven 52 (38 males and 14 females) patients with adenocarcinoma of colorectum. MMR protein loss was determined by using immunohistochemistry for MLH1, MSH2, PMS2 and MSH6. Results: 52 patients (38 males and 14 females) underwent resection for colorectal cancer with the median age of 52 years (16-81 years). 35% of the patients (n=18) were younger than 50 years of the age. 3 patients had associated history of malignancy in the family. 29 (56%) patients had right colon cancer, 9 (17%) left colon cancer and 14 (27%) rectal cancer. 2 patients each had synchronous and metachronous cancer. Histology revealed well-differentiated tumour in 16, moderately differentiated in 10 and poorly differentiated tumour in 26 patients. MMR protein loss was seen in 15 (29%) patients. Seven (46%) of these patients were less than 50 years of age. Combined loss of MSH2 and MSH6 was seen most commonly and it was found in 6 patients. 12 (80%) patients with MMR protein loss had tumour located proximal to the splenic flexure compared to 3 (20%) located distal to the splenic flexure. There was no difference in MMR protein loss based on patients' age, gender, degree of tumour differentiation, stage of the disease and tumour histological characteristics. Conclusions: This study revealed that there was less than 30% MMR protein loss in colorectal cancer patients. The loss was most commonly seen in right sided colon cancer than left. A larger study is further required to validate these findings.

Keywords: colorectal cancer, mismatch repair protein, immunohitochemistry, clinicopathological correlation

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233 Force Measurement for E-Cadherin-Mediated Intercellular Adhesion Probed by Protein Micropattern and Traction Force Microscopy

Authors: Chieh-Chung Tsou, Chun-Min Lo, Yeh-Shiu Chu

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Cell’s mechanical forces provide important physical cues in regulation of proper cellular functions, such as cell differentiation, proliferation and migration. It is believed that adhesive forces generated by cell-cell interaction are able to transmit to the interior of cell through filamentous cortical cytoskeleton. Prominent among other membrane receptors, Cadherins are prototypical adhesive molecules able to generate remarkable forces to regulate intercellular adhesion. However, the mechanistic steps of mechano-transduction in Cadherin-mediated adhesion remain very controversial. We are interested in understanding how Cadherin protein complexes enable force generation and transmission at cell-cell contact in the initial stage of intercellular adhesion. For providing a better control of time, space, and substrate stiffness, in this study, a combination of protein micropattern, micropipette manipulation, and traction force microscopy is used. Pair micropattern with different forms confines cell spreading area and the gaps in pairs varied from 2 to 8 microns are applied for monitoring the forces that cell pairs generated, measured by traction force microscopy. Moreover, cell clones obtained from epithelial cells undergone genome editing are used to score the importance for known components of Cadherin complexes in force generation. We believe that our results from this combinatory mechanobiological method will provide deep insights on understanding the biophysical principle governing mechano- transduction of Cadherin-mediated intercellular adhesion.

Keywords: cadherin, intercellular adhesion, protein micropattern, traction force microscopy

Procedia PDF Downloads 231
232 Genetic Diversity and Variation of Nigerian Pigeon (Columba livia domestica) Populations Based on the Mitochondrial Coi Gene

Authors: Foluke E. Sola-Ojo, Ibraheem A. Abubakar, Semiu F. Bello, Isiaka H. Fatima, Sule Bisola, Adesina M. Olusegun, Adeniyi C. Adeola

Abstract:

The domesticated pigeon, Columba livia domestica, has many valuable characteristics, including high nutritional value and fast growth rate. There is a lack of information on its genetic diversity in Nigeria; thus, the genetic variability in mitochondrial cytochrome oxidase subunit I (COI) sequences of 150 domestic pigeons from four different locations was examined. Three haplotypes (HT) were identified in Nigerian populations; the most common haplotype, HT1, was shared with wild and domestic pigeons from Europe, America, and Asia, while HT2 and HT3 were unique to Nigeria. The overall haplotype diversity was 0.052± 0.025, and nucleotide diversity was 0.026± 0.068 across the four investigated populations. The phylogenetic tree showed significant clustering and genetic relationship of Nigerian domestic pigeons with other global pigeons. The median-joining network showed a star-like pattern suggesting population expansion. AMOVA results indicated that genetic variations in Nigerian pigeons mainly occurred within populations (99.93%), while the Neutrality tests results suggested that the Nigerian domestic pigeons’ population experienced recent expansion. This study showed a low genetic diversity and population differentiation among Nigerian domestic pigeons consistent with a relatively conservative COI sequence with few polymorphic sites. Furthermore, the COI gene could serve as a candidate molecular marker to investigate the genetic diversity and origin of pigeon species. The current data is insufficient for further conclusions; therefore, more research evidence from multiple molecular markers is required.

Keywords: Nigeria pigeon, COI, genetic diversity, genetic variation, conservation

Procedia PDF Downloads 148
231 Agritourism Development Mode Study in Rural Area of Boshan China

Authors: Lingfei Sun

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Based on the significant value of ecology, the strategic planning for ecological civilization construction was mentioned in the 17th and 18th National Congress of the Communist Party of China. How to generate economic value based on the environmental capacity is not only an economic decision but also a political decision to make. Boshan took the full use of “Ecology” and transformed it as an inexhaustible green resource to benefit people, reflecting the sustainable value of new agriculture development mode. The Strawberry Harvest Festival and Blueberry Harvest Festival hosted approximately 96,000 and 54,000 leisure tourists respectively in 2014. For the Kiwi Harvest Festival in August 2014, in average, it attracted about 4600 tourists per day, which generated daily kiwi sales of 50,000 lbs and 3 million RMB (About 476,000 USD) of daily revenue. The purpose of this study is to elaborate the modes of agritourism development, by analyzing the cases in rural area of Boshan, China. Interviews with the local government officers were applied to discover operation mode of agritourism operation. The financial data was used to demonstrate the strength of government policy and improvement of the income of rural people. The result indicated that there are mainly three types of modes: the Intensive Mode, the Model Mode and the Mixed Mode, supported by case study respectively. With the boom of tourism, the development of agritourism in Boshan relies on the agriculture encouraging policy of China and the effort of local government; meanwhile, large scale of cultivation and the product differentiation are the crucial elements for the success of rural agritourism projects.

Keywords: agriculture, agritourism, economy, rural area development

Procedia PDF Downloads 279
230 Expression Profiling and Immunohistochemical Analysis of Squamous Cell Carcinoma of Head and Neck (Tumor, Transition Zone, Normal) by Whole Genome Scale Sequencing

Authors: Veronika Zivicova, Petr Broz, Zdenek Fik, Alzbeta Mifkova, Jan Plzak, Zdenek Cada, Herbert Kaltner, Jana Fialova Kucerova, Hans-Joachim Gabius, Karel Smetana Jr.

Abstract:

The possibility to determine genome-wide expression profiles of cells and tissues opens a new level of analysis in the quest to define dysregulation in malignancy and thus identify new tumor markers. Toward this long-term aim, we here address two issues on this level for head and neck cancer specimen: i) defining profiles in different regions, i.e. the tumor, the transition zone and normal control and ii) comparing complete data sets for seven individual patients. Special focus in the flanking immunohistochemical part is given to adhesion/growth-regulatory galectins that upregulate chemo- and cytokine expression in an NF-κB-dependent manner, to these regulators and to markers of differentiation, i.e. keratins. The detailed listing of up- and down-regulations, also available in printed form (1), not only served to unveil new candidates for testing as marker but also let the impact of the tumor in the transition zone become apparent. The extent of interindividual variation raises a strong cautionary note on assuming uniformity of regulatory events, to be noted when considering therapeutic implications. Thus, a combination of test targets (and a network analysis for galectins and their downstream effectors) is (are) advised prior to reaching conclusions on further perspectives.

Keywords: galectins, genome scale sequencing, squamous cell carcinoma, transition zone

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229 Indoleamine 2,3 Dioxygenase and Regulatory T Cells in Acute Myeloid Leukemia

Authors: Iman M. Mansour, Rania A. Zayed, Fadwa S. Abdel-Azim, Lamyaa H. Abdel-Latif

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Background and Objectives: The microenvironment of acute myeloid leukemia (AML) is suppressive for immune cells. Regulatory T cells (Tregs) have been recognized to play a role in helping leukemic cells to evade immunesurveillance. The mesenchymal stem cells (MSCs) are essential contributors in immunomodulation of the microenvironment as they can promote differentiation of Tregs via the indoleamine 2,3-dioxygenase (IDO) pathway. The aim of the present work was to evaluate the expression of IDO in bone marrow derived MSCs and to study its correlation to percentage of Tregs. Methods: 37 adult bone marrow samples were cultured in appropriate culture medium to isolate MSCs. Successful harvest of MSCs was determined by plastic adherence, morphology and positive expression of CD271 and CD105; negative expression of CD34 and CD45 using flowcytometry. MSCs were examined for IDO expression by immunocytochemistry using anti-IDO monoclonal antibody. CD4+ CD25+ cells (Tregs) were measured in bone marrow samples by flowcytometry. Results: MSCs were successfully isolated from 20 of the 37 bone marrow samples cultured. MSCs showed higher expression of IDO and Tregs percentage was higher in AML patients compared to control subjects (p=0.002 and p<0.001 respectively). A positive correlation was found between IDO expression and Tregs percentage (p value=0.012, r=0.5). Conclusion: In this study, we revealed an association between high IDO expression in MSCs and elevated levels of Tregs which has an important role in the pathogenesis of AML, providing immunosuppressive microenvironment.

Keywords: acute myeloid leukemia, indoleamine 2, 3-dioxygenase, mesenchymal stem cells, T regulatory cells

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228 Effect of Papaverine on Neurospheres

Authors: Noura Shehab-Eldeen, Mohamed Elsherbeeny, Hossam Elmetwally, Mohamed Salama, Ahmed Lotfy, Mohamed Elgamal, Hussein Sheashaa, Mohamed Sobh

Abstract:

Mitochondrial toxins including papaverine may be implicated in the etiology and pathogenesis of Parkinson's disease. The aim was to detect the effect of papaverine on the proliferation and viability of neural stem cells. Rat neural progenitor cells were isolated from embryos (E14) brains. The dispersed tissues were allowed to settle, then, The supernatant was centrifuged at 1,000 g for 5 min. The pellet was placed in Hank’s solution cultured as free-floating neurospheres Dulbecco’s modified Eagle medium (DMEM) and Hams F12 (3:1) supplemented with B27 (Invitrogen GmBH, Karlsruhe, Germany), 20 ng/mL epidermal growth factor (EGF; Biosource, Karlsruhe, Germany), 20 ng/mL recombinant human fibroblast growth factor (rhFGF; R&D Systems, Wiesbaden-Nordenstadt, Germany), and penicillin and streptomycin (1:100; Invitrogen) at 37°C with 7.5% CO2 . Differentiation was initiated by growth factor withdrawal and plating onto a poly-d-lysine/ laminin matrix. The neurospheres were fed every 2-3 days by replacing 50% of the culture media with fresh media. The culture suspension was transferred to a dish containing 16 wells. The wells were divided as follows: 4 wells received no papaverine (control), 4 wells 1 u, 4 wells 5 u and 4 wells 10 u of papaverine solution. In the next 2 weeks, photography (0,4,5,11days) and viability test were done. The photographs were analysed. Results : papaverine didn't affect proliferation of neurospheres, while it affected viability compared to control , this was dose related. Conclusion: This indicates the harmful effect of papaverine suggesting it to be a candidate neurotoxin causing Parkinsonism.

Keywords: neurospheres, neural stem cells, papaverine, Parkinsonism

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227 Screening for Non-hallucinogenic Neuroplastogens as Drug Candidates for the Treatment of Anxiety, Depression, and Posttraumatic Stress Disorder

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

Procedia PDF Downloads 102