Search results for: genes expression

Authors: Sharmeen Rahman, Daniel Schmidt, Jane Hughes

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Paratya australiensis Kemp (Decapoda: Atyidae) is a widely distributed indigenous freshwater shrimp, highly abundant in eastern Australia. This species has been considered as a model stream organism to study genetics, dispersal, biology, behaviour and evolution in Atyids. Paratya has a filter feeding and scavenging habit which plays a significant role in the formation of lotic community structure. It has been shown to reduce periphyton and sediment from hard substrates of coastal streams and hence acts as a strongly-interacting ecosystem macroconsumer. Besides, Paratya is one of the major food sources for stream dwelling fishes. Paratya australiensis is a cryptic species complex consisting of 9 highly divergent mitochondrial DNA lineages. Among them, one lineage has been observed to favour upstream sites at higher altitudes, with cooler water temperatures. This study aims to identify local adaptation in upstream and downstream populations of this lineage in three streams in the Conondale Range, North-eastern Brisbane, Queensland, Australia. Two populations (up and down stream) from each stream have been chosen to test for local adaptation, and a parallel pattern of adaptation is expected across all streams. Six populations each consisting of 24 individuals were sequenced using the Restriction Site Associated DNA-seq (RAD-seq) technique. Genetic markers (SNPs) were developed using double digest RAD sequencing (ddRAD-seq). These were used for de novo assembly of Paratya genome. De novo assembly was done using the STACKs program and produced 56, 344 loci for 47 individuals from one stream. Among these individuals, 39 individuals shared 5819 loci, and these markers are being used to test for local adaptation using Fst outlier tests (Arlequin) and Bayesian analysis (BayeScan) between up and downstream populations. Fst outlier test detected 27 loci likely to be under selection and the Bayesian analysis also detected 27 loci as under selection. Among these 27 loci, 3 loci showed evidence of selection at a significance level using BayeScan program. On the other hand, up and downstream populations are strongly diverged at neutral loci with a Fst =0.37. Similar analysis will be done with all six populations to determine if there is a parallel pattern of adaptation across all streams. Furthermore, multi-locus among population covariance analysis will be done to identify potential markers under selection as well as to compare single locus versus multi-locus approaches for detecting local adaptation. Adaptive genes identified in this study can be used for future studies to design primers and test for adaptation in related crustacean species.

Keywords: Paratya australiensis, rainforest streams, selection, single nucleotide polymorphism (SNPs)

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Authors: Benyam Zenebe, Tesfaye Sisay, Gurja Belay, Workabeba Abebe

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Background: The prevalence and antibiogram of pathogenic E. coli strains, which cause diarrhea vary from region to region, and even within countries in the same geographical area. In Ethiopia, diagnostic approaches to E. coli induced diarrhea in children less than five years of age are not standardized. The aim of this study was to determine the involvement of pathogenic E. coli strains in child diarrhea and determine the antibiograms of the isolates in children less than 5 years of age with diarrhea at Addis Ababa University College of Health Sciences TikurAnbessa Specialized Hospital, Addis Ababa, Ethiopia. Methods: A purposive study that included 98 diarrheic children less than five years of age was conducted at Addis Ababa University College of Health Sciences, TikurAnbessa Specialized Hospital, Addis Ababa, Ethiopia to detect pathogenic E. coli biotypes. Stool culture was used to identify presumptive E. coliisolates. Presumptive isolates were confirmed by biochemical tests, and antimicrobial susceptibility tests were performed on confirmed E. coli isolates by the disk diffusion method. DNA was extracted from confirmed isolates by a heating method and subjected to Polymerase Chain Reaction or the presence of virulence genes. Amplified PCR products were analyzed by agarose gel electrophoresis. Data were collected on child demographics and clinical conditions using administered questionnaires. The prevalence of E. coli strains from the total diarrheic children, and the prevalence of pathogenic strains from total E. coli isolates along with their susceptibility profiles; the distribution of pathogenic E.coli biotypes among different age groups and between the sexes were determined by using descriptive statistics. Result: Out of 98 stool specimens collected from diarrheic children less than 5 years of age, 75 presumptive E. coli isolates were identified by culture; further confirmation by biochemical tests showed that only 56 of the isolates were E. coli; 29 of the isolates were found in male children and 27 of them in female children. Out of the 58 isolates of E. coli, 25 pathotypes belonging to different classes of pathogenic strains: STEC, EPEC, EHEC, EAEC were detected by using the PCR technique. Pathogenic E. coli exhibited high rates of antibiotic resistance to many of the antibiotics tested. Moreover, they exhibited multiple drug resistance. Conclusion: This study found that the isolation rate of E. coli and the involvement of antibiotic-resistant pathogenic E. coli in diarrheic children is prominent, and hence focus should be given on the diagnosis and antimicrobial sensitivity testing of pathogenic E. coli at Addis Ababa University College of Health Sciences TikurAnbessa Specialized Hospital. Among antibiotics tested, Cefotitan could be a drug of choice to treat E. coli.

Keywords: antibiotic susceptibility profile, children, diarrhea, E. coli, pathogenic

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Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi

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Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.

Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham

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Authors: Ahmed A. Sedik, Doaa Mahmoud Shuaib

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Brain injury is a cause of disability and death worldwide. Potassium dichromate (PD) is an environmental contaminant widely recognized as teratogenic, carcinogenic, and mutagenic towards animals and humans. The aim of the present study was to investigate the possible neuroprotective effects of tangeretin (TNG) on PD-induced brain injury in rats. Forty male adult Wistar rats were randomly and blindly allocated into four groups (8 rats /group). The first group received saline intranasally (i.n.). The second group received a single dose of PD (2 mg/kg, i.n.). The third group received TNG (50 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. Four groups received TNG (100 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. 18- hours after the final treatment, behavioral parameters, neuro-biochemical indices, FTIR analysis, and histopathological studies were evaluated. Results of the present study revealed that rats intoxicated with PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in Nrf2 signaling pathway and GSH levels with an increase in brain contents of TNF-α, IL-10, and NF-kβ and reduced AKT levels in brain homogenates. Treatment with TNG (100 mg/kg; orally) ameliorated behavioral, cholinergic activities and oxidative stress, decreased the elevated levels of pro-inflammatory mediators; TNF-α, IL-10, and NF-κβ elevated AKT pathway with corrected FTIR spectra with a decrease in brain content of chromium residues detected by atomic absorption spectrometry. Also, TNG administration restored the morphological changes as degenerated neurons and necrosis associated with PD intoxication. Additionally, TNG decreased Caspase-3 expression in the brain of PD rats. TNG plays a crucial role in AKT/Nrf2 pathway that is responsible for their antioxidant, anti-inflammatory effects, and apoptotic pathway against PD-induced brain injury in rats.

Keywords: tangeretin, potassium dichromate, brain injury, AKT/Nrf2 signaling pathway, FTIR, atomic absorption spectrometry

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Authors: Simont Toussi

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Cameroon and the Central African Republic arebound by the provisions of many regional and international charters, which condemn the manipulation of information, obstacles to access reliable information, or the limitation of freedoms of expression and opinion. These two countries also have constitutional guarantees for free speech and access to true and liable information. However, they are yet to define specific policies and regulations for access to information, disinformation, or misinformation. Yet, certain countries’ laws and regulations related to information and communication technologies, to criminal procedures, to terrorism, or intelligence services contain provisions that rather hider human rights by condemning false information. Like many other African countries, Cameroon and the Central African Republic face a profound democratic regression, and governments use multiple methods to stifle online discourse and digital rights. Despite the increased uptake of digital tools for political participation, there is a lack of interactivity and adoption of these tools. This enables a scarcity of information and creates room for the spreading of disinformation in the public space, hamperingdemocracy and the respect for human rights. This research aims to analyse the adequacy of stakeholders’ responses to disinformation in Cameroon and the Central African Republic in periods of political contestation, such as elections and anti-government protests, to highlight the nature, perpetrators, strategies, and channels of disinformation, as well as its effects on democratic actors, including civil society, bloggers, government critics, activists, and other human rights defenders. The study follows a qualitative method with literature review, content analysis, andkey informant’sinterviews with stakeholders’ representatives, emphasized crowdsourcing as a data and information collecting method in the two countries.

Keywords: disinformation, democracy, political manipulation, social media, media, fake news, central Africa, cameroon, misinformation, free speech

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Authors: Elaine Stavro

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In our present world where acts of incivility, intolerance and anger towards minority communities is on the rise, the ways museum practices cultivate ethical generosity is of interest. Democratic theorists differ as to how they believe respect can be generated through active participation. Allowing minority communities a role in determining what artifacts will be displayed and how they will be displayed has been an important step in generating respect. In addition, the rise of indigenous museums, slave museums and curators who represent these communities, contribute to the communication of their history of oppression. These institutional practices have been supplemented by the handling of objects, recognition stories and multisensory exhibitions. Psychoanalysis, object relations theorists believe that the handling of objects: amenable objects and responsive listeners will trigger the expression of anomie, alienation and traumatizing experiences. Not only memorializing but engaging with one’s lose in a very personal way can facilitate the process of mourning. Manchester Museum (UK) gathered together Somalian refugees, who in the process of handling their own objects and those offered at the museum, began to tell their stories. Democratic theorists (especially affect theorists or vital materialists or Actor Network theorists) believe that things can be social actants- material objects have agentic capacities that humans should align with. In doing so, they challenge social constructivism that attributes power to interpreted things, but like them they assume an openness or responsiveness to Otherness can be cultivated. Rich sensory experiences, corporeal engagement (devices that involve bodily movement or objects that involve handling) auditory experiences (songs) all contribute to improve one’s responsiveness and openness to Others. This paper will focus specifically on slave museums/ and exhibits in the U.K, the USA., South Africa to explore and evaluate their democratic strategies in cultivating tolerant practices via the various democratic avenues outlined above.

Keywords: democratic pedagogy, slave exhibitions, affect/emotion, object handling

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Authors: Markus Feufel, Friederike Kendel, Caren Hilger, Selamawit Woldai

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Since the corona pandemic, the use of video consultation has increased remarkably. For vulnerable groups such as oncological patients, the advantages seem obvious. But how does video consultation potentially change the doctor-patient relationship compared to face-to-face consultation? Which barriers may hinder the effective use of this consultation format in practice? We are presenting first results from a mixed-methods field study, funded by Federal Ministry of Health, which will provide the basis for a hands-on guide for both physicians and patients on how to improve the quality of video consultations. We use a quasi-experimental design to analyze qualitative and quantitative differences between face-to-face and video consultations based on video recordings of N = 64 actual counseling sessions (n = 32 for each consultation format). Data will be recorded from n = 32 gynecological and n = 32 urological cancer patients at two clinics. After the consultation, all patients will be asked to fill out a questionnaire about their consultation experience. For quantitative analyses, the counseling sessions will be systematically compared in terms of verbal and nonverbal communication patterns. Relative frequencies of eye contact and the information exchanged will be compared using 𝝌2 -tests. The validated questionnaire MAPPIN'Obsdyad will be used to assess the expression of shared decision-making parameters. In addition, semi-structured interviews will be conducted with n = 10 physicians and n = 10 patients experienced with video consultation, for which a qualitative content analysis will be conducted. We will elaborate the comprehensive methodological approach we used to compare video vs. face-to-face consultations and present first evidence on how video consultations change the doctor-patient interaction. We will also outline possible barriers of video consultations and best practices on how they may be overcome. Based on the results, we will present and discuss recommendations outlining best practices for how to prepare and conduct high-quality video consultations from the perspective of both physicians and patients.

Keywords: video consultation, patient-doctor-relationship, digital applications, technical barriers

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

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Introduction: Tuberculosis (TB) is a known disease with hidden features caused by Mycobacterium tuberculosis (MTB). This disease, which is one of the 10 deadliest in the world, has caused millions of deaths in recent decades. Furthermore, TB is responsible for infecting about 30% population of world. Like any infection, TB can activate the immune system by locating and colonization in the human body, especially in the alveoli. TB is granulomatosis, so MTB can absorb the host’s immune cells and other cells to form granuloma. Method: Different databases (e.g., PubMed) were recruited to prepare this paper and fulfill our goals to search and find effective papers and investigations. Results: Immune response to MTB is related to T cell killers and contains CD1, CD4, and CD8 T lymphocytes. CD1 lymphocytes can recognize glycolipids, which highly exist in the Mycobacterial fatty cell wall. CD4 lymphocytes and macrophages form granuloma, and it is the main line of immune response to Mycobacteria. On the other hand, CD8 cells have cytolytic function for directly killing MTB by secretion of granulysin. Other functions and secretion to the deal are interleukin-12 (IL-12) by induction of expression interferon-γ (INF-γ) for macrophages activation and creating a granuloma, and tumor necrosis factor (TNF) by promoting macrophage phagolysosomal fusion. Conclusion: Immune cells in battle with MTB are macrophages, dendritic cells (DCs), neutrophils, and natural killer (NK) cells. These immune cells can recognize the Mycobacterium by various receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and C-type lectin receptors (CLRs) located in the cell surface. In human alveoli exist about 50 dendritic macrophages, which have close communication with other immune cells in the circulating system and epithelial cells to deal with Mycobacteria. Against immune cells, MTB handles some factors (e.g., cordfactor, O-Ag, lipoarabinomannan, sulfatides, and adenylate cyclase) and practical functions (e.g., inhibition of macrophages).

Keywords: mycobacterium tuberculosis, immune responses, immunological mechanisms, respiratory tuberculosis

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Authors: Leticia Leandro Rade, Amanda Silva de Sousa, Suman Das, Wesley Generoso, Mayara Chagas Ávila, Plinio Salmazo Vieira, Antonio Bonomi, Gabriela Persinoti, Mario Tyago Murakami, Thomas Michael Makris, Leticia Maria Zanphorlin

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Alkenes have an economic appeal, especially in the biofuels field, since they are precursors for drop-in biofuels production, which have similar chemical and physical properties to the conventional fossil fuels, with no oxygen in their composition. After the discovery of the first P450 CYP152 OleTJE in 2011, reported with its unique property of decarboxylating fatty acids (FA), by using hydrogen peroxide as a cofactor and producing 1-alkenes as the main product, the scientific and technological interest in this family of enzymes vastly increased. In this context, the present work presents a new decarboxylase (OleTRN) with low similarity with OleTJE (32%), its biochemical characterization, and structure elucidation. As main results, OleTRN presented a high yield of expression and purity, optimum reaction conditions at 35 °C and pH from 6.5 to 8.0, and higher specificity for oleic acid. Besides that, structure-guided mutations were performed and according to the functional characterizations, it was observed that some mutations presented different specificity and chemoselectivity by varying the chain-length of FA substrates from 12 to 20 carbons. These results are extremely interesting from a biotechnological perspective as those characteristics could diversify the applications and contribute to designing better cytochrome P450 decarboxylases. Considering that peroxygenases have the potential activity of decarboxylating and hydroxylating fatty acids and that the elucidation of the intriguing mechanistic involved in the decarboxylation preferential from OleTJE is still a challenge, the elucidation of OleTRN structure and the functional characterizations of OleTRN and its mutants contribute to new information about CYP152. Besides that, the work also contributed to the discovery of a new decarboxylase with a different selectivity profile from OleTJE, which allows a wide range of applications.

Keywords: P450, decarboxylases, alkenes, biofuels

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Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Ada Yurman

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Using the case of Israeli Atomic Spy Mordechai Vanunu as an example, this study sought to examine social response to political deviance whereby social response can be mobilized in order to achieve social control. Mordechai Vanunu, a junior technician in the Dimona Atomic Research Center, played a normative role in the militaristic discourse while working in the “holy shrine” of the Israeli defense system for many years. At a certain stage, however, Vanunu decided to detach himself from this collective and launched an assault on this top-secret circle. Israeli society in general and the security establishment in particular found this attack intolerable and unforgivable. They presented Vanunu as a ticking time bomb, delegitimized him and portrayed him as “other”. In addition, Israeli enforcement authorities imposed myriad prohibitions and sanctions on Vanunu even after his release from prison – “as will be done to he who desecrates holiness.” Social response to Vanunu at the time of his capture and trial was studied by conducting a content analysis of six contemporary daily newspapers. The analysis focused on use of language and forms of expression. In contrast with traditional content analysis methodology, this study did not just look at frequency of expressions of ideas and terms in the text and covert content; rather, the text was analyzed as a structural whole, and included examination of style, tone and unusual use of imagery, and more, in order to uncover hidden messages within the text. The social response to this case was extraordinarily intense, not only because in this case of political deviance, involving espionage and treason, Vanunu’s actions comprised a real potential threat to the country, but also because of the threat his behavior posed to the symbolic universe of society. Therefore, the response to this instance of political deviance can be seen as being part of a mechanism of social control aiming to protect world view of society as a whole, as well as to punish the criminal.

Keywords: militarism, political deviance, social construction, social control

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Authors: Sofia Papadimitriou

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INTRODUCTION: The differential diagnosis between acute viral and bacterial infections is an important cost-effectiveness parameter at the stage of the treatment process in order to achieve the maximum benefits in therapeutic intervention by combining the minimum cost to ensure the proper use of antibiotics.The discovery of sensitive and robust molecular diagnostic tests in response to the role of the host in infections has enhanced the accurate diagnosis and differentiation of infections. METHOD: The study used a sample of six independent blood samples (total=756) which are associated with human proteins-proteins, each of which at the transcription stage expresses a different response in the host network between viral and bacterial infections.Τhe individual blood samples are subjected to a sequence of computer filters that identify a gene panel corresponding to an autonomous diagnostic score. The data set and the correspondence of the gene panel to the diagnostic patents a new Bangalore -Viral Bacterial (BL-VB). FINDING: We use a biomarker based on the blood of 10 genes(Panel-VB) that are an important prognostic value for the detection of viruses from bacterial infections with a weighted average AUROC of 0.97(95% CL:0.96-0.99) in eleven independent samples (sets n=898). We discovered a base with a patient score (VB 10 ) according to the table, which is a significant diagnostic value with a weighted average of AUROC 0.94(95% CL: 0.91-0.98) in 2996 patient samples from 56 public sets of data from 19 different countries. We also studied VB 10 in a new cohort of South India (BL-VB,n=56) and found 97% accuracy in confirmed cases of viral and bacterial infections. We found that VB 10 (a)accurately identifies the type of infection even in unspecified cases negative to the culture (b) shows its clinical condition recovery and (c) applies to all age groups, covering a wide range of acute bacterial and viral infectious, including non-specific pathogens. We applied our VB 10 rating to publicly available COVID 19 data and found that our rating diagnosed viral infection in patient samples. RESULTS: Τhe results of the study showed the diagnostic power of the biomarker VB 10 as a diagnostic test for the accurate diagnosis of acute infections in recovery conditions. We look forward to helping you make clinical decisions about prescribing antibiotics and integrating them into your policies management of antibiotic stewardship efforts. CONCLUSIONS: Overall, we are developing a new property of the RNA-based biomarker and a new blood test to differentiate between viral and bacterial infections to assist a physician in designing the optimal treatment regimen to contribute to the proper use of antibiotics and reduce the burden on antimicrobial resistance, AMR.

Keywords: acute infections, antimicrobial resistance, biomarker, blood transcriptome, systems biology, classifier diagnostic score

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Authors: Hyeon Sop Baek

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This paper will briefly investigate Jeong Do-jeon’s political philosophy. Jeong Do-jeon was a Korean Confucian philosopher and politician during the turbulent 14th Century who revolted against the old order, founded Joseon Dynasty, and significantly impacted the development of Korean culture. Jeong’s vision of an ideal state involved a polity that has its roots in the people -that is, an ideal government prioritizes caring for the welfare of the people, respecting and attending to the diverse opinions and concerns of the people, and relies on the genuine, voluntary support of the people. With the neo-Confucian worldview in mind -that every human being has the equal potential to become a moral person- Jeong sought to create a world suitable for everybody to contribute to the decision-making procedure and be able to realize their potential fully. This paper will first examine his works and present a quick overview of his vision of the ideal government. Then, it will examine the Confucian virtues of ren (仁) and yi (義) and how they formulate the basis of his philosophy, and then discuss the central features of his vision of government: popular mandate, equity of wealth, promoting freedom of expression and political participation, and elevating caring disposition as the paramount quality of the political leaders. Furthermore, this paper aims to analyze the element of care inherent within his political philosophy, namely his view on the dynamics of power, nurturing the people, and noncoercive justice. Finally, a discussion on why his philosophy is still relevant in the contemporary context will be provided. Jeong’s view aimed at building a sustainable model of government, by proposing that the people should be the foundation of a state and that they need to be carefully nurtured so they can realize their inborn potential and continue to contribute to the sustenance of the world, is the focal point of Jeong’s philosophy. Just as he sought to rebuild his world following the turmoils of the 14th Century, his philosophy still has a substantial implication on how we should strive to rebuild our society today.

Keywords: Korea, Confucianism, Jeong Do-jeon, Joseon, Korean philosophy, political philosophy

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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Authors: Pavitra Sharma, Anuradha Singh, Nupur Mathur

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There exist more than 100 trillion bacteria in the digestive system of human-beings. Such bacteria are referred to as gut microbiota. Gut microbiota comprises around 75% of our immune system. The bacteria that comprise the gut microbiota are unique to every individual and their composition keeps changing with time owing to factors such as the host’s age, diet, genes, environment, and external medication. Of these factors, the variable easiest to control is one’s diet. By modulating one’s diet, one can ensure an optimal composition of the gut microbiota yielding several health benefits. Prebiotics and probiotics are two compounds that have been considered as viable options to modulate the host’s diet. Prebiotics are basically plant products that support the growth of good bacteria in the host’s gut. Examples include garden asparagus, aloe vera etc. Probiotics are living microorganisms that exist in our intestines and play an integral role in promoting digestive health and supporting our immune system in general. Examples include yogurt, kimchi, kombucha etc. In the context of modulating the host’s diet, the key attribute of prebiotics is that they support the growth of probiotics. By developing the right combination of prebiotics and probiotics, food products or supplements can be created to enhance the host’s health. An effective combination of prebiotics and probiotics that yields health benefits to the host is referred to as synbiotics. Synbiotics comprise of an optimal proportion of prebiotics and probiotics, their application benefits the host’s health more than the application of prebiotics and probiotics used in isolation. When applied to food supplements, synbiotics preserve the beneficial probiotic bacteria during storage period and during the bacteria’s passage through the intestinal tract. When applied to the gastrointestinal tract, the composition of the synbiotics assumes paramount importance. Reason being that for synbiotics to be effective in the gastrointestinal tract, the chosen probiotic must be able to survive in the stomach’s acidic environment and manifest tolerance towards bile and pancreatic secretions. Further, not every prebiotic stimulates the growth of a particular probiotic. The prebiotic chosen should be one that not only maintains 2 balance in the host’s digestive system, but also provides the required nutrition to probiotics. Hence in each application of synbiotics, the prebiotic-probiotic combination needs to be carefully selected. Once the combination is finalized, the exact proportion of prebiotics and probiotics to be used needs to be considered. When determining this proportion, only that amount of a prebiotic should be used that activates metabolism of the required number of probiotics. It was observed that while probiotics are active is both the small and large intestine, the effect of prebiotics is observed primarily in the large intestine. Hence in the host’s small intestine, synbiotics are likely to have the maximum efficacy. In small intestine, prebiotics not only assist in the growth of probiotics, but they also enable probiotics to exhibit a higher tolerance to pH levels, oxygenation, and intestinal temperature

Keywords: microbiota, probiotics, prebiotics, synbiotics

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Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

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Authors: Eli Buchbinder

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Introduction. Language is the basis to our experience as human being. We use language in describing our experiences and construct meaning and narratives from experiences. Metaphors are a valuable linguistic tool commonly use. Metaphors link two domains that are ordinarily not related. Metaphors achieve simultaneously multi-level integration: abstract and concrete, rational and imaginative, familiar and the unfamiliar, conscious and preconscious/unconscious. As such, metaphors epistemological and ontological tool that are important in social work in every field and domain. Goals and Methods The presentation’s aim is to validate the value of metaphors through the first psychiatric breakdown is a traumatic for families. The presentation is based on two pooled qualitative studies. The first study focused on 12 spouses: 7 women and 5 men, between the ages of 22 and 57, regarding their experiences and meanings of the first psychiatric hospitalization of their partners diagnosed with affective disorders. The second study focused on 10 parents, between the ages of 47 and 62, regarding their experiences and meanings following their child's first psychotic breakdown during young adulthood. Results Two types of major metaphors evolved from the interviews in farming the trauma of the first mental breakdown. The first mode - orientation (spatial) metaphors, reflect symbolic expression of the loss of a secure base, represented in the physical environment, e.g., describing hospitalization as "falling into an abyss." The second mode- ontological metaphors, reflect how parents and spouses present their traumatic experiences of hospitalization in terms of discrete, powerful and coherent entities, e.g., describing the first hospitalization as "swimming against the tide." The two metaphors modes reflect the embodiment of the unpredictability, being mired in distress, shock, intense pain and the experience the collapse of continuity on the life course and cuts off the experience of control. Conclusions Metaphors are important and powerful guide in assessing individuals and families’ phenomenological reality. As such, metaphors are useful for understanding and orientated therapeutic intervening, in the studies above, with the first psychiatric hospitalization experienced, as well as in others social workers’ interventions.

Keywords: first mental breakdown, metaphors, family perspective, qualitative research

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Authors: Yun-Chin Chung, Nileema Divate, Gen-Hung Chen, Pei-Ru Huang, Rupesh Divate

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Many environmental factors, such as glucose concentration, ethanol, temperature, osmotic pressure and pH, decrease the production rate of ethanol using yeast as a starter. Fermentation starters with high tolerance to various stresses are always demanded for brewing industry. Trehalose, a storage carbohydrate in cell wall of yeast, plays an important role in tolerance of environmental stress by preserving integrity of plasma membrane and stabilizing proteins. Furan aldehydes are toxic to yeast and the growth rate of yeast is significantly reduced if furan aldehydes were present in the fermentation medium. In yeast, aldehyde reductase is involved in the detoxification of reactive aldehydes and consequently the growth of yeast is improved. The aims of this study were to construct a genetic recombinant Saccharomyces cerevisiae or Pichia pastoris with furfural and HMF degrading and high ethanol tolerance capacities. Yeast strains were engineered by genetic recombination for overexpression of trehalose-6-phosphate synthase gene (tps1) and aldehyde reductase gene (ari1). TPS1 gene was cloned from S. cerevisiae by reverse transcription-polymerase chain reaction (RT-PCR) and then ligated with pGAPZαC vector. The constructed vector, pGAPZC-tps1, was transformed to recombinant yeasts strain with overexpression of ari1. The transformants with pGAPZC-tps1-ari1 were generated called STA (S. cerevisiae) and PTA (P. pastoris) with overexpression of tps1, ari1. PCR with tps1-specific primers and western blot with his-tag confirmed the gene insertion and protein expression of tps1 in the transformants, respectively. The neutral trehalase gene (nth1) of STA was successfully deleted and the novel strain STAΔN will be used for further study, including the measurement of trehalose concentration and ethanol, furfural tolerance assay.

Keywords: genetic recombinant, yeast, ethanol tolerance, trehalase, aldehyde reductase

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Authors: Yi Sun, George Ed Rainger, Steve P. Watson

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Background: Beyond the classical roles in haemostasis and thrombosis, platelets are important in the initiation and development of various thrombo-inflammatory diseases. In atherosclerosis and deep vein thrombosis, for example, platelets bridge monocytes with endothelium and form heterotypic aggregates with monocytes in the circulation. This can alter monocyte phenotype by inducing their activation, stimulating adhesion and migration. These interactions involve cell surface receptor-ligand pairs on both cells. This list is likely incomplete as new interactions of importance to platelet biology are continuing to be discovered as illustrated by our discovery of PEAR-1 binding to FcεR1α. Results: We have developed a highly sensitive avidity-based assay to identify novel extracellular interactions among 126 recombinantly-expressed platelet cell surface and secreted proteins involved in platelet aggregation. In this study, we will use this method to identify novel platelet-monocyte interactions. We aim to identify ligands for orphan receptors and novel partners of well-known proteins. Identified interactions will be studied in preliminary functional assays to demonstrate relevance to the inflammatory processes supporting atherogenesis. Conclusions: Platelet-monocyte interactions are essential for the development of thromboinflammatory disease. Up until relatively recently, technologies only allow us to limit our studies on each individual protein interaction at a single time. These studies propose for the first time to study the cell surface platelet-monocyte interactions in a systematic large-scale approach using a reliable screening method we have developed. If successful, this will likely to identify previously unknown ligands for important receptors that will be investigated in details and also provide a list of novel interactions for the field. This should stimulate studies on developing alternative therapeutic strategies to treat vascular inflammatory disorders such as atherosclerosis, DVT and sepsis and other clinically important inflammatory conditions.

Keywords: membrane proteins, large-scale screening, platelets, recombinant expression

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Authors: Jorn Fricke, Frans Melissen

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Citizens in urban areas are prone to increased levels of stress due to urbanization, inadequate and overburdened infrastructure and services, and environmental degradation. Moreover, communities are fragile and subject to shocks and stresses through various social and political processes. A loss of (a sense of) community is often seen as related to increasing political and civic disintegration. Feelings of community can manifest themselves in various ways but underlying all these manifestations is the need for trust between people. One of the main drivers of trust between individuals is (shared) experiences. It is these shared experiences that may play an important role in building resilience, i.e., the ability of a community and its members to adapt to and deal with stresses, as well as ensure the ongoing development of a community. So far, experience design, as a discipline and academic field, has mainly focused on designing products or services. However, people-to-people experiences are the ones that play a pivotal role in building inclusiveness, safety, and resilience in communities. These experiences represent challenging objects of design as they develop in an interactive space of spontaneity, serendipity, and uniqueness that is based on intuition, freedom of expression, and interaction. Therefore, there is a need for research to identify which elements are required in designing the social and physical environment (or ‘experience scape’) to increase the chance for people-to-people experiences to be successful and what elements are required for these experiences to help in building resilience in urban communities that can resist shocks and stresses. By means of a comparative case study approach in urban areas in Germany and the Netherlands, using a range of qualitative research methods such as in-depth interviews, focus groups, participant observation, storytelling techniques, and life stories, this research identifies relevant actors and their roles in creating building blocks of optimal experience scrapes for building resilience in communities.

Keywords: community development, experiences, experience scapes, resilience

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Authors: O. Benabdeljelil, A. Karioun, S. Amami, R. Rouger, M. Hamidine

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A model for preventing the risks related to climate conditions in the agricultural sector is presented. It will determine the yearly optimum premium to be paid by a producer in order to reach his required turnover. The model is based on both climatic stability and 'soft' responses of usually grown species to average climate variations at the same place and inside a safety ball which can be determined from past meteorological data. This allows the use of linear regression expression for dependence of production result in terms of driving meteorological parameters, the main ones of which are daily average sunlight, rainfall and temperature. By simple best parameter fit from the expert table drawn with professionals, optimal representation of yearly production is determined from records of previous years, and yearly payback is evaluated from minimum yearly produced turnover. The model also requires accurate pricing of commodity at N+1. Therefore, a pricing model is developed using 3 state variables, namely the spot price, the difference between the mean-term and the long-term forward price, and the long-term structure of the model. The use of historical data enables to calibrate the parameters of state variables, and allows the pricing of commodity. Application to beet sugar underlines pricer precision. Indeed, the percentage of accuracy between computed result and real world is 99,5%. Optimal premium is then deduced and gives the producer a useful bound for negotiating an offer by insurance companies to effectively protect its harvest. The application to beet production in French Oise department illustrates the reliability of present model with as low as 6% difference between predicted and real data. The model can be adapted to almost any agricultural field by changing state parameters and calibrating their associated coefficients.

Keywords: agriculture, production model, optimal price, meteorological factors, 3-factor model, parameter calibration, forward price

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Authors: Mehrdad Abkenari, Orod Zarrinkafsh, Mohsen Ramezan Shirazi

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Construction projects initiate in complicated dynamic environments and, due to the close relationships between project parameters and the unknown outer environment, they are faced with several uncertainties and risks. Success in time, cost and quality in large scale construction projects is uncertain in consequence of technological constraints, large number of stakeholders, too much time required, great capital requirements and poor definition of the extent and scope of the project. Projects that are faced with such environments and uncertainties can be well managed through utilization of the concept of risk management in project’s life cycle. Although the concept of risk is dependent on the opinion and idea of management, it suggests the risks of not achieving the project objectives as well. Furthermore, project’s risk analysis discusses the risks of development of inappropriate reactions. Since evaluation and prioritization of construction projects has been a difficult task, the network structure is considered to be an appropriate approach to analyze complex systems; therefore, we have used this structure for analyzing and modeling the issue. On the other hand, we face inadequacy of data in deterministic circumstances, and additionally the expert’s opinions are usually mathematically vague and are introduced in the form of linguistic variables instead of numerical expression. Owing to the fact that fuzzy logic is used for expressing the vagueness and uncertainty, formulation of expert’s opinion in the form of fuzzy numbers can be an appropriate approach. In other words, the evaluation and prioritization of construction projects on the basis of risk factors in real world is a complicated issue with lots of ambiguous qualitative characteristics. In this study, evaluated and prioritization the risk parameters and factors with fuzzy logy method by combination of three method DEMATEL (Decision Making Trial and Evaluation), ANP (Analytic Network Process) and TOPSIS (Technique for Order-Preference by Similarity Ideal Solution) on Construction Management.

Keywords: fuzzy logy, risk, prioritization, assessment

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Authors: Neeraj Shetye

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A common phenomenon between the rise of leaders like Mussolini and Adolf Hitler in the 20th century is their 'charisma'. They possessed the ability to seduce the crowd not just by the things they said but also by the way they said it. Aristotle defined rhetoric as an art of persuasion and reasoning which is how social scientists understand the concept. Political rhetoric in a modern democracy has several complexities including the huge number of speakers, quantity of information, diverse viewpoints, number of candidates and the impact of digital age. Politics in India since the seventies have been 'visibly dominated' by uses of rhetorical language and with a number of slogans. This idea of how language can steer an individual to establish or adopt a certain viewpoint has not been a focus of study in the Indian discourse. In a linguistically diverse region such as India, the idea of political rhetoric is vast and may not be accomplished in a year. There are in-depth studies by western thinkers on European or American political rhetoric unlike their Asian counterparts such as China, India or any of the Pacific nations. India saw an integration of states based on languages. Keeping this idea in mind, this paper aims to cover one political party that rose to its prominence over five decades and most significantly known for its conservative expression: Shivsena. Shivsena’s rise during the eighties and eventually establishing their government in the nineties are two fascinating periods to focus especially with a simultaneous rise of Bombay underworld, Babri demolition and major economic policy changes in the form of liberalisation (1991) and globalization (1995). This project attempts to study this with a two-fold methodology: literature review and fieldwork. There is an immense literature on Shivsena by both its admirers and critiques, contributing to both sides of the debate. Scholars have been writing about this party over these years and have keenly observed its growing popularity amongst the masses. There is just one intention behind this project, and it is to connect and analyse the vast, dispersed literature that is available and contribute to a field that has not been adequately analysed in the academic discourse.

Keywords: India, language, political rhetoric, Shivsena, slogans

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Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

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Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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Authors: Saima Murtaza

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Ethics and aesthetics have invariably remained the two closely integrated artistic appurtenances for the production of any work of art. These artistic devices configure themselves into a complex synthesis in our contemporary literature. The labyrinthine integration of ethics and aesthetics, operating in the lives of human characters, to the extent of transcending all limits has resulted in an artistic puzzle for the readers. Art, no doubt, is an extrinsic expression of the intrinsic life of man. The use of aesthetics in literature pertaining to human existence; aesthetic solipsism, has resulted in the artistic objectification of these characters. The practice of the like aestheticism deprives the characters of their souls, rendering them as mere objects of aesthetic gaze at the hands of their artists-creators. Artists orchestrate their lives founding it on a plot which deviates from normal social and ethical standards. Their perverse attitude can be seen in dealing with characters, their feelings and the incidents of their lives. Morality is made to appear not as a religious construct but as an individual’s private affair. Furthermore, the idea of beauty incarnated, in other words hedonistic aesthetic does not placate a true aesthete. Ethics and aesthetics are the two most recurring motifs of our contemporary literature, especially of Nabokov’s world. The purpose of this study is to peruse these aforementioned motifs in Nabokov’s most enigmatic novel Lolita, a story of pedophilia, which is in fact reflective of our complex individual psychic and societal patterns. The narrative subverts all the traditional and hitherto known notions of aesthetics and ethics. When applied to literature, aesthetic does not simply mean ‘beautiful’ in the text. It refers to an intricate relationship between feelings and perception and also incorporates within its range wide-ranging emotional reactions to text. The term aesthetics in literature is connected with the readers whose critical responses to the text determine the merit of any work to be really a piece of art. Aestheticism is the child of ethics. Morality sets the grounds for the production of any work and the idea of aesthetics gives it transcendence.

Keywords: ethics, aesthetics and hedonistic aesthetic, nymphet syndrome, pedophilia

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Authors: Sandra Smieszek, Jonathan Haines

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Introduction: Numerous research efforts have focused on searching for ‘longevity genes’. However, attempting to decipher the genetic component of the longevous phenotype have resulted in limited success and the mechanisms governing longevity remain to be explained. We conducted a genome-wide homozygosity analysis (GWHA) of the founder population of the Amish community in central Ohio. While genome-wide association studies using unrelated individuals have revealed many interesting longevity associated variants, these variants are typically of small effect and cannot explain the observed patterns of heritability for this complex trait. The Amish provide a large cohort of extended kinships allowing for in depth analysis via family-based approach excellent population due to its. Heritability of longevity increases with age with significant genetic contribution being seen in individuals living beyond 60 years of age. In our present analysis we show that the heritability of longevity is estimated to be increasing with age particularly on the paternal side. Methods: The present analysis integrated both phenotypic and genotypic data and led to the discovery of a series of variants, distinct for stratified populations across ages and distinct for paternal and maternal cohorts. Specifically 5437 subjects were analyzed and a subset of 893 successfully genotyped individuals was used to assess CHIP heritability. We have conducted the homozygosity analysis to examine if homozygosity is associated with increased risk of living beyond 90. We analyzed AMISH cohort genotyped for 614,957 SNPs. Results: We delineated 10 significant regions of homozygosity (ROH) specific for the age group of interest (>90). Of particular interest was ROH on chromosome 13, P < 0.0001. The lead SNPs rs7318486 and rs9645914 point to COL4A2 and our lead SNP. COL25A1 encodes one of the six subunits of type IV collagen, the C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. The second region of interest points to IRS2. Furthermore we built a classifier using the obtained SNPs from the significant ROH region with 0.945 AUC giving ability to discriminate between those living beyond to 90 years of age and beyond. Conclusion: In conclusion our results suggest that a history of longevity does indeed contribute to increasing the odds of individual longevity. Preliminary results are consistent with conjecture that heritability of longevity is substantial when we start looking at oldest fifth and smaller percentiles of survival specifically in males. We will validate all the candidate variants in independent cohorts of centenarians, to test whether they are robustly associated with human longevity. The identified regions of interest via ROH analysis could be of profound importance for the understanding of genetic underpinnings of longevity.

Keywords: regions of homozygosity, longevity, SNP, Amish

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Authors: Hanan Khojah, RuAngelie Edrada-Ebel

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Neurodegenerative disease including Alzheimer’s disease is a major cause of long-term disability. Oxidative stress is frequently implicated as one of the key contributing factors to neurodegenerative diseases. Protection against neuronal damage remains a great challenge for researchers. Ficus carica (commonly known as fig) is a species of great antioxidant nutritional value comprising a protective mechanism against innumerable health disorders related to oxidative stress as well as Alzheimer’s disease. The purpose of this work was to characterize the non-polar active metabolites in Ficus carica endocarp, mesocarp, and exocarp. Crude extracts were prepared using several extraction solvents, which included 1:1 water: ethylacetate, acetone and methanol. The dried extracts were then solvent partitioned between equivalent amounts of water and ethylacetate. Purification and fractionation were accomplished by high-throughput chromatography. The isolated metabolites were tested on their effect on human neuroblastoma cell line by cell viability test and cell cytotoxicity assay with acrolein. Molecular weights of the active metabolites were determined via LC–HRESIMS and GC-EIMS. Metabolomic profiling was performed to identify the active metabolites by using differential expression analysis software (Mzmine) and SIMCA for multivariate analysis. Structural elucidation and identification of the interested active metabolites were studied by 1-D and 2-D NMR. Significant differences in bioactivity against a concentration-dependent assay on acrolein radicals were observed between the three fruit parts. However, metabolites obtained from mesocarp and the endocarp demonstrated bioactivity to scavenge ROS radical. NMR profiling demonstrated that aliphatic compounds such as γ-sitosterol tend to induce neuronal bioactivity and exhibited bioactivity on the cell viability assay. γ-Sitosterol was found in higher concentrations in the mesocarp and was considered as one of the major phytosterol in Ficus carica.

Keywords: alzheimer, Ficus carica, γ-Sitosterol, metabolomics

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Authors: Deniz Dincel, Sena Ardicli, Hale Samli, Mustafa Ogan, Faruk Balci

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The aim of the study was to determine the effects of some environmental and genetic factors on growth, fertility traits, milk yield and composition in Saanen goats. For this purpose, the total of 173 Saanen goats and kids were investigated for growth, fertility and milk traits in Marmara Region of Turkey. Fertility parameters (n=70) were evaluated during two years. Milk samples were collected during the lactation and the milk yield/components (n=59) of each goat were calculated. In terms of CSN3 and AGPAT6 gene; the genotypes were defined by PCR-RFLP. Saanen kids (n=86-112) were measured from birth to 6 months of life. The birth, weaning, 60ᵗʰ, 90ᵗʰ, 120ᵗʰ and 180tᵗʰ days of average live weights were calculated. The effects of maternal age on pregnancy rate (p < 0.05), birth rate (p < 0.05), infertility rate (p < 0.05), single born kidding (p < 0.001), twinning rate (p < 0.05), triplet rate (p < 0.05), survival rate of kids until weaning (p < 0.05), number of kids per parturition (p < 0.01) and number of kids per mating (p < 0.01) were found significant. The impacts of year on birth rate (p < 0.05), abortion rate (p < 0.001), single born kidding (p < 0.01), survival rate of kids until weaning (p < 0.01), number of kids per mating (p < 0.01) were found significant for fertility traits. The impacts of lactation length on all milk yield parameters (lactation milk, protein, fat, totally solid, solid not fat, casein and lactose yield) (p < 0.001) were found significant. The effects of age on all milk yield parameters (lactation milk, protein, fat, total solid, solid not fat, casein and lactose yield) (p < 0.001), protein rate (p < 0.05), fat rate (p < 0.05), total solid rate (p < 0.01), solid not fat rate (p < 0.05), casein rate (p < 0.05) and lactation length (p < 0.01), were found significant too. However, the effect of AGPAT6 gene on milk yield and composition was not found significant in Saanen goats. The herd was found monomorphic (FF) for CSN3 gene. The effects of sex on live weights until 90ᵗʰ days of life (birth, weaning and 60ᵗʰ day of average weight) were found significant statistically (p < 0.001). The maternal age affected only birth weight (p < 0,001). The effects month at birth on all of the investigated day [the birth, 120ᵗʰ, 180ᵗʰ days (p < 0.05); the weaning, 60ᵗʰ, 90ᵗʰ days (p < 0,001)] were found significant. The birth type was found significant on the birth (p < 0,001), weaning (p < 0,01), 60ᵗʰ (p < 0,01) and 90ᵗʰ (p < 0,01) days of average live weights. As a result, screening the other regions of CSN3, AGPAT6 gene and also investigation the phenotypic association of them should be useful to clarify the efficiency of target genes. Environmental factors such as maternal age, year, sex and birth type were found significant on some growth, fertility and milk traits in Saanen goats. So consideration of these factors could be used as selection criteria in dairy goat breeding.

Keywords: fertility, growth, milk yield, Saanen goats

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Authors: Igor V. Grigoriev

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Understanding of biological processes encoded in fungi is instrumental in addressing future food, feed, and energy demands of the growing human population. Genomics is a powerful and quickly evolving tool to understand these processes. The Fungal Genomics Program of the US Department of Energy Joint Genome Institute (JGI) partners with researchers around the world to explore fungi in several large scale genomics projects, changing the fungal genomics landscape. The key trends of these changes include: (i) rapidly increasing scale of sequencing and analysis, (ii) developing approaches to go beyond culturable fungi and explore fungal ‘dark matter,’ or unculturables, and (iii) functional genomics and multi-omics data integration. Power of comparative genomics has been recently demonstrated in several JGI projects targeting mycorrhizae, plant pathogens, wood decay fungi, and sugar fermenting yeasts. The largest JGI project ‘1000 Fungal Genomes’ aims at exploring the diversity across the Fungal Tree of Life in order to better understand fungal evolution and to build a catalogue of genes, enzymes, and pathways for biotechnological applications. At this point, at least 65% of over 700 known families have one or more reference genomes sequenced, enabling metagenomics studies of microbial communities and their interactions with plants. For many of the remaining families no representative species are available from culture collections. To sequence genomes of unculturable fungi two approaches have been developed: (a) sequencing DNA from fruiting bodies of ‘macro’ and (b) single cell genomics using fungal spores. The latter has been tested using zoospores from the early diverging fungi and resulted in several near-complete genomes from underexplored branches of the Fungal Tree, including the first genomes of Zoopagomycotina. Genome sequence serves as a reference for transcriptomics studies, the first step towards functional genomics. In the JGI fungal mini-ENCODE project transcriptomes of the model fungus Neurospora crassa grown on a spectrum of carbon sources have been collected to build regulatory gene networks. Epigenomics is another tool to understand gene regulation and recently introduced single molecule sequencing platforms not only provide better genome assemblies but can also detect DNA modifications. For example, 6mC methylome was surveyed across many diverse fungi and the highest among Eukaryota levels of 6mC methylation has been reported. Finally, data production at such scale requires data integration to enable efficient data analysis. Over 700 fungal genomes and other -omes have been integrated in JGI MycoCosm portal and equipped with comparative genomics tools to enable researchers addressing a broad spectrum of biological questions and applications for bioenergy and biotechnology.

Keywords: fungal genomics, single cell genomics, DNA methylation, comparative genomics

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