Search results for: Kynurenine pathway
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 732

Search results for: Kynurenine pathway

372 Analysis of Osmotin as Transcription Factor/Cell Signaling Modulator Using Bioinformatic Tools

Authors: Usha Kiran, M. Z. Abdin

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Osmotin is an abundant cationic multifunctional protein discovered in cells of tobacco (Nicotiana tabacum L. var Wisconsin 38) adapted to an environment of low osmotic potential. It provides plants protection from pathogens, hence placed in the PRP family of proteins. The osmotin induced proline accumulation has been reported in plants including transgenic tomato and strawberry conferring tolerance against both biotic and abiotic stresses. The exact mechanism of induction of proline by osmotin is however, not known till date. These observations have led us to hypothesize that osmotin induced proline accumulation could be due to its involvement as transcription factor and/or cell signal pathway modulator in proline biosynthesis. The present investigation was therefore, undertaken to analyze the osmotin protein as transcription factor /cell signalling modulator using bioinformatics tools. The results of available online DNA binding motif search programs revealed that osmotin does not contain DNA-binding motifs. The alignment results of osmotin protein with the protein sequence from DATF showed the homology in the range of 0-20%, suggesting that it might not contain a DNA binding motif. Further to find unique DNA-binding domain, the superimposition of osmotin 3D structure on modeled Arabidopsis transcription factors using Chimera also suggested absence of the same. We, however, found evidence implicating osmotin in cell signaling. With these results, we concluded that osmotin is not a transcription factor but regulating proline biosynthesis and accumulation through cell signaling during abiotic stresses.

Keywords: osmotin, cell signaling modulator, bioinformatic tools, protein

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

Authors: Janneth Gonzalez, Marco Avila, George Barreto

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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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370 Climate Change Adaptation of the Portuguese Viticultural Sector

Authors: H. Fraga, J. A. Santos

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Vitiviniculture in Portugal is a key socio-economic sector, with a strong connection to local traditions and culture. Despite being a relatively small country, with prevailing Mediterranean environments, Portugal comprises an exceptionally large diversity of growth conditions (Terroirs). The vineyard area in Portugal is over 190 thousand hectares, being the eleventh wine producer and ninth wine exporter worldwide. Owing to the strong impact of weather and climate conditions on grapevine physiological development, grape berry quantity and quality show important inter-annual variability. Grapevines are also susceptible to climate change, as their responses will be unavoidably different under future climates. These impacts may change wine typicity of a given region or even its viticultural suitability. The current study reveals that the projected warming and drying trends for Portugal under the Representative Concentration Pathway (RCP) 4.5 and 8.5, are projected to 1) significantly shift current grapevine growing thermal conditions (e.g., heat and chill accumulation), 2) enhance water stress, 3) anticipate phenological timings and 4) modify yields. Moreover, the present study provides some hints regarding the effectiveness of mulching and irrigation as climate change adaptation measures. Our results show that the effectiveness of these adaptation measures will strongly rest on the strength of the climate change signal at a local scale, thus emphasizing the need for local-to-regional climate change assessments.

Keywords: viticulture, climate change, adaptation measures, Portugal

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369 Combating Malaria: A Drug Discovery Approach Using Thiazole Derivatives Against Prolific Parasite Enzyme PfPKG

Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

Abstract:

Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

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368 Experimental and Numerical Determination of the Freeze Point Depression of a Multi-Phase Flow in a Scraped Surface Heat Exchanger

Authors: Carlos A. Acosta, Amar Bhalla, Ruyan Guo

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Scraped surface heat exchangers (SSHE) use a rotor shaft assembly with scraping blades to homogenize viscous fluids during the heat transfer process. Obtaining in-situ measurements is difficult because the rotor and scraping blades spin continuously inside the mixing chamber, obstructing the instrumentation pathway. Computational fluid dynamics simulations provide useful insight into the flow behavior around the scraper blades for a variety of fluids and blade geometries. However, numerical solutions often focus on the fluid dynamics and heat transfer phenomena of rotating flow, ignoring the glass-transition temperature and freezing point depression. This research studies the multi-phase fluid dynamics and freezing point depression inside the SSHE with non-isothermal conditions in a time dependent process using an aqueous solution that contains 13.5 wt.% high fructose corn syrup and CO₂. The computational results were validated with in-situ pressure, temperature, and optical spectroscopy measurements. Results from the numerical model show good quantitatively agreement with experimental values.

Keywords: computational fluid dynamics, freezing point depression, phase-transition temperature, multi-phase flow

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367 Association of Hypoxia-Inducible Factor-1α in Patients with Chronic Obstructive Pulmonary Diseases

Authors: Kriti Upadhyay, Ashraf Ali, Puja Sohal, Randeep Guleria

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Background: In Chronic Obstructive Pulmonary diseases (COPD) pathogenesis oxidative stress plays an important role. Hypoxia-Inducible factor (HIF-1α) is a dimeric protein complex which Functions as a master transcriptional regulator of the adaptive response to hypoxiaand is a risk factor that increases when oxidative stress triggers. The role ofHIF-1αin COPD due to smoking is lacking. Aim: This study aims to evaluate the role of HIF-1α in smoker COPD patients comparing its association with diseases severity. Method: In this cross-sectional study, we recruited 87 subjects, 57 were smokers with COPD,15 were smokers without COPD and other 15 were non-smoker healthy controls. The mean age was 54.6± 9.32 (cases 57.08±8.15; controls 50.0± 9.8). There were 62%smokers, 25% non-smokers,7% tobacco chewers and 6% ex-smokers. Enzyme-linked immune sorbent assay (ELISA) method was used for analyzing serum samples wherein HIF-1α was analyzed by Sandwich-ELISA. Results: In smoker COPD patients, a significantly higher HIF-1α level showed positive association with hypoxia, smoking status and severity of disease (p=0.03). The mean value of HIF-1α was not significantly different in smokers without COPD and healthy controls. Conclusion: It is found that HIF-1α level was increased in smoker COPD, but not in smokers without COPD. This suggests that development of COPD drive the HIF-1α pathway and it correlates with the severity of diseases.

Keywords: COPD, chronic obstructive pulmonary diseases, smokers, nonsmokers, hypoxia

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366 Expression of Fused Plasmodium falciparum Orotate Phosphoribosyltransferase and Orotidine 5'-Monophosphate Decarboxylase in Escherichia coli

Authors: Waranya Imprasittichai, Patsarawadee Paojinda, Sudaratana R. Krungkrai, Nirianne Marie Q. Palacpac, Toshihiro Horii, Jerapan Krungkrai

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Fusion of the last two enzymes in the pyrimidine biosynthetic pathway in the inversed order by having COOH-terminal orotate phosphoribosyltransferase (OPRT) and NH2-terminal orotidine 5'-monophosphate decarboxylase (OMPDC), as OMPDC-OPRT, are described in many organisms. In this study, we constructed gene fusions of Plasmodium falciparum OMPDC-OPRT (1,836 bp) in pTrcHisA vector and expressed as an 6xHis-tag bifunctional protein in three Escherichia coli strains (BL21, Rosetta, TOP10) at 18 °C, 25 °C and 37 °C. The recombinant bifunctional protein was partially purified by Ni-Nitrilotriacetic acid-affinity chromatography. Specific activities of OPRT and OMPDC domains in the bifunctional enzyme expressed in E. coli TOP10 cells were approximately 3-4-fold higher than those in BL21 cells. There were no enzymatic activities when the construct vector expressed in Rosetta cells. Maximal expression of the fused gene was observed at 18 °C and the bifunctional enzyme had specific activities of OPRT and OMPDC domains in a ratio of 1:2. These results provide greater yields and better catalytic activities of the bifunctional OMPDC-OPRT enzyme for further purification and kinetic study.

Keywords: bifunctional enzyme, orotate phosphoribosyltransferase, orotidine 5'-monophosphate decarboxylase, plasmodium falciparum

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365 [Keynote Talk]: A Blueprint for an Educational Trajectory: The Power of Discourse in Constructing “Naughty” and “Adorable” Kindergarten Students

Authors: Fernanda T. Orsati, Julie Causton

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Discursive practices enacted by educators in kindergarten create a blueprint for how the educational trajectories of students with disabilities are constructed. This two-year ethnographic case study critically examine educators’ relationships with students considered to present challenging behaviors in one kindergarten classroom located in a predominantly White middle-class school district in the Northeast of the United States. Focusing on the language and practices used by one special education teacher and three teaching assistants, this paper analyzes how teacher responses to students’ behaviors constructs and positions students over one year of kindergarten education. Using a critical discourse analysis, it shows that educators understand students’ behaviors as a deficit and needing consequences. This study highlights how educators’ responses reflect students' individual characteristics including family background, socioeconomics and ability status. This paper offers in-depth analysis of two students’ stories, which evidenced that the language used by educators amplifies the social positioning of students within the classroom and creates a foundation for who they are constructed to be. Through exploring routine language and practices, this paper demonstrates that educators outlined a blueprint of kindergartners, which positioned students as learners in ways that became the ground for either a limited or a promising educational pathway for them.

Keywords: behavior, early education, special education, critical discourse analysis

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364 Enhanced Boiling Heat Transfer Using Wettability Patterned Surfaces

Authors: Dong Il Shim, Geehong Choi, Donghwi Lee, Namkyu Lee, Hyung Hee Cho

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Effective cooling technology is required to secure thermal stability in extreme heat generated systems such as integrated electronic devices and power generated systems. Pool boiling heat transfer is one of the powerful cooling mechanisms using phase change phenomena. Critical heat flux (CHF) and heat transfer coefficient (HTC) are main factors to evaluate the performance of boiling heat transfer. CHF is the limitation of boiling heat transfer before film boiling which occurs thermal failure. Surface wettability is an important surface characteristic of boiling heat transfer. A hydrophilic surface has higher CHF through effective working fluid supply to local hot spots. A hydrophobic surface promotes the onset of nucleate boiling (ONB) to enhance HTC. In this study, superbiphilic surfaces, which is combined with superhydrophillic and superhydrophobic, are applied on boiling experiments to maximize boiling performance. We conducted pool boiling heat transfer using DI water at a saturated temperature and recorded bubble dynamics using a high-speed camera with 2000 fps. As a result, superbiphilic patterned surfaces promote ONB and enhance both CHF and HTC. This study demonstrates the enhanced boiling performance using superbiphilic surfaces by effective nucleation and separation of liquid/vapor pathway. We expect that further enhancement of heat transfer could be achieved in future work using optimized patterned surfaces.

Keywords: boiling heat transfer, wettability, critical heat flux, heat transfer coefficient

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363 Impregnation Reduction Method for the Preparation of Platinum-Nickel/Carbon Black Alloy Nanoparticles as Faor Electrocatalyst

Authors: Maryam Kiani

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In order to enhance the efficiency and stability of an electrocatalyst for formic acid electro-oxidation reaction (FAOR), we developed a method to create Pt/Ni nanoparticles with carbon black. These nanoparticles were prepared using a simple impregnation reduction technique. During the observation, it was found that the nanoparticles had a spherical shape. Additionally, the average particle size remained consistent, falling within the range of about 4 nm. This approach aimed to obtain a loaded Pt-based electrocatalyst that would exhibit improved performance and stability when used in FAOR applications. By utilizing the impregnation reduction method and incorporating Ni nanoparticles along with Pt, we sought to enhance the catalytic properties of the material. By incorporating Ni atoms into the Pt structure, the electronic properties of Pt are modified, resulting in a delay in the chemisorption of harmful CO intermediate species. This modification also promotes the dehydrogenation pathway of the formic acid oxidation reaction (FAOR). Through electrochemical analysis, it has been observed that the Pt3Ni-C catalyst exhibits enhanced performance in FAOR compared to traditional Pt catalysts. This means that the addition of Ni atoms improves the efficiency and effectiveness of the Pt3Ni-C catalyst in facilitating the FAOR process. Overall, the utilization of these alloy nanoparticles as electrocatalysts represents a significant advancement in fuel cell technology.

Keywords: electrocatalyst, impregnation reduction method, formic acid electro-oxidation reaction, fuel cells

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362 Competitive Coordination Strategy Towards Reversible Hybrid Hetero-Homogeneous Oxygen-Evolving Catalyst

Authors: Peikun Zhang, Chunhua Cui

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Photoelectrochemical (PEC) water splitting provides a promising pathway to convert solar energy into renewable fuels. However, the main and seemingly insurmountable obstacle is that the sluggish kinetics of oxygen evolution reaction (OER) severely jeopardizes the overall efficiency, thus exploring highly active, stable, and appreciable catalysts is urgently requested. Herein a competitive coordination strategy was demonstrated to form a reversible hybrid homo-heterogeneous catalyst for efficient OER in alkaline media. The dynamic process involves an in-situ anchoring of soluble nickel–bipyridine pre-catalyst to a conductive substrate under OER and a re-dissolution course under open circuit potential, induced by the competitive coordination between nickel–bipyridine and nickel-hydroxyls. This catalyst allows to elaborately self-modulate a charge-transfer layer thickness upon the catalytic on-off operation, which affords substantially increased active sites, yet remains light transparency, and sustains the stability of over 200 hours of continuous operation. The integration of this catalyst with exemplified state-of-the-art Ni-sputtered Si photoanode can facilitate a ~250 mV cathodic shift at a current density of 20 mA cm-2. This finding helps the understanding of catalyst from a “dynamic” perspective, which represents a viable alternative to address remaining hurdles toward solar-driven water oxidation.

Keywords: molecular catalyst, oxygen evolution reaction, solar energy, transition metal complex, water splitting

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361 Time-Course Lipid Accumulation and Transcript Analyses of Lipid Biosynthesis Gene of Chlorella sp.3 under Nitrogen Limited Condition

Authors: Jyoti Singh, Swati Dubey, Mukta Singh, R. P. Singh

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The freshwater microalgae Chlorella sp. is alluring considerable interest as a source for biofuel production due to its fast growth rate and high lipid content. Under nitrogen limited conditions, they can accumulate significant amounts of lipids. Thus, it is important to gain insight into the molecular mechanism of their lipid metabolism. In this study under nitrogen limited conditions, regular pattern of growth characteristics lipid accumulation and gene expression analysis of key regulatory genes of lipid biosynthetic pathway were carried out in microalgae Chlorella sp 3. Our results indicated that under nitrogen limited conditions there is a significant increase in the lipid content and lipid productivity, achieving 44.21±2.64 % and 39.34±0.66 mg/l/d at the end of the cultivation, respectively. Time-course transcript patterns of lipid biosynthesis genes i.e. acetyl coA carboxylase (accD) and diacylglycerol acyltransferase (dgat) showed that during late log phase of microalgae Chlorella sp.3 both the genes were significantly up regulated as compared to early log phase. Moreover, the transcript level of the dgat gene is two-fold higher than the accD gene. The results suggested that both the genes responded sensitively to the nitrogen limited conditions during the late log stage, which proposed their close relevance to lipid biosynthesis. Further, this transcriptome data will be useful for engineering microalgae species by targeting these genes for genetic modification to improve microalgal biofuel quality and production.

Keywords: biofuel, gene, lipid, microalgae

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360 A Survey of Chronic Pain Patients’ Experiences in the Emergency Department

Authors: G. Fitzpatrick, S. O. Chonghaile, D. Harmon

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Objective: Chronic pain patients represent a unique challenge in the Emergency Department. Very little literature has been published regarding this group of patients. Our aim was to determine the attitude of patients with chronic pain to the Emergency Department in order to improve and streamline their future visits. Methods: A two-year survey was carried out on Chronic Pain Patients regarding their Emergency Department Attendances. Patients attending the Pain Clinic in Croom Hospital, Co. Limerick were asked to complete a 20-part questionnaire regarding their experiences of visiting the Emergency Department in the preceding year. 46 questionnaires were completed. Results: Unbearable breakthrough pain was the main reason for visiting the Emergency Department. More than half (54%) of those surveyed were not satisfied with the treatment received. Problems indicated included under-treatment of pain (59%), a sense of being under undue suspicion of drug-seeking behaviour (33%) and a perception that the patient themselves understood their condition better than the treating doctor (76%). Paracetamol, NSAIDs, or time off work comprised 72% of the treatments offered – all of which could have been provided by their General Practitioner. Only 4% were offered a nerve block. 67% felt that the creation of personalised Patient Plans, consisting of an agreed plan between the patient, their pain specialist, and the Emergency Department, would expedite their trip through the Emergency Department. Conclusions: Chronic pain patients generally have a negative experience in the ED. Possible future solutions include increasing our empathy and levels of knowledge, provision of nerve blocks in the ED, and use of personalised “Patient Plans” to streamline the treatment pathway for this group of patients.

Keywords: chronic pain, survey, patients, emergency department

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359 Resort to Religious and Faith Healing Practices in the Pathway to Care for Mental Illness: A Study among Mappila Muslims of Malabar, Kerala

Authors: K. P. Farsana

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Belief in supernatural causation of mental illnesses and resort to religious and faith healing as the method of intervention still continue in many parts of the world. The proposed study intended to find out the belief and causation on health and illness and utilization of religious and faith healing, its implications, and associated socio-cultural and religious factors among Mappila Muslims of Malabar, Kerala, a southern state of India.Thangals are the endogamous community in Kerala, of Yemeni heritage who claim direct descent from the Prophet Mohammed’s family. Because of their sacrosanct status, many Thangal works as religious healers in Malabar, Northern Kerala. Using the case of one Thangal healer as an illustration of the many religious healers in Kerala who engage in the healing practices, it is intended, in this paper to illustrate the religious and ritual healing practices among Mappila Muslims of Malabar. It was found that the majority of the Mappila Muslims believed in supernatural causation on illness, and majority of them consulted religious and faith healers for various health problems before seeking professional help, and a considerable proportion continued to believe in the healing efficiency of the religious and faith healing. A significant proportion of the population found religious and faith healing practices are supportive and more acceptable within the community. Religion and belief system play an important role in the heath seeking behavior of a person.

Keywords: religious and faith healing, mental illness, Mappila Muslims, Malabar

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358 Protective Role of Phycobiliproteins in ROS-Associated Physiological Anomalies

Authors: Ravi Raghav Sonani, Niraj Kumar Singh, Jitendra Kumar, Datta Madamwar

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Phycobiliproteins (PBPs) are light harvesting proteins showing very strong absorbance and fluorescence in the visible range of the solar spectrum. Phycoerythrin (PE) and phycocyanin (PC) are majorly found PBPs in the cyanobacteria and red algae. In the present study, we have investigated the reactive oxygen species (ROS)-averting capacity of purified PE and PC of cyanobacterial origin. Furthermore, the possibility - whether the ROS-averting potential of PBPs can be explored in the therapeutics of oxidative stress associated physiological anomalies including aging and neurodegenerative diseases. The nematode Caenorhabditis elegans has been used as model organism in this study. PE and PC treatment moderated normal aging and associated physiological functionalities like pharyngeal pumping and locomotion of C. elegans. Moreover, PE-treatment enhanced the stress (oxidative and heat) tolerance upon PE and PC treatment. Specifically, PE treatment was also noted to moderate the progression of Alzheimer’s disease in transgenic C. elegans CL4176. However, PC-treatment curtailed the polyQ aggregation mediated proteotoxicity in C. elegans AM141 (Huntington disease model) under stressed (paraquat stress) as well as normal conditions. The effectiveness of PE and PC in expanding the lifespan of mutant C. elegans knockout for some up- (daf 16) and down- (daf-2 and age-1) stream regulators of insulin/IGF-1 signalling (IIS) shows the independency of their effects from DAF-2–AGE-1–DAF-16 signalling pathway. In conclusion, the present report demonstrates the anti-aging and neuro-protective potential of cyanobacterial PE and PC.

Keywords: phycobiliproteins, aging, alzheimer, huntington, C. elegans

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357 Inclusion of Transgender in Mainstream Secondary Schools of Bangladesh: Perceptions and Issues

Authors: Shanaj Parvin Jonaki

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After the first wave of the feminist movement, gender has become one of the most important issues to be researched in social science. Many gender theories have been invented and opened a new window to look at. These works showed how gender is a social construct, how gender has been used to oppress, how to rule. While it's the education system’s duty to guide students to understand the concept of gender, it sometimes shows gender-based discrimination. Transgenders exclusion from educational institutes of Bangladesh justifies this very statement. This study aims to figure out how people perceive transgenders’ identity, their inclusion in secondary schools, as well as the underlying barriers in the pathway of inclusion in the context of Bangladesh. A qualitative approach was taken to explore different perspectives towards transgender inclusion from several stakeholders such as students, parents, and teachers of secondary schools and transgenders as well. Data were collected through focus group discussion and interview by convenient sampling. 15 students, 10 parents, and 5 teachers were selected from Bangla Medium school as well as from Madrasha. Collected data were analyzed thematically and were run by experts of gender, education, and psychology to identify the core barriers of inclusion. The study revealed that most of the students, teachers, and parents lacked the knowledge of non-binary gender identities, and they showed unwillingness towards the inclusion of transgender in schools because of the cultural context of Bangladesh. Moreover, this study suggests future initiatives to be taken to ensure the inclusion of transgenders in a secondary school in our country and analyzes it through the lens of feminist theories.

Keywords: education, gender, inclusion, transgender

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356 Structure-Based Virtual Screening and in Silico Toxicity Test of Compounds against Mycobacterium tuberculosis 7,8-Diaminopelargonic Acid Aminotransferase (MtbBioA)

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

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One of the major interferences in the Philippines’ tuberculosis control program is the widespread prevalence of Mtb strains that are resistant to known drugs, such as the MDR-TB (Multi Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug Resistant Tuberculosis). Therefore, there is a pressing need to search for novel Mtb drug targets in order to be able to combat these drug resistant strains. The enzyme 7,8-diaminopelargonic acid aminotransferase enzyme, or more commonly known as BioA, is one such ideal target, as it is known that humans do not possess this enzyme. BioA primarily plays a key role in Mtb’s lipid biosynthesis pathway; more specifically in the synthesis of the enzyme cofactor biotin. In this study, structure-based pharmacophore screening, docking, and ADMET evaluation of compounds obtained from the DrugBank chemical database were performed against the MtbBioA enzyme. Results of the screening, docking, ADMET, and TOPKAT calculations revealed that out of the 6,516 compounds in the library, only 7 compounds indicated more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM), as well as good solubility and toxicity properties. Moreover, out of these 7 compounds, Molecule 6 exhibited the best solubility and toxicity properties. In the future, these lead compounds may then be subjected to bioactivity assays in vitro or in vivo for further evaluation of its therapeutic efficacy.

Keywords: 7, 8-diaminopelargonic acid aminotransferase, BioA, pharmacophore, molecular docking, ADMET, TOPKAT

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355 Nitric Oxide and Potassium Channels but Not Opioid and Cannabinoid Receptors Mediate Tramadol-Induced Peripheral Antinociception in Rat Model of Paw Pressure Withdrawal

Authors: Raquel R. Soares-Santos, Daniel P. Machado, Thiago L. Romero, Igor D. G. Duarte

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Tramadol, an analgesic classified as an 'atypical opioid,' exhibits both opioid and non-opioid mechanisms of action. This study aimed to explore these mechanisms, specifically the opioid-, cannabinoid-, nitric oxide-, and potassium channel-based mechanisms, which contribute to the peripheral antinociception effect of tramadol, in an experimental rat model. The nociceptive threshold was determined using paw pressure withdrawal. To examine the mechanisms of action, several substances were administered intraplantarly: naloxone, a non-selective opioid antagonist (50 μg/paw); AM251 (80 μg/paw) and AM630 (100 μg/paw) as the selective antagonists for type 1 and type 2 cannabinoid receptors, respectively; nitric oxide synthase inhibitors L-NOArg, L-NIO, L-NPA, and L-NIL (24 μg/paw); and the enzyme inhibitors of guanylatocyclase and phosphodiesterase of cGMP, ODQ and zaprinast. Additionally, potassium channel blockers glibenclamide, tetraethylammonium, dequalinium, and paxillin were used. The results showed that opioid and cannabinoid receptor antagonists did not reverse tramadol’s effects. L-NOarg, L-NIO, and L-NPA partially reversed antinociception, while ODQ completely reversed, and zaprinast enhanced tramadol’s antinociception effect. Notably, glibenclamide blocked tramadol’s antinociception in a dose-dependent manner. These findings suggest that tramadol’s peripheral antinociception effect is likely mediated by the nitrergic pathway and sensitive ATP potassium channels, rather than the opioid and cannabinoid pathways.

Keywords: tramadol, nitric oxide, potassium channels, peripheral analgesia, opioid

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354 Exploring Public Trust in Democracy

Authors: Yaron Katz

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The investigation of immigrants' electoral choices has remained relatively uncharted territory despite the fact that numerous nations extend political rights to their expatriates. This paper centers its attention on the matter of public trust in democracy, with a focus on the intricacies of Israeli politics as a divided system. It delves into the potential implications of political and social transformations stemming from the involvement of expatriate voters in elections taking place in their country of origin. In doing so, the article endeavors to explore a pathway for resolving a persistent challenge facing the stability of the Israeli political landscape over the past decade: the difficulty in forming a resilient government that genuinely represents the majority of voters. An examination is conducted into the role played by a demographic with the capacity to exert significant influence on election outcomes, namely, individuals residing outside of Israel. The objective of this research is to delve into this subject, dissecting social developments and political prospects that may shape the country's trajectory in the coming decades. This inquiry is especially pertinent given the extensive engagement of migrants in Israeli politics and the link between Israelis living abroad and their home country. Nevertheless, the study's findings reveal that while former citizens exhibit extensive involvement in Israeli politics and are cognizant of the potential consequences of permitting them to participate in elections, they maintain steadfastly unfavorable views regarding the inclusion of Israelis living overseas in their home country's electoral processes.

Keywords: trust, globalization, policy, democracy

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353 Estimation of Maize Yield by Using a Process-Based Model and Remote Sensing Data in the Northeast China Plain

Authors: Jia Zhang, Fengmei Yao, Yanjing Tan

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The accurate estimation of crop yield is of great importance for the food security. In this study, a process-based mechanism model was modified to estimate yield of C4 crop by modifying the carbon metabolic pathway in the photosynthesis sub-module of the RS-P-YEC (Remote-Sensing-Photosynthesis-Yield estimation for Crops) model. The yield was calculated by multiplying net primary productivity (NPP) and the harvest index (HI) derived from the ratio of grain to stalk yield. The modified RS-P-YEC model was used to simulate maize yield in the Northeast China Plain during the period 2002-2011. The statistical data of maize yield from study area was used to validate the simulated results at county-level. The results showed that the Pearson correlation coefficient (R) was 0.827 (P < 0.01) between the simulated yield and the statistical data, and the root mean square error (RMSE) was 712 kg/ha with a relative error (RE) of 9.3%. From 2002-2011, the yield of maize planting zone in the Northeast China Plain was increasing with smaller coefficient of variation (CV). The spatial pattern of simulated maize yield was consistent with the actual distribution in the Northeast China Plain, with an increasing trend from the northeast to the southwest. Hence the results demonstrated that the modified process-based model coupled with remote sensing data was suitable for yield prediction of maize in the Northeast China Plain at the spatial scale.

Keywords: process-based model, C4 crop, maize yield, remote sensing, Northeast China Plain

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352 An Inverse Docking Approach for Identifying New Potential Anticancer Targets

Authors: Soujanya Pasumarthi

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Inverse docking is a relatively new technique that has been used to identify potential receptor targets of small molecules. Our docking software package MDock is well suited for such an application as it is both computationally efficient, yet simultaneously shows adequate results in binding affinity predictions and enrichment tests. As a validation study, we present the first stage results of an inverse-docking study which seeks to identify potential direct targets of PRIMA-1. PRIMA-1 is well known for its ability to restore mutant p53's tumor suppressor function, leading to apoptosis in several types of cancer cells. For this reason, we believe that potential direct targets of PRIMA-1 identified in silico should be experimentally screened for their ability to inhibitcancer cell growth. The highest-ranked human protein of our PRIMA-1 docking results is oxidosqualene cyclase (OSC), which is part of the cholesterol synthetic pathway. The results of two followup experiments which treat OSC as a possible anti-cancer target are promising. We show that both PRIMA-1 and Ro 48-8071, a known potent OSC inhibitor, significantly reduce theviability of BT-474 breast cancer cells relative to normal mammary cells. In addition, like PRIMA-1, we find that Ro 48-8071 results in increased binding of mutant p53 to DNA in BT- 474cells (which highly express p53). For the first time, Ro 48-8071 is shown as a potent agent in killing human breast cancer cells. The potential of OSC as a new target for developing anticancer therapies is worth further investigation.

Keywords: inverse docking, in silico screening, protein-ligand interactions, molecular docking

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351 Evaluation of DNA Oxidation and Chemical DNA Damage Using Electrochemiluminescent Enzyme/DNA Microfluidic Array

Authors: Itti Bist, Snehasis Bhakta, Di Jiang, Tia E. Keyes, Aaron Martin, Robert J. Forster, James F. Rusling

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DNA damage from metabolites of lipophilic drugs and pollutants, generated by enzymes, represents a major toxicity pathway in humans. These metabolites can react with DNA to form either 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), which is the oxidative product of DNA or covalent DNA adducts, both of which are genotoxic and hence considered important biomarkers to detect cancer in humans. Therefore, detecting reactions of metabolites with DNA is an effective approach for the safety assessment of new chemicals and drugs. Here we describe a novel electrochemiluminescent (ECL) sensor array which can detect DNA oxidation and chemical DNA damage in a single array, facilitating a more accurate diagnostic tool for genotoxicity screening. Layer-by-layer assembly of DNA and enzyme are assembled on the pyrolytic graphite array which is housed in a microfluidic device for sequential detection of two type of the DNA damages. Multiple enzyme reactions are run on test compounds using the array, generating toxic metabolites in situ. These metabolites react with DNA in the films to cause DNA oxidation and chemical DNA damage which are detected by ECL generating osmium compound and ruthenium polymer, respectively. The method is further validated by the formation of 8-oxodG and DNA adduct using similar films of DNA/enzyme on magnetic bead biocolloid reactors, hydrolyzing the DNA, and analyzing by liquid chromatography-mass spectrometry (LC-MS). Hence, this combined DNA/enzyme array/LC-MS approach can efficiently explore metabolic genotoxic pathways for drugs and environmental chemicals.

Keywords: biosensor, electrochemiluminescence, DNA damage, microfluidic array

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350 Interaction of Chemical, Microbiological and Ecological Aspects in the Brown Alga Zonaria Tournefortii

Authors: Sonia Hamiche, Naima Bouzidi, Mohamed Reda Zahi, Yasmina Daghbouche, Abdelmalek Badis, Mohamed El Hattab

Abstract:

This study was carried out on the brown alga Zonaria tourfortii harvested on the central coast of Algeria. The chemical study enabled the characterization of phenolic compounds, mainly acyl phloroglucinol and chromone metabolites. The study isolated a significant quantity of all-cis-5,8,11,14,17 eicosapentanoic acid (EPA). Based on a literature review, we have proposed a biosynthetic pathway leading from EPA to phenolic metabolites. Bacterial screening from the algal surface led to isolate 30 bacterial strains, including 26 Gram+ containing the Staphylococcus and Bacillus genus, and 4 Gram- containing the Acinetobacter and Enterobacteracea genus. In terms of activity profiles, strain S13 (identified as Bacillus amyloliquefaciens based on 16S rRNA technique) proved highly interesting inhibitory activities against target germs, as well as its production of diffusible and volatile compounds. Bacterial cells from the B. amyloliquefaciens S13 strain were used to recover a volatile fraction. Analysis was carried out by gas chromatography-mass spectrometry. The main volatile compounds identified were: 13-epi-manoyl oxide (29.39%), manool (17.39%), 15,16-dinorlabd-8(20)-en-13-one (13.17%), labda-8(17),13Z-dien-15-ol (9. 51%) and 3-acetoxy-13 epimanoyl oxide (5.26%) belonging to the labdane class of diterpenes, the latter having never been described in the category of microbial volatile organic compounds. Ecological aspects were discussed.

Keywords: chemical analysis, acylphloroglucinols, phenolic compounds, microbial volatiles, Zonaria tournefortii

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349 Embracing Circular Economy: Unlocking Sustainable Growth in Emerging Markets

Authors: Mario Jose Paillacho Silva, José Ángel Pérez López

Abstract:

This article delves into the critical role of circular economy principles in unlocking sustainable growth and addressing environmental inequalities in emerging markets. Circular economy practices, rooted in regenerative systems and resource conservation, offer a transformative pathway for dynamic economies to achieve prosperity while minimizing environmental impact. The article comprehensively explores the understanding of the circular economy in emerging markets, emphasizing its economic benefits, social implications, and environmental advantages. It highlights key challenges and opportunities faced by these markets and emphasizes the crucial role of governments in creating supportive policy frameworks. It emphasizes how circular economy practices empower local communities and promote social inclusion and equality. Furthermore, the article underscores how the adoption of circular economy practices can mitigate waste, pollution, and resource scarcity, thus contributing to climate change mitigation and adaptation. Integrating circular economy principles with the United Nations' sustainable development goals (SDGs), the article showcases the potential of circularity in fostering responsible consumption and production, sustainable economic growth, and environmental protection. Overall, the article advocates for cross-sector collaboration and knowledge sharing to overcome barriers and scale circular economy practices in emerging markets, ultimately leading to a more equitable, prosperous, and environmentally sustainable future.

Keywords: circular economy, sustainability, emerging markets, circularity

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348 Neighborhood Linking Social Capital as a Predictor of Drug Abuse: A Swedish National Cohort Study

Authors: X. Li, J. Sundquist, C. Sjöstedt, M. Winkleby, K. S. Kendler, K. Sundquist

Abstract:

Aims: This study examines the association between the incidence of drug abuse (DA) and linking (communal) social capital, a theoretical concept describing the amount of trust between individuals and societal institutions. Methods: We present results from an 8-year population-based cohort study that followed all residents in Sweden, aged 15-44, from 2003 through 2010, for a total of 1,700,896 men and 1,642,798 women. Social capital was conceptualized as the proportion of people in a geographically defined neighborhood who voted in local government elections. Multilevel logistic regression was used to estimate odds ratios (ORs) and between-neighborhood variance. Results: We found robust associations between linking social capital (scored as a three level variable) and DA in men and women. For men, the OR for DA in the crude model was 2.11 [95% confidence interval (CI) 2.02-2.21] for those living in areas with the lowest vs. highest level of social capital. After accounting for neighborhood-level deprivation, the OR fell to 1.59 (1.51-1-68), indicating that neighborhood deprivation lies in the pathway between linking social capital and DA. The ORs remained significant after accounting for age, sex, family income, marital status, country of birth, education level, and region of residence, and after further accounting for comorbidities and family history of comorbidities and family history of DA. For women, the OR decreased from 2.15 (2.03-2.27) in the crude model to 1.31 (1.22-1.40) in the final model, adjusted for multiple neighborhood-level and individual-level variables. Conclusions: Our study suggests that low linking social capital may have important independent effects on DA.

Keywords: drug abuse, social linking capital, environment, family

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347 Effects of New Anthraquinone Derivatives on Resistance Ovarian Cancer Cells and The Mechanism Investigation

Authors: Hui-Hsin Huang, Sheng-Tung Huang, Chi-Ming Lee, Chiao-Han Yen, Chun-Mao Lin

Abstract:

At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future.

Keywords: anthraquinone, camptothecin, resistance, ovarian cancer

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346 Clarifying the Possible Symptomatic Pathway of Comorbid Depression, Anxiety, and Stress Among Adolescents Exposed to Childhood Trauma: Insight from the Network Approach

Authors: Xinyuan Zou, Qihui Tang, Shujian Wang, Yulin Huang, Jie Gui, Xiangping Liu, Gang Liu, Yanqiang Tao

Abstract:

Childhood trauma can have a long-lasting influence on individuals and contribute to mental disorders, including depression and anxiety. The current study aimed to explore the symptomatic and developmental patterns of depression, anxiety, and stress among adolescents who have suffered from childhood trauma. A total of 3,598 college students (female = 1,617 (44.94%), Mean Age = 19.68, SD Age = 1.35) in China completed the Childhood Trauma Questionnaire (CTQ) and the Depression, Anxiety, and Stress Scales (DASS-21), and 2,337 participants met the selection standard based on the cut-off scores of the CTQ. The symptomatic network and directed acyclic graph (DAG) network approaches were used. The results revealed that males reported experiencing significantly more physical abuse, physical neglect, emotional neglect, and sexual abuse compared to females. However, females scored significantly higher than males on all items of DASS-21, except for “Worthless”. No significant difference between the two genders was observed in the network structure and global strength. Meanwhile, among all participants, “Down-hearted” and “Agitated” appeared to be the most interconnected symptoms, the bridge symptoms in the symptom network, as well as the most vital symptoms in the DAG network. Apart from that, “No-relax” also served as the most prominent symptom in the DAG network. The results suggested that intervention targeted at assisting adolescents in developing more adaptive coping strategies with stress and regulating emotion could benefit the alleviation of comorbid depression, anxiety, and stress.

Keywords: symptom network, childhood trauma, depression, anxiety, stress

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345 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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344 Characterization and Quantification of Relatives Amounts of Phosphorylated Glucosyl Residues in C6 and C3 Position in Banana Starch Granules by 31P-NMR

Authors: Renata Shitakubo, Hanyu Yangcheng, Jay-lin Jane, Fernanda Peroni Okita, Beatriz Cordenunsi

Abstract:

In the degradation transitory starch model, the enzymatic activity of glucan/water dikinase (GWD) and phosphoglucan/water dikinase (PWD) are essential for the granule degradation. GWD and PWD phosphorylate glucose molecules in the positions C6 and C3, respectively, in the amylopectin chains. This action is essential to allow that β-amylase degrade starch granules without previous action of α-amylase. During banana starch degradation, as part of banana ripening, both α- and β-amylases activities and proteins were already detected and, it is also known that there is a GWD and PWD protein bounded to the starch granule. Therefore, the aim of this study was to quantify both Gluc-6P and Gluc-3P in order to estimate the importance of the GWD-PWD-β-amylase pathway in banana starch degradation. Starch granules were isolated as described by Peroni-Okita et al (Carbohydrate Polymers, 81:291-299, 2010), from banana fruit at different stages of ripening, green (20.7%), intermediate (18.2%) and ripe (6.2%). Total phosphorus content was determinate following the Smith and Caruso method (1964). Gluc-6P and Gluc-3P quantifications were performed as described by Lim et al (Cereal Chemistry, 71(5):488-493, 1994). Total phosphorous content in green banana starch is found as 0.009%, intermediary banana starch 0.006% and ripe banana starch 0.004%, both by the colorimetric method and 31P-NMR. The NMR analysis showed the phosphorus content in C6 and C3. The results by NMR indicate that the amylopectin is phosphorylate by GWD and PWD before the bananas become ripen. Since both the total content of phosphorus and phosphorylated glucose molecules at positions C3 and C6 decrease with the starch degradation, it can be concluded that this phosphorylation occurs only in the surface of the starch granule and before the fruit be harvested.

Keywords: starch, GWD, PWD, 31P-NMR

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343 Formulation and in Vitro Evaluation of Cubosomes Containing CeO₂ Nanoparticles Loaded with Glatiramer Acetate Drug

Authors: Akbar Esmaeili, Zahra Salarieh

Abstract:

Cerium oxide nanoparticles (nano-series) are used as catalysts in industrial applications due to their free radical scavenging properties. Given that free radicals play an essential role in the pathology of many neurological diseases, we investigated the use of nanocrystals as a potential therapeutic agent for oxidative damage. This project synthesized nano-series from a new and environmentally friendly bio-pathway. Investigation of cerium nitrate in culture medium containing inoculated Lactobacillus acidophilus strain before incubation produces nano-series. Loaded with glatiramer acetate (GA) was formed by coating carboxymethylcellulose (CMC) and CeO2. FE-SEM analysis showed nano-series in the 9-11 nm range, spherical shape, and uniform particle size distribution. Cubic nanoparticles containing anti-multiple sclerosis (anti-Ms) treatment called GA were used. Glycerol monostearate (GMS) was used as a fat base, and evening primrose extract was used as an anti-inflammatory in cubosomes. Design-Expert® software was used to study the effects of different formulation factors on the properties of GAloaded cubic dispersions. Thirty GA-labeled cubic dispersions were prepared with GA-labeled carboxymethylcellulose and evaluated in vitro. The results showed an average nano-series size of 89.02 and a zeta potential of -49.9. Cubosomes containing GA-CMC/CeO2 showed a stable release profile for 180 min. The results showed that cubosomes containing GA-CMC/CeO2 could be a promising drug carrier with normal release behavior.

Keywords: ciochemistry, biotechnology, molecular, biology

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