Search results for: betel leaves extracts
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1659

Search results for: betel leaves extracts

9 The Future of Adventure Tourism in a Warmer World: An Exploratory Study of Mountain Guides’ Perception of Environmental Change in Canada

Authors: Brooklyn Rushton, Michelle Rutty, Natalie Knowles, Daniel Scott

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As people are increasingly on the search for extraordinary experiences and connections with nature, adventure tourism is experiencing significant growth and providing tourists with life-changing experiences. Unlike built attraction-based tourism, adventure tourism relies entirely on natural heritage, which leaves communities dependent on adventure tourism extremely vulnerable to environmental and climatic changes. A growing body of evidence suggests that global climate change will influence the future of adventure tourism and mountain outdoor recreation opportunities on a global scale. Across Canada, more specifically, climate change is broadly anticipated to present risks for winter-snow sports, while opportunities are anticipated to arise for green season activities. These broad seasonal shifts do not account for the indirect impacts of climate change on adventure tourism, such as the cost of adaptation or the increase of natural hazards and the associated likelihood of accidents. While some research has examined the impact of climate change on natural environments that adventure tourism relies on, a very small body of research has specifically focused on guides’ perspectives or included hard adventure tourism activities. The guiding industry is unique, as guides are trained through an elegant blend of art and science to make decisions based on experience, observation, and intuition. While quantitative research can monitor change in natural environments, guides local knowledge can provide eye-witness accounts and outline what environmental changes mean for the future sustainability of adventure tourism. This research will capture the extensive knowledge of mountain guides to better understand the implications of climate change for mountain adventure and potential adaptive responses for the adventure tourism industry. This study uses a structured online survey with open and close-ended questions that will be administered using Qualtrics (an online survey platform). This survey is disseminated to current members of the Association of Canadian Mountain Guides (ACMG). Participation in this study will be exclusive to members of the ACMG operating in the outdoor guiding streams. The 25 survey questions are organized into four sections: demographic and professional operation (9 questions), physical change (4 questions), climate change perception (6 questions), and climate change adaptation (6 questions). How mountain guides perceive and respond to climate change is important knowledge for the future of the expanding adventure tourism industry. Results from this study are expected to provide important information to mountain destinations on climate change vulnerability and adaptive capacity. Expected results of this study include guides insight into: (1) experience-safety relevant observed physical changes in guided regions (i.e. glacial coverage, permafrost coverage, precipitation, temperature, and slope instability) (2) changes in hazards within the guiding environment (i.e. avalanches, rockfall, icefall, forest fires, flooding, and extreme weather events), (3) existing and potential adaptation strategies, and (4) key information and other barriers for adaptation. By gaining insight from the knowledge of mountain guides, this research can help the tourism industry at large understand climate risk and create adaptation strategies to ensure the resiliency of the adventure tourism industry.

Keywords: adventure tourism, climate change, environmental change, mountain hazards

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8 Cluster Randomized Trial of 'Ready to Learn': An After-School Literacy Program for Children Starting School

Authors: Geraldine Macdonald, Oliver Perra, Nina O’Neill, Laura Neeson, Kathryn Higgins

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Background: Despite improvements in recent years, almost one in six children in Northern Ireland (NI) leaves primary school without achieving the expected level in English and Maths. By early adolescence, this ratio is one in five. In 2010-11, around 9000 pupils in NI had failed to achieve the required standard in literacy and numeracy by the time they left full-time education. This paper reports the findings of an experimental evaluation of a programmed designed to improve educational outcomes of a cohort of children starting primary school in areas of high social disadvantage in Northern Ireland. The intervention: ‘Ready to Learn’ comprised two key components: a literacy-rich After School programme (one hour after school, three days per week), and a range of activities and support to promote the engagement of parents with their children’s learning, in school and at home. The intervention was delivered between September 2010 and August 2013. Study aims and objectives: The primary aim was to assess whether, and to what extent, ‘Ready to Learn’ improved the literacy of socially disadvantaged children entering primary schools compared with children in schools without access to the programme. Secondary aims included assessing the programme’s impact on children’s social, emotional and behavioural regulation, and parents’ engagement with their children’s learning. In total, 505 children (almost all) participated in the baseline assessment for the study, with good retention over seven sweeps of data collection. Study design: The intervention was evaluated by means of a cluster randomized trial, with schools as the unit of randomization and analysis. It included a qualitative component designed to examine process and implementation, and to explore the concept of parental engagement. Sixteen schools participated, with nine randomized to the experimental group. As well as outcome data relating to children, 134 semi-structured interviews were conducted with parents over the three years of the study, together with 88 interviews with school staff. Results: Given the children’s ages, not all measures used were direct measures of reading. Findings point to a positive impact of “Ready to Learn” on children’s reading achievement (comprehension and fluency), as assessed by the York Assessment of Reading Comprehension (YARC) and decoding, assessed using the Word Recognition and Phonic Skills (WRaPS3). Effects were not large, but evidence suggests that it is unusual for an after school programme to clearly to demonstrate effects on reading skills. No differences were found on three other measures of literacy-related skills: British Picture Vocabulary Scale (BPVS-II), Naming Speed and Non-word Reading Tests from the Phonological Assessment Battery (PhAB) or Concepts about Print (CAP) – the last due to an age-related ceiling effect). No differences were found between the two groups on measures of social, emotional and behavioural regulation, and due to low levels of participation, it was not possible directly to assess the contribution of the parent component to children’s outcomes. The qualitative data highlighted conflicting concepts of engagement between parents and school staff. Ready to Learn is a promising intervention that merits further support and evaluation.

Keywords: after-school, education, literacy, parental engagement

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7 Deciphering Information Quality: Unraveling the Impact of Information Distortion in the UK Aerospace Supply Chains

Authors: Jing Jin

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The incorporation of artificial intelligence (AI) and machine learning (ML) in aircraft manufacturing and aerospace supply chains leads to the generation of a substantial amount of data among various tiers of suppliers and OEMs. Identifying the high-quality information challenges decision-makers. The application of AI/ML models necessitates access to 'high-quality' information to yield desired outputs. However, the process of information sharing introduces complexities, including distortion through various communication channels and biases introduced by both human and AI entities. This phenomenon significantly influences the quality of information, impacting decision-makers engaged in configuring supply chain systems. Traditionally, distorted information is categorized as 'low-quality'; however, this study challenges this perception, positing that distorted information, contributing to stakeholder goals, can be deemed high-quality within supply chains. The main aim of this study is to identify and evaluate the dimensions of information quality crucial to the UK aerospace supply chain. Guided by a central research question, "What information quality dimensions are considered when defining information quality in the UK aerospace supply chain?" the study delves into the intricate dynamics of information quality in the aerospace industry. Additionally, the research explores the nuanced impact of information distortion on stakeholders' decision-making processes, addressing the question, "How does the information distortion phenomenon influence stakeholders’ decisions regarding information quality in the UK aerospace supply chain system?" This study employs deductive methodologies rooted in positivism, utilizing a cross-sectional approach and a mono-quantitative method -a questionnaire survey. Data is systematically collected from diverse tiers of supply chain stakeholders, encompassing end-customers, OEMs, Tier 0.5, Tier 1, and Tier 2 suppliers. Employing robust statistical data analysis methods, including mean values, mode values, standard deviation, one-way analysis of variance (ANOVA), and Pearson’s correlation analysis, the study interprets and extracts meaningful insights from the gathered data. Initial analyses challenge conventional notions, revealing that information distortion positively influences the definition of information quality, disrupting the established perception of distorted information as inherently low-quality. Further exploration through correlation analysis unveils the varied perspectives of different stakeholder tiers on the impact of information distortion on specific information quality dimensions. For instance, Tier 2 suppliers demonstrate strong positive correlations between information distortion and dimensions like access security, accuracy, interpretability, and timeliness. Conversely, Tier 1 suppliers emphasise strong negative influences on the security of accessing information and negligible impact on information timeliness. Tier 0.5 suppliers showcase very strong positive correlations with dimensions like conciseness and completeness, while OEMs exhibit limited interest in considering information distortion within the supply chain. Introducing social network analysis (SNA) provides a structural understanding of the relationships between information distortion and quality dimensions. The moderately high density of ‘information distortion-by-information quality’ underscores the interconnected nature of these factors. In conclusion, this study offers a nuanced exploration of information quality dimensions in the UK aerospace supply chain, highlighting the significance of individual perspectives across different tiers. The positive influence of information distortion challenges prevailing assumptions, fostering a more nuanced understanding of information's role in the Industry 4.0 landscape.

Keywords: information distortion, information quality, supply chain configuration, UK aerospace industry

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6 Photosynthesis Metabolism Affects Yield Potentials in Jatropha curcas L.: A Transcriptomic and Physiological Data Analysis

Authors: Nisha Govender, Siju Senan, Zeti-Azura Hussein, Wickneswari Ratnam

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Jatropha curcas, a well-described bioenergy crop has been extensively accepted as future fuel need especially in tropical regions. Ideal planting material required for large-scale plantation is still lacking. Breeding programmes for improved J. curcas varieties are rendered difficult due to limitations in genetic diversity. Using a combined transcriptome and physiological data, we investigated the molecular and physiological differences in high and low yielding Jatropha curcas to address plausible heritable variations underpinning these differences, in regard to photosynthesis, a key metabolism affecting yield potentials. A total of 6 individual Jatropha plant from 4 accessions described as high and low yielding planting materials were selected from the Experimental Plot A, Universiti Kebangsaan Malaysia (UKM), Bangi. The inflorescence and shoots were collected for transcriptome study. For the physiological study, each individual plant (n=10) from the high and low yielding populations were screened for agronomic traits, chlorophyll content and stomatal patterning. The J. curcas transcriptomes are available under BioProject PRJNA338924 and BioSample SAMN05827448-65, respectively Each transcriptome was subjected to functional annotation analysis of sequence datasets using the BLAST2Go suite; BLASTing, mapping, annotation, statistical analysis and visualization Large-scale phenotyping of the number of fruits per plant (NFPP) and fruits per inflorescence (FPI) classified the high yielding Jatropha accessions with average NFPP =60 and FPI > 10, whereas the low yielding accessions yielded an average NFPP=10 and FPI < 5. Next generation sequencing revealed genes with differential expressions in the high yielding Jatropha relative to the low yielding plants. Distinct differences were observed in transcript level associated to photosynthesis metabolism. DEGs collection in the low yielding population showed comparable CAM photosynthetic metabolism and photorespiration, evident as followings: phosphoenolpyruvate phosphate translocator chloroplastic like isoform with 2.5 fold change (FC) and malate dehydrogenase (2.03 FC). Green leaves have the most pronounced photosynthetic activity in a plant body due to significant accumulation of chloroplast. In most plants, the leaf is always the dominant photosynthesizing heart of the plant body. Large number of the DEGS in the high-yielding population were found attributable to chloroplast and chloroplast associated events; STAY-GREEN chloroplastic, Chlorophyllase-1-like (5.08 FC), beta-amylase (3.66 FC), chlorophyllase-chloroplastic-like (3.1 FC), thiamine thiazole chloroplastic like (2.8 FC), 1-4, alpha glucan branching enzyme chloroplastic amyliplastic (2.6FC), photosynthetic NDH subunit (2.1 FC) and protochlorophyllide chloroplastic (2 FC). The results were parallel to a significant increase in chlorophyll a content in the high yielding population. In addition to the chloroplast associated transcript abundance, the TOO MANY MOUTHS (TMM) at 2.9 FC, which code for distant stomatal distribution and patterning in the high-yielding population may explain high concentration of CO2. The results were in agreement with the role of TMM. Clustered stomata causes back diffusion in the presence of gaps localized closely to one another. We conclude that high yielding Jatropha population corresponds to a collective function of C3 metabolism with a low degree of CAM photosynthetic fixation. From the physiological descriptions, high chlorophyll a content and even distribution of stomata in the leaf contribute to better photosynthetic efficiency in the high yielding Jatropha compared to the low yielding population.

Keywords: chlorophyll, gene expression, genetic variation, stomata

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5 Shakespeare's Hamlet in Ballet: Transformation of an Archival Recording of a Neoclassical Ballet Performance into a Contemporary Transmodern Dance Video Applying Postmodern Concepts and Techniques

Authors: Svebor Secak

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This four-year artistic research project hosted by the University of New England, Australia has set the goal to experiment with non-conventional ways of presenting a language-based narrative in dance using insights of recent theoretical writing on performance, addressing the research question: How to transform an archival recording of a neoclassical ballet performance into a new artistic dance video by implementing postmodern philosophical concepts? The Creative Practice component takes the form of a dance video Hamlet Revisited which is a reworking of the archival recording of the neoclassical ballet Hamlet, augmented by new material, produced using resources, technicians and dancers of the Croatian National Theatre in Zagreb. The methodology for the creation of Hamlet Revisited consisted of extensive field and desk research after which three dancers were shown the recording of original Hamlet and then created their artistic response to it based on their reception and appreciation of it. The dancers responded differently, based upon their diverse dancing backgrounds and life experiences. They began in the role of the audience observing video of the original ballet and transformed into the role of the choreographer-performer. Their newly recorded material was edited and juxtaposed with the archival recording of Hamlet and other relevant footage, allowing for postmodern features such as aleatoric content, synchronicity, eclecticism and serendipity, that way establishing communication on a receptive reader-response basis, thus blending the roles of the choreographer, performer and spectator, creating an original work of art whose significance lies in the relationship and communication between styles, old and new choreographic approaches, artists and audiences and the transformation of their traditional roles and relationships. In editing and collating, the following techniques were used with the intention to avoid the singular narrative: fragmentation, repetition, reverse-motion, multiplication of images, split screen, overlaying X-rays, image scratching, slow-motion, freeze-frame and simultaneity. Key postmodern concepts considered were: deconstruction, diffuse authorship, supplementation, simulacrum, self-reflexivity, questioning the role of the author, intertextuality and incredulity toward grand narratives - departing from the original story, thus personalising its ontological themes. From a broad brush of diverse concepts and techniques applied in an almost prescriptive manner, the project focuses on intertextuality that proves to be valid on at least two levels. The first is the possibility of a more objective analysis in combination with a semiotic structuralist approach moving from strict relationships between signs to a multiplication of signifiers, considering the dance text as an open construction, containing the elusive and enigmatic quality of art that leaves the interpretive position open. The second one is the creation of the new work where the author functions as the editor, aware and conscious of the interplay of disparate texts and their sources which co-act in the mind during the creative process. It is argued here that the eclectic combination of the old and new material through constant oscillations of different discourses upon the same topic resulted in a transmodern integrationist recent work of art that might be applied as a model for reconsidering existing choreographic creations.

Keywords: Ballet Hamlet, intertextuality, transformation, transmodern dance video

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4 Phytochemicals and Photosynthesis of Grape Berry Exocarp and Seed (Vitis vinifera, cv. Alvarinho): Effects of Foliar Kaolin and Irrigation

Authors: Andreia Garrido, Artur Conde, Ana Cunha, Ric De Vos

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Climate changes predictions point to increases in abiotic stress for crop plants in Portugal, like pronounced temperature variation and decreased precipitation, which will have negative impact on grapevine physiology and consequently, on grape berry and wine quality. Short-term mitigation strategies have, therefore, been implemented to alleviate the impacts caused by adverse climatic periods. These strategies include foliar application of kaolin, an inert mineral, which has radiation reflection proprieties that decreases stress from excessive heat/radiation absorbed by its leaves, as well as smart irrigation strategies to avoid water stress. However, little is known about the influence of these mitigation measures on grape berries, neither on the photosynthetic activity nor on the photosynthesis-related metabolic profiles of its various tissues. Moreover, the role of fruit photosynthesis on berry quality is poorly understood. The main objective of our work was to assess the effects of kaolin and irrigation treatments on the photosynthetic activity of grape berry tissues (exocarp and seeds) and on their global metabolic profile, also investigating their possible relationship. We therefore collected berries of field-grown plants of the white grape variety Alvarinho from two distinct microclimates, i.e. from clusters exposed to high light (HL, 150 µmol photons m⁻² s⁻¹) and low light (LL, 50 µmol photons m⁻² s⁻¹), from both kaolin and non-kaolin (control) treated plants at three fruit developmental stages (green, véraison and mature). Plant irrigation was applied after harvesting the green berries, which also enabled comparison of véraison and mature berries from irrigated and non-irrigated growth conditions. Photosynthesis was assessed by pulse amplitude modulated chlorophyll fluorescence imaging analysis, and the metabolite profile of both tissues was assessed by complementary metabolomics approaches. Foliar kaolin application resulted in, for instance, an increased photosynthetic activity of the exocarp of LL-grown berries at green developmental stage, as compared to the control non-kaolin treatment, with a concomitant increase in the levels of several lipid-soluble isoprenoids (chlorophylls, carotenoids, and tocopherols). The exocarp of mature berries grown at HL microclimate on kaolin-sprayed non-irrigated plants had higher total sugar levels content than all other treatments, suggesting that foliar application of this mineral results in an increased accumulation of photoassimilates in mature berries. Unbiased liquid chromatography-mass spectrometry-based profiling of semi-polar compounds followed by ASCA (ANOVA simultaneous component analysis) and ANOVA statistical analysis indicated that kaolin had no or inconsistent effect on the flavonoid and phenylpropanoid composition in both seed and exocarp at any developmental stage; in contrast, both microclimate and irrigation influenced the level of several of these compounds depending on berry ripening stage. Overall, our study provides more insight into the effects of mitigation strategies on berry tissue photosynthesis and phytochemistry, under contrasting conditions of cluster light microclimate. We hope that this may contribute to develop sustainable management in vineyards and to maintain grape berries and wines with high quality even at increasing abiotic stress challenges.

Keywords: climate change, grape berry tissues, metabolomics, mitigation strategies

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3 Cultivation of Halophytes: Effect of Salinity on Nutritional and Functional Properties

Authors: Luisa Barreira, Viana Castaneda, Maria J. Rodrigues, Florinda Gama, Tamara Santos, Marta Oliveira, Catarina Pereira, Maribela Pestana, Pedro Correia, Miguel Salazar, Carla Nunes, Luisa Custodio, Joao Varela

Abstract:

In the last century, the world witnessed an exponential demographic increase that has put an enormous pressure on agriculture and food production. Associated also with climate changes, there has been a decrease in the amount of available freshwater and an increased salinization of soils which can affect the production of most food crops. Halophytes, however, are plants able to withstand high salinities while maintaining a good growth productivity. To cope with the excess salt, they produce secondary metabolites (e.g. vitamins and phenolic compounds) which, along with the natural presence of some minerals, makes them not only nutritionally rich but also functional foods. Some halophytes, as quinoa or salicornia, are already used in some countries, mostly as gourmet food. Hydroponic cultivation of halophytes using seawater or diluted seawater for watering can decrease the pressure on freshwater resources while producing a nutritional and functional food. The XtremeGourmet project funded by the EU aims to develop and optimize the production of different halophytes by hydroponics. One of the more specific objectives of this project is the study of halophytes’ productivity and chemical composition under different abiotic conditions, e.g. salt and nutrient concentration and light intensity. Three species of halophytes commonly occurring in saltmarshes of the South of Portugal (Inula chrithmoides, Salicornia ramosissima and Mesembryanthemum nodiflorum) were cultivated using hydroponics under different salinities, ranging from 5 to 45 dS/m. For each condition, several parameters were assessed namely: total and commercial productivity, electrical conductivity, total soluble solids, proximal composition, mineral profile, total phenolics, flavonoids and condensed tannins content and antioxidant activity. Results show that productivity was significantly reduced for all plants with increasing salinity up to salinity 29 dS/m and remained low onwards. Oppositely, the electrical conductivity and the total soluble solids content of the produced plants increased with salinity, reaching a plateau at 29 dS/m. It seems that plants reflect the salt concentration of the water up to some point, being able to regulate their salt content for higher salinities. The same tendency was observed for the ash content of these plants, which is related to the mineral uptake from the cultivating media and the plants’ capacity to both accumulate and regulate ions’ concentration in their tissues. Nonetheless, this comes with a metabolic cost which is observed by a decrease in productivity. The mineral profile of these plants shows high concentrations of sodium but also high amounts of potassium. In what concerns the microelements, these plants appear to be a good source of manganese and iron and the low amounts of toxic metals account for their safe consumption in moderate amounts. Concerning the phenolics composition, plants presented moderate concentrations of phenolics but high amounts of condensed tannins, particularly I. crithmoides which accounts for its characteristic sour and spicy taste. Contrary to some studies in which higher amounts of phenolics were found in plants cultivated under higher salinities, in this study, the highest amount of phenolic compounds were found in plants grown at the lowest or intermediate salinities. Nonetheless, there was a positive correlation between the concentration of these compounds and the antioxidant capacity of the plants’ extracts.

Keywords: functional properties, halophytes, hydroponics, nutritional composition, salinity effect

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2 Impact of Elevated Temperature on Spot Blotch Development in Wheat and Induction of Resistance by Plant Growth Promoting Rhizobacteria

Authors: Jayanwita Sarkar, Usha Chakraborty, Bishwanath Chakraborty

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Plants are constantly interacting with various abiotic and biotic stresses. In changing climate scenario plants are continuously modifying physiological processes to adapt to changing environmental conditions which profoundly affect plant-pathogen interactions. Spot blotch in wheat is a fast-rising disease in the warmer plains of South Asia where the rise in minimum average temperature over most of the year already affecting wheat production. Hence, the study was undertaken to explore the role of elevated temperature in spot blotch disease development and modulation of antioxidative responses by plant growth promoting rhizobacteria (PGPR) for biocontrol of spot blotch at high temperature. Elevated temperature significantly increases the susceptibility of wheat plants to spot blotch causing pathogen Bipolaris sorokiniana. Two PGPR Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) isolated from wheat (Triticum aestivum L.) and blady grass (Imperata cylindrical L.) rhizophere respectively, showing in vitro antagonistic activity against Bipolaris sorokiniana were tested for growth promotion and induction of resistance against spot blotch in wheat. GC-MS analysis showed that Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) produced antifungal and antimicrobial compounds in culture. Seed priming with these two bacteria significantly increase growth, modulate antioxidative signaling and induce resistance and eventually reduce disease incidence in wheat plants at optimum as well as elevated temperature which was further confirmed by indirect immunofluorescence assay using polyclonal antibody raised against Bipolaris sorokiniana. Application of the PGPR led to enhancement in activities of plant defense enzymes- phenylalanine ammonia lyase, peroxidase, chitinase and β-1,3 glucanase in infected leaves. Immunolocalization of chitinase and β-1,3 glucanase in PGPR primed and pathogen inoculated leaf tissue was further confirmed by transmission electron microscopy using PAb of chitinase, β-1,3 glucanase and gold labelled conjugates. Activity of ascorbate-glutathione redox cycle related enzymes such as ascorbate peroxidase, superoxide dismutase and glutathione reductase along with antioxidants such as carotenoids, glutathione and ascorbate and osmolytes like proline and glycine betain accumulation were also increased during disease development in PGPR primed plant in comparison to unprimed plants at high temperature. Real-time PCR analysis revealed enhanced expression of defense genes- chalcone synthase and phenyl alanineammonia lyase. Over expression of heat shock proteins like HSP 70, small HSP 26.3 and heat shock factor HsfA3 in PGPR primed plants effectively protect plants against spot blotch infection at elevated temperature as compared with control plants. Our results revealed dynamic biochemical cross talk between elevated temperature and spot blotch disease development and furthermore highlight PGPR mediated array of antioxidative and molecular alterations responsible for induction of resistance against spot blotch disease at elevated temperature which seems to be associated with up-regulation of defense genes, heat shock proteins and heat shock factors, less ROS production, membrane damage, increased expression of redox enzymes and accumulation of osmolytes and antioxidants.

Keywords: antioxidative enzymes, defense enzymes, elevated temperature, heat shock proteins, PGPR, Real-Time PCR, spot blotch, wheat

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1 Magnetic Single-Walled Carbon Nanotubes (SWCNTs) as Novel Theranostic Nanocarriers: Enhanced Targeting and Noninvasive MRI Tracking

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

Abstract:

Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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