Search results for: GntR transcriptional regulator

Authors: Moshe Davidian, Shlomo Mark, Yotam Lurie

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With the rapid development of technology and the concomitant growth in the capability of Artificial Intelligence (AI) systems and their power, the ethical challenges involved in these systems are also evolving and increasing. In recent years, various organizations, including governments, international institutions, professional societies, civic organizations, and commercial companies, have been choosing to address these various challenges by publishing ethical codes for AI systems. However, despite the apparent agreement that AI should be “ethical,” there is debate about the definition of “ethical artificial intelligence.” This study investigates the various AI ethical codes and their key ethical values. From the vast collection of codes that exist, it analyzes and compares 25 ethical codes that were found to be representative of different types of organizations. In addition, as part of its literature review, the study overviews data collected in three recent reviews of AI codes. The results of the analyses demonstrate a convergence around seven key ethical values. However, the key finding is that the different AI ethical codes eventually reflect the type of organization that designed the code; i.e., the organizations’ role as regulator, user, or developer affects the view of what ethical AI is. The results show a relationship between the organization’s role and the dominant values in its code. The main contribution of this study is the development of a list of the key values for all AI systems and specific values that need to impact the development and design of AI systems, but also allowing for differences according to the organization for which the system is being developed. This will allow an analysis of AI values in relation to stakeholders.

Keywords: artificial intelligence, ethical codes, principles, values

Procedia PDF Downloads 65

Authors: Sangyeop Shin, D. C. M. Kulatunga, S. H. S. Dananjaya, Chamilani Nikapitiya, Jehee Lee, Mahanama De Zoysa

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Saprolegniasis is one of the most devastating fungal diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated fungi belong to the member of S. parasitica, supported by its typical fungal features including cotton-like whitish mycelium, zoospores (primary and secondary) and phylogenetic analysis with internal transcribed spacer (ITS) region. Pathogenicity of isolated S. parasitica was developed in embryo, larvae, juvenile and adult zebrafish as a disease model. Up regulation of host genes encoding ZfTnf-α, Zfc-Rel, ZfIl-12, ZfLyz-c, Zfβ-def, and ZfHsp-70 was identified in zebrafish larvae after experimental challenge of S. parasitica showing the host immune responses against the S. parasitica. Survival of the juveniles upon fungal infection might be due to the increased immune protection in the host. Investigation of antifungal susceptibility of S. parasitica with natural lawsone (2-hydroxy-1,4-naphthoquinone) revealed the minimum inhibitory concentration (MIC) and percentage inhibition of radial growth (PIRG %) as 200 µg/mL and 31.8%, respectively. Lawsone was able to change the membrane permeability, and cause irreversible damage and disintegration to the cellular membranes of S. parasitica which might have effect on fungi growth inhibition. Moreover, the mycelium exposed to lawsone (MIC level) changed the transcriptional responses of S. parasitica genes. Overall results indicate that lawsone could be a potential and novel anti-S. parasitica agent for controlling S. parasitica infection.

Keywords: host-pathogen interactions, lawsone, rainbow trout, Saprolegnia parasitica, Saprolegniasis, zebrafish

Procedia PDF Downloads 220

Authors: Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K. Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J. Perera

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Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has a complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its novel predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

Keywords: metabolism, microRNA, mitochondria, vitiligo

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Authors: Anjan Hazra, Nirjhar Dasgupta, Chandan Sengupta, Sauren Das

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Tea (Camellia sinensis) has received substantial attention from the scientific world time to time, not only for its commercial importance, but also for its demand to the health-conscious people across the world for its extensive use as potential sources of antioxidant supplement. These health-benefit traits primarily rely on some regulatory networks of different metabolic pathways. Development of microsatellite markers from the conserved genomic regions is being worthwhile for studying the genetic diversity of closely related species or self-pollinated species. Although several SSR markers have been reported, in tea the trait-specific Simple Sequence Repeats (SSRs) are yet to be identified, which can be used for marker assisted breeding technique. MicroRNAs are endogenous, noncoding, short RNAs directly involved in regulating gene expressions at the post-transcriptional level. It has been found that diversity in miRNA gene interferes the formation of its characteristic hair pin structure and the subsequent function. In the present study, the precursors of small regulatory RNAs (microRNAs) has been fished out from tea Expressed Sequence Tag (EST) database. Furthermore, the simple sequence repeat motifs within the putative miRNA precursor genes are also identified in order to experimentally validate their existence and function. It is already known that genic-SSR markers are very adept and breeder-friendly source for genetic diversity analysis. So, the potential outcome of this in-silico study would provide some novel clues in understanding the miRNA-triggered polymorphic genic expression controlling specific metabolic pathways, accountable for tea quality.

Keywords: micro RNA, simple sequence repeats, tea quality, trait specific marker

Procedia PDF Downloads 278

Authors: Tsai-chun Lai, Szu-ju Fu, Tzu-lin Lee, Yuh-Lien Chen

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There is much evidence that exposure to fine particulate matter (PM) from air pollution increases the risk of cardiovascular morbidity and mortality. According to previous reports, PM in the air enters the respiratory tract, contacts the alveoli, and enters the blood circulation, leading to the progression of cardiovascular disease. PM pollution may also lead to cardiometabolic disturbances, increasing the risk of cardiovascular disease. The effects of PM on cardiac function and mitochondrial damage are currently unknown. We used mice and rat cardiomyocytes (H9c2) as animal and in vitro cell models, respectively, to simulate an air pollution environment using PM. These results indicate that the apoptosis-related factor PUMA, a regulator of apoptosis upregulated by p53, is increased in mice treated with PM. Apoptosis was aggravated in cardiomyocytes treated with PM, as measured by TUNEL assay and Annexin V/PI. Western blot results showed that CASPASE3 was significantly increased and BCL2 (B-cell lymphoid 2) was significantly decreased under PM treatment. Concurrent exposure to PM increases mitochondrial reactive oxygen species (ROS) production by MitoSOX Red staining. Furthermore, using Mitotracker staining, PM treatment significantly shortened mitochondrial length, indicating mitochondrial fission. The expression of mitochondrial fission-related proteins p-DRP1 (phosphodynamics-related protein 1) and FIS1 (mitochondrial fission 1 protein) was significantly increased. Based on these results, the exposure to PM worsens mitochondrial function and leads to cardiomyocyte apoptosis.

Keywords: particulate matter, cardiomyocyte, apoptosis, mitochondria

Procedia PDF Downloads 75

Authors: Sara Lamari, Toufik Madani

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This study aimed to explore the relationship between reproduction performances and coat characteristics of Montbéliarde cows born in Algeria or imported from Europe during the hot season in Algeria. Hair coat traits (hair coat color, Hair Weight, hair length, the number of hair per unit area, total hair diameters and hair medulla diameters) were estimated in 18 imported cattle and 49 locally born cows. These traits were measured in an area of 20cm below the dorsal line in the center of the thorax. Results showed that hair coats were significantly different between locally born and imported cows. Imported cows had whiter coats when compared to locally born cows for Montbéliarde cows. A significant effect of total hair diameter was observed on the interval from calving to conception (IC) for imported Montbéliarde cows, suggesting less incidence of heat stress on reproduction efficiency of cows with thin diameter hair coats. Montbéliarde cows with short hair coat registered significantly more number of mating per conception (2, 28±1, 93 Vs. 1,67±0,92) and IC (98,04±78,81Vs 74.53 ± 35.60 days) when compared to cows with long hairs. Hair works as a temperature regulator in association with muscles in the skin and may affect reproduction performances during hit stress season. It can be assumed that the length and a total diameter of hairs for the Montbeliarde breed appears to be related to their reproductive efficiency.

Keywords: hair coat, reproduction, Montbeliarde cow, hot season

Procedia PDF Downloads 129

Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

Procedia PDF Downloads 278

Authors: Hossein Edrisi

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To study the impact of the amount and volume of power of isolation transformer on the lamps in airfield Ground Lighting Systems. A test was conducted in Persian Gulf International Airport, This airport is situated in the south of Iran and it is one of the most cutting-edge airports, the same one that owns modern devices. Iran uses materials and auxiliary equipment which are made by ADB Company from Belgium. Airfield ground lighting (AGL) systems are responsible for providing visual issue to aircrafts and helicopters in the runways. In an AGL system a great deal of lamps are connected in serial circuits to each other and each ring has its individual constant current regulators (CCR), which through that provide energy to the lamps. Control of lamps is crucial for maintenance and operation in the AGL systems. Thanks to the Programmable Logic Controller (PLC) that is a cutting-edge technology can help the system to connect the elements from substations and ATC (TOWER). For this purpose, a test in real conditions of the airport done for all element that used in the airport such as isolation transformer in different power capacity and different consuming power and brightness of the lamps. The data were analyzed with Lux meter and Multimeter. The results had shown that the increase in the power of transformer caused a significant increase in brightness. According to the Ohm’s law and voltage division, without changing the characteristics of the light bulb, it is not possible to change the voltage, just need to change the amount of transformer with which it connects to the lamps. When the voltage is increased, the current through the bulb has to increase as well, because of Ohm's law: I=V/R and I=V/R which means that if V increases, so do I increase. The output voltage on the constant current regulator emerges between the lamps and the transformers.

Keywords: AGL, CCR, lamps, transformer, Ohm’s law

Procedia PDF Downloads 216

Authors: Bernice Lottering, Yi-Wen Lin

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Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

Procedia PDF Downloads 105

Authors: Ahmed Y. Kutbi, C. Russell. J. Baird, M. McNaughtan, Francis Wayman

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Wastewaters from antibiotic production facilities are characterized with high concentrations of dissolved organic substances. Subsequently, it challenges wastewater treatment plant operator to achieve successful biological treatment and to meet regulatory emission levels. Of the dissolved organic substances, this research is investigating the fate of organic nitrogenous compounds (i.e., Chitin) in an antibiotic production wastewater treatment plant located in Irvine, Scotland and its impact on the WWTP removal performance. Dissolved organic nitrogen (DON) in WWTP effluents are of significance because 1) its potential to cause eutrophication in receiving waters, 2) the formation of nitrogenous disinfection by products in drinking waters and 3) limits WWTPs ability to achieve very low total nitrogen (TN) emissions limits (5 – 25 mg/l). The latter point is where the knowledge gap lays between the operator and the regulator in setting viable TN emission levels. The samples collected from Irvine site at the different stages of the treatment were analyzed for TN and DON. Results showed that the average TN in the WWTP influents and effluents are 798 and 261 mg/l respectively, in other words, the plant achieved 67 % removal of TN. DON Represented 51% of the influents TN, while the effluents accounted 26 % of the TN concentrations. Therefore, an ongoing investigation is carried out to identify DON constituents in WWTP effluent and evaluate its impact on the WWTP performance and its potential bioavailability for algae in receiving waters, which is, in this case, Irvine Bay.

Keywords: biological wastewater treatment plant, dissolved organic nitrogen, bio-availability, Irvine Bay

Procedia PDF Downloads 221

Authors: Maximiliano K. Pagliarini, Ana Carolina T. Malavolta, Isabela M. Morita, Regina Maria M. Castilho

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Among the ornamental plants, the Amaryllis (Hippeastrum X hybridum Hort.) is one of the most cultivated plants in Brazil because of their large and showy flowers. Thus, the consumer market wants better quality plants or to flourish more in less time. One of the devices that can make such improvements or accelerate the flowering process is the use of growth regulators. The objective of this research was to evaluate the use of different Stimulate® growth regulator doses and its constituents separately in the development and flowering of Hippeastrum X hybridum Hort. Cv Orange Souvereign. The experiment was conducted in a Pad & Fan greenhouse at UNESP, São Paulo State, Brazil from August to October 2014. The bulbs were placed in black vases of 1.2 L filled with commercial substrate and divided into 9 treatments: T1 – 10 mL L-1 of Stimulate®, T2 – 5 mL L-1 of Stimulate®, T3 – 0.5 mg L-1 of gibberellic acid (GA), T4 – 0.25 mg L-1 of GA, T5 – 0.45 mg L-1 of kinetin, T6 – 0.9 mg L-1 of kinetin, T7 – 0.5 mg L-1 of indolbutiric acid (IBA), T8 – 0.25 mg L-1 of IBA and T9 – distilled water (control). All treatments were diluted in water. The used design was completely randomized with six repetitions and two vessels, totalling 12 vessels per treatment. The evaluated characteristics were: number of leaves, length of leaf, number of rods, maximum height of rods, maximum diameter of rods, maximum number of flowers, beginning of flowering, flowering duration, and weight of bulbs. The results showed that the Stimulate® was not efficient in the conducted experiment conditions. However, the best treatment was 0.5 mg L-1 of IBA.

Keywords: bulbs, gibberellic acid, indolbutiric acid, kinetin, ornamental plants

Procedia PDF Downloads 513

Authors: Zinhle Cindi, Collet Dandara, Mpiko Ntsekhe, Edson Makambwa, Miguel Larceda

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Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed. Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C > T, VKORC1 g.-1639G > A and VKORC1 c.1173C > T among South African Mixed Ancestry (MA) and Black African patients. Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs. Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G > A genotypes (p < 0.006) and all VKORC1 c.1173C > T genotypes (p < 0.007). Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.

Keywords: algorithms, pharmacogenetics, thromboembolic disease, warfarin

Procedia PDF Downloads 230

Authors: Clotilde Guyon, Nada Jmari, Yen-Chin Li, Jean Denoyel, Noriyuki Fujikado, Christophe Blanchet, David Root, Matthieu Giraud

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Aire induces ectopic expression of a large repertoire of tissue-specific antigen (TSA) genes in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in maturing T cells. Although important mechanisms of Aire-induced transcription have recently been disclosed through the identification and the study of Aire’s partners, the fine transcriptional functions underlied by a number of them and conferred to Aire are still unknown. Alternative cleavage and polyadenylation (APA) is an essential mRNA processing step regulated by the termination complex consisting of 85 proteins, 10 of them have been related to Aire. We evaluated APA in MECs in vivo by microarray analysis with mRNA-spanning probes and RNA deep sequencing. We uncovered the preference of Aire-dependent transcripts for short-3’UTR isoforms and for proximal poly(A) site selection marked by the increased binding of the cleavage factor Cstf-64. RNA interference of the 10 Aire-related proteins revealed that Clp1, a member of the core termination complex, exerts a profound effect on short 3’UTR isoform preference. Clp1 is also significantly upregulated in the MECs compared to 25 mouse tissues in which we found that TSA expression is associated with longer 3’UTR isoforms. Aire-dependent transcripts escape a global 3’UTR lengthening associated with MEC differentiation, thereby potentiating the repressive effect of microRNAs that are globally upregulated in mature MECs. Consistent with these findings, RNA deep sequencing of actinomycinD-treated MECs revealed the increased stability of short 3’UTR Aire-induced transcripts, resulting in TSA transcripts accumulation and contributing for their enrichment in the MECs.

Keywords: Aire, central tolerance, miRNAs, transcription termination

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Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

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Authors: Vincent Murray

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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

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Authors: D. Leibman, D. Wolf, A. Gal-On

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Viral diseases of tomato crops result in heavy yield losses and may even jeopardize the production of these crops. Classical tomato breeding for disease resistance against Tomato yellow leaf curl virus (TYLCV), leads to partial resistance associated with a number of recessive genes. To author’s best knowledge Pepino mosaic virus (PepMV) genetic resistance is not yet available. The generation of viral resistance by means of genetic engineering was reported and implemented for many crops, including tomato. Transgenic resistance against viruses is based, in most cases, on Post Transcriptional Gene Silencing (PTGS), an endogenous mechanism which destroys the virus genome. In this work, we developed immunity against PepMV and TYLCV in a tomato based on a PTGS mechanism. Tomato plants were transformed with a hairpin-construct-expressed transgene-derived double-strand-RNA (tr-dsRNA). In the case of PepMV, the binary construct harbored three consecutive fragments of the replicase gene from three different PepMV strains (Italian, Spanish and American), to provide resistance against a range of virus strains. In the case of TYLCV, the binary vector included three consecutive fragments of the IR, V2 and C2 viral genes constructed in a hairpin configuration. Selected transgenic lines (T0) showed a high accumulation of transgene siRNA of 21-24 bases, and T1 transgenic lines showed complete immunity to PepMV and TYLCV. Graft inoculation displayed immunity of the transgenic scion against PepMV and TYLCV. The study presents the engineering of resistance in tomato against two serious diseases, which will help in the production of high-quality tomato. However, unfortunately, these resistant plants have not been implemented due to public ignorance and opposition against breeding by genetic engineering.

Keywords: PepMV, PTGS, TYLCV, tr-dsRNA

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Authors: Eugene Mashapa

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The age of information has witnessed countless unprecedented technological developments, which signal the articulation of succinct technological capabilities that can match these cutting-edge technological trends. These changes have impacted patterns in the production, distribution, and consumption of media content, a space that the Film and Publication Board (FPB) is concerned with. Consequently, the FPB is keen to understand the nature and impact of these technological changes on media content regulation. This exploratory study sought to investigate how content regulators in high and middle-income economies have adapted to the changes in this space, seeking insights into innovations, technological and operational, that facilitate continued relevance during this fast-changing environment. The study is aimed at developing recommendations that could assist and inform the organisation in regulating media content as it evolves. Thus, the overall research strategy in this analysis is applied research, and the analytical model adopted is a mixed research design guided by both qualitative and quantitative research instruments. It was revealed in the study that the FPB was significantly impacted by the unprecedented technological advancements in the media regulation space. Additionally, there exists a need for the FPB to understand the current and future penetrations of 4IR technology in the industry and its impact on media governance and policy implementation. This will range from reskilling officials to align with the technological skills to developing technological innovations as well as adopting co-regulatory or self-regulatory arrangements together with content distributors, where more content is distributed in higher volumes and with increased frequency. Importantly, initiating an interactive learning process for both FPB employees and the general public can assist the regulator and improve FPB’s operational efficiency and effectiveness.

Keywords: media, regulation, technology, film and publications board

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Authors: Qing Cao, Fei Wang, Yu-Qiang Wang, Li-Ya Huang, Tian-Tian Sang, Shu-Yan Chen

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Aims: TNF Receptor-Associated Factor 6 (TRAF6) acts as a multifunctional regulator of the Transforming Growth Factor (TGF)-β signaling pathway, and mediates Smad-independent JNK and p38 activation via TGF-β. This study was performed to test the hypothesis that TGF-β/TRAF6 is essential for angiotensin-II (Ang II)-induced differentiation of rat c-kit+ Cardiac Stem Cells (CSCs). Methods and Results: c-kit+ CSCs were isolated from neonatal Sprague Dawley (SD) rats, and their c-kit status was confirmed with immunofluorescence staining. A TGF-β type I receptor inhibitor (SB431542) or the small interfering RNA (siRNA)-mediated knockdown of TRAF6 were used to investigate the role of TRAF6 in TGF-β signaling. Rescue of TRAF6 siRNA transfected cells with a 3'UTR deleted siRNA insensitive construct was conducted to rule out the off target effects of the siRNA. TRAF6 dominant negative (TRAF6DN) vector was constructed and used to infect c-kit+ CSCs, and western blotting was used to assess the expression of TRAF6, JNK, p38, cardiac-specific proteins, and Wnt signaling proteins. Physical interactions between TRAF6 and TGFβ receptors were studied by coimmunoprecipitation. Cardiac differentiation was suppressed in the absence of TRAF6. Forced expression of TRAF6 enhanced the expression of TGF-β-activated kinase1 (TAK1), and inhibited Wnt signaling. Furthermore, TRAF6 increased the expression of cardiac-specific proteins (cTnT and Cx-43) but inhibited the expression of Wnt3a. Conclusions: Our data suggest that TRAF6 plays an important role in Ang II induced differentiation of c-kit+ CSCs via the non-canonical signaling pathway.

Keywords: cardiac stem cells, differentiation, TGF-β, TRAF6, ubiquitination, Wnt

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Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.

Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa

Procedia PDF Downloads 258

Authors: Rostika Flora, Muhammad Zulkarnain, Syokumawena

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Background: Aerobic physical exercises are recommended to keep body fit and healthy although physical exercises themselves can increase body metabolism and oxygen and can lead into tissue hypoxia. Oxygen pressure can serve as Vascular Endhothelial Growth Factor (VEGF) regulator. Hypoxia increases gene expression of VEGF through ascendant regulation of HIF-1. VEGF is involved in regulating angiogenesis process. Aerobic physical exercises can increase the concentration of VEGF in brain and enables angiogenesis process. We have investigated the influence of aerobic physical exercise to the VGEF concentration of wistar rat’s brain. Methods: This was experimental study using post test only control group design. Independent t-test was used as statistical test. The samples were twenty four wistar rat (Rattus Norvegicus) which were divided into four groups: group P1 (control group), group P2 (treatment group with once-a-week exercise), group P3 (treatment group with three time-a-week exercise), and group P4 (treatment group with seven time-a-week exercise). Group P2, P3, and P4 were treated with treadmil with speed of 20 m/minute for 30 minutes. The concentration of VEGF was determined by ELISA. Results: There was a significant increase of VEGF in treatment group compared with control one (<0.05). The maximum increase was found in group P2 (129.02±64.49) and the minimum increase was in group P4 (96.98±11.20). Conclusion: The frequency of aerobic physical exercises influenced the concentration of Vascular Endhothelial Growth Factor (VEGF) of brain tissue of Rattus Norvegicus.

Keywords: brain tissue, hypoxia, physical exercises, vascular endhothelial growth factor

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Authors: Abdul Soofi, Katherine Wolf, Egon Ranghini, Gregory Dressler

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Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissues differentiation. The Kielin/Chordin-like Protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and Activin signals while enhancing the Bone Morphogenetic protein (BMP) signaling. However, the effects of KCP on metabolism and obesity have not been studied in animal models. Thus, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high fat diet. Loss of KCP sensitized mice to obesity and associated complications such as hepatic steatosis and glucose intolerance. In contrast, transgenic mice that expressed KCP in the kidney, liver and adipose tissues were resistant to developing high fat diet induced obesity and had significantly reduced white adipose tissue. KCP over-expression was able to shift the pattern of Smad signaling in vivo, to increase the levels of P-Smad1 and decrease P-Smad3, resulting in resistance to high fat diet induced hepatic steatosis and glucose intolerance. In aging mice, loss of KCP promoted liver pathology even when mice were fed a normal diet. The data demonstrate that shifting the TGF-β superfamily signaling with a secreted inhibitor or enhancer can alter the physiology of adipose tissue to reduce obesity and can inhibit the initiation and progression of hepatic steatosis to significantly reduce the effects of high fat diet induced metabolic disease.

Keywords: adipose tissue, KCP, obesity, TGF-β, BMP, hepatic steatosis, metabolic syndrome

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Authors: Vanessa Caroline De Barros Bonato, Bruna Lima Gomes, Luciano Freschi, Eduardo Purgatto

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The plant hormone ethylene is closely related to the metabolic changes that occur during fruit ripening, including volatile biosynthesis. Although knowledge about the biochemistry pathways that produce flavor compounds and the importance of ethylene to these processes are extensively covered, little is known about the regulation mechanisms. In addition, growing body of evidences indicates that auxin is also involved in controlling ripening. However, there is scarce information about the involvement of auxin in fruit volatile production. This study aimed to assess auxin-ethylene interactions and its influence on tomato fruit volatile profile. Fruits from tomato cultivar Micro-Tom were treated with IAA and ethylene, separately and in combination. The hormonal treatment was performed by injection (IAA) or gas exposure (ethylene) and the volatiles were extracted by Solid Phase Microextraction (SPME) and analyzed by GC-MS. Ethylene levels and color were measured by gas chromatography and colorimetry, respectively. The results indicate that the treatment with IAA (even in the presence of high concentrations of exogenous ethylene), impacted the profile of volatile compounds derived from fatty acids, amino acids, carbohydrates and isoprenoids. Ethylene is a well-known regulator of the transition from green to red color and also is implicated in the biosynthesis of characteristic volatile compounds of tomato fruit. The effects observed suggest the existence of a crosstalk between IAA and ethylene in the aroma volatile formation in the fruit. A possible interference of IAA in the ethylene sensitivity in the fruit flesh is discussed. The data suggest that auxin plays an important role in the volatile synthesis in the tomato fruit and introduce a new level of complexity in the regulation of the fruit aroma formation during ripening.

Keywords: aroma compounds, fruit ripening, fruit quality, phytohormones

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Authors: Olfat Shaker, Miriam Wadie, Reham Ali, Ayman Yosry

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Colorectal cancer (CRC) is a major cause of mortality and morbidity and accounts for over 9% of cancer incidence worldwide. Silent information regulator 2 homolog 1 (SIRT1) gene is located in the nucleus and exert its effects via modulation of histone and non-histone targets. They function in the cell via histone deacetylase (HDAC) and/or adenosine diphosphate ribosyl transferase (ADPRT) enzymatic activity. The aim of this work was to study the relationship between SIRT1 polymorphism and its protein level in colorectal cancer patients in comparison to control cases. This study includes 2 groups: thirty healthy subjects (control group) & one hundred CRC patients. All subjects were subjected to: SIRT-1 serum level was measured by ELISA and gene polymorphisms of rs12778366, rs375891 and rs3740051 were detected by real time PCR. For CRC patients clinical data were collected (size, site of tumor as well as its grading, obesity) CRC patients showed high significant increase in the mean level of serum SIRT-1 compared to control group (P<0.001). Mean serum level of SIRT-1 showed high significant increase in patients with tumor size ≥5 compared to the size < 5 cm (P<0.05). In CRC patients, percentage of T allele of rs12778366 was significantly lower than controls, CC genotype and C allele C of rs 375891 were significantly higher than control group. In CRC patients, the CC genotype of rs12778366, was 75% in rectosigmoid and 25% in cecum & ascending colon. According to tumor size, the percentage of CC genotype was 87.5% in tumor size ≥5 cm. Conclusion: serum level of SIRT-1 and T allele, C allele of rs12778366 and rs 375891 respectively can be used as diagnostic markers for CRC patients.

Keywords: CRC, SIRT1, polymorphisms, ELISA

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Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and has been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. The prickly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, the southwestern region of Korea, and used as a functional food. The present study investigated the effects of OFS on adipogenesis, lipolysis, glucose uptake, and glucose transporter (GLUT4) expression using preadipocyte 3T3-L1 cells. Adipogenesis was determined by preadipocyte differentiation and triglyceride accumulation assessed by Oil Red O staining. Lipolysis was determined as the rate of glycerol release. Insulin-stimulated glucose uptake and GLUT4 expression were measured using fluorescent glucose analogue, 2-NBDG, and ELISA, respectively. Quantitative real-time RT-PCR was performed to investigate the effects of OFS on the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation. Ethanol extracts of OFS dose-dependently enhanced adipocyte differentiation and cellular triglyceride levels indicating the enhancement of the differentiation of preadipocytes into adipocytes. Insulin-stimulated glucose uptake and GLUT4 expression were also dose-dependently increased by OFS treatment. Furthermore, OFS treatment also increased the mRNA levels of PPARγ. These effects of OFS on adipocytes suggest that OFS is potentially beneficial for type 2 diabetes by due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

Keywords: 3T3-L1 preadipocyte cell, adipogenesis, GLUT4, lipolysis, Opuntia ficus-indica var. Saboten, PPARγ, prickly pear cactus

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Authors: Naoki Yamamoto, Hidenobu Ozaki, Taiichiro Ookawa, Youming Liu, Kazunori Okada, Aiping Zheng

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Rice sheath blight is one of the destructive fungal diseases in rice. We have thought that rice sheath blight resistance is a polygenic trait. Host-pathogen interactions and secondary metabolites such as lignin and phytoalexins are likely to be involved in defense against R. solani. However, to our knowledge, it is still unknown how sheath blight resistance can be enhanced in rice breeding. To seek for an alternative genetic factor that contribute to sheath blight resistance, we mined relevant allelic variations from rice core collections created in Japan. Based on disease lesion length on detached leaf sheath, we selected 30 varieties of the top tail-end and the bottom tail-end, respectively, from the core collections to perform genome-wide association mapping. Re-sequencing reads for these varieties were used for calling single nucleotide polymorphisms among the 60 varieties to create a SNP panel, which contained 1,137,131 homozygous variant sites after filitering. Association mapping highlighted a locus on the long arm of chromosome 11, which is co-localized with three sheath blight QTLs, qShB11-2-TX, qShB11, and qSBR-11-2. Based on the localization of the trait-associated alleles, we identified an ankyryn repeat-containing protein gene (ANK-M) as an uncharacterized candidate factor for rice sheath blight resistance. Allelic distributions for ANK-M in the whole rice population supported the reliability of trait-allele associations. Gene expression characteristics were checked to evaluiate the functionality of ANK-M. Since an ANK-M homolog (OsPIANK1) in rice seems a basal defense regulator against rice blast and bacterial leaf blight, ANK-M may also play a role in the rice immune system.

Keywords: allele mining, GWAS, QTL, rice sheath blight

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Authors: Rian O. Miranda, Lidia V. de Sa, Julio C. Suita

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The Brazilian Nuclear Energy Commission (CNEN) is the main manufacturer of radiopharmaceuticals in Brazil. The Nuclear Engineering Institute (IEN), located at Rio de Janeiro, is one of its main centers of research and production, attending public and private hospitals in the state. This radiopharmaceutical production is used in diagnostic and therapy procedures and allows one and a half million nuclear medicine procedures annually. Despite this, the country is not self-sufficient to meet national demand, creating the need for importation and consequent dependence on other countries. However, IEN facilities were designed in the 60's, and today its structure is inadequate in relation to the good manufacturing practices established by sanitary regulator (ANVISA) and radiological protection leading to the need for a new project. In order to adapt and increase production in the country, a new plant will be built and integrated to the existing facilities with a new 30 MeV Cyclotron that is actually in project detailing process. Thus, it is proposed to survey current CNEN and ANVISA standards for radiopharmaceutical production facilities, as well as the radiological protection analysis of each area of the plant, following good manufacturing practices recommendations adopted nationally besides licensing exigencies for radioactive facilities. In this way, the main requirements for proper operation, equipment location, building materials, area classification, and maintenance program have been implemented. The access controls, interlocks, segregation zones and pass-through boxes integrated into the project were also analyzed. As a result, IEN will in future have the flexibility to produce all necessary radioisotopes for nuclear medicine application, more efficiently by simultaneously bombarding two targets, allowing the simultaneous production of two different radioisotopes, minimizing radiation exposure and saving operating costs.

Keywords: cyclotron, legislation, norms, production, radiopharmaceuticals

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Authors: Ayesha Iftikhar, Faisal Hafeez, Muhammad Jawad Saleem, Afifa Naeem, Muhammad Sohaib

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To further develop integrated pest management (IPM) tactics against insect pests, demographic toxicology is considered important and efficient to evaluate the long-term effects of pesticides on biological control agents. In this study, lethal and sub-lethal effects of Pyriproxyfen (insect growth regulator) two concentrations of LC10 and LC30 were tested on second instar larvae of convergent lady beetle, Hippodamia convergens (Goeze) in order to evaluate the effect of insecticide on demographic parameters of the predator under laboratory conditions. The life table parameters were analysed statistically by using age-stage, two sex life table procedure. The results of this study show that developmental time for immature was prolonged in treated population (LC30 and LC10) rather than in control. Similarly, male and female longevity was also longer in the control group as compared to the treated population. Adult pre-oviposition period and fecundity were also greater in control as compared to the treated population. In addition, population parameters such as net reproductive rate (R0), intrinsic rate of increase (r) and finite rate of increase (λ) were also greater in control group rather than treated population. However, mean generation time (T) was greater in the treated group. The results revealed that pyriproxyfen, even at low concentrations, has potential to greatly affect the population growth of predatory lady beetle, therefore care should be taken when insect growth regulators are used within an IPM framework.

Keywords: ladybird beetle, IGR, integrated pest management, population inhibition

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Authors: Jae Bok Heo, Yun Mi Lee, Hee Rang Yun

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Several GTPases are required for ribosome biogenesis and assembly. We recently characterized rice (Oryza sativa) nuclear/nucleolar GTPase 2 (OsNug2), belonging to the YlqF/YawG family of GTPases, as playing a role in pre-60S ribosomal subunit maturation. To investigate the potential factors involved in regulating the function of OsNug2, yeast two-hybrid screens were carried out using OsNug2 as bait. Rice serine/threonine kinase 1 (OsSTK1) was identified as a potential interacting protein candidate. In vitro pull down and bimolecular fluorescence complementation assays confirmed the interaction between OsNug2 and OsSTK1, and like green fluorescent protein-tagged OsNug2, green fluorescent protein-tagged OsSTK1 was targeted to the nucleus of Arabidopsis protoplasts. OsSTK1 was not found to affect the GTP-binding activity of OsNug2; however, when recombinant OsSTK1 was included in OsNug2 assay reaction mixtures, OsSTK1 increased the GTPase activity of OsNug2. To test whether OsSTK1 phosphorylates OsNug2 in vitro, a kinase assay was performed. OsSTK1 was found to have weak autophosphorylation activity and strongly phosphorylated serine 209 of OsNug2. Yeast complementation testing resulted in a GAL::OsNug2(S209N) mutant-harboring yeast strain exhibiting a growth-defective phenotype on galactose medium at 39°C, divergent from that of a yeast strain harboring GAL::OsNug2. The intrinsic GTPase activity of mutant OsNug2(S209N) was found to be similar to that of OsNug2, was not fully enhanced upon weak binding of OsSTK1. Our findings reported here indicate that OsSTK1 functions as a positive regulator protein of OsNug2 by enhancing the GTPase activity of OsNug2, and that the phosphorylation of serine 209 of OsNug2 is essential for the complete function of OsNug2 in ribosome biogenesis.

Keywords: OsSTK1, OsNug2, GTPase activity, GTP binding activity, phosphorylation

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Authors: O. B. Iskender, K. V. Ling, V. Dubanchet, L. Simonini

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This paper presents a Guidance and Control (G&C) strategy to address spacecraft maneuvering problem for future Rendezvous and Docking (RVD) missions. The proposed strategy allows safe and propellant efficient trajectories for space servicing missions including tasks such as approaching, inspecting and capturing. This work provides the validation test results of the G&C laws using a Hardware-In-the-Loop (HIL) setup with two robotic mockups representing the chaser and the target spacecraft. Through this paper, the challenges of the relative motion control in space are first summarized, and in particular, the constraints imposed by the mission, spacecraft and, onboard processing capabilities. Second, the proposed algorithm is introduced by presenting the formulation of constrained Model Predictive Control (MPC) to optimize the fuel consumption and explicitly handle the physical and geometric constraints in the system, e.g. thruster or Line-Of-Sight (LOS) constraints. Additionally, the coupling between translational motion and rotational motion is addressed via dual quaternion based kinematic description and accordingly explained. The resulting convex optimization problem allows real-time implementation capability based on a detailed discussion on the computational time requirements and the obtained results with respect to the onboard computer and future trends of space processors capabilities. Finally, the performance of the algorithm is presented in the scope of a potential future mission and of the available equipment. The results also cover a comparison between the proposed algorithms with Linear–quadratic regulator (LQR) based control law to highlight the clear advantages of the MPC formulation.

Keywords: autonomous vehicles, embedded optimization, real-time experiment, rendezvous and docking, space robotics

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Authors: Houda Zouar, Hanane Sarnou

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In the 21st, century the concept of learners' autonomy is crucial. The concept of self-regulated learning has come forward as a result of enabling learners to direct their learning with autonomy towards academic goals achievement. Academic self-regulation is defined as the process by which learners systematically plan, monitor and asses their learning to achieve their academic established goals. In the field of English as a foreign language, teachers emphasise the role of learners’ autonomy to foster the process of English language learning. Consequently, academic self-regulation is considered as a vehicle to enhance autonomy among English language learners. However, not all learners can be equally self-regulators if not well assisted, mainly those novice pupils of basic education. For this matter, understanding the role of teachers in fostering academic self- regulation must be among the preliminary objectives in searching and developing this area. The present research work targets the role of the Algerian middle school teachers in enhancing academic self-regulation and teaching pupils how to learn, besides their role as models in the trajectory of teaching their pupils to become self-regulators. Despite the considerable endeavours in the field of educational setting on Self-Regulated Learning, the literature of the Algerian context indicates confined endeavours to undertake and divulge this notion. To go deeper into this study, a mixed method approach was employed to confirm our hypothesis. For data collection, teachers were observed and addressed by a questionnaire on their role in enhancing academic self- regulation among their pupils. The result of the research indicates that the attempts of middle school Algerian teachers are implicit and limited. This study emphasises the need to prepare English language teachers with the necessary skills to promote autonomous and self-regulator English learners.

Keywords: Algeria, English as a foreign language, middle school, self-regulation, Teachers' role

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