Search results for: nucleic acid binding

Authors: Kayvan Khoramipour, Abbas Ali Gaeini, Elham Shirzad, Øyvind Sandbakk

Abstract:

Basketball has different positions with individual movement profiles, which may influence metabolic demands. Accordingly, the present study aimed to compare the movement and metabolic load between different positions during elite male basketball games. Five main players of 14 teams (n = 70), who participated in the 2017-18 Iranian national basketball leagues, were selected as participants. The players were defined as backcourt (Posts 1-3) and frontcourt (Posts 4-5). Video based time motion analysis (VBTMA) was performed based on players’ individual running and shuffling speed using Dartfish software. Movements were classified into high and low intensity running with and without having the ball, as well as high and low-intensity shuffling and static movements. Mean frequency, duration, and distance were calculated for each class, except for static movements where only frequency was calculated. Saliva samples were collected from each player before and after 40-minute basketball games and analyzed using metabolomics. Principal component analysis (PCA) and Partial least square discriminant analysis (PLSDA) (for metabolomics data) and independent T-tests (for VBTMA) were used as statistical tests. Movement frequency, duration, and distance were higher in backcourt players (all p ≤ 0.05), while static movement frequency did not differ. Saliva samples showed that the levels of Taurine, Succinic acid, Citric acid, Pyruvate, Glycerol, Acetoacetic acid, Acetone, and Hypoxanthine were all higher in backcourt players, whereas Lactate, Alanine, 3-Metyl Histidine, and Methionine were higher in frontcourt players Based on metabolomics, we demonstrate that backcourt and frontcourt players have different metabolic profiles during games, where backcourt players move clearly more during games and therefore rely more on aerobic energy, whereas frontcourt players rely more on anaerobic energy systems in line with less dynamic but more static movement patterns.

Keywords: basketball, metabolomics, saliva, sport loadomics

Procedia PDF Downloads 116

Authors: Cristina Lavilla, Andreas Heise

Abstract:

The synthesis of sequence-controlled polymers has received increasing attention in the last years. Well-defined polyacrylates, polyacrylamides and styrene-maleimide copolymers have been synthesized by sequential or kinetic addition of comonomers. However this approach has not yet been introduced to the synthesis of polypeptides, which are in fact polymers developed by nature in a sequence-controlled way. Polypeptides are natural materials that possess the ability to self-assemble into complex and highly ordered structures. Their folding and properties arise from precisely controlled sequences and compositions in their constituent amino acid monomers. So far, solid-phase peptide synthesis is the only technique that allows preparing short peptide sequences with excellent sequence control, but also requires extensive protection/deprotection steps and it is a difficult technique to scale-up. A new strategy towards sequence control in the synthesis of polypeptides is introduced, based on the sequential addition of α-amino acid-N-carboxyanhydrides (NCAs). The living ring-opening process is conducted to full conversion and no purification or deprotection is needed before addition of a new amino acid. The length of every block is predefined by the NCA:initiator ratio in every step. This method yields polypeptides with a specific sequence and controlled molecular weights. A series of polypeptides with varying block sequences have been synthesized with the aim to identify structure-property relationships. All of them are able to adopt secondary structures similar to natural polypeptides, and display properties in the solid state and in solution that are characteristic of the primary structure. By design the prepared polypeptides allow selective modification of individual block sequences, which has been exploited to introduce functionalities in defined positions along the polypeptide chain. Poly(ethylene glycol)(PEG) was the functionality chosen, as it is known to favor hydrophilicity and also yield thermoresponsive materials. After PEGylation, hydrophilicity of the polypeptides is enhanced, and their thermal response in H2O has been studied. Noteworthy differences in the behavior of the polypeptides having different sequences have been found. Circular dichroism measurements confirmed that the α-helical conformation is stable over the examined temperature range (5-90 °C). It is concluded that PEG units are the main responsible of the changes in H-bonding interactions with H2O upon variation of temperature, and the position of these functional units along the backbone is a factor of utmost importance in the resulting properties of the α-helical polypeptides.

Keywords: α-amino acid N-carboxyanhydrides, multiblock copolymers, poly(ethylene glycol), polypeptides, ring-opening polymerization, sequence control

Procedia PDF Downloads 200

Authors: Ajaya Acharya, Prem Narayan Paudel, Rajendra Gyawali

Abstract:

Due to strong tyrosinase inhibition and antioxidant effects, green tea and Licorice are valuable in cosmetics for the skin. However, data on the addition of essential oils to green tea and Licorice in cream formulation to examine antioxidant activities are limited. The purpose of this study was to develop and assess a phytocosmetic cream’s antioxidant and tyrosinase inhibitory characteristics using crude aqueous extracts of green tea, Licorice, and loaded with essential oils. To load the best concentration on cream formulations, plant aqueous extracts were designed, evaluated, and correlated in terms of total phenolic content (TPC), total flavonoids content (TFC), and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. Moreover, o. tenuiflorum and o. basilicum essential oils were extracted and added to a cream formulation. The spreadability profile, water washability, centrifugation test, and organoleptic characteristics of formulated oil in water cream were all satisfactory. The cream exhibited a non-Newtonian rheological profile and pH range of 6.353 ± 0.065 to 6.467±0.050 over successive 0, 1, 2, and 3 months at normal room temperature. The 50% inhibition concentrations shown by herbal cream were 13.764 ± 0.153 µg/ml, 301.445 ± 1.709 µg/ml and 8.082 ± 0.055 respectively for 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, ferric (Fe³⁺) reducing antioxidant power (FRAP) and 2, 2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity, and that of standard ascorbic acid were 6.716 ± 0.077 µg/ml, 171.604 ± 1.551µg/ml and 5.645±0.034µg/ml which showed formulated cream had strong antioxidant characteristics. The formulated herbal cream with a 50% tyrosinase inhibition concentration of 22.254 ± 0.369µg/ml compared to standard Kojic acid 12.535 ± 0.098µg/ml demonstrated a satisfactory tyrosinase inhibition profile for skin whitening property. Herbal cream was reportedly stable in physical and chemical parameters for successive 0, 1, 2, and 3 months at both real and accelerated time study zones, according to obtained stability study results.

Keywords: crude extracts, antioxidant, tyrosinase inhibition, green tea polyphenols

Procedia PDF Downloads 23

Authors: Leila Rashki Ghaleno, Mohamad Amin Hajari, Leila Montazeri, Abdolhossein Shahverdi, Mojtaba Rezazadeh Valojerdi

Abstract:

Background: Spermatogonia stem cells (SSCs) exhibit pluripotency, enabling them to undergo differentiation into many cell lineages, including neurons, glia, endothelial cells, and hepatocytes when cultured in vitro. Although the specific mechanisms are not yet fully understood, it has been observed that biopolymer agents, such as hyaluronic acid (HA) and alginate (Alg), have the potential to induce transdifferentiation of SSCs. The current work aimed to examine the process of in vitro spermatogenesis and the conversion of mouse testicular cells into hepatocytes and erythrocyte-like cells utilizing the HA-Alg hydrogel. Method: After being extracted from the testes of a 5-day postpartum mouse (5 DPP), the testicular cells were separated into two enzymatic stages and then put into a composite hydrogel containing 0.5% HA and 1% alginate. On days 14 and 28 of culture, the colonies' growth, the cells' viability, and their histology were assessed. Result: Despite observing significant cell proliferation on day 14 and the development of circular-shaped organoids on day 28, it was noted that the organoids generated in the HA-Alg medium tended to maintain their circular morphology on day 28. Notably, the testicular cells underwent transdifferentiation into cell types resembling erythrocytes and hepatocytes. The hepatocyte-like cells exhibited the presence of glycogen and lipid deposits, indicating their hepatocyte-like characteristics. Interestingly, immunostaining analysis revealed the secretion of albumin and the presence of VEGFR on day 14. However, on day 28, albumin expression was not detected, while the expression of Sox9 (a marker for hepatocytes), Vegf, CD34, and C-kit (markers for erythrocytes) showed increased levels in the gene expression evaluation. Conclusion: The present findings indicated that HA-Alg could be a potent and effective agent for the transdifferentiation of testis cells into erythrocyte and hepatocyte-like cells, as recent studies have confirmed the transformation of SSCs into hepatocyte cells during in vitro culture.

Keywords: 3D culture, mouse testicular cell, hyaluronic acid, liver organoids

Procedia PDF Downloads 71

Authors: Farid Shekari

Abstract:

Salicylic Acid (SA) is a plant hormone that improves some physiological responses of plants under stress conditions. Seeds of two desi type chickpea cultivars, viz., Kaka and Pirooz, primed with 250, 500, 750, and 1000 μM of SA and a group of seeds without any treating (as control) were evaluated under rain fed conditions. Seed priming in both cultivars led to higher efficiency compare to non-primed treatments. In general, seed priming with 500 and 750 μM of SA had appropriate effects; however the cultivars responses were different in this regard. Kaka showed better performance both in primed and non-primed seed than Pirooz. Results of this study revealed that not only yield quantity but also yield quality, as seed protein amounts, could positively affect by SA treatments. It seems that SA by enhancing of soluble sugars and proline amounts enhanced total water potential (ψ) and RWC. The increment in RWC led to rose of chlorophyll content of plants chlorophyll stability. In general, SA increased water use efficiency, both in biologic and seed yield base, and drought tolerance of chickpea plants. HI was a little decreased in SA treatments and it shows that SA more effective in biomass production than seed yield.

Keywords: chlorophyll, harvest index, proline, seed protein, soluble sugar, water use efficiency, yield component

Procedia PDF Downloads 424

Authors: H. Elmsellem, A. Aouniti, S. Radi, A. Chetouani, B. Hammouti

Abstract:

The synthesis of new organic molecules offers various molecular structures containing heteroatoms and substituents for corrosion protection in acid pickling of metals. The most synthesized compounds are the nitrogen heterocyclic compounds, which are known to be excellent complex or chelate forming substances with metals. The choice of the inhibitor is based on two considerations: first it could be synthesized conveniently from relatively cheap raw materials, secondly, it contains the electron cloud on the aromatic ring or, the electro negative atoms such as nitrogen and oxygen in the relatively long chain compounds. In the present study, (NE)‐2‐methyl‐N‐(thiophen‐2‐ylmethylidene) aniline(T) was synthesized and its inhibiting action on the corrosion of mild steel in 1 M hydrochloric acid was examined by different corrosion methods, such as weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The experimental results suggest that this compound is an efficient corrosion inhibitor and the inhibition efficiency increases with the increase in inhibitor concentration. Adsorption of this compound on mild steel surface obeys Langmuir’s isotherm. Correlation between quantum chemical calculations and inhibition efficiency of the investigated compound is discussed using the Density Functional Theory method (DFT).

Keywords: mild steel, Schiff base, inhibition, corrosion, HCl, quantum chemical

Procedia PDF Downloads 333

Authors: Marzia Hoque Tania, Oishy Roy, ASW Kurny, Fahmida Gulshan

Abstract:

This paper presents results of the investigation on the characterization of silica sand of northern region of Bangladesh on the basis of material composition, particle shape, and size, density, transportation, crystallinity, etc. before and after upgradation. The raw sand samples collected from Nilphamari and Lalmonirhat district were studied and compared for the prospect silica as a high valued commodity rather than heavy minerals. The raw sand particles were colorful in appearance with varying particle size distribution. Scanning Electron Microscopy (SEM) showed uniformity in grain size and mineralogical composition. X-ray fluorescence (XRF) analysis indicated the silica content of the as-received sample to be 75%. Thermogravimetric and Differential Thermal Analysis (DTA) did not detect the presence of any organic material. These tests revealed the sample to be alpha-quartz. Samples were washed with organic and inorganic acid with a combination of varying rotation speed, concentration, solid-liquid ratio. Experiments showed the silica content could be enhanced to more than 85% by washing with 15% sulphuric acid in room temperature. Beneficiation can be improved in further work considering the effect of varying temperature or advanced technology.

Keywords: beneficiation, characterization, commercial grade sand, glass sand, silica, upgradation

Procedia PDF Downloads 136

Authors: Boukli Hacene Faiza, Soufi Wassila, Ghalem Said

Abstract:

The oral antidiabetics drugs such as alpha glucosidase inhibitors present undesirable effects like acarbose. Flavonoids are class of molecules widely distributed in plants, for this reason we are interested in our work to study the inhibition in silico of alpha glucosidase by natural ligands ( flavonoids analogues) using molecular modeling methods using MOE (Molecular Operating Environment) software to predict their interaction with this enzyme with score energy, ADME /T tests and druglikeness properties experiments. Two flavonoids Beicalein and Apigenin have high binding affinity with alpha glucosidase with lower IC50 supposed potent inhibitors.

Keywords: alpha glucosidase, flavonoides analogues, drug research, molecular modeling

Procedia PDF Downloads 108

Authors: Tuji Jemal Ahmed

Abstract:

Fresh produce is an essential component of a healthy diet. However, it can also be a potential source of pathogenic microorganisms that can cause foodborne illnesses. Traditional disinfection methods, such as washing with water and chlorine, have limitations and may not effectively remove or inactivate all microorganisms. This has led to the development of alternative/new methods of fresh produce disinfection, including physical and chemical methods. In this paper, we explore the physical and chemical new methods of fresh produce disinfection, their advantages and disadvantages, and their suitability for different types of produce. Physical methods of disinfection, such as ultraviolet (UV) radiation and high-pressure processing (HPP), are crucial in ensuring the microbiological safety of fresh produce. UV radiation uses short-wavelength UV-C light to damage the DNA and RNA of microorganisms, and HPP applies high levels of pressure to fresh produce to reduce the microbial load. These physical methods are highly effective in killing a wide range of microorganisms, including bacteria, viruses, and fungi. However, they may not penetrate deep enough into the product to kill all microorganisms and can alter the sensory characteristics of the product. Chemical methods of disinfection, such as acidic electrolyzed water (AEW), ozone, and peroxyacetic acid (PAA), are also important in ensuring the microbiological safety of fresh produce. AEW uses a low concentration of hypochlorous acid and a high concentration of hydrogen ions to inactivate microorganisms, ozone uses ozone gas to damage the cell membranes and DNA of microorganisms, and PAA uses a combination of hydrogen peroxide and acetic acid to inactivate microorganisms. These chemical methods are highly effective in killing a wide range of microorganisms, but they may cause discoloration or changes in the texture and flavor of some products and may require specialized equipment and trained personnel to produce and apply. In conclusion, the selection of the most suitable method of fresh produce disinfection should take into consideration the type of product, the level of microbial contamination, the effectiveness of the method in reducing the microbial load, and any potential negative impacts on the sensory characteristics, nutritional composition, and safety of the produce.

Keywords: fresh produce, pathogenic microorganisms, foodborne illnesses, disinfection methods

Procedia PDF Downloads 74

Authors: E. M. AbdelRazek, G. S. ElBahy, M. A. Allam, A. M. Abdelghany, A. M. Hezma

Abstract:

Polymeric biocomposite of hydroxyapatite/polyacrylic acid were prepared and their thermal and mechanical properties were improved by addition of cellulose acetate. FTIR spectroscopy technique and X-ray diffraction analysis were employed to examine the physical and chemical characteristics of the biocomposites. Scanning electron microscopy shows a uniform distribution of HAp nano-particles through the polymeric matrix of two organic/inorganic composites weight ratios (60/40 and 70/30), at which the material crystallinity reaches a considerable value appropriate for the needed applications were studied and revealed that the HAp nano-particles are uniformly distributed in the polymeric matrix. Kinetic parameters were determined from the weight loss data using non isothermal thermogravimetric analysis (TGA). Also, the main degradation steps were described and discussed. The mechanical properties of composites were evaluated by measuring tensile strength and elastic modulus. The data indicate that the addition of cellulose acetate can make homogeneous composites scaffold significantly resistant to higher stress. Elastic modulus of the composites was also improved by the addition of cellulose acetate, making them more appropriate for bioapplications.

Keywords: biocomposite, chemical synthesis, infrared spectroscopy, mechanical properties

Procedia PDF Downloads 459

Authors: N. Khater, S. A. Menina, H. Benbouza

Abstract:

Juniperus thurefera is an endemic cupressacée constitutes a forest cover in the mountains of Aures (Algeria). It is a heritage and important ecological richness but continues to decline, highly endangered species in danger of extinction, these populations show significant originality due to climatic conditions of the environment, because of its strength and extraordinary vitality, made a powerful but fragile and unique ecosystem in which natural regeneration by seed is almost absent in Algeria. Because of the quality of seeds that are either dormant or affected at the tree and the ground level by a large number of pests and parasites, which will lead to the total disappearance of this species and consequently leading to the biodiversity. View the ecological and socio- economic interest presented by this case, it deserves to be preserved and produced in large quantities in this respect. The present work aims to try to regenerate the Juniperus thurefera via vegetative propagation. We studied the potential of cuttings to form adventitious roots and buds. Cuttings were taken from young subjects from 5 to 20 years treated with indole butyric acid (AIB) and planted out-inside perlite under atomizer whose temperature and light are controlled. Results indicated that the percentage of developing buds on cuttings is better than the rooting ones.

Keywords: Juniperus thurefera, indole butyric acid, cutting, buds, rooting

Procedia PDF Downloads 272

Authors: Ziaul Islam, Asad Sultan, Sarzamin Khan

Abstract:

Organic acids and micro encapsulated phyto essential oils have revealed great potential as an antibiotic replacement and as an additive to work tremendously for the health maintenance of broiler chicken. To explore more about organic acids, a total of 600 day-old broiler chicks (Cobb-500) were procured from a local hatchery and distributed into 5 treatment groups having 6 replicates of 20 birds each; the duration of the biological trial was of 35 days. Group T1 served as a control group that were fed on corn soy-based diet only. T2 were fed with a diet having 6% poultry by-product meal (PBM) diet, T3, T4, and T5 were served as the same diet as T2 but supplemented with an organic acid, phyto essential oils alone, and a combination, respectively. The findings declared significant improvement (p<0.05) in body weight gain and FCR in groups T3, T4, and T5 while feed intake was not affected. European broiler performance indicators like production efficiency factor (EPEF) and broiler index (EBI) were improved significantly (p<0.05) by the treatments T3, T4, and T5 compared with T1 and T2. Carcass evaluation depicted significantly better (p<0.05) dressed and eviscerated weight along with carcass yield (T3, T4, T5). Broilers fed organic acid and phyto essential oils supplemented diet had significantly lower (p<0.05) Clostridium perfringens, Escherichia coliand Salmonella and increased Lactobacillus counts. Likewise, antibody titer against ND, IB, and IBD were also significantly (p<0.05) improved by the treatments T3, T4 and T5compared with the T1and T2. Litter moisture content was significantly (p<0.05) reduced by treatmentsT3, T4, and T5 on day 28 and 35 compared with the T1 and T2. These findings of the present study revealed that supplementation of organic acids blend and phyto-essential oils as an as an substitute to improve the performance of broilers without the use of feed antibiotics in broilers fed with 6% poultry by-product meal based diet.

Keywords: organic acid, phyto essential oils, growth performance, PBM, gut health, microbiota, immunity

Procedia PDF Downloads 129

Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar

Abstract:

The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.

Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU

Procedia PDF Downloads 352

Authors: M. Bouhoun Ali, A. Y. Badjah Hadj Ahmed, M. Attou, A. Elias, M. A. Didi

Abstract:

The extraction of uranium(VI) from aqueous solutions has been investigated using 1-hydroxyhexadecylidene-1,1-diphosphonic acid (HHDPA) and 1-hydroxydodecylidene-1,1-diphosphonic acid (HDDPA), which were synthesized and characterized by elemental analysis and by FT-IR, 1H NMR, 31P NMR spectroscopy. In this paper, we propose a tentative assignment for the shifts of those two ligands and their specific complexes with uranium(VI). We carried out the extraction of uranium(VI) by HHDPA and HDDPA from [carbon tetrachloride + 2-octanol (v/v: 90%/10%)] solutions. Various factors such as contact time, pH, organic/aqueous phase ratio and extractant concentration were considered. The optimum conditions obtained were: contact time= 20 min, organic/aqueous phase ratio = 1, pH value = 3.0 and extractant concentration = 0.3M. The extraction yields are more significant in the case of the HHDPA which is equipped with a hydrocarbon chain, longer than that of the HDDPA. Logarithmic plots of the uranium(VI) distribution ratio vs. pHeq and the extractant concentration showed that the ratio of extractant to extracted uranium(VI) (ligand/metal) is 2:1. The formula of the complex of uranium(VI) with the HHDPA and the DHDPA is UO2(H3L)2 (HHDPA and DHDPA are denoted as H4L). A spectroscopic analysis has showed that coordination of uranium(VI) takes place via oxygen atoms.

Keywords: liquid-liquid extraction, uranium(vi), 1-hydroxyalkylidene-1, 1-diphosphonic acids, hhdpa, hddpa, aqueous solution

Procedia PDF Downloads 269

Authors: Sukhila Krishnan, Smita Mohanty, Sanjay K. Nayak

Abstract:

Polylactide (PLA) and thermoplastic starch (TPS) are the most promising bio-based materials presently available on the market. Polylactic acid is one of the versatile biodegradable polyester showing wide range of applications in various fields and starch is a biopolymer which is renewable, cheap as well as extensively available. The usual increase in the cost of petroleum-based commodities in the next decades opens bright future for these materials. Their biodegradability and compostability was an added advantage in applications that are difficult to recycle. Currently, thermoplastic starch (TPS) has been used as a substitute for synthetic plastic in several commercial products. But, TPS shows some limitations mainly due to its brittle and hydrophilic nature, which has to be resolved to widen its application.The objective of the work we report here was to initiate chemical modifications on TPS and to build up a process to control its chemical structure using a solution process which can reduce its water sensitive properties and then blended it with PLA to improve compatibility between PLA and TPS. The method involves in cleavage of starch amylose and amylopectin chain backbone to plasticize with glycerol and water in batch mixer and then the prepared TPS was reacted in solution with diisocyanates i.e, 4,4'-Methylenediphenyl Diisocyanate (MDI).This diisocyanate was used before with great success for the chemical modification of TPS surface. The method utilized here will form an urethane-linkages between reactive isocyanate groups (–NCO) and hydroxyl groups (-OH) of starch as well as of glycerol. New polymer synthesised shows a reduced crystallinity, less hydrophilic and enhanced compatibility with other polymers. The TPS was prepared by Haake Rheomix 600 batch mixer with roller rotors operating at 50 rpm. The produced material is then refluxed for 5hrs with MDI in toluene with constant stirring. Finally, the modified TPS was melt blended with PLA in different compositions. Blends obtained shows an improved mechanical properties. These materials produced are characterized by Fourier Transform Infrared Spectra (FTIR), DSC, X-Ray diffraction and mechanical tests.

Keywords: polylactic acid, thermoplastic starch, Methylenediphenyl Diisocyanate, Polylactide (PLA)

Procedia PDF Downloads 385

Authors: M. Mohammadi

Abstract:

In order to evaluate the effect of phosphate and Zn bio-fertilizers on the yield, phytic acid (PA), Zn concentration and PA/Zn molar ratio in bean, a field experiment was carried out for two years. The treatments included two cultivars of bean (Talash and Sadri), four levels of P (P₀, P₁: 100 kg ha^-1 triple super phosphate (TSP), P2: 50 kg ha^-1 TSP + phosphate bio-fertilizer, P₃: phosphate bio-fertilizer), three levels of Zn (Zn₀, Zn₁: 50 kg ha^-1 ZnSO4, Zn₂: Zn bio-fertilizer). Phosphate bio-fertilizer consisted of inoculum of mycorrhizal fungus and Azotobacter and Zn bio-fertilizer consisted of Pseudomonas bacteria. The results revealed that there was significant difference between yield and Zn concentration between years. The effect of cultivar was significant on studied parameters. The lowest content of PA and PA/Zn were obtained from Talash. P treatment caused to significant difference on parameters in which P₂ caused to increase yield, P and Zn concentration, and decrease PA and PA/Zn by 21.8%, 38.2%, 33.4%, 17.4% and 38.6% respectively. Zn treatment caused to significant difference on studied parameters. The maximum number of parameters were obtained from Zn₁ and Zn₂. The higher Zn concentration led to lower content of PA and PA/Zn. Using of P and Zn bio–fertilizers were caused to increasing nutrient uptake, improving growth condition and reducing PA and PA/Zn molar ratio.

Keywords: mycorrhizae, phosphorus, pseudomonas, zinc

Procedia PDF Downloads 262

Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

Procedia PDF Downloads 124

Authors: R. Reshma srilakshmi, S. Shalini, P. Yogeeswari, D. Sriram

Abstract:

Lysine aminotransferase is a crucial enzyme for dormancy in M. tuberculosis. It is involved in persistence and antibiotic resistance. In present work, we attempted to develop benzthiazole derivatives as lysine aminotransferase inhibitors. In our attempts, we also unexpectedly arrived at an interesting compound 21 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)benzoic acid which even though has moderate activity against persistent phase of mycobacterium, it has significant potency against active phase. In the entire series compound 22 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)isophthalic acid emerged as potent molecule with LAT IC50 of 2.62 µM. It has a significant log reduction of 2.9 and 2.3 fold against nutrient starved and biofilm forming mycobacteria. It was found to be inactive in MABA assay and M.marinum induced zebra fish model. It is also devoid of cytotoxicity. Compound 22 was also found to possess bactericidal effect which is independent of concentration and time. It was found to be effective in combination with Rifampicin in 3D granuloma model. The results are very encouraging as the hit molecule shows activity against active as well as persistent forms of tuberculosis. The identified hit needs further more pharmacokinetic and dynamic screening for development as new drug candidate.

Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation

Procedia PDF Downloads 331

Authors: Fernandes A. C. B. C. J., de Jesus V. C., Sepideh N., Vilela OFGG, Somarin K. K., França R., Pinheiro F. H. S. L.

Abstract:

Objective: The purpose of this study was to look at the effect of pre-treatment of enamel with pumice and/or 37% phosphoric acid on the shear bond strength (SBS) of orthodontic tubes bonded to enamel while simultaneously evaluating the efficacy of orthodontic tubes bonded by self-etch primer (SEP). Materials and Methods: 39 of the crown halves were divided into 3 groups at random. Group, I was the control group utilizing both prophy paste and the conventional double etching pre-treatment method. Group II excluded the use of prophy paste prior to double etching. Group III excluded the use of both prophy paste and double etching and only utilized SEP. Bond strength of the orthodontic tubes was measured by SBS. One way ANOVA and Tukey’s HSD test were used to compare SBS values between the three groups. The statistical significance was set to p<0.05. Results: The difference in SBS values of groups I (36.672 ± 9.315 Mpa), II (34.242 ± 9.986 Mpa), and III (39.055 ± 5.565) were not statistically significant (P<0.05). Conclusion: This study suggested that the use of prophy paste or pre-acid etch of the enamel surface did not provide a statistically significant difference in SBS between the three groups.

Keywords: shear bond strength, orthodontic bracket, self-etch primer, pumice, prophy

Procedia PDF Downloads 179

Authors: Pyar S. Jassal, Sonal Gupta, Neema Chand, Rajni Johar

Abstract:

In present study, Low molecular weight chitosan naoparticles (LMWCNP) were synthesized by using low molecular weight chitosan (LMWC) and sodium tripolyphosphate for the adsorption of anthraquinone dyes from waste water. The ionic-gel technique was used for this purpose. Size of nanoparticles was determined by “Scherrer equation”. The absorbance was carried out with UV-visible spectrophotometer for Acid Green 25 (AG25) and Reactive Blue 4 (RB4) dyes solutions at λmax 644 and λmax 598 nm respectively. The removal of dyes was dependent on the pH and the optimum adsorption was between pH 2 to 9. The extraction of dyes was linearly dependent on temperature. The equilibrium parameters, RL was calculated by using the Langmuir isotherm and shows that adsorption of dyes is favorable on the LMWCNP. The XRD images of LMWC show a crystalline nature whereas LMWCNP is amorphous one. The thermo gravimetric analysis (TGA) shows that LMWCNP thermally more stable than LMWC. As the contact time increases, percentage removal of Acid Green 25 and Reactive Blue 4 dyes also increases. TEM images reveal the size of the LMWCNP were in the range of 45-50 nm. The capacity of AG25 dye on LMWC was 5.23 mg/g, it compared with LMWCNP capacity which was 6.83 mg/g respectively. The capacity of RB4 dye on LMWC was 2.30 mg/g and 2.34 mg/g was on LMWCNP.

Keywords: low molecular weight chitosan nanoparticles, anthraquinone dye, removal efficiency, adsorption isotherm

Procedia PDF Downloads 136

Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

Abstract:

The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

Procedia PDF Downloads 274

Authors: Mohd Moiz Khan, S. M. Mahajani, G. N. Jadhav

Abstract:

Waste foundry sand (total clay content 15%) contains toxic heavy metals and particulate matter which make dumping of waste sand an environmental and health hazard. Disposal of waste foundry sand (WFS) remains one of the substantial challenges faced by Indian foundries nowadays. To cope up with this issue, the chemical method was used to reclaim WFS. A stirrer tank reactor was used for chemical reclamation. Experiments were performed to reduce the total clay content from 15% to as low as 0.9% in chemical reclamation. This method, although found to be effective for WFS reclamation, it may face a challenge due to the possibly high operating cost. Reclaimed sand was found to be satisfactory in terms of sand qualities such as total clay (0.9%), active clay (0.3%), acid demand value (ADV) (2.6%), loss on igniting (LOI) (3 %), grain fineness number (GFN) (56), and compressive strength (60 kPa). The experimental data generated on chemical reactor under different conditions is further used to optimize the design and operating parameters (rotation speed, sand to acidic solution ratio, acid concentration, temperature and time) for the best performance. The use of reclaimed sand within the foundry would improve the economics and efficiency of the process and reduce environmental concerns.

Keywords: chemical reclamation, clay content, environmental concerns, recycle, waste foundry sand

Procedia PDF Downloads 148

Authors: M. S. Tajul Islam, Md. Zahangir Alam

Abstract:

To enhance biogas production through anaerobic digestion, the application of various type of pre-treatment method has some limitations in terms of sustainable environmental management. Many studies on pretreatments especially chemical and physical processes are carried out to evaluate the anaerobic digestion for enhanced biogas production. Among the pretreatment methods acid and alkali pre-treatments gained the highest importance. Previous studies have showed that although acid and alkali pretreatment has significant effect on degradation of biomass, these methods have some negative impact on environment due to their hazard in nature while enzymatic pre-treatment is environmentally friendly. One of the constrains to use of enzyme in pretreatment process for biogas production is high cost which is currently focused to reduce cost through fermentation of waste-based media. As such palm oil mill effluent (POME) as an abundant resource generated during palm oil processing at mill is being used a potential fermentation media for enzyme production. This low cost of enzyme could be an alternative to biogas pretreatment process. This review is to focus direct application of enzyme as enzymatic pre-treatment on POME to enhanced production of biogas.

Keywords: POME, enzymatic pre-treatment, biogas, lignocellulosic biomass, anaerobic digestion

Procedia PDF Downloads 550

Authors: Goksen Arik, Mihriban Korukluoglu

Abstract:

Lactic acid bacteria (LAB) and some yeast species are common microorganisms found in dairy products and most of them are responsible for the fermentation of foods. Such cultures are isolated and used as a starter culture in the food industry because of providing standardisation of the final product during the food processing. Choice of starter culture is the most important step for the production of fermented food. Isolated LAB and yeast cultures which have the ability to create a biofilm layer can be preferred as a starter in the food industry. The biofilm formation could be beneficial to extend the period of usage time of microorganisms as a starter. On the other hand, it is an undesirable property in pathogens, since biofilm structure allows a microorganism become more resistant to stress conditions such as antibiotic presence. It is thought that the resistance mechanism could be turned into an advantage by promoting the effective microorganisms which are used in the food industry as starter culture and also which have potential to stimulate the gastrointestinal system. Development of the biofilm layer is observed in some LAB and yeast strains. The resistance could make LAB and yeast strains dominant microflora in the human gastrointestinal system; thus, competition against pathogen microorganisms can be provided more easily. Based on this circumstance, in the study, 10 LAB and 10 yeast strains were isolated from various dairy products, such as cheese, yoghurt, kefir, and cream. Samples were obtained from farmer markets and bazaars in Bursa, Turkey. As a part of this research, all isolated strains were identified and their ability of biofilm formation was detected with two different methods and compared with each other. The first goal of this research was to determine whether isolates have the potential for biofilm production, and the second was to compare the validity of two different methods, which are known as “Tube method” and “96-well plate-based method”. This study may offer an insight into developing a point of view about biofilm formation and its beneficial properties in LAB and yeast cultures used as a starter in the food industry.

Keywords: biofilm, dairy products, lactic acid bacteria, yeast

Procedia PDF Downloads 264

Authors: Sakeena Naikwadi, K. Jagaluraiah Sannapapamma

Abstract:

Vetiveria zizanioides is an aromatic grass and traditionally been used in aromatherapy and ayurvedic medicine. Vetiver root is multi-functional biopolymer and has highly aromatic, antimicrobial, UV blocking, antioxidant properties suitable for textile finishing. The vetiver root (Gulabi) powder of different concentration (2, 4, 6,8 percent) were extracted by aqueous and solvent methods subjected to bioassay for antimicrobial efficiency and GCMS spectral analysis. The organic cotton fabric was finished with vetiver root extract (8 percent) by exhaust and pad dry cure methods. The finished fabric was assessed for functional properties viz., UV protective factor, antimicrobial efficiency and aroma intensity. The results revealed that Ethanol extraction showed a greater zone of inhibition compared to aqueous extract in root powder. Among the concentrations, 8 percent root extract in ethanol showed a greater zone of inhibition against gram-positive organism S. aureus and gram-negative organism E. coli. The major compounds present in vetiver root extracts were diethyl pathalate with greater percentage (87.73 %) followed by 7- Isopropyl dimethyl carboxylic acid (4.05 %), 2-butanone 4-trimethyle cyclohexen (1.21 %), phenanthrene carboxylic acid (1.03 %), naphthalene pentanoic acid (0.99 %), 1-phenanthrene carboxylic acid and 1 cyclohexenone 2-methyl oxobuty (0.89 %). The sample finished by pad dry cure method exhibited better UV protection even after 10th wash as compared to exhaust method. Vetiver extract treated samples exhibited maximum zone of inhibition against S. aureus than the E. coli organism. The vetiver root extract treated organic cotton fabric through pad dry cure method possessed good antimicrobial activity against S. aureus and E. coli even after 20th washes compared to vetiver root extract treated by exhaust method. The olfactory analysis was carried out by 30 panels of members and opined that vetiver root extract treated fabric has very good and pleasant aroma with better tactile properties that provide cooling, soothing effect and enhances the mood of the wearer. Vetiver root extract finished organic cotton fabric possessed aroma, antimicrobial and UV properties which are aptly suitable for medical and healthcare textiles viz., wound dressing, bandage gauze, surgical cloths, baby diapers and sanitary napkins. It can be used as after finishing agent for variegated garments and made-ups and can be replaced with commercial after finishing agents.

Keywords: antimicrobial, olfactory analysis, UV protection factor, vetiver root extract

Procedia PDF Downloads 236

Authors: Stephen Osakue Amiandamhen, Schwaller Andreas, Martina Meincken, Luvuyo Tyhoda

Abstract:

Invasive alien tree species are currently being cleared in South Africa as a result of the forest and water imbalances. These species grow wildly constituting about 40% of total forest area. They compete with the ecosystem for natural resources and are considered as ecosystem engineers by rapidly changing disturbance regimes. As such, they are harvested for commercial uses but much of it is wasted because of their form and structure. The waste is being sold to local communities as fuel wood. These species can be considered as potential feedstock for the production of phosphate bonded composites. The presence of bark in wood-based composites leads to undesirable properties, and debarking as an option can be cost implicative. This study investigates the potentials of these invasive species processed without debarking on some fundamental properties of wood-based panels. Some invasive alien tree species were collected from EC Biomass, Port Elizabeth, South Africa. They include Acacia mearnsii (Black wattle), A. longifolia (Long-leaved wattle), A. cyclops (Red-eyed wattle), A. saligna (Golden-wreath wattle) and Eucalyptus globulus (Blue gum). The logs were chipped as received. The chips were hammer-milled and screened through a 1 mm sieve. The wood particles were conditioned and the quantity of bark in the wood was determined. The binding matrix was prepared using a reactive magnesia, phosphoric acid and class S fly ash. The materials were mixed and poured into a metallic mould. The composite within the mould was compressed at room temperature at a pressure of 200 KPa. After initial setting which took about 5 minutes, the composite board was demoulded and air-cured for 72 h. The cured product was thereafter conditioned at 20°C and 70% relative humidity for 48 h. Test of physical and strength properties were conducted on the composite boards. The effect of binder formulation and fly ash content on the properties of the boards was studied using fitted response surface technology, according to a central composite experimental design (CCD) at a fixed wood loading of 75% (w/w) of total inorganic contents. The results showed that phosphate/magnesia ratio of 3:1 and fly ash content of 10% was required to obtain a product of good properties and sufficient strength for intended applications. The proposed products can be used for ceilings, partitioning and insulating wall panels.

Keywords: invasive alien tree species, phosphate bonded composites, physical properties, strength

Procedia PDF Downloads 295

Authors: Antonio Montes, Antonio Cozar, Clara Pereyra, Diego Valor, Enrique Martinez de la Ossa

Abstract:

Tissues and organs can be damaged because of traumatism, congenital illnesses, or cancer and the traditional therapeutic alternatives, such as surgery, cannot usually completely repair the damaged tissues. Tissue engineering allows regeneration of the patient's tissues, reducing the problems caused by the traditional methods. Scaffolds, polymeric structures with interconnected porosity, can be promoted the proliferation and adhesion of the patient’s cells in the damaged area. Furthermore, by means of impregnation of the scaffold with beneficial active substances, tissue regeneration can be induced through a drug delivery process. The objective of the work is the fabrication of a PVA scaffold coated with Gallic Acid and polypyrrole through a one-step foaming and impregnation process using the SSI technique (Supercritical Solvent Impregnation). In this technique, supercritical CO₂ penetrates into the polymer chains producing the plasticization of the polymer. In the depressurization step a CO₂ cellular nucleation and growing to take place to an interconnected porous structure of the polymer. The foaming process using supercritical CO₂ as solvent and expansion agent presents advantages compared to the traditional scaffolds’ fabrication methods, such as the polymer’s high solubility in the solvent or the possibility of carrying out the process at a low temperature, avoiding the inactivation of the active substance. In this sense, the supercritical CO₂ avoids the use of organic solvents and reduces the solvent residues in the final product. Moreover, this process does not require long processing time that could cause the stratification of substance inside the scaffold reducing the therapeutic efficiency of the formulation. An experimental design has been carried out to optimize the SSI technique operating conditions, as well as a study of the morphological characteristics of the scaffold for its use in tissue engineerings, such as porosity, conductivity or the release profiles of the active substance. It has been proved that the obtained scaffolds are partially porous, conductors of electricity and are able to release Gallic Acid in the long term.

Keywords: scaffold, foaming, supercritical, PVA, polypyrrole, gallic acid

Procedia PDF Downloads 183

Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

Abstract:

MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

Procedia PDF Downloads 567

Authors: Rajiv Arora

Abstract:

Biodiesel may be economical if produced from inexpensive feedstock which commonly contains high level of free fatty acids (FFA) as an inhibitor in production of methyl ester. In this study, a two-step process for biodiesel production from high FFA spent bleach earth oil in a batch reactor is developed. Oil sample extracted from spent bleaching earth (SBE) was utilized for biodiesel process. In the first step, FFA of the SBE oil was reduced to 1.91% through sulfuric acid catalyzed esterification. In the second step, the product prepared from the first esterification process was carried out transesterification with an alkaline catalyst. The influence of four variables on conversion efficiency to methyl ester, i.e., methanol/ SBE oil molar ratio, catalyst amount, reaction temperature and reaction time, was studied in the second stage. The optimum process variables in the transesterification were methanol/oil molar ratio 6:1, heterogeneous catalyst conc. 5 wt %, reaction temperature 65 °C and reaction time 60 minutes to produce biodiesel. Major fuel properties of SBE biodiesel were measured to comply with ASTM and EN standards. Therefore, an optimized process for production of biodiesel from a low-cost high FFA source was accomplished.

Keywords: biodiesel, esterification, free fatty acids, residual oil, spent bleaching earth, transesterification

Procedia PDF Downloads 177

Authors: Pramod Somvanshi, Manu Tomar, K. V. Venkatesh

Abstract:

Insulin and glucagon are responsible for homeostasis of key plasma metabolites like glucose, amino acids and fatty acids in the blood plasma. These hormones act antagonistically to each other during the secretion and signaling stages. In the present work, we analyze the effect of macronutrients on the response from integrated insulin and glucagon signaling pathways. The insulin and glucagon pathways are connected by DAG (a calcium signaling component which is part of the glucagon signaling module) which activates PKC and inhibits IRS (insulin signaling component) constituting a crosstalk. AKT (insulin signaling component) inhibits cAMP (glucagon signaling component) through PDE3 forming the other crosstalk between the two signaling pathways. Physiological level of anabolism and catabolism is captured through a metric quantified by the activity levels of AKT and PKA in their phosphorylated states, which represent the insulin and glucagon signaling endpoints, respectively. Under resting and starving conditions, the phosphorylation metric represents homeostasis indicating a balance between the anabolic and catabolic activities in the tissues. The steady state analysis of the integrated network demonstrates the presence of a bistable response in the phosphorylation metric with respect to input plasma glucose levels. This indicates that two steady state conditions (one in the homeostatic zone and other in the anabolic zone) are possible for a given glucose concentration depending on the ON or OFF path. When glucose levels rise above normal, during post-meal conditions, the bistability is observed in the anabolic space denoting the dominance of the glycogenesis in liver. For glucose concentrations lower than the physiological levels, while exercising, metabolic response lies in the catabolic space denoting the prevalence of glycogenolysis in liver. The non-linear positive feedback of AKT on IRS in insulin signaling module of the network is the main cause of the bistable response. The span of bistability in the phosphorylation metric increases as plasma fatty acid and amino acid levels rise and eventually the response turns monostable and catabolic representing diabetic conditions. In the case of high fat or protein diet, fatty acids and amino acids have an inhibitory effect on the insulin signaling pathway by increasing the serine phosphorylation of IRS protein via the activation of PKC and S6K, respectively. Similar analysis was also performed with respect to input amino acid and fatty acid levels. This emergent property of bistability in the integrated network helps us understand why it becomes extremely difficult to treat obesity and diabetes when blood glucose level rises beyond a certain value.

Keywords: bistability, diabetes, feedback and crosstalk, obesity

Procedia PDF Downloads 277