Search results for: litter pathways

Authors: Mohammad Aladwan

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Alzheimer’s disease (AD) is a widespread dementing illness with a complex and poorly understood etiology. An important role in improving our understanding of the AD process is the modeling of disease-associated changes in tau protein phosphorylation, a protein known to mediate events essential to the onset and progression of AD. A main feature of AD is the abnormal phosphorylation of tau protein and the presence of neurofibrillary tangles. In order to evaluate the respective roles of the microtubule-binding region (MTBR) and alternatively spliced exons in the N-terminal projection domains in AD, we have constructed SHSY-5Y cell lines that stably overexpress four different species of tau protein (4R2N, 4R0N, N(E-2), N(E+2)). Since the toxicity and spreading of tau lesions in AD depends on the interactions of tau with other proteins, we have performed a proteomic analysis of exosome-fraction interactomes for cell lysates and media samples that were isolated from SHSY-5Y cell lines. Functional analysis of tau interactomes based on gene ontology (GO) terms was performed using the String 10.5 database program. The highest number of exosomes proteomes and tau associated proteins were found with 4R2N isoform (2771 and 159) in cell lysate and they have a high strength of connectivity (78%) between proteins, while N(E-2) isoform in the media proteomes has the highest number of proteins and tau associated protein (1829 and 205). Moreover, known AD markers were significantly enriched in secreted interactomes relative to lysate interactomes in the SHSY-5Y cells of tau isoforms lacking exons 2 and 3 in the N-terminal. The lack of exon 2 (E-2) from tau protein can be mediated by tau secretion and spreading to different cells. Enriched functions in the secreted E-2 interactome include signaling and developmental pathways that have been linked to a) tau misprocessing and lesion development and b) tau secretion and which, therefore, could play novel roles in AD pathogenesis.

Keywords: Alzheimer's disease, dementia, tau protein, neurodegenration disease

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Authors: Javad Mohiti-Ardekani, Shabodin Asadii, Ali Moradi

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Introduction: Curcumin, the yellow pigment in turmeric, has been shown as an anti-diabetic agent for centuries but only in recent few years, its mechanism of action has been under investigation. Some studies showed that curcumin might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in cells. To investigate this possibility, we investigate the effects of extract and commercial curcumin with and without insulin on GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). Methods and Material: C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 40 µmolar Extract and Commercial curcumin, with or without insulin as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two independent samples t-test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM groups curcumin and curcumin with insulin in comparison to 1 % DMSO-treated myotubes control group. Results: As our results have shown extract and commercial curcumin induces GLUT4 translocation from intra-cell into cell surface. The results have also shown synergic effect of curcumin on translocation of GLUT4 from intra-cell into cell surface in the presence of 100 nm insulin. Discussion: We conclude that curcumin may be a choice of type-2 diabetes mellitus treatment because its extract and commercial enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However, it is necessary to trace the signaling pathways which are activated by curcumin.

Keywords: Curcumin, insulin, Diabetes type-2, GLUT4

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Authors: Agustyas Tjiptaningrum, Intanri Kurniati, Fadilah Fadilah, Linda Erlina, Tiwuk Susantiningsih

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Coronavirus disease-19 (COVID-19) is still one of the health problems. It can be a severe condition that is caused by a cytokine storm. In a cytokine storm, several proinflammatory cytokines are released massively. It destroys epithelial cells, and subsequently, it can cause death. The anti-inflammatory agent can be used to decrease the number of severe Covid-19 conditions. Melaleuca cajuputi is a plant that has antiviral, antibiotic, antioxidant, and anti-inflammatory activities. This study was carried out to analyze the prediction mechanism of the M. cajuputi extract from Lampung, Indonesia, as an anti-inflammatory agent for COVID-19. This study constructed a database of protein host target that was involved in the inflammation process of COVID-19 using data retrieval from GeneCards with the keyword “SARS-CoV2”, “inflammation,” “cytokine storm,” and “acute respiratory distress syndrome.” Subsequent protein-protein interaction was generated by using Cytoscape version 3.9.1. It can predict the significant target protein. Then the analysis of the Gene Ontology (GO) and KEGG pathways was conducted to generate the genes and components that play a role in COVID-19. The result of this study was 30 nodes representing significant proteins, namely NF-κβ, IL-6, IL-6R, IL-2RA, IL-2, IFN2, C3, TRAF6, IFNAR1, and DOX58. From the KEGG pathway, we obtained the result that NF-κβ has a role in the production of proinflammatory cytokines, which play a role in the COVID-19 cytokine storm. It is an important factor for macrophage transcription; therefore, it will induce inflammatory gene expression that encodes proinflammatory cytokines such as IL-6, TNF-α, and IL-1β. In conclusion, the blocking of NF-κβ is the prediction mechanism of the M. cajuputi extract as an anti-inflammation agent for COVID-19.

Keywords: antiinflammation, COVID-19, cytokine storm, NF-κβ, M. cajuputi

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Authors: Antonella Poce, Deborah Seid Howes, Maria Rosaria Re, Mara Valente

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The Creative Industries education contexts, Museum Education in particular, generally presents a low emphasis on the use of new digital technologies, digital abilities and transversal skills development. The spread of the Covid-19 pandemic has underlined the importance of these abilities and skills in cultural heritage education contexts: gaining digital skills, museum professionals will improve their career opportunities with access to new distribution markets through internet access and e-commerce, new entrepreneurial tools, or adding new forms of digital expression to their work. However, the use of web, mobile, social, and analytical tools is becoming more and more essential in the Heritage field, and museums, in particular, to face the challenges posed by the current worldwide health emergency. Recent studies highlight the need for stronger partnerships between the cultural and creative sectors, social partners and education and training providers in order to provide these sectors with the combination of skills needed for creative entrepreneurship in a rapidly changing environment. Considering the above conditions, the paper presents different examples of digital learning experiences carried out in Italian and USA contexts with the aim of promoting digital skills in museum professionals. In particular, a quali-quantitative research study has been conducted on two international Postgraduate courses, “Advanced Studies in Museum Education” (2 years) and “Museum Education” (1 year), in order to identify the educational effectiveness of the online learning strategies used (e.g., OBL, Digital Storytelling, peer evaluation) for the development of digital skills and the acquisition of specific content. More than 50 museum professionals participating in the mentioned educational pathways took part in the learning activity, providing evaluation data useful for research purposes.

Keywords: digital skills, museum professionals, technology, education

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Authors: Vanja Skoric

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The paper examines whether the impacts of artificial intelligence (AI) can be meaningfully addressed through the rights-based approach to AI design, investigating in particular how the inclusive, participatory process of assessing the AI impact would make this viable. There is a significant gap between envisioning rights-based AI systems and their practical application. Plausibly, internalizing human rights approach within AI design process might be achieved through identifying and assessing implications of AI features human rights, especially considering the case of vulnerable individuals and communities. However, there is no clarity or consensus on how such an instrument should be operationalised to usefully identify the impact, mitigate harms and meaningfully ensure relevant stakeholders’ participation. In practice, ensuring the meaningful inclusion of those individuals, groups, or entire communities who are affected by the use of the AI system is a prerequisite for a process seeking to assess human rights impacts and risks. Engagement in the entire process of the impact assessment should enable those affected and interested to access information and better understand the technology, product, or service and resulting impacts, but also to learn about their rights and the respective obligations and responsibilities of developers and deployers to protect and/or respect these rights. This paper will provide an overview of the study and practice of the participatory design process for AI, including inclusive impact assessment, its main elements, propose a framework, and discuss the lessons learned from the existing theory. In addition, it will explore pathways for enhancing and promoting individual and group rights through such engagement by discussing when, how, and whom to include, at which stage of the process, and what are the pre-requisites for meaningful and engaging. The overall aim is to ensure using the technology that works for the benefit of society, individuals, and particular (historically marginalised) groups.

Keywords: rights-based design, AI impact assessment, inclusion, harm mitigation

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Authors: Enjie Xu, Zhen Huang, Kunpeng Zhu, Jianping Hu, Xiaolong Ma, Yongjie Wang, Jiazhuang Zhu, Chunlin Zhang

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Abstract: Hypoxia and dedifferentiation of osteosarcoma (OS) cells leads to poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated signaling pathways. We performed a sphere formation assay and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the expression relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and the effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS metastasis. Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A promoted the expression of PDGFRB, subsequently activated ras homolog family member A (RhoA), and increased the phosphorylation of myosin light chain (MLC). PDGFRB also enhanced the phosphorylation of focal adhesion kinase (FAK). The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB also promoted cell dedifferentiation and had a significant impact on the metastasis of OS cells both in vitro and in vivo. Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton by activating RhoA and subsequently phosphorylating MLC, thereby promoting OS dedifferentiation and pulmonary metastasis.

Keywords: osteosarcoma, dedifferentiation, metastasis, cytoskeleton rearrangement, PDGFRB, hypoxia

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Authors: G. Wojcik, J. Gindlhuber, A. Syarif, K. Hoetzenecker, P. Bohm, P. Vesely, V. Biasin, G. Kwapiszewska

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Pulmonary fibrosis is a rare disease where uncontrolled wound healing processes damage the lung structure. Intensive changes within the extracellular matrix (ECM) and its interaction with fibroblasts have a major role in pulmonary fibrosis development. Among others, collagen is one of the main components of the ECM, and it is important for lung structure. In IPF, constant production of collagen by fibroblast, through TGFβ1-SMAD2/3 pathways, leads to an uncontrolled deposition of matrix and hence lung remodeling. Abnormal changes in lipid production, alterations in fatty acids (FAs) metabolism, enhanced oxidative stress, and lipid peroxidation in fibrotic lung and fibrotic fibroblasts have been reported; however, the interplay between the collagen and lipids is not yet established. One of the FAs influx regulators is Angiopoietin-like 4 (ANGPTL4), which inhibits lipoprotein lipase work, decreasing the availability of FAs. We hypothesized that altered lipid composition or availability could have the capability to influence the phenotype of different fibroblast populations in the lung and hence influence lung fibrosis. To prove our hypothesis, we aim to investigate lipids and their influence on human, animal, and in vitro levels. In the bleomycin model, treatment with the well-known metabolic drugs Rosiglitazone or Metformin significantly lower collagen production. Similar results were noticed in ANGPTL4 KO animals, where the KO of ANGPTL4 leads to an increase of FAs availability and lower collagen deposition after the bleomycin challenge. Currently, we study the treatment of different FAs on human lung para fibroblasts (hPF) isolated from donors. To understand the lipid composition, we are collecting human lung tissue from donors and pulmonary fibrosis patients for Liquid chromatography-mass spectrometry. In conclusion, our results suggest the lipid influence on collagen deposition during lung fibrosis, but further research needs to be conducted to understand the matter of this relationship.

Keywords: collagen, fibroblasts, lipidomics, lung, pulmonary fibrosis

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Authors: Elham Shakerian, Reza Afarin

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The hepatic disease causes approximately 2 million deaths/year worldwide. Liver fibrosis is the last stage of numerous chronic liver diseases, and until now there is no definite cure or drug for it. Activation of hepatic stellate cells (HSCs) is the main reason for fibrosis. Transforming growth factor (TGF-β), as a main profibrogenic cytokine, if increased in these cells, leads to liver fibrosis through smad3 signaling pathways and increasing the expressions of Collagen type I and III, and actin-alpha smooth muscle (αSMA) genes. Curcumin (CUR) is a polyphenolic compound and an active ingredient derived from the rhizome of the turmeric plant that exerts effective antioxidant, anti-inflammatory, and antimicrobial activity. It has been shown that daily consumption of curcumin may have a protective effect on the liver against oxidative stress associated with alcohol consumption. In this study, we investigate the role of Curcumin in decreasing HSC activation and treating liver fibrosis. First, the human HSCs were treated with 2 ng/ml of (TGF-β) for 24 hours to become activated, then with Silibinin for 24 hours. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR, and western blot were performed. The mRNA expression levels of Collagen type I and III, αSMA genes, and the level of smad3 phosphorylation in TGF-β activated human HSCs treated with Curcumin were significantly reduced compared to human HSCs untreated with Curcumin. Curcumin is effective in reducing the expression of fibrogenic genes in the activated human HSCs treated with TGFB through downregulation of the TGF-β/smad3 signaling pathway. Therefore, Curcumin possesses significant antifibrotic properties in hepatic fibrosis

Keywords: hepatic fibrosis, human HSCs, curcumin, fibrogenic genes

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Authors: Farhood Rismanchian, Seong Hyeon Park, Young Hoon Lee

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This paper proposes a method to optimize the layout of an emergency department (ED) based on real executions of care processes by considering several planning objectives simultaneously. Recently, demand for healthcare services has been dramatically increased. As the demand for healthcare services increases, so do the need for new healthcare buildings as well as the need for redesign and renovating existing ones. The importance of implementation of a standard set of engineering facilities planning and design techniques has been already proved in both manufacturing and service industry with many significant functional efficiencies. However, high complexity of care processes remains a major challenge to apply these methods in healthcare environments. Process mining techniques applied in this study to tackle the problem of complexity and to enhance care process analysis. Process related information such as clinical pathways extracted from the information system of an ED. A 0-1 goal programming approach is then proposed to find a single layout that simultaneously satisfies several goals. The proposed model solved by optimization software CPLEX 12. The solution reached using the proposed method has 42.2% improvement in terms of walking distance of normal patients and 47.6% improvement in walking distance of critical patients at minimum cost of relocation. It has been observed that lots of patients must unnecessarily walk long distances during their visit to the emergency department because of an inefficient design. A carefully designed layout can significantly decrease patient walking distance and related complications.

Keywords: healthcare operation management, goal programming, facility layout problem, process mining, clinical processes

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Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam

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Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.

Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide

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Authors: Jin Young Kim, Kwon Kyoo Kang

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The SGR1 (STAYGREEN1) protein is a critical regulator of plant leaves in chlorophyll degradation and senescence. The functions and mechanisms of tomato SGR1 action are poorly understood and worthy of further investigation. To investigate the function of the SGR1 gene, we generated a SGR1-knockout (KO) null line via clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene editing and conducted RNA sequencing and gas chromatography tandem mass spectrometry (GC-MS/MS) analysis to identify the differentially expressed genes. The SlSGR1 (Solanum lycopersicum SGR1) knockout null line clearly showed a turbid brown color with significantly higher chlorophyll and carotenoid content compared to wild-type (WT) fruit. Differential gene expression analysis revealed 728 differentially expressed genes (DEGs) between WT and sgr1 #1-6 line, including 263 and 465 downregulated and upregulated genes, respectively, for which fold change was >2, and the adjusted p-value was <0.05. Most of the DEGs were related to photosynthesis and chloroplast function. In addition, the pigment, carotenoid changes in sgr1 #1-6 line was accumulated of key primary metabolites such as sucrose and its derivatives (fructose, galactinol, raffinose), glycolytic intermediates (glucose, G6P, Fru6P) and tricarboxylic acid cycle (TCA) intermediates (malate and fumarate). Taken together, the transcriptome and metabolite profiles of SGR1-KO lines presented here provide evidence for the mechanisms underlying the effects of SGR1 and molecular pathways involved in chlorophyll degradation and carotenoid biosynthesis.

Keywords: tomato, CRISPR/Cas9, null line, RNA-sequencing, metabolite profiling

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Authors: Kadeejah Alsolami, Zainab Alrefay, Husaam Awad

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Obesity and vitamin D deficiency have both been related to cardiovascular disease. The present work aimed to investigate the possible protective effect of vitamin D on cardiac apoptosis in a rat model of dietary-induced obesity. Methods: 30 male Wistar rats included in this study. They were allocated into 4 groups: Control (n=5), animal were fed standard diet for 3 months: Control + vitamin D (VD) (n=5),animals were fed a standard diet with 400IU VD/kg for 3 months: hypercaloric diets group (n=10), animals were fed a high fat diet for 3 months: hypercaloric diet with VD group (n=10), animals were fed a high fat diet with 400IU VD/kg for 3 months. At the beginning of the experiment, the weight and length were measured to assess body mass index (BMI) and repeated every 45 days. Food intake and body weight were monitored throughout the study period. Then rats were sacrificed and heart tissues collected for Quantitative Real-time polymerase chain reaction (qRT-PCR). qRT-PCR used to detect different genetic markers of apoptosis (anti-apoptotic gene (BCL2), a pro-apoptotic gene(BAX), pro-apoptotic genes (FAS, FAS-L), tumour necrosis factor (TNF), mitogen-activated protein kinases (MAPK). Results: FAS and FAS-L gene expression were significantly upregulated in rats fed with high fat diet. And FAS-L gene expression was significantly upregulated in all groups on comparison with control. Whereas Bax gene expression was significantly downregulated in rats fed with high-fat diet supplied with vitamin D. TNF was significantly upregulated in rats fed with high-fat diet treated with vitamin D. MAPK was significantly upregulated in rats fed with high fat diet group, and in rats fed with high-fat diet supplied with vitamin D. Conclusion: The cardiac apoptotic pathways were more activated in rats fed with high-fat than lean rats. And vitamin D protect the heart from the cardiac mitochondrial-dependent apoptotic pathway.

Keywords: apoptosis, heart, obesity, Vitamin D

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Authors: Yaping Gao

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With the increasing globalization of education and the continued momentum and wider adoption of online and digital learning all over the world, post pandemic, how could best practices and extensive experience gained from the higher education community over the past few decades be adopted and adapted to benefit international communities, which can be vastly different culturally and pedagogically? How can schools and institutions adopt, adapt and apply these proven practices to develop strategic plans for digital transformation at institutional levels, and to improve or create quality online or digital learning environments at course and program levels to help all students succeed? The presenter will introduce the primary components of the US-based quality assurance process, including : 1) five sets of research-supported standards to guide the design, development and review of online and hybrid courses; 2) professional development offerings and pathways for administrators, faculty and instructional support staff; 3) a peer-review process for course/program reviews resulting in constructive recommendations for continuous improvement, certification of quality and international recognition; and 4) implementation of the quality assurance process on a continuum to program excellence, achievement of institutional goals, and facilitation of accreditation process and success. Regardless language, culture, pedagogical practices, or technological infrastructure, the core elements of quality teaching and learning remain the same across all delivery formats. What is unique is how to ensure quality of teaching and learning in online education and digital learning. No one knows all the answers to everything but no one needs to reinvent the wheel either. Together the international education community can support and learn from each other to achieve institutional goals and ensure all students succeed in the digital learning environments.

Keywords: Online Education, Digital Learning, Quality Assurance, Standards and Best Practices

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Authors: Ximena Calle, Plinio Cantero-López, Felipe Muñoz-Córdova, Mayarling-Francisca Troncoso, Sergio Lavandero, Valentina Parra

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MUL1, a mitochondrial E3 ubiquitin ligase anchored to the outer mitochondrial membrane, is highly expressed in the heart. MUL1 is involved in multiple biological pathways associated with mitochondrial dynamics. Increased MUL1 affects the balance between fission and fusion, affecting mitochondrial function, which plays a crucial role in myocardial function. Therefore, it is interesting to evaluate the effect of cardiac-specific overexpression of MUL1 on myocardial function. Aim: To determine heart functionality in a mouse model with cardio-specific overexpression MUL1 protein. Methods and Results: Male C57BL/Tg transgenic mice with cardiomyocyte-specific overexpression of MUL1 (n=10) and control (n=4) were evaluated at 12, 27, and 35 weeks of age. Glucose tolerance curve determination was performed after a 6-hours fast to assess metabolic capacity, treadmill test, and systolic, and diastolic pressure was evaluated by the mouse tail-cuff blood pressure system equipment. The result showed no glucose tolerance curve, and the treadmill test demonstrated no significant changes between groups. However, substantial changes in diastolic function were observed by ultrasound and determination of cardiac hypertrophy proteins by western blot. Conclusions: Cardio-specific overexpression of MUL1 in mice without any treatment affects diastolic cardiac function, thus showing the important role contributed by MUL1 in the heart. Future research should evaluate the effect of cardiomyocyte-specific overexpression of MUL1 in pathological conditions such as a high-fat diet is one of the main risk factors for cardiovascular disease.

Keywords: diastolic dysfunction, hypertrophy cardiac, mitochondrial E3 ubiquitin ligase 1, MUL1

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Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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Authors: Max Butler

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Melanoma accounts for 80% of skin cancer-related deaths globally. The poor prognosis and increasing incidence of melanoma impose a significant burden on global healthcare systems. Early detection, precise diagnosis, and preventative strategies are critical to improving patient outcomes. Dermoscopy is the gold standard for specialist assessments of pigmented skin lesions, as it can differentiate between benign and malignant growths with greater accuracy than visual inspection. In the United Kingdom, guidelines from the National Institute of Clinical Excellence (NICE) state dermoscopy should be used in all specialist assessments of pigmented skin lesions. Compliance with this guideline is low, resulting in missed and delayed melanoma diagnoses. To address this problem, a quality improvement project was initiated at Buckinghamshire Healthcare Trust (BHT) within the plastic surgery department. The target group was a trainee and consultant plastic surgeons conducting outpatient skin cancer clinics. Analysis of clinic documentation over a one-month period found that only 62% (38/61) of patients referred with pigmented skin lesions were examined using dermoscopy. To increase dermoscopy rates, teaching was delivered to the department highlighting national guidelines and the evidence base for dermoscopic examination. In addition, clinic paperwork was redesigned to include a text box for dermoscopic examination. Reauditing after the intervention found a significant increase in dermoscopy rates (52/61, p = 0.014). In conclusion, implementing a quality improvement project with targeted teaching and documentation template templates successfully increased dermoscopy rates. This is a promising step toward improving early melanoma detection and patient outcomes.

Keywords: melanoma, dermoscopy, plastic surgery, quality improvement

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Authors: Qinghua Xing, Xinyi Tao, Haisheng Wang, Baisuo Zhao

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The first true anaerobic, halophilic alkali thermophile, Natranaerobius thermophilus DSM 18059T, serves as a valuable model for studying cellular adaptations to saline, alkaline and thermal extremes. To uncover the adaptive strategies employed by N. thermophilus in coping with these challenges, we conducted a comprehensive iTRAQ-based quantitative proteomic analysis under different conditions of salinity (3.5 M vs. 2.5 M Na+), pH (pH 9.6 vs. pH 8.6), and temperature (52°C vs. 42°C). The increased intracellular accumulation of glycine betaine, through both synthesis and transport, plays a critical role in N. thermophilus' adaptation to these combined stresses. Under all three stress conditions, the up-regulation of Trk family proteins responsible for K+ transport is observed. Intracellular K+ concentration rises in response to salt and pH levels. Multiple types of Na+/H+ antiporter (NhaC family, Mrp family and CPA family) and a diverse range of FOF1-ATP synthase are identified as vital components for maintaining ionic balance under different stress conditions. Importantly, proteins involved in amino acid metabolism, carbohydrate metabolism, ABC transporters, signaling and chemotaxis, as well as biological macromolecule repair and protection, exhibited significant up-regulation in response to these extreme conditions. These metabolic pathways emerge as critical factors in N. thermophilus' adaptation mechanisms under extreme environmental stress. To validate the proteomic data, ddPCR analysis confirmed changes in mRNA expression, thereby corroborating the up-regulation and down-regulation patterns of 19 co-up-regulated and 36 key proteins under saline, alkaline and thermal stresses. This research enriches our understanding of the complex regulatory systems that enable polyextremophiles to survive in combined extreme conditions.

Keywords: polyextremophiles, natranaerobius thermophilus, saline- alkaline- thermal stresses, combined extremes

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Authors: Ali Mohammed Yimer, Ayalew H. Assen, Youssef Belmabkhout

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This study delves into sustainable approaches for valorizing phosphatic wastes, specifically phosphate mining wastes and phosphogypsum, which are byproducts of phosphate industries and pose significant environmental challenges due to their accumulation. We propose a unified strategic synthesis method aimed at converting these wastes into hetero-functional porous materials. Our approach involves isolating the primary components of phosphatic wastes, such as CaO, SiO2 and Al2O3 to fabricate functional porous materials falling into two distinct classes. Firstly, alumina and silica components are extracted or isolated to produce zeolites (including CAN, GIS, SOD, FAU, and LTA), characterized by a Si/Al ratio of less than 5. Secondly, residual calcium is utilized to synthesize calcium-based metal–organic frameworks (Ca-MOFs) employing various organic linkers like Ca-BDC, Ca-BTC and Ca-TCPB (SBMOF-2), thereby providing flexibility in material design. Characterization techniques including XRD, SEM-EDX, FTIR, and TGA-MS affirm successful material assembly, while sorption analyses using N2, CO2, and H2O demonstrate the porosity of the materials. Particularly noteworthy is the water/alcohol separation potential exhibited by the Ca-BTC MOF, owing to its optimal pore aperture size (∼3.4 Å). To enhance replicability and scalability, detailed protocols for each synthesis step and specific conditions for each process are provided, ensuring that the methodology can be easily reproduced and scaled up for industrial applications. This synthetic transformation approach represents a valorization route for converting phosphatic wastes into extended porous structures, promising significant environmental and economic benefits.

Keywords: calcium-based metal-organic frameworks, low-silica zeolites, porous materials, sustainable synthesis, valorization

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Authors: C. Panebianco, K. Adamberg, S. Adamberg, C. Saracino, M. Jaagura, K. Kolk, A. Di Chio, P. Graziano, R. Vilu, V. Pazienza

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Background/Aims: Despite recent advances in treatment options, a modest impact on the outcome of the pancreatic cancer (PC) is observed so far. Short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. However, diseased people may refuse to follow the fasting regimen and fasting may worsen the weight loss often occurring in cancer patients. Therefore, alternative approaches are needed. The aim of this study was to assess the effect of Engineered Low glycemic food ELGIF mimicking diet on growth of cancer cell lines in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in control and ELGIF mimicking diet culturing condition to evaluate the tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to ELGIF to assess the tumor volume and weight as compared to mice fed with control diet. Results: Pancreatic cancer cells cultured in ELGIF mimicking medium showed decreased levels of proliferation as compared to those cultured in the standard medium. Consistently, xenograft pancreatic cancer mice subjected to ELGIF diet displayed a significant decrease in tumor growth. Conclusion: A positive effect of ELGIF diet on proliferation in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

Keywords: functional food, microbiota, mouse model, pancreatic cancer

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Authors: Eleni Akritopoulou, Katerina Topouzoglou

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The last 20 years marine debris has been identified as one of the main marine pollution sources caused by anthropogenic activities. Plastics has reached the farthest marine areas of the planet affecting all marine trophic levels including the, recently discovered, amphipoda Eurythenes plasticus inhabiting Mariana Trench to large cetaceans, marine reptiles and sea birds causing immunodeficiency disorders, deteriorating health and death overtime. For the time period 2016-20, in the framework of the national initiative ‘Keep Aegean Blue”, All for Blue team has been collecting marine debris (coastline and underwater) following a modified in situ MEDSEALITTER monitoring protocol from eight Greek islands. After collection, marine debris was weighted, sorted and categorised according to material; plastic (PL), glass (G), metal (M), wood (W), rubber (R), cloth (CL), paper (P), mixed (MX). The goal of the project included the documentation of marine debris sources, human trends, waste management and public marine environmental awareness. Waste management was focused on plastics recycling and utilisation into daily useful products. This research is focused on the island of Mykonos due to its continuous touristic activity and lack of scientific information. In overall, a field work area of 1.832.856 m2 was cleaned up yielding 5092 kg of marine debris. The preliminary results indicated PL as main source of marine debris (62,8%) followed by M (15,5%), GL (13,2%) and MX (2,8%). Main items found were fishing tools (lines, nets), disposable cutlery, cups and straws, cigarette butts, flip flops and other items like plastic boat compartments. In collaboration with a local company for plastic management and the Circular Economy and Eco Innovation Institute (Sweden), all plastic debris was recycled. Granulation process was applied transforming plastic into building materials used for refugees’ houses, litter bins bought by municipalities and schools and, other items like shower components. In terms of volunteering and attendance in public awareness seminars, there was a raise of interest by 63% from different age ranges and professions. Regardless, the research being fairly new for Mykonos island and logistics issues potentially affected systemic sampling, it appeared that plastic debris is the main littering source attributed, possibly to the intense touristic activity of the island all year around. However, marine environmental awareness activities were pointed out to be an effective tool in forming public perception against marine debris and, alter the daily habits of local society. Since the beginning of this project, three new local environmental teams were formed against marine pollution supported by the local authorities and stakeholders. The continuous need and request for the production of items made by recycled marine debris appeared to be beneficial socio-economically to the local community and actions are taken to expand the project nationally. Finally, as an ongoing project and whilst, new scientific information is collected, further funding and research is needed.

Keywords: Greece, marine debris, marine environmental awareness, Mykonos island, plastics debris, plastic granulation, recycled plastic, tourism, waste management

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Authors: Kai-Yao Huang, Tzong-Yi Lee, Pin-Hao Ho, Tzu-Hao Chang, Cheng-Wei Chang

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Background: Human cytomegalovirus (HCMV) infects much people around the world, and there were many researches mention that many diseases were caused by HCMV. To understand the mechanism of HCMV lead to diseases during infection. We observe a microRNA (miRNA) – miRNA interaction between HCMV and host during infection. We found HCMV miRNA sequence component complementary with host miRNA precursors, and we also found that the host miRNA abundances were decrease in HCMV infection. Hence, we focus on the host miRNA which may target by the other HCMV miRNA to find theirs target mRNAs expression and analysis these mRNAs affect what kind of signaling pathway. Interestingly, we found the affected mRNA play an important role in some diseases related pathways, and these diseases had been annotated by HCMV infection. Results: From our analysis procedure, we found 464 human miRNAs might be targeted by 26 HCMV miRNAs and there were 291 human miRNAs shows the concordant decrease trend during HCMV infection. For case study, we found hcmv-miR-US22-5p may regulate hsa-mir-877 and we analysis the KEGG pathway which built by hsa-mir-877 validate target mRNA. Additionally, through survey KEGG Disease database found that these mRNA co-regulate some disease related pathway for instance cancer, nerve disease. However, there were studies annotated that HCMV infection casuse cancer and Alzheimer. Conclusions: This work supply a different scenario of miRNA target interactions(MTIs). In previous study assume miRNA only target to other mRNA. Here we wonder there is possibility that miRNAs might regulate non-mRNA targets, like other miRNAs. In this study, we not only consider the sequence similarity with HCMV miRNAs and human miRNA precursors but also the expression trend of these miRNAs. Then we analysis the human miRNAs validate target mRNAs and its associated KEGG pathway. Finally, we survey related works to validate our investigation.

Keywords: human cytomegalovirus, HCMV, microRNA, miRNA

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Authors: Jan Luxa, Vlastimil Mazanek, Petr Malinsky, Alexander Romanenko, Mariapompea Cutroneo, Vladimir Havranek, Josef Novak, Eva Stepanovska, Anna Mackova, Zdenek Sofer

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Using accelerated energetic ions is an interesting method for the introduction of structural changes in various carbon-based materials. This way, the properties can be altered in two ways: a) the ions lead to the formation of conductive pathways in graphene oxide structures due to the elimination of oxygen functionalities and b) doping with selected ions to form metal nanoclusters, thus increasing the conductivity. In this work, energetic beams were employed in two ways to prepare capacitor structures in graphene oxide (GO), reduced graphene oxide (rGO) and polyimide (PI) on a micro-scale. The first method revolved around using ion beam writing with a focused ion beam, and the method involved ion implantation via a polymeric mask. To prepare the polymeric mask, a direct spin-coating of PMMA on top of the foils was used. Subsequently, proton beam writing and development in isopropyl alcohol were employed. Finally, the mask was removed using acetone solvent. All three materials were exposed to ion beams with an energy of 2.5-5 MeV and an ion fluence of 3.75x10¹⁴ cm-² (1800 nC.mm-²). Thus, prepared microstructures were thoroughly characterized by various analytical methods, including Scanning electron microscopy (SEM) with Energy-Dispersive X-ray spectroscopy (EDS), X-ray Photoelectron spectroscopy (XPS), micro-Raman spectroscopy, Rutherford Back-scattering Spectroscopy (RBS) and Elastic Recoil Detection Analysis (ERDA) spectroscopy. Finally, these materials were employed and tested as sensors for humidity using electrical conductivity measurements. The results clearly demonstrate that the type of ions, their energy and fluence all have a significant influence on the sensory properties of thus prepared sensors.

Keywords: graphene, graphene oxide, polyimide, ion implantation, sensors

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Authors: Hadeer Ibrahiem, Mahmoud Nasr, Masarrat M. M. Migahid, Mohamed A. Ghazy

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The release of textile wastewater loaded with 1,4 dioxane into aquatic ecosystems has been associated with various human health risks and adverse environmental impacts. In parallel, phytoremediation has been recently employed to treat highly polluted wastewater because various plant species tend to produce certain enzymes as a defense mechanism against a toxic environment. To our best knowledge, this study is the first to investigate the ability of phytoremediation using Eichhornia crassipes for the removal of various pollutants, including 1,4 dioxane, from textile wastewater. A phytoremediation system composed of Eichhornia crassipes was acclimatized for 10 d, and then operated in four lab-scale hydroponic systems, viz., negative control, positive control, and two different 1,4 dioxane concentration (400 and 500 mg/L). After 11 d of operation, the phytoremediation system achieved removal efficiencies of 67.5±3.4%, 89.4±4.4%, 83.6±3.8% for 1,4 dioxane (at initial concentration 400 mg/L), chemical oxygen demand (COD) (at initial concentration 679 mg/L), and cumulative heavy metals, respectively. The removal of these pollutants was mainly supported by the phyto-sorption and phytodegradation mechanisms. The economic feasibility of this phytoremediation system was validated by estimating the capital and operating costs, requiring 4.6 USD for the treatment of 1 m3 textile wastewater. The study concluded that the phytoremediation process could be used as a practical and economical approach to treat textile wastewater laden with various organic and inorganic pollutants. Due to the observed pollution reduction and human health protection, the study objectives would fulfill the targets of SDG 3 “Good Health and Well-being” and SDG 6 “Clean Water and Sanitation”. Further studies are required to (i) investigate the ability of plant species to withstand higher concentrations of 1,4 dioxane for an extended operation time and (ii) understand the biochemical pathways for the degradation of 1,4 dioxane via the action of plant enzymes and the associated microbial community.

Keywords: 1, 4 dioxane concentrations, hydrophytes, Eichhornia crassipes, phytoremediation effectiveness, SDGs, textile industrial effluent

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Authors: Ja'afar Umar, Salisu Naziru

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Submergence stress in plants refers to the physiological and biochemical challenges that occur when plants are partially or fully submerged in water. This type of stress primarily affects plants in flood-prone areas or regions with heavy rainfall, where oxygen availability and other essential resources are limited. Salicylic acid (SA) is an important plant hormone involved in various physiological processes and responses to environmental stress, particularly in plant defense mechanisms against pathogens. Its role as a signaling molecule in plants is crucial for activating defense pathways, regulating growth, and managing responses to biotic (living) and abiotic (non-living) stresses. The study involved using salicylic acid (SA) at concentrations of 1g/L, 2g/L, and 3g/L, dissolved in water, to treat rice plants during submergence stress. The experiment had four treatments: 0g/L (control), 1g/L, 2g/L, and 3g/L of SA, each with four replications. Rice seedlings were submerged in water for 11 days and then desubmerged for 7 days. During the experiment, all plants except the control received a foliar spray of SA solutions, while control plants were sprayed with distilled water. The results indicate a significant difference (P<0.05) between the control and salicylic acid (SA)-treated rice plants. SalicyJalic acid, particularly at concentrations of 1g/L, 2g/L, and 3g/L, generally improved the recovery of all four rice cultivars from submergence stress, as reflected by increased numbers of nodes, longer internodes, taller plants, and longer root lengths compared to untreated controls. Salicylic acid, particularly at concentrations of 1g/L, 2g/L, and 3g/L, generally improved the recovery of all four rice cultivars from submergence stress, as reflected by increased numbers of nodes, longer internodes, taller plants, and longer root lengths compared to untreated controls.

Keywords: submergence, stress, rice, salicylic

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Authors: Joanna Fidelus-Orzechowska, Dominika Wronska-Walach, Jaroslaw Cebulski

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Mountain areas are very often exposed to numerous transformations connected with the development of tourist infrastructure. In mountain areas in Poland ski tourism is very popular, so agricultural areas are often transformed into tourist areas. The construction of new ski runs can change the direction and rate of slope development. The main aim of this research was to determine geomorphological and hydrological changes within slopes caused by ski run constructions. The study was conducted in the Remiaszów catchment in the Inner Polish Carpathians (southern Poland). The mean elevation of the catchment is 859 m a.s.l. and the maximum is 946 m a.s.l. The surface area of the catchment is 1.16 km2, of which 16.8% is the area of the two studied ski runs. The studied ski runs were constructed in 2014 and 2015. In order to determine the relief transformations connected with new ski run construction high resolution LIDAR data was analyzed. The general relief changes in the studied catchment were determined on the basis of ALS (Airborne Laser Scanning ) data obtained before (2013) and after (2016) ski run construction. Based on the two sets of ALS data a digital elevation models of differences (DoDs) was created, which made it possible to determine the quantitative relief changes in the entire studied catchment. Additionally, cross and longitudinal profiles were calculated within slopes where new ski runs were built. Detailed data on relief changes within selected test surfaces was obtained based on TLS (Terrestrial Laser Scanning). Hydrological changes within the analyzed catchment were determined based on the convergence and divergence index. The study shows that the construction of the new ski runs caused significant geomorphological and hydrological changes in the entire studied catchment. However, the most important changes were identified within the ski slopes. After the construction of ski runs the entire catchment area lowered about 0.02 m. Hydrological changes in the studied catchment mainly led to the interruption of surface runoff pathways and changes in runoff direction and geometry.

Keywords: hydrological changes, mountain areas, relief transformations, ski run construction

Procedia PDF Downloads 143

Authors: Azadeh Yasari, Michael Ganzle, Stephen Strelkov, Nuanyi Liang, Jonathan Curtis, Nat N. V. Kav

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Pathogenic fungi cause significant yield losses and quality reductions to major crops including wheat, canola, and barley. Toxic metabolites produced by phytopathogenic fungi also pose significant risks to animal and human health. Extensive application of synthetic fungicides is not a sustainable solution since it poses risks to human, animal and environmental health. Unsaturated fatty acids may provide an environmentally friendly alternative because of their direct antifungal activity against phytopathogens as well as through the stimulation of plant defense pathways. The present study assessed the in vitro and in vivo efficacy of two hydroxy fatty acids, coriolic acid and ricinoleic acid, against the phytopathogens Fusarium graminearum, Pyrenophora tritici-repentis, Pyrenophora teres f. teres, Sclerotinia sclerotiorum, and Leptosphaeria maculans. Antifungal activity of coriolic acid and ricinoleic acid was evaluated using broth micro-dilution method to determine the minimum inhibitory concentration (MIC). Results indicated that both ricinoleic acid and coriolic acid showed antifungal activity against phytopathogens, with the strongest inhibitory activity against L. maculans, but the MIC varied greatly between species. An antifungal effect was observed for coriolic acid in vivo against pathogenic fungi of wheat and barley. This effect was not correlated to the in vitro activity because ricinoleic acid with equivalent in vitro antifungal activity showed no protective effect in vivo. Moreover, neither coriolic acid nor ricinoleic acid controlled fungal pathogens of canola. In conclusion, coriolic acid inhibits some phytopathogens in vivo and may have the potential to be an effective crop protection agent.

Keywords: coriolic acid, minimum inhibitory concentration, pathogenic fungi, ricinoleic acid

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Authors: Irshad Ali Khan, Jian-Ping Lu, Xiao-Hong Liu, Fu-Cheng Lin

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This study reports the functional analysis of a gene MoNUC1 in M. oryzae, which is homologous to the Saccharomyces cerevisiae NUC1 encoding a mitochondrial nuclease protein. The MoNUC1 having a gene locus MGG_05324 is 1002-bp in length and encodes an identical protein of 333 amino acids. We disrupted the gene through gene disruption strategy and isolated two mutants confirmed by southern blotting. The deleted mutants were then used for phenotypic studies and their phenotypes were compared to those of the Guy-11 strain. The mutants were first grown on CM medium to find the effect of MoNUC1 gene disruption on colony growth and the mutants were found to show normal culture colony growth similar to that of the Guy-11 strain. Conidial germination and appressorial formation were also similar in both the mutants and Guy-11 strains showing that this gene plays no significant role in these phenotypes. For pathogenicity, the mutants and Guy-11 mycelium blocks were inoculated on blast susceptible barley seedlings and it was found that both the strains exhibited full pathogenicity showing coalesced and necrotic blast lesions suggesting that this gene is not involved in pathogenicity. Mating of the mutants with 2539 strain formed numerous perithecia showing that MoNUC1 is not essential for sexual reproduction in M. oryzae. However, the mutants were found to form reduced conidia (1.06±8.03B and 1.08±9.80B) than those of the Guy-11 strain (1.46±10.61A) and we conclude that this protein is not required for the blast fungus to cause pathogenicity but plays significant role in conidiation. Proteins of signal transduction pathways that could be disrupted/ intervened genetically or chemically could lead to antifungal products of important fungal cereal diseases and reduce rice yield losses. Tipping the balance toward understanding the whole of pathogenesis, rather than simply conidiation will take some time, but clearly presents the most exciting challenge of all.

Keywords: appressorium formation, conidiation, NUC1, Magnaporthe oryzae, pathogenicity

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Authors: Liong-Rung Liu, Yu-Hui Chiu, Wen-Han Chang

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Firearm injuries are high-energy injuries. The ballistic pathways could cause severe burns or chemical damages to vessels, musculoskeletal or other major organs. The high mortality rate is accompanied by complications such as sepsis. As laws prohibit gun possession, civilian gunshot wounds (GSW) are relatively rare in Taiwan. Our hospital, Mackay Memorial Hospital, located at the center of Taipei city is surrounded by nightclubs and red-light districts. Due to this unique location, our hospital becomes the first-line trauma center managing gunshot victims in Taiwan. To author’s best knowledge, there are few published research articles regarding this unique situation. We hereby analyze the distinct characteristics and length of stay (LOS) of GSW patients in the emergency room (ER) at Mackay Memorial Hospital. A 6-year retrospective analysis of 27 patients treated for GSW injuries from January 2012 to December 2017 was performed. The patients’ records were reviewed for the following analyses, 1) wound position and the correlated clinical presentations; 2) the LOS in ED of patients receiving emergency surgery for major organ or vascular injuries. We found males (96.3%) were injured by guns more often than females (3.7%) in all age groups. The most common injured site was in the extremities. With regards to the ER LOS, the average time were 72.2 ± 34.5 minutes for patients with triage I and 207.4 ± 143.9 minutes for patients with triage II. The ED LOS of patients whose ISS score were more than 15 was 59.9 ± 25.6 minutes, and 179.4 ± 119.8 minutes for patients whose ISS score were between 9 to 15, respectively. Among these 27 patients, 10 patients had emergency surgery and their average ED stay time was 104.5 ± 33.3 minutes. Even more, the average ED stay time could be shortened to 88.8 ± 32.3 minutes in the 5 patients with trauma team activation. In conclusion, trauma team activation in severe GSW patients indeed shortens the ED LOS and might initially improve the quality of patient care. This is the result of better trauma systems, including advances in care from emergency medical services and acute care surgical management.

Keywords: gunshot, length of stay, trauma, mortality

Procedia PDF Downloads 131

Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

Procedia PDF Downloads 104

Authors: Chinyere Ori Elom, Ikechukwu Ogeze Ukeje, Chukwudum Collins Umoke

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This paper aims to stimulate scholarly interest in AI, ICT and the existing (complex) systems trajectory- theory, practice, and aspirations within the African continent and to shed fresh light on the shortcomings of the higher education sector (HEs) through the prism of AI-driven Solutions for enhancing Guidance and Counseling and sound governance framework (SGF) in higher education modeling. It further seeks to investigate existing prospects yet to be realized in Nigerian universities by probing innovation neglect in the localities, exploring practices in the global ICT spaces neglected by Nigeria universities’ governance regimes (UGRs), and suggesting area applicability, sustainability and solution modeling in response to peculiar ‘wicked ICT-driven problems’ and or issues facing the continent as well as other universities in emerging societies. This study will adopt a mixed-method approach to collect both qualitative and quantitative data. This paper argues that it will command great relevance in the local and global university system by developing ICT relevance sustainability policy initiatives (SPIs) powered by a multi-stakeholder engagement governance model (MSEGm) that is sufficiently dynamic, eclectic and innovative to surmount complex and constantly rising challenges of the modern-developing world. Hence, it will consider diverse actors both as producers and users alike as victims and beneficiaries of common concerns in the ICT world; thereby providing pathways on how AI’s integration into education governance can significantly reduce counseling gaps, ensuring more students are attended to especially when human counselors are unavailable.

Keywords: AI-counseling solution, stakeholder engagement, university governance, higher education

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