Search results for: regulatory genes
404 The Women Entrepreneur Support Fund in Bangladesh: Challenges and Prospects
Authors: Chowdhury Dilruba Shoma
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Gender is about equal rights that both males and females having access to responsibilities and opportunities in decision making is a fundamental human right. It is also a precondition for, and a mark of, sustainable people-oriented development. In Bangladesh, women have fewer opportunities than men do to access credit from banks and financial institutions. Entrenched patriarchal attitudes, unequal inheritance rights, and male-dominated hierarchies in the financial system, plus high interest rates and a lack of security/collateral, make it harder for women to obtain bank loans. Limited access to institutional credit is a serious restraint on the productivity and income of women entrepreneurs, (and the wider economy). These gender-biased and structural barriers inhibit women’s access to fundamental economic rights. Using a liberal feminist theoretical lens, this study provides some useful insights into the relationship between gender inequality and entrepreneurship, leading to a better understanding of women’s entrepreneurship development in Bangladesh. Recently, the Bangladesh Government, the United Nations Capital Development Fund, and Bangladesh Bank opened up the Women Entrepreneur Support Fund (WESF) ‒ Credit Guarantee Scheme (CGS) pilot project to cover collateral shortfalls for women entrepreneurs in the small and medium enterprise sector. The aim is to improve gender equality and advance women’s rights in relation to receiving credit. This article examines the challenges and prospects of the WESF-CGS, and suggests that implementation of measures in WESF-CGS policymaking, coupled with a combination of legislatory and regulatory reforms that implement the fundamental tenets of liberal feminism, can lead to a comprehensive and effective credit policy to boost women’s agency and economic empowerment. This may ultimately lead to more sustainable development in Bangladesh.Keywords: Bangladesh, credit guarantee scheme, liberal feminist theory, women entrepreneur support fund
Procedia PDF Downloads 142403 Diversity and Distribution of Cytochrome P450 2C9 Genes Related with Medical Cannabis in Thai Patients
Authors: Tanakrit Doltanakarn
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Introduction: These days, cannabis is being accepted in many countries due to the fact that cannabis could be use in medical. The medical cannabis is used to treat and reduce the pain many diseases. For example, neuropathic pain, Parkinson, autism disorders, cancer pain reduce the adverse effect of chemotherapy, diabetes, and migraine. Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. However, there is an adverse effect of cannabis, cardiovascular effects, psychosis, schizophrenia, mood disorder, and cognitive alternation. These effects are from the THC and CBD ingredients in the cannabis. The metabolize processes of delta-9 THC to 11-OH-delta 9 -THC (inactive form), THC were cause of adverse effects. Interestingly, the distributions of CYP2C9 gene (CYP2C9*2 and CYP2C9*3, poor metabolizer) that might affect incidences of adverse effects in patients who treated with medical cannabis. Objective: The aim of this study we want to investigate the association between genetic polymorphism of CYP2C9 frequency and Thai patients who treated with medical cannabis. Materials and Methods:We recruited sixty-five unrelated Thai patients from the College of Pharmacy, Rangsit University. DNA were extracted using Genomic DNA Mini Kit. Genotyping of CYP2C9*2 (430C>T, rs1799853) and CYP2C9*3 (1075A>C, rs1057910) were genotyped by the TaqMan Real-time PCR assay. Results: Among these 31 medicals cannabis-induced ADRs patients, they were diagnosed with 22 (33.85%) tachycardia and 3 (4.62%) arrhythmia. There were 34 (52.31%) medical cannabis-tolerant controls who were included in this study.40 (61.53%) Thai patients were female, and 25 (38.46%) were male, with median age of 57 (range 27 – 87) years. In this study, we found none of the medical cannabis-induced ADRs carried CYP2C9*2 variant along with medical cannabis-tolerant control group. CYP2C9*3 variant (intermediate metabolizer, IM) was found just only one of thirty-one (3.23%) in the medical cannabis-induced ADRs and two of thirty-fourth (5.88%) in the tolerant controls. Conclusions: Thus, the distribution of CYP2C9 alleles offer a comprehensive view of pharmacogenomics marker in Thai population that could be used as a reference for worldwide to investigate the pharmacogenomics application.Keywords: medical cannabis, adverse effect, CYP2C9, thai patients
Procedia PDF Downloads 101402 Expression of ULK-1 mRNA in Human Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease
Authors: Ali Bayram, Remzi Yiğiter
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Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR
Procedia PDF Downloads 398401 Chemotrophic Signal Exchange between the Host Plant Helianthemum sessiliflorum and Terfezia boudieri
Authors: S. Ben-Shabat, T. Turgeman, O. Leubinski, N. Roth-Bejerano, V. Kagan-Zur, Y. Sitrit
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The ectomycorrhizal (ECM) desert truffle Terfezia boudieri produces edible fruit bodies and forms symbiosis with its host plant Helianthemum sessiliflorum (Cistaceae) in the Negev desert of Israel. The symbiosis is vital for both partners' survival under desert conditions. Under desert habitat conditions, ECMs must form symbiosis before entering the dry season. To secure a successful encounter, in the course of evolution, both partners have responded by evolving special signals exchange that facilitates recognition. Members of the Cistaceae family serve as host plants for many important truffles. Conceivably, during evolution a common molecule present in Cistaceae plants was recruited to facilitate successful encounter with ectomycorrhizas. Arbuscular vesicular fungi (AM) are promiscuous in host preferences, in contrast, ECM fungi show specificity to host plants. Accordingly, we hypothesize that H. sessiliflorum secretes a chemotrophic-signaling, which is common to plants hosting ECM fungi belonging to the Pezizales. However, thus far no signaling molecules have been identified in ECM fungi. We developed a bioassay for chemotrophic activity. Fractionation of root exudates revealed a substance with chemotrophic activity and molecular mass of 534. Following the above concept, screening the transcriptome of Terfezia, grown under chemoattraction, discovered genes showing high homology to G proteins-coupled receptors of plant pathogens involved in positive chemotaxis and chemotaxis suppression. This study aimed to identify the active molecule using analytical methods (LC-MS, NMR etc.). This should contribute to our understanding of how ECM fungi communicate with their hosts in the rhizosphere. In line with the ability of Terfezia to form also endomycorrhizal symbiosis like AM fungi, analysis of the mechanisms may likewise be applicable to AM fungi. Developing methods to manipulate fungal growth by the chemoattractant can open new ways to improve inoculation of plants.Keywords: chemotrophic signal, Helianthemum sessiliflorum, Terfezia boudieri, ECM
Procedia PDF Downloads 409400 Organic Agriculture in Pakistan: Opportunities, Challenges, and Future Directions
Authors: Sher Ali
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Organic agriculture has gained significant momentum globally as a sustainable and environmentally friendly farming practice. In Pakistan, amidst growing concerns about food security, environmental degradation, and health issues related to conventional farming methods, the adoption of organic agriculture presents a promising pathway for agricultural development. This abstract aims to provide an overview of the status, opportunities, challenges, and future directions of organic agriculture in Pakistan. It delves into the current state of organic farming practices, including the extent of adoption, key crops cultivated, and the regulatory framework governing organic certification. Furthermore, the abstract discusses the unique opportunities that Pakistan offers for organic agriculture, such as its diverse agro-climatic zones, rich biodiversity, and traditional farming knowledge. It highlights successful initiatives and case studies that showcase the potential of organic farming to improve rural livelihoods, enhance food security, and promote sustainable agricultural practices. However, the abstract also addresses the challenges hindering the widespread adoption of organic agriculture in Pakistan, ranging from limited awareness and technical know-how among farmers to inadequate infrastructure and market linkages. It emphasizes the need for supportive policies, capacity-building programs, and investment in research and extension services to overcome these challenges and promote the growth of the organic agriculture sector. Lastly, the abstract outlines future directions and recommendations for advancing organic agriculture in Pakistan, including strategies for scaling up production, strengthening certification mechanisms, and fostering collaboration among stakeholders. By shedding light on the opportunities, challenges, and potential of organic agriculture in Pakistan, this abstract aims to contribute to the discourse on sustainable farming practices at the upcoming Agro Conference in the USA. It invites participants to engage in dialogue, share experiences, and explore avenues for collaboration toward promoting organic agriculture for a healthier, more resilient food system.Keywords: agriculture, challenges, organic, Pakistan
Procedia PDF Downloads 52399 Smart Transportation: Bringing Back Sunshine City Harare
Authors: R. Shayamapiki
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This study explores the applicability of applying new urbanism principles in cities of developing countries as a panacea towards building sustainable cities through implementing smart transportation. Smart transportation approach to planning has been growing remarkably around the globe in the past decade. In conquest to curb traffic congestion and reducing automobile dependency in the inner-city Harare, Smart Transportation has been a strong drive towards building sustainable cities. Conceptually, Smart Transportation constitutes of principles which include walking, cycling and mass transit. The Smart Transportation approach has been a success story in the cities of developing world but its application in the cities of developing countries has been doubtful. Cities of developing countries being multifaceted with several urban sustainability challenges, the study consolidates that there are no robust policy, legislative and institutional frameworks to govern the application of Smart Transportation in urban planning hence no clear roadway towards its success story. Questions regarding this investigation proliferate to; how capable are cities of developing countries to transform Smart Transportation principles to a success story? What victory can Smart Transportation bring to sustainable urban development? What are constraints of embracing the principles and how can they be manipulated? Methodologically the case study of urban syntax in Harare Central Business District and arterial roads of the city, legislation and institutional settings underpins various research outcomes. The study finds out the hindrances of policy, legislative and institutional incapacities cooked with economic constraints, lack of political will and technically inflexible zoning regulations. The study also elucidates that there is need to adopt a localized approach to Smart Transportation. The paper then calls for strengthening of institutional and legal reform in conquest to embrace the concept, policy and legislative support, feasible financial mechanism, coordination of responsible stakeholders, planning standards and regulatory frameworks reform to celebrate the success story of Smart Transportation in the developing world.Keywords: inner-city Harare, new urbanism, smart transportation, sustainable cities
Procedia PDF Downloads 469398 T Cell Immunity Profile in Pediatric Obesity and Asthma
Authors: Mustafa M. Donma, Erkut Karasu, Burcu Ozdilek, Burhan Turgut, Birol Topcu, Burcin Nalbantoglu, Orkide Donma
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The mechanisms underlying the association between obesity and asthma may be related to a decreased immunological tolerance induced by a defective function of regulatory T cells (Tregs). The aim of this study is to establish the potential link between these diseases and CD4+, CD25+ FoxP3+ Tregs as well as T helper cells (Ths) in children. This is a prospective case control study. Obese (n:40), asthmatic (n:40), asthmatic obese (n:40), and healthy children (n:40), who don't have any acute or chronic diseases, were included in this study. Obese children were evaluated according to WHO criteria. Asthmatic patients were chosen based on GINA criteria. Parents were asked to fill up the questionnaire. Informed consent forms were taken. Blood samples were marked with CD4+, CD25+ and FoxP3+ in order to determine Tregs and Ths by flow cytometric method. Statistical analyses were performed. p≤0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0,16%; p≤0,001), asthmatic (0,25%; p≤0,01) and asthmatic obese (0,29%; p≤0,05) groups than the control group (0,38%). Ths were counted higher in asthma group than the control (p≤0,01) and obese (p≤0,001)) groups. T cell immunity plays important roles in obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic and asthmatic obese children may help to elucidate some questions in pathophysiology of these diseases. For HOMA-IR levels, any significant difference was not noted between control and obese groups, but statistically higher values were found for obese asthmatics. The values obtained in all groups were found to be below the critical cut off points. This finding has made the statistically significant difference observed between Tregs of obese, asthmatic, obese asthmatic, and control groups much more valuable. These findings will be useful in diagnosis and treatment of these disorders and future studies are needed. The production and propagation of Tregs may be promising in alternative asthma and obesity treatments.Keywords: asthma, flow cytometry, pediatric obesity, T cells
Procedia PDF Downloads 346397 Metagenomic Identification of Cave Microorganisms in Lascaux and Other Périgord Caves
Authors: Lise Alonso, Audrey Dubost, Patricia Luis, Thomas Pommier, Yvan Moënne-Loccoz
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The Lascaux Cave in South-Est France is an archeological landmark renowned for its Paleolithic paintings dating back c.18.000 years. Extensive touristic frequenting and repeated chemical treatments have resulted in the development of microbial stains on cave walls, which is a major issue in terms of art conservation. Therefore, it is of prime importance to better understand the microbiology specific to the Lascaux Cave, in comparison to regional situations. To this end, we compared the microbial community (i.e. both prokaryotic and eukaryotic microbial populations) of Lascaux Cave with three other anthropized Périgord caves as well as three pristine caves from the same area. We used state-of-the-art metagenomic analyses of cave wall samples to obtain a global view of the composition of the microbial community colonizing cave walls. We measured the relative abundance and diversity of four DNA markers targeting different fractions of the ribosomal genes of bacteria (i.e. eubacteria), archaea (i.e. archeobacteria), fungi and other micro-eukaryotes. All groups were highly abundant and diverse in all Périgord caves, as several hundred genera of microorganisms were identified in each. However, Lascaux Cave displayed a specify microbial community, which differed from those of both pristine and anthropized caves. Comparison of stains versus non-stained samples from the Passage area of the Lascaux Cave indicated that a few taxa (e.g. the Sordiaromycetes amongst fungi) were more prevalent within than outside stains, yet the main difference was in the relative proportion of the different microbial taxonomic groups and genera, which supposedly supports the biological origin of the stains. Overall, metagenomic sequencing of cave wall samples was effective to evidence the large colonization of caves by a diversified range of microorganisms. It also showed that Lascaux Cave represented a very particular situation in comparison with neighboring caves, probably in relation to the extent of disturbance it had undergone. Our results provide key baseline information to guide conservation efforts in anthropized caves such as Lascaux and pave the way to modern monitoring of ornamented caves.Keywords: cave conservation, Lascaux cave, microbes, paleolithic paintings
Procedia PDF Downloads 244396 Digitalization: The Uneven Geography of Information and Communication Technology (ICTS) CTSoss Four Major States in India
Authors: Sanchari Mukhopadhyay
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Today, almost the entire realm of human activities are becoming increasingly dependent on the power of information, where through ICTs it is now possible to cater distances and avail various services at a few clicks. In principle, ICTs are thus expected to blur location-specific differences and affiliations of development and bring in an inclusive society at the wake of globalization. However, eventually researchers and policy analysts realized that ICTs are also generating inequality in spite of the hope for an integrated world and widespread social well-being. Regarding this unevenness, location plays a major role as often ICT development is seen to be concentrated into pockets, leaving behind large tracks as underprivileged. Thus, understanding the spatial pattern of ICT development and distribution is significant in relation to exploring the extent to which ICTs are fulfilling the promises or reassuring the existing divisions. In addition, it is also profoundly crucial to investigate how regions are connecting and competing both locally and globally. The focus of the research paper is to evaluate the spatial structure of ICT led development in India. Thereby, it attempts to understand the state level (four selected states) pattern of ICT penetration, the pattern of diffusion across districts with respect to large urban centres and the rural-urban disparity of technology adoption. It also tries to assess the changes in access dynamisms of ICTs as one move away from a large metropolitan city towards the periphery. In brief, the analysis investigates into the tendency towards the uneven growth of development through the identification of the core areas of ICT advancement within the country and its diffusion from the core to the periphery. In order to assess the level of ICT development and rural-urban disparity across the districts of selected states, two indices named ICT Development Index and Rural-Urban Digital Divide Index have been constructed. The study mostly encompasses the latest Census (2011) of the country and TRAI (Telecom Regulatory Authority of India) in some cases.Keywords: ICT development, diffusion, core-periphery, digital divide
Procedia PDF Downloads 333395 Collaborative Approaches in Achieving Sustainable Private-Public Transportation Services in Inner-City Areas: A Case of Durban Minibus Taxis
Authors: Lonna Mabandla, Godfrey Musvoto
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Transportation is a catalytic feature in cities. Transport and land use activity are interdependent and have a feedback loop between how land is developed and how transportation systems are designed and used. This recursive relationship between land use and transportation is reflected in how public transportation routes internal to the inner-city enhance accessibility, therefore creating spaces that are conducive to business activity, while the business activity also informs public transportation routes. It is for this reason that the focus of this research is on public transportation within inner-city areas where the dynamic is evident. Durban is the chosen case study where the dominating form of public transportation within the central business district (CBD) is minibus taxis. The paradox here is that minibus taxis still form part of the informal economy even though they are the leading form of public transportation in South Africa. There have been many attempts to formalise this industry to follow more regulatory practices, but minibus taxis are privately owned, therefore complicating any proposed intervention. The argument of this study is that the application of collaborative planning through a sustainable partnership between the public and private sectors will improve the social and environmental sustainability of public transportation. One of the major challenges that exist within such collaborative endeavors is power dynamics. As a result, a key focus of the study is on power relations. Practically, power relations should be observed over an extended period, specifically when the different stakeholders engage with each other, to reflect valid data. However, a lengthy data collection process was not possible to observe during the data collection phase of this research. Instead, interviews were conducted focusing on existing procedural planning practices between the inner-city minibus taxi association (South and North Beach Taxi Association), the eThekwini Transport Authority (ETA), and the eThekwini Town Planning Department. Conclusions and recommendations were then generated based on these data.Keywords: collaborative planning, sustainability, public transport, minibus taxis
Procedia PDF Downloads 59394 Evaluation of the Spatial Regulation of Hydrogen Sulphide Producing Enzymes in the Placenta during Labour
Authors: F. Saleh, F. Lyall, A. Abdulsid, L. Marks
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Background: Labour in human is a complex biological process that involves interactions of neurological, hormonal and inflammatory pathways, with the placenta being a key regulator of these pathways. It is known that uterine contractions and labour pain cause physiological changes in gene expression in maternal and fetal blood, and in placenta during labour. Oxidative and inflammatory stress pathways are implicated in labour and they may cause alteration of placental gene expression. Additionally, in placental tissues, labour increases the expression of genes involved in placental oxidative stress, inflammatory cytokines, angiogenic regulators and apoptosis. Recently, Hydrogen Sulphide (H2S) has been considered as an endogenous gaseous mediator which promotes vasodilation and exhibits cytoprotective anti-inflammatory properties. The endogenous H2S is synthesised predominantly by two enzymes: cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). As the H2S pathway has anti-oxidative and anti-inflammatory characteristics thus, we hypothesised that the expression of CBS and CSE in placental tissues would alter during labour. Methods: CBS and CSE expressions were examined in placentas using western blotting and RT-PCR in inner, middle and outer placental zones in placentas obtained from healthy non labouring women who delivered by caesarian section. These were compared with the equivalent zone of placentas obtained from women who had uncomplicated labour and delivered vaginally. Results: No differences in CBS and CSE mRNA or protein levels were found between the different sites within placentas in either the labour or non-labour group. There were no significant differences in either CBS or CSE expression between the two groups at the inner site and middle site. However, at the outer site there was a highly significant decrease in CBS protein expression in the labour group when compared to the non-labour group (p = 0.002). Conclusion: To the best of author’s knowledge, this is the first report to suggest that, CBS is expressed in a spatial manner within the human placenta. Further work is needed to clarify the precise function and mechanism of this spatial regulation although it is likely that inflammatory pathways regulation is a complex process in which this plays a role.Keywords: anti-inflammatory, hydrogen sulphide, labour, oxidative stress
Procedia PDF Downloads 241393 Expression of Micro-RNA268 in Zinc Deficient Rice
Authors: Sobia Shafqat, Saeed Ahmad Qaisrani
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MicroRNAs play an essential role in the regulation and development of all processes in most eukaryotes because of their prospective part as mediators controlling cell growth and differentiation towards the exact position of RNAs response in plants under biotic and abiotic factors or stressors. In a few cases, Zn is oblivious poisonous for plants due to its heavy metal status. Some other metals are extremely toxic, like Cd, Hg, and Pb, but these elements require in rice for the programming of genes under abiotic stress resembling Zn stress when micro RNAs268 was importantly introduced in rice. The micro RNAs overexpressed in transgenic plants with an accumulation of a large amount of melanin dialdehyde, hydrogen peroxide, and an excessive quantity of Zn in the seedlings stage. Let out results for rice pliability under Zn stress micro RNAs act as negative controllers. But the role of micro RNA268 act as a modulator in different ecological condition. It has been explained clearly with a long understanding of the role of micro RNA268 under stress conditions; pliability and practically showed outcome to increase plant sufferance under Zn stress because micro RNAs is an intervention technique for gene regulation in gene expression. The proposed study was experimented with by using genetic factors of Zn stress and toxicity effect on rice plants done at District Vehari, Pakistan. The trial was performed randomly with three replications in a complete block design (RCBD). These blocks were controlled with different concentrations of genetic factors. By overexpression of micro RNA268 rice, seedling growth was not stopped under Zn deficiency due to the accumulation of a large amount of melanin dialdehyde, hydrogen peroxide, and an excessive quantity of Zn in their seedlings. Results showed that micro RNA268 act as a negative controller under Zn stress. In the end, under stress conditions, micro RNA268 showed the necessary function in the tolerance of rice plants. The directorial work sketch gave out high agronomic applications and yield outcomes in rice with a specific amount of Zn application.Keywords: micro RNA268, zinc, rice, agronomic approach
Procedia PDF Downloads 61392 The Youth Employment Peculiarities in Post-Soviet Georgia
Authors: M. Lobzhanidze, N. Damenia
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The article analyzes the current structural changes in the economy of Georgia, liberalization and integration processes of the economy. In accordance with this analysis, the peculiarities and the problems of youth employment are revealed. In the paper, the Georgian labor market and its contradictions are studied. Based on the analysis of materials, the socio-economic losses caused by the long-term and mass unemployment of young people are revealed, the objective and subjective circumstances of getting higher education are studied. The youth employment and unemployment rates are analyzed. Based on the research, the factors that increase unemployment are identified. According to the analysis of the youth employment, it has appeared that the unemployment share in the number of economically active population has increased in the younger age group. It demonstrates the high requirements of the labour market in terms of the quality of the workforce. Also, it is highlighted that young people are exposed to a highly paid job. The following research methods are applied in the presented paper: statistical (selection, grouping, observation, trend, etc.) and qualitative research (in-depth interview), as well as analysis, induction and comparison methods. The article presents the data by the National Statistics Office of Georgia and the Ministry of Agriculture of Georgia, policy documents of the Parliament of Georgia, scientific papers by Georgian and foreign scientists, analytical reports, publications and EU research materials on similar issues. The work estimates the students and graduates employment problems existing in the state development strategy and priorities. The measures to overcome the challenges are defined. The article describes the mechanisms of state regulation of youth employment and the ways of improving this regulatory base. As for major findings, it should be highlighted that the main problems are: lack of experience and incompatibility of youth qualification with the requirements of the labor market. Accordingly, it is concluded that the unemployment rate of young people in Georgia is increasing.Keywords: migration of youth, youth employment, migration management, youth employment and unemployment
Procedia PDF Downloads 148391 Coronin 1C and miR-128A as Potential Diagnostic Biomarkers for Glioblastoma Multiform
Authors: Denis Mustafov, Emmanouil Karteris, Maria Braoudaki
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Glioblastoma multiform (GBM) is a heterogenous primary brain tumour that kills most affected patients. To the authors best knowledge, despite all research efforts there is no early diagnostic biomarker for GBM. MicroRNAs (miRNAs) are short non-coding RNA molecules which are deregulated in many cancers. The aim of this research was to determine miRNAs with a diagnostic impact and to potentially identify promising therapeutic targets for glioblastoma multiform. In silico analysis was performed to identify deregulated miRNAs with diagnostic relevance for glioblastoma. The expression profiles of the chosen miRNAs were then validated in vitro in the human glioblastoma cell lines A172 and U-87MG. Briefly, RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed using the mirVANA miRNA isolation kit. Quantitative Real-Time Polymerase Chain Reaction was performed to verify their expression. The presence of five target proteins within the A172 cell line was evaluated by Western blotting. The expression of the CORO1C protein within 32 GBM cases was examined via immunohistochemistry. The miRNAs identified in silico included miR-21-5p, miR-34a and miR-128a. These miRNAs were shown to target deregulated GBM genes, such as CDK6, E2F3, BMI1, JAG1, and CORO1C. miR-34a and miR-128a showed low expression profiles in comparison to a control miR-RNU-44 in both GBM cell lines suggesting tumour suppressor properties. Opposing, miR-21-5p demonstrated greater expression indicating that it could potentially function as an oncomiR. Western blotting revealed expression of all five proteins within the A172 cell line. In silico analysis also suggested that CORO1C is a target of miR-128a and miR-34a. Immunohistochemistry demonstrated that 75% of the GBM cases showed moderate to high expression of CORO1C protein. Greater understanding of the deregulated expression of miR-128a and the upregulation of CORO1C in GBM could potentially lead to the identification of a promising diagnostic biomarker signature for glioblastomas.Keywords: non-coding RNAs, gene expression, brain tumours, immunohistochemistry
Procedia PDF Downloads 89390 Phenotypic Characterization of Desi Naked Neck Chicken and Its Association with Insulin-Like Growth Factor-I (IGF-I) Gene Polymorphism in Pakistan
Authors: Akbar Nawaz Khan, Abdul Ghaffar, Muhammad Naeem Riaz
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The study was conducted to investigate the phenotypic features, morphometry and production potentialities of indigenous naked neck chicken (NN) of Pakistan under intensive management condition. A total of 35 NN chicks were randomly selected, and the experiment was performed at Poultry and wildlife research section NARC Islamabad for a period of 22 weeks. The predominant plumage color was black and golden while skin color was observed white. The average shank length, leg length, thigh length, keel length, chest breadth, head width, wing space, wing length, body length, body girth, body height and pubic bone width in adult males and females were 69.19 ± 3.34mm, 117.93 ± 4.42mm, 117.93 ± 4.42mm, 90.87 ± 6.53mm, 95.03 ± 4.56mm, 49.77 ± 2.53mm, 30.63 ± 1.50cm, 27.24 ± 2.71cm, 18.88 ± 0.65cm, 17.77 ± 1.01cm, 25.96 ± 0.56cm, 47.81 ± 1.41cm and 35.69 ± 4.09mm respectively. The average age and live body weight of NN chicken at sexual maturity were recorded as 165.85 days and 1269.38 g. While hen-day egg production of NN was recorded as 45%. The present study was aimed to investigate the existence of polymorphism at IGF-I gene in indigenous naked neck chicken through PCR based Restriction Fragment Length Polymorphism. Based on restriction analysis using Hinf I restriction enzyme, three genotypes were detected designated as AA, AC, and CC. Restriction analysis of PCR amplified product showed the presence of DNA fragments of 622, 378, 244 and 191, (genotypes). The PCR-RFLP analysis is easy, cost effective method which permits the easy characterization of IGF-I gene. This showed the investigated IGF-I genes can serve as good molecular markers for marker assisted selection (MAS) concerning growth related traits in chicken.Keywords: Desi chicken, naked neck, morphology, morphometry, production potential, egg traits, egg geometry, IGF-I, growth, PCR- RFLP, chicken
Procedia PDF Downloads 389389 Brachypodium: A Model Genus to Study Grass Genome Organisation at the Cytomolecular Level
Authors: R. Hasterok, A. Betekhtin, N. Borowska, A. Braszewska-Zalewska, E. Breda, K. Chwialkowska, R. Gorkiewicz, D. Idziak, J. Kwasniewska, M. Kwasniewski, D. Siwinska, A. Wiszynska, E. Wolny
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In contrast to animals, the organisation of plant genomes at the cytomolecular level is still relatively poorly studied and understood. However, the Brachypodium genus in general and B. distachyon in particular represent exceptionally good model systems for such study. This is due not only to their highly desirable ‘model’ biological features, such as small nuclear genome, low chromosome number and complex phylogenetic relations, but also to the rapidly and continuously growing repertoire of experimental tools, such as large collections of accessions, WGS information, large insert (BAC) libraries of genomic DNA, etc. Advanced cytomolecular techniques, such as fluorescence in situ hybridisation (FISH) with evermore sophisticated probes, empowered by cutting-edge microscope and digital image acquisition and processing systems, offer unprecedented insight into chromatin organisation at various phases of the cell cycle. A good example is chromosome painting which uses pools of chromosome-specific BAC clones, and enables the tracking of individual chromosomes not only during cell division but also during interphase. This presentation outlines the present status of molecular cytogenetic analyses of plant genome structure, dynamics and evolution using B. distachyon and some of its relatives. The current projects focus on important scientific questions, such as: What mechanisms shape the karyotypes? Is the distribution of individual chromosomes within an interphase nucleus determined? Are there hot spots of structural rearrangement in Brachypodium chromosomes? Which epigenetic processes play a crucial role in B. distachyon embryo development and selective silencing of rRNA genes in Brachypodium allopolyploids? The authors acknowledge financial support from the Polish National Science Centre (grants no. 2012/04/A/NZ3/00572 and 2011/01/B/NZ3/00177)Keywords: Brachypodium, B. distachyon, chromosome, FISH, molecular cytogenetics, nucleus, plant genome organisation
Procedia PDF Downloads 351388 Integration of the Battery Passport into the eFTI Platform to Improve Digital Data Exchange in the Context of Battery Transport
Authors: Max Plotnikov, Arkadius Schier
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To counteract climate change, the European Commission adopted the European Green Deal (EDG) in 2019. Some of the main objectives of the EDG are climate neutrality by 2050, decarbonization, sustainable mobility, and the shift from a linear economy to a circular economy in the European Union. The mobility turnaround envisages, among other things, the switch from classic internal combustion vehicles to electromobility. The aforementioned goals are therefore accompanied by increased demand for lithium-ion batteries (LIBs) and the associated logistics. However, this inevitably gives rise to challenges that need to be addressed. Depending on whether the LIB is transported by road, rail, air, or sea, there are different regulatory frameworks in the European Union that relevant players in the value chain must adhere to. LIBs are classified as Dangerous Goods Class 9, and against this backdrop, there are various restrictions that need to be adhered to when transporting them for various actors. Currently, the exchange of information in the value chain between the various actors is almost entirely paper-based. Especially in the transport of dangerous goods, this often leads to a delay in the transport or to incorrect data. The exchange of information with the authorities is particularly essential in this context. A solution for the digital exchange of information is currently being developed. Electronic freight transport information (eFTI) enables fast and secure exchange of information between the players in the freight transport process. This concept is to be used within the supply chain from 2025. Another initiative that is expected to improve the monitoring of LIB in this context, among other things, is the battery pass. In July 2023, the latest battery regulation was adopted in the Official Journal of the European Union. This battery pass gives different actors static as well as dynamic information about the batteries depending on their access rights. This includes master data such as battery weight or battery category or information on the state of health or the number of negative events that the battery has experienced. The integration of the battery pass with the eFTI platform will be investigated for synergy effects in favor of the actors for battery transport.Keywords: battery logistics, battery passport, data sharing, eFTI, sustainability
Procedia PDF Downloads 79387 The Molecular Analysis of Effect of Phytohormones and Spermidine on Tomato Growth under Biotic Stress
Authors: Rumana Keyani, Haleema Sadia, Asia Nosheen, Rabia Naz, Humaira Yasmin, Sidra Zahoor
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Tomato is a significant crop of the world and is one of the staple foods of Pakistan. A vast number of plant pathogens from simple viruses to complex parasites cause diseases in tomatoes but fungal infection in our country is quite high. Sometimes the symptoms are too harsh destroying the crop altogether. Countries like our own with continuously increasing massive population and limited resources cannot afford such an economic loss. There is an array of morphological, genetic, biochemical and molecular processes involved in plant resistance mechanisms to biotic stress. The study of different metabolic pathways like Jasmonic acid (JA) pathways and most importantly signaling molecules like ROS/RNS and their redoxin enzymes i.e. TRX and NRX is crucial to disease management, contributing to healthy plant growth. So, improving tolerance in crop plants against biotic stresses is a dire need of our country and world as whole. In the current study, fungal pathogenic strains Alternaria solani and Rhizoctonia solani were used to inoculate tomatoes to check the defense responses of tomato plant against these pathogens at molecular as well as phenotypic level with jasmonic acid and spermidine pretreatment. All the growth parameters (root and shoot length, dry and weight root, shoot weight measured 7 days post-inoculation, exhibited that infection drastically declined the growth of the plant whereas jasmonic acid and spermidine assisted the plants to cope up with the infection. Thus, JA and Spermidine treatments maintained comparatively better growth factors. Antioxidant assays and expression analysis through real time quantitative PCR following time course experiment at 24, 48 and 72 hours intervals also exhibited that activation of JA defense genes and a polyamine Spermidine helps in mediating tomato responses against fungal infection when used alone but the two treatments combined mask the effect of each other.Keywords: fungal infection, jasmonic acid defence, tomato, spermidine
Procedia PDF Downloads 128386 Ratification of the United Nations Convention for the Promotion and Protection of Their Human Rights and the Paradoxes of the Discriminatory Right to Acquire the Status of Persons with Disabilities in Cameroon
Authors: Dakeyi Athanase
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The ratification of an international human rights legal instrument provides signatory States with an opportunity to assume a set of obligations and rights for the benefit of their citizens, offering increased possibilities, opportunities, and means to access an improved quality of life – to be, to appear, and to become. Developed nations typically experience cultural, political, social, economic, legal, and regulatory transformations in response to this transition. In a methodologically proactive approach, mechanisms undergo a visible and comprehensible process of qualitative and quantitative change. Conversely, in nations undergoing development, the response to such ratification varies. Some demonstrate positive policy changes, while others remain stagnant or regress. Cameroon falls into the second category, despite efforts, as it legally prohibits 50% of its population with disabilities from acquiring the status of a person with a disability. The overarching goal of this communication is to highlight these deficiencies and their detrimental effects on various aspects of life, fostering awareness among beneficiaries and advocating for more inclusive transformations in the country. Our project employs a popular and participatory methodological approach by involving beneficiaries and their organizations in its preparation. It is also inclusive, representing the diversity of disabilities and engaging natural and legal persons from various backgrounds. Active consultations occur at all levels of the activities. Anticipated outcomes include raising awareness globally among nations, international cooperation organizations, NGOs, and other inclusive development actors. We seek their support for local advocacy efforts to fully implement the United Nations Convention on the Rights of Persons with Disabilities (CRPD). Concurrently, we hope they express solidarity with the victims in Cameroon who have been left behind and recommend legal reforms to align domestic and international legislation with the promotion and protection of disability rights.Keywords: droit, convention, handicap, discrimination, participation, inclusion
Procedia PDF Downloads 54385 The Molecular Rationale for Steroid Based Therapy of Leukemia: Diagnostic and Therapeutic Implications
Authors: Eitan Yefenof
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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.Keywords: apoptosis, leukemia, micro-RNA, steroids
Procedia PDF Downloads 246384 Investigation p53 Codon 72 Polymorphism and miR-146a rs2910164 Polymorphism in Breast Cancer
Authors: Marjan Moradi Fard, Hossein Rassi, Masoud Houshmand
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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.Keywords: breast cancer, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism, genotypes
Procedia PDF Downloads 336383 Expression of PGC-1 Alpha Isoforms in Response to Eccentric and Concentric Resistance Training in Healthy Subjects
Authors: Pejman Taghibeikzadehbadr
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Background and Aim: PGC-1 alpha is a transcription factor that was first detected in brown adipose tissue. Since its discovery, PGC-1 alpha has been known to facilitate beneficial adaptations such as mitochondrial biogenesis and increased angiogenesis in skeletal muscle following aerobic exercise. Therefore, the purpose of this study was to investigate the expression of PGC-1 alpha isoforms in response to eccentric and concentric resistance training in healthy subjects. Materials and Methods: Ten healthy men were randomly divided into two groups (5 patients in eccentric group - 5 in eccentric group). Isokinetic contraction protocols included eccentric and concentric knee extension with maximum power and angular velocity of 60 degrees per second. The torques assigned to each subject were considered to match the workload in both protocols, with a rotational speed of 60 degrees per second. Contractions consisted of a maximum of 12 sets of 10 repetitions for the right leg, a rest time of 30 seconds between each set. At the beginning and end of the study, biopsy of the lateral broad muscle tissue was performed. Biopsies were performed in both distal and proximal directions of the lateral flank. To evaluate the expression of PGC1α-1 and PGC1α-4 genes, tissue analysis was performed in each group using Real-Time PCR technique. Data were analyzed using dependent t-test and covariance test. SPSS21 software and Exell 2013 software were used for data analysis. Results: The results showed that intra-group changes of PGC1α-1 after one session of activity were not significant in eccentric (p = 0.168) and concentric (p = 0.959) groups. Also, inter-group changes showed no difference between the two groups (p = 0.681). Also, intra-group changes of PGC1α-4 after one session of activity were significant in an eccentric group (p = 0.012) and concentric group (p = 0.02). Also, inter-group changes showed no difference between the two groups (p = 0.362). Conclusion: It seems that the lack of significant changes in the desired variables due to the lack of exercise pressure is sufficient to stimulate the increase of PGC1α-1 and PGC1α-4. And with regard to reviewing the answer, it seems that the compatibility debate has different results that need to be addressed.Keywords: eccentric contraction, concentric contraction, PGC1α-1 و PGC1α-4, human subject
Procedia PDF Downloads 78382 Rewilding the River: Assessing the Environmental Effects and Regulatory Influences of the Condit Dam Removal Process
Authors: Neda Safari, Jacob Petersen-Perlman
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There are more than two million dams in the United States, and a considerable portion of them are either non-operational or approaching the end of their designed lifespan. However, this emerging trend is new, and the majority of dam sites have not undergone thorough research and assessments after their removal to determine the overall effectiveness of restoration initiatives, particularly in the case of large-scale dams that may significantly impact their surrounding areas. A crucial factor to consider is the lack of specific regulations pertaining to dam removal at the federal level. Consequently, other environmental regulations that were not originally designed with dam removal considerations are used to execute these projects. This can result in delays or challenges for dam removal initiatives. The process of removing dams is usually the most important first step to restore the ecological and biological health of the river, but often there is a lack of measurable indicators to assess if it has achieved its intended objectives. In addition, the majority of studies on dam removal are only short-term and focus on a particular measure of response. Therefore, it is essential to conduct extensive and continuous monitoring to analyze the river's response throughout every aspect. Our study is divided into two sections. The first section of my research will analyze the establishment and utilization of dam removal laws and regulations in the Condit Dam removal process. We will highlight the areas where the frameworks for policy and dam removal projects remain in need of improvement in order to facilitate successful dam removals in the future. In this part, We will review the policies and plans that affected the decision-making process to remove the Condit dam while also looking at how they impacted the physical changes to the river after the dam was removed. In the second section, we will look at the effects of the dam removal over a decade later and attempt to determine how the river's physical response has been impacted by this modification. Our study aims to investigate the Condit dam removal process and its impact on the ecological response of the river. We anticipate identifying areas for improvement in policies pertaining to dam removal projects and exploring ways to enhance them to ensure improved project outcomes in the future.Keywords: dam removal, ecolocgical change, water related regulation, water resources
Procedia PDF Downloads 45381 Economic and Environmental Life Cycle Analysis of Construction and Demolition Waste Management System
Authors: Yanqing Yi, Maria Cristina Lavagnolo, Alessandro Manzardo
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Construction and demolition waste (C&DW) is a major challenge in the European Union, emphasizing the urgent need for appropriate waste management processes. Selecting these solutions is challenging, as it requires identifying efficient C&DW management techniques that balance acceptable practices, regulatory compliance, resource conservation, economic viability, and environmental concerns. Techniques for analyzing many kinds of criteria allow for the use of multi-criteria analysis in life cycle assessment (LCA). Although LCA is commonly used to analyze environmental effects, the economic factor has not been fully integrated into the LCA approach in C&DW management. The life cycle costing (LCC) approach was designed to assess economic performance in the C&DW management process. The choice of an effective multi-criteria decision-making (MCDM) technique is critical for the C&DW system. This study seeks to propose a model that employs MCDM by considering LCA and LCC results, thereby augmenting both environmental and economic sustainability. A widely used compensatory MCDM technique, TOPSIS, has been chosen to identify the most effective C&DW management scheme by comparing and ranking various scenarios. Four waste management alternatives were examined in the Lombardy region of Italy, namely, (i) landfill; (ii) recycling for concrete production and road construction, incineration with energy recovery; (iii) recycling for road construction; (iv) recycling for concrete production and road construction. We determine that, with the implementation of various scenarios, the most suitable scenario emerges to be recycled for concrete production and road construction, with a score of 0.711/1; recycling for road construction, with a final score of 0.291/1, ranks second; recycling for concrete production and road construction, incineration with energy recovery scores 0.002/1, ranks third; and landfill (scores: 0/1) is the worst choice, indicating it has the highest environmental impact. Finally, suggestions were developed to improve the system's environmental performance.Keywords: life cycle assessment, life cycle costing, construction and demolition waste, multi-criteria decision making
Procedia PDF Downloads 71380 Trans-Activator of Transcription-Tagged Active AKT1 Variants for Delivery to Mammalian Cells
Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue
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Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation
Procedia PDF Downloads 118379 Genotypic and Allelic Distribution of Polymorphic Variants of Gene SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) and Their Association to the Clinical Response to Metformin in Adult Pakistani T2DM Patients
Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid
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Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.Keywords: diabetes, T2DM, SLC47A1, Pakistan, polymorphism
Procedia PDF Downloads 159378 Loss of Function of Only One of Two CPR5 Paralogs Causes Resistance Against Rice Yellow Mottle Virus
Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar
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Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus
Procedia PDF Downloads 118377 Hepatocyte-Intrinsic NF-κB Signaling Is Essential to Control a Systemic Viral Infection
Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder
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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance
Procedia PDF Downloads 191376 In Silico Study of Cell Surface Structures of Parabacteroides distasonis Involved in Its Maintain Within the Gut Microbiota and Its Potential Pathogenicity
Authors: Jordan Chamarande, Lisiane Cunat, Corentine Alauzet, Catherine Cailliez-Grimal
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Gut microbiota (GM) is now considered a new organ mainly due to the microorganism’s specific biochemical interaction with its host. Although mechanisms underlying host-microbiota interactions are not fully described, it is now well-defined that cell surface molecules and structures of the GM play a key role in such relation. The study of surface structures of GM members is also fundamental for their role in the establishment of species in the versatile and competitive environment of the digestive tract and as a potential virulence factor. Among these structures are capsular polysaccharides (CPS), fimbriae, pili and lipopolysaccharides (LPS), all well-described for their central role in microorganism colonization and communication with host epithelium. The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and as a new potential biotherapeutic product. However, to the best of the authors’ knowledge, the cell surface molecules and structures of P. distasonis that allow its maintain within the GM are not identified. Moreover, although P. distasonis is strongly recognized as intestinal commensal species with benefits for its host, it has also been recognized as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of the capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-Typing classification in order to better understand and characterize the beneficial/pathogenic behaviour related to P. distasonis strains. In context, 2 different types of fimbriae, 3 of pilus and up to 14 capsular polysaccharide loci, have been identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-Type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed in P. distasonis adhesion capacities and its potential pathogenicity.Keywords: gut microbiota, Parabacteroides distasonis, capsular polysaccharide, fimbriae, pilus, O-antigen, pathogenicity, probiotic, comparative genomics
Procedia PDF Downloads 103375 A System Dynamics Approach for Assessing Policy Impacts on Closed-Loop Supply Chain Efficiency: A Case Study on Electric Vehicle Batteries
Authors: Guannan Ren, Thomas Mazzuchi, Shahram Sarkani
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Electric vehicle battery recycling has emerged as a critical process in the transition toward sustainable transportation. As the demand for electric vehicles continues to rise, so does the need to address the end-of-life management of their batteries. Electric vehicle battery recycling benefits resource recovery and supply chain stability by reclaiming valuable metals like lithium, cobalt, nickel, and graphite. The reclaimed materials can then be reintroduced into the battery manufacturing process, reducing the reliance on raw material extraction and the environmental impacts of waste. Current battery recycling rates are insufficient to meet the growing demands for raw materials. While significant progress has been made in electric vehicle battery recycling, many areas can still improve. Standardization of battery designs, increased collection and recycling infrastructures, and improved efficiency in recycling processes are essential for scaling up recycling efforts and maximizing material recovery. This work delves into key factors, such as regulatory frameworks, economic incentives, and technological processes, that influence the cost-effectiveness and efficiency of battery recycling systems. A system dynamics model that considers variables such as battery production rates, demand and price fluctuations, recycling infrastructure capacity, and the effectiveness of recycling processes is created to study how these variables are interconnected, forming feedback loops that affect the overall supply chain efficiency. Such a model can also help simulate the effects of stricter regulations on battery disposal, incentives for recycling, or investments in research and development for battery designs and advanced recycling technologies. By using the developed model, policymakers, industry stakeholders, and researchers may gain insights into the effects of applying different policies or process updates on electric vehicle battery recycling rates.Keywords: environmental engineering, modeling and simulation, circular economy, sustainability, transportation science, policy
Procedia PDF Downloads 92