Search results for: core protein
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4273

Search results for: core protein

1453 Transcriptomic Analyses of Kappaphycus alvarezii under Different Wavelengths of Light

Authors: Vun Yee Thien, Kenneth Francis Rodrigues, Clemente Michael Vui Ling Wong, Wilson Thau Lym Yong

Abstract:

Transcriptomes associated with the process of photosynthesis have offered insights into the mechanism of gene regulation in terrestrial plants; however, limited information is available as far as macroalgae are concerned. This investigation aims to decipher the underlying mechanisms associated with photosynthesis in the red alga, Kappaphycus alvarezii, by performing a differential expression analysis on a de novo assembled transcriptomes. Comparative analysis of gene expression was designed to examine the alteration of light qualities and its effect on physiological mechanisms in the red alga. High-throughput paired-end RNA-sequencing was applied to profile the transcriptome of K. alvarezii irradiated with different wavelengths of light (blue 492-455 nm, green 577-492 nm and red 780-622 nm) as compared to the full light spectrum, resulted in more than 60 million reads individually and assembled using Trinity and SOAPdenovo-Trans. The transcripts were annotated in the NCBI non-redundant (nr) protein, SwissProt, KEGG and COG databases with a cutoff E-value of 1e-5 and nearly 30% of transcripts were assigned to functional annotation by Blast searches. Differential expression analysis was performed using edgeR. The DEGs were designated to six categories: BL (blue light) regulated, GL (green light) regulated, RL (red light) regulated, BL or GL regulated, BL or RL regulated, GL or RL regulated, and either BL, GL or RL regulated. These DEGs were mapped to terms in KEGG database and compared with the whole transcriptome background to search for genes that regulated by light quality. The outcomes of this study will enhance our understanding of molecular mechanisms underlying light-induced responses in red algae.

Keywords: de novo transcriptome sequencing, differential gene expression, Kappaphycus alvareziired, red alga

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1452 Using the SMT Solver to Minimize the Latency and to Optimize the Number of Cores in an NoC-DSP Architectures

Authors: Imen Amari, Kaouther Gasmi, Asma Rebaya, Salem Hasnaoui

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The problem of scheduling and mapping data flow applications on multi-core architectures is notoriously difficult. This difficulty is related to the rapid evaluation of Telecommunication and multimedia systems accompanied by a rapid increase of user requirements in terms of latency, execution time, consumption, energy, etc. Having an optimal scheduling on multi-cores DSP (Digital signal Processors) platforms is a challenging task. In this context, we present a novel technic and algorithm in order to find a valid schedule that optimizes the key performance metrics particularly the Latency. Our contribution is based on Satisfiability Modulo Theories (SMT) solving technologies which is strongly driven by the industrial applications and needs. This paper, describe a scheduling module integrated in our proposed Workflow which is advised to be a successful approach for programming the applications based on NoC-DSP platforms. This workflow transform automatically a Simulink model to a synchronous dataflow (SDF) model. The automatic transformation followed by SMT solver scheduling aim to minimize the final latency and other software/hardware metrics in terms of an optimal schedule. Also, finding the optimal numbers of cores to be used. In fact, our proposed workflow taking as entry point a Simulink file (.mdl or .slx) derived from embedded Matlab functions. We use an approach which is based on the synchronous and hierarchical behavior of both Simulink and SDF. Whence, results of running the scheduler which exist in the Workflow mentioned above using our proposed SMT solver algorithm refinements produce the best possible scheduling in terms of latency and numbers of cores.

Keywords: multi-cores DSP, scheduling, SMT solver, workflow

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1451 Distribution of Gamma-Radiation Levels in Core Sediment Samples in Gulf of İzmir, Eastern Aegean Sea, Turkey

Authors: D. Kurt, İ. F. Barut, Z. Ü. Yümün, E. Kam

Abstract:

After development of the industrial revolution, industrial plants and settlements have spread widely on the sea coasts. This concentration also brings environmental pollution in the sea. This study focuses on the Gulf of İzmir where is located in West of Turkey and it is a fascinating natural gulf of the Eastern Aegean Sea. Investigating marine current sediment is extremely important to detect pollution. Natural radionuclides’ pollution of the marine environment which is also known as a significant environmental anxiety. Ground drilling cores (the depth of each sediment is variant) were collected from the Gulf of İzmir’s four different locations which were Karşıyaka, İnciraltı, Çeşmealtı and Bayraklı. These sediment cores were put in preserving bags with weight around 1 kg, and they were dried at room temperature in a week for moisture removal. Then, they were sieved with 1 mm sieve holes, and finally these powdered samples were relocation to polyethylene Marinelli beakers of 100 ml versions. Each prepared sediment was waited to reach radioactive equilibrium between uranium and thorium for 40 days. Gamma spectrometry measurements were settled using a HPG (High- Purity Germanium) semiconductor detector. Semiconductor detectors are very good at separating power of the energy, they are easily able to differentiate peaks that are pretty close to each other. That is why, gamma spectroscopy’s usage is common for the determination of the activities of U - 238, Th - 232, Ra - 226, Cr - 137 and K - 40 in Bq kg⁻¹. In this study, the results display that the average concentrations of activities’ values are in respectively; 2.2 ± 1.5 Bq/ kg⁻¹, 0.98 ± 0.02 Bq/ kg⁻¹, 8 ± 0.96 Bq/ kg⁻¹, 0.93 ± 0.14 Bq/ kg⁻¹, and 76.05 ± 0.93 Bq/ kg⁻¹. The outcomes of the study are able to be used as a criterion for forthcoming research and the obtained data would be pragmatic for radiological mapping of the precise areas.

Keywords: gamma, Gulf of İzmir (Eastern Aegean Sea-Turkey), natural radionuclides, pollution

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1450 Applying Knowledge Management and Attitude Based on Holistic Approach in Learning Andragogy, as an Effort to Solve Environmental Problems after Mining Activities

Authors: Aloysius Hardoko, Susilo

Abstract:

The root cause of environmental damage post coal mining activities as determined by the province of East Kalimantan as a corridor of economic activity masterplan acceleration of economic development expansion (MP3EI) is the behavior of adults. Adult behavior can be changed through knowledge management and attitude. Based on the root of the problem, the objective of the research is to apply knowledge management and attitude based on holistic approach in learning andragogy as an effort to solve environmental problems after coal mining activities. Research methods to achieve the objective of using quantitative research with pretest posttest group design. Knowledge management and attitudes based on a holistic approach in adult learning are applied through initial learning activities, core and case-based cover of environmental damage. The research instrument is a description of the case of environmental damage. The data analysis uses t-test to see the effect of knowledge management attitude based on holistic approach before and after adult learning. Location and sample of representative research of adults as many as 20 people in Kutai Kertanegara District, one of the districts in East Kalimantan province, which suffered the worst environmental damage. The conclusion of the research result is the application of knowledge management and attitude in adult learning influence to adult knowledge and attitude to overcome environmental problem post coal mining activity.

Keywords: knowledge management and attitude, holistic approach, andragogy learning, environmental damage

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1449 RhoA Regulates E-Cadherin Intercellular Junctions in Oral Squamous Carcinoma Cells

Authors: Ga-Young Lee, Hyun-Man Kim

Abstract:

The modulation of the cell-cell junction is critical in epithelial-mesenchymal transition during tumorigenesis. As RhoA activity is known to be up-regulated to dissociate cell-cell junction by contracting acto-myosin complex in various cancer cells, the present study investigated if RhoA activity was also associated with the disruption of the cell-cell junction of oral cancer cells. We studied SCC-25 cells which are established from oral squamous cell carcinoma if their E-cadherin junction (ECJ) was under control of RhoA. Interestingly, development of ECJ of SCC-25 cells depended on the amount of fibronectin (FN) coated on the culture dishes. Seeded cells promptly aggregated to develop ECJ on the substrates coated with a low amount of FN, whereas they were retarded in the development of ECJ on the substrates coated with a high amount of FN. However, it was an unexpected finding that total RhoA activity was lower in the dissociated cells on the substrates of high FN than in the aggregated cells on the substrates of low FN. Treating the dissociated cells on the substrates of high FN with LPA, a RhoA activator, promoted the development to ECJ. In contrast, treating the aggregated cells on the substrates of low FN with Clostridium botulinum C3, a toxin decreasing RhoA activity, dissociated cells concomitant with the disruption of ECJ. Genetical knockdown of RhoA expression by transfecting RhoA siRNA also down-regulated the development of ECJ in SCC-25 cells. Furthermore, PMA, an activator of protein kinase C (PKC), down-regulated the development of ECJ junction of SCC-25 cells on the substrates coated with low FN. In contrast, GO6976, a PKC inhibitor, up-regulated the development of ECJ of SCC-25 cells with the activation of RhoA on the substrates coated with high FN. In conclusion, in the present study, we demonstrated unexpected results that the activation of RhoA promotes the development of ECJ, whereas the inhibition of RhoA retards the development of ECJ in SCC-25 cells.

Keywords: E-cadherin junction, oral squamous cell carcinoma, PKC, RhoA, SCC-25

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1448 Programmed Cell Death in Datura and Defensive Plant Response toward Tomato Mosaic Virus

Authors: Asma Alhuqail, Nagwa Aref

Abstract:

Programmed cell death resembles a real nature active defense in Datura metel against TMV after three days of virus infection. Physiological plant response was assessed for asymptomatic healthy and symptomatic infected detached leaves. The results indicated H2O2 and Chlorophyll-a as the most potential parameters. Chlorophyll-a was considered the only significant predictor variant for the H2O2 dependent variant with a P value of 0.001 and R-square of 0.900. The plant immune response was measured within three days of virus infection using the cutoff value of H2O2 (61.095 lmol/100 mg) and (63.201 units) for the tail moment in the Comet Assay. Their percentage changes were 255.12% and 522.40% respectively which reflects the stress of virus infection in the plant. Moreover, H2O2 showed 100% specificity and sensitivity in the symptomatic infected group using the receiver-operating characteristic (ROC). All tested parameters in the symptomatic infected group had significant correlations with twenty-five positive and thirty-one negative correlations where the P value was <0.05 and 0.01. Chlorophyll-a parameter had a crucial role of highly significant correlation between total protein and salicylic acid. Contrarily, this correlation with tail moment unit was (r = _0.930, P <0.01) where the P value was < 0.01. The strongest significant negative correlation was between Chlorophyll-a and H2O2 at P < 0.01, while moderate negative significant correlation was seen for Chlorophyll-b where the P value < 0.05. The present study discloses the secret of the three days of rapid transient production of activated oxygen species (AOS) that was enough for having potential quantitative physiological parameters for defensive plant response toward the virus.

Keywords: programmed cell death, plant–adaptive immune response, hydrogen peroxide (H2O2), physiological parameters

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1447 Academic Performance of Adolescents Living with Single Parent Families

Authors: Akbar Ali

Abstract:

The aim of this study is to explore the academic performance of adolescents who are living with their single parents. Living with single parents is challenging experience especially when children are in adolescence phase. The core aim of study was to investigate how family environment, social status and parental support affect adolescents’ academic performance. This study is carried out in Punjab, Pakistan on adolescents who are experiencing the single family environment either my divorce or natural parental marital transition. Qualitative methodology was employed to evaluate the different aspects of aspects of academic performance. A sample of 40 students in-between age 14 to 18 years was selected from different institutions coming from different socio cultural backgrounds and having different family situations comprising different types of single family structure. Data was collected through semi structured interviews to explore the academics performance and family dynamics. Findings of the study indicated that adolescents living with single parents show poor academic performance due to lack of interest, absentees, poor social and economic support, less parental involvement. Students were showing less or no interest in extracurricular activities and less social interaction with fellows. Parental economic status , Parenting style, parental involvement and academic support are the key factors which directly academic outcomes. Research experience was challenging because students were reluctant to share family issues. Proper academic and counselling centre should be established to provide emotional and academic counselling for such students. Longitudinal research should be carried out to trace the academic outcomes and social adjustments.

Keywords: academic counselling, marital transitions, parenting style, parental involvement

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1446 Development and Optimization of Colon Targeted Drug Delivery System of Ayurvedic Churna Formulation Using Eudragit L100 and Ethyl Cellulose as Coating Material

Authors: Anil Bhandari, Imran Khan Pathan, Peeyush K. Sharma, Rakesh K. Patel, Suresh Purohit

Abstract:

The purpose of this study was to prepare time and pH dependent release tablets of Ayurvedic Churna formulation and evaluate their advantages as colon targeted drug delivery system. The Vidangadi Churna was selected for this study which contains Embelin and Gallic acid. Embelin is used in Helminthiasis as therapeutic agent. Embelin is insoluble in water and unstable in gastric environment so it was formulated in time and pH dependent tablets coated with combination of two polymers Eudragit L100 and ethyl cellulose. The 150mg of core tablet of dried extract and lactose were prepared by wet granulation method. The compression coating was used in the polymer concentration of 150mg for both the layer as upper and lower coating tablet was investigated. The results showed that no release was found in 0.1 N HCl and pH 6.8 phosphate buffers for initial 5 hours and about 98.97% of the drug was released in pH 7.4 phosphate buffer in total 17 hours. The in vitro release profiles of drug from the formulation could be best expressed first order kinetics as highest linearity (r2= 0.9943). The results of the present study have demonstrated that the time and pH dependent tablets system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of Embelin and Gallic acid for treatment of Helminthiasis.

Keywords: embelin, gallic acid, Vidangadi Churna, colon targeted drug delivery

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1445 Thermodynamics of Water Condensation on an Aqueous Organic-Coated Aerosol Aging via Chemical Mechanism

Authors: Yuri S. Djikaev

Abstract:

A large subset of aqueous aerosols can be initially (immediately upon formation) coated with various organic amphiphilic compounds whereof the hydrophilic moieties are attached to the aqueous aerosol core while the hydrophobic moieties are exposed to the air thus forming a hydrophobic coating thereupon. We study the thermodynamics of water condensation on such an aerosol whereof the hydrophobic organic coating is being concomitantly processed by chemical reactions with atmospheric reactive species. Such processing (chemical aging) enables the initially inert aerosol to serve as a nucleating center for water condensation. The most probable pathway of such aging involves atmospheric hydroxyl radicals that abstract hydrogen atoms from hydrophobic moieties of surface organics (first step), the resulting radicals being quickly oxidized by ubiquitous atmospheric oxygen molecules to produce surface-bound peroxyl radicals (second step). Taking these two reactions into account, we derive an expression for the free energy of formation of an aqueous droplet on an organic-coated aerosol. The model is illustrated by numerical calculations. The results suggest that the formation of aqueous cloud droplets on such aerosols is most likely to occur via Kohler activation rather than via nucleation. The model allows one to determine the threshold parameters necessary for their Kohler activation. Numerical results also corroborate previous suggestions that one can neglect some details of aerosol chemical composition in investigating aerosol effects on climate.

Keywords: aqueous aerosols, organic coating, chemical aging, cloud condensation nuclei, Kohler activation, cloud droplets

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1444 Sustainable Urban Mobility: Rethinking the Bus Stop Infrastructures of Dhaka South

Authors: Hasnun Wara Khondker, M. Tarek Morad

Abstract:

Bangladesh is one of the most populous countries of the world in terms of density. Dhaka, the capital of Bangladesh currently has a population of approximately 15-16 million of which around 9 million people are accommodated in Dhaka South City Corporation (DSCC) within around 109 square kilometer area. Despite having various urban issues, country is at its pick of economic progress and Dhaka is the core of this economic growth. To ensure the proper economic development and citizens wellbeing, city needs an ingenious, congestion-free public transportation network. Bus stop/bus bay is an essential infrastructure for ensuring efficient public transportation flow within the city along with enhancing accessibility, user comfort, and safety through public amenities. At present, there is no established Mass Rapid Transit or Bus Rapid Transit network within the city and therefore these private owned buses are the only major mode of mass transportation of Dhaka city. DSCC has undertaken a project to re-design several bus stops and bus bays according to the universal standard for better urban mobility and user satisfaction. This paper will analyze the design approach of the bus stop/bay infrastructure within Dhaka South, putting the research lens on sustainable urban mobility with case studies of similar kind of urban context. The paper will also study the design process with setting several parameters, i.e., accessibility, passenger safety, comfort, sustainability, etc. Moreover, this research will recommend a guideline for designing a bus stop based on the analysis of the design methods.

Keywords: bus stop, Dhaka, public transportation, sustainable urban mobility, universal accessibility, user safety

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1443 Organic Co-Polymer Monolithic Columns for Liquid Chromatography Mixed Mode Protein Separations

Authors: Ahmed Alkarimi, Kevin Welham

Abstract:

Organic mixed mode monolithic columns were fabricated from; glycidyl methacrylate-co-ethylene dimethacrylate-co-stearyl methacrylate, using glycidyl methacrylate and stearyl methacrylate as co monomers representing 30% and 70% respectively of the liquid volume with ethylene dimethacrylate crosslinker and 2,2-dimethoxy-2-phenylacetophenone as the free radical initiator. The monomers were mixed with a binary porogenic solvent, comprising propan-1-ol, and methanol (0.825 mL each). The monolith was formed by photo polymerization (365 nm) inside a borosilicate glass tube (1.5 mm ID and 3 mm OD x 50 mm length). The monolith was observed to have formed correctly by optical examination and generated reasonable backpressure, approximately 650 psi at a flow rate of 0.2 mL min⁻¹ 50:50 acetonitrile: water. The morphological properties of the monolithic columns were investigated using scanning electron microscopy images, and Brunauer-Emmett-Teller analysis, the results showed that the monolith was formed properly with 19.98 ± 0.01 mm² surface area, 0.0205 ± 0.01 cm³ g⁻¹ pore volume and 6.93 ± 0.01 nm average pore size. The polymer monolith formed was further investigated using proton nuclear magnetic resonance, and Fourier transform infrared spectroscopy. The monolithic columns were investigated using high-performance liquid chromatography to test their ability to separate different samples with a range of properties. The columns displayed both hydrophobic/hydrophilic and hydrophobic/ion exchange interactions with the compounds tested indicating that true mixed mode separations. The mixed mode monolithic columns exhibited significant separation of proteins.

Keywords: LC separation, proteins separation, monolithic column, mixed mode

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1442 Assessment of the Association between Serum Thrombospondin-1 Levels at the Time of Admission and the Severity of Neurological Deficit in Patients with Ischemic Stroke

Authors: A. Alhusban, M. Alqawasmeh, F. Alfawares

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Introduction: Despite improvements in stroke management, it remains the leading cause of disability worldwide. It has been suggested that enhancing brain angiogenesis after stroke will improve stroke outcome. Promoting post stroke angiogenesis requires the upregulation of angiogenic factors with a simultaneous reduction of anti-angiogenic factors. Thrombospondin-1 is the main anti-angiogenic protein in the living cells. Counterintuitively, it has been shown that animals with Thrombospondin-1 knockdown will have better stroke outcome. Data about the clinical significance of Thrombspondin-1 levels at the time of admission is still lacking. The objective of this work is to assess the association between serum Thrombospondin-1 levels measured at the time of admission and baseline neurologic severity after stroke. Patients and Methods: Blood samples were collected from patients admitted to the King Abdullah University Hospital (KAUH) with ischemic stroke at the time of admission and serum Thrombopsondin-1 levels were measured using ELISA. Patients neurologic severity was evaluated using the National Institute of Health Stroke Scale (NIHSS). Results: Samples from 50 patients admitted between January 2016 and December 2016 were collected. The median age of participants was 68 years and the median NIHSS was 3. Multinomial regression identified serum Thrombospondin-1 as an independent predictor of stroke outcome (p=0.003). Baseline serum Thrombsopondin-1 was negatively associated with NIHSS at the time of admission (spearman rho correlation coefficient=0.272, p=0.032). Conclusion: Serum Thrombospondin-1 at the time of admission may be a useful marker of stroke severity that predicts more severe neurologic severity.

Keywords: thrombospondin, stroke, neuroprotection, biomarkers

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1441 Cybersecurity Assessment of Decentralized Autonomous Organizations in Smart Cities

Authors: Claire Biasco, Thaier Hayajneh

Abstract:

A smart city is the integration of digital technologies in urban environments to enhance the quality of life. Smart cities capture real-time information from devices, sensors, and network data to analyze and improve city functions such as traffic analysis, public safety, and environmental impacts. Current smart cities face controversy due to their reliance on real-time data tracking and surveillance. Internet of Things (IoT) devices and blockchain technology are converging to reshape smart city infrastructure away from its centralized model. Connecting IoT data to blockchain applications would create a peer-to-peer, decentralized model. Furthermore, blockchain technology powers the ability for IoT device data to shift from the ownership and control of centralized entities to individuals or communities with Decentralized Autonomous Organizations (DAOs). In the context of smart cities, DAOs can govern cyber-physical systems to have a greater influence over how urban services are being provided. This paper will explore how the core components of a smart city now apply to DAOs. We will also analyze different definitions of DAOs to determine their most important aspects in relation to smart cities. Both categorizations will provide a solid foundation to conduct a cybersecurity assessment of DAOs in smart cities. It will identify the benefits and risks of adopting DAOs as they currently operate. The paper will then provide several mitigation methods to combat cybersecurity risks of DAO integrations. Finally, we will give several insights into what challenges will be faced by DAO and blockchain spaces in the coming years before achieving a higher level of maturity.

Keywords: blockchain, IoT, smart city, DAO

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1440 Analyzing Emerging Scientific Domains in Biomedical Discourse: Case Study Comparing Microbiome, Metabolome, and Metagenome Research in Scientific Articles

Authors: Kenneth D. Aiello, M. Simeone, Manfred Laubichler

Abstract:

It is increasingly difficult to analyze emerging scientific fields as contemporary scientific fields are more dynamic, their boundaries are more porous, and the relational possibilities have increased due to Big Data and new information sources. In biomedicine, where funding, medical categories, and medical jurisdiction are determined by distinct boundaries on biomedical research fields and definitions of concepts, ambiguity persists between the microbiome, metabolome, and metagenome research fields. This ambiguity continues despite efforts by institutions and organizations to establish parameters on the core concepts and research discourses. Further, the explosive growth of microbiome, metabolome, and metagenomic research has led to unknown variation and covariation making application of findings across subfields or coming to a consensus difficult. This study explores the evolution and variation of knowledge within the microbiome, metabolome, and metagenome research fields related to ambiguous scholarly language and commensurable theoretical frameworks via a semantic analysis of key concepts and narratives. A computational historical framework of cultural evolution and large-scale publication data highlight the boundaries and overlaps between the competing scientific discourses surrounding the three research areas. The results of this study highlight how discourse and language distribute power within scholarly and scientific networks, specifically the power to set and define norms, central questions, methods, and knowledge.

Keywords: biomedicine, conceptual change, history of science, philosophy of science, science of science, sociolinguistics, sociology of knowledge

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1439 Antioxidant Effects of C-Phycocyanin on Oxidized Astrocyte in Brain Injury Using 2D and 3D Neural Nanofiber Tissue Model

Authors: Seung Ju Yeon, Seul Ki Min, Jun Sang Park, Yeo Seon Kwon, Hoo Cheol Lee, Hyun Jung Shim, Il-Doo Kim, Ja Kyeong Lee, Hwa Sung Shin

Abstract:

In brain injury, depleting oxidative stress is the most effective way to reduce the brain infarct size. C-phycocyanin (C-Pc) is a well-known antioxidant protein that has neuroprotective effects obtained from green microalgae. Astrocyte is glial cell that supports the nerve cell such as neuron, which account for a large portion of the brain. In brain injury, such as ischemia and reperfusion, astrocyte has an important rule that overcomes the oxidative stress and protect from brain reactive oxygen species (ROS) injury. However little is known about how C-Pc regulates the anti-oxidants effects of astrocyte. In this study, when the C-Pc was treated in oxidized astrocyte, we confirmed that inflammatory factors Interleukin-6 and Interleukin-3 were increased and antioxidants enzyme, Superoxide dismutase (SOD) and catalase was upregulated, and neurotrophic factors, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) was alleviated. Also, it was confirmed to reduce infarct size of the brain in ischemia and reperfusion because C-Pc has anti-oxidant effects in middle cerebral artery occlusion (MCAO) animal model. These results show that C-Pc can help astrocytes lead neuroprotective activities in the oxidative stressed environment of the brain. In summary, the C-PC protects astrocytes from oxidative stress and has anti-oxidative, anti-inflammatory, neurotrophic effects under ischemic situations.

Keywords: c-phycocyanin, astrocyte, reactive oxygen species, ischemia and reperfusion, neuroprotective effect

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1438 Therapeutical Role of Copper Oxide Nanoparticles (CuO NPs) for Breast Cancer Therapy

Authors: Dipranjan Laha, Parimal Karmakar

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Metal oxide nanoparticles are well known to generate oxidative stress and deregulate normal cellular activities. Among these, transition metals copper oxide nanoparticles (CuO NPs) are more compelling than others and able to modulate different cellular responses. In this work, we have synthesized and characterized CuO NPs by various biophysical methods. These CuO NPs (~30 nm) induce autophagy in human breast cancer cell line, MCF7 in a time and dose-dependent manner. Cellular autophagy was tested by MDC staining, induction of green fluorescent protein light chain 3 (GFP-LC3B) foci by confocal microscopy, transfection of pBABE-puro mCherry-EGFP-LC3B plasmid and western blotting of autophagy marker proteins LC3B, beclin1, and ATG5. Further, inhibition of autophagy by 3-Methyladenine (3-MA) decreased LD50 doses of CuO NPs. Such cell death was associated with the induction of apoptosis as revealed by FACS analysis, cleavage of PARP, dephosphorylation of Bad and increased cleavage product of caspase3. siRNA-mediated inhibition of autophagy-related gene beclin1 also demonstrated similar results. Finally, induction of apoptosis by 3-MA in CuO NPs treated cells were observed by TEM. This study indicates that CuO NPs are a potent inducer of autophagy which may be a cellular defense against the CuO NPs mediated toxicity and inhibition of autophagy switches the cellular response into apoptosis. A combination of CuO NPs with the autophagy inhibitor is essential to induce apoptosis in breast cancer cells. Acknowledgments: The authors would like to acknowledge for financial support for this research work to the Department of Biotechnology (No. BT/PR14661/NNT/28/494/2010), Government of India.

Keywords: nanoparticle, autophagy, apoptosis, siRNA-mediated inhibition

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1437 Prophylactic Effects of Dairy Kluyveromyces marxianus YAS through Overexpression of BAX, CASP 3, CASP 8 and CASP 9 on Human Colon Cancer Cell Lines

Authors: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

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Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

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1436 Synergistic Effect of Doxorubicin-Loaded Silver Nanoparticles – Polymeric Conjugates on Breast Cancer Cells

Authors: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

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Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

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1435 Encapsulation of Probiotic Bacteria in Complex Coacervates

Authors: L. A. Bosnea, T. Moschakis, C. Biliaderis

Abstract:

Two probiotic strains of Lactobacillus paracasei subsp. paracasei (E6) and Lactobacillus paraplantarum (B1), isolated from traditional Greek dairy products, were microencapsulated by complex coacervation using whey protein isolate (WPI, 3% w/v) and gum arabic (GA, 3% w/v) solutions mixed at different polymer ratio (1:1, 2:1 and 4:1). The effect of total biopolymer concentration on cell viability was assessed using WPI and GA solutions of 1, 3 and 6% w/v at a constant ratio of 2:1. Also, several parameters were examined for optimization of the microcapsule formation, such as inoculum concentration and the effect of ionic strength. The viability of the bacterial cells during heat treatment and under simulated gut conditions was also evaluated. Among the different WPI/GA weight ratios tested (1:1, 2:1, and 4:1), the highest survival rate was observed for the coacervate structures made with the ratio of 2:1. The protection efficiency at low pH values is influenced by both concentration and the ratio of the added biopolymers. Moreover, the inoculum concentration seems to affect the efficiency of microcapsules to entrap the bacterial cells since an optimum level was noted at less than 8 log cfu/ml. Generally, entrapment of lactobacilli in the complex coacervate structure enhanced the viability of the microorganisms when exposed to a low pH environment (pH 2.0). Both encapsulated strains retained high viability in simulated gastric juice (>73%), especially in comparison with non-encapsulated (free) cells (<19%). The encapsulated lactobacilli also exhibited enhanced viability after 10–30 min of heat treatment (65oC) as well as at different NaCl concentrations (pH 4.0). Overall, the results of this study suggest that complex coacervation with WPI/GA has a potential to deliver live probiotics in low pH food systems and fermented dairy products; the complexes can dissolve at pH 7.0 (gut environment), releasing the microbial cells.

Keywords: probiotic, complex coacervation, whey, encapsulation

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1434 Effect of Miconazole Nitrate on Immunological Response and Its Preventive Efficacy in Labeo rohita Fingerlings against Oomycetes Saprolegnia parasitica

Authors: Mukta Singh, Ratan Kumar Saha, Himadri Saha, Paramveer Singh

Abstract:

The present study evaluated the effect of sub-lethal doses of antifungal drug miconazole nitrate (MCZ) on immunological responses including immune-related gene expression and its role as a prophylactic drug against S. parasitica in Labeo rohita fingerlings. Fish were fed with sub lethal doses of MCZ i.e., T1- 6.30 mg MCZ kgBW⁻¹, T2- 12.61 mg MCZ kgBW⁻¹ and T3- 25.22 mg MCZ kgBW⁻¹ and sampling was done at different time intervals for 240 h. Immunological parameters viz. lysozyme activity, oxygen radical production and plasma anti-protease activity showed significant enhancement (p < 0.05) in fish fed with T2 and T3 doses. Significant reduction in plasma protein content was observed in all the dietary groups as compared to control. Expression of immune-relevant genes like TLR-22 and β2-M showed significantly higher expression at six h and 24 h of sampling in both liver and head-kidney. However, these genes showed a down-regulation after 120 h of sampling in both the tissues. Preventive efficacy study showed that single dose of MCZ provides protection against oomycetes up to the fourth day of infection. Significantly higher mortality was observed in control diet-fed fish as compared to fish fed with MCZ medicated diet. Thus, from the study, it can be concluded that the MCZ can act as a potent antifungal agent for preventing oomycetes infection as well as to enhance the immune response.

Keywords: antifungal, immune gene, immunological, miconazole nitrate, prophylactic

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1433 WT1 Exprassion in Malignant Surface Epithelial Ovarian Tumors

Authors: Mahmoodreza Tahamtan

Abstract:

Background: Malignant surface epithelial ovarian tumors (SEOT) account for approximately 90% of primary ovarian cancer. Wilms tumor gene (WT1) product was defined as a tumor suppressor gene, but today it is considered capable of performing oncogenic functions. There seems to be differences in WT1 expression patterns among SEOT subtypes. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Materials and Methods: Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors, 3 mucinous cystadenocarcinomas, 10 borderline mucinous tumors, 7 endometrioid ovarian carcinomas, 3 clear cell carcinomas, 1 malignant Brenner tumor, 2 metastatic adenocarcinomas, and 6 endometrial adenocarcinomas. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Results: Of the 35 cases of ovarian serous cystadenocarcinoma, 30(85.7%) were diffusely positive (3+,4+),4 showed reactivity of < 50% of the tumor cells (1+,2+), and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. All the mucinous tumors(n:13), endometrioid carcinomas (n: 7), clear cell carcinomas (n: 3), metastatic adenocarcinomas (n: 2) and primary endometrial carcinomas (n:6) were negative. The single malignant Brenner tumor showed a positive reaction for WT1(4+) Conclusion: WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors (especially endometrioid subtype) and metastatic carcinomas (especially endometrial serous carcinoma), other than malignant mesothelioma. We cannot rely to the degree of expression inorder to separate high grade borderline serous tumors from low grade ones.

Keywords: WT1, ovary, epithelial tumors, malignant

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1432 Architecture for QoS Based Service Selection Using Local Approach

Authors: Gopinath Ganapathy, Chellammal Surianarayanan

Abstract:

Services are growing rapidly and generally they are aggregated into a composite service to accomplish complex business processes. There may be several services that offer the same required function of a particular task in a composite service. Hence a choice has to be made for selecting suitable services from alternative functionally similar services. Quality of Service (QoS)plays as a discriminating factor in selecting which component services should be selected to satisfy the quality requirements of a user during service composition. There are two categories of approaches for QoS based service selection, namely global and local approaches. Global approaches are known to be Non-Polynomial (NP) hard in time and offer poor scalability in large scale composition. As an alternative to global methods, local selection methods which reduce the search space by breaking up the large/complex problem of selecting services for the workflow into independent sub problems of selecting services for individual tasks are coming up. In this paper, distributed architecture for selecting services based on QoS using local selection is presented with an overview of local selection methodology. The architecture describes the core components, namely, selection manager and QoS manager needed to implement the local approach and their functions. Selection manager consists of two components namely constraint decomposer which decomposes the given global or workflow level constraints in local or task level constraints and service selector which selects appropriate service for each task with maximum utility, satisfying the corresponding local constraints. QoS manager manages the QoS information at two levels namely, service class level and individual service level. The architecture serves as an implementation model for local selection.

Keywords: architecture of service selection, local method for service selection, QoS based service selection, approaches for QoS based service selection

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1431 Tectono-Thermal Evolution of Ningwu-Jingle Basin in North China Craton: Constraints from Apatite (U–Th-Sm)/He and Fission Track Thermochronology

Authors: Zhibin Lei, Minghui Yang

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Ningwu-Jingle basin is a structural syncline which has undergone a complex tectono-thermal history since Cretaceous. It stretches along the strike of the northern Lvliang Mountains which are the most important mountains in the middle and west of North China Craton. The Mesozoic units make up of the core of Ningwu-Jingle Basin, with pre-Mesozoic units making up of its flanks. The available low-temperature thermochronology implies that Ningwu-Jingle Basin has experienced two stages of uplifting: 94±7Ma to 111±8Ma (Albian to Cenomanian) and 62±4 to 75±5Ma (Danian to Maastrichtian). In order to constrain its tectono-thermal history in the Cenozoic, both apatite (U-Th-Sm)/He and fission track dating analysis are applied on 3 Middle Jurassic and 3 Upper Triassic sandstone samples. The central fission track ages range from 74.4±8.8Ma to 66.0±8.0Ma (Campanian to Maastrichtian) which matches well with previous data. The central He ages range from 20.1±1.2Ma to 49.1±3.0Ma (Ypresian to Burdigalian). Inverse thermal modeling is established based on both apatite fission track data and (U-Th-Sm)/He data. The thermal history obtained reveals that all 6 sandstone samples cross the high-temperature limit of fission track partial annealing zone by the uppermost Cretaceous and that of He partial retention zone by the uppermost Eocene to the early Oligocene. The result indicates that the middle and west of North China Craton is not stable in the Cenozoic.

Keywords: apatite fission track thermochronology, apatite (u–th)/he thermochronology, Ningwu-Jingle basin, North China craton, tectono-thermal history

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1430 Assessing the Celebrity Effects on Change in Brand Association and Consumer’s Attitude in a Celebrity-Collaborated Fashion Brand in Hong Kong

Authors: Chu Wai Ching, Kan Chi Wai

Abstract:

Fashion industry is fast moving with intense competitions; it is hard for fashion retailers to stand out among their peers. In order to promote and enhance uniqueness, fashion retailers have collaborated with different brands or celebrity in their marketing campaign recently. As brand-celebrity collaboration is a growing phenomenon in the Hong Kong fashion industry, this research aims to investigate the effect of celebrity on altering consumer’s brand association and the overall attitude towards the co-branded products. One of the popular celebrity-collaborated fashion brands was chosen for this study and a survey was conducted among university students in Hong Kong which yielded 222 responses. By using factor analysis, linear regression and bootstrap test for the mediation, the results show that three celebrity attributes namely “expertise”, “trustworthiness” and “attractiveness” affect the evaluation of the co-branded products. In addition, the change in the association of the brand and co-branded product attributes mediates the relationship between the characteristics of the celebrity and the overall attitude of the co-branded product. The result shows “expertise” of the celebrity has a perfect mediation, while “trustworthiness” and “attractiveness” of the celebrity have partial mediation. This implies that expertise of the celebrity is capable in altering the association towards both the brand and core product attributes and bringing a positive attitude towards the co-brand. The trustworthiness and the attractiveness of the celebrity are able to alter the consumer association towards the brand, but do not guarantee a complete positive attitude towards the co-branded product. This means that change in brand attributes is not a definite mediator as direct relationship may happen or there may be other factors that can affect the relationship between the celebrity’s persuasiveness and the overall attitude towards the co-branded collection.

Keywords: brand attribute, brand-celebrity collaborations, co-branding, fashion industry

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1429 Level of IGF-I and IGFBP-3 in Gingival Crevicular Fluid and Plasma in Patients with Aggressive Periodontitis

Authors: Youjeong Hwang

Abstract:

Purpose: Insulin-like growth factor-I (IGF-I) promotes B-cell development, immunoglobulin formation, and interleukin-6 (IL-6) production, then regulate the immune response and inflammation. As IGF-I and their receptor also exist in the periodontal tissue, they may affect the immune response caused by periodontal pathogens in aggressive periodontitis (AgP) patients. The function of IGF is regulated by IGF binding proteins (IGFBPs), and IGFBP-3 is known to most abundant in plasma. The aim of the present study was to assess the concentration of IGF-I and IGFBP-3 in plasma and gingival crevicular fluid (GCF) in AgP patients and to find out their association. Methods: Nine patients with AgP (test group) and nine healthy subjects (control group) were included in this study. None of the subjects had a history of systemic disease, smoking or steroids medication. GCF samples were collected by microcapillary pipettes and plasma samples were obtained by venipuncture. Probing pocket depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded. Samples were assayed for IGF-I and IGFBP-3 levels using ELISA. Results: Mean IGF-I level in GCF was higher in the test group than control. Mean IGF-I level in plasma and IGFBP-3 level in GCF and plasma in control group were higher than that of the test group. However, there was no statistical significance (p > 0.05). The mean level of IGF-I and IGFBP-3 in GCF was lower than those in plasma. Mean IGF-I level in plasma showed a negative correlation with PD and CAL (p < 0.05) in both groups. The levels of IGF-I and IGFBP-3 in GCF seemed to be negatively correlated with BOP in the test group (p < 0.05). Conclusions: The difference in the level of IGF-I and IGFBP-3 between AgP and healthy subjects was not significant. Further studies that explain the mechanism of the protective role of IGF-I with more samples are needed.

Keywords: aggressive periodontitis, pathogenesis, insulin-like growth factor, insulin-like growth factor binding protein

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1428 Isolation and Elimination of Latent and Productive Herpes Simplex Virus from the Sacral and Trigeminal Ganglions

Authors: Bernard L. Middleton, Susan P. Cosgrove

Abstract:

There is an immediate need for alternative anti-herpetic treatment options effective for both primary infections and reoccurring reactivations of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Alternatives currently approved for the purposes of clinical administration includes antivirals and a reduced set of nucleoside analogues. The present article tests a treatment based on a systemic understanding of how the herpes virus affects cell inhibition and breakdown and targets different phases of the viral cycle, including the entry stage, reproductive cross mutation, and cell-to-cell infection. The treatment consisted of five immunotherapeutic core compounds (5CC), which were hypothesized to be capable of neutralizing human monoclonal antibodies. The tested 5CC were noted as being functional in the application of eliminating the DNA synthesis of herpes viral interferon (IFN) - induced cellular antiviral response. They were here found to neutralize antiviral reproduction by blocking cell-to-cell infection. The activity of the 5CC was tested on RC-37 in vitro using an assay plaque reduction and in vivo against HSV-1 and HSV-2. The 50% inhibitory concentration (IC50) of 5CC was 0.0009% for HSV-1 plaque formation and 0.0008% for HSV-2 plaque formation. Further tests were performed to evaluate the susceptibility of HSV-1 and HSV-2 to anti-herpetic drugs in Vero cells after virus entry. There were high-level markers of the 5CC virucidal activity in the viral suspension of HSV-1 and HSV-2. These concentrations of the 5CC are nontoxic and reduced plaque formation by 98.2% for HSV-1 and 93.0% for HSV-2. Virus HSV-1 and HSV-2 titers were reduced significantly by 5CC to the point of being negative, ranging 0.01–0.09 in 72%. The results concluded the 5CC as being an effective treatment option for the herpes simplex virus.

Keywords: synergy pharmaceuticals, herpes treatment, herpes cure, synergy pharmaceuticals treatment

Procedia PDF Downloads 241
1427 Research Progress of the Relationship between Urban Rail Transit and Residents' Travel Behavior during 1999-2019: A Scientific Knowledge Mapping Based on Citespace and Vosviewer

Authors: Zheng Yi

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Among the attempts made worldwide to foster urban and transport sustainability, transit-oriented development certainly is one of the most successful. Residents' travel behavior is a concern in the researches about the impacts of transit-oriented development. The study takes 620 English journal papers in the core collection database of Web of Science as the study objects; the paper tries to map out the scientific knowledge mapping in the field and draw the basic conditions by co-citation analysis, co-word analysis, a total of citation network analysis and visualization techniques. This study teases out the research hotspots and evolution of the relationship between urban rail transit and resident's travel behavior from 1999 to 2019. According to the results of the analysis of the time-zone view and burst-detection, the paper discusses the trend of the next stage of international study. The results show that in the past 20 years, the research focuses on these keywords: land use, behavior, model, built environment, impact, travel behavior, walking, physical activity, smart card, big data, simulation, perception. According to different research contents, the key literature is further divided into these topics: the attributes of the built environment, land use, transportation network, transportation policies. The results of this paper can help to understand the related researches and achievements systematically. These results can also provide a reference for identifying the main challenges that relevant researches need to address in the future.

Keywords: urban rail transit, travel behavior, knowledge map, evolution of researches

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1426 Nutritional Status of Morbidly Obese Patients Prior to Bariatric Surgery

Authors: Azadeh Mottaghi, Reyhaneh Yousefi, Saeed Safari

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Background: Bariatric surgery is widely proposed as the most effective approach to mitigate the growing pace of morbid obesity. As bariatric surgery candidates suffer from pre-existing nutritional deficiencies, it is of great importance to assess nutritional status of candidates before surgery in order to establish appropriate nutritional interventions. Objectives: The present study assessed and represented baseline data according to the nutritional status among candidates for bariatric surgery. Methods: A cross-sectional analysis of pre-surgery data was collected on 170 morbidly obese patients undergoing bariatric surgery between October 2017 and February 2018. Dietary intake data (evaluated through 147-item food frequency questionnaire), anthropometric measures and biochemical parameters were assessed. Results: Participants included 145 females (25 males) with average age of 37.3 ± 10.2 years, BMI of 45.7 ± 6.4 kg/m² and reported to have a total of 72.3 ± 22.2 kg excess body weight. The most common nutritional deficiencies referred to iron, ferritin, transferrin, albumin, vitamin B12, and vitamin D, the prevalence of which in the study population were as followed; 6.5, 6.5, 3, 2, 17.6 and 66%, respectively. Mean energy, protein, fat, and carbohydrate intake were 3887.3 ± 1748.32 kcal/day, 121.6 ± 57.1, 144.1 ± 83.05, and 552.4 ± 240.5 gr/day, respectively. The study population consumed lower levels of iron, calcium, folic acid, and vitamin B12 compared to the Dietary Reference Intake (DRI) recommendations (2, 26, 2.5, and 13%, respectively). Conclusion: According to the poor dietary quality of bariatric surgery candidates, leading to nutritional deficiencies pre-operatively, close monitoring and tailored supplementation pre- and post-bariatric surgery are required.

Keywords: bariatric surgery, food frequency questionnaire, obesity, nutritional status

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1425 Collagen Scaffold Incorporated with Macrotyloma uniflorum Plant Extracts as a–Burn/Wound Dressing Material, in Vitro and in Vivo Evaluation

Authors: Thangavelu Muthukumar, Thotapalli Parvathaleswara Sastry

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Collagen is the most abundantly available connective tissue protein, which is being used as a biomaterial for various biomedical applications. Presently, fish wastes are disposed improperly which is causing serious environmental pollution resulting in offensive odour. Fish scales are promising source of Type I collagen. Medicinal plants have been used since time immemorial for treatment of various ailments of skin and dermatological disorders especially cuts, wounds, and burns. Developing biomaterials from the natural sources which are having wound healing properties within the search of a common man is the need of hour, particularly in developing and third world countries. With these objectives in view we have developed a wound dressing material containing fish scale collagen (FSC) incorporated with Macrotyloma uniflorum plant extract (PE). The wound dressing composite was characterized for its physiochemical properties using conventional methods. SEM image revealed that the composite has fibrous and porous surface which helps in transportation of oxygen as well as absorbing wound fluids. The biomaterial has shown 95% biocompatibility with required mechanical strength and has exhibited antimicrobial properties. This biomaterial has been used as a wound dressing material in experimental wounds of rats. The healing pattern was evaluated by macroscopic observations, panimetric studies, biochemical, histopathological observations. The results showed faster healing pattern in the wounds treated with CSPE compared to the other composites used in this study and untreated control. These experiments clearly suggest that CSPE can be used as wound/burn dressing materials.

Keywords: collagen, wound dressing, Macrotyloma uniflorum, burn dressing

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1424 Hippocampus Proteomic of Major Depression and Antidepressant Treatment: Involvement of Cell Proliferation, Differentiation, and Connectivity

Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

Abstract:

Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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