Search results for: expression

Authors: Sunita Boro, Saurabh Kumar Dixit

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Terroir, an intricate fusion of geography, climate, soil, and human expertise, has long been acknowledged as a defining factor in the character of wines and foods. This research embarks on an exploration of terroir's profound influence on gastronomic tourism, shedding light on the intricate interplay between the physical environment and culinary artistry. Delving into the intricate science of terroir, we scrutinize its role in shaping the sensory profiles of wines and foods, emphasizing the profound impact of specific regions on flavor, aroma, and texture. We deploy a multifaceted methodology, amalgamating sensory analysis, chemical profiling, geographical information systems, and qualitative interviews to unearth the nuanced nuances of terroir expression. Through an exhaustive review of the literature, we elucidate the historical roots of terroir, unveil the intricate cultural dimensions shaping it, and provide a comprehensive examination of prior studies in the field. Our findings underscore the pivotal role of terroir in promoting regional identities, enhancing the economic viability of locales, and attracting gastronomic tourists. The paper also dissects the marketing strategies employed to promote terroir-driven food and wine experiences. We elucidate the utilization of storytelling, branding, and collaborative endeavors in fostering a robust terroir-based tourism industry. This elucidates both the potential for innovation and the challenges posed by oversimplification or misrepresentation of terroir. Our research spotlights the intersection of terroir and sustainability, emphasizing the significance of environmentally conscious practices in terroir-driven productions. We discern the harmonious relationship between sustainable agriculture, terroir preservation, and responsible tourism, encapsulating the essence of ecological integrity in gastronomic tourism. Incorporating compelling case studies of regions and businesses excelling in the terroir-based tourism realm, we offer in-depth insights into successful models and strategies, with an emphasis on their replicability and adaptability to various contexts. Ultimately, this paper not only contributes to the scholarly understanding of terroir's role in the world of food and wine tourism but also provides actionable recommendations for stakeholders to leverage terroir's allure, preserve its authenticity, and foster sustainable and enriching culinary tourism experiences.

Keywords: terroir, food tourism, wine tourism, sustainability

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Authors: Gamze Safak, Umut Arslanoglu

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Cultural and tourism conservation and development zones and tourism centers are the boundaries declared for the purpose of protecting, using, and evaluating the sectoral development and planned development in areas where historical and cultural values are heavily involved and/or where tourism potential is high. The most rapidly changing regions in Turkey are tourism areas, especially the coastal areas. Planning these regions is not about only an economic gain but also a natural and physical environment and refers to a complex process. If the tourism sector is not well controlled, excessive use of natural resources and wrong location choices may cause damage to natural areas, historical values, and socio-cultural structure. Since the strategic decisions taken in the environmental order and zoning plans, which are the means of guiding the physical environment of the Ministry of Culture and Tourism, which have the authority to make plans in tourism centers, are transformed into plan decisions that find the spatial expression, comprehensive evaluation of all kinds of data, following the historical development and based on the correct and current data is required. In addition, the authority has a number of competences in tourism promotion as well as the authority to plan, leading to the necessity of taking part in the applications requiring complex analysis such as the management and integration of the country's economic, political, social and cultural resources. For this purpose, Tourism Inventory System (TES) project, which consists of a series of subsystems, has been developed in order to solve complex planning and method problems in the management of site-related information. The scope of the project is based on the integration of numerical and verbal data in the regions within the jurisdiction of the authority, and the monitoring of the historical development of urban planning studies, making the spatial data of the institution easily accessible, shared, questionable and traceable in international standards. A dynamic and continuous system design has been put into practice by utilizing the advantage of the use of Geographical Information Systems in the planning process to play a role in making the right decisions, revealing the tools of social, economic, cultural development, and preservation of natural and cultural values. This paper, which is prepared by the project team members in TES (Tourism Inventory System), will present a study regarding the applicability of GIS in cultural and natural heritage conservation.

Keywords: cultural conservation, GIS, geographic information system, tourism inventory system, urban planning

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Authors: Meiying Liao, Poya Huang

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The aesthetic domain is one of the six major domains in the Taiwanese preschool curriculum, encompassing visual arts, music, and dramatic play. Its primary objective is to cultivate children’s abilities in exploration and awareness, expression and creation, and response and appreciation. The purpose of this study was to explore the effects of hosting a vocal music concert on aesthetic inspiration and learning among preschoolers in a preschool setting. The primary research method employed was a case study focusing on a private preschool in Northern Taiwan that organized a school-wide event featuring two vocalists. The concert repertoires included children’s songs, folk songs, and arias performed in Mandarin, Hakka, English, German, and Italian. In addition to professional performances, preschool teachers actively participated by presenting a children’s song. A total of 5 classes, comprising approximately 150 preschoolers, along with 16 teachers and staff, participated in the event. Data collection methods included observation, interviews, and documents. Results indicated that both teachers and children thoroughly enjoyed the concert, with high levels of acceptance when the program was appropriately designed and hosted. Teachers reported that post-concert discussions with children revealed the latter’s ability to recall people, events, and elements observed during the performance, expressing their impressions of the most memorable segments. The concert effectively achieved the goals of the aesthetic domain, particularly in fostering response and appreciation. It also inspired preschoolers’ interest in music. Many teachers noted an increased desire for performance among preschoolers after exposure to the concert, with children imitating the performers and their expressions. Remarkably, one class extended this experience by incorporating it into the curriculum, autonomously organizing a high-quality concert in the music learning center. Parents also reported that preschoolers enthusiastically shared their concert experiences at home. In conclusion, despite being a single event, the positive responses from preschoolers towards the music performance suggest a meaningful impact. These experiences extended into the curriculum, as firsthand exposure to performances allowed teachers to deepen related topics, fostering a habit of autonomous learning in the designated learning centers.

Keywords: concert, early childhood music education, aesthetic education, music develpment

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Authors: Sridhar A. Malkaram, Tamer E. Fandy

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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.

Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics

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Authors: Murray Anderson, Galina Freed, Karli Jahn

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Trauma is increasingly recognized as an important construct that has health implications for those who struggle with various mental health issues. For those individuals who meet the criteria for a diagnosis of hoarding disorder (HD), many have experienced some form of trauma. Further, some of the therapeutic interventions for those with HD can further perpetuate or magnify the experience of trauma. Therefore, the aim of this scoping review is to identify and document the nature and extent of research evidence related to trauma as it connects with HD. This review was guided by the questions, ‘How can our understanding of the trauma cycle help us to better appreciate the experiences of individuals who hoard, and how will a trauma informed lens inform the interventions for hoarding disorder? A comprehensive literature search was performed to identify original studies that contained the words “hoarding” and “trauma.” PsychINFO”,''EBSCO host,” “CINAHL” and “PubMed” were searched between January 2005 and April 2021. Articles were screened by three reviewers. Data extracted included publication date, demographics, study design, type of analysis, and noted connections between hoarding and trauma. Of the 329 articles, all duplicates, articles on hoardings of animals, articles not in English, and those without full-text availability were removed. Five categories were found in the remaining 45 articles, including (a) traumatic and stressful life events; (b) the link between posttraumatic stress disorder, trauma, and hoarding; (c) the relationships between different comorbidities, trauma, and hoarding; (d) the lack of early emotional expression and other forms of parental deprivation; and (e) the role of attachment. Lastly, the literature explains how the links between hoarding and trauma are difficult to study due to the highly stigmatized identities with this population. The review provided strong support for the connections between the experience of trauma and HD. What is missing from the literature is the use of a trauma-informed lens to better account for the ways in which hoarding disorder is understood. Other missing pieces in the literature are the potential uses of a trauma-informed lens to enhance the therapeutic process, to understand and reduce treatment attrition, and to improve treatment outcomes. The application of a trauma informed lens could improve our understanding of effective interactions among clients, families, and communities and improve the education around hoarding-related matters. Exploring the connections between trauma and HD can improve therapeutic delivery and destigmatize the experience of dealing with clutter and hoarding concerns. This awareness can also provide health care professionals with both the language and skills to liberate them from a reductionist view on HD.

Keywords: hoarding, attachment, parental deprivation, trauma

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Authors: Yuanyuan Zhang, Yujuan Zheng, Giuseppina Barutello, Sumako Kameishi, Kungchun Chiu, Katharina Hennig, Martial Balland, Federica Cavallo, Lars Holmgren

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Angiogenesis describes that new blood vessels migrate from pre-existing ones to form 3D lumenized structure and remodeling. During directional migration toward the gradient of pro-angiogenic factors, the endothelial cells, especially the tip cells need filopodia to sense the environment and exert the pulling force. Of particular interest are the integrin proteins, which play an essential role in focal adhesion in the connection between migrating cells and extracellular matrix (ECM). Understanding how these biomechanical complexes orchestrate intrinsic and extrinsic forces is important for our understanding of the underlying mechanisms driving angiogenesis. We have previously identified Angiomotin (Amot), a member of Amot scaffold protein family, as a promoter for endothelial cell migration in vitro and zebrafish models. Hence, we established inducible endothelial-specific Amot knock-out mice to study normal retinal angiogenesis as well as tumor angiogenesis. We found that the migration ratio of the blood vessel network to the edge was significantly decreased in Amotec- retinas at postnatal day 6 (P6). While almost all the Amot defect tip cells lost migration advantages at P7. In consistence with the dramatic morphology defect of tip cells, there was a non-autonomous defect in astrocytes, as well as the disorganized fibronectin expression pattern correspondingly in migration front. Furthermore, the growth of transplanted LLC tumor was inhibited in Amot knockout mice due to fewer vasculature involved. By using MMTV-PyMT transgenic mouse model, there was a significantly longer period before tumors arised when Amot was specifically knocked out in blood vessels. In vitro evidence showed that Amot binded to beta-actin, Integrin beta 1 (ITGB1), Fibronectin, FAK, Vinculin, major focal adhesion molecules, and ITGB1 and stress fibers were distinctly induced by Amot transfection. Via traction force microscopy, the total energy (force indicater) was found significantly decreased in Amot knockdown cells. Taken together, we propose that Amot is a novel partner of the ITGB1/Fibronectin protein complex at focal adhesion and required for exerting force transition between endothelial cell and extracellular matrix.

Keywords: angiogenesis, angiomotin, endothelial cell migration, focal adhesion, integrin beta 1

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Authors: Vaida Jurgile

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Intercultural learning is one of the approaches taken to understand the cultural diversity of the modern world and to accept changes in cultural identity and otherness and the expression of tolerance. During intercultural learning, students develop their abilities to interact and communicate with their group members. These abilities help to understand social and cultural differences, to form one’s identity, and to give meaning to intercultural learning. Intercultural education recognizes that a true understanding of differences and similarities of another culture is necessary in order to lay the foundations for working together with others, which contributes to the promotion of intercultural dialogue, appreciation of diversity, and cultural exchange. Therefore, it is important to examine the concept of intercultural learning, revealed through students’ learning experiences and understanding of how this learning takes place and what significance this phenomenon has in higher education. At a scientific level, intercultural learning should be explored in order to uncover the influence of cultural identity, i.e., intercultural learning should be seen in a local context. This experience would provide an opportunity to learn from various everyday intercultural learning situations. Intercultural learning can be not only a form of learning but also a tool for building understanding between people of different cultures. The research object of the study is the process of intercultural learning. The aim of the dissertation is to develop a grounded theory of the process of learning in an intercultural study environment, revealing students’ learning experiences. The research strategy chosen in this study is a constructivist grounded theory (GT). GT is an inductive method that seeks to form a theory by applying the systematic collection, synthesis, analysis, and conceptualization of data. The targeted data collection was based on the analysis of data provided by previous research participants, which revealed the need for further research participants. During the research, only students with at least half a year of study experience, i.e., who have completed at least one semester of intercultural studies, were purposefully selected for the research. To select students, snowballing sampling was used. 18 interviews were conducted with students representing 3 different fields of sciences (social sciences, humanities, and technology sciences). In the process of intercultural learning, language expresses and embodies cultural reality and a person’s cultural identity. It is through language that individual experiences are expressed, and the world in which Others exist is perceived. The increased emphasis is placed on the fact that language conveys certain “signs’ of communication and perception with cultural value, enabling the students to identify the Self and the Other. Language becomes an important tool in the process of intercultural communication because it is only through language that learners can communicate, exchange information, and understand each other. Thus, in the process of intercultural learning, language either promotes interpersonal relationships with foreign students or leads to mutual rejection.

Keywords: intercultural learning, grounded theory, students, other

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Authors: Sujata Sharma, Avinash Singh, Lovely Gautam, Pradeep Sharma, Mau Sinha, Asha Bhushan, Punit Kaur, Tej P. Singh

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Peptidyl-tRNA hydrolase (Pth) Pth is an essential bacterial enzyme that catalyzes the release of free tRNA and peptide moeities from peptidyl tRNAs during stalling of protein synthesis. In order to design inhibitors of Pth from Pseudomonas aeruginosa (PaPth), we have determined the structures of PaPth in its native state and in the bound states with two compounds, amino acylate-tRNA analogue (AAtA) and 5-azacytidine (AZAC). The peptidyl-tRNA hydrolase gene from Pseudomonas aeruginosa was amplified by Phusion High-Fidelity DNA Polymerase using forward and reverse primers, respectively. The E. coliBL21 (λDE3) strain was used for expression of the recombinant peptidyl-tRNA hydrolase from Pseudomonas aeruginosa. The protein was purified using a Ni-NTA superflow column. The crystallization experiments were carried out using hanging drop vapour diffusion method. The crystals diffracted to 1.50 Å resolution. The data were processed using HKL-2000. The polypeptide chain of PaPth consists of 194 amino acid residues from Met1 to Ala194. The centrally located β-structure is surrounded by α-helices from all sides except the side that has entrance to the substrate binding site. The structures of the complexes of PaPth with AAtA and AZAC showed the ligands bound to PaPth in the substrate binding cleft and interacted with protein atoms extensively. The residues that formed intermolecular hydrogen bonds with the atoms of AAtA included Asn12, His22, Asn70, Gly113, Asn116, Ser148, and Glu161 of the symmetry related molecule. The amino acids that were involved in hydrogen bonded interactions in case of AZAC included, His22, Gly113, Asn116, and Ser148. As indicated by fittings of two ligands and the number of interactions made by them with protein atoms, AAtA appears to be a more compatible with the structure of the substrate binding cleft. However, there is a further scope to achieve a better stacking than that of O-tyrosyl moiety because it is not still ideally stacked. These observations about the interactions between the protein and ligands have provided the information about the mode of binding of ligands, nature and number of interactions. This information may be useful for the design of tight inhibitors of Pth enzymes.

Keywords: peptidyl tRNA hydrolase, Acinetobacter baumannii, Pth enzymes, O-tyrosyl

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Authors: Anjali Sadanand, R. V. Nagarajan

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Architecture morphs with advances in technology and the roof, wall, and floor as basic elements of a building, follow in redefining themselves over time. Their contribution is bound by time and held by design principles that deal with function, sturdiness, and beauty. Architecture engages with people to give joy through its form, material, design structure, and spatial qualities. This paper attempts to re-interpret John Ruskin’s “Seven lamps of Architecture” in the context of the architecture of the modern and present period. The paper focuses on the “wall” as an element of study in this context. Four of Ruskin’s seven lamps will be discussed, namely beauty, truth, life, and memory, through examples of architecture ranging from modernism to contemporary architecture of today. The study will focus on the relevance of Ruskin’s principles to the “wall” in specific, in buildings of different materials and over a range of typologies from all parts of the world. Two examples will be analyzed for each lamp. It will be shown that in each case, there is relevance to the significance of Ruskin’s lamps in modern and contemporary architecture. Nature to which Ruskin alludes to for his lamp of “beauty” is found in the different expressions of interpretation used by Corbusier in his Villa Stein façade based on proportion found in nature and in the direct expression of Toyo Ito in his translation of an understanding of the structure of trees into his façade design of the showroom for a Japanese bag boutique. “Truth” is shown in Mies van der Rohe’s Crown Hall building with its clarity of material and structure and Studio Mumbai’s Palmyra House, which celebrates the use of natural materials and local craftsmanship. “Life” is reviewed with a sustainable house in Kerala by Ashrams Ravi and Alvar Aalto’s summer house, which illustrate walls as repositories of intellectual thought and craft. “Memory” is discussed with Charles Correa’s Jawahar Kala Kendra and Venturi’s Vana Venturi house and discloses facades as text in the context of its materiality and iconography. Beauty is reviewed in Villa Stein and Toyo Ito’s Branded Retail building in Tokyo. The paper thus concludes that Ruskin’s Lamps can be interpreted in today’s context and add richness to meaning to the understanding of architecture.

Keywords: beauty, design, facade, modernism

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Pedro Cardoso Alves, Ana Lucia Galinkin, José Carlos Ribeiro

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Political participation, can be a somewhat tricky subject to define, not in small part due to the constant changes in the concept fruit of the effort to include new forms of participatory behavior that go beyond traditional institutional channels. With the advent of the internet and mobile technologies, defining political participation has become an even more complicated endeavor, given de amplitude of politicized behaviors that are expressed throughout these mediums, be it in the very organization of social movements, in the propagation of politicized texts, videos and images, or in the micropolitical behaviors that are expressed in daily interaction. In fact, the very frontiers that delimit physical and digital spaces have become ever more diluted due to technological advancements, leading to a hybrid existence that is simultaneously physical and digital, not limited, as it once was, to the temporal limitations of classic communications. Moving away from those institutionalized actions of traditional political behavior, an idea of constant and fluid participation, which occurs in our daily lives through conversations, posts, tweets and other digital forms of expression, is discussed. This discussion focuses on the factors that precede more direct forms of political participation, interpreting the relation between informational habits, ideology, and political efficacy. Though some of the informational habits can be considered political participation, by some authors, a distinction is made to establish a logical flow of behaviors leading to participation, that is, one must gather and process information before acting on it. To reach this objective, a quantitative survey is currently being applied in Brazilian social media, evaluating feelings of political efficacy, social and economic issue-based ideological stances and informational habits pertaining to collection, fact-checking, and diversity of sources and ideological positions present in the participant’s political information network. The measure being used for informational habits relies strongly on a mix of information literacy and political sophistication concepts, bringing a more up-to-date understanding of information and knowledge production and processing in contemporary hybrid (physical-digital) environments. Though data is still being collected, preliminary analysis point towards a strong correlation between information habits and political efficacy, while ideology shows a weaker influence over efficacy. Moreover, social ideology and economic ideology seem to have a strong correlation in the sample, such intermingling between social and economic ideals is generally considered a red flag for political polarization.

Keywords: political efficacy, ideology, information literacy, cyberpolitics

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Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

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Authors: Ratneev Kaur, Tajinder Kaur, Anupam Kaur

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Introduction: Polycystic Ovary Syndrome (PCOS) is a heterogenous disorder of endocrine system among women of reproductive age. PCOS is characterized by hyperandrogenism, anovulation, polycystic ovaries, hirsutism, obesity, and hyperinsulinemia. Several pathways are implicated in its etiology including the metabolic pathway of steroid hormone synthesis regulatory pathways. PCOS is an androgen excess disorder, genes operating in steroidogenesis may alter pathogenesis of PCOS. The cytochrome P450scc is a cholesterol side chain cleavage enzyme coded by CYP11A1 gene and catalyzes conversion of cholesterol to pregnenolone, the initial and rate-limiting step in steroid hormone synthesis. It is postulated that polymorphisms in this gene may play an important role in the regulation of CYP11A1 expression and leading to increased or decreased androgen production. The present study will be the first study from north India to best of our knowledge, to analyse the association of CYP11A1 (rs11632698) polymorphism in women suffering from PCOS. Methodology: The present study was approved by ethical committee of Guru Nanak Dev University in consistent with declaration of Helsinki. A total of 300 samples (150 PCOS cases and 150 controls) were recruited from Hartej hospital, for the present study. Venous blood sample (3ml) was withdrawn from women diagnosed with PCOS by doctor, according to Rotterdam 2003 criteria and from healthy age matched controls only after informed consent and detailed filled proforma. For molecular genetics analysis, blood was stored in EDTA vials. After DNA isolation by organic method, PCR-RFLP approach was used for genotyping and association analysis of rs11632698 polymorphism. Statistical analysis was done to check for significance of selected polymorphism with PCOS. Results: In 150 PCOS cases, the frequency of AA, AG and GG genotype was found to be 48%, 35%, and 13% compared to 62%, 27% and 8% in 150 controls. The major allele (A) and minor allele (G) frequency was 68% and 32% in cases and 78% and 22% in controls. Minor allele frequency was higher in cases as compared to controls, as well as the distribution of genotype was observed to be statistically significant (ᵡ²=6.525, p=0.038). Odds ratio in dominant, co-dominant and recessive models observed was 1.81 (p=0.013), 1.54 (p=0.012) and 1.77 (p=0.132) respectively. Conclusion: The present study showed statistically significant association of rs11632698 with PCOS (p=0.038) in North Indian women.

Keywords: polycystic ovary syndrome, CYP11A1, rs11632698, hyperandrogenism

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Authors: P. Vindin, R. Cordier, N. J. Wilson, H. Lee

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Engagement in community-based activities such as education, employment, and social relationships can improve the quality of life for individuals with Autism Spectrum Disorder (ASD). Community mobility is vital to attaining independence for individuals with ASD. Learning to drive and gaining a driver’s license is a critical link to community mobility; however, for individuals with ASD acquiring safe driving skills can be a challenging process. Issues related to anxiety, executive function, and social communication may affect driving behaviours. Driving training and education aimed at addressing barriers faced by learner drivers with ASD can help them improve their driving performance. A multi-site randomized controlled trial (RCT) was conducted to evaluate the effectiveness of an autism-specific driving training intervention for improving the on-road driving performance of learner drivers with ASD. The intervention was delivered via a training manual and interactive website consisting of five modules covering varying driving environments starting with a focus on off-road preparations and progressing through basic to complex driving skill mastery. Seventy-two learner drivers with ASD aged 16 to 35 were randomized using a blinded group allocation procedure into either the intervention or control group. The intervention group received 10 driving lessons with the instructors trained in the use of an autism-specific driving training protocol, whereas the control group received 10 driving lessons as usual. Learner drivers completed a pre- and post-observation drive using a standardized driving route to measure driving performance using the Driving Performance Checklist (DPC). They also completed anxiety, executive function, and social responsiveness measures. The findings showed that there were significant improvements in driving performance for both the intervention (d = 1.02) and the control group (d = 1.15). However, the differences were not significant between groups (p = 0.614) or study sites (p = 0.842). None of the potential moderator variables (anxiety, cognition, social responsiveness, and driving instructor experience) influenced driving performance. This study is an important step toward improving community mobility for individuals with ASD showing that an autism-specific driving training intervention can improve the driving performance of leaner drivers with ASD. It also highlighted the complexity of conducting a multi-site design even when sites were matched according to geography and traffic conditions. Driving instructors also need more and clearer information on how to communicate with learner drivers with restricted verbal expression.

Keywords: autism spectrum disorder, community mobility, driving training, transportation

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Authors: Elif Gencturk, Ekin Yurdakul, Ahmet Y. Celik, Senol Mutlu, Kutlu O. Ulgen

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Yeast cells are generally used as a model system of eukaryotes due to their complex genetic structure, rapid growth ability in optimum conditions, easy replication and well-defined genetic system properties. Thus, yeast cells increased the knowledge of the principal pathways in humans. During fermentation, carbohydrates (hexoses and pentoses) degrade into some toxic by-products such as 5-hydroxymethylfurfural (5-HMF or HMF) and furfural. HMF influences the ethanol yield, and ethanol productivity; it interferes with microbial growth and is considered as a potent inhibitor of bioethanol production. In this study, yeast single cell behavior under HMF application was monitored by using a continuous flow single phase microfluidic platform. Microfluidic device in operation is fabricated by hot embossing and thermo-compression techniques from cyclo-olefin polymer (COP). COP is biocompatible, transparent and rigid material and it is suitable for observing fluorescence of cells considering its low auto-fluorescence characteristic. The response of yeast cells was recorded through Red Fluorescent Protein (RFP) tagged Nop56 gene product, which is an essential evolutionary-conserved nucleolar protein, and also a member of the box C/D snoRNP complexes. With the application of HMF, yeast cell proliferation continued but HMF slowed down the cell growth, and after HMF treatment the cell proliferation stopped. By the addition of fresh nutrient medium, the yeast cells recovered after 6 hours of HMF exposure. Thus, HMF application suppresses normal functioning of cell cycle but it does not cause cells to die. The monitoring of Nop56 expression phases of the individual cells shed light on the protein and ribosome synthesis cycles along with their link to growth. Further computational study revealed that the mechanisms underlying the inhibitory or inductive effects of HMF on growth are enriched in functional categories of protein degradation, protein processing, DNA repair and multidrug resistance. The present microfluidic device can successfully be used for studying the effects of inhibitory agents on growth by single cell tracking, thus capturing cell to cell variations. By metabolic engineering techniques, engineered strains can be developed, and the metabolic network of the microorganism can thus be manipulated such that chemical overproduction of target metabolite is achieved along with the maximum growth/biomass yield.  

Keywords: COP, HMF, ribosome biogenesis, thermoplastic microbioreactor, yeast

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Authors: Deepak Kumar, Ravi Rajwanshi, Mohd. Aslam Yusuf, Nisha Kant Pandey, Preeti Singh, Mukesh Saxena, Neera Bhalla Sarin

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Global issues are leading to concerns over food security. These include climate change, urbanization, increase in population subsequently leading to greater energy and water demand. Futuristic approach for crop improvement involves gene pyramiding for agronomic traits that empower the plants to withstand multiple stresses. In an earlier study from the laboratory, the efficacy of overexpressing γ-tocopherol methyl transferase (γ-TMT) gene from the vitamin E biosynthetic pathway has been shown to result in six-fold increase of the most biologically active form, the α-tocopherol in Brassica juncea which resulted in alleviation of salt, heavy metal and osmoticum induced stress by the transgenic plants. The glyoxalase I (gly I) gene from the glyoxalase pathway has also been earlier shown by us to impart tolerance against multiple abioitc stresses by detoxification of the cytotoxic compound methylglyoxal in Brassica juncea. Recently, both the transgenes were pyramided in Brassica juncea lines through sexual crosses involving two stable Brassica juncea lines overexpressing γ-TMT and gly I genes respectively. The transgene integration was confirmed by PCR analysis and their mRNA expression was evident by RT-PCR analysis. Preliminary physiological investigations showed ~55% increased seed germination under 200 mM NaCl stress in the pyramided line and 81% higher seed germination under 200 mM mannitol stress as compared to the WT control plants. The pyramided lines also retained more chlorophyll content when the leaf discs were floated on NaCl (200, 400 and 600 mM) or mannitol (200, 400 and 600 mM) compared to the WT control plants. These plants had higher Relative Water Content and greater solute accumulation under stress compared to the parental plants having γ-TMT or the glyI gene respectively. The studies revealed the synergy of two components from different metabolic pathways in enhancing stress hardiness of the transgenic B. juncea plants. It was concluded that pyramiding of genes (γ-TMT and glyI) from diverse pathways can lead to enhanced tolerance to salt and mannitol stress (simulating drought conditions). This strategy can prove useful in enhancing the crop yields under various abiotic stresses.

Keywords: abiotic stress, brassica juncea, glyoxalase I, α-tocopherol

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Authors: Natasha Perez

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This autobiographical narrative inquiry explores the relationship between religious practice, identity, language and literacy in the author’s life experience as a second-generation Cuban-American growing up in the bilingual spaces of South Florida. The author describes how the social practices around language, including the flexibility to communicate in English and Spanish simultaneously, known as translanguaging, were instrumental to developing a biliterate cosmopolitan identity, along with a greater sense of Latinidad through interactions with diverse Latinx church members. This narrative study involved cycles of writing, reading, and reflection within a three-dimensional narrative inquiry space in order to discover the ways in which language and literacy development in the relationship between the personal and the social, across time and space, as historically situated phenomena. The findings show that Catholic faith practices have always been a source and expression of Cuban-ness, a means of sustaining Cuban identity, as well as a medium for bilingual language and literacy practice in the author’s life. Despite lacking formal literacy education in Spanish, she benefitted from the Catholic Church’s response to the surge of Spanish-speaking immigrants in South Florida in the 1980s and the subsequent flexibility of language practice in church-sponsored youth groups. The faith-sharing practices of the youth group created a space to use Spanish in more sophisticated ways that served to build confidence as a bilingual speaker and expand bilingual competence. These experiences also helped the author develop a more salient identity as Cuban-American and a deeper connection to her Cuban-ness in relation to the Nicaraguan, Venezuelan, and first-generation Cuban identities of my peers. The youth group also fostered cosmopolitan identity building through interactions with pan-ethnic Spanish speakers, with Catholicism as a common language and culture that served as a uniting force. Interaction with these peers also fostered cosmopolitan understandings that deepened the author’s knowledge of the geographical boundaries, political realities, and socio-historical differences between these groups of immigrants. This narrative study opens a window onto the micro-processes and socio-cultural dynamics of language and identity development in the second generation, with the potential to deepen our understanding of the impact of religious practice on these.

Keywords: literacy, religion, identity, comopolitanism, culture, language, translanguaging

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Authors: Judit Perjessy, Zsolt Zalan, Ferenc Hegyi, Eniko Horvath-Szanics, Krisztina Takacs, Andras Nagy, Adel Klupacs, Erika Koppany-Szabo, Zhirong Wang, Kaituo Wang, Muying Du, Jianquan Kan

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The post-harvest diseases cause great economic losses in the fruit and vegetables; the prevention of these deterioration has great importance. Against the fungi, which cause most of the diseases, are extensively used the fungicides. However, there are increasing consumer concerns over the presence of pesticide residues in food. An alternative and in recent years, increasingly studied method for the prevention of the diseases is biocontrol, where antagonistic microorganisms are used for the control of fungi. The genera of Lactobacillus is well known and extensively studied, but its applicability as biocontrol agents in post-harvest preservation of fruit and vegetables is poorly investigated. However these bacteria can be found on the surface of the plants and have great antimicrobial activity. In our study we have investigated the chitinase activity, the antifungal effect and the applicability of several Lactobacillus strains to select potential biocontrol agents. We investigated the determination of the environmental parameters of a gene (encoding chitinase) expression and we also investigated the relationship between actual antifungal activity and potential chitinase activity. Mixed cultures were also developed to enhance the antifungal activity and determined the optimal mold spore and bacteria concentration ratio for the appropriate efficacy. Five Lactobacillus strains (L. acidophilus N2, L. delbrueckii subsp. bulgaricus B397, L. sp. 2231, L. sake subsp. sake 2471, L. buchneri 1145) possess chitinase-coding gene from the 43 investigated Lactobacillus strains. Proteins with similar molecular weight and separation properties like bacterial chitinases were detected from these strains, which also possess chitin-binding property. Nevertheless, they were inactive, lacks the chitinolytic activity. In point of the cumulative activity of inhibition, our results showed that certain strains were statistically significant in a positive direction compared to other strains, e.g., L. rhamnosus VT1 and L. Casey 154 have shown great general antifungal effect against 11 molds from the genera Penicillium and Botrytis and isolated from spoiled fruit and vegetables. Also, some mixed cultures (L. rhamnosus VT1 - L. Plantarum 299v) showed significant antifungal effects against the indigenous molds on the surface of apple fruit during the industrial storage experiment. Thus, they could be promising for post-harvest biopreservation.

Keywords: biocontrol, chitinase, Lactobacillus, post-harvest

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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Authors: Krithika Lakshmi Sathiya Moorthy

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Introduction: Young people’s attitude towards Intimate partner violence (IPV) is likely to influence their indulgence in or abstinence from IPV in future. We aimed to assess the knowledge and attitudes of college students in a south Indian city regarding IPV, its associated factors and redressal mechanisms. Methods: A convenient sample of 247 students, pursuing medicine and engineering, participated in this analytical cross sectional study. They responded to a self-administered questionnaire developed and pretested for this study. The questionnaire comprises statements from a third person’s perspective and vignettes to reduce social desirability bias. Clearance was obtained from the Institute Ethical Committee of Velammal Medical College Hospital and Research Institute, Madurai, India. Data were entered in Epidata Entry v3.1, Odense, Denmark and analysed using SPSS v20.0. Results: Among 247 students, 116 (47%) were males and 59 (24.9%) hailed from rural areas. About 18% (43) of students believed that IPV was a problem only among females. Almost half of the students had witnessed IPV; at home between their parents (9.7%), other family members (13.4%), in their neighbourhood (13%) or public places (15%). Only 118 (47.8%) were aware that a law was in place in India to address IPV. The perceived risk factors for IPV were alcoholic spouse (78.9%), low income families (53.8%), personality traits (52.2%) and dowry system (51%). A sizeable number of students (38.4%) believed that some amount of physical violence was allowable in a marital relationship while 57.6% even considered IPV as an expression of love. Males as compared to females were more in agreement with negative gender stereotypes such as husband can– ‘threaten wife to ensure welfare of family’ (55% vs. 34%, p < 0.001), ‘spy on wife to check fidelity’ (41% vs. 27%, p < 0.001), ‘financially deprive housewife to punish’ (13% vs. 3.8%, p=0.001) and agreed with the statement that it is ‘duty of wife to comply with demands for sex from the husband’ (9.5% vs 4.6%, p=0.3). About 32% males and 25.6% females foresaw themselves as perpetrators of IPV in future. Conclusion: Knowledge about IPV and the associated risk factors among the study population was satisfactory. However, there was widespread acceptance of negative societal gender stereotypes, more so among males and some degrees of IPV were acceptable between married couples. The study advocates the need to halt the propagation of negative gender stereotypes in the impressionable young minds and the necessity to spread the awareness that no degree of IPV is acceptable. This knowledge is also required to plan the content and choose the appropriate media to effectively communicate the awareness about IPV among young persons.

Keywords: attitude, India, intimate partner violence, knowledge, students

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Authors: Ana L. Gonzalez-Celis, Edgardo Ruiz-Carrillo, Karina Reyes-Jarquin, Margarita Chavez-Becerra

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Since recent decades, the aging has been viewed from a more positive perspective, where is not only about losses and damage, but also about being on a stage where you can enjoy life and live with well-being and quality of life. The challenge to feel better is to find those resources that seniors have. For that reason, psychological well-being has shown interest in the study of the affect and life satisfaction (hedonic well-being), while from a more recent tradition, focus on the development of capabilities and the personal growth, considering both as the main indicators of the quality of life. A resource that can be used in the later age is generativity, which refers to the ability of older people to develop and grow through activities that contribute with the improvement of the context in which they live and participate. In this way the generative interest is understood as a favourable attitude that contribute to the common benefit while strengthening and enriching the social institutions, to ensure continuity between generations and social development. On the other hand, generative behavior, differentiating from generative interest, is the expression of that attitude reflected in activities that make a social contribution and a benefit for generations to come. Hence the purpose of the research was to test if there is an association between the generative behaviour type and the psychological well-being with their dimensions. For this reason 188 Mexican adults from 60 to 94 years old (M = 69.78), 67% women, 33% men, completed two instruments: The Ryff’s Well-Being Scales to measure psychological well-being with 39 items with two dimensions (Hedonic and Eudaimonic well-being), and the Loyola’s Generative Behaviors Scale, grouped in five categories: Knowledge transmitted to the next generation, things to be remember, creativity, be productive, contribution to the community, and responsibility of other people. In addition, the socio-demographic data sheet was tested, and self-reported health status. The results indicated that the psychological well-being and its dimensions were significantly associated with the presence of generative behavior, where the level of well-being was higher when the frequency of some generative behaviour excelled; finding that the behavior with greater psychological well-being (M = 81.04, SD = 8.18) was "things to be remembered"; while with greater hedonic well-being (M = 73.39, SD = 12.19) was the behavior "responsibility of other people"; and with greater Eudaimonic well-being (M = 84.61, SD = 6.63), was the behavior "things to be remembered”. The most important findings highlight the importance of generative behaviors in adulthood, finding empirical evidence that the generativity in the last stage of life is associated with well-being. However, by finding differences in the types of generative behaviors at the level of well-being, is proposed the idea that generativity is not situated as an isolated construct, but needs other contextualized and related constructs that can simultaneously operate at different levels, taking into account the relationship between the environment and the individual, encompassing both the social and psychological dimension.

Keywords: eudaimonic well-being, generativity, hedonic well-being, Mexican elders, psychological well-being

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Authors: Salma A. Mahmoud

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Epigenetic, or alteration in gene expression influenced by extragenetic factors, has emerged as one of the most promising areas that will address some of the gaps in our current knowledge in understanding patterns of human variation. In the last decade, the research investigating epigenetic mechanisms in many fields has flourished and witnessed significant progress. It paved the way for a new era of integrated research especially between anthropology/archeology and life sciences. Skeletal remains are considered the most significant source of information for studying human variations across history, and by utilizing these valuable remains, we can interpret the past events, cultures and populations. In addition to archeological, historical and anthropological importance, studying bones has great implications in other fields such as medicine and science. Bones also can hold within them the secrets of the future as they can act as predictive tools for health, society characteristics and dietary requirements. Bones in their basic forms are composed of cells (osteocytes) that are affected by both genetic and environmental factors, which can only explain a small part of their variability. The primary objective of this project is to examine the epigenetic landscape/signature within bones of archeological remains as a novel marker that could reveal new ways to conceptualize chronological events, gender differences, social status and ecological variations. We attempted here to address discrepancies in common variants such as methylome as well as novel epigenetic regulators such as chromatin remodelers, which to our best knowledge have not yet been investigated by anthropologists/ paleoepigenetists using plethora of techniques (biological, computational, and statistical). Moreover, extracting epigenetic information from bones will highlight the importance of osseous material as a vector to study human beings in several contexts (social, cultural and environmental), and strengthen their essential role as model systems that can be used to investigate and construct various cultural, political and economic events. We also address all steps required to plan and conduct an epigenetic analysis from bone materials (modern and ancient) as well as discussing the key challenges facing researchers aiming to investigate this field. In conclusion, this project will serve as a primer for bioarcheologists/anthropologists and human biologists interested in incorporating epigenetic data into their research programs. Understanding the roles of epigenetic mechanisms in bone structure and function will be very helpful for a better comprehension of their biology and highlighting their essentiality as interdisciplinary vectors and a key material in archeological research.

Keywords: epigenetics, archeology, bones, chromatin, methylome

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Authors: Yi Li, Yinan Zheng, Ya Ke, Yungwing Ho

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Motor learning is a process that frequently happens among humans and rodents, which is defined as the changes in the capability to perform a skill that is conformed to have a relatively permanent improvement through practice or experience. There are many ways to learn a behavior, among which is observational learning. Observational learning is the process of learning by watching the behaviors of others, for example, a child imitating parents, learning a new sport by watching the training videos or solving puzzles by watching the solutions. Many research explores observational learning in humans and primates. However, the neuronal mechanism of which, especially observational motor learning, was uncertain. It’s well accepted that mirror neurons are essential in the observational learning process. These neurons fire when the primate performs a goal-directed action and sees someone else demonstrating the same action, which suggests they have high firing activity both completing and watching the behavior. The mirror neurons are assumed to mediate imitation or play a critical and fundamental role in action understanding. They are distributed in many brain areas of primates, i.e., posterior parietal cortex (PPC), premotor cortex (M2), and primary motor cortex (M1) of the macaque brain. However, few researchers report the existence of mirror neurons in rodents. To verify the existence of mirror neurons and the possible role in motor learning in rodents, we performed customised string-pulling behavior combined with multiple behavior analysis methods, photometry, electrophysiology recording, c-fos staining and optogenetics in healthy mice. After five days of training, the demonstrator (demo) mice showed a significantly quicker response and shorter time to reach the string; fast, steady and accurate performance to pull down the string; and more precisely grasping the beads. During three days of observation, the mice showed more facial motions when the demo mice performed behaviors. On the first training day, the observer reduced the number of trials to find and pull the string. However, the time to find beads and pull down string were unchanged in the successful attempts on the first day and other training days, which indicated successful action understanding but failed motor learning through observation in mice. After observation, the post-hoc staining revealed that the c-fos expression was increased in the cognitive-related brain areas (medial prefrontal cortex) and motor cortices (M1, M2). In conclusion, this project indicated that the observation led to a better understanding of behaviors and activated the cognitive and motor-related brain areas, which suggested the possible existence of mirror neurons in these brain areas.

Keywords: observation, motor learning, string-pulling behavior, prefrontal cortex, motor cortex, cognitive

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Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

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Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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Authors: Elizabeth Laguaite, Alexandria Purdy

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Heart transplant recipients face psycho-physiological stressors, including pain, lengthy hospitalizations, delirium, and existential crises. They pose an increased risk for Post Traumatic Stress Disorder (PTSD) and can be a predictor of poorer mental and physical Health-Related Quality of Life (HRQOL) outcomes and increased mortality. There is limited research on the prevention of Post Traumatic Stress Symptoms (PTSS) in transplant patients. This case report focuses on a collaborative Music and Art Therapy intervention used to improve outcomes for HMH transplant recipient John (Alias). John, a 58-year-old man with congestive heart failure, was admitted to HMH in February of 2021 with cardiogenic shock, cannulated with an Intra-aortic Balloon Pump, Impella 5.5, and Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) as a bridge to heart and kidney transplant. He was listed as status 1 for transplant. Music Therapy and Art Therapy (MT and AT) were ordered by the physician for mood regulation, trauma processing and anxiety management. During MT/AT sessions, John reported a history of anxiety and depression exacerbated by medical acuity, shortness of breath, and lengthy hospitalizations. He expressed difficulty sleeping, pain, and existential questions. Initially seen individually by MT/AT, it was determined he could benefit from a collaborative approach due to similar thematic content within sessions. A Life Review intervention was developed by MT/AT. The purpose was for him to creatively express, reflect and process his medical narrative, including the identification of positive and negative events leading up to admission at HMH, the journey to transplant, and his hope for the future. Through this intervention, he created artworks that symbolized each event and paired them with songs, two of which were composed with the MT during treatment. As of September 2023, John has not been readmitted to the hospital and expressed that this treatment is what “got him through transplant”. MT and AT can provide opportunities for a patient to reminisce through creative expression, leading to a shift in the personal meaning of these experiences, promoting resolution, and ameliorating associated trauma. The closer to trauma it is processed, the less likely to develop PTSD. This collaborative MT/AT approach could improve long-term outcomes by reducing mortality and readmission rates for transplant patients.

Keywords: art therapy, music therapy, critical care, PTSD, trauma, transplant

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Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

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The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

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Authors: Hortènsia Curell, Ana Fernández-Montraveta

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This paper presents the creation, development, and analysis of a corpus designed to study the presence of attitude markers and author’s stance in research articles in two different areas of linguistics (theoretical linguistics and sociolinguistics). These two disciplines are expected to behave differently in this respect, given the disparity in their discursive conventions. Attitude markers in this work are understood as the linguistic elements (adjectives, nouns and verbs) used to convey the writer's stance towards the content presented in the article, and are crucial in understanding writer-reader interaction and the writer's position. These attitude markers are divided into three broad classes: assessment, significance, and emotion. In addition to them, we also consider first-person singular and plural pronouns and possessives, modal verbs, and passive constructions, which are other linguistic elements expressing the author’s stance. The corpus, Corpus of Attitude in Academic Writing (CAAW), comprises a collection of 21 articles, collected from six journals indexed in JCR. These articles were originally written in English by a single native-speaker author from the UK or USA and were published between 2022 and 2023. The total number of words in the corpus is approximately 222,400, with 106,422 from theoretical linguistics (Lingua, Linguistic Inquiry and Journal of Linguistics) and 116,022 from sociolinguistics journals (International Journal of the Sociology of Language, Language in Society and Journal of Sociolinguistics). Together with the corpus, we present the tool created for the creation and storage of the corpus, along with a tool for automatic annotation. The steps followed in the compilation of the corpus are as follows. First, the articles were selected according to the parameters explained above. Second, they were downloaded and converted to txt format. Finally, examples, direct quotes, section titles and references were eliminated, since they do not involve the author’s stance. The resulting texts were the input for the annotation of the linguistic features related to stance. As for the annotation, two articles (one from each subdiscipline) were annotated manually by the two researchers. An existing list was used as a baseline, and other attitude markers were identified, together with the other elements mentioned above. Once a consensus was reached, the rest of articles were annotated automatically using the tool created for this purpose. The annotated corpus will serve as a resource for scholars working in discourse analysis (both in linguistics and communication) and related fields, since it offers new insights into the expression of attitude. The tools created for the compilation and annotation of the corpus will be useful to study author’s attitude and stance in articles from any academic discipline: new data can be uploaded and the list of markers can be enlarged. Finally, the tool can be expanded to other languages, which will allow cross-linguistic studies of author’s stance.

Keywords: academic writing, attitude, corpus, english

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Authors: Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Teklehaimanot Hailesslasie Teklu

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Recent developments in targeted genome editing accelerated genetic research and opened new potentials to improve crops for better yields and quality. Given the significance of cereal crops as a primary source of food for the global population, the utilization of contemporary genome editing techniques like CRISPR/Cas9 is timely and crucial. CRISPR/Cas technology has enabled targeted genomic modifications, revolutionizing genetic research and exploration. Application of gene editing through CRISPR/Cas9 in enhancing sorghum is particularly vital given the current ecological, environmental, and agricultural challenges exacerbated by climate change. As sorghum is one of the main staple foods of our region and is known to be a resilient crop with a high potential to overcome the above challenges, the application of genome editing technology will enhance the investigation of gene functionality. CRISPR/Cas9 enables the improvement of desirable sorghum traits, including nutritional value, yield, resistance to pests and diseases, and tolerance to various abiotic stresses. Furthermore, CRISPR/Cas9 has the potential to perform intricate editing and reshape the existing elite sorghum varieties, and introduce new genetic variations. However, current research primarily focuses on improving the efficacy of the CRISPR/Cas9 system in successfully editing endogenous sorghum genes, making it a feasible and successful undertaking in sorghum improvement. Recent advancements and developments in CRISPR/Cas9 techniques have further empowered researchers to modify additional genes in sorghum with greater efficiency. Successful application and advancement of CRISPR techniques in sorghum will aid not only in gene discovery and the creation of novel traits that regulate gene expression and functional genomics but also in facilitating site-specific integration events. The purpose of this review is, therefore, to elucidate the current advances in sorghum genome editing and highlight its potential in addressing food security issues. It also assesses the efficiency of CRISPR-mediated improvement and its long-term effects on crop improvement and host resistance against parasites, including tissue-specific activity and the ability to induce resistance. This review ends by emphasizing the challenges and opportunities of CRISPR technology in combating parasitic plants and proposing directions for future research to safeguard global agricultural productivity.

Keywords: CRISPR/Cas9, genome editing, quality, sorghum, stress, yield

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Authors: B. K. Manjunatha Goud, Aruna Chanu Oinam

Abstract:

The undergraduate medical curriculum is oriented towards training the students to undertake the responsibilities of a physician. During the training period, adequate emphasis is placed on inculcating logical and scientific habits of thought; clarity of expression and independence of judgment; and ability to collect and analyze information and to correlate them. At Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Biochemistry a basic medical science subject is taught in the 1st year of 5 years medical course with vertical interdisciplinary interaction with all subjects, which needs to be taught and learned adequately by the students to be related to clinical case or clinical problem in medicine and future diagnostics so that they can practice confidently and skillfully in the community. Based on these facts study was done to know the extent of usage of library resources by the students and the impact of study materials on their preparation for examination. It was a comparative cross sectional study included 100 and 80 1st and 2nd-year students who had successfully completed Biochemistry course. The purpose of the study was explained to all students [participants]. Information was collected on a pre-designed, pre-tested and self-administered questionnaire. The questionnaire was validated by the senior faculties and pre tested on students who were not involved in the study. The study results showed that 80.30% and 93.15% of 1st and 2nd year students have the clear idea of course outline given in course handout or study guide. We also found a statistically significant number of students agreed that they were benefited from the practical session and writing notes in the class hour. A high percentage of students [50% and 62.02%] disagreed that that reading only the handouts is enough for their examination as compared to other students. The study also showed that only 35% and 41% of students visited the library on daily basis for the learning process, around 65% of students were using lecture notes and text books as a tool for learning and to understand the subject and 45% and 53% of students used the library resources (recommended text books) compared to online sources before the examinations. The results presented here show that students perceived that e-learning resources like power point presentations along with text book reading using SQ4R technique had made a positive impact on various aspects of their learning in Biochemistry. The use of library by students has overall positive impact on learning process especially in medical field enhances the outcome, and medical students are better equipped to treat the patient. But it’s also true that use of library use has been in decline which will impact the knowledge aspects and outcome. In conclusion, a student has to be taught how to use the library as learning tool apart from lecture handouts.

Keywords: medical education, learning resources, study guide, biochemistry

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