Search results for: biosynthesis pathways

Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

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Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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Authors: Casta Guillaume, Robert Jagers, Deborah Rivas-Drake

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Civically engaged youth are critical to maintaining and/or improving the functioning of local, national and global communities and their institutions. The present study investigated how school climate and academic beliefs (academic self-efficacy and school belonging) may inform emergent civic behaviors (emergent citizenship) among self-identified middle school youth of color (African American, Multiracial or Mixed, Latino, Asian American or Pacific Islander, Native American, and other). Study aims: 1) Understand whether and how school climate is associated with civic engagement behaviors, directly and indirectly, by fostering a positive sense of connection to the school and/or engendering feelings of self-efficacy in the academic domain. Accordingly, we examined 2) The association of youths’ sense of school connection and academic self-efficacy with their personally responsible and participatory civic behaviors in school and community contexts—both concurrently and longitudinally. Data from two subsamples of a larger study of social/emotional development among middle school students were used for longitudinal and cross sectional analysis. The cross-sectional sample included 324 6th-8th grade students, of which 43% identified as African American, 20% identified as Multiracial or Mixed, 18% identified as Latino, 12% identified as Asian American or Pacific Islander, 6% identified as Other, and 1% identified as Native American. The age of the sample ranged from 11 – 15 (M = 12.33, SD = .97). For the longitudinal test of our mediation model, we drew on data from the 6th and 7th grade cohorts only (n =232); the ethnic and racial diversity of this longitudinal subsample was virtually identical to that of the cross-sectional sample. For both the cross-sectional and longitudinal analyses, full information maximum likelihood was used to deal with missing data. Fit indices were inspected to determine if they met the recommended thresholds of RMSEA below .05 and CFI and TLI values of at least .90. To determine if particular mediation pathways were significant, the bias-corrected bootstrap confidence intervals for each indirect pathway were inspected. Fit indices for the latent variable mediation model using the cross-sectional data suggest that the hypothesized model fit the observed data well (CFI = .93; TLI =. 92; RMSEA = .05, 90% CI = [.04, .06]). In the model, students’ perceptions of school climate were significantly and positively associated with greater feelings of school connectedness, which were in turn significantly and positively associated with civic engagement. In addition, school climate was significantly and positively associated with greater academic self-efficacy, but academic self-efficacy was not significantly associated with civic engagement. Tests of mediation indicated there was one significant indirect pathway between school climate and civic engagement behavior. There was an indirect association between school climate and civic engagement via its association with sense of school connectedness, indirect association estimate = .17 [95% CI: .08, .32]. The aforementioned indirect association via school connectedness accounted for 50% (.17/.34) of the total effect. Partial support was found for the prediction that students’ perceptions of a positive school climate are linked to civic engagement in part through their role in students’ sense of connection to school.

Keywords: civic engagement, early adolescence, school climate, school belonging, developmental niche

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Authors: Nicole Selvi Hill, Archchana Radhakrishnan

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Introduction: Traumatic brain injury (TBI) is a leading cause of mortality among trauma patients. In the management of TBI, the main principle is avoiding cerebral ischemia, as this is a strong determiner of neurological outcomes. The use of vasoactive drugs, such as vasopressin, has an important role in maintaining cerebral perfusion pressure to prevent secondary brain injury. Current guidelines do not suggest a preferred vasoactive drug to administer in the management of TBI, and there is a paucity of information on the therapeutic potential of vasopressin following TBI. Vasopressin is also an endogenous anti-diuretic hormone (AVP), and pathways mediated by AVP play a large role in the underlying pathological processes of TBI. This creates an overlap of discussion regarding the therapeutic potential of vasopressin following TBI. Currently, its popularity lies in vasodilatory and cardiogenic shock in the intensive care setting, with increasing support for its use in haemorrhagic and septic shock. Methodology: This is a review article based on a literature review. An electronic search was conducted via PubMed, Cochrane, EMBASE, and Google Scholar. The aim was to identify clinical studies looking at the therapeutic administration of vasopressin in severe traumatic brain injury. The primary aim was to look at the neurological outcome of patients. The secondary aim was to look at surrogate markers of cerebral perfusion measurements, such as cerebral perfusion pressure, cerebral oxygenation, and cerebral blood flow. Results: Eight papers were included in the final number. Three were animal studies; five were human studies, comprised of three case reports, one retrospective review of data, and one randomised control trial. All animal studies demonstrated the benefits of vasopressors in TBI management. One animal study showed the superiority of vasopressin in reducing intracranial pressure and increasing cerebral oxygenation over a catecholaminergic vasopressor, phenylephrine. All three human case reports were supportive of vasopressin as a rescue therapy in catecholaminergic-resistant hypotension. The retrospective review found vasopressin did not increase cerebral oedema in TBI patients compared to catecholaminergic vasopressors; and demonstrated a significant reduction in the requirements of hyperosmolar therapy in patients that received vasopressin. The randomised control trial results showed no significant differences in primary and secondary outcomes between TBI patients receiving vasopressin versus those receiving catecholaminergic vasopressors. Apart from the randomised control trial, the studies included are of low-level evidence. Conclusion: Studies favour vasopressin within certain parameters of cerebral function compared to control groups. However, the neurological outcomes of patient groups are not known, and animal study results are difficult to extrapolate to humans. It cannot be said with certainty whether vasopressin’s benefits stand above usage of other vasoactive drugs due to the weaknesses of the evidence. Further randomised control trials, which are larger, standardised, and rigorous, are required to improve knowledge in this field.

Keywords: catecholamines, cerebral perfusion pressure, traumatic brain injury, vasopressin, vasopressors

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Authors: Mara Aparecida De Castilho Lopes. Maria Eliza Mattosinho Bernardes

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The education of deaf individuals in Brazil is grounded in the bilingual approach, which presupposes Brazilian Sign Language (Libras) as the first language for these students. In this perspective, Portuguese should be taught as a second language in its written form, ensuring that deaf students also have access to various academic subjects in sign language. Brazilian legislation (Federal Decree No. 5626 of 2005) mandates the teaching of Brazilian Sign Language in university teacher training programs, but there is no pre-established minimum workload. As a result, there is a significant disparity in the teaching and quality of teacher education across the Brazilian territory. Added to this fact is the general lack of awareness within society regarding the linguistic status of Libras, leading to a shortage of competent teachers for its use and instruction, particularly in higher education. Recently, Federal Law No. 14191 of 2021 established bilingual education for the deaf as a mode of instruction, indicating the need for adjustments in teacher training within higher education teacher preparation programs. Given this context, the objective of the present study was to analyze the teaching proposals for Brazilian Sign Language for students in teacher training programs at public universities in Brazil, presenting alternatives to overcome the current models and academic pathways of teaching and learning. In addition to analyzing Brazilian teaching models, an analysis of a continuing education model for teachers in a French institution was also conducted - considering the historical Franco-Brazilian path of deaf education in Brazil. The analysis of the current teacher training model for deaf education in Brazil revealed that initial exposure to sign language and its linguistic structure is not sufficient to provide future teachers with opportunities to reflect on bilingual teaching methods and practices, as seen in other definitions of bilingualism - bilingual education for proficient listeners in two oral languages. As a result, a training proposal was developed for an experimental interdisciplinary course, integrating the curriculum of an initial and continuing teacher training program alongside the Alfredo Bossi Chair at the University of São Paulo. This proposal is structured into three disciplines, which constitute consecutive moments in teacher education: Fundamental Aspects of Brazilian Sign Language, Bilingual Teaching Methodology, and Teaching Investigation Project - interdisciplinary engagement in the field of deafness. The last offered discipline represents an interdisciplinary supervised internship proposal, considering the multi-professional context that constitutes deaf education within a bilingual approach. In interdisciplinary work within the field of deafness, dialogue between teachers and other professionals who work with deaf students from different perspectives - teachers, speech therapists, and sign language interpreters - is frequently necessary. Through alternative avenues, these actions aim to direct the linguistic development of deaf students within their learning processes. Based on the innovative curriculum proposal described here, the intention is to contribute to the enhancement of teacher education in Brazil, with the goal of ensuring bilingual education for deaf students.

Keywords: bilingual education, teacher training, historical-cultural approach, interdisciplinary education, inclusive education

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Authors: Andrés Quiroz, Emilio Hormazabal, Ana Mutis, Fernando Ortega, Manuel Chacón-Fuentes, Leonardo Parra

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Red clover (Trifolium pratense L.) is an important forage species in temperate regions of the world. The main limitation of this species worldwide is a lack of persistence related to the high mortality of plants due to a complex of biotic and abiotic factors, determining a life span of two or three seasons. Because of the importance of red clover in Chile, a red clover breeding program was started at INIA Carillanca Research Center in 1989, with the main objective of improving the survival of plants, forage yield, and persistence. The main selection criteria for selecting new varieties have been based on agronomical parameters and biotic factors. The main biotic factor associated with red clover mortality in Chile is Hylastinus obscurus (Coleoptera: Curculionidae). Both larval and adults feed on the roots, causing weakening and subsequent death of clover plants. Pesticides have not been successful for controlling infestations of this root borer. Therefore, alternative strategies for controlling this pest are a high priority for red clover producers. Currently, the role of semiochemical in the interaction between H. obscurus and red clover plants has been widely studied for our group. Specifically, from the red clover foliage has been identified limonene is eliciting repellency from the root borer. Limonene is generated in the plant from two independent biosynthetic pathways, the mevalonic acid, and deoxyxylulose pathway. Mevalonate pathway enzymes are localized in the cytosol, whereas the deoxyxylulose phosphate pathway enzymes are found in plastids. In summary, limonene can be determinated by enzymatic bioassay using GPP as substrate and by limonene synthase expression. Therefore, the main objective of this work was to study genetic variation of limonene in material provided by INIA´s Red Clover breeding program. Protein extraction was carried out homogenizing 250 mg of leave tissue and suspended in 6 mL of extraction buffer (PEG 1500, PVP-30, 20 mM MgCl2 and antioxidants) and stirred on ice for 20 min. After centrifugation, aliquots of 2.5 mL were desalted on PD-10 columns, resulting in a final volume of 3.5 mL. Protein determination was performed according to Bradford with BSA as a standard. Monoterpene synthase assays were performed with 50 µL of protein extracts transferred into gas-tight 2 mL crimp seal vials after addition of 4 µL MgCl₂ and 41 µL assay buffer. The assay was started by adding 5 µL of a GPP solution. The mixture was incubated for 30 min at 40 °C. Biosynthesized limonene was quantified in a GC equipped with a chiral column and using synthetic R and S-limonene standards. The enzymatic the production of R and S-limonene from different Superqueli-Carillanca genotypes is shown in this work. Preliminary results showed significant differences in limonene content among the genotypes analyzed. These results constitute an important base for selecting genotypes with a high content of this repellent monoterpene towards H. obscurus.

Keywords: head space, limonene enzymatic determination, red clover, Hylastinus obscurus

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Authors: Fernanda Bravo Cornejo, Camilo Cerda Sarabia, Belén Díaz Díaz, Diego Santibañez Oyarce, Esteban Gómez Terán, Hugo Osses Prado, Raúl Caulier-Cisterna, Jorge Vergara-Quezada, Ana Moya-Beltrán

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Streptococcus pyogenes is a gram-positive bacteria involved in a wide range of diseases and is a major-human-specific bacterial pathogen. In Chile, this year the 'Ministerio de Salud' declared an alert due to the increase in strains throughout the year. This increase can be attributed to the multitude of factors including antimicrobial resistance (AMR) and Virulence Factors (VF). Understanding these VF and AMR is crucial for developing effective strategies and improving public health responses. Moreover, experimental identification and characterization of these pathogenic mechanisms are labor-intensive and time-consuming. Therefore, new computational methods are required to provide robust techniques for accelerating this identification. Advances in Machine Learning (ML) algorithms represent the opportunity to refine and accelerate the discovery of VF associated with Streptococcus pyogenes. In this work, we evaluate the accuracy of various machine learning models in predicting the virulence factors and antimicrobial resistance of Streptococcus pyogenes, with the objective of providing new methods for identifying the pathogenic mechanisms of this organism.Our comprehensive approach involved the download of 32,798 genbank files of S. pyogenes from NCBI dataset, coupled with the incorporation of data from Virulence Factor Database (VFDB) and Antibiotic Resistance Database (CARD) which contains sequences of AMR gene sequence and resistance profiles. These datasets provided labeled examples of both virulent and non-virulent genes, enabling a robust foundation for feature extraction and model training. We employed preprocessing, characterization and feature extraction techniques on primary nucleotide/amino acid sequences and selected the optimal more for model training. The feature set was constructed using sequence-based descriptors (e.g., k-mers and One-hot encoding), and functional annotations based on database prediction. The ML models compared are logistic regression, decision trees, support vector machines, neural networks among others. The results of this work show some differences in accuracy between the algorithms, these differences allow us to identify different aspects that represent unique opportunities for a more precise and efficient characterization and identification of VF and AMR. This comparative analysis underscores the value of integrating machine learning techniques in predicting S. pyogenes virulence and AMR, offering potential pathways for more effective diagnostic and therapeutic strategies. Future work will focus on incorporating additional omics data, such as transcriptomics, and exploring advanced deep learning models to further enhance predictive capabilities.

Keywords: antibiotic resistance, streptococcus pyogenes, virulence factors., machine learning

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Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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Authors: Sharon Millen, Sarah Miller, Laura Dunne, Clare McGeady, Laura Neeson

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This paper presents the findings from a randomised controlled trial (RCT) and process evaluation of the Lifestart parenting programme. Lifestart is a structured child-centred programme of information and practical activity for parents of children aged from birth to five years of age. It is delivered to parents in their own homes by trained, paid family visitors and it is offered to parents regardless of their social, economic or other circumstances. The RCT evaluated the effectiveness of the programme and the process evaluation documented programme delivery and included a qualitative exploration of parent and child outcomes. 424 parents and children participated in the RCT: 216 in the intervention group and 208 in the control group across the island of Ireland. Parent outcomes included: parental knowledge of child development, parental efficacy, stress, social support, parenting skills and embeddedness in the community. Child outcomes included cognitive, language and motor development and social-emotional and behavioural development. Both groups were tested at baseline (when children were less than 1 year old), mid-point (aged 3) and at post-test (aged 5). Data were collected during a home visit, which took two hours. The process evaluation consisted of interviews with parents (n=16 at baseline and end-point), and focus groups with Lifestart Coordinators (n=9) and Family Visitors (n=24). Quantitative findings from the RCT indicated that, compared to the control group, parents who received the Lifestart programme reported reduced parenting-related stress, increased knowledge of their child’s development, and improved confidence in their parenting role. These changes were statistically significant and consistent with the hypothesised pathway of change depicted in the logic model. There was no evidence of any change in parents’ embeddedness in the community. Although four of the five child outcomes showed small positive change for children who took part in the programme, these were not statistically significant and there is no evidence that the programme improves child cognitive and non-cognitive skills by immediate post-test. The qualitative process evaluation highlighted important challenges related to conducting trials of this magnitude and design in the general population. Parents reported that a key incentive to take part in study was receiving feedback from the developmental assessment, which formed part of the data collection. This highlights the potential importance of appropriate incentives in relation to recruitment and retention of participants. The interviews with intervention parents indicated that one of the first changes they experienced as a result of the Lifestart programme was increased knowledge and confidence in their parenting ability. The outcomes and pathways perceived by parents and described in the interviews are also consistent with the findings of the RCT and the theory of change underpinning the programme. This hypothesises that improvement in parental outcomes, arising as a consequence of the programme, mediate the change in child outcomes. Parents receiving the Lifestart programme reported great satisfaction with and commitment to the programme, with the role of the Family Visitor being identified as one of the key components of the programme.

Keywords: parent-child relationship, parental self-efficacy, parental stress, school readiness

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Authors: Mustafa Metin Donma, Orkide Donma

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Childhood obesity is an important clinical problem because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21), and fetuin-A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver-derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21, and fetuin-A in childhood obesity, to point out possible differences between the obesity groups, and to investigate possible associations among these three hepatokines in obese and morbidly obese children. A total of one hundred and thirty-two children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean ± SD values of ages. Body mass index values of obese and morbidly obese groups were 25.0 ± 3.5 kg/m² and 29.8 ± 5.7 kg/m², respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants. The ethics committee of the institution approved the study protocol. Blood samples were obtained after overnight fasting. Routine biochemical tests, including glucose- and lipid-related parameters, were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study was performed by SPSS for Windows. Statistical difference was accepted significant when p is smaller than 0.05. Statistically significant differences were found for insulin, triglyceride, high-density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbidly obese group. Higher adropin and fetuin-A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbidly obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin-A (r=0.373, p=0.001). In conclusion, increased levels observed in adropin, FGF-21, and fetuin-A have shown that these hepatokines possess increasing potential going from obese to morbid obese state. Out of the correlations found with the IR index, the most affected hepatokine was fetuin-A, the parameter possibly used as the indicator of the advanced obesity stage.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

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Authors: Sascha Kraus, Wolfgang Hora, Philipp Stieg, Thomas Niemand, Ferdinand Thies, Matthias Filser

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In most countries, small and medium-sized enterprises (SME) are the backbone of the economy due to their impact on job creation, innovation and wealth creation. Moreover, the ongoing globalization makes it inevitable – even for SME that traditionally focused on their domestic markets – to internationalize their business activities to realize further growth and survive in international markets. Thus, internationalization has become one of the most common growth strategies for SME and has received increasing scholarly attention over the last two decades. One the downside internationalization can be also regarded as the most complex strategy that a firm can undertake. Particularly for family firms, that are often characterized by limited financial capital, a risk-averse nature and limited growth aspirations, it could be argued that family firms are more likely to face greater challenges when taking the pathway to internationalization. Especially the triangulation of family, ownership, and management (so-called ‘familiness’) manifests in a unique behavior and decision-making process which is often characterized by the importance given to noneconomic goals and distinguishes a family firm from other businesses. Taking this into account, the concept of socio-emotional wealth (SEW) has been evolved to describe the behavior of family firms. In order to investigate how different internal and external firm characteristics shape internationalization success of family firms, we drew on a sample consisting of 297 small and medium-sized family firms from Germany, Austria, Switzerland, and Liechtenstein. Thus, we include SEW as essential family firm characteristic and added the two major intra-organizational characteristics, entrepreneurial orientation (EO), absorptive capacity (AC) as well as collaboration intensity (CI) and relational knowledge (RK) as two major external network characteristics. Based on previous research we assume that these characteristics are important to explain internationalization success of family firm SME. Regarding the data analysis, we applied a Fuzzy Set Qualitative Comparative Analysis (fsQCA), an approach that allows identifying configurations of firm characteristics, specifically used to study complex causal relationships where traditional regression techniques reach their limits. Results indicate that several combinations of these family firm characteristics can lead to international success, with no permanently required key characteristic. Instead, there are many roads to walk down for family firms to achieve internationalization success. Consequently, our data states that family owned SME are heterogeneous and internationalization is a complex and dynamic process. Results further show that network related characteristics occur in all sets, thus represent an essential element in the internationalization process of family owned SME. The contribution of our study is twofold, as we investigate different forms of international expansion for family firms and how to improve them. First, we are able to broaden the understanding of the intersection between family firm and SME internationalization with respect to major intra-organizational and network-related variables. Second, from a practical perspective, we offer family firm owners a basis for setting up internal capabilities to achieve international success.

Keywords: entrepreneurial orientation, family firm, fsQCA, internationalization, socio-emotional wealth

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Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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Authors: Abouchouaib Belahmira, Joerg W. Schneider, Hafid Saber

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Continental sediments of the uppermost Carboniferous (late Pennsylvanian) El Menizla and Oued Issene formations of the Souss basin, Southwestern High Atlas Mountains, Morocco have yielded abundant well-preserved arthropods. The latter comprise freshwater and terrestrial elements, were found associated with plants, freshwater jellyfish and pelecypods. Arthropods are ubiquitous and typically restricted to the dominated lacustrine black shale taphofacies. The lithofacies interpretation and its correlation with the taphofacies led to the determination of the original depositional environment that was reconstructed as a fluvial-dominated with braided wide channel system and floodplain lakes to peat local backswamps sub-environments. The late Carboniferous fossiliferous strata have been correlated biostratigraphically with many other Pennsylvanian (Kasimovian/Gzhelian) deposits of North America and Europe on the basis of entomological studies. The faunal elements of the lentic biocoenosis of the Souss basin are depauperate, with the vagile forms slightly diverse than sessile ones. The prevailing groups are small shelly fauna, other habitat guild such as apterygotan Monura insect dasyleptids. The fossils recorded from the Souss basin includes crustaceans, of various sizes (µm- to mm) and morphologies, preservation state ranging from poorly preserved to rarely well-preserved specimens. Their remains sporadically found clustered and preserved as internal or external shell molds or steinkerns often disarticulated specimens. Ostracods as more likely Carbonita, their shells are preserved three-dimensionally. The clam shrimps conchostracans record of the Souss basin are often determined as pseudestherids and the Spinicaudatan leaiids. The moldic preservation is somewhat similar to pelecypods, they are known from internal casts or impressions. Monura insects are characterized by their low diversity, thus, only two species are known Dasyleptus lucasi Brongniart and Dasyleptus noli Rasnitsyn. The terrestrial component consists of pterygotan insects. They are diverse, significantly more frequent throughout the Souss basin fossil localities, numerically dominated by the members of Blattodea (cockroaches). The fossil record includes Blattodea, Protorthoptera, Diaphanopterodea, Ephemeroptera (mayfly) , Calneurodea, Grylloblattodea, Miomoptera and Palaeodictyoptera. Additionally, the composition of the preserved insect is mostly represented by completely isolated forewings, rare membranous hindwings, parts of the body or exceptionally preserved specimens, which may reflect a wide spectrum of taphonomic pathways. The steady increase in taxonomic diversity of fossil sites in the Souss basin, together with the taphonomic interpretation of arthropods assemblages, have contributed to provide a novel insight into the complex terrestrial ecosystem that thrived in this paleotropical key region during the late Pennsylvanian and additionally to understand climate-driven paleobiogeography and paleoecology of late Paleozoic non-marine arthropods.

Keywords: Souss, carboniferous, arthropods, taphonomy, paleoecology.

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Authors: Waqas Ahmed Khan, Faheem Khokhaar

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Air pollution is one of the main perpetrators of climate change. GHGs cause melting of glaciers and cause change in temperature and heavy rain fall many gasses like Formaldehyde is not direct precursor that damage ozone like CO2 or Methane but Formaldehyde (HCHO) form glyoxal (CHOCHO) that has effect on ozone. Countries around the globe have unique air quality monitoring protocols to describe local air pollution. Formaldehyde is a colorless, flammable, strong-smelling chemical that is used in building materials and to produce many household products and medical preservatives. Formaldehyde also occurs naturally in the environment. It is produced in small amounts by most living organisms as part of normal metabolic processes. Pakistan lacks the monitoring facilities on larger scale to measure the atmospheric gasses on regular bases. Formaldehyde is formed from Glyoxal and effect mountain biodiversity and livelihood. So its monitoring is necessary in order to maintain and preserve biodiversity. Objective: Present study is aimed to measure atmospheric HCHO vertical column densities (VCDs) obtained from ground-base and compute HCHO data in Punjab and elevated areas (Rawalpindi & Islamabad) by satellite observation during the time period of 2014-2015. Methodology: In order to explore the spatial distributing of H2CO, various fields campaigns including international scientist by using car Max-Doas. Major focus was on the cities along national highways and industrial region of Punjab Pakistan. Level 2 data product of satellite instruments OMI retrieved by differential optical absorption spectroscopy (DOAS) technique are used. Spatio-temporal distribution of HCHO column densities over main cities and region of Pakistan has been discussed. Results: Results show the High HCHO column densities exceeding permissible limit over the main cities of Pakistan particularly the areas with rapid urbanization and enhanced economic growth. The VCDs value over elevated areas of Pakistan like Islamabad, Rawalpindi is around 1.0×1016 to 34.01×1016 Molecules’/cm2. While Punjab has values revolving around the figure 34.01×1016. Similarly areas with major industrial activity showed high amount of HCHO concentrations. Tropospheric glyoxal VCDs were found to be 4.75 × 1015 molecules/cm2. Conclusion: Results shows that monitoring site surrounded by Margalla hills (Islamabad) have higher concentrations of Formaldehyde. Wind data shows that industrial areas and areas having high economic growth have high values as they provide pathways for transmission of HCHO. Results obtained from this study would help EPA, WHO and air protection departments in order to monitor air quality and further preservation and restoration of mountain biodiversity.

Keywords: air quality, formaldehyde, Max-Doas, vertical column densities (VCDs), satellite instrument, climate change

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Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

Procedia PDF Downloads 139

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

Procedia PDF Downloads 122

Authors: Frank Adusah-Poku, John Bosco Dramani, Prince Boakye Frimpong

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Climate change is considered a principal threat to human existence and livelihood. The persistence and intensity of droughts and floods in recent years have adversely affected food production systems and value chains, making it impossible to end global hunger by 2030. Thus, this study aims to examine the effect of climate change on food consumption for both farm and non-farm households in Ghana. An important focus of the analysis is to investigate how climate change affects alternative dimensions of food security, examine the extent to which these effects vary across heterogeneous groups, and explore the channels through which climate change affects food consumption. Finally, we conducted a pilot study to understand the significance of farm and non-farm diversification measures in reducing the harmful impact of climate change on farm households. The approach of this article is to use two secondary and one primary datasets. The first secondary dataset is the Ghana Socioeconomic Panel Survey (GSPS). The GSPS is a household panel dataset collected during the period 2009 to 2019. The second dataset is monthly district rainfall and temperature gridded data from the Ghana Meteorological Agency. This data was matched to the GSPS dataset at the district level. Finally, the primary data was obtained from a survey of farm and non-farm adaptation practices used by farmers in three regions in Northern Ghana. The study employed the household fixed effects model to estimate the effect of climate change (measured by temperature and rainfall) on food consumption in Ghana. Again, it used the spatial and temporal variation in temperature and rainfall across the districts in Ghana to estimate the household-level model. Evidence of potential mechanisms through which climate change affects food consumption was explored using two steps. First, the potential mechanism variables were regressed on temperature, rainfall, and the control variables. In the second and final step, the potential mechanism variables were included as extra covariates in the first model. The results revealed that extreme average temperature and drought had caused a decrease in food consumption as well as reduced the intake of important food nutrients such as carbohydrates, protein and vitamins. The results further indicated that low rainfall increased food insecurity among households with no education compared with those with primary and secondary education. Again, non-farm activity and silos have been revealed as the transmission pathways through which the effect of climate change on farm households can be moderated. Finally, the results indicated over 90% of the small-holder farmers interviewed had no farm diversification adaptation strategies for climate change, and a little over 50% of the farmers owned unskilled or manual non-farm economic ventures. This makes it very difficult for the majority of the farmers to withstand climate-related shocks. These findings suggest that achieving the Sustainable Development Goal of Zero Hunger by 2030 needs an integrated approach, such as reducing the over-reliance on rainfed agriculture, educating farmers, and implementing non-farm interventions to improve food consumption in Ghana.

Keywords: climate change, food consumption, Ghana, non-farm activity

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Authors: Nadia K. Thalji

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In the timeless tapestry of human culture, theater, mythology, and psychology intersect to weave narratives that transcend temporal and spatial boundaries. For millennia, actors have stood as guardians of intuitive wisdom, their craft serving as a conduit for the collective unconscious. This paper embarks on a journey through the realms of creative expression, melding the insights of cross-cultural psychology with the mystical allure of serendipity and synchronicity. At the nexus of these disciplines lies the enigmatic process of active imagination, a gateway to the depths of the psyche elucidated by Jung. Within the hallowed confines of the black box theater at the Department of Performing Arts, UFRGS University in Brazil, this study unfolds. Over the span of four months, a cadre of artists embarked on a voyage of exploration, harnessing the powers of imagery, movement, sound, and dreams to birth a performance that resonated with the echoes of ancient wisdom. Drawing inspiration from the fabled Oracle of Delphi and the priestesses who once dwelled within its sacred precincts, the production delves into the liminal spaces where myth and history intertwine. Through the alchemy of storytelling, participants navigate the labyrinthine corridors of cultural memory, unraveling the threads that bind the past to the present. Central to this endeavor is the phenomenon of synchronicity, wherein seemingly disparate elements coalesce in a dance of cosmic resonance. Serendipity becomes a guiding force, leading actors and audience alike along unexpected pathways of discovery. As the boundaries between performer and spectator blur, the performance becomes a crucible wherein individual narratives merge to form a collective tapestry of shared experience. Yet, beneath the surface of spectacle lies a deeper truth: the exploration of the spiritual dimensions of artistic expression. Through intuitive inquiry and embodied practice, artists tap into reservoirs of insight that transcend rational comprehension. In the communion of minds and bodies, the stage becomes a sacred space wherein the numinous unfolds in all its ineffable glory. In essence, this paper serves as a testament to the transformative power of the creative act. Across cultures and epochs, the theater has served as a crucible wherein humanity grapples with the mysteries of existence. Through the lens of cross-cultural psychology, we glimpse the universal truths that underlie the myriad manifestations of human creativity. As we navigate the turbulent currents of modernity, the wisdom of the ancients beckons us to heed the call of the collective unconscious. In the synthesis of myth and meaning, we find solace amidst the chaos, forging connections that transcend the boundaries of time and space. And in the sacred precincts of the theater, we discover the eternal truth that art is, and always shall be, the soul's journey into the unknown.

Keywords: theater, mythology, cross-cultural, synchronicity, creativity, serendipity, spiritual

Procedia PDF Downloads 57

Authors: Angelos Evangelou, Katerina Loizou, Loukas Koutsokeras, Orestes Marangos, Giorgos Constantinides, Stylianos Yiatros, Katerina Sofocleous, Vasileios Drakonakis

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Owing to their outstanding strength to weight properties, carbon fiber reinforced polymer (CFRPs) composites have attracted significant attention finding use in various fields (sports, automotive, transportation, etc.). The current momentum indicates that there is an increasing demand for their employment in high value bespoke applications such as avionics and electronic casings, damage sensing structures, EMI (electromagnetic interference) structures that dictate the use of materials with increased electrical conductivity both in-plane and through the thickness. Several efforts by research groups have focused on enhancing the through-thickness electrical conductivity of FRPs, in an attempt to combine the intrinsically high relative strengths exhibited with improved z-axis electrical response as well. However, only a limited number of studies deal with printing of nano-enhanced polymer inks to produce a pattern on dry fabric level that could be used to fabricate CFRPs with improved through thickness electrical conductivity. The present study investigates the employment of screen-printing process on technical dry fabrics using nano-reinforced polymer-based inks to achieve the required through thickness conductivity, opening new pathways for the application of fiber reinforced composites in niche products. Commercially available inks and in-house prepared inks reinforced with electrically conductive nanoparticles are employed, printed in different patterns. The aim of the present study is to investigate both the effect of the nanoparticle concentration as well as the droplet patterns (diameter, inter-droplet distance and coverage) to optimize printing for the desired level of conductivity enhancement in the lamina level. The electrical conductivity is measured initially at ink level to pinpoint the optimum concentrations to be employed using a “four-probe” configuration. Upon printing of the different patterns, the coverage of the dry fabric area is assessed along with the permeability of the resulting dry fabrics, in alignment with the fabrication of CFRPs that requires adequate wetting by the epoxy matrix. Results demonstrated increased electrical conductivities of the printed droplets, with increase of the conductivity from the benchmark value of 0.1 S/M to between 8 and 10 S/m. Printability of dense and dispersed patterns has exhibited promising results in terms of increasing the z-axis conductivity without inhibiting the penetration of the epoxy matrix at the processing stage of fiber reinforced composites. The high value and niche prospect of the resulting applications that can stem from CFRPs with increased through thickness electrical conductivities highlights the potential of the presented endeavor, signifying screen printing as the process to to nano-enable z-axis electrical conductivity in composite laminas. This work was co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research and Innovation Foundation (Project: ENTERPRISES/0618/0013).

Keywords: CFRPs, conductivity, nano-reinforcement, screen-printing

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Authors: Zofia Wlodarczyk

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I study the experiences of domestic violence survivors who flee their countries of origin in times of political conflict using insight and evidence from forty-five biographical interviews with female Chechen refugees and twelve refugee resettlement professionals in Poland. Both refugees and women are often described as having less agency—that is, they lack the power to decide to migrate – refugees less than economic migrants and women less than men. In this paper, I focus on how female refugees who have been victims of domestic violence make decisions about leaving their countries of origin during times of political conflict. I use several existing migration theories to trace how the migration experience of these women is shaped by dynamics at different levels of society: the macro level, the meso level and the micro level. At the macro level of analysis, I find that political conflict can be both a source of and an escape from domestic violence. Ongoing conflict can strengthen the patriarchal cultural norms, increase violence and constrain women’s choices when it comes to marriage. However, political conflict can also destabilize families and make pathways for women to escape. At the meso level I demonstrate that other political migrants and institutions that emerge due to politically triggered migration can guide those fleeing domestic violence. Finally, at the micro level, I show that family dynamics often force domestic abuse survivors to make their decision to escape alone or with the support of only the most trusted female relatives. Taken together, my analyses show that we cannot look solely at one level of society when describing decision-making processes of women fleeing domestic violence. Conflict-related micro, meso and macro forces interact with and influence each other: on the one hand, strengthening an abusive trap, and on the other hand, opening a door to escape. This study builds upon several theoretical and empirical debates. First, it expands theories of migration by incorporating both refugee and gender perspectives. Few social scientists have used the migration theory framework to discuss the unique circumstances of refugee flows. Those who have mainly focus on “political” migrants, a designation that frequently fails to account for gender, does not incorporate individuals fleeing gender-based violence, including domestic-violence victims. The study also enriches migration scholarship, typically focused on the US and Western-European context, with research from Eastern Europe and Caucasus. Moreover, it contributes to the literature on the changing roles of gender in the context of migration. I argue that understanding how gender roles and hierarchies influence the pre-migration stage of female refugees is crucial, as it may have implications for policy-making efforts in host countries that recognize the asylum claims of those fleeing domestic violence. This study also engages in debates about asylum and refugee law. Domestic violence is normatively and often legally considered an individual-level problem whereas political persecution is recognized as a structural or societal level issue. My study challenges these notions by showing how the migration triggered by domestic violence is closely intertwined with politically motivated refuge.

Keywords: AGENCY, DOMESTIC VIOLENCE, FEMALE REFUGEES, POLITICAL REFUGE, SOCIAL NETWORKS

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Authors: Iman Farasat, Howard M. Salis

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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

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Authors: Andreas Kerstan, Darren Robey, Wesam Alvan, David Troiani

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Over the last 3.5 years, Quantum Cascade Lasers (QCL) technology has become increasingly important in infrared (IR) microscopy. The advantages over fourier transform infrared (FTIR) are that large areas of a few square centimeters can be measured in minutes and that the light intensive QCL makes it possible to obtain spectra with excellent S/N, even with just one scan. A firmly established solution of the laser direct infrared imaging (LDIR) 8700 is the analysis of microplastics. The presence of microplastics in the environment, drinking water, and food chains is gaining significant public interest. To study their presence, rapid and reliable characterization of microplastic particles is essential. Significant technical hurdles in microplastic analysis stem from the sheer number of particles to be analyzed in each sample. Total particle counts of several thousand are common in environmental samples, while well-treated bottled drinking water may contain relatively few. While visual microscopy has been used extensively, it is prone to operator error and bias and is limited to particles larger than 300 µm. As a result, vibrational spectroscopic techniques such as Raman and FTIR microscopy have become more popular, however, they are time-consuming. There is a demand for rapid and highly automated techniques to measure particle count size and provide high-quality polymer identification. Analysis directly on the filter that often forms the last stage in sample preparation is highly desirable as, by removing a sample preparation step it can both improve laboratory efficiency and decrease opportunities for error. Recent advances in infrared micro-spectroscopy combining a QCL with scanning optics have created a new paradigm, LDIR. It offers improved speed of analysis as well as high levels of automation. Its mode of operation, however, requires an IR reflective background, and this has, to date, limited the ability to perform direct “on-filter” analysis. This study explores the potential to combine the filter with an infrared reflective surface filter. By combining an IR reflective material or coating on a filter membrane with advanced image analysis and detection algorithms, it is demonstrated that such filters can indeed be used in this way. Vibrational spectroscopic techniques play a vital role in the investigation and understanding of microplastics in the environment and food chain. While vibrational spectroscopy is widely deployed, improvements and novel innovations in these techniques that can increase the speed of analysis and ease of use can provide pathways to higher testing rates and, hence, improved understanding of the impacts of microplastics in the environment. Due to its capability to measure large areas in minutes, its speed, degree of automation and excellent S/N, the LDIR could also implemented for various other samples like food adulteration, coatings, laminates, fabrics, textiles and tissues. This presentation will highlight a few of them and focus on the benefits of the LDIR vs classical techniques.

Keywords: QCL, automation, microplastics, tissues, infrared, speed

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Authors: Jo Mitchell, Daniel Johnson

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MindMax is a digital community and learning platform built to maximise the wellbeing and resilience of AFL Players and Australian men. The MindMax application engages men, via their existing connection with sport and video games, in a range of wellbeing ideas, stories and actions, because we believe fit minds, kick goals. MindMax is an AFL Players Association led project, supported by a Movember Foundation grant, to improve the mental health of Australian males aged between 16-35 years. The key engagement and delivery strategy for the project was digital technology, sport (AFL) and video games, underpinned by evidenced based wellbeing science. The project commenced April 2015, and the expected completion date is March 2017. This paper describes the conceptual model underpinning product development, including progress, key learnings and challenges, as well as the research agenda. Evaluation of the MindMax project is a multi-pronged approach of qualitative and quantitative methods, including participatory design workshops, online reference groups, longitudinal survey methods, a naturalistic efficacy trial and evaluation of the social and economic return on investment. MindMax is focused on the wellness pathway and maximising our mind's capacity for fitness by sharing and promoting evidence-based actions that support this. A range of these ideas (from ACT, mindfulness and positive psychology) are already being implemented in AFL programs and services, mostly in face-to-face formats, with strong engagement by players. Player's experience features strongly as part of the product content. Wellbeing science is a discipline of psychology that explores what helps individuals and communities to flourish in life. Rather than ask questions about illness and poor functioning, wellbeing scientists and practitioners ask questions about wellness and optimal functioning. While illness and wellness are related, they operate as separate constructs and as such can be influenced through different pathways. The essential idea was to take the evidence-based wellbeing science around building psychological fitness to the places and spaces that men already frequent, namely sport and video games. There are 800 current senior AFL players, 5000+ past players, and 11 million boys and men that are interested in the lives of AFL Players; what they think and do to be their best both on and off field. AFL Players are also keen video gamers – using games as one way to de-stress, connect and build wellbeing. There are 9.5 million active gamers in Australia with 93% of households having a device for playing games. Video games in MindMax will be used as an engagement and learning tool. Gamers (including AFL players) can also share their personal experience of how games help build their mental fitness. Currently available games (i.e., we are not in the game creation business) will also be used to motivate and connect MindMax participants. The MindMax model is built with replication by other sport codes (e.g., Cricket) in mind. It is intended to not only support our current crop of athletes but also the community that surrounds them, so they can maximise their capacity for health and wellbeing.

Keywords: Australian football league, digital application, positive psychology, wellbeing

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Authors: T. Ul Rehman, S. Agnello, F. M. Gelardi, M. M. Calvino, G. Lazzara, G. Buscarino, M. Cannas

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Metal-Organic Frameworks (MOFs) have emerged as promising candidates for detecting metal ions owing to their large surface area, customizable porosity, and diverse functionalities. In recent years, there has been a surge in research focused on MOFs with luminescent properties. These frameworks are constructed through coordinated bonding between metal ions and multi-dentate ligands, resulting in inherent fluorescent structures. Their luminescent behavior is influenced by factors like structural composition, surface morphology, pore volume, and interactions with target analytes, particularly metal ions. MOFs exhibit various sensing mechanisms, including photo-induced electron transfer (PET) and charge transfer processes such as ligand-to-metal (LMCT) and metal-to-ligand (MLCT) transitions. Among these, MIL-53(Al) stands out due to its flexibility, stability, and specific affinity towards certain metal ions, making it a promising platform for selective metal ion sensing. This study investigates the structural, thermal, and luminescent properties of MIL-53(Al) metal-organic framework (MOF) upon Fe3+ cation exchange. Two separate sets of samples were prepared to activate the MOF powder at different temperatures. The first set of samples, referred to as MIL-53(Al), activated (120°C), was prepared by activating the raw powder in a glass tube at 120°C for 12 hours and then sealing it. The second set of samples, referred to as MIL-53(Al), activated (300°C), was prepared by activating the MIL-53(Al) powder in a glass tube at 300°C for 70 hours. Additionally, 25 mg of MIL-53(Al) powder was dispersed in 5 mL of Fe3+ solution at various concentrations (0.1-100 mM) for the cation exchange experiment. The suspension was centrifuged for five minutes at 10,000 rpm to extract MIL-53(Al) powder. After three rounds of washing with ultrapure water, MIL-53(Al) powder was heated at 120°C for 12 hours. For PXRD and TGA analyses, a sample of the obtained MIL-53(Al) was used. We also activated the cation-exchanged samples for time-resolved photoluminescence (TRPL) measurements at two distinct temperatures (120 and 300°C) for comparative analysis. Powder X-ray diffraction patterns reveal amorphization in samples with higher Fe3+ concentrations, attributed to alterations in coordination environments and ion exchange dynamics. Thermal decomposition analysis shows reduced weight loss in Fe3+-exchanged MOFs, indicating enhanced stability due to stronger metal-ligand bonds and altered decomposition pathways. Raman spectroscopy demonstrates intensity decrease, shape disruption, and frequency shifts, indicative of structural perturbations induced by cation exchange. Photoluminescence spectra exhibit ligand-based emission (π-π* or n-π*) and ligand-to-metal charge transfer (LMCT), influenced by activation temperature and Fe3+ incorporation. Quenching of luminescence intensity and shorter lifetimes upon Fe3+ exchange result from structural distortions and Fe3+ binding to organic linkers. In a nutshell, this research underscores the complex interplay between composition, structure, and properties in MOFs, offering insights into their potential for diverse applications in catalysis, gas storage, and luminescent devices.

Keywords: Fe³⁺ cation exchange, luminescent metal-organic frameworks (LMOFs), MIL-53(Al), solid-state analysis

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Authors: Jenson George, Thoa Nguyen, Garth Sanewski, Craig Hardner, Heather Eunice Smyth

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Pineapple (Ananas comosus), with its unique sweet flavour, is one of the most popular tropical, non-climacteric fruits consumed worldwide. It is also the third most important tropical fruit in world production. In Australia, 99% of the pineapple production is from the Queensland state due to the favourable subtropical climatic conditions. The flavourful fruit is known to contain around 500 volatile organic compounds (VOC) at varying concentrations and greatly contribute to the flavour quality of pineapple fruit by providing distinct aroma sensory properties that are sweet, fruity, tropical, pineapple-like, caramel-like, coconut-like, etc. The aroma of pineapple is one of the important factors attracting consumers and strengthening the marketplace. To better understand the aroma of Australian-grown pineapples, the matrix-matched Gas chromatography–mass spectrometry (GC-MS), Head Space - Solid-phase microextraction (HS-SPME), Stable-isotope dilution analysis (SIDA) method was developed and validated. The developed method represents a significant improvement over current methods with the incorporation of multiple external reference standards, multiple isotopes labeled internal standards, and a matching model system of pineapple fruit matrix. This method was employed to quantify 28 key aroma compounds in more than 200 genetically diverse pineapple varieties from a breeding program. The Australian pineapple cultivars varied in content and composition of free volatile compounds, which were predominantly comprised of esters, followed by terpenes, alcohols, aldehydes, and ketones. Using selected commercial cultivars grown in Australia, and by employing the sensorial analysis, the appearance (colour), aroma (intensity, sweet, vinegar/tang, tropical fruits, floral, coconut, green, metallic, vegetal, fresh, peppery, fermented, eggy/sulphurous) and texture (crunchiness, fibrousness, and juiciness) were obtained. Relationships between sensory descriptors and volatiles were explored by applying multivariate analysis (PCA) to the sensorial and chemical data. The key aroma compounds of pineapple exhibited a positive correlation with corresponding sensory properties. The sensory and volatile data were also used to explore genetic diversity in the breeding population. GWAS was employed to unravel the genetic control of the pineapple volatilome and its interplay with fruit sensory characteristics. This study enhances our understanding of pineapple aroma (flavour) compounds, their biosynthetic pathways and expands breeding option for pineapple cultivars. This research provides foundational knowledge to support breeding programs, post-harvest and target market studies, and efforts to optimise the flavour of commercial pineapple varieties and their parent lines to produce better tasting fruits for consumers.

Keywords: Ananas comosus, pineapple, flavour, volatile organic compounds, aroma, Gas chromatography–mass spectrometry (GC-MS), Head Space - Solid-phase microextraction (HS-SPME), Stable-isotope dilution analysis (SIDA).

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Milica Carević, Katarina Banjanac, Marija ĆOrović, Ana Milivojević, Nevena Prlainović, Aleksandar Marinković, Dejan Bezbradica

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Nowadays, considering the growing awareness of functional food beneficial effects on human health, due attention is dedicated to the research in the field of obtaining new prominent products exhibiting improved physiological and physicochemical characteristics. Therefore, different approaches to valuable bioactive compounds synthesis have been proposed. β-Galactosidase, for example, although mainly utilized as hydrolytic enzyme, proved to be a promising tool for these purposes. Namely, under the particular conditions, such as high lactose concentration, elevated temperatures and low water activities, reaction of galactose moiety transfer to free hydroxyl group of the alternative acceptor (e.g. different sugars, alcohols or aromatic compounds) can generate a wide range of potentially interesting products. Up to now, galacto-oligosaccharides and lactulose have attracted the most attention due to their inherent prebiotic properties. The goal of this study was to obtain a novel product sorbitol galactoside, using the similar reaction mechanism, namely transgalactosylation reaction catalyzed by β-galactosidase from Aspergillus oryzae. By using sugar alcohol (sorbitol) as alternative acceptor, a diverse mixture of potential prebiotics is produced, enabling its more favorable functional features. Nevertheless, an introduction of alternative acceptor into the reaction mixture contributed to the complexity of reaction scheme, since several potential reaction pathways were introduced. Therefore, the thorough optimization using response surface method (RSM), in order to get an insight into different parameter (lactose concentration, sorbitol to lactose molar ratio, enzyme concentration, NaCl concentration and reaction time) influences, as well as their mutual interactions on product yield and productivity, was performed. In view of product yield maximization, the obtained model predicted optimal lactose concentration 500 mM, the molar ratio of sobitol to lactose 9, enzyme concentration 0.76 mg/ml, concentration of NaCl 0.8M, and the reaction time 7h. From the aspect of productivity, the optimum substrate molar ratio was found to be 1, while the values for other factors coincide. In order to additionally, improve enzyme efficiency and enable its reuse and potential continual application, immobilization of β-galactosidase onto tailored silica nanoparticles was performed. These non-porous fumed silica nanoparticles (FNS)were chosen on the basis of their biocompatibility and non-toxicity, as well as their advantageous mechanical and hydrodinamical properties. However, in order to achieve better compatibility between enzymes and the carrier, modifications of the silica surface using amino functional organosilane (3-aminopropyltrimethoxysilane, APTMS) were made. Obtained support with amino functional groups (AFNS) enabled high enzyme loadings and, more importantly, extremely high expressed activities, approximately 230 mg proteins/g and 2100 IU/g, respectively. Moreover, this immobilized preparation showed high affinity towards sorbitol galactoside synthesis. Therefore, the findings of this study could provided a valuable contribution to the efficient production of physiologically active galactosides in immobilized enzyme reactors.

Keywords: β-galactosidase, immobilization, silica nanoparticles, transgalactosylation

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Authors: Shanaka Gunasekara, Maleen Jayasuriya, Nalin Harischandra, Lilantha Samaranayake, Gamini Dissanayake

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One serious facet of the worsening Human-Elephant conflict (HEC) in nations such as Sri Lanka involves elephant-train collisions. Endangered Asian elephants are maimed or killed during such accidents, which also often result in orphaned or disabled elephants, contributing to the phenomenon of lone elephants. These lone elephants are found to be more likely to attack villages and showcase aggressive behaviour, which further exacerbates the overall HEC. Furthermore, Railway Services incur significant financial losses and disruptions to services annually due to such accidents. Most elephant-train collisions occur due to a lack of adequate reaction time. This is due to the significant stopping distance requirements of trains, as the full braking force needs to be avoided to minimise the risk of derailment. Thus, poor driver visibility at sharp turns, nighttime operation, and poor weather conditions are often contributing factors to this problem. Initial investigations also indicate that most collisions occur in localised “hotspots” where elephant pathways/corridors intersect with railway tracks that border grazing land and watering holes. Taking these factors into consideration, this work proposes the leveraging of recent developments in Convolutional Neural Network (CNN) technology to detect elephants using an RGB/infrared capable camera around known hotspots along the railway track. The CNN was trained using a curated dataset of elephants collected on field visits to elephant sanctuaries and wildlife parks in Sri Lanka. With this vision-based detection system at its core, a prototype unit of an early warning system was designed and tested. This weatherised and waterproofed unit consists of a Reolink security camera which provides a wide field of view and range, an Nvidia Jetson Xavier computing unit, a rechargeable battery, and a solar panel for self-sufficient functioning. The prototype unit was designed to be a low-cost, low-power and small footprint device that can be mounted on infrastructures such as poles or trees. If an elephant is detected, an early warning message is communicated to the train driver using the GSM network. A mobile app for this purpose was also designed to ensure that the warning is clearly communicated. A centralized control station manages and communicates all information through the train station network to ensure coordination among important stakeholders. Initial results indicate that detection accuracy is sufficient under varying lighting situations, provided comprehensive training datasets that represent a wide range of challenging conditions are available. The overall hardware prototype was shown to be robust and reliable. We envision a network of such units may help contribute to reducing the problem of elephant-train collisions and has the potential to act as an important surveillance mechanism in dealing with the broader issue of human-elephant conflicts.

Keywords: computer vision, deep learning, human-elephant conflict, wildlife early warning technology

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