Search results for: gene regulation

Authors: Kerekoppa Puttaiah Bhatta Ramesha, Uday Kannegundla, Praseeda Mol, Lathika Gopalakrishnan, Jagish Kour Reen, Gourav Dey, Manish Kumar, Sakthivel Jeyakumar, Arumugam Kumaresan, Kiran Kumar M., Thottethodi Subrahmanya Keshava Prasad

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Spermatozoa are the highly specialized transcriptionally and translationally inactive haploid male gamete. The understanding of proteome of sperm is indispensable to explore the mechanism of sperm motility and fertility. Though there is a large number of human sperm proteomic studies, in-depth proteomic information on Bos indicus spermatozoa is not well established yet. Therefore, we illustrated the profile of sperm proteome in indigenous cattle, Malnad gidda (Bos Indicus), using high-resolution mass spectrometry. In the current study, two semen ejaculates from 3 breeding bulls were collected employing the artificial vaginal method. Using 45% percoll purification, spermatozoa cells were isolated. Protein was extracted using lysis buffer containing 2% Sodium Dodecyl Sulphate (SDS) and protein concentration was estimated. Fifty micrograms of protein from each individual were pooled for further downstream processing. Pooled sample was fractionated using SDS-Poly Acrylamide Gel Electrophoresis, which is followed by in-gel digestion. The peptides were subjected to C18 Stage Tip clean-up and analyzed in Orbitrap Fusion Tribrid mass spectrometer interfaced with Proxeon Easy-nano LC II system (Thermo Scientific, Bremen, Germany). We identified a total of 6773 peptides with 28426 peptide spectral matches, which belonged to 1081 proteins. Gene ontology analysis has been carried out to determine the biological processes, molecular functions and cellular components associated with sperm protein. The biological process chiefly represented our data is an oxidation-reduction process (5%), spermatogenesis (2.5%) and spermatid development (1.4%). The highlighted molecular functions are ATP, and GTP binding (14%) and the prominent cellular components most observed in our data were nuclear membrane (1.5%), acrosomal vesicle (1.4%), and motile cilium (1.3%). Seventeen percent of sperm proteins identified in this study were involved in metabolic pathways. To the best of our knowledge, this data represents the first total sperm proteome from indigenous cattle, Malnad Gidda. We believe that our preliminary findings could provide a strong base for the future understanding of bovine sperm proteomics.

Keywords: Bos indicus, Malnad Gidda, mass spectrometry, spermatozoa

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Authors: Irina Belozerova

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In the recent years, the number of crimes against peace and humanity has constantly been increasing. The development of the international community is inseparably connected to the compliance with the law which protects the rights and interests of citizens in all of their manifestations. The provisions of the law of criminal procedure are no exception. The rights of the victims of genocide, of the war crimes and the crimes against humanity, require particular attention. These crimes fall within the jurisdiction of the International Criminal Court governed by the Rome Statute of the International Criminal Court. These crimes have the following features. First, any such crime has a mass character and therefore requires specific regulation in the international criminal law and procedure and the national criminal law and procedure of different countries. Second, the victims of such crimes are usually children, women and old people; the entire national, ethnic, racial or religious groups are destroyed. These features influence the classification of victims by the age criterion. Article 68 of the Rome Statute provides for protection of the safety, physical and psychological well-being, dignity and privacy of victims and witnesses and thus determines the procedural status of these persons. However, not all the persons whose rights have been violated by the commission of these crimes acquire the status of victims. This is due to the fact that such crimes affect a huge number of persons and it is impossible to mention them all by name. It is also difficult to assess the entire damage suffered by the victims. While assessing the amount of damages it is essential to take into account physical and moral harm, as well as property damage. The procedural status of victims thus gains an exclusive character. In order to determine the full extent of the damage suffered by the victims it is necessary to collect sufficient evidence. However, it is extremely difficult to collect the evidence that would ensure the full and objective protection of the victims’ rights. While making requests for the collection of evidence, the International Criminal Court faces the problem of protection of national security information. Religious beliefs and the family life of victims are of great importance. In some Islamic countries, it is impossible to question a woman without her husband’s consent which affects the objectivity of her testimony. Finally, the number of victims is quantified by hundreds and thousands. The assessment of these elements demands time and highly qualified work. These factors justify the creation of a mechanism that would help to collect the evidence and establish the truth in the international criminal proceedings. This mechanism will help to impose a just and appropriate punishment for the persons accused of having committed a crime, since, committing the crime, criminals could not misunderstand the outcome of their criminal intent.

Keywords: crimes against humanity, evidence in international criminal proceedings, international criminal proceedings, protection of victims

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Authors: Antonio Davola

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Moving from the evaluations operated by Richard Posner in his judgment on the case Carhart v. Halaska, the paper seeks to analyse the so-called ‘litigation troll’ phenomenon and the development of a damage claims market, i.e. a market in which the right to propose claims is voluntary exchangeable for money and can be asserted by private buyers. The aim of our study is to assess whether the implementation of a ‘damage claims market’ might represent a resource for victims or if, on the contrary, it might operate solely as a speculation tool for private investors. The analysis will move from the US experience, and will then focus on the EU framework. Firstly, the paper will analyse the relation between the litigation troll phenomenon and the patent troll activity: even though these activities are considered similar by Posner, a comparative study shows how these practices significantly differ in their impact on the market and on consumer protection, even moving from similar economic perspectives. The second part of the paper will focus on the main specific concerns related to the litigation trolling activity. The main issues that will be addressed are the risk that the circulation of damage claims might spur non-meritorious litigation and the implications of the misalignment between the victim of a tort and the actual plaintiff in court arising from the sale of a claim. In its third part, the paper will then focus on the opportunities and benefits that the introduction and regulation of a claims market might imply both for potential claims sellers and buyers, in order to ultimately assess whether such a solution might actually increase individual’s legal empowerment. Through the damage claims market compensation would be granted more quickly and easily to consumers who had suffered harm: tort victims would, in fact, be compensated instantly upon the sale of their claims without any burden of proof. On the other hand, claim-buyers would profit from the gap between the amount that a consumer would accept for an immediate refund and the compensation awarded in court. In the fourth part of the paper, the analysis will focus on the legal legitimacy of the litigation trolling activity in the US and the EU framework. Even though there is no express provision that forbids the sale of the right to pursue a claim in court - or that deems such a right to be non-transferable – procedural laws of single States (especially in the EU panorama) must be taken into account in evaluating this aspect. The fifth and final part of the paper will summarize the various data collected to suggest an evaluation on if, and through which normative solutions, the litigation trolling might comport benefits for competition and which would be its overall effect over consumer’s protection.

Keywords: competition, claims, consumer's protection, litigation

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Authors: Indu Gaur, Neha Bhadauria, Shilpi Shilpi, Susmita Goswami, Prem D. Sharma, Prabir K. Paul

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The concept of organic agriculture has been accepted as novelty in Indian society, but there is no data available on the human pathogens colonizing plant parts due to such practices. Also, the pattern and mechanism of their colonization need to be understood in order to devise possible strategies for their prevention. In the present study, human pathogenic bacteria were isolated from organically grown tomato plants and five of them were identified as Klebsiella pneumoniae, Enterobacter ludwigii, Serratia fonticola, Stenotrophomonas maltophilia and Chryseobacterium jejuense. Tomato plants were grown in controlled aseptic conditions with 25±1˚C, 70% humidity and 12 hour L/D photoperiod. Six weeks old plants were divided into 6 groups of 25 plants each and treated as follows: Group 1: K. pneumonia, Group 2: E. ludwigii, Group 3: S. fonticola, Group 4: S. maltophilia, Group 5: C. jejuense, Group 6: Sterile distilled water (control). The inoculums for all treatments were prepared by overnight growth with uniform concentration of 108 cells/ml. Leaf samples from above groups were collected at 0.5, 2, 4, 6 and 24 hours post inoculation for the colony forming unit counts (CFU/cm2 of leaf area) of individual pathogens using leaf impression method. These CFU counts were used for the in vivo colonization assay and adherence assay of individual pathogens. Also, resistance of these pathogens to at least 12 antibiotics was studied. Based on these findings S. fonticola was found to be most prominently colonizing the phylloplane of tomato and was further studied. Tomato plants grown in controlled aseptic conditions same as mentioned above were divided into 2 groups of 25 plants each and treated as follows: Group 1: S. fonticola, Group 2: Sterile distilled water (control). Leaf samples from above groups were collected at 0, 24, 48, 72 and 96 hours post inoculation and homogenized in suitable buffers for surface and cell wall protein isolation. Protein samples thus obtained were subjected to isocratic SDS-gel electrophoresis and analyzed. It was observed that presence of S. fonticola could induce the expression of at least 3 additional cell wall proteins at different time intervals. Surface proteins also showed variation in the expression pattern at different sampling intervals. Further identification of these proteins by MALDI-MS and bioinformatics tools revealed the gene(s) involved in the interaction of S. fonticola with tomato phylloplane.

Keywords: cell wall proteins, human pathogenic bacteria, phylloplane, solanum lycopersicum

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

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Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Suchhanda Ghosh, A. K. Paul

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Nickel, an industrially important metal is not mined in India, due to the lack of its primary mining resources. But, the chromite deposits occurring in the Sukinda and Baula-Nuasahi region of Odhisa, India, is reported to contain around 0.99% of nickel entrapped in the goethite matrix of the lateritic iron rich ore. Weathering of the dumped chromite mining overburden often leads to the contamination of the ground as well as the surface water with toxic nickel. Microbes inherent to this metal contaminated environment are reported to be capable of removal as well as detoxification of various metals including nickel. Nickel resistant fungal isolates obtained in pure form from the metal rich overburden were evaluated for their potential to biosorb nickel by using their dried biomass. Penicillium simplicissimum SAU203 was the best nickel biosorbant among the 20 fungi tested and was capable to sorbing 16.85 mg Ni/g biomass from a solution containing 50 mg/l of Ni. The identity of the isolate was confirmed using 18S rRNA gene analysis. The sorption capacity of the isolate was further standardized following Langmuir and Freundlich adsorption isotherm models and the results reflected energy efficient sorption. Fourier-transform infrared spectroscopy studies of the nickel loaded and control biomass in a comparative basis revealed the involvement of hydroxyl, amine and carboxylic groups in Ni binding. The sorption process was also optimized for several standard parameters like initial metal ion concentration, initial sorbet concentration, incubation temperature and pH, presence of additional cations and pre-treatment of the biomass by different chemicals. Optimisation leads to significant improvements in the process of nickel biosorption on to the fungal biomass. P. simplicissimum SAU203 could sorb 54.73 mg Ni/g biomass with an initial Ni concentration of 200 mg/l in solution and 21.8 mg Ni/g biomass with an initial biomass concentration of 1g/l solution. Optimum temperature and pH for biosorption was recorded to be 30°C and pH 6.5 respectively. Presence of Zn and Fe ions improved the sorption of Ni(II), whereas, cobalt had a negative impact. Pre-treatment of biomass with various chemical and physical agents has affected the proficiency of Ni sorption by P. simplicissimum SAU203 biomass, autoclaving as well as treatment of biomass with 0.5 M sulfuric acid and acetic acid reduced the sorption as compared to the untreated biomass, whereas, NaOH and Na₂CO₃ and Twin 80 (0.5 M) treated biomass resulted in augmented metal sorption. Hence, on the basis of the present study, it can be concluded that P. simplicissimum SAU203 has the potential for the removal as well as detoxification of nickel from contaminated environments in general and particularly from the chromite mining areas of Odhisa, India.

Keywords: nickel, fungal biosorption, Penicillium simplicissimum SAU203, Indian chromite mines, mining overburden

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Authors: Shirly Bar-Lev, Michal Morag

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Cults are usually thought of as suppressive organizations, where creativity is systematically stifled. Except for few scholars, creativity in cults remains an uncharted terrain (Boeri and Pressley, 2010). This paperfocuses on how cult members sought real and imaginary spaces to express themselves and even used their bodies as canvases on which to assert their individuality, resistance, devotion, pain, and anguish. We contend that cult members’ creativity paves their way out of the cult. This paper is part of a larger study into the experiences of former members of cults and cult-like NewReligiousMmovements (NRM). The research is based on in-depth interviews conducted with thirtyIsraeli men and women, aged 24 to 50, who either joined an NRM or were born into one. Their stories reveal that creativity is both emplaced and embedded in power relations. That is why Foucault’s idea of Heterotopia and Winnicott’s idea of the battle between True and False self canbenefit our understanding of how cult members creatively assert their autonomy over their bodies and thoughts while in the cult. Cults’ operate on a complex tension between submission and autonomy. On the one hand, they act as heterotopias byallowing for a ‘simultaneousmythic and real contestation of the space in which we live. Ascounter-hegemonic sites, they serve as‘the greatest reserve of theimagination’, to use Foucault’s words. Cults definitely possesselements of mystery, danger, and transgression where an alternative social ordering can emerge. On the other hand, cults are set up to format alternative identities. Often, the individuals who inhibit these spaces look for spiritual growth, self-reflection, and self-actualization. They might willingly relinquish autonomy over vast aspects of their lives in pursuit of self-improvement. In any case, cultsclaim the totality of their members’ identities and absolute commitment and compliance with the cult’s regimes. It, therefore, begs the question how the paradox between autonomy and submissioncan spur instances of creativity. How can cult members escape processes of performative regulation to assert their creative self? Both Foucault and Winnicott recognize the possibility of an authentic self – one that is spontaneous and creative. Both recognize that only the true self can feel real andmust never comply. Both note the disciplinary regimes that push the true self into hiding, as well as the social and psychological mechanisms that individuals develop to protect their true self. But while Foucault spoke of the power of critic as a way of salvaging the true self, Winnicott spoke of recognition and empathy - feeling known by others. Invitinga dialogue between the two theorists can yield a productive discussion on how cult members assert their ‘true self’ to cultivate a creative self within the confines of the cult.

Keywords: cults, creativity, heterotopia, true and false self

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Authors: Shraddha Rane, Richard Warren, Stephen Eyre

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L-23 is a pro-inflammatory molecule that signals T cells to release cytokines such as IL-17A and IL-22. Psoriasis is driven by a dysregulated immune response, within which IL-23 is now thought to play a key role. Genome-wide association studies (GWAS) have identified a number of genetic risk loci that support the involvement of IL-23 signalling in psoriasis; in particular a robust susceptibility locus at a gene encoding a subunit of the IL-23 receptor (IL23R) (Stuart et al., 2015; Tsoi et al., 2012). The lead psoriasis-associated SNP rs9988642 is located approximately 500 bp downstream of IL23R but is in tight linkage disequilibrium (LD) with a missense SNP rs11209026 (R381Q) within IL23R (r2 = 0.85). The minor (G) allele of rs11209026 is present in approximately 7% of the population and is protective for psoriasis and several other autoimmune diseases including IBD, ankylosing spondylitis, RA and asthma. The psoriasis-associated missense SNP R381Q causes an arginine to glutamine substitution in a region of the IL23R protein between the transmembrane domain and the putative JAK2 binding site in the cytoplasmic portion. This substitution is expected to affect the receptor’s surface localisation or signalling ability, rather than IL23R expression. Recent studies have also identified a psoriatic arthritis (PsA)-specific signal at IL23R; thought to be independent from the psoriasis association (Bowes et al., 2015; Budu-Aggrey et al., 2016). The lead PsA-associated SNP rs12044149 is intronic to IL23R and is in LD with likely causal SNPs intersecting promoter and enhancer marks in memory CD8+ T cells (Budu-Aggrey et al., 2016). It is therefore likely that the PsA-specific SNPs affect IL23R function via a different mechanism compared with the psoriasis-specific SNPs. It could be hypothesised that the risk allele for PsA located within the IL23R promoter causes an increase IL23R expression, relative to the protective allele. An increased expression of IL23R might then lead to an exaggerated immune response. The independent genetic signals identified for psoriasis and PsA in this locus indicate that different mechanisms underlie these two conditions; although likely both affecting the function of IL23R. It is very important to further characterise these mechanisms in order to better understand how the IL-23 receptor and its downstream signalling is affected in both diseases. This will help to determine how psoriasis and PsA patients might differentially respond to therapies, particularly IL-23 biologics. To investigate this further we have developed an in vitro model using CD4 T cells which express either wild type IL23R and IL12Rβ1 or mutant IL23R (R381Q) and IL12Rβ1. Model expressing different isotypes of IL23R is also underway to investigate the effects on IL23R expression. We propose to further investigate the variants for Ps and PsA and characterise key intracellular processes related to the variants.

Keywords: IL23R, psoriasis, psoriatic arthritis, SNP

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Authors: Junwen Chen, Celina Feleppa, Tingyue Sun, Satoko Sasagawa, Michael Smithson

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School refusal behaviours refer to behaviours to avoid school attendance, chronic lateness in arriving at school, or regular early dismissal. Poor attendance in schools is highly correlated with anxiety, depression, suicide attempts, delinquency, violence, and substance use and abuse. Poor attendance is also a strong indicator of lower achievement in school, as well as problematic social-emotional development. Long-term consequences of school refusal behaviours include fewer opportunities for higher education, employment, and social difficulties, and high risks of later psychiatric illness. Given its negative impacts on youth educational outcomes and well-being, a thorough understanding of factors that are involved in the development of this phenomenon is warranted for developing effective management approaches. This study investigated parental and adolescent factors that may contribute to school refusal behaviours by specifically focusing on the role of parental and adolescents’ anxiety and depression, emotion dysregulation, and parental rearing style. Findings are expected to inform the identification of both parental and adolescents’ factors that may contribute to school refusal behaviours. This knowledge will enable novel and effective approaches that incorporate these factors to managing school refusal behaviours in adolescents, which in turn improve their school and daily functioning. Results are important for an integrative understanding of school refusal behaviours. Furthermore, findings will also provide information for policymakers to weigh the benefits of interventions targeting school refusal behaviours in adolescents. One-hundred-and-six adolescents aged 12-18 years (mean age = 14.79 years old, SD = 1.78, males = 44) and their parents (mean age = 47.49 years old, SD = 5.61, males = 27) completed an online questionnaire measuring both parental and adolescents’ anxiety, depression, emotion dysregulation, parental rearing styles, and adolescents’ school refusal behaviours. Adolescents with school refusal behaviours reported greater anxiety and depression, with their parents showing greater emotion dysregulation. Parental emotion dysregulation and adolescents’ anxiety and depression predicted school refusal behaviours independently. To date, only limited studies have investigated the interplay between parental and youth factors in relation to youth school refusal behaviours. Although parental emotion dysregulation has been investigated in relation to youth emotion dysregulation, little is known about its role in the context of school refusal. This study is one of the very few that investigated both parental and adolescent factors in relation to school refusal behaviours in adolescents. The findings support the theoretical models that emphasise the role of youth and parental psychopathology in school refusal behaviours. Future management of school refusal behaviours should target adolescents’ anxiety and depression while incorporating training for parental emotion regulation skills.

Keywords: adolescents, school refusal behaviors, parental factors, anxiety and depression, emotion dysregulation

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Authors: Evelyn Asante Yeboah, Kwabena O. Asubonteng, Justice Camillus Mensah, Christine Furst

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Smallholder-dominated mosaic landscapes in rural Africa are relevant for food production, biodiversity conservation, and climate regulation. Land-use transitions threaten the multifunctionality of such landscapes, especially the production capacity of arable lands resulting in food security challenges. Using land-cover maps derived from maximum likelihood classification of Landsat satellite images for the years 2002, 2015, and 2020, post-classification change detection, landscape metrics, and key informant interviews, the study assessed the implications of rubber plantation expansion and oil business development on the food production capacity of Ahanta West District, Ghana. The analysis reveals that settlement and rubber areas expanded by 5.82% and 10.33% of the landscape area, respectively, between 2002 and 2020. This increase translates into over twice their initial sizes (144% in settlement change and 101% in rubber change). Rubber plantation spread dominates the north and southwestern areas, whereas settlement is widespread in the eastern parts of the landscape. Rubber and settlement expanded at the expense of cropland, palm, and shrublands. Land-use transitions between cropland, palm, and shrubland were targeting each other, but the net loss in shrubland was higher (-17.27%). Isolation, subdivision, connectedness, and patch adjacency indices showed patch consolidation in the landscape configuration from 2002 to 2015 and patch fragmentation from 2015 to 2020. The study also found patches with consistent increasing connectivity in settlement areas indicating the influence of oil discovery developments and fragmentation tendencies in rubber, shrubland, cropland, and palm, indicating springing up of smaller rubber farms, the disappearance of shrubland, and splitting up of cropland and palm areas respectively. The results revealed a trend in land-use transitions in favor of smallholder rubber plantation expansion and oil discovery developments, which suggest serious implications on food production systems and poses a risk for food security and landscape multifunctional characteristics. To ensure sustainability in land uses, this paper recommends the enforcement of legislative instruments governing spatial planning and land use in Ghana as embedded in the 2016 land-use and spatial planning act.

Keywords: food production systems, food security, Ghana’s west coast, land-use transitions, multifunctional rural landscapes

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Authors: R. Pussinen, V. Jankovic, U. Herzberg, M. Cerrada-Gimenez, T. Huhtala, A. Nurmi, T. Ahtoniemi

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Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies. We have previously shown how AAV-mediated expression of α-synuclein is seen in the chronic phenotype of the rats over 16 week follow-up period. In the context of these findings, we attempted to further characterize this long term PD related functional and motor deficits as well as neurochemical and neuropathological changes in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period. Different titers of recombinant AAV expressing human α-synuclein (A53T) were stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. A similar behavioral test battery was applied again at weeks 5, 9,12 and 15. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic gait performance monitoring was applied during the follow-up period. Evaluation focused on animal gait between groups. Tremor analysis was performed on weeks 9, 12 and 15. In addition to behavioral end-points, neurochemical evaluation of dopamine and its metabolites were evaluated in striatum. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection. Histopathology was examined from end-point samples at 3 or 12 weeks after AAV- α-synuclein transfection to evaluate dopaminergic cell viability and microglial (Iba-1) activation status in substantia nigra by using stereological analysis techniques. This study focused on the characterization and validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points. We present the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and tremor analysis which provide new insight to unilateral effects of AAV α-synuclein transfection. We also present data about neurochemical and neuropathological end-points for the dopaminergic system in the model and how well they correlate with behavioral phenotype.

Keywords: adeno-associated virus, alphasynuclein, animal model, Parkinson’s disease

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Iyad Jadalhaq, Mohammed El Hadi El Maknouzi

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The place of Islamic law in the legal system of the UAE is best understood by introducing a differentiation between its role as a formal source of law and its influence as a material source of law. What this differentiation helps clarify is that the corpus of Islamic law constitutes a much deeper influence on adjudication, law-making and the legal profession in the UAE, than it might appear at first sight, by considering its formal position in the division of labor between courts, or legislative lists of sources of law. This paper aims to examine the role of Shariah in the UAE private law system by determining the comprehensiveness of Sharia in the legal system as a whole, and not in a limited way related to it as a source of law according to Article 1 of the Civil Transactions Law. Turning to the role of the Shariah as a formal source of law, it is useful to start from Article 1 of the UAE Civil Code. This provision lays out the formal hierarchy of sources of UAE private law, these being legislation, Islamic law, and custom. Hence, when deciding a civil dispute, a judge should first refer to positive legislation in force in the UAE. Lacking the rule to cover the case before him/her, the judge ought then to refer directly to Islamic law. If the matter lacks regulation in Islamic law, only then may the judge appeal to custom. Accordingly, in connection to civil transactions, Shariah is presented here, formally, as the second source of law. Still, Shariah law addresses many other issues beyond civil transactions, including matters of morals, worship, and belief. However, in Article 1 of the UAE Civil Code, the reference to Islamic law ought to be understood as limited to the rules it lays out for civil transactions. There are four main sets of courts in the judicial systems of the UAE, whose competence is based on whether a dispute touches upon civil and commercial transactions, criminal offenses, personal statuses, or labor relations. This sectorial and multi-tiered organization of courts as a whole constitutes an institutional development compatible with the long-standing affirmation in the Shariah of the legitimacy of the judiciary. Indeed, Islamic law authorizes the governing authorities to organize the judiciary, including by allocating specific types of cases to particular kinds of judges depending on the value of the case, or by assigning judges to a specific place in which they are to exercise their jurisdictional function. In view of this, the contemporary organization of courts in the UAE can be regarded as an organic adaptation, aligned with Shariah rules on the assignment of jurisdictional authority, to the growing complexity of modern society. Therefore, we can conclude to the comprehensive role of Shariah in the entire legal system of the United Arab Emirates, including legislation, a judicial system, institutional, and administrative work.

Keywords: Islamic jurisprudence, Shariah, UAE civil code, UAE private law

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Authors: Golnoush Rostami, Farzam Kharvari

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In recent years, developments in the field of architectural education have resulted in a shift from conventional teaching methods to alternative state-of-the-art approaches in teaching methods and strategies. Criticism in architecture has been a key player both in the profession and education, but it has been mostly offered by renowned individuals. Hence, not only students or other professionals but also critics themselves may not have the option to experience buildings and rely on available 2D materials, such as images and plans, that may not result in a holistic understanding and evaluation of buildings. On the other hand, immersive environments provide students and professionals the opportunity to experience buildings virtually and reflect their evaluation by experiencing rather than judging based on 2D materials. Therefore, the aim of this study is to compare the effect of experiencing buildings in immersive environments and 2D drawings, including images and plans, on architecture criticism and architectural education. As a result, three buildings that have parametric brick facades were studied through 2D materials and in Unreal Engine v. 24 as an immersive environment among 22 architecture students that were selected using convenient sampling and were divided into two equal groups using simple random sampling. This study used mixed methods, including quantitative and qualitative methods; the quantitative section was carried out by a questionnaire, and deep interviews were used for the qualitative section. A questionnaire was developed for measuring three constructs, including privacy regulation based on Altman’s theory, the sufficiency of illuminance levels in the building, and the visual status of the view (visually appealing views based on obstructions that may have been caused by facades). Furthermore, participants had the opportunity to reflect their understanding and evaluation of the buildings in individual interviews. Accordingly, the collected data from the questionnaires were analyzed using independent t-test and descriptive analyses in IBM SPSS Statistics v. 26, and interviews were analyzed using the content analysis method. The results of the interviews showed that the participants who experienced the buildings in the immersive environment were able to have a thorough and more precise evaluation of the buildings in comparison to those who studied them through 2D materials. Moreover, the analyses of the respondents’ questionnaires revealed that there were statistically significant differences between measured constructs among the two groups. The outcome of this study suggests that integrating immersive environments into the profession and architectural education as an effective and efficient tool for architecture criticism is vital since these environments allow users to have a holistic evaluation of buildings for vigorous and sound criticism.

Keywords: immersive environments, architecture criticism, architectural education, occupant-centric evaluation, pre-occupancy evaluation

Procedia PDF Downloads 139

Authors: S. Arias

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New housing developments and the technological changes that this implies, adapt the styles of living of its residents, as well as new family structures and forms of work due to the particular needs of a specific group of people which involves different techniques of dealing with, organize, equip and use a particular territory. Currently, own their own space is increasingly important and the cities are faced with the challenge of providing the opportunity for such demands, as well as energy, water and waste removal necessary in the process of construction and occupation of new human settlements. Until the day of today, not has failed to give full response to these demands and needs, resulting in cities that grow without control, badly used land, avenues and congested streets. Buildings and dwellings have an important impact on the environment and on the health of the people, therefore environmental quality associated with the comfort of humans to the sustainable development of natural resources. Applied to architecture, this concept involves the incorporation of new technologies in all the constructive process of a dwelling, changing customs of developers and users, what must be a greater effort in planning energy savings and thus reducing the emissions Greenhouse Gases (GHG) depending on the geographical location where it is planned to develop. Since the techniques of occupation of the territory are not the same everywhere, must take into account that these depend on the geographical, social, political, economic and climatic-environmental circumstances of place, which in modified according to the degree of development reached. In the analysis that must be undertaken to check the degree of sustainability of the place, it is necessary to make estimates of the energy used in artificial air conditioning and lighting. In the same way is required to diagnose the availability and distribution of the water resources used for hygiene and for the cooling of artificially air-conditioned spaces, as well as the waste resulting from these technological processes. Based on the results obtained through the different stages of the analysis, it is possible to perform an energy audit in the process of proposing recommendations of sustainability in architectural spaces in search of energy saving, rational use of water and natural resources optimization. The above can be carried out through the development of a sustainable building code in develop technical recommendations to the regional characteristics of each study site. These codes would seek to build bases to promote a building regulations applicable to new human settlements looking for is generated at the same time quality, protection and safety in them. This building regulation must be consistent with other regulations both national and municipal and State, such as the laws of human settlements, urban development and zoning regulations.

Keywords: building regulations, housing, sustainability, technology

Procedia PDF Downloads 349

Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

Procedia PDF Downloads 107

Authors: Paul E. Jose

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A new self-report measure named the General Emotion Regulation Measure (GERM) assesses four key goals for experiencing broad valenced groups of emotions: 1) trying to experience positive emotions (e.g., joy, pride, liking a person); 2) trying to avoid experiencing positive emotions; 3) trying to experience negative emotions (e.g., anger, anxiety, contempt); and 4) trying to avoid experiencing negative emotions. Although individual differences in GERM motives have been identified, evidence of validity with common mood outcomes is lacking. In the present study, whether GERM motives predict self-reported subjective happiness and depressive symptoms (CES-D) was tested with a community sample of 833 young adults. It was predicted that the GERM motive of trying to experience positive emotions would positively predict subjective happiness, and analogously trying to experience negative emotions would predict depressive symptoms. An initial path model was constructed in which the four GERM motives predicted both subjective happiness and depressive symptoms. The fully saturated model included three non-significant paths, which were subsequently pruned, and a good fitting model was obtained (CFI = 1.00; RMR = .007). Two GERM motives significantly predicted subjective happiness: 1) trying to experience positive emotions ( = .38, p < .001) and 2) trying to avoid experiencing positive emotions ( = -.48, p <.001). Thus, individuals who reported high levels of trying to experience positive emotions reported high levels of happiness, and individuals who reported low levels of trying to avoid experiencing positive emotions also reported high levels of happiness. Three GERM motives significantly predicted depressive symptoms: 1) trying to avoid experiencing positive emotions ( = .20, p <.001); 2) trying to experience negative emotions ( = .15, p <.001); and 3) trying to experience positive emotions (= -.07, p <.001). In agreement with predictions, trying to experience positive emotions was positively associated with subjective happiness and trying to experience negative emotions was positively associated with depressive symptoms. In essence, these two valenced mood states seem to be sustained by trying to experience similarly valenced emotions. However, the three other significant paths in the model indicated that emotional motives play a complicated role in supporting both positive and negative mood states. For subjective happiness, the GERM motive of not trying to avoid positive emotions, i.e., not avoiding happiness, was also a strong predictor of happiness. Thus, people who report being the happiest are those individuals who not only strive to experience positive emotions but also are not ambivalent about them. The pattern for depressive symptoms was more nuanced. Individuals who reported higher depressive symptoms also reported higher levels of avoiding positive emotions and trying to experience negative emotions. The strongest predictor for depressed mood was avoiding positive emotions, which would suggest that happiness aversion or fear of happiness is an important motive for dysphoric people. Future work should determine whether these patterns of association are similar among clinically depressed people, and longitudinal data are needed to determine temporal relationships between motives and mood states.

Keywords: emotions motives, depression, subjective happiness, path model

Procedia PDF Downloads 211

Authors: Jafar S. Noori, Jan Romano-deGea, Maria Dimaki, John Mortensen, Winnie E. Svendsen

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Pesticides have been intensively used in agriculture to control weeds, insects, fungi, and pest. One of the most commonly used pesticides is glyphosate. Glyphosate has the ability to attach to the soil colloids and degraded by the soil microorganisms. As glyphosate led to the appearance of resistant species, the pesticide was used more intensively. As a consequence of the heavy use of glyphosate, residues of this compound are increasingly observed in food and water. Recent studies reported a direct link between glyphosate and chronic effects such as teratogenic, tumorigenic and hepatorenal effects although the exposure was below the lowest regulatory limit. Today, pesticides are detected in water by complicated and costly manual procedures conducted by highly skilled personnel. It can take up to several days to get an answer regarding the pesticide content in water. An alternative to this demanding procedure is offered by electrochemical measuring techniques. Electrochemistry is an emerging technology that has the potential of identifying and quantifying several compounds in few minutes. It is currently not possible to detect glyphosate directly in water samples, and intensive research is underway to enable direct selective and quantitative detection of glyphosate in water. This study focuses on developing and modifying a sensor chip that has the ability to selectively measure glyphosate and minimize the signal interference from other compounds. The sensor is a silicon-based chip that is fabricated in a cleanroom facility with dimensions of 10×20 mm. The chip is comprised of a three-electrode configuration. The deposited electrodes consist of a 20 nm layer chromium and 200 nm gold. The working electrode is 4 mm in diameter. The working electrodes are modified by creating molecularly imprinted polymers (MIP) using electrodeposition technique that allows the chip to selectively measure glyphosate at low concentrations. The modification included using gold nanoparticles with a diameter of 10 nm functionalized with 4-aminothiophenol. This configuration allows the nanoparticles to bind to the working electrode surface and create the template for the glyphosate. The chip was modified using electrodeposition technique. An initial potential for the identification of glyphosate was estimated to be around -0.2 V. The developed sensor was used on 6 different concentrations and it was able to detect glyphosate down to 0.5 mgL⁻¹. This value is below the accepted pesticide limit of 0.7 mgL⁻¹ set by the US regulation. The current focus is to optimize the functionalizing procedure in order to achieve glyphosate detection at the EU regulatory limit of 0.1 µgL⁻¹. To the best of our knowledge, this is the first attempt to modify miniaturized sensor electrodes with functionalized nanoparticles for glyphosate detection.

Keywords: pesticides, glyphosate, rapid, detection, modified, sensor

Procedia PDF Downloads 179

Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

Procedia PDF Downloads 71

Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Dilyara R. Khusnutdinova, Dilyara R. Kamaldinova, Alexander V. Shestopalov

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Background. Obese patients have unequal risks of metabolic disorders. It is accepted to distinguish between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). MUHO patients have a high risk of metabolic disorders, insulin resistance, and diabetes mellitus. Among the other things, the gut microbiota also contributes to the development of metabolic disorders in obesity. Obesity is accompanied by significant changes in the gut microbial community. In turn, bacterial translocation from the intestine is the basis for the blood microbiome formation. The aim was to study the features of the blood microbiome in patients with various metabolic types of obesity. Patients, materials, methods. The study included 116 healthy donors and 101 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=36) and MUHO (n=53). Quantitative and qualitative assessment of the blood microbiome was based on metagenomic analysis. Blood samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene. Alpha diversity indices (Simpson index, Shannon index, Chao1 index, phylogenetic diversity, the number of observed operational taxonomic units) were calculated. Moreover, we compared taxa (phyla, classes, orders, and families) in terms of isolation frequency and the taxon share in the total bacterial DNA pool between different patient groups. Results. In patients with MHO, the characteristics of the alpha-diversity of the blood microbiome were like those of healthy donors. However, MUHO was associated with an increase in all diversity indices. The main phyla of the blood microbiome were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Cyanobacteria, TM7, Thermi, Verrucomicrobia, Chloroflexi, Acidobacteria, Planctomycetes, Gemmatimonadetes, and Tenericutes were found to be less significant phyla of the blood microbiome. Phyla Acidobacteria, TM7, and Verrucomicrobia were more often isolated in blood samples of patients with MUHO compared with healthy donors. Obese patients had a decrease in some taxonomic ranks (Bacilli, Caulobacteraceae, Barnesiellaceae, Rikenellaceae, Williamsiaceae). These changes appear to be related to the increased diversity of the blood microbiome observed in obesity. An increase of Lachnospiraceae, Succinivibrionaceae, Prevotellaceae, and S24-7 was noted for MUHO patients, which, apparently, is explained by a magnification in intestinal permeability. Conclusion. Blood microbiome differs in obese patients and healthy donors at class, order, and family levels. Moreover, the nature of the changes is determined by the metabolic type of obesity. MUHO linked to increased diversity of the blood microbiome. This appears to be due to increased microbial translocation from the intestine and non-intestinal sources.

Keywords: blood microbiome, blood bacterial DNA, obesity, metabolically healthy obesity, metabolically unhealthy obesity

Procedia PDF Downloads 167

Authors: Shan Jiang

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China is a country with a distinct cultural system. The Chinese Communist Party (CCP) is the central factor for everything, which naturally includes culture. There are quite a lot of cultural policies in China. The same goes for TV dramas. This paper traces the evolution of Chinese TV drama policy since 1986, examines the realistic situation behind the changes, and explores the structure and role of the government in shaping the process. Using historical documents and media reports, it first analyzes four key time nodes: 1986, 2003, 2012, and 2022. It shows how the policy shifts from restricting private production to opening up to public participation, from imposing one censorship to another, and from promoting some content to restricting some other area. It finds that the policy process is not simply rectilinear but rather wandering between deregulation and strengthening control. Secondly, it divides the policies into "basic" policies that establish the overall layout and more refined "strategic" policies that respond to more refined needs. It argues that the "basic" policy process is caused by China's political, economic, and cultural system reform, and then the "strategic" policy process is affected by more environmental factors, such as the government's follow-up development strategy, industrial development, technological innovation, and specific situations. Thirdly, it analysis the main body of the 104 policies from 2000 to 2021 and puts these subjects into China's power structure and cultural system, revealing that the policy issuers are all under the highest leadership of the Chinese Central Committee. Further, the paper challenges the typical description of Chinese cultural policy, which focuses on state control exclusively, identifies the forces within and outside the system that participate in or affect the policy-making process, and reveals the inter-subjective mechanism of policy change. In conclusion, the paper reveals that China's TV drama policy is under the unified leadership of the Party and the government, which greatly guarantees the consistency of the overall direction of cultural policy, that is, the right to speak firmly in the hands. The forces within the system can sometimes promote policy changes due to common development needs. However, folk discourse is only the object of control: when it breeds a certain amount of industrial space, the government will strengthen control over this space, suppress its potential "adverse effects", and instead provide protection and create conditions for the cultivation and growth of its mainstream discourse. However, the policy combination of basic policy and strategic policy, while having a strong effect and emergency capacity, also inhibits the innovation and diversification of the TV drama market. However, the state's substantial regulation will continue to exist in the future.

Keywords: TV Policy, China, policy process, cultural policy, culture management

Procedia PDF Downloads 95

Authors: Nasser Alsadoun

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Today's companies in Saudi Arabian capital market must comply with strict criteria and adhere to rigid corporate governance rules and continuous disclosure requirements. Unlike other regulators in the region, decision makers of the Capital Market Authority (hereafter CMA) of Saudi Arabia believes that the announcements of economic sanctions and penalties for non-compliance firms will foster more effective regulatory compliance and hence improve the quality of financial reporting. An implied argument put forward by the opponents, however, states that such penalties are unnecessary and stated to be onerous for non-compliance firms. Over that last years, the CMA has publicly announced several economic fines levied on some listed companies for their failing to comply with corporate governance and continuous disclosure regulation clauses, with the amount of fine levied ranges between 50,000 SR to 100,000 SR for each failing. Economic theory suggests that rational investors make decisions based on a cost-benefit principal. The regulatory intervention made by CMA on the announcement of economic sanctions has been costly to the society (economy) hoping that it improves the transparency of financial statements. It is argued, therefore, that threat of regulators and economic sanctions will provide incentives for firms’ managers to report more relevant and reliable accounting information, and the benefit of such announcements is likely to be reflected in the context of the quality of the financial reports. Yet, the economic consequences of the revealed fines announcement for non-compliance firms in Saudi Arabian market have not been examined. Thus, this study attempts to empirically examine whether market participants are pricing the supposed benefits of rigid governance and disclosure rules in the Saudi market. The study employs an event study methodology to assess the impact of CMA economic sanctions announcements on the market price of non-compliance firms. The study also estimates and examines bid–ask spread behavior of violated firms around the CMA announcements. The findings indicate that the CMA fines announcements for failing to comply with governance and disclosure rules do not appear to play any significant role in securities pricing. In addition, tests of bid-ask behavior does not indicate any significant increases in information asymmetry surrounding these announcements. While the CMA has developed many goals to increase the awareness of listed companies with the best governance and disclosure practices, it seems they have to develop more goals to improve market efficiency and increase investors and public awareness.

Keywords: governance and disclosure violations, financial reporting quality, regulatory intervention, market efficiency

Procedia PDF Downloads 310

Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

Procedia PDF Downloads 506

Authors: Güllü Yakar, Adnan Tepecik

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A university campus resembles an independent city that is spread over a wide area. Campuses that incorporate thousands of new domestic and international users at the beginning of every academic period also host scientific, cultural and sportive events, in addition to embodying regular users such as students and staff. Wayfinding and signage systems are necessary for the regulation of vehicular traffic, and they enable users’ to navigate without losing time or feeling anxiety. While designing the system or testing the functionality of it, opinions of existing users or likely behaviors of typical user profiles (personas) provide designers with insight. The purpose of this study is to identify the wayfinding attitudes and expectations of Kastamonu University Kuzeykent Campus users. This study applies a mixed method in which a questionnaire, developed by the researcher, constitute the quantitative phase of the study. The survey was carried out with 850 participants who filled a questionnaire form which was tested in terms of construct validity by using Exploratory Factor Analysis. While interpreting the data obtained, Chi-Square, T- Test and ANOVA analyses were applied as well as descriptive analyses such as frequency (f) and percentage (%) values. The results of this survey, which was conducted during the absence of systematic wayfinding signs in the campus, reveals the participants expectations for insertion of floor plans and wayfinding signs to indoors, maps to outdoors, symbols and color codes to the existing signs and for the adequate arrangement of those for the use of visually impaired people. The fact that there is a direct proportional relation between the length of institution membership and wayfinding competency within campus, leads to the conclusion that especially the new comers are in need of wayfinding signs. In order to determine the effectiveness of campus-wide wayfinding system implemented after the survey and in order to identify the further expectations of users in this respect, a semi-structured interview form developed by the researcher and assessments of 20 participants are compiled. Subjected to content analysis, this data constitute the qualitative dimension of the study. Research results indicate that despite the presence of the signs, the participants experienced either inability or stress while finding their way, showed tendency to receive help from others and needed outdoor maps and signs, in addition to bigger-sized texts.

Keywords: environmental graphic design, environmental perception, wayfinding and signage design, wayfinding system

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

Procedia PDF Downloads 422

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

Procedia PDF Downloads 83

Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

Abstract:

Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

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Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

Abstract:

A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

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Authors: Mjellma Rexhepi, Blerta Rexhepi Kelmendi, Blana Krasniqi, Shaip Krasniqi

Abstract:

Rheumatoid arthritis is a chronic disease that causes inflammation of the joints which can be so severe that can cause not only deformities but also impairment of function that limits movement. This also contributes to the pain that accompanies this disease. This remains a problematic and challenging disease of modern medicine because treatment is still symptomatic. The main purpose of drug treatment is to reduce the activity of the disease, achieve remission, avoid disability and death. The etiology of the disease is idiopathic, but can also be linked to genetic, nongenetic factors such as hormonal, environmental or infectious. Current scientific evidence shows that vitamin D plays an important role in immune regulation mechanisms. Lack of this vitamin has been linked to loss of immune tolerance and the appearance of autoimmune processes, including rheumatoid arthritis. The purpose of the work was to define Vitamin D in patients hospitalized with rheumatoid arthritis in University Clinical Center of Kosova, as a basis of their connection with lifestyle and physical inactivity. The sample for the work was selected from patients with criteria met for rheumatoid arthritis who were hospitalized at the tertiary level of health care in Kosova. During the work have been investigated 100 consecutive patients fulfilling diagnostic criteria for rheumatoid arthritis, whereas in addition to the general characteristics are also determined the values of vitamin D at the beginning of hospitalization. The average age of the sample analyzed was 50.9±5.7 years old, with an average duration of rheumatoid arthritis disease 7.8±3.4 years. At the beginning of hospitalization, before treatment was initiated, the average value of vitamin D was 15.86±3.43, which according to current reference values is classified into the category of insufficient values. Correlating the duration of the disease, from the time of diagnosis to the day of hospitalization, on one side and the level of vitamin D on the other side, the negative correlation of a lower degree derived (r =-0.1). Physical activity affects the concentration of vitamin D in the blood through increased metabolism of fat and the release of vitamin D and its metabolites from adipose tissue. To now it is evident that physical activity is also accompanied by higher levels of vitamin D. In patients with rheumatoid arthritis, vitamin D levels were low compared to normal. Future works should be oriented toward investigating in detail the bone structure, quality of life and pain in patients with rheumatoid arthritis. More detailed scientific projects, with larger numbers of participants, should be designed for the future to clarify more possible mechanisms as factors related to this phenomenon such as inactivity, lifestyle and the duration of the disease, as well as the importance of keeping vitamin D values at normal limits.

Keywords: hospitalization, lifestyle, rheumatoid arthritis, vitamin D

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Authors: Ivette Gonzalez-Rivera, Diana B. Paz-Trejo, Oscar Galicia-Castillo, David N. Velazquez-Martinez, Hugo Sanchez-Castillo

Abstract:

Prolonged exposure to stress can cause disorders related with dysfunction in the prefrontal cortex such as generalized anxiety and depression. These disorders involve alterations in neurotransmitter systems; the serotonergic system—a target of the drugs that are commonly used as a treatment to these disorders—is one of them. Recent studies suggest that 5-HT1A receptors play a pivotal role in the serotonergic system regulation and in stress responses. In the same way, there is increasing evidence that astrocytes are involved in the pathophysiology of stress. The aim of this study was to examine the effects of 8-OH-DPAT, a selective agonist of 5-HT1A receptors, in the behavioral signs of anxiety and anhedonia as well as in the number of astrocytes in the medial prefrontal cortex (mPFC) after exposure to chronic stress. They used 50 male Wistar rats of 250-350 grams housed in standard laboratory conditions and treated in accordance with the ethical standards of use and care of laboratory animals. A protocol of chronic unpredictable stress was used for 10 consecutive days during which the presentation of stressors such as motion restriction, water deprivation, wet bed, among others, were used. 40 rats were subjected to the stress protocol and then were divided into 4 groups of 10 rats each, which were administered 8-OH-DPAT (Tocris, USA) intraperitoneally with saline as vehicle in doses 0.0, 0.3, 1.0 and 2.0 mg/kg respectively. Another 10 rats were not subjected to the stress protocol or the drug. Subsequently, all the rats were measured in an open field test, a forced swimming test, sucrose consume, and a cero maze test. At the end of this procedure, the animals were sacrificed, the brain was removed and the tissue of the mPFC (Bregma: 4.20, 3.70, 2.70, 2.20) was processed in immunofluorescence staining for astrocytes (Anti-GFAP antibody - astrocyte maker, ABCAM). Statistically significant differences were found in the behavioral tests of all groups, showing that the stress group with saline administration had more indicators of anxiety and anhedonia than the control group and the groups with administration of 8-OH-DPAT. Also, a dose dependent effect of 8-OH-DPAT was found on the number of astrocytes in the mPFC. The results show that 8-OH-DPAT can modulate the effect of stress in both behavioral and anatomical level. Also they indicate that 5-HT1A receptors and astrocytes play an important role in the stress response and may modulate the therapeutic effect of serotonergic drugs, so they should be explored as a fundamental part in the treatment of symptoms of stress and in the understanding of the mechanisms of stress responses.

Keywords: anxiety, prefrontal cortex, serotonergic system, stress

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