Search results for: Human Cbl-b protein

Authors: Cheila Pereira, Sara C. Cunha, Miguel A. Faria, José O. Fernandes

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The increasing world population brings several concerns, one of which is food security and sustainability. To meet this challenge, aquaculture, the farming of aquatic animals and plants, including fish, mollusks, bivalves, and algae, has experienced sustained growth and development in recent years. Recent advances in this industry have focused on reducing its economic and environmental costs, for example, the substitution of protein sources in fish feed. Plant-based proteins are now a common approach, and while it is a greener alternative to animal-based proteins, there are some disadvantages, such as their putative content and intoxicants such as mycotoxins. These are naturally occurring plant contaminants, and their exposure in fish can cause health problems, stunted growth or even death, resulting in economic losses for the producers and health concerns for the consumers. Different works have demonstrated the presence of both AFB1 (aflatoxin B1) and ENNB1 (enniatin B1) in fish feed and their capacity to be absorbed and bioaccumulate in the fish organism after digestion, further reaching humans through fish ingestion. The aim of this work was to evaluate the bioaccessibility of both mycotoxins in samples of Sparus aurata muscle using a static digestion model based on the INFOGEST protocol. The samples were subjected to different cooking procedures – raw, grilled and fried – and different seasonings – none, thyme and ginger – in order to evaluate their potential reduction effect on mycotoxins bioaccessibility, followed by the evaluation of the intestinal transport of both compounds with an in vitro cell model composed of Caco-2/HT-29 co-culture monolayers, simulating the human intestinal epithelium. The bioaccessible fractions obtained in the digestion studies were used in the transport studies for a more realistic approach to bioavailability evaluation. Results demonstrated the effect of the use of different cooking procedures and seasoning on the toxin's bioavailability. Sparus aurata was chosen in this study for its large production in aquaculture and high consumption in Europe. Also, with the continued evolution of fish farming practices and more common usage of novel feed ingredients based on plants, there is a growing concern about less studied contaminants in aquaculture and their consequences for human health. In pair with greener advances in this industry, there is a convergence towards alternative research methods, such as in vitro applications. In the case of bioavailability studies, both in vitro digestion protocols and intestinal transport assessment are excellent alternatives to in vivo studies. These methods provide fast, reliable and comparable results without ethical restraints.

Keywords: AFB1, aquaculture, bioaccessibility, ENNB1, intestinal transport.

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Authors: Sonam Kumari

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Tuberculosis is the deadliest disease worldwide. Millions of people lose their lives every year due to this disease. It has turned lethal due to the erratic nature of its causative organism, Mycobacterium tuberculosis (Mtb). Mtb tends to enter into an inactive, dormant state and emerge to replicating state upon encountering favorable conditions. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes. Mtb has seven such proteins (WhiB1 to WhiB7). WhiB proteins are transcriptional regulators; they regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical parameters of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: mycobacterium tuberculosis, TB, whiB proteins, ITC

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Authors: Mariam Azam, Sajjad Ur Rahman, Mukarram Bashir, Muhammad Tahir, Seemal Javaid, Jawad, Aoun Muhammad, Muhammad Zohaib, Hannan Khan

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Products of microbial origin are of great importance as they have proved their value in healthcare and nutrition, use of these microbial metabolites acquired from partially fermented soya hulls and wheat bran along with Saccharomyces cerevisiae (DL-22 S/N) substantiates to be a great source for an increase in the total milk production and quality yield.1×109 CFU/ml cells of Saccharomyces cerevisiae (DL-22 S/N) were further grown under in-vivo conditions for the assessment of quality milk production. Two groups with twelve cows, each having the same physical characteristics (Group A and Group B), were under study, Group A was daily fed with 12gm of biological metabolites and 22% protein-pelleted feed. On the other hand, the animals of Group B were provided with no metabolites in their feed. In thirty days of trial, improvement in the overall health, body score, milk protein, milk fat, yield, incidence rate of mastitis, ash, and solid not fat (SNF) was observed. The collected data showed that the average quality milk production was elevated up to 0.45 liter/h/d. However, a reduction in the milk fats up to 0.45% and uplift in the SNF value up to 0.53% of cow milk was also observed. At the same time, the incidence rate of mastitis recorded for the animals under trial was reduced to half, and improved non specific immunity was reported.

Keywords: microbial metabolites, post-biotics, animal supplements, animal nutrition, proteins, animal production, fermentation

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Authors: Jinpa Palmo

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In many research, omega 3 fatty acid which is a polyunsaturated fatty acids is proved to be very important and essential nutrients having many different health benefits but apart from other fatty acids, it cannot be synthesise by our human body. Therefore, we have to get these fatty acids by consuming diets and supplements rich in it. Even though human beings can live by consuming other important nutrients but can live much healthier and longer by consuming omega 3 fatty acids. American heart association AHA recommends for daily intake of omega 3 fatty acids specially by those people with coronary heart disease. Fish considering as nutritional valuable animal is mostly due to its lipid content (fish oil) in which these omega 3 fatty acids are present very significantly. Fish does not actually produce these omega 3 fatty acid in their body, but receive these fatty acids through the food web in which phytoplankton are the chief source of these omega fatty acids.

Keywords: fatty acid, fish, disease, health

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Authors: Anna Tokajuk, Agnieszka Zakrzeska, Ewa Chabielska, Halina Car

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Whey is a by-product generated mainly in the production of cheese and casein. Powder forms of whey are used widely in the food industry as well as a high-protein food for infants, for convalescents, by athletes and especially by bodybuilders to increase muscle mass during exercise. Whey protein concentrate-80 (WPC-80) is a source of bioactive peptides with beneficial effects on the cardiovascular system. It is known that whey proteins health beneficial properties include antidiabetic, blood pressure lowering, improving cardiovascular system function, antibacterial, antiviral and other effects. To study its influence on the development of thrombosis, venous thrombosis model was performed according to the protocol featured by Reyers with modification by Chabielska and Gromotowicz. Male Wistar-Crl: WI (Han) rats from researched groups were supplemented with two doses of WPC-80 (0.3 or 0.5 g/kg) for 7, 14 or 21 days and after these periods, one-hour venous thrombosis model was performed. Control group received 0.9 % NaCl solution and was sham operated. The statistical significance of results was computed by Mann – Whitney’s test. We observed that thrombus weight was decreased in animals obtaining WPC-8080 and that was statistically significant in 14 and 21-day supplemented groups. Blood count parameters did not differ significantly in rats with and without thrombosis induction whether they were fed with WPC-80 or not. Moreover, the number of platelets (PLT) was within the normal range in each group. The examined coagulation parameters in rats of the control groups were within normal limits. After WPC-80 supplementation there was the tendency to prolonged activated partial thromboplastin time (aPTT), but in comparison, the results did not turn out significant. In animals that received WPC-80 0.3 g·kg-1 for 21 days with and without induced thrombosis, prothrombin time (PT) and an international normalized ratio (INR) was somewhat decreased, remaining within the normal range, but the nature and significance of this observation are beyond the framework of the current study. Additionally, fibrinogen and thrombin time (TT) did not differ significantly between groups. Therefore the exact effect of WPC-80 on coagulation system is still elusive and requires further thorough research including mechanisms of action. Determining the potential clinical application of WPC-80 requires the selection of the optimal dose and duration of supplementation.

Keywords: antithrombotic, rats, venous thrombosis, WPC-80

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Authors: Han Xiao

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The development of nanomedicines has recently achieved several breakthroughs in the field of cancer treatment; however, the biocompatibility and targeted burst release of these medications remain a limitation, which leads to serious side effects and significantly narrows the scope of their applications. The self-assembly of intermediate filament protein (IFP) peptides was triggered by a hydrophobic cation drug 7-amino actinomycin D (7-AAD) to synthesize pH-activatable nanoparticles (NPs) that could simultaneously locate tumors and produce antitumor effects. The designed IFP peptide included a target peptide (arginine–glycine–aspartate), a negatively charged region, and an α-helix sequence. It also possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. 7-AAD molecules with excellent near-infrared fluorescence properties could be target delivered into tumor cells by NPs and released immediately in the acidic environments of tumors and endosome/lysosomes, ultimately inducing cytotoxicity by arresting the tumor cell cycle with inserted DNA. It is noteworthy that the IFP/7-AAD NPs tail vein injection approach demonstrated not only high tumor-targeted imaging potential, but also strong antitumor therapeutic effects in vivo. The proposed strategy may be used in the delivery of cationic antitumor drugs for precise imaging and cancer therapy.

Keywords: 7-amino actinomycin D, intermediate filament protein, nanoparticle, tumor image

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Authors: Ji Hye Im, Nguyen T. T. Phuong, Keon Wook Kang

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Estrogens are important for the development and growth of estrogen receptor (ER)-positive breast cancer, for which anti-estrogen therapy is one of the most effective treatments. However, its efficacy can be limited by either de novo or acquired resistance. Aromatase is a key enzyme for the biosynthesis of estrogens, and inhibition of this enzyme leads to profound hypoestrogenism. Here, we found that the basal expression and activity of aromatase were significantly increased in tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells compared to control MCF-7 cells. We further revealed that aromatase immunoreactivity in tumor tissues was increased in recurrence group after TAM therapy compared to non-recurrence group after TAM therapy. Phosphorylation of Akt, extracellular signal-regulated kinase (ERK), and p38 kinase were all increased in TAMR-MCF-7 cells. Inhibition of phosphoinositide 3-kinase (PI3K) suppressed the transactivation of the aromatase gene and its enzyme activity. Furthermore, we have also shown that PI3K/Akt-dependent cAMP-response element binding protein (CREB) activation was required for the enhanced expression of aromatase in TAMR-MCF-7 cells. Our findings suggest that aromatase expression is up-regulated in TAM-resistant breast cancer via PI3K/Akt-dependent CREB activation.

Keywords: TAMR-MCF-7, CREB, estrogen receptor, aromatase

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Authors: Anandit Sachdev

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Auroville, a settlement in Tamil Nadu, India, is based on the principles of ‘human unity’as defined by Indian philosopher Sri Aurobindo. The settlement was conceptualized on these principles by Sri Aurobindo’s spiritual partner Mirra Alfassa, known as ‘The Mother’ to the Aurovillians. In common perception, the settlement is an experiment in achieving ‘human unity’ through sustainable living. Since its inception in late 1960s, the settlement has attracted people from a variety of nationalities, each understanding, seeking, and rendering ‘human unity’ in their own unique way. This multiplicity of inhabitation has created and continues to create complex and layered human and more-than-human geographies, which are collectively understood as Auroville. This essay builds on these multiple narratives of local metaphysical and every inhabitation of spiritual and philosophical ideas of Sri Aurobindo as rendered in materiality by the Mother. The research aims to assess how theseforms of everyday spirituality conflict, interact, and engage with the principles of Auroville. The research further aims to understands how, if at all, the diverse landscapes of social, cultural, and infrastructural conflictssynthesizewhen perceived through the lens of spirituality. The research does so by detailing the different forms of the built environment which evoke the transcendental and its underlying processes. While doing so, it aims to understand how different manifestations of interiority within the Aurovillian landscape tie back to the self and its entanglements. By analysing the settlement through a spiritual lens, the research ultimately ties together questions relating to the built environment and ontology and asks how each facilitates a continuous synthesis with the other. Lastly, the paper enquires if these ongoing processes of synthesis of built space and ontological entanglements are what can be conceptualized as ‘human unity’ as perceived by Sri Aurobindo himself.

Keywords: sacrality, sacred, spirituality, philosophy, Indian philosophy, auroville, India

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Authors: Ben Otange, Wolfgang Parak, Florian Schulz, Michael Alexander Rubhausen

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The feasibility of extending the usage of molecular imprinting technique in complex biomolecules is demonstrated in this research. This technique is promising in diverse applications in areas such as drug delivery, diagnosis of diseases, catalysts, and impurities detection as well as treatment of various complications. While molecularly imprinted polymers MIP remain robust in the synthesis of molecules with remarkable binding sites that have high affinities to specific molecules of interest, extending the usage to complex biomolecules remains futile. This work reports on the successful synthesis of MIP from complex proteins: BSA, Transferrin, and MUC1. We show in this research that despite the heterogeneous binding sites and higher conformational flexibility of the chosen proteins, relying on their respective epitopes and motifs rather than the whole template produces highly sensitive and selective MIPs for specific molecular binding. Introduction: Proteins are vital in most biological processes, ranging from cell structure and structural integrity to complex functions such as transport and immunity in biological systems. Unlike other imprinting templates, proteins have heterogeneous binding sites in their complex long-chain structure, which makes their imprinting to be marred by challenges. In addressing this challenge, our attention is inclined toward the targeted delivery, which will use molecular imprinting on the particle surface so that these particles may recognize overexpressed proteins on the target cells. Our goal is thus to make surfaces of nanoparticles that specifically bind to the target cells. Results and Discussions: Using epitopes of BSA and MUC1 proteins and motifs with conserved receptors of transferrin as the respective templates for MIPs, significant improvement in the MIP sensitivity to the binding of complex protein templates was noted. Through the Fluorescence Correlation Spectroscopy FCS measurements on the size of protein corona after incubation of the synthesized nanoparticles with proteins, we noted a high affinity of MIPs to the binding of their respective complex proteins. In addition, quantitative analysis of hard corona using SDS-PAGE showed that only a specific protein was strongly bound on the respective MIPs when incubated with similar concentrations of the protein mixture. Conclusion: Our findings have shown that the merits of MIPs can be extended to complex molecules of higher biomolecular mass. As such, the unique merits of the technique, including high sensitivity and selectivity, relative ease of synthesis, production of materials with higher physical robustness, and higher stability, can be extended to more templates that were previously not suitable candidates despite their abundance and usage within the body.

Keywords: molecularly imprinted polymers, specific binding, drug delivery, high biomolecular mass-templates

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Authors: Navkiran Kaur, Apoorva Mathur, Abhishree Agarwal, Sakshi Gupta, Tuhin Rashmi

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Aim: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. Glycosylation of proteins is one of the most important post-translational modifications. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. Alterations in cell surface glycosylation, can promote invasive behavior of tumor cells that ultimately lead to the progression of cancer. In breast cancer, there is an increasing evidence pertaining to the role of glycosylation in tumor formation and metastasis. In the present study, an attempt has been made to study the disease associated sialoglycoproteins in breast cancer by using bioinformatics tools. The sequence will be retrieved from UniProt database. A database in the form of a word document was made by a collection of FASTA sequences of breast cancer gene sequence. Glycosylation was studied using yinOyang tool on ExPASy and Differential genes expression and protein analysis was done in context of breast cancer metastasis. The number of residues predicted O-glc NAc threshold containing 50 aberrant glycosylation sites or more was detected and recorded for individual sequence. We found that the there is a significant change in the expression profiling of glycosylation patterns of various proteins associated with breast cancer. Differential aberrant glycosylated proteins in breast cancer cells with respect to non-neoplastic cells are an important factor for the overall progression and development of cancer.

Keywords: breast cancer, bioinformatics, cancer, metastasis, glycosylation

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Authors: Portia Muehlbauer

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This paper examines the evolving landscape of preventing and countering violent extremism (PCVE) by delving into the growing importance of integrating human rights principles into violence prevention strategies on the local, community level. This study sheds light on the underlying theoretical frameworks of violent extremism and the influence of gender while investigating the intersection between human rights preservation and violent extremism prevention. To gain practical insight, the research focuses on two prominent international non-governmental organizations, Women without Borders (WwB) and Hedayah, and their distinct PCVE initiatives. WwB adopts a gender-sensitive approach, implementing parental education programs that empower mothers in at-risk communities to prevent the spread of violent extremism. In contrast, Hedayah takes an indirect route, employing capacity building programs that enhance the capabilities of educators, social workers, and psychologists in early intervention, rehabilitation and reintegration efforts. Qualitative data for this comparative analysis was collected through an extensive four-month internship at WwB during the fall of 2020, a three-month internship at Hedayah in the spring of 2021, a thought-provoking semi-structured interview with the executive director of WwB, personal field notes, and a comprehensive discourse analysis of the prevailing literature on human rights considerations in PCVE practices. This study examines the merits and challenges of integrating human rights into PCVE programming through the lens of both organizations, WwB and Hedayah. The findings of this study will inform policymakers, practitioners, and researchers on the intricate relationship between human rights protection and effective PCVE strategies.

Keywords: preventing and countering violent extremism, human rights, counterterrorism, peacebuilding, capacity building programs, gender studies

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Authors: Sheetla Prasad

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The focus issue of this article is to determine the mechanism of mind with geometrical analysis of human face. Research paradigm has been designed for study of spatial dynamic of face and it was found that different shapes of face have their own function for determine the action of mind. The functional ratio (FR) of face has determined the behaviour operation of human beings. It is not based on the formulistic approach of prediction but scientific dogmatism and mathematical analysis is the root of the prediction of behaviour. For analysis, formulae were developed and standardized. It was found that human psyche is designed in three forms; manipulated, manifested and real psyche. Functional output of the psyche has been determined by degree of energy flow in the psyche and reserve energy for future. Face is the recipient and transmitter of energy but distribution and control is the possible by mind. Mind directs behaviour. FR indicates that the face is a power house of energy and as per its geometrical domain force of behaviours has been designed and actions are possible in the nature of individual. The impact factor of this study is the promotion of human capital for job fitness objective and minimization of criminalization in society.

Keywords: functional ratio, manipulated psyche, manifested psyche, real psyche

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Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

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Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

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Authors: Mustafa M. Donma, Orkide Donma

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A growing list of cancers might be influenced by obesity. Obesity is associated with an increased risk for the occurrence and development of some cancers. Inflammation can lead to cancer. It is one of the characteristic features of cancer and plays a critical role in cancer development. C-reactive protein (CRP) is under evaluation related to the new and simple prognostic factors in patients with metastatic renal cell cancer. Obesity can predict and promote systemic inflammation in healthy adults. BMI is correlated with hs-CRP. In this study, SII index and CRP values were evaluated in children with normal BMI and those within the range of different obesity grades to detect the tendency towards cancer in pediatric obesity. A total of one hundred and ninety-four children; thirty-five children with normal BMI, twenty overweight (OW), forty-seven obese (OB) and ninety-two morbid obese (MO) participated in the study. Age- and sex-matched groups were constituted using BMI-for age percentiles. Informed consent was obtained. Ethical Committee approval was taken. Weight, height, waist circumference (C), hip C, head C and neck C of the children were measured. The complete blood count test was performed. C-reactive protein analysis was performed. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. SII index values were progressively increasing starting from normal weight (NW) to MO children. There is a statistically significant difference between NW and OB as well as MO children. No significant difference was observed between NW and OW children, however, a correlation was observed between NW and OW children. MO constitutes the only group, which exhibited a statistically significant correlation between SII index and CRP. Obesity-related bladder, kidney, cervical, liver, colorectal, endometrial cancers are still being investigated. Obesity, characterized as a chronic low-grade inflammation, is a crucial risk factor for colon cancer. Elevated childhood BMI values may be indicative of processes leading to cancer, initiated early in life. Prevention of childhood adiposity may decrease the cancer incidence in adults. To authors’ best knowledge, this study is the first to introduce SII index values during obesity of varying degrees of severity. It is suggested that this index seems to affect all stages of obesity with an increasing tendency and may point out the concomitant status of obesity and cancer starting from very early periods of life.

Keywords: children, C-reactive protein, systemic immune-inflammation index, obesity

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Authors: A. Kabiri-Samani, M. J. Seddighi

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There is no doubt that a key factor in the manifestation of architecture is the interaction of human and nature. Explaining the type of relationship defined by “the architect” between architecture and nature opens a window towards understanding the theoretical conceptions of the architect as the creator of “architecture”. Now, if these theoretical foundations are put under scrutiny from the viewpoint of Islam, and an architect considers the relationship of human and nature within the context of Islam, he would let nature to manifest itself in architecture. The reasons for such a relationship is explicable in terms of the degree and nature of knowledge of the architect about nature; while the way it comes to existence is explained by defining the force of nature – ruling the entire nature – and its acts. It is by the scientific command of the architect and his mastery in the hermetic force of nature that the material bodies of buildings evolve from artificial to natural. Additionally, the presence of nature creates hermetic architectural spaces for the spiritual development of humans while serving for living at different levels.

Keywords: nature, Islam, cognition, science, presence, elixir

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Yen-Ni Teng, Hsing-Yi Chen, Hsien-An Pan, Yung-Ming Lin, Hany A. Omar, Jui-Hsiang Hung

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Leucine-rich repeats and WD repeat domain containing 1 (LRWD1) is highly expressed in the testes of healthy males. On the other hand, LRWD1 is significantly down-regulated in the testicular tissues of patients with severe spermatogenic defects. In our study, the downregulation of LRWD1 expression by shRNA caused a significant reduction of cell growth and mitosis and a noteworthy increase in the cell microtubule atrophy rate. Here, we used EMBOSS CpG plot analysis to explore the promoter region of LRWD1 gene. We found that CpG islands are located between positions -253 to +5 nucleotides upstream from the LRWD1 transcription start site. Luciferase reporter assay revealed that the hypermethylation of the LRWD1 promoter reduced the transcription activity in cells. In addition, quantitative methylation-specific PCR and immunostaining showed that the methylation inhibitor, 5-Aza-2'-deoxycytidine, increased LRWD1 promoter activity, LRWD1 mRNA, protein expression and cell viability. Whereas, the methylation activator, S-adenosylmethionine, caused opposite effects. The overexpression of p53 and Nrf2 in NT2/D1 cells increased LRWD1 promoter activity while 5-fluorodeoxyuridine decreased it. In conclusion, this study highlights evidence that the methylation status of LRWD1 promoter is associated with LRWD1 expression. Since the expression level of LRWD1 plays an important role in spermatogenesis, the methylation status of LRWD1 may serve as a novel molecular diagnostic or therapeutic approach in male's infertility.

Keywords: LRWD1, DNA methylation, p53, Nrf2

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Authors: Seraphina Bakta

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On many occasions, the link between human rights and culture in Africa is tainted with speculations that African traditions and culture impede human rights. Seemingly also, literature from Africa highly supports the approach of cultural relativism instead of the universalism approach to human rights. This approach has been regarded by many as an unwillingness to accept human rights as universal. While it has to be appreciated that in different communities, there are positive and negative elements of culture, including in Africa, the positive aspect is hardly seen in African culture. This paper, employed documentary review and interviews to collect data. Various documents were reviewed including international and domestic legal materials and literature. Data from documentary review were verified through interviews in Morogoro and Shinyanga regions in Tanzania. Qualitative approach was used to analyse such data where a thematic content analysis was used. The study found that there are positive aspects of African tradition and culture including those promoting child work (as opposed to child labour); some aspects on child protection which should be embraced. However, still some aspects such as child marriage and inconsistent with child rights. It is pivotal that therefore that measures are be adopted to address them.

Keywords: child rights, customs, tradition, Africa

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Authors: Abdelbaky Abouzeid

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The study aimed at determining the effect of using the active learning on achievement and attitudes toward studying the human rights course for the Bahrain Teachers College students and the extent to which any differences of statistical significance according to gender and section can exist. To achieve the objectives of the study, the researcher developed and implemented research tools such as academic achievement test and the scale of attitudes towards the study of the Human Rights Course. The scale of attitudes towards Human Rights was constructed of 40 items investigating four dimensions; the cognitive dimension, the behavioral dimension, the affective dimension, and course quality dimension. The researcher then applied some of the active learning strategies in teaching this course to all students of the first year of the Bahrain Teachers College (102 male and female students) after excluding two students who did not complete the course requirements. Students were divided into five groups. These strategies included interactive lecturing, presentations, role playing, group projects, simulation, brainstorming, concept maps and mind maps, reflection and think-pair-share. The course was introduced to students during the second semester of the academic year 2016-2017. The study findings revealed that the use of active learning strategies affected the achievement of students of Bahrain Teachers College in the Human Rights course. The results of the T-test showed statistically significant differences on the pre-test and post-test in favor of the post-test. No statistically significant differences in the achievement of students according to the section and gender were found. The results also indicated that the use of active learning strategies had a positive effect on students' attitudes towards the study of the Human Rights Course on all the scale’s items. The general average reached (4.26) and the percentage reached (85.19%). Regarding the effect of using active learning strategies on students’ attitudes towards all the four dimensions of the scale, the study concluded that the behavioral dimension came first; the quality of the course came second, the cognitive dimension came third and in the fourth place came the affective dimension. No statistically significant differences in the attitude towards studying the Human Rights Course for the students according to their sections or gender were found. Based on the findings of the study, the researchers suggested some recommendations that can contribute to the development of teaching Human Rights Course at the University of Bahrain.

Keywords: attitudes, academic achievement, human rights, behavioral dimension, cognitive dimension, affective dimension, quality of the course

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Authors: Tsai-chun Lai, Szu-ju Fu, Tzu-lin Lee, Yuh-Lien Chen

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There is much evidence that exposure to fine particulate matter (PM) from air pollution increases the risk of cardiovascular morbidity and mortality. According to previous reports, PM in the air enters the respiratory tract, contacts the alveoli, and enters the blood circulation, leading to the progression of cardiovascular disease. PM pollution may also lead to cardiometabolic disturbances, increasing the risk of cardiovascular disease. The effects of PM on cardiac function and mitochondrial damage are currently unknown. We used mice and rat cardiomyocytes (H9c2) as animal and in vitro cell models, respectively, to simulate an air pollution environment using PM. These results indicate that the apoptosis-related factor PUMA, a regulator of apoptosis upregulated by p53, is increased in mice treated with PM. Apoptosis was aggravated in cardiomyocytes treated with PM, as measured by TUNEL assay and Annexin V/PI. Western blot results showed that CASPASE3 was significantly increased and BCL2 (B-cell lymphoid 2) was significantly decreased under PM treatment. Concurrent exposure to PM increases mitochondrial reactive oxygen species (ROS) production by MitoSOX Red staining. Furthermore, using Mitotracker staining, PM treatment significantly shortened mitochondrial length, indicating mitochondrial fission. The expression of mitochondrial fission-related proteins p-DRP1 (phosphodynamics-related protein 1) and FIS1 (mitochondrial fission 1 protein) was significantly increased. Based on these results, the exposure to PM worsens mitochondrial function and leads to cardiomyocyte apoptosis.

Keywords: particulate matter, cardiomyocyte, apoptosis, mitochondria

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Authors: Prakash Singh, Thembinkosi Twalo

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The sustainability of the Buffalo City Metropolitan Municipality (BCMM), in South Africa, is being threatened by the reported cases of poor administration, weak management of resources, inappropriate job performance, and inappropriate job behaviour of some of the workers. Since the structural-functionalists assume that formal education is a solution to societal challenges, it therefore means that the BCMM should not be experiencing this threat since many of its workers have various levels of formal education. Consequently, this study using the mixed method research approach, set out to investigate the paradoxical co-existence of inappropriate job behaviour and performance with formal education at the BCMM. Considering the impact of human factors in the labour process, this study draws attention to the divergent objectives of skill and skill bearer, with the application of knowledge subject to the knowledge bearer’s motives, will, attitudes, ethics and values. Consequently, inappropriate job behaviour and performance practices could be due to numerous factors such as lack of the necessary capabilities or refusal to apply what has been learnt due to racial or other prejudices. The role of the human factor in the labour process is a serious omission in human capital theory, which regards schooling as the only factor contributing to the ability to do a job. For this reason this study’s theoretical framework is an amalgamation of the four theories - human capital, social capital, cultural capital, and reputation capital – in an effort to obtain a broader view of the factors that shape job behaviour and performance. Since it has been established that human nature plays a crucial role in how workers undertake their responsibilities, it is important that this be taken into consideration in the BCMM’s monitoring and evaluation of the workers’ job performance practices. Hence, this exploratory study brings to the fore, the effects of poor job performance practices on the job satisfaction of workers.

Keywords: human capital, poor job performance practices, service delivery, workers’ job satisfaction

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Authors: Chenlu Zhang, Wanni Zhang, Florian Schaule

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Indoor environment in office buildings directly affects comfort, productivity, health, and well-being of building occupants. Wireless environmental sensor networks have been deployed in many modern offices to monitor and control the indoor environments. However, indoor environmental variables are not strong enough predictors of comfort and productivity levels of every occupant due to personal differences, both physiologically and psychologically. This study proposes human-centric sensor networks that integrate wireless environmental sensors, body area network sensors and participatory sensing technologies to collect data from both environment and human and support building operations. The sensor networks have been tested in one small-size and one medium-size office rooms with 22 participants for five months. Indoor environmental data (e.g., air temperature and relative humidity), physiological data (e.g., skin temperature and Galvani skin response), and physiological responses (e.g., comfort and self-reported productivity levels) were obtained from each participant and his/her workplace. The data results show that: (1) participants have different physiological and physiological responses in the same environmental conditions; (2) physiological variables are more effective predictors of comfort and productivity levels than environmental variables. These results indicate that the human-centric sensor networks can support human-centric building control and improve comfort and productivity in offices.

Keywords: body area network, comfort and productivity, human-centric sensors, internet of things, participatory sensing

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Authors: Alok Raghav, Jamal Ahmad

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Background: Serum albumin glycation and advanced glycation end products (AGE) formation correlates in diabetes and its associated complications. Extensive modified human serum albumin is used to study the biochemical, electrochemical and functional properties in hyperglycemic environment with relevance to diabetes. We evaluate Spectroscopic, side chain modifications, amino acid analysis, biochemical and functional group properties in four glucose modified samples. Methods: A series four human serum albumin samples modified with glucose was characterized in terms of amino acid analysis, spectroscopic properties and side chain modifications. The diagnostic technique employed incorporates UV Spectroscopy, Fluorescence Spectroscopy, biochemical assays for side chain modifications, amino acid estimations, electrochemical and optical characterstic of glycated albumin. Conclusion: Glucose modified human serum albumin confers AGEs formation alters biochemical, electrochemical, optical, and functional property that depend on the reactivity of glucose and its concentration used for in-vitro glycation. A biochemical, electrochemical, optical, and functional characterization of modified albumin in-vitro produced AGE product that will be useful to interpret the complications and pathophysiological significance in diabetes.

Keywords: human serum albumin, glycated albumin, adavanced glycation end products, associated pathologies

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Authors: Himani Sharma, Amit Agrawal

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Stability of the Cassie and Wenzel wetting states depends on intrinsic contact angle and geometric features on a surface that was exploited in capturing biofluids in microwells. However, the mechanism of imbibition of biofluids in the microwells is not well implied in terms of wettability of a substrate. In this work, we experimentally demonstrated filling dynamics in hydrophilic and hydrophobic microwells by protein solutions. Towards this, we utilized lotus leaf as a mold to fabricate microwells on a Polydimethylsiloxane (PDMS) surface. Lotus leaf containing micrometer-sized blunt-conical shaped pillars with a height of 8-15 µm and diameter of 3-8 µm were transferred on to PDMS. Furthermore, PDMS surface was treated with oxygen plasma to render the hydrophilic nature. A 10µL droplets containing fluorescein isothiocyanate (FITC) - labelled bovine serum albumin (BSA) were rested on both hydrophobic (θa = 108o, where θa is the apparent contact angle) and hydrophilic (θa = 60o) PDMS surfaces. A time-dependent fluorescence microscopy was conducted on these modified PDMS surfaces by recording the fluorescent intensity over a 5 minute period. It was observed that, initially (at t=1 min) FITC-BSA was accumulated on the periphery of both hydrophilic and hydrophobic microwells due to incomplete penetration of liquid-gas meniscus. This deposition of FITC-BSA on periphery of microwell was not changed with time for hydrophobic surfaces, whereas, a complete filling was occurred in hydrophilic microwells (at t=5 mins). This attributes to a gradual movement of three-phase contact line along the vertical surface of the hydrophilic microwells as compared to stable pinning in the hydrophobic microwells as confirmed by Surface Evolver simulations. In addition, if the cavities are presented on hydrophobic surfaces, air bubbles will be trapped inside the cavities once the aqueous solution is placed over these surfaces, resulting in the Cassie-Baxter wetting state. This condition hinders trapping of proteins inside the microwells. Thus, it is necessary to impart hydrophilicity to the microwell surfaces so as to induce the Wenzel state, such that, an entire solution will be fully in contact with the walls of microwells. Imbibition of microwells by protein solutions was analyzed in terms fluorescent intensity versus time. The present work underlines the importance of geometry of microwells and surface wettability of substrate in wetting and effective capturing of solid sub-phases in biofluids.

Keywords: BSA, microwells, surface evolver, wettability

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Authors: Yingyi Luo

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Cross-border commercial surrogacy, where Australians travel overseas to access reproduction through a surrogate mother, is an increasing phenomenon. This paper focuses on the role of Australian surrogacy facilitators, including lawyers, non-for-profit agents, fertility counselors, who act as intermediaries managing cross-border surrogacy arrangements in Australia. It explores the extent to which surrogacy facilitators are concerned with the human rights of children born through cross-border surrogacy, surrogate mothers in developing countries, and intended parents. Commercial surrogacy is a matter that is often cast in the language of human rights. This paper will contribute to an in-depth understanding of the dynamics between intended parents, surrogates, and surrogacy facilitators by adopting a human rights framework to inform data analysis regarding the role of facilitators. The purpose of this research is to inform debate and discussion on law reform related to surrogacy. This paper presented here centers on interviews with surrogacy facilitators in Australia and non-participant observations in Australia to generate thick, empirical data about the fertility industry. The data showed that the process of facilitating surrogacy arrangements had prompted facilitators to form a view on human rights as they applied to their works. Although facilitators claimed that the right of intended parents, surrogate mothers, and children were all taken into consideration, the researcher observed that the commercial surrogacy contracts described by these facilitators favored the interests of intended parents with the baby acting as their unique selling point. The interests and needs of surrogate mothers were not prioritized in the views or actions of facilitators. The result was a commercial transaction that entailed the purchase, through cross-border surrogacy, of a child, as a commodity, by relatively affluent intended parents from disadvantaged surrogate mothers through unfair contracts.

Keywords: cross-border surrogacy, facilitators, human rights, surrogacy

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Authors: Hakam Alkhateeb

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Oleuropein, the main constituent of leaves and fruits of the olive tree, has been demonstrated to exert beneficial effects on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle. However, the antidiabetic effect of oleuropein, to our knowledge, has not been examined. Therefore, in this study, we examined whether oleuropein ameliorated palmitate-induced insulin resistance in skeletal muscle. To examine this question, insulin resistance was rapidly induced by incubating (12h) soleus muscle with a high concentration of palmitate(2mM). Subsequently, we attempted to restore insulin sensitivity by incubating (12h) muscles with oleuropien (1.5mM), while maintaining high concentrations of palmitate. Palmitate treatment for 12 h reduced insulin-stimulated glucose transport, GLUT4 translocationandAS160 phosphorylation. Oleuropein treatment (12 h) fully restoredinsulin-stimulated glucose transport, GLUT4translocationandAS160 phosphorylation. Inhibition of PI3K phosphorylation with wortmannin (1µM)did not affect the oleuropein-induced improvements in insulin-stimulated glucose transport, GLUT4 translocation, and AS160 phosphorylation. These results suggested that the improvements in these parameters cannot account for activating PI3K pathway. Taken altogether, it appears that oleuropein, through activation of another pathway like activated protein kinase (AMPK), may provide a possible strategy by which they ameliorate palmitate-induced insulin resistance in skeletal muscles.

Keywords: AS160, diabetes, GLUT4, oleuropein

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Authors: Pirzada Sami Ullah Sabri

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The present study examines the relationship between work engagement (WE) and employee turnover intentions (TI) in telecommunication sector using human resource development climate (HRDC) as a moderator. Based on 538 employees of telecommunication sector Hierarchal regression analysis is employed to examine the influence of HRDC on the relationship of work engagement and turnover intentions. The result indicates the negative correlation between work engagement and turnover intentions; HRD climate support as a powerful moderator increases the work engagement and lessens the turnover intentions. The study shows the importance of favorable and supportive HRD climate which foster the work engagement of the employees in the organization. By understanding the importance of human resource development climate and work engagement in reducing the turnover intentions can increase the productivity and performance of the organization.

Keywords: turnover intentions, work engagement, human resource development, climate, hierarchal regression analysis, telecommunication sector

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Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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Authors: Harish Rajak, Preeti Patel

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The application of histone deacetylase inhibitors is a well-known strategy in prevention of cancer which shows acceptable preclinical antitumor activity due to its ability of growth inhibition and apoptosis induction of cancer cell. Molecular docking were performed using Histone Deacetylase protein (PDB ID:1t69) and prepared series of hydroxamic acid based HDACIs. On the basis of docking study, it was predicted that compound 1 has significant binding interaction with HDAC protein and three hydrogen bond interactions takes place, which are essential for antitumor activity. On docking, most of the compounds exhibited better glide score values between -8 to -10 which is close to the glide score value of suberoylanilide hydroxamic acid. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. The 3D-QSAR models provided a good correlation between predicted and actual anticancer activity. Best QSAR model showed Q2 (0.7974), R2 (0.9200) and standard deviation (0.2308). QSAR visualization maps suggest that hydrogen bond acceptor groups at carbonyl group of cap region and hydrophobic groups at ortho, meta, para position of R9 were favorable for HDAC inhibitory activity. We established structure activity correlation using docking, pharmacophore modeling and atom based 3D QSAR model for hydroxamic acid based HDACIs.

Keywords: HDACIs, QSAR, e-pharmacophore, docking, suberoylanilide hydroxamic acid

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Authors: D. Berg, N. Hartley, L. Nasr

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This paper presents a conceptual model of human-robot interaction within service encounters and the effect on the well-being of both consumers and service providers. In this paper, service providers are those employees who work alongside frontline service robots. The significance of this paper lies in the knowledge created which outlines how frontline service robots can be effectively utilized in service encounters for the benefit of organizations and society as a whole. As this paper is conceptual in nature, the main methodologies employed are theoretical, namely problematization and theory building. The significance of this paper is underpinned by the shift of service robots from manufacturing plants and factory floors to consumer-facing service environments. This service environment places robots in direct contact with frontline employees and consumers creating a hybrid workplace where humans work alongside service robots. This change from back-end to front-end roles may have implications not only on the physical environment, servicescape, design, and strategy of service offerings and encounters but also on the human parties of the service encounter itself. Questions such as ‘how are frontline service robots impacting and changing the service encounter?’ and ‘what effect are such changes having on the well-being of the human actors in a service encounter?’ spring to mind. These questions form the research question of this paper. To truly understand social service robots, an interdisciplinary perspective is required. Besides understanding the function, system, design or mechanics of a service robot, it is also necessary to understand human-robot interaction. However not simply human-robot interaction, but particularly what happens when such robots are placed in commercial settings and when human-robot interaction becomes consumer-robot interaction and employee-robot interaction? A service robot in this paper is characterized by two main factors; its social characteristics and the consumer-facing environment within which it operates. The conceptual framework presented in this paper contributes to interdisciplinary discussions surrounding social robotics, service, and technology’s impact on consumer and service provider well-being, and hopes that such knowledge will help improve services, as well as the prosperity and well-being of society.

Keywords: frontline service robots, human-robot interaction, service encounters, well-being

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