Search results for: protein functional module
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5547

Search results for: protein functional module

4077 Explicit Chain Homotopic Function to Compute Hochschild Homology of the Polynomial Algebra

Authors: Zuhier Altawallbeh

Abstract:

In this paper, an explicit homotopic function is constructed to compute the Hochschild homology of a finite dimensional free k-module V. Because the polynomial algebra is of course fundamental in the computation of the Hochschild homology HH and the cyclic homology CH of commutative algebras, we concentrate our work to compute HH of the polynomial algebra.by providing certain homotopic function.

Keywords: hochschild homology, homotopic function, free and projective modules, free resolution, exterior algebra, symmetric algebra

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4076 Factors Associated with Hand Functional Disability in People with Rheumatoid Arthritis: A Systematic Review and Best-Evidence Synthesis

Authors: Hisham Arab Alkabeya, A. M. Hughes, J. Adams

Abstract:

Background: People with Rheumatoid Arthritis (RA) continue to experience problems with hand function despite new drug advances and targeted medical treatment. Consequently, it is important to identify the factors that influence the impact of RA disease on hand function. This systematic review identified observational studies that reported factors that influenced the impact of RA on hand function. Methods: MEDLINE, EMBASE, CINAL, AMED, PsychINFO, and Web of Science database were searched from January 1990 up to March 2017. Full-text articles published in English that described factors related to hand functional disability in people with RA were selected following predetermined inclusion and exclusion criteria. Pertinent data were thoroughly extracted and documented using a pre-designed data extraction form by the lead author, and cross-checked by the review team for completion and accuracy. Factors related to hand function were classified under the domains of the International Classification of Functioning, Disability, and Health (ICF) framework and health-related factors. Three reviewers independently assessed the methodological quality of the included articles using the quality of cross-sectional studies (AXIS) tool. Factors related to hand function that was investigated in two or more studies were explored using a best-evidence synthesis. Results: Twenty articles form 19 studies met the inclusion criteria from 1,271 citations; all presented cross-sectional data (five high quality and 15 low quality studies), resulting in at best limited evidence in the best-evidence synthesis. For the factors classified under the ICF domains, the best-evidence synthesis indicates that there was a range of body structure and function factors that were related with hand functional disability. However, key factors were hand strength, disease activity, and pain intensity. Low functional status (physical, emotional and social) level was found to be related with limited hand function. For personal factors, there is limited evidence that gender is not related with hand function; whereas, conflicting evidence was found regarding the relationship between age and hand function. In the domain of environmental factors, there was limited evidence that work activity was not related with hand function. Regarding health-related factors, there was limited evidence that the level of the rheumatoid factor (RF) was not related to hand function. Finally, conflicting evidence was found regarding the relationship between hand function and disease duration and general health status. Conclusion: Studies focused on body structure and function factors, highlighting a lack of investigation into personal and environmental factors when considering the impact of RA on hand function. The level of evidence which exists was limited, but identified that modifiable factors such as grip or pinch strength, disease activity and pain are the most influential factors on hand function in people with RA. The review findings suggest that important personal and environmental factors that impact on hand function in people with RA are not yet considered or reported in clinical research. Well-designed longitudinal, preferably cohort, studies are now needed to better understand the causality between personal and environmental factors and hand functional disability in people with RA.

Keywords: factors, hand function, rheumatoid arthritis, systematic review

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4075 Visualizing Matrix Metalloproteinase-2 Activity Using Extracellular Matrix-Immobilized Fluorescence Resonance Energy Transfer Bioprobe in Cancer Cells

Authors: Hawon Lee, Young-Pil Kim

Abstract:

Visualizing matrix metalloproteinases (MMPs) activity is necessary for understanding cancer metastasis because they are implicated in cell migration and invasion by degrading the extracellular matrix (ECM). While much effort has been made to sense the MMP activity, but extracellularly long-term monitoring of MMP activity still remains challenging. Here, we report a collagen-bound fluorescent bioprobe for the detection of MMP-2 activity in the extracellular environment. This bioprobe consists of ECM-immobilized part (including collagen-bound protein) and MMP-sensing part (including peptide substrate linked with fluorescence resonance energy transfer (FRET) coupler between donor green fluorescent protein (GFP) and acceptor TAMRA dye), which was constructed through intein-mediated self-splicing conjugation. Upon being immobilized on the collagen-coated surface, this bioprobe enabled efficient long-lasting observation of MMP-2 activity in the cultured cells without affecting cell growth and viability. As a result, the FRET ratio (acceptor/donor) decreased as the MMP2 activity increased in cultured cancer cells. Furthermore, unlike wild-type MMP-2, mutated MMP-2 expression (Y580A in the hemopexin region) gave rise to lowering the secretion of MMP-2 in HeLa. Conclusively, our method is anticipated to find applications for tracing and visualizing enzyme activity.

Keywords: collagen, ECM, FRET, MMP

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4074 Toward Understanding the Glucocorticoid Receptor Network in Cancer

Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

Abstract:

The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

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4073 Antioxidant Properties of Snack Crackers Incorporated with Mahaleb (Prunus mahaleb L.) Powder

Authors: Elif Yildiz, Gizem Gungor, Hatice Yilmaz, Duygu Gocmen

Abstract:

Nowadays, consumer demand has been increasing for the healthy and functional food. In this context, some natural products rich in phenolic compounds are also added to cereal based food for health benefits. Natural phenolic compounds have many beneficial bioactivities such as anti-allergic, antiviral, anti-inflammatory and anti-mutagenic activities. It has been found that various plant species contain natural bioactive phytochemicals with antioxidant function. One of these plant species is mahaleb (Prunus mahaleb L). Mahaleb berries with dark blue or red colours have the highest antioxidant capacities among all common fruits and vegetables. The aim of this study was to determine the possibilities of improving the antioxidant properties of novel snack crackers by supplementing with mahaleb (Prunus mahaleb L) powder. For this purpose mahaleb powder were used to replace wheat flour in the snack cracker formulation at two different levels (5%, and 7.5% w/w). As a result, mahaleb supplementation caused an increase in total phenolic contents and antioxidant activities of crackers. It can be say that mahaleb powder can be used as an alternative functional and nutritional ingredient in bakery products.

Keywords: antioxidant activity, cracker, mahaleb (Prunus mahaleb L), phenolic contents

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4072 The Use of Intraarticular Aqueous Sarapin for Treatment of Chronic Knee Pain in Elderly Patients in a Primary Care Setting

Authors: Robert E. Kenney, Richard B. Aguilar, Efrain Antunez, Gregory Schor-Haskin, Rafael Rey, Catie Falcon, Luis Arce

Abstract:

This study sought to explore the effect of Sarapin injections on chronic knee pain (CKP). Many adults suffer from CKP which is most often attributed to osteoarthritis. Current treatment regimens for CKP involve the use NSAIDS medications, injections with steroids/analgesic, platelet rich plasma injections, or orthopedic surgical interventions. Sarapin is a commercially available homeopathic aqueous extract from the pitcher plant. Studies on the use of Sarapin as a treatment for cervical, thoracic, and lumbosacral facet joint nerve blocks have been performed with mixed results. There is little available evidence on the use of Sarapin in CKP. This study examines the effect of a series of 3 weekly injections of aqueous Sarapin in 95 elderly patients with CKP in a primary care setting. Cano Health, a primary care group, identified 95 successive patients with CKP from its multimodal physiotherapy program for chronic pain. Patients underwent evaluation by a clinician, underwent diagnostic Xrays of the knees, and the treatment plan with three weekly Sarapin injections was discussed. A pain and functional limitation survey (a modified Lower Extremity Functional Scale (mLEFS)) was administered prior to initiating treatment (Entry Survey (ES)). Each patient received an intraarticular injection of 2 cc of aqueous Sarapin with 1cc 1% lidocaine during weeks 1, 2 and 3. The mLEFS was administered again at week 4, one week after the third Sarapin injection (Exit Survey (ExS)). Demographics: Mean Age 62 +/- 9.8; 73% female; 89% Hispanic/Latino; mean time between ES and ExS was 27.5 +/-8.2 days. Survey: The mLEFS was based on a published Lower Extremity Functional Scale and each patient rated their pain or functional limitation from 0 (no difficulty) to 5 (severe difficulty) for 10 questions. Answers were summed and compared. Maximum score for severe difficulty would be 50 points. Results: Mean pain/functional scores: ES was 30.3 +/-12.1 and ExS was 19.5 +/- 12.5. This represents a relative improvement of 35.7% (P<0.00001). A total of 81% (77/95) of the patients showed improvement in symptoms at week four as assessed by the mLEFS. There were 11 patients who reported an increase in their survey scores while 7 patients reported no change. When evaluating the cohort that reported improvement, the ES was 30.9 +/-11.4 and ExS was 16.3 +/-9.8 yielding a 47.2% relative improvement (P<0.00001). Injections were well tolerated, and no adverse events were reported. Conclusions: In this cohort of 95 elderly patients with CKP, treatment with 3 weekly injections of Sarapin significantly improved pain and function as assessed by a mLEFS survey. The majority (81%) of patients responded positively to therapy, 12% had worsening symptoms and 7% reported no change. The use of intraarticular injections of Sarapin for CKP was shown to be an effective modality of treatment. Sarapin’s low cost, tolerability, and ease of use make it an attractive alternative to NSAIDS, steroids, PRP or surgical intervention for this common debilitating condition.

Keywords: Sarapin, intraarticular, chronic knee pain, osteoarthritis

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4071 Exfoliation of Functionalized High Structural Integrity Graphene Nanoplatelets at Extremely Low Temperature

Authors: Mohannad N. H. Al-Malichi

Abstract:

Because of its exceptional properties, graphene has become the most promising nanomaterial for the development of a new generation of advanced materials from battery electrodes to structural composites. However, current methods to meet requirements for the mass production of high-quality graphene are limited by harsh oxidation, high temperatures, and tedious processing steps. To extend the scope of the bulk production of graphene, herein, a facile, reproducible and cost-effective approach has been developed. This involved heating a specific mixture of chemical materials at an extremely low temperature (70 C) for a short period (7 minutes) to exfoliate functionalized graphene platelets with high structural integrity. The obtained graphene platelets have an average thickness of 3.86±0.71 nm and a lateral size less than ~2 µm with a low defect intensity ID/IG ~0.06. The thin film (~2 µm thick) exhibited a low surface resistance of ~0.63 Ω/sq⁻¹, confirming its high electrical conductivity. Additionally, these nanoplatelets were decorated with polar functional groups (epoxy and carboxyl groups), thus have the potential to toughen and provide multifunctional polymer nanocomposites. Moreover, such a simple method can be further exploited for the novel exfoliation of other layered two-dimensional materials such as MXenes.

Keywords: functionalized graphene nanoplatelets, high structural integrity graphene, low temperature exfoliation of graphene, functional graphene platelets

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4070 Midterm Clinical and Functional Outcomes After Treatment with Ponseti Method for Idiopathic Clubfeet: A Prospective Cohort Study

Authors: Neeraj Vij, Amber Brennan, Jenni Winters, Hadi Salehi, Hamy Temkit, Emily Andrisevic, Mohan V. Belthur

Abstract:

Idiopathic clubfoot is a common lower extremity deformity with an incidence of 1:500. The Ponseti Method is well known as the gold standard of treatment. However, there is limited functional data demonstrating correction of the clubfoot after treatment with the Ponseti method. The purpose of this study was to study the clinical and functional outcomes after the Ponseti method with the Clubfoot Disease-Specific Instrument (CDS) and pedobarography. This IRB-approved prospective study included patients aged 3-18 who were treated for idiopathic clubfoot with the Ponseti method between January 2008 and December 2018. Age-matched controls were identified through siblings of clubfoot patients and other community members. Treatment details were collected through a chart review of the included patients. Laboratory assessment included a physical exam, gait analysis, and pedobarography. The Pediatric Outcomes Data Collection Instrument and the Clubfoot Disease-Specific Instrument were also obtained on clubfoot patients (CF). The Wilcoxson rank-sum test was used to study differences between the CF patients and the typically developing (TD) patients. Statistical significance was set at p < 0.05. There were a total of 37 enrolled patients in our study. 21 were priorly treated for CF and 16 were TD. 94% of the CF patients had bilateral involvement. The age at the start of treatment was 29 days, the average total number of casts was seven to eight, and the average total number of casts after Achilles tenotomy was one. The reoccurrence rate was 25%, tenotomy was required in 94% of patients, and ≥1 tenotomy was required in 25% of patients. There were no significant differences between step length, step width, stride length, force-time integral, maximum peak pressure, foot progression angles, stance phase time, single-limb support time, double limb support time, and gait cycle time between children treated with the Ponseti method and typically developing children. The average post-treatment Pirani and Dimeglio scores were 5.50±0.58 and 15.29±1.58, respectively. The average post-treatment PODCI subscores were: Upper Extremity: 90.28, Transfers: 94.6, Sports: 86.81, Pain: 86.20, Happiness: 89.52, Global: 88.6. The average post-treatment Clubfoot Disease-Specific Instrument scores subscores were: Satisfaction: 73.93, Function: 80.32, Overall: 78.41. The Ponseti Method has a very high success rate and remains to be the gold standard in the treatment of idiopathic clubfoot. Timely management leads to good outcomes and a low need for repeated Achilles tenotomy. Children treated with the Ponseti method demonstrate good functional outcomes as measured through pedobarography. Pedobarography may have clinical utility in studying congenital foot deformities. Objective measures for hours of brace wear could represent an improvement in clubfoot care.

Keywords: functional outcomes, pediatric deformity, patient-reported outcomes, talipes equinovarus

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4069 Development of Ferric Citrate Complex Draw Solute and Its Application for Liquid Product Enrichment through Forward Osmosis

Authors: H. Li, L. Ji, J. Su

Abstract:

Forward osmosis is an emerging technology for separation and has great potential in the concentration of liquid products such as protein, pharmaceutical, and natural products. In pharmacy industry, one of the very tough talks is to concentrate the product in a gentle way since some of the key components may lose bioactivity when exposed to heating or pressurization. Therefore, forward osmosis (FO), which uses inherently existed osmosis pressure instead of externally applied hydraulic pressure, is attractive for pharmaceutical enrichments in a much efficient and energy-saving way. Recently, coordination complexes have been explored as the new class of draw solutes in FO processes due to their bulky configuration and excellent performance in terms of high water flux and low reverse solute flux. Among these coordination complexes, ferric citrate complex with lots of hydrophilic groups and ionic species which make them good solubility and high osmotic pressure in aqueous solution, as well as its low toxicity, has received much attention. However, the chemistry of ferric complexation by citrate is complicated, and disagreement prevails in the literature, especially for the structure of the ferric citrate. In this study, we investigated the chemical reaction with various molar ratio of iron and citrate. It was observed that the ferric citrate complex (Fe-CA2) with molar ratio of 1:1 for iron and citrate formed at the beginning of the reaction, then Fecit would convert to ferric citrate complex at the molar ratio of 1:2 with the proper excess of citrate in the base solution. The structures of the ferric citrate complexes synthesized were systematically characterized by X-ray diffraction (XRD), UV-vis spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Thermogravimetric analysis (TGA). Fe-CA2 solutions exhibit osmotic pressures more than twice of that for NaCl solutions at the same concentrations. Higher osmotic pressure means higher driving force, and this is preferable for the FO process. Fe-CA2 and NaCl draw solutions were prepared with the same osmotic pressure and used in FO process for BSA protein concentration. Within 180 min, BSA concentration was enriched from 0.2 to 0.27 L using Fe-CA draw solutions. However, it was only increased from 0.20 to 0.22 g/L using NaCl draw solutions. A reverse flux of 11 g/m²h was observed for NaCl draw solutes while it was only 0.1 g/m²h for Fe-CA2 draw solutes. It is safe to conclude that Fe-CA2 is much better than NaCl as draw solute and it is suitable for the enrichment of liquid product.

Keywords: draw solutes, ferric citrate complex, forward osmosis, protein enrichment

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4068 Estrogen Controls Hepatitis C Virus Entry and Spread through the GPR30 Pathway

Authors: Laura Ulitzky, Dougbeh-Chris Nyan, Manuel M. Lafer, Erica Silberstein, Nicoleta Cehan, Deborah R. Taylor

Abstract:

Hepatitis C virus (HCV)-associated hepatocellular carcinoma, fibrosis and cirrhosis are more frequent in men and postmenopausal women than in premenopausal women and women receiving hormone replacement therapy, suggesting that β-estradiol (estrogen) plays an innate role in preventing viral infection and liver disease. Estrogen classically acts through nuclear estrogen receptors or, alternatively, through the membrane-bound G-protein-coupled estrogen receptor (GPR30 or GPER). We observed a marked decrease in detectable virus when HCV-infected human hepatoma cells were treated with estrogen. The effect was mimicked by both Tamoxifen (Tam) and G1, a GPR30-specific agonist, and was reversed by the GPR30-specific antagonist, G15. Through GPR30, estrogen-mediated the down-regulation of occludin; a tight junction protein and HCV receptor, by promoting activation of matrix metalloproteinases (MMPs). Activated MMP-9 was secreted in response to estrogen, cleaving occludin in the extracellular Domain D, the motif required for HCV entry and spread. This pathway gives new insight into a novel innate immune pathway and the disparate host-virus responses to HCV demonstrated by the two sexes. Moreover, these data suggest that hormone replacement therapy may have beneficial antiviral properties for HCV-infected postmenopausal women and show promise for new antiviral treatments for both men and women.

Keywords: HCV, estrogen, occludin, MMPs

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4067 Biomass and Biogas Yield of Maize as Affected by Nitrogen Rates with Varying Harvesting under Semi-Arid Condition of Pakistan

Authors: Athar Mahmood, Asad Ali

Abstract:

Management considerations including harvesting time and nitrogen application considerably influence the biomass yield, quality and biogas production. Therefore, a field study was conducted to determine the effect of various harvesting times and nitrogen rates on the biomass yield, quality and biogas yield of maize crop. This experiment was consisted of various harvesting times i.e., harvesting after 45, 55 and 65 days of sowing (DAS) and nitrogen rates i.e., 0, 100, 150 and 200 kg ha-1 respectively. The data indicated that maximum plant height, leaf area, dry matter (DM) yield, protein, acid detergent fiber, neutral detergent fiber, crude fiber contents and biogas yield were recorded 65 days after sowing while lowest was recorded 45 days after sowing. In contrary to that significantly higher chlorophyll contents were observed at 45 DAS. In case of nitrogen rates maximum plant height, leaf area, and DM yield, protein contents, ash contents, acid detergent fiber, neutral detergent fiber, crude fiber contents and chlorophyll contents were determined with nitrogen at the rate of 200 kg ha-1, while minimum was observed when no N was applied. Therefore, harvesting 65 DAS and N application @ 200 kg ha-1 can be suitable for getting the higher biomass and biogas production.

Keywords: chemical composition, fiber contents, biogas, nitrogen, harvesting time

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4066 Protein Stabilized Foam Structures as Protective Carrier Systems during Microwave Drying of Probiotics

Authors: Jannika Dombrowski, Sabine Ambros, Ulrich Kulozik

Abstract:

Due to the increasing popularity of healthy products, probiotics are still of rising importance in food manufacturing. With the aim to amplify the field of probiotic application to non-chilled products, the cultures have to be preserved by drying. Microwave drying has proved to be a suitable technique to achieve relatively high survival rates, resulting from drying at gentle temperatures, among others. However, diffusion limitation due to compaction of cell suspension during drying can prolong drying times as well as deteriorate product properties (grindability, rehydration performance). Therefore, we aimed to embed probiotics in an aerated matrix of whey proteins (surfactants) and di-/polysaccharides (foam stabilization, probiotic protection) during drying. As a result of the manifold increased inner surface of the cell suspension, drying performance was enhanced significantly as compared to non-foamed suspensions. This work comprises investigations on suitable foam matrices, being stable under vacuum (variation of protein concentration, type and concentration of di-/polysaccharide) as well as development of an applicable microwave drying process in terms of microwave power, chamber pressure and maximum product temperatures. Performed analyses included foam characteristics (overrun, drainage, firmness, bubble sizes), and properties of the dried cultures (survival, activity). In addition, efficiency of the drying process was evaluated.

Keywords: foam structure, microwave drying, polysaccharides, probiotics

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4065 Does Mirror Therapy Improve Motor Recovery After Stroke? A Meta-Analysis of Randomized Controlled Trials

Authors: Hassan Abo Salem, Guo Feng, Xiaolin Huang

Abstract:

The objective of this study is to determine the effectiveness of mirror therapy on motor recovery and functional abilities after stroke. The following databases were searched from inception to May 2014: Cochrane Stroke, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, and PEDro. Two reviewers independently screened and selected all randomized controlled trials that evaluate the effect of mirror therapy in stroke rehabilitation.12 randomized controlled trials studies met the inclusion criteria; 10 studies utilized the effect of mirror therapy for the upper limb and 2 studies for the lower limb. Mirror therapy had a positive effect on motor recover and function; however, we found no consistent influence on activity of daily living, Spasticity and balance. This meta-analysis suggests that, Mirror therapy has additional effect on motor recovery but has a small positive effect on functional abilities after stroke. Further high-quality studies with greater statistical power are required in order to accurately determine the effectiveness of mirror therapy following stroke.

Keywords: mirror therapy, motor recovery, stroke, balance

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4064 GGA-PBEsol+TB-MBJ Studies of SrxPb1-xS Ternary Semiconductor Alloys

Authors: Y. Benallou, K. Amara, O. Arbouche

Abstract:

In this paper, we report a density functional study of the structural, electronic and elastic properties of the ordered phases of SrxPb1-xS ternary semiconductor alloys namely rocksalt compounds: PbS and SrS and the rocksalt-based compounds: SrPb3S4, SrPbS2, and Sr3PbS4. These First-principles calculations have been performed using the full potential linearized augmented plane wave method (FP-LAPW) within the Generalized Gradient Approximation developed by Perdew–Burke–Ernzerhor for solids (PBEsol). The calculated structural parameters like the lattice parameters, the bulk modulus B and their pressure derivative B' are in reasonable agreement with the available experimental and theoretical data. In addition, the elastic properties such as elastic constants (C11, C12, and C44), the shear modulus G, the Young modulus E, the Poisson’s ratio ν and the B/G ratio are also given. For the electronic properties calculations, the exchange and correlation effects were treated by the Tran-Blaha modified Becke-Johnson (TB-mBJ) potential to prevent the shortcoming of the underestimation of the energy gaps in both LDA and GGA approximations. The obtained results are compared to available experimental data and to other theoretical calculations.

Keywords: SrxPb1-xS, GGA-PBEsol+TB-MBJ, density functional, Perdew–Burke–Ernzerhor, FP-LAPW

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4063 Expression of Fused Plasmodium falciparum Orotate Phosphoribosyltransferase and Orotidine 5'-Monophosphate Decarboxylase in Escherichia coli

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

Abstract:

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

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

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4062 Corn Flakes Produced from Different Cultivars of Zea Mays as a Functional Product

Authors: Milenko Košutić, Jelena Filipović, Zvonko Nježić

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Extrusion technology is thermal processing that is applied to improve the nutritional, hygienic, and physical-chemical characteristics of the raw material. Overall, the extrusion process is an efficient method for the production of a wide range of food products. It combines heat, pressure, and shear to transform raw materials into finished goods with desired textures, shapes, and nutritional profiles. The extruded products’ quality is remarkably dependent upon feed material composition, barrel temperature profile, feed moisture content, screw speed, and other extrusion system parameters. Given consumer expectations for snack foods, a high expansion index and low bulk density, in addition to crunchy texture and uniform microstructure, are desired. This paper investigates the effects of simultaneous different types of corn (white corn, yellow corn, red corn, and black corn) addition and different screw speed (350, 500, 650 rpm) on the physical, technological, and functional properties of flakes products. Black corn flour and screw speed at 350 rpm positively influenced physical, technological characteristics, mineral composition, and antioxidant properties of flake products with the best total score analysis of 0,59. Overall, the combination of Tukey's HSD test and PCA enables a comprehensive analysis of the observed corn products, allowing researchers to identify them. This research aims to analyze the influence of different types of corn flour (white corn, yellow corn, red corn, and black corn) on the nutritive and sensory properties of the product (quality, texture, and color), as well as the acceptance of the new product by consumers on the territory of Novi Sad. The presented data point that investigated corn flakes from black corn flour at 350 rpm is a product with good physical-technological and functional properties due to a higher level of antioxidant activity.

Keywords: corn types, flakes product, nutritive quality, acceptability

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4061 Ipsilateral Weakness Caused by Ipsilateral Stroke: A Case Series

Authors: Naim Izet Kajtazi

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Introduction: There are few reported cases of ipsilateral weakness following ischemic or hemorrhagic stroke. In these rare cases, ipsilateral weakness is typically the result of damage to uncrossed components of the corticospinal tract (CST), which were recruited in response to previous CST injury. Patients and Methods: We report a series of six cases of acute ipsilateral weakness or numbness following a hemorrhagic or ischemic stroke from three medical institutions in Saudi Arabia. Results: Three of these patients presented with right-sided weakness caused by an ipsilateral right hemispheric stroke, while two exhibited left-sided symptoms and one had only left-sided numbness. In all six cases, the ipsilateral corona radiata, internal capsule, basal ganglia, insula, and thalamus were involved. No concomitant opposite hemisphere or brainstem lesion in none of the patients was evident. Two patients had previous strokes affecting the brainstem and left corona radiata, respectively. A complete stroke workup to reveal the cause of the stroke was carried out, however, no functional MRI was performed. Conclusion: Ischemic or hemorrhagic stroke may indeed result in ipsilateral weakness or numbness, though in very rare cases. We assume that the most likely mechanism of their ipsilateral weakness subsequent to the ipsilateral stroke was a functional reorganization favoring CST pathways within the ipsilateral hemisphere.

Keywords: stroke, weakness, MRI brain, stroke unit

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4060 Resting-State Functional Connectivity Analysis Using an Independent Component Approach

Authors: Eric Jacob Bacon, Chaoyang Jin, Dianning He, Shuaishuai Hu, Lanbo Wang, Han Li, Shouliang Qi

Abstract:

Objective: Refractory epilepsy is a complicated type of epilepsy that can be difficult to diagnose. Recent technological advancements have made resting-state functional magnetic resonance (rsfMRI) a vital technique for studying brain activity. However, there is still much to learn about rsfMRI. Investigating rsfMRI connectivity may aid in the detection of abnormal activities. In this paper, we propose studying the functional connectivity of rsfMRI candidates to diagnose epilepsy. Methods: 45 rsfMRI candidates, comprising 26 with refractory epilepsy and 19 healthy controls, were enrolled in this study. A data-driven approach known as independent component analysis (ICA) was used to achieve our goal. First, rsfMRI data from both patients and healthy controls were analyzed using group ICA. The components that were obtained were then spatially sorted to find and select meaningful ones. A two-sample t-test was also used to identify abnormal networks in patients and healthy controls. Finally, based on the fractional amplitude of low-frequency fluctuations (fALFF), a chi-square statistic test was used to distinguish the network properties of the patient and healthy control groups. Results: The two-sample t-test analysis yielded abnormal in the default mode network, including the left superior temporal lobe and the left supramarginal. The right precuneus was found to be abnormal in the dorsal attention network. In addition, the frontal cortex showed an abnormal cluster in the medial temporal gyrus. In contrast, the temporal cortex showed an abnormal cluster in the right middle temporal gyrus and the right fronto-operculum gyrus. Finally, the chi-square statistic test was significant, producing a p-value of 0.001 for the analysis. Conclusion: This study offers evidence that investigating rsfMRI connectivity provides an excellent diagnosis option for refractory epilepsy.

Keywords: ICA, RSN, refractory epilepsy, rsfMRI

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4059 A Novel Gene Encoding Ankyrin-Repeat Protein, SHG1, Is Indispensable for Seed Germination under Moderate Salt Stress

Authors: H. Sakamoto, J. Tochimoto, S. Kurosawa, M. Suzuki, S. Oguri

Abstract:

Salt stress adversely affects plant growth at various stages of development including seed germination, seedling establishment, vegetative growth and finally reproduction. Because of their immobile nature, plants have evolved mechanisms to sense and respond to salt stress. Seed dormancy is an adaptive trait that enables seed germination to coincide with favorable environmental conditions. We identified a novel locus of Arabidopsis, designated SHG1 (salt hypersensitive germination 1), whose disruption leads to reduced germination rate under moderate salt stress conditions. SHG1 encodes a transmembrane protein with an ankyrin repeat motif that has been implicated in diverse cellular processes such as signal transduction. The SGH1-disrupted Arabidopsis mutant died at the cotyledon stage when sown on salt-containing medium, although wild type plants could form true leaves under the same conditions. On the other hand, this mutant showed similar phenotypes to wild type plants when sown on medium without salt and transferred to salt-containing medium at the vegetative stage. These results suggested that SHG1 played indispensable role in the seed germination and seedling establishment under moderate salt stress conditions. SHG1 may be involved in the release of seed dormancy.

Keywords: germination, ankyrin repeat, arabidopsis, salt tolerance

Procedia PDF Downloads 377
4058 An Approach on the Design of a Solar Cell Characterization Device

Authors: Christoph Mayer, Dominik Holzmann

Abstract:

This paper presents the development of a compact, portable and easy to handle solar cell characterization device. The presented device reduces the effort and cost of single solar cell characterization to a minimum. It enables realistic characterization of cells under sunlight within minutes. In the field of photovoltaic research the common way to characterize a single solar cell or a module is, to measure the current voltage curve. With this characteristic the performance and the degradation rate can be defined which are important for the consumer or developer. The paper consists of the system design description, a summary of the measurement results and an outline for further developments.

Keywords: solar cell, photovoltaics, PV, characterization

Procedia PDF Downloads 402
4057 Application of Electronic Nose Systems in Medical and Food Industries

Authors: Khaldon Lweesy, Feryal Alskafi, Rabaa Hammad, Shaker Khanfar, Yara Alsukhni

Abstract:

Electronic noses are devices designed to emulate the humane sense of smell by characterizing and differentiating odor profiles. In this study, we build a low-cost e-nose using an array module containing four different types of metal oxide semiconductor gas sensors. We used this system to create a profile for a meat specimen over three days. Then using a pattern recognition software, we correlated the odor of the specimen to its age. It is a simple, fast detection method that is both non-expensive and non-destructive. The results support the usage of this technology in food control management.

Keywords: e-nose, low cost, odor detection, food safety

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4056 Prognostic Value of C-Reactive Protein (CRP) in SARS-CoV-2 Infection: A Simplified Biomarker of COVID-19 Severity in Sub-Saharan Africa

Authors: Teklay Gebrecherkos, Mahmud Abdulkader, Tobias Rinke De Wit, Britta C. Urban, Feyissa Chala, Yazezew Kebede, Dawit Welday

Abstract:

Background: C-reactive protein (CRP) levels are a reliable surrogate for interleukin-6 bioactivity that plays a pivotal role in the pathogenesis of cytokine storm associated with severe COVID-19. There is a lack of data on the role of CRP as a determinant of COVID-19 severity status in the African context. Methods: We determined the longitudinal kinetics of CRP levels on 78 RT-PCR-confirmed COVID-19 patients (49 non-severe and 29 severe cases) and 50 PCR-negative controls. Results: COVID-19 patients had overall significantly elevated CRP at baseline when compared to PCR-negative controls [median 11.1 (IQR: 2.0-127.8) mg/L vs. 0.9 (IQR: 0.5-1.9) mg/L; p=0.0004)]. Moreover, severe COVID-19 patients had significantly higher median CRP levels than non-severe cases [166.1 (IQR: 48.6-332.5) mg/L vs. 2.4 (IQR: 1.2-7.6) mg/L; p<0.00001)]. In addition, persistently elevated levels of CRP were exhibited among those with comorbidities and higher age groups. Area under receiver operating characteristic curve (AUC) analysis of CRP levels distinguished PCR-confirmed COVID-19 patients from the ones with PCR-negative non-COVID-19 individuals, with an AUC value of 0.77 (95% CI: 0.68-0.84; p=0.001). Moreover, it clearly distinguished severe from non-severe COVID-19 patients, with an AUC value of 0.83 (95% CI: 0.73-0.91). After adjusting for age and the presence of comorbidities, CRP levels above 30 mg/L were significantly associated with an increased risk of developing severe COVID-19 (adjusted relative risk 3.99 (95%CI: 1.35-11.82; p=0.013). Conclusions: Determining CRP levels in COVID-19 patients in African settings may provide a simple, prompt, and inexpensive assessment of the severity status at baseline and monitoring of treatment outcomes.

Keywords: CRP, COVID-19, SARS-CoV-2, biomarker

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4055 Combined Optical Coherence Microscopy and Spectrally Resolved Multiphoton Microscopy

Authors: Bjorn-Ole Meyer, Dominik Marti, Peter E. Andersen

Abstract:

A multimodal imaging system, combining spectrally resolved multiphoton microscopy (MPM) and optical coherence microscopy (OCM) is demonstrated. MPM and OCM are commonly integrated into multimodal imaging platforms to combine functional and morphological information. The MPM signals, such as two-photon fluorescence emission (TPFE) and signals created by second harmonic generation (SHG) are biomarkers which exhibit information on functional biological features such as the ratio of pyridine nucleotide (NAD(P)H) and flavin adenine dinucleotide (FAD) in the classification of cancerous tissue. While the spectrally resolved imaging allows for the study of biomarkers, using a spectrometer as a detector limits the imaging speed of the system significantly. To overcome those limitations, an OCM setup was added to the system, which allows for fast acquisition of structural information. Thus, after rapid imaging of larger specimens, navigation within the sample is possible. Subsequently, distinct features can be selected for further investigation using MPM. Additionally, by probing a different contrast, complementary information is obtained, and different biomarkers can be investigated. OCM images of tissue and cell samples are obtained, and distinctive features are evaluated using MPM to illustrate the benefits of the system.

Keywords: optical coherence microscopy, multiphoton microscopy, multimodal imaging, two-photon fluorescence emission

Procedia PDF Downloads 492
4054 Development of an Asset Database to Enhance the Circular Business Models for the European Solar Industry: A Design Science Research Approach

Authors: Ässia Boukhatmi, Roger Nyffenegger

Abstract:

The expansion of solar energy as a means to address the climate crisis is undisputed, but the increasing number of new photovoltaic (PV) modules being put on the market is simultaneously leading to increased challenges in terms of managing the growing waste stream. Many of the discarded modules are still fully functional but are often damaged by improper handling after disassembly or not properly tested to be considered for a second life. In addition, the collection rate for dismantled PV modules in several European countries is only a fraction of previous projections, partly due to the increased number of illegal exports. The underlying problem for those market imperfections is an insufficient data exchange between the different actors along the PV value chain, as well as the limited traceability of PV panels during their lifetime. As part of the Horizon 2020 project CIRCUSOL, an asset database prototype was developed to tackle the described problems. In an iterative process applying the design science research methodology, different business models, as well as the technical implementation of the database, were established and evaluated. To explore the requirements of different stakeholders for the development of the database, surveys and in-depth interviews were conducted with various representatives of the solar industry. The proposed database prototype maps the entire value chain of PV modules, beginning with the digital product passport, which provides information about materials and components contained in every module. Product-related information can then be expanded with performance data of existing installations. This information forms the basis for the application of data analysis methods to forecast the appropriate end-of-life strategy, as well as the circular economy potential of PV modules, already before they arrive at the recycling facility. The database prototype could already be enriched with data from different data sources along the value chain. From a business model perspective, the database offers opportunities both in the area of reuse as well as with regard to the certification of sustainable modules. Here, participating actors have the opportunity to differentiate their business and exploit new revenue streams. Future research can apply this approach to further industry and product sectors, validate the database prototype in a practical context, and can serve as a basis for standardization efforts to strengthen the circular economy.

Keywords: business model, circular economy, database, design science research, solar industry

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4053 Extraction and Encapsulation of Carotenoids from Carrot

Authors: Gordana Ćetković, Sanja Podunavac-Kuzmanović, Jasna Čanadanović-Brunet, Vesna Tumbas Šaponjac, Vanja Šeregelj, Jelena Vulić, Slađana Stajčić

Abstract:

The color of food is one of the decisive factors for consumers. Potential toxicity of artificial food colorants has led to the consumers' preference for natural products over products with artificial colors. Natural pigments have many bioactive functions, such as antioxidant, provitamin and many other. Having this in mind, the acceptability of natural colorants by the consumers is much higher. Being present in all photosynthetic plant tissues carotenoids are probably most widespread pigments in nature. Carrot (Daucus carota) is a good source of functional food components. Carrot is especially rich in carotenoids, mainly α- and β-carotene and lutein. For this study, carrot was extracted using classical extraction with hexane and ethyl acetate, as well as supercritical CO₂ extraction. The extraction efficiency was evaluated by estimation of carotenoid yield determined spectrophotometrically. Classical extraction using hexane (18.27 mg β-carotene/100 g DM) was the most efficient method for isolation of carotenoids, compared to ethyl acetate classical extraction (15.73 mg β-carotene/100 g DM) and supercritical CO₂ extraction (0.19 mg β-carotene/100 g DM). Three carrot extracts were tested in terms of antioxidant activity using DPPH and reducing power assay as well. Surprisingly, ethyl acetate extract had the best antioxidant activity on DPPH radicals (AADPPH=120.07 μmol TE/100 g) while hexane extract showed the best reducing power (RP=1494.97 μmol TE/100 g). Hexane extract was chosen as the most potent source of carotenoids and was encapsulated in whey protein by freeze-drying. Carotenoid encapsulation efficiency was found to be high (89.33%). Based on our results it can be concluded that carotenoids from carrot can be efficiently extracted using hexane and classical extraction method. This extract has the potential to be applied in encapsulated form due to high encapsulation efficiency and coloring capacity. Therefore it can be used for dietary supplements development and food fortification.

Keywords: carotenoids, carrot, extraction, encapsulation

Procedia PDF Downloads 250
4052 The Stem Cell Transcription Co-factor Znf521 Sustains Mll-af9 Fusion Protein In Acute Myeloid Leukemias By Altering The Gene Expression Landscape

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

Abstract:

ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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4051 Non-Canonical Beclin-1-Independent Autophagy and Apoptosis in Cell Death Induced by Rhus coriaria in Human Colon HT-29 Cancer Cells

Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

Abstract:

Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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4050 Helicoverpa armigera Hubner (Lepidoptera: Noctuidae) Susceptibility to Bacillus thuringiensis Crystal Toxins

Authors: Muhammad Jawad Saleem, Faisal Hafeez, Muhammad Arshad, Afifa Naeem, Ayesha Iftekhar

Abstract:

Bacillus thuringiensis is a gram-positive spore-forming bacterium that belongs to the Bacillus cereus group of Bacilli and it produces ICP (insecticidal crystal protein) Cry toxins or Cysts toxins. Spores are produced as parasporal crystalline inclusions bodies (also known as endotoxins) at the onset of sporulation during the stationary growth phase. During vegetative growth that does not form crystals and is called vegetative insecticidal proteins (VIP) and secreted an insecticidal protein (SIP). Bacillus thuringiensis (Bt) is important for pest management either in the form of insecticides or through incorporated in the gene of the crop. Bioassays were conducted on the F2 generation of 1st instar larvae of H. armigera by the diet incorporation method to determine the susceptibility to Bt Cry toxins (Cry1Ac, Cry2Ab, Cry2A). The median lethal concentration (LC₅₀) of Cry1Ac, Cry2Ab, Cry2A ranged from 0.11 to 1.06 µg/ml and moult inhibitory concentration (MIC₅₀) of Cry1Ac, Cry2Ab, Cry2A ranged from 0.05 to 0.25 µg/ml. Cry1Ac was found most toxic to 1st instar larvae of H. armigera as compared to other Bt Cry toxins (Cry1Ac, Cry2Ab, Cry2A). The experimental results are important to policy-makers and technology providers to develop strategies for the exploitation of transgenic Bt cotton varieties as a component of integrated pest management.

Keywords: Bt toxin, Cry1Ac, Cry2Ab, Cry2A, susceptibility, Helicoverpa armigera

Procedia PDF Downloads 158
4049 In Silico Design of Organometallic Complexes as Potential Antibacterial Agents

Authors: Sanja O. Podunavac-Kuzmanović, Strahinja Z. Kovačević, Lidija R. Jevrić, Stela Jokić

Abstract:

The complexes of transition metals with various organic ligands have been extensively studied as models of some important pharmaceutical molecules. It was found that biological properties of different substituted organic molecules are improved when they are complexed by different metals. Therefore, it is of great importance for the development of coordination chemistry to explore the assembly of functional organic ligands with metal ion and to investigate the relationship between the structure and property. In the present work, we have bioassayed the antibacterial potency of benzimidazoles and their metal salts (Cu or Zn) against yeast Sarcina lutea. In order to validate our in vitro study, we performed in silico studies using molecular docking software. The investigated compounds and their metal complexes (Cu, Zn) showed good to moderate inhibitory activity against Sarcina lutea. In silico docking studies of the synthesized compounds suggested that complexed benzimidazoles have a greater binding affinity and improved antibacterial activity in comparison with non-complexed ligands. These results are part of the CMST COST Action No. 1105 "Functional metal complexes that bind to biomolecules".

Keywords: organometallic complexes, benzimidazoles, chemometric design, Sarcina lutea

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4048 The Second Generation of Tyrosine Kinase Inhibitor Afatinib Controls Inflammation by Regulating NLRP3 Inflammasome Activation

Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

Abstract:

Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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