Search results for: lignocellulosic residues

Authors: Shady S. Hassan, Brijesh K. Tiwari, Gwilym A. Williams, Amit K. Jaiswal

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EU is known as the destination with the highest rate of the coffee consumption per capita in the world. Spent coffee grounds (SCG) are the main by-product of coffee brewing. SCG is either disposed as a solid waste or employed as compost, although the polysaccharides from such lignocellulosic biomass might be used as feedstock for fermentation processes. However, SCG as a lignocellulose have a complex structure and pretreatment process is required to facilitate an efficient enzymatic hydrolysis of carbohydrates. However, commonly used pretreatment methods, such as chemical, physico-chemical and biological techniques are still insufficient to meet optimal industrial production requirements in a sustainable way. Ultrasound is a promising candidate as a sustainable green pretreatment solution for lignocellulosic biomass utilization in a large scale biorefinery. Thus, ultrasound pretreatment of SCG without adding harsh chemicals investigated as a green technology to enhance enzyme hydrolysis. In the present work, ultrasound pretreatment experiments were conducted on SCG using different ultrasound frequencies (25, 35, 45, 130, and 950 kHz) for 60 min. Regardless of ultrasound power, low ultrasound frequency is more effective than high ultrasound frequency in pretreatment of biomass. Ultrasound pretreatment of SCG (at ultrasound frequency of 25 kHz for 60 min) followed by enzymatic hydrolysis resulted in total reducing sugars of 56.1 ± 2.8 mg/g of biomass. Fourier transform Infrared Spectroscopy (FTIR) was employed to investigate changes in functional groups of biomass after pretreatment, while high-performance liquid chromatography (HPLC) was employed for determination of glucose. Pretreatment of lignocellulose by low frequency ultrasound in water only was found to be an effective green approach for SCG to improve saccharification and glucose yield compared to native biomass. Pretreatment conditions will be optimized, and the enzyme hydrolysate will be used as media component substitute for the production of ethanol.

Keywords: lignocellulose, ultrasound, pretreatment, spent coffee grounds

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Authors: Nayara Torres B. Acioli, José Fernando T. Jucá

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The uncontrolled emission of gases in urban residues' embankment located near urban areas is a social and environmental problem, common in Brazilian cities. Several environmental impacts in the local and global scope may be generated by atmospheric air contamination by the biogas resulted from the decomposition of solid urban materials. In Brazil, the cities of small size figure mostly with 90% of all cities, with the population smaller than 50,000 inhabitants, according to the 2011 IBGE' census, most of the landfill covering layer is composed of clayey, pure soil. The embankments undertaken with pure soil may reach up to 60% of retention of methane, for the other 40% it may be dispersed into the atmosphere. In face of this figures the oxidative covering layer is granted some space of study, envisaging to reduce this perceptual available in the atmosphere, releasing, in spite of methane, carbonic gas which is almost 20 times as less polluting than Methane. This paper exposes the results of studies on the characteristics of the soil used for the oxidative coverage layer of the experimental embankment of Solid Urban Residues (SUR), built in Muribeca-PE, Brazil, supported of the Group of Solid Residues (GSR), located at Federal University of Pernambuco, through laboratory vacuum experiments (determining the characteristics curve), granularity, and permeability, that in soil with saturation over 85% offers dramatic drops in the test of permeability to the air, by little increments of water, based in the existing Brazilian norm for this procedure. The suction was studied, as in the other tests, from the division of prospection of an oxidative coverage layer of 60cm, in the upper half (0.1 m to 0.3 m) and lower half (0.4 m to 0.6 m). Therefore, the consequences to be presented from the lixiviation of the fine materials after 5 years of finalization of the embankment, what made its permeability increase. Concerning its humidity, it is most retained in the upper part, that comprises the compound, with a difference in the order of 8 percent the superior half to inferior half, retaining the least suction from the surface. These results reveal the efficiency of the oxidative coverage layer in retaining the rain water, it has a lower cost when compared to the other types of layer, offering larger availability of this layer as an alternative for a solution for the appropriate disposal of residues.

Keywords: oxidative coverage layer, permeability, suction, saturation

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Authors: Samriti Wadhwa, Beena Kumari

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Background and Significance: Residue levels of ready mix (chlorpyriphos 50% and cypermethrin 5%), cypermethrin and chlorpyriphos individually in sandy loam soil under okra fruits (Variety, Varsha Uphar) were determined; a field experiment was conducted at Research Farm of Department of Entomology of Chaudhary Charan Singh Haryana Agriculture University, Hisar, Haryana, India. Persistence behavior of cypermethrin and chlorpyriphos was studied following application of a pre-mix formulation of insecticides viz. Action-505EC, chlorpyriphos (Radar 20 EC) and cypermethrin (Cyperkill 10 EC) at the recommended dose and double the recommended dose along with control at fruiting stage. Pesticide application also leads to decline in soil acarine fauna which is instrumental in the breakdown of the litter because of which minerals are released into the soil. So, by this study, one can evaluate the safety of pesticides for the soil health. Methodology: Action-505EC (chlorpyriphos 50% and cypermethrin 5%) at 275 g a .i. ha⁻¹ (single dose) and 550 g a. i. ha⁻¹ (double dose), chlorpyriphos (Radar 20 EC) at 200 g a. i. ha⁻¹ (single dose) and 400 g a. i. ha⁻¹ (double dose) and cypermethrin (Cyperkill 10 EC) at 50 g a. i. ha⁻¹ (single dose) and 100 g a. i. ha⁻¹ (double dose) were applied at the fruiting stage on okra crop. Samples of soils from okra field were collected periodically at 0 (1h after spray), 1, 3, 5, 7, 10, 15 days and at harvest after application as well of control soil sample. After air drying, adsorbing through Florisil and activated charcoal and eluting with hexane: acetone (9:1) then residues in soils were estimated by a gas chromatograph equipped with a capillary column and electron capture detector. Results: No persistence of cypermethrin in ready-mix in soil under okra fruits at single and double dose was observed. In case of chlorpyriphos in ready-mix, average initial deposits on 0 (1 h after treatment) day was 0.015 mg kg⁻¹ and 0.036 mg kg⁻¹ which persisted up to 5 days and up to 7 days for single and double dose, respectively. After that residues reached below a detectable level of 0.010 mg kg⁻¹. Experimental studies on cypermethrin individually revealed that average initial deposits on 0 (1 h after treatment) were 0.008 mg kg⁻¹ and 0.012 mg kg⁻¹ which persisted up to 3 days and 5 days for single and double dose, respectively after that residues reached to below detectable level. The initial deposits of chlorpyriphos individually in soil were found to be 0.055 mg kg⁻¹ and 0.113 mg kg⁻¹ which persisted up to 7 days and 10 days at a lower dose and higher dose, respectively after that residues reached to below determination level. Conclusion: In soil under okra crop, only individual cypermethrin in both the doses persisted whereas no persistence of cypermethrin in ready-mix was observed. Persistence of chlorpyriphos individually is more as compared to chlorpyriphos in ready-mix in both the doses. Overall, the persistence of chlorpyriphos in soil under okra crop is more than cypermethrin.

Keywords: chlorpyriphos, cypermethrin, okra, ready mix, soil

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Authors: Richard G. Boakye, Dara A Stanley, Mathavan Vickneswaran, Blanaid White

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The cultivation of cocoa (Theobroma cocoa), an important cash crop that contributes immensely towards the economic growth of several Western African countries, depends almost entirely on pesticide application owing to the plant’s vulnerability to pest and disease attacks. However, the extent to which pesticides inputted for cocoa cultivation impact bees and bee products has rarely received attention in research. Through this study, the effects of pesticides applied for cocoa cultivation on honey in Ghana were examined by evaluating honey samples from cocoa and forest ecosystems in Ghana. An analysis of five honey samples from each land use type confirmed pesticide contaminants from these land use types at measured concentrations for acetamiprid (0.051mg/kg); imidacloprid (0.004-0.02 mg/kg), thiamethoxam (0.013-0.017 mg/kg); indoxacarb (0.004-0.045 mg/kg) and sulfoxaflor (0.004-0.026 mg/kg). None of the observed pesticide concentrations exceeded EU maximum residue levels, indicating no compromise of the honey quality for human consumption. However, from the results, it could be inferred that toxic effects on bees may not be ruled out because observed concentrations largely exceeded the threshold of 0.001 mg/kg at which sublethal effects on bees have previously been reported. One of the most remarkable results to emerge from this study is the detection of imidacloprid in all honey samples analyzed, with sulfoxaflor and thiamethoxam also being detected in 93% and 73% of the honey samples, respectively. This suggests the probable prevalence of pesticide use in the landscape. However, the conclusions reached in this study should be interpreted within the scope of pesticide applications within Bia West District and not necessarily extended to other cocoa-producing districts in Ghana. Future studies should therefore include multiple cocoa-growing districts and other non-cocoa farming landscapes. Such an approach can give a broader outlook on pesticide residues in honey produced in Ghana.

Keywords: honey, cocoa, pesticides, bees, land use, landscape, residues, Ghana

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Authors: Binod Shrestha, Sandrine Hoppe, Thierry Ghislain, Phillipe Marchal, Nicolas Brosse, Anthony Dufour

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The thermochemical conversion of lignin has received an increasing interest in the frame of different biorefinery concepts for the production of chemicals or energy. It is needed to better understand the physical and chemical conversion of lignin for feeder and reactor designs. In-situ rheology reveals the viscoelastic behaviour of lignin upon thermal conversion. The softening, re-solidification (char formation), swelling and shrinking behaviours are quantified during pyrolysis in real-time [1]. The in-situ rheology of an alkali lignin (Protobind 1000) was conducted in high torque controlled strain rheometer from 35°C to 400°C with a heating rate of 5°C.min-1. The swelling, through glass phase transition overlapped with depolymerization, and solidification (crosslinking and “char” formation) are two main phenomena observed during lignin pyrolysis. The onset of temperatures for softening and solidification for this lignin has been found to be 141°C and 248°C respectively. An ex-situ characterization of lignin/char residues obtained at different temperatures after quenching in the rheometer gives a clear understanding of the pathway of lignin degradation. The lignin residues were sampled from the mid-point temperatures of the softening range and solidification range to study the chemical transformations undergoing. Elemental analysis, FTIR and solid state NMR were conducted after quenching the solid residues (lignin/char). The quenched solid was also extracted by suitable solvent and followed by acetylation and GPC-UV analysis. The combination of 13C NMR and GPC-UV reveals the depolymerization followed by crosslinking of lignin/char. NMR and FTIR provide the evolution of functional moieties upon temperature. Physical and chemical mechanisms occurring during lignin pyrolysis are accounted in this study. Thanks to all these complementary methods.

Keywords: pyrolysis, bio-chemicals, valorization, mechanism, softening, solidification, cross linking, rheology, spectroscopic methods

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Authors: Michal Štros, Eva Polanská, Šárka Pospíšilová

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HMGB1 is an architectural protein in chromatin, acting also as a signaling molecule outside the cell. Recent reports from several laboratories provided evidence that a number of both the intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein. MALDI-TOF analysis revealed that mild oxidization of HMGB1 resulted in a conformational change of the protein due to formation of an intramolecular disulphide bond by opposing Cys23 and Cys45 residues. We have demonstrated that redox state of HMGB1 could significantly modulate the ability of the protein to bind and bend DNA. We have also shown that reduced HMGB1 could easily displace histone H1 from DNA, while oxidized HMGB1 had limited capacity for H1 displacement. Using microscale thermophoresis (MST) we have further studied mechanism of HMGB1 interaction with histone H1 in free solution or when histone H1 was bound to DNA. Our MST analysis indicated that reduced HMGB1 exhibited in free solution > 1000 higher affinity of for H1 (KD ~ 4.5 nM) than oxidized HMGB1 (KD <10 M). Finally, we present a novel mechanism for the HMGB1-mediated modulation of histone H1 binding to DNA.

Keywords: HMGB1, histone H1, redox state, interaction, cross-linking, DNA bending, DNA end-joining, microscale thermophoresis

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Authors: Leo Paul Vaurs, Sonia Heaven, Charles Banks

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Municipal solid waste (MSW) is a virtually unlimited source of lignocellulosic material in the form of a waste paper/cardboard mixture which can be converted into fermentable sugars via cellulolytic enzyme hydrolysis in a biorefinery. The extraction of the lignocellulosic fraction and its preparation, however, are energy and water demanding processes. The waste water generated is a rich organic liquor with a high Chemical Oxygen Demand that can be partially cleaned while generating biogas in an Upflow Anaerobic Sludge Blanket bioreactor and be further re-used in the process. In this work, an experiment was designed to determine the critical contaminant concentrations in water affecting either anaerobic digestion or enzymatic hydrolysis by simulating multiple water re-circulations. It was found that re-using more than 16.5 times the same water could decrease the hydrolysis yield by up to 65 % and led to a complete granules desegregation. Due to the complexity of the water stream, the contaminant(s) responsible for the performance decrease could not be identified but it was suspected to be caused by sodium, potassium, lipid accumulation for the anaerobic digestion (AD) process and heavy metal build-up for enzymatic hydrolysis. The experimental data were incorporated into a Water Pinch technology based model that was used to optimize the water re-utilization in the modelled system to reduce fresh water requirement and wastewater generation while ensuring all processes performed at optimal level. Multiple scenarios were modelled in which sub-process requirements were evaluated in term of importance, operational costs and impact on the CAPEX. The best compromise between water usage, AD and enzymatic hydrolysis yield was determined for each assumed contaminant degradations by anaerobic granules. Results from the model will be used to build the first MSW based biorefinery in the USA.

Keywords: anaerobic digestion, enzymatic hydrolysis, municipal solid waste, water optimization

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Authors: Suliman A. I. Ali, Mory Mandiana Diakite, Saqib Ali, Man-Qun Wang

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Lesser grain borer, Rhyzopertha dominica, is a causing damages of stored grains all tropical and subtropical area in the global, according to the information of antenna cDNA library of R. dominica, three olfactory protein genes, including R.domica CSPs2, R.domica PBPs1, R.domica PBPs2 genes (GenBank accessions are KJ186798.1, KJ186830.1, KJ186831.1 separately.), were successfully cloned. For sequencing and phylogenetic analysis, R.domica CSPs1 and R.domica CSPs2 belonged to Minus-C CSPs showed that have 4 conserved cysteine residues, while R.domica PBPs1 and R.domica PBPs2 showed conserved amino acids in all PBPs six conserved cysteine residues. The results of transcription expression level of PBPs1 and PBPs2 of R. dominica showed that the expression level of R.domnica PBP2 is much higher than that of R.domnica PBP1. The variation transcription level at the different developmental time suggested the PBP1, and PBP2 had their particular job in searching food sources, mates and oviposition sites.

Keywords: Rhyzopertha dominica, CSPs, PBPs, molecular cloning

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Authors: Zineb Kassab, Nassima El Miri, A. Aboulkas, Abdellatif Barakat, Mounir El Achaby

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Recently, more attention has been given to biopolymers with a focus on sustainable development and environmental preservation. Following this tendency, the attempt has been made to replace polymers derived from petroleum with superior biodegradable polymers (biopolymers). In this context, biopolymers are considered potential replacements for conventional plastic materials. However, some of their properties must be improved for better competitiveness, especially regarding their mechanical, thermal and barrier properties. Bio-nanocomposite technology using nanofillers has already been proven as an effective way to produce new materials with specific properties and high performances. With the emergence of nanostructured bio-composite materials, incorporating elongated rod-like cellulose nanocrystals (CNC) has attracted more and more attention in the field of nanotechnology. This study is aimed to develop bio-composite films of biopolymer matrices [Carboxymethyle cellulose (CMC), Starch (ST), Chitosan (CS) and Polyvinyl alcohol (PVA)] reinforced with cellulose nanocrystals (CNC) using the solution casting method. The CNC were extracted at a nanometric scale from lignocellulosic fibers via sulfuric acid hydrolysis and then characterized using X-ray diffraction (XRD), thermogravimetric analysis (TGA), confocal microscopy, infrared spectroscopy (IR), atomic force and transmission electron microscopies (AFM and TEM) techniques. The as extracted CNC were used as a reinforcing phase to produce a variety of bio-composite films at different CNC loading (0.5-10 wt %) with specific properties. The rheological properties of film-forming solutions (FFS) of bio-composites were studied, and their relation to the casting process was evaluated. Then, the structural, optical transparency, water vapor permeability, thermal stability and mechanical properties of all prepared bio-composite films were evaluated and studied in this report. The high performances of these bio-composite films are expected to have potential in biomaterials or packaging applications.

Keywords: biopolymer composites, cellulose nanocrystals, food packaging, lignocellulosic fibers

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Authors: Md. Z. Alam, Amal A. Elgharbawy, Muhammad Moniruzzaman, Nassereldeen A. Kabbashi, Parveen Jamal

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The enzymatic hydrolysis of lignocellulosic biomass is one of the obstacles in the process of sugar production, due to the presence of lignin that protects the cellulose molecules against cellulases. Although the pretreatment of lignocellulose in ionic liquid (IL) system has been receiving a lot of interest; however, it requires IL removal with an anti-solvent in order to proceed with the enzymatic hydrolysis. At this point, introducing a compatible cellulase enzyme seems more efficient in this process. A cellulase enzyme that was produced by Trichoderma reesei on palm kernel cake (PKC) exhibited a promising stability in several ILs. The enzyme called PKC-Cel was tested for its optimum pH and temperature as well as its molecular weight. One among evaluated ILs, 1,3-diethylimidazolium dimethyl phosphate [DEMIM] DMP was applied in this study. Evaluation of six factors was executed in Stat-Ease Design Expert V.9, definitive screening design, which are IL/ buffer ratio, temperature, hydrolysis retention time, biomass loading, cellulase loading and empty fruit bunches (EFB) particle size. According to the obtained data, IL-enzyme system shows the highest sugar concentration at 70 °C, 27 hours, 10% IL-buffer, 35% biomass loading, 60 Units/g cellulase and 200 μm particle size. As concluded from the obtained data, not only the PKC-Cel was stable in the presence of the IL, also it was actually stable at a higher temperature than its optimum one. The reducing sugar obtained was 53.468±4.58 g/L which was equivalent to 0.3055 g reducing sugar/g EFB. This approach opens an insight for more studies in order to understand the actual effect of ILs on cellulases and their interactions in the aqueous system. It could also benefit in an efficient production of bioethanol from lignocellulosic biomass.

Keywords: cellulase, hydrolysis, lignocellulose, pretreatment

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Authors: Srinivasa Reddy Mallampati, Byoung Ho Lee, Yoshiharu Mitoma, Simion Cristian

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In recent years, environmental nanotechnology has risen to the forefront and the new properties and enhanced reactivates offered by nanomaterial may offer a new, low-cost paradigm to solving complex environmental pollution problems. This study assessed the synthesis and application of multi-functioned nano-size metallic calcium (nMC) composite for detoxification of hazardous inorganic (heavy metals (HMs)/organic chlorinated/brominated compound (CBCs) contaminants in automobile shredder residue (ASR). ASR residues ball milled with nMC composite can achieve about 90-100% of HMs immobilization and CBCs decomposition. The results highlight the low quantity of HMs leached from ASR residues after treatment with nMC, which was found to be lower than the standard regulatory limit for hazardous waste landfills. The use of nMC composite in a mechanochemical process to treat hazardous ASR (dry conditions) is a simple and innovative approach to remediate hazardous inorganic/organic cross-contaminates in ASR.

Keywords: nano-sized metallic calcium, automobile shredder residue, organic/inorganic contaminants, immobilization, detoxification

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Authors: Sahar Heidary

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Breast cancer is a main public common obstacle global. Additionally, it is the second top reason for tumor death across women. Considering breast cancer cure choices can aid private doctors in precaution for their patients through future cancer treatment. This article reviews usual management centered on stage, histology, and biomarkers. The growth of breast cancer is a multi-stage procedure including numerous cell kinds and its inhibition residues stimulating in the universe. Timely identification of breast cancer is one of the finest methods to stop this illness. Entirely chief therapeutic administrations mention screening mammography for women aged 40 years and older. Breast cancer metastasis interpretations for the mainstream of deaths from breast cancer. The discovery of breast cancer metastasis at the initial step is essential for managing and estimate of breast cancer development. Developing methods consuming the exploration of flowing cancer cells illustrate talented outcomes in forecasting and classifying the initial steps of breast cancer metastasis in patients. In public, mammography residues are the key screening implement though the efficiency of medical breast checks and self-checkup is less. Innovative screening methods are doubtful to exchange mammography in the close upcoming for screening the overall people.

Keywords: breast cancer, screening, metastasis, methods

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Authors: U. L. Fulco, E. L. Albuquerque, José X. Lima Neto, L. R. Da Silva

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The binding of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) to human serum albumin (HSA) is investigated using density functional theory (DFT) calculations within a fragmentation strategy. Crystallographic data for the IBU–HSA supramolecular complex shows that the ligand is confined to a large cavity at the subdomain IIIA and at the interface between the subdomains IIA and IIB, whose binding sites are FA3/FA4 and FA6, respectively. The interaction energy between the IBU molecule and each amino acid residue of these HSA binding pockets was calculated using the Molecular Fractionation with Conjugate Caps (MFCC) approach employing a dispersion corrected exchange–correlation functional. Our investigation shows that the total interaction energy of IBU bound to HSA at binding sites of the fatty acids FA3/FA4 (FA6) converges only for a pocket radius of at least 8.5 °A, mainly due to the action of residues Arg410, Lys414 and Ser489 (Lys351, Ser480 and Leu481) and residues in nonhydrophobic domains, namely Ile388, Phe395, Phe403, Leu407, Leu430, Val433, and Leu453 (Phe206, Ala210, Ala213, and Leu327), which is unusual. Our simulations are valuable for a better understanding of the binding mechanism of IBU to albumin and can lead to the rational design and the development of novel IBU-derived drugs with improved potency.

Keywords: ibuprofen, human serum albumin, density functional theory, binding energies

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Authors: Fatemeh Cheraghali, Saeedeh Shojaee-Aliabadi, Seyede Marzieh Hosseini, Leila Mirmoghtadaie

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In recent years, the field of natural antimicrobial and antioxidant compounds is one of the main research topics in the food industry. Application of agricultural residues is mainly cheap, and available resources are receiving increased attention. Walnut green husk is one of the agricultural residues that is considered as natural compounds with biological properties because of phenolic compounds. In this study, maltodextrin 10% was used for microencapsulation of walnut green husk extract. At first, the extract was examined to consider extraction yield, total phenolic compounds, and antioxidant activation. The results showed the extraction yield of 81.43%, total phenolic compounds of 3997 [mg GAE/100 g], antioxidant activity [DPPH] of 84.85% for walnut green husk extract. Antioxidant activity is about 75%-81% and by DPPH. At the next stage, microencapsulation was done by spry-drying method. The microencapsulation efficiency was 72%-79%. The results of SEM tests confirmed this microencapsulation process. In addition, microencapsulated and free extract was more effective on gram-positive bacteria’s rather than the gram-negative ones. According to the study, walnut green husk can be used as a cheap antioxidant and antimicrobial compounds due to sufficient value of phenolic compounds.

Keywords: biopolymer, microencapsulation, spray-drying, walnut green husk

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Authors: Francielo Vendruscolo

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During industrial processing of raw materials of animal and vegetable origin, large amounts of solid, liquid and gaseous wastes are generated. Solid residues are usually materials rich in carbohydrates, protein, fiber and minerals. Brewer’s spent grain (BSG) is the main waste generated in the brewing industry, representing 85% of the waste generated in this industry. It is estimated that world’s BSG generation is approximately 38.6 x 106 t per year and represents 20-30% (w/w) of the initial mass of added malt, resulting in low commercial value by-product, however, does not have economic value, but it must be removed from the brewery, as its spontaneous fermentation can attract insects and rodents. For every 100 grams in dry basis, BSG has approximately 68 g total fiber, being divided into 3.5 g of soluble fiber and 64.3 g of insoluble fiber (cellulose, hemicellulose and lignin). In addition to dietary fibers, depending on the efficiency of the grinding process and mashing, BSG may also have starch, reducing sugars, lipids, phenolics and antioxidants, emphasizing that its composition will depend on the barley variety and cultivation conditions, malting and technology involved in the production of beer. BSG demands space for storage, but studies have proposed alternatives such as the use of drying, extrusion, pressing with superheated steam, and grinding to facilitate storage. Other important characteristics that enhance its applicability in bioremediation, effluent treatment and biotechnology, is the surface area (SBET) of 1.748 m2 g-1, total pore volume of 0.0053 cm3 g-1 and mean pore diameter of 121.784 Å, characterized as a macroporous and possess fewer adsorption properties but have great ability to trap suspended solids for separation from liquid solutions. It has low economic value; however, it has enormous potential for technological applications that can improve or add value to this agro-industrial waste. Due to its composition, this material has been used in several industrial applications such as in the production of food ingredients, fiber enrichment by its addition in foods such as breads and cookies in bioremediation processes, substrate for microorganism and production of biomolecules, bioenergy generation, and civil construction, among others. Therefore, the use of this waste or by-product becomes essential and aimed at reducing the amount of organic waste in different industrial processes, especially in breweries.

Keywords: brewer’s spent malt, agro-industrial residue, lignocellulosic material, waste generation

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Authors: Yamma Rose, Kone Martine, Yonli Arsène, Wanko Ngnien Adrien

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Soil pollution and, consequently, water resources by micropollutants from gold mine tailings constitute a major threat in developing countries due to the lack of waste treatment. Phytoremediation is an alternative for extracting or trapping micropollutants from contaminated soils by mining residues. The potentialities of Chrysopogon zizanioides (acclimated plant) and Andropogon gayanus (native plant) to accumulate arsenic (As), mercury (Hg), iron (Fe) and zinc (Zn) were studied in artisanal gold mine in Ouagadougou, Burkina Faso. The phytoremediation effectiveness of two plant species was studied in 75 pots of 30 liters each, containing mining residues from the artisanal gold processing site in the rural commune of Nimbrogo. The experiments cover three modalities: Tn - planted unpolluted soils; To – unplanted mine tailings and Tp – planted mine tailings arranged in a randomized manner. The pots were amended quarterly with compost to provide nutrients to the plants. The phytoremediation assessment consists of comparing the growth, biomass and capacity of these two herbaceous plants to extract or to trap Hg, Fe, Zn and As in mining residues in a controlled environment. The analysis of plant species parameters cultivated in mine tailings shows indices of relative growth of A. gayanus very significantly high (34.38%) compared to 20.37% for C.zizanioides. While biomass analysis reveals that C. zizanioides has greater foliage and root system growth than A. gayanus. The results after a culture time of 6 months showed that C. zizanioides and A. gayanus have the potential to accumulate Hg, Fe, Zn and As. Root biomass has a more significant accumulation than aboveground biomass for both herbaceous species. Although the BCF bioaccumulation factor values for both plants together are low (<1), the removal efficiency of Hg, Fe, Zn and As is 45.13%, 42.26%, 21.5% and 2.87% respectively in 24 weeks of culture with C. zizanioides. However, pots grown with A. gayanus gives an effectiveness rate of 43.55%; 41.52%; 2.87% and 1.35% respectively for Fe, Zn, Hg and As. The results indicate that the plant species studied have a strong phytoremediation potential, although that of A. gayanus is relatively less than C. zizanioides.

Keywords: artisanal gold mine tailings, andropogon gayanus, chrysopogon zizanioides, phytoremediation

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Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

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Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST, and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands, cannabinol, and cannabidiol, were obtained from PubChem. After the necessary process of the obtained files, AutoDock Vina was used to perform molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

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Authors: A. Aly Salwa, H. Diekmann, S. Hafiz Ragaa, DG Abo Elhassan

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This study was aimed to evaluate the effect of Milbond (HSCAS) on aflatoxin M1 in artificially contaminated cows milk. Chemisorption compounds used in this experiment were MIlBond, hydrated sodium calcium aluminosilicate (HSCAS). Raw cow milk were artificially exposed to aflatoxin M1 in a concentration of 100 ppb) with addition of Nilbond at 0.5, 1, 2 and 3 % at room temperature for 30 minutes. Aflatoxin M1 was decreased more than 95% by HSCAS at 2%. Milk composition consist of protein, fat, lactose, solid non fat and total solid were affected by addition of some adsorbents were not significantly affected (p 0.05). Tthis method did not involve degrading the toxin, milk may be free from toxin degradation products and is safe for consumption. In addition, the added material may be easily separated from milk after the substance adsorbs the toxin. Thus, this method should be developed by further researches for determining effects of these compounds on functional properties of milk. The ability of hydrated sodium calcium aluminosilicate to prevent or reduce the level of aflatoxin MI residues in milk is critically needed. This finding has important implications, because milk is ultimately consumed by humans and animals, and the reduction of aflatoxin contamination in the milk could have an important impact on their health.

Keywords: aflatoxin M1, Hydrated sodium calcium aluminium silicate, detoxification, raw cow milk

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Authors: Purva Mishra, Rajesh Potlia, Kuljeet Singh Sandhu

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The role of glycyl residues in the protein structure has lingered within the research community for the last several decades. Glycyl residue is the only amino acid that is achiral due to the lack of a side chain and can, therefore, exhibit Ramachandran conformations that are disallowed for L-amino acids. The structural and functional significance of glycyl residues with L-disallowed conformation, however, remains obscure. Through statistical analysis of various datasets, we found that the glycyls with L-disallowed conformations are over-represented at disease-associated sites and tend to be evolutionarily conserved. The mutations of L-disallowed glycyls tend to destabilize the native conformation, reduce protein solubility, and promote inter-molecular aggregations. We uncovered a structural motif referred to as “β-crescent” formed around the L-disallowed glycyl, which prevents β-sheet aggregation by disrupting the alternating pattern of β-pleats. The L-disallowed conformation of glycyls also holds predictive power to infer the pathogenic missense variants. Altogether, our observations highlight that the L-disallowed conformation of glycyls is selected to facilitate native folding and prevent inter-molecular aggregations. The findings may also have implications for designing more stable proteins and prioritizing the genetic lesions implicated in diseases.

Keywords: Ramachandran plot, β-sheet, protein stability, protein aggregation

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Authors: Edgard Gnansounoua, Pavel Vaskan, Elia Ruiz Pachón

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This work addresses the economic and environmental performance of integrated biorefineries based on sugarcane juice and residues in the context of Brazil. We have considered four multiproduct scenarios; two from existing Brazilian sugar mills and the others from ethanol autonomous distilleries. They are integrated biorefineries producing first (1G) and second (2G) generation ethanol, sugar, molasses (for animal feed) and electricity. We show the results for the analysis and comparison of the different scenarios using a techno-economic value-based approach and LCA methodology. We have found that all the analysed scenarios show positive values of Climate change and Fossil depletion reduction as compared to the reference systems. However the scenario producing only ethanol shows less efficiency in Human toxicity, Freshwater ecotoxicity and Freshwater eutrophication impacts. The best economic configuration is provided by the scenario with the largest ethanol production. On the other hand, the best environmental performance is presented by the scenario with full integration sugar – 1G2G ethanol production. The integration of 2G based residues in a 1G ethanol production plant leads to positive environmental impacts compared to the conventional 1G industrial plant but proves to be more expensive.

Keywords: sugarcane, biorefinery, 1G/2G bioethanol integration, LCA, Brazil

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Authors: Chayonnat Thanamun, Kreangkrai Maneeintr

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For petroleum industry, polymer flooding is the one of the main methods in enhanced oil recovery (EOR) that is used water-soluble polymer such as partially hydrolyzed polyacrylamide (HPAM) to increase oil production. It is added to the flooding water to improve the mobility ratio in the flooding process. During the polymer flooding process, water is produced as a by-product along with oil and gas production. This produced water is a mixture of inorganic and organic compound. Moreover, produced water is more difficult to treat than that from water flooding. In this work, the effect of HPAM residue on the wastewater treatment from polymer flooding is studied. Polyaluminium chloride (PAC) is selected to use as a flocculant. Therefore, the objective of this study is to evaluate the effect of polymer residues in produced water on the wastewater treatment by using PAC. The operating parameters of this study are flocculant dosage ranging from 300,400 and 500 mg/L temperature from 30-50 Celsius degree and HPAM concentrations from 500, 1000 and 2000 mg/L. Furthermore, the turbidity, as well as total suspended solids (TSS), are also studied. The results indicated that with an increase in HPAM concentration, the TSS and turbidity increase gradually with the increasing of coagulant dosage under the same temperature. Also, the coagulation-flocculation performance is improved with the increasing temperature. This can be applied to use in the wastewater treatment from oil production before this water can be injected back to the reservoir.

Keywords: wastewater treatment, petroleum production, polyaluminium chloride, polyacrylamide

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Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

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Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis, were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands cannabinol and cannabidiol were obtained from PubChem. After a necessary process of the obtained files, AutoDock Vina was used to performing molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

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Authors: B. Raghu, Shashi Vemuri, Ch. Sreenivasa Rao

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The survey on pesticide use pattern was carried out by interviewing farmers growing chill in open fields and poly houses based on the questionnaire prepared to assess their knowledge and practices on crop cultivation, general awareness on pesticide recommendations and use. Education levels of poly house farmers are high compared to open field farmers, where 57.14% poly house farmers are high school educated, whereas 35% open field farmers are illiterates. Majority farmers use nursery of 35 days and grow in <0.5 acre poly house in summer and rabi and < 1 acre in open field during kharif. Awareness on pesticide related issues is varying among poly house and open field farmers with some commonality, where 28.57% poly house farmers know about recommended pesticides while only 10% open field farmers are aware of this issue. However, in general, all farmers contact pesticide dealer for recommendations, poly house farmers prefer to contact scientists (35.71%) and open field farmers prefer to contact agricultural officers (33.33). Most farmers are unaware about pesticide classification and toxicity symbols on packing. Farmers are aware about endosulfan ban, but only 21.42% poly house and 11.66% open field farmers know about ban of monocrotofos on vegetables. Very few farmers know about pesticide residues and related issues, but know washing helps to reduce contamination.

Keywords: open field, pesticide usage, polyhouses, residues survey

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Authors: Adem Rama, Rabiha Seboussi, Mahmoud Muhamadin, Sultan Alzarooni, Fatima Mohamed, Khuloud Al Ali

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To assess public health hazards associated with the occurrence of Antibiotics and AFM1 residues in UHT milk, a survey was carried out in Sharjah, UAE. In the present study, a total of 42 UHT milk samples analyzed were from different commercial brands manufactured in industrial dairy units in the UAE and from foreign producers. Milk samples were collected for four months (January to April 2020). The occurrence and concentration range of Antibiotics (Streptomycin and Gentamycin) and AFM1 in the samples were investigated by applying the ELISA method. According to the methodology used in this study, in total, 2 (5%) out of 42(95%) samples tested positive on the presence of AFM1. While, 1(2.4%) out of 41(97.6%) positive samples were found to contain Streptomycin and Gentamycin, respectively. The positive incidence of AFM1 in the UHT milk samples ranged from 58.8 to 1074 µg/L, for Streptomycin from up to 1004 µg/L, and Gentamycin up to 6909 µg/L. There were no positive samples found in locally produced UHT milk. AFM1 and antibiotic levels in positive samples UHT milk samples exceeded the maximum tolerable limits as set by the European Union - EC guidelines/standards. These levels in the samples show a presence of contaminants that might constitute a human health risk in Sharjah. The results of this study imply that more emphasis should be given to the routine inspection of milk and dairy products in the Sharjah region.

Keywords: milk, contaminant residues, ELISA, public health, Sharjah

Procedia PDF Downloads 91

Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: Bartosz Piechowicz, Stanislaw Sadlo, Przemyslaw Grodzicki, Magdalena Podbielska

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Apples are popular fruits. They are eaten freshly and/or after processing. For instance Golden Delicious is an apple variety commonly used in production of foods for babies and toddlers. It is no wonder that complex analyses of the pesticide residue levels in those fruits have been carried out since eighties, and continued for the next years up to now. The results obtained were presented, usually as a teamwork, at the scientific sessions organised by the (IOR) Institute of Plant Protection-National Research Institute in Poznań and published in Scientific Works of the Institute (now Progress in Plant Protection/ Postępy w Ochronie Roślin) or Journal of Plant Protection Research, and in many non-periodical publications. These reports included studies carried out by IOR Laboratories in Poznań, Sośnicowice, Rzeszów and Bialystok. First detailed studies on the presence of pesticide residues in apple fruits by the laboratory in Rzeszów were published in 1991 in the article entitled 'The presence of pesticides in apples of late varieties from the area of south-eastern Poland in the years 1986-1989', in Annals of National Institute of Hygiene in Warsaw. These surveys gave the scientific base for business contacts between the Polish company Alima and the American company Gerber. At the beginning of XXI century, in Poland, systematic and complex studies on the deposition of pesticide residues in apples were initiated. First of all, the levels of active ingredients of plant protection products applied against storage diseases at 2-3 weeks before the harvest were determined. It is known that the above mentioned substances usually generate the highest residue levels. Also, the assessment of the fungicide residues in apples during their storage in controlled atmosphere and during their processing was carried out. Taking into account the need of actualisation the Maximum Residue Levels of pesticides, in force in Poland and in other European countries, and rationalisation of the ways of their determination, a lot of field tests on the behaviour of more important fungicides on the mature fruits just before their harvesting, were carried out. A rate of their disappearance and mathematical equation that showed the relationship between the residue level of any substance and the used dose, have been determined. The two parameters have allowed to evaluate the Maximum Residue Levels (MRLs) of pesticides, which were in force at that time, and to propose a coherent model of their determination in respect to the new substances. The obtained results were assessed in terms of the health risk for adult consumers and children, and to such determination of terms of treatment that mature apples could meet the rigorous level of 0.01 mg/kg.

Keywords: apple, disappearance, health risk, MRL, pesticide residue, research

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Authors: Saeed Qaisrani

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The study was conducted to observe carbon and nutrient loss by burning of rice residues on rice-wheat cropping system The rice crop was harvested to conduct the experiment in a randomized complete block design (RCBD) with factors and 4 replications with a net plot size of 10 m x 20 m. Rice stubbles were managed by two methods i.e. Incorporation & burning of rice residues. Soil samples were taken to a depth of 30 cm before sowing & after harvesting of wheat. Wheat was sown after harvesting of rice by three practices i.e. Conventional tillage, Minimum tillage and Zero tillage to observe best tillage practices. Laboratory and field experiments were conducted on wheat to assess best tillage practice and residues management method with estimation of carbon losses. Data on the following parameters; establishment count, plant height, spike length, number of grains per spike, biological yield, fat content, carbohydrate content, protein content, and harvest index were recorded to check wheat quality & ensuring food security in the region. Soil physico-chemical analysis i.e. pH, electrical conductivity, organic matter, nitrogen, phosphorus, potassium, and carbon were done in soil fertility laboratory. Substantial results were found on growth, yield and related parameters of wheat crop. The collected data were examined statistically with economic analysis to estimate the cost-benefit ratio of using different tillage techniques and residue management practices. Obtained results depicted that Zero tillage method have positive impacts on growth, yield and quality of wheat, Moreover, it is cost effective methodology. Similarly, Incorporation is suitable and beneficial method for soil due to more nutrients provision and reduce the need of fertilizers. Burning of rice stubbles has negative impact including air pollution, nutrient loss, microbes died and carbon loss. Recommended the zero tillage technology to reduce carbon losses along with food security in Pakistan.

Keywords: agricultural agronomy, food security, carbon sequestration, rice-wheat cropping system

Procedia PDF Downloads 252

Authors: Swarupa Shashi Senivarapu Vemuri

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Curry leaf (Murraya koeinigii (L.)) exported from India had insecticide residues above maximum residue limits, which are hazardous to consumer health and caused rejection of the commodity at the point of entry in Europe and middle east resulting in a check on export of curry leaf. Hence to study current pesticide usage patterns in major curry leaf growing areas, a survey on pesticide use pattern was carried out in curry leaf growing areas in Guntur districts of Andhra Pradesh during 2014-15, by interviewing farmers growing curry leaf utilizing the questionnaire to assess their knowledge and practices on crop cultivation, general awareness on pesticide recommendations and use. Education levels of farmers are less, where 13.96 per cent were only high school educated, and 13.96% were illiterates. 18.60% farmers were found cultivating curry leaf crop in less than 1 acre of land, 32.56% in 2-5 acres, 20.93% in 5-10 acres and 27.91% of the farmers in more than 10 acres of land. Majority of the curry leaf farmers (93.03%) used pesticide mixtures rather than applying single pesticide at a time, basically to save time, labour, money and to combat two or more pests with single spray. About 53.48% of farmers applied pesticides at 2 days interval followed by 34.89% of the farmers at 4 days interval, and about 11.63% of the farmers sprayed at weekly intervals. Only 27.91% of farmers thought that the quantity of pesticides used at their farm is adequate, 90.69% of farmers had perception that pesticides are helpful in getting good returns. 83.72% of farmers felt that crop change is the only way to control sucking pests which damages whole crop. About 4.65% of the curry leaf farmers opined that integrated pest management practices are alternative to pesticides and only 11.63% of farmers felt natural control as an alternative to pesticides. About 65.12% of farmers had perception that high pesticide dose will give higher yields. However, in general, Curry leaf farmers preferred to contact pesticide dealers (100%) and were not interested in contacting either agricultural officer or a scientist. Farmers were aware of endosulfan ban 93.04%), in contrast, only 65.12, per cent of farmers knew about the ban of monocrotophos on vegetables. Very few farmers knew about pesticide residues and decontamination by washing. Extension educational interventions are necessary to produce fresh curry leaf free from pesticide residues.

Keywords: Curry leaf, decontamination, endosulfan, leaf roller, psyllids, tetranychid mite

Procedia PDF Downloads 305

Authors: Janneth Gonzalez, Marco Avila, George Barreto

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

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

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

Procedia PDF Downloads 103