Search results for: human α-1-acid glycoprotein

Authors: Jagdish S. Patel, Piyush Chudasama

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Context: Over-expression of P-glycoprotein (P-gp) plays critical role in absorption of many drug candidates which results into lower bioavailability of the drug. P-glycoprotein also over expresses in many pathological conditions like diabetes, affecting the drug therapy. Modulation of P-gp expression using inhibitors can help in designing novel formulation enhancing the bioavailability of the drug in question. Objectives: The main focus of the study was to develop advanced glycation end products (AGEs) induced P-gp over expression in Caco-2 cells. Curcumin, piperine and epigallocatechin gallate were used to evaluate their P-gp inhibitory action using combinatorial approach. Materials and methods: Methylglyoxal (MG) induced P-gp over expression was checked in Caco-2 cells using real time PCR. P-gp inhibitory effects of the phytochemicals were measured after induction with MG alone and in combination of any two compounds. Cytotoxicity of each of the phytochemical was evaluated using MTT assay. Results: Induction with MG (100mM) significantly induced the over expression of P-glycoprotein in Caco-2 cells after 24 hr. Curcumin, piperine and epigallocatechin gallate alone significantly reduced the level of P-gp within 6 hr of treatment period monitored by real time PCR. The combination of any two phytochemical also down regulated the expression of P-gp in cells. Combinations of Curcumin and epigallocatechin gallate have shown significant down regulation when compared with other two combinations. Conclusions: Combinatorial approach for down regulating the expression of P-gp, in pathological conditions like diabetes, has demonstrated promising approach for therapeutic purpose.

Keywords: p-glycoprotein, curcumin, piperine, epigallocatechin gallate, p-gp inhibition

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Authors: Kinga Mylkie, Pawel Nowak, Marta Z. Borowska

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The most important proteins in human serum responsible for drug binding are human serum albumin (HSA) and α1-acid glycoprotein (AGP). The AGP molecule is a glycoconjugate containing a single polypeptide chain composed of 183 amino acids (the core of the protein), and five glycan branched chains (sugar part) covalently linked by an N-glycosidic bond with aspartyl residues (Asp(N) -15, -38, -54, -75, - 85) of polypeptide chain. This protein plays an important role in binding alkaline drugs, a large group of drugs used in psychiatry, some acid drugs (e.g., coumarin anticoagulants), and neutral drugs (steroid hormones). The main goal of the research was to obtain magnetic nanoparticles coated with biopolymers in a chemically modified form, which will have highly reactive functional groups able to effectively immobilize the glycoprotein (acid α1-glycoprotein) without losing the ability to bind active substances. The first phase of the project involved the chemical modification of biopolymer starch. Modification of starch was carried out by methods of organic synthesis, leading to the preparation of a polymer enriched on its surface with aldehyde groups, which in the next step was coupled with 3-aminophenylboronic acid. Magnetite nanoparticles coated with starch were prepared by in situ co-precipitation and then oxidized with a 1 M sodium periodate solution to form a dialdehyde starch coating. Afterward, the reaction between the magnetite nanoparticles coated with dialdehyde starch and 3-aminophenylboronic acid was carried out. The obtained materials consist of a magnetite core surrounded by a layer of modified polymer, which contains on its surface dihydroxyboryl groups of boronic acids which are capable of binding glycoproteins. Magnetic nanoparticles obtained as carriers for plasma protein immobilization were fully characterized by ATR-FTIR, TEM, SEM, and DLS. The glycoprotein was immobilized on the obtained nanoparticles. The amount of mobilized protein was determined by the Bradford method.

Keywords: glycoproteins, immobilization, magnetic nanoparticles, polysaccharides

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Authors: Maysam Mard-Soltani, Mohamad Javad Rasaee, Saeed Khalili, Abdol Karim Sheikhi, Mehdi Hedayati

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Production of specific antibody responses against hTSH is a cumbersome process due to the high identity between the hTSH and the other members of the glycoprotein hormone family (FSH, LH and HCG) and the high identity between the human hTSH and host animals for antibody production. Therefore, two polyclonal antibodies were purified against two recombinant proteins. Four possible ELISA tests were designed based on these antibodies. These ELISA tests were checked against hTSH and other glycoprotein hormones, and their sensitivity and specificity were assessed. Bioinformatics tools were used to analyze the immunological properties. After the immunogen region selection from hTSH protein, c terminal of B hTSH was selected and applied. Two recombinant genes, with these cut pieces (first: two repeats of C terminal of B hTSH, second: tetanous toxin+B hTSH C terminal), were designed and sub-cloned into the pET32a expression vector. Standard methods were used for protein expression, purification, and verification. Thereafter, immunizations of the white New Zealand rabbits were performed and the serums of them were used for antibody titration, purification and characterization. Then, four ELISA tests based on two antibodies were employed to assess the hTSH and other glycoprotein hormones. The results of these assessments were compared with standard amounts. The obtained results indicated that the desired antigens were successfully designed, sub-cloned, expressed, confirmed and used for in vivo immunization. The raised antibodies were capable of specific and sensitive hTSH detection, while the cross reactivity with the other members of the glycoprotein hormone family was minimum. Among the four designed tests, the test in which the antibody against first protein was used as capture antibody, and the antibody against second protein was used as detector antibody did not show any hook effect up to 50 miu/l. Both proteins have the ability to induce highly sensitive and specific antibody responses against the hTSH. One of the antibody combinations of these antibodies has the highest sensitivity and specificity in hTSH detection.

Keywords: hTSH, bioinformatics, protein expression, cross reactivity

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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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: Tomáš Nejedlý, Dominika Mrázková, Jitka Viktorová

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The blood-brain barrier (BBB) serves as a protective shield, preventing the entry of harmful substances into the central nervous system. On the other hand, it also restricts the transport of neuroactive drugs, such as antiepileptics, which mitigate epileptic seizures. Drug-resistant epilepsy is often associated with the overexpression of efflux transporters, including P-glycoprotein (P-gp) or multidrug resistance protein 1 (MRP1), on the BBB. The aim of this work is to find P-gp and MRP1 inhibitors derived from phytocannabinoids and terpenes. The work evaluates whether these compounds interact directly with P-gp or MRP1 by rhodamine 123 or fluorescein efflux assay. The effect of phytocannabinoids on the gene expression of these transporters is also studied using qPCR and Western blot. These transporters are found in BBB cells; however, we decided to use the human ovarian cancer cell line (A2780ADR) due to its overproduction of P-gp and malignant glioma cell line (U87) due to its overproduction of MRP1. The results showed that while terpenes suppressed the activity of efflux transporters, phytocannabinoids tended to decrease their expression. Terpenes demonstrated an average inhibition of 65%, surpassing phytocannabinoids, which exhibited an average inhibition of approximately 30%. Particularly noteworthy was the modulating effect of (-)-α-bisabolol with the highest activity among the compounds tested. Based on these findings, phytocannabinoids and terpenes emerge as promising natural candidates for addressing drug resistance linked to efflux transporters. Acknowledgment: The project was funded by the Grant No 22-20860S of The Czech Science Foundation.

Keywords: drug-resistant epilepsy, efflux transporters, multidrug resistance protein 1, P-glycoprotein, phytocannabinoids, terpens

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Authors: Isobel Hambleton, Mark Carrington

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Trypanosoma brucei, the causal agent of a range of diseases in humans and livestock, evades the mammalian immune system through a population survival strategy based on the expression of a series of antigenically distinct variant surface glycoproteins (VSGs). RNAi mediated knockdown of the active VSG gene triggers a precytokinesis cell cycle arrest. To determine whether this phenotype is the result of reduced VSG transcript or depleted VSG protein, we used morpholino antisense oligonucleotides to block translation of VSG mRNA. The same precytokinesis cell cycle arrest was observed, suggesting that VSG protein abundance is monitored closely throughout the cell cycle. An inducible expression system has been developed to test various GPI-anchored proteins for their ability to rescue this cell cycle arrest. This system has been used to demonstrate that wild-type VSG expressed from a T7 promoter rescues this phenotype. This indicates that VSG expression from one of the specialised bloodstream expression sites (BES) is not essential for cell division. The same approach has been used to define the minimum essential features of a VSG necessary for function.

Keywords: bloodstream expression site, morpholino, precytokinesis cell cycle arrest, variant surface glycoprotein

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Authors: Ekin D. Horzum

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The aim of the proposal is to examine the relationship between human trafficking related corruption and human security. The proposal suggests that the human trafficking related corruption is about willingness of the states to turn a blind eye to the human trafficking cases. Therefore, it is important to approach human trafficking related corruption in terms of human security and human rights violation to find an effective way to fight against human trafficking. In this context, the purpose of this proposal is to examine the human trafficking related corruption as a safe haven in which trafficking thrives for perpetrators.

Keywords: human trafficking, human security, human rights, corruption, organized crime

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Authors: Camelia Porey, Binaya Kumar Jaiswal

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BACKGROUND: Antiphospholipid antibody (APLA) syndrome is an autoimmune disorder predisposing to thrombotic complications affecting CNS either by arterial vasooclusion or venous thrombosis. Cerebral venous sinus thrombosis (CVST) secondarily causes raised intracranial pressure (ICP). However, intracranial hypertension without evidence of CVST is a rare entity. Here we present two cases of elevated ICP with absence of identifiable CVST. CASE SUMMARY: Case 1, 28-year female had a 2 months history of holocranial headache followed by bilateral painless vision loss reaching lack of light perception over 20 days. CSF opening pressure was elevated. Fundoscopy showed bilateral grade 4 papilledema. MRI revealed a partially empty sella with bilateral optic nerve tortuosity. Idiopathic intracranial hypertension (IIH) was diagnosed. With acetazolamide, there was complete resolution of the clinical and radiological abnormalities. 5 months later she presented with acute onset right-sided hemiparesis. MRI was suggestive of acute left MCA infarct.MR venogram was normal. APLA came positive with high titres of Anticardiolipin and Beta 2 glycoprotein both IgG and IgM. Case 2, 23-year female, presented with headache and diplopia of 2 months duration. CSF pressure was elevated and Grade 3 papilledema was seen. MRI showed bilateral optic nerve hyperintensities with nerve head protrusion with normal MRV. APLA profile showed elevated beta 2 glycoprotein IgG and IgA. CONCLUSION: This is an important non thrombotic complication of APLA syndrome and requires further large-scale study for insight into the pathogenesis and early recognition to avoid future complications.

Keywords: APLA syndrome, idiopathic intracranial hypertension, MR venogram, papilledema

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Authors: Romany Wagih Farag Zaky

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The relationship between development and human rights has long been the subject of academic debate. To understand the dynamics between these two concepts, various principles are adopted, from the right to development to development-based human rights. Despite the initiatives taken, the relationship between development and human rights remains unclear. However, the overlap between these two views and the idea that efforts should be made in the field of human rights have increased in recent years. It is then evaluated whether the right to sustainable development is acceptable or not. The article concludes that the principles of sustainable development are directly or indirectly recognized in various human rights instruments, which is a good answer to the question posed above. This book therefore cites regional and international human rights agreements such as , as well as the jurisprudence and interpretative guidelines of human rights institutions, to prove this hypothesis.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Kieren Luellman, Makenzi Rockwell, Eduardo Callegari, Nichole Haag, Chun Wu

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Multiple sclerosis (MS) is an autoimmune disorder that damages the myelin sheath of neurons in the central nervous system. The presence of Acinetobacter bacteria and anti-Acinetobacter antibodies in MS patients has led to the hypothesis that the bacteria may contribute to MS pathogenesis. In this study, the protein sequences of Acinetobacter baumannii were compared to five peptides from three mammalian myelin proteins, i.e., Proteolipid Protein (PLP): PLP 139-151, PLP 178-191, Myelin Basic Protein (MBP): MBP 84-104 and Myelin Oligodendrocyte Glycoprotein (MOG): MOG 35-55 and MOG 92-106 respectively, known to induce experimental autoimmune encephalomyelitis (EAE), a condition similar to MS. We found 11 hits (i.e., with five or more amino acid sequence similarity) in Acinetobacter baumannii, which are identical or similar to PLP139-151, 32 hits to PLP178-191, 35 to MBP 84-104, 41 hits to MOG 35-55 and 26 hits to MOG92-106. In addition, Western blotting was used to assess possible interaction between the bacterial proteins and human anti-MBP, anti-MOG, and anti-PLP antibodies produced in rabbits, corresponding to MBP 84-104, MOG 35-55, and PLP 139-151, respectively. We found that both human Polyclonal anti-MOG antibody and anti-PLP antibody recognized a protein or more proteins of the same molecular mass of around 25 kDa. in Acinetobacter baumannii. The results suggested that this/these protein(s) might potentially serve as antigen(s) to induce anti-MOG antibody and anti-PLP antibody production in mammalian B cells. The proteomic study identified 433 hits, among which the sequence of Acinetobacter baumannii protein 491 subunit A matches a previously published enzyme Acinetobacter 3-Oxoadipate CoA-Transferase, in which a fragment of its peptide was observed to recognize MS patient serum via ELISA method. Our findings might pave the road to understanding one of the pathogenesis mechanisms of MS.

Keywords: multiple sclerosis, pathogenesis, Acinetobacter baumannii, antibody recognition

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Authors: Bola George Asaad Bekledas

Abstract:

Relationship between development and human rights has long been the subject of academic debate. To understand the dynamics between these two concepts, various principles are adopted, from the right to development to development-based human rights. Despite the initiatives taken, the relationship between development and human rights remains unclear. However, the compatibility between these two concepts and the idea that these efforts should be made to respect human rights guarantees have gained momentum in recent years. It is then evaluated whether the right to sustainable development is acceptable or not. The article concludes that the principles of sustainable development are directly or indirectly recognized in various human rights instruments, which is a good answer to the question posed above. This study, therefore, cites regional and international human rights agreements such as, as well as the jurisprudence and interpretative guidelines of human rights institutions, to prove this hypothesis.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security.

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Authors: Sahar Essa, Hussain A. Safar, Raj Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications in immunologically immature and immunocompromised hosts. Effective CMV vaccines that help diminish CMV disease in transplant patients and avoid congenital infection are of great importance. Though the exact roles of defense mechanisms are unidentified, viral-specific antibodies and cytokine responses are known to be involved in controlling CMV infections. CMV envelope glycoprotein B (UL55/gB), matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. We immunized mice intraperitoneally with these five CMV-related proteins (commercial) for their ability to induce specific antibody responses (in-house immunoassay) and cytokine production (commercial assay) in a mouse model. We observed a significant CMV-antigen-specific antibody response to pp38 and pp65 (E/C ˃2.0, p˂0.001). Mice immunized with pp38 had significantly higher concentrations of GM-CSF, IFN-α, IL-2 IL-4, IL-5, and IL-17A (p˂0.05). Mice immunized with pp65 showed significantly higher concentrations of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF-α. Th1 to Th2 cytokines ratios revealed a Th1 cytokine bias in mice immunized with pp38, pp65, pp150, and gB. We suggest that stimulation with multiple CMV-related proteins, which include pp38, pp65, and gB antigens, will allow both humoral and cellular immune responses to be efficiently activated, thus serving as appropriate CMV antigens for future vaccines.

Keywords: cytomegalovirus, UL99/pp28, UL80a/pp38, UL83/pp65, UL32/pp150, UL55/gB, CMV-antigen-specific antibody, CMV antigen-specific cytokine responses

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Authors: Amal Balila, Maria Vahdati

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Earth is a green building material with very low embodied energy and almost zero greenhouse gas emissions. However, it lacks strength and durability in its natural state. By responsibly sourcing stabilisers, it's possible to enhance its strength. This research draws inspiration from the robustness of termite mounds, where termites incorporate glycoproteins from their saliva during construction. Biomimicry explores the potential of these termite stabilisers in producing bio-inspired adobe bricks. The meat industry generates significant waste during slaughter, including blood, skin, bones, tendons, gastrointestinal contents, and internal organs. While abundant, many meat by-products raise concerns regarding human consumption, religious orders, cultural and ethical beliefs, and also heavily contribute to environmental pollution. Extracting and utilising proteins from this waste is vital for reducing pollution and increasing profitability. Exploring the untapped potential of meat industry waste, this research investigates how glycoproteins could revolutionize adobe brick construction. Bovine serum albumin (BSA) from cows' blood and mucin from porcine stomachs were the chosen glycoproteins used as stabilisers for adobe brick production. Despite their wide usage across various fields, they have very limited utilisation in food processing. Thus, both were identified as potential stabilisers for adobe brick production in this study. Two soil types were utilised to prepare adobe bricks for testing, comparing controlled unstabilised bricks with glycoprotein-stabilised ones. All bricks underwent testing for unconfined compressive strength and erosion resistance. The primary finding of this study is the efficacy of BSA, a glycoprotein derived from cows' blood and a by-product of the beef industry, as an earth construction stabiliser. Adding 0.5% by weight of BSA resulted in a 17% and 41% increase in the unconfined compressive strength for British and Sudanese adobe bricks, respectively. Further, adding 5% by weight of BSA led to a 202% and 97% increase in the unconfined compressive strength for British and Sudanese adobe bricks, respectively. Moreover, using 0.1%, 0.2%, and 0.5% by weight of BSA resulted in erosion rate reductions of 30%, 48%, and 70% for British adobe bricks, respectively, with a 97% reduction observed for Sudanese adobe bricks at 0.5% by weight of BSA. However, mucin from the porcine stomach did not significantly improve the unconfined compressive strength of adobe bricks. Nevertheless, employing 0.1% and 0.2% by weight of mucin resulted in erosion rate reductions of 28% and 55% for British adobe bricks, respectively. These findings underscore BSA's efficiency as an earth construction stabiliser for wall construction and mucin's efficacy for wall render, showcasing their potential for sustainable and durable building practices.

Keywords: biomimicry, earth construction, industrial waste management, sustainable building materials, termite mounds.

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Authors: Sameh Sarwat Melek Mikheal

Abstract:

The relationship between development and human rights has long been the subject of academic debate. To understand the dynamics between these two concepts, various principles are adopted, from the right to development to development-based human rights. Despite the initiatives taken, the relationship between development and human rights remains unclear. However, the overlap between these two views and the idea that efforts should be made in the field of human rights have increased in recent years. It is then evaluated whether the right to sustainable development is acceptable or not. This article concludes that the principles of sustainable development are directly or indirectly recognized in various human rights instruments, and this is a good answer to the question posed above. This book therefore cites regional and international human rights agreements such as , as well as the jurisprudence and interpretative guidelines of human rights institutions, to prove this hypothesis.

Keywords: balance, counter-terrorism, cyber-terrorism, human rights, security, violation sustainable development, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Joseph Marzouk Gerais Abdelmalak

Abstract:

The interface between development and human rights has long been the subject of academic debate. Therefore, to understand the dynamics between the two concepts, a number of principles have been adopted, ranging from the right to development to a human rights-based approach to development. Despite these attempts, the exact connection between development and human rights is not yet fully understood. However, the inherent interdependence between these two concepts and the idea that development efforts should be undertaken with respect for human rights guarantees have gained momentum in recent years. It will then be examined whether the right to sustainable development is recognized.The article therefore concludes that the principles of sustainable development are recognized, directly or indirectly, in various human rights instruments, which represents a positive answer to the question posed above. Therefore, this work discusses international and regional human rights instruments as well as case law and interpretative guidelines from human rights bodies to demonstrate this hypothesis.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Mindaugas Kazlauskas

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In this paper, it is presupposed that the description of the relationship between animal and human should begin with a description of the direct experience of the animal and how, in this experience, the human experiences itself (a self awareness mode). A human is concerned first and foremost with himself as a human through the experience of another as an animal. The questionsare: In the encounter with an animal, how is the animal constituted in the acts of human experience? How does human-animal interaction influence human behavioral patterns, and how does the human identifies itself in this interaction? The paper will present the results of interpretative phenomenological descriptions (IPA) of the relationship between human and animal in the face of death phenomenon through the experience of pet owners who lost their beloved companions and hunters, veterinatians, and farmers who face animal death. The results of IPA analysis reveal different relations such as the identification with an animal, the alienation experience, the experience of resistance, and an experience of detachment. Within these themes, IPA qualitative research results will be presented by highlighting patterns of human behavior, following Friedrich Schlachermacher's hermeneutics methodological principles, and reflecting on changes in value and attitude within society during daily interaction with the animal.

Keywords: animal human interaction, phenomenology, philosophy, death phenomenon

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Authors: Yong-Hui Zheng

Abstract:

Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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Authors: Manotar Tampubolon

Abstract:

Although the Indonesian human rights protection has increased in recent years, but human rights violations still occur in the industrial sector. Crimes against human rights continue to occur and go unnoticed in spite of the government's legislation on human rights, employment law in addition to an international treaty that has been ratified by Indonesia. The increasing number of garment companies in Bekasi, also give rise to increased human rights violations since the government does not have a commitment to protect it. The Indonesian government and industry owners should pay attention to and protect the human rights of workers and treat them accordingly. This paper will review the human rights violations experienced by workers at garment factories in the context of the law, as well as ideas to improve the protection of workers' rights.

Keywords: human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Hosam Gamil Sharoubim Abdalla

Abstract:

The interface between development and human rights has long been the subject of academic debate. Therefore, to understand the dynamics between the two concepts, a number of principles have been adopted, ranging from the right to development to a human rights-based approach to development. Despite these attempts, the exact connection between development and human rights is not yet fully understood. However, the inherent interdependence between these two concepts and the idea that development efforts should be undertaken with respect for human rights guarantees have gained momentum in recent years. It will then be examined whether the right to sustainable development is recognized. The article, therefore, concludes that the principles of sustainable development are recognized, directly or indirectly, in various human rights instruments, which represents a positive answer to the question posed above. Therefore, this work discusses international and regional human rights instruments as well as case law and interpretative guidelines from human rights bodies to demonstrate this hypothesis.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Perihan Hazel Kaya, Mustafa Göktuğ Kaya

Abstract:

Turkey has been a busy destination for immigration and it will always be as it is the geographical and cultural exit door of the East and the entrance door of the West. Among these immigrations, we can see the victims of human trafficking, human smuggling, refugees and those who came here to work and live. Human smuggling, which is one of the movements of illegal immigration, is the specific subject of this work. The fact that our country lies on the transportation destinations between the continents of Asia, Europe and Africa, the crime of human smuggling is highly committed in our country. The aim of the victims of human smuggling is to go to a more developed country to have higher standards of living, to get a better job and to escape from the economic and social instability of their countries. The human smuggling, which has gathered pace due to the improvements in communication and transportation, is not a regional issue and has become one of the most important problems for almost all countries. Accordingly, the reasons, methods and extent of human smuggling will be dealt firstly. Later, it will be studied why Turkey is preffered in human smuggling. Finally, statistical data will be given to show how much human smuggling has gone far in Turkey and the study will be finished with that what is being done and what can be done to prevent it.

Keywords: human smuggling, immigration, immigrator, human trafficking, Turkey

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Authors: Mina Rashad Saad Abdelnoor

Abstract:

The interface between development and human rights has long been the subject of academic debate. Therefore, to understand the dynamics between the two concepts, a number of principles have been adopted, ranging from the right to development to a human rights-based approach to development. Despite these attempts, the exact connection between development and human rights is not yet fully understood. However, the inherent interdependence between these two concepts and the idea that development efforts should be undertaken with respect for human rights guarantees have gained momentum in recent years. It will then be examined whether the right to sustainable development is recognized. The article therefore concludes that the principles of sustainable development are recognized, directly or indirectly, in various human rights instruments, which represents a positive answer to the question posed above. Therefore, this work discusses international and regional human rights instruments as well as case law and interpretative guidelines from human rights bodies to demonstrate this hypothesis.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Samy Ayoub Abdou Ghobrial

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The interface between development and human rights has long been the subject of academic debate. Therefore, to understand the dynamics between the two concepts, a number of principles have been adopted, ranging from the right to development to a human rights-based approach to development. Despite these attempts, the exact connection between development and human rights is not yet fully understood. However, the inherent interdependence between these two concepts and the idea that development efforts should be undertaken with respect for human rights guarantees have gained momentum in recent years. It will then be examined whether the right to sustainable development is recognized. The article therefore concludes that the principles of sustainable development are recognized, directly or indirectly, in various human rights instruments, which represents a positive answer to the question posed above. Therefore, this work discusses international and regional human rights instruments as well as case law and interpretative guidelines from human rights bodies to demonstrate this hypothesis.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Seung-Un Chae, Heung-Yul Kim, Sa-Kil Kim

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This paper presents the findings of preliminary study on human control performance in case of fire. The relationship between human control and human decision is studied in decision processes and stress model of human in a fire. Human behavior aspects involved in the decision process during a fire incident. The decision processes appear that six of individual perceptual processes: recognition, validation, definition, evaluation, commitment, and reassessment. Then, human may be stressed in order to get an optimal decision for their activity. This paper explores problems in human control processes and stresses in a catastrophic situation. Thus, the future approach will be concerned to reduce stresses and ambiguous irrelevant information.

Keywords: human reliability, decision processes, stress model, fire

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Authors: S. Essa, H. Safar, R. Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications to immunologically immature and immune-compromised hosts. Effective CMV vaccine that diminishes CMV disease in transplant patients and avoids congenital infection remains of high importance as no approved vaccines exist. Though the exact links of defense mechanisms are unidentified, viral-specific antibodies and Th1/Th2 cytokine responses have been involved in controlling viral infections. CMV envelope glycoprotein B (UL55/gB), the matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and the assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. In this study, mice were immunized with five HCMV antigens (UL32/pp150, UL80a/pp38, UL99/pp28, and UL83/pp65), and serum samples were collected and evaluated for eliciting viral-specific antibody responses. Moreover, Splenocytes were collected, stimulated, and assessed for cytokine responses. The results demonstrated a CMV-antigen-specific antibody response to pp38 and pp65 (E/C >2.0). The highest titers were detected with pp38 (average E/C 16.275) followed by pp65 (average E/C 7.72). Compared to control cells, splenocytes from PP38 antigen immunized mice gave a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-5, and IL-17A (P<0.05). Also, splenocytes from pp65 antigen immunized mice resulted in a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF- α. The designation of target CMV peptides by identifying viral-specific antibodies and cytokine responses is vital for understanding the protective immune mechanisms during CMV infection and identifying appropriate viral antigens to develop novel vaccines.

Keywords: hepatitis C virus, peripheral blood mononuclear cells, neutrophils, cytokines

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Authors: Arenca Trashani

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20 years after its first entrance in a General Assembly of the United Nation’s Resolution, human security has became a very important tool in a global debate affecting directly the whole main rules and regulations in international law and more closely in international human rights law. This paper will cover a very important issue of today at how the human security has its impact to the development of international human rights law, not as far as a challenge as it is seen up now but a tool of moving toward development and globalization. In order to analyze the impact of human security to the global agenda, we need to look to the main pillars of the international legal order which are affected by the human security in itself and its application in the policy making for this international legal order global and regional ones. This paper will focus, also, on human security, as a new and very important tool of measuring development, stability and the level of democratic consolidation and the respect for human rights especially in developing countries such as Albania. The states are no longer capable to monopolize the use of human security just within their boundaries and separated from the other principles of a functioning democracy. In this context, human security would be best guaranteed under the respect of the rule of law and democratization. During the last two decades the concept security has broadly developed, from a state-centric to a more human-centric approach: from state security to respect for human rights, to economic security, to environmental security as well. Last but not least we would see that human rights could be affected by human security not just at their promotion but also at their enforcement and mainly at the international institutions, which are entitled to promote and to protect human rights.

Keywords: human security, international human rights law, development, Albania, international law

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Authors: Allan Munyao Mukuki

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The nexus between terrorism and human rights has become a big challenge in the fight against terrorism globally. This is hinged on the fact that terrorism and human rights are interrelated to the extent that, when the former starts, the latter is violated. This direct linkage was recognised in the Vienna Declaration and Programme of Action as adopted by the World Conference on Human Rights in Vienna on 25 June 1993 which agreed that acts of terrorism in all its forms and manifestations are aimed at the destruction of human rights. Hence, terrorism constitutes an assault on our most basic human rights. To this end, the first part of this paper will focus on the nexus between terrorism and human rights and endeavors to draw a co-relation between these two concepts. The second part thereafter will analyse the emerging concept of cyber-terrorism and how it takes place. Further, an analysis of cyber counter-terrorism balanced as against human rights will also be undertaken. This will be done through the analysis of the concept of ‘securitisation’ of human rights as well as the need to create a balance between counterterrorism efforts as against the protection of human rights at all costs. The paper will then concludes with recommendations on how to balance counter-terrorism and human rights in the modern age.

Keywords: balance, counter-terrorism, cyber-terrorism, human rights, security, violation

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Authors: Ayyoub Jamali

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At the first glance, it seems that the African Court on Human and People’s Rights has achieved a tremendous development in the protection of human rights in Africa. Since its first judgement in 2009, the court has taken a robust approach/ assertive stance, showing its strength by finding states to be in violation of the Africana Charter and other human rights treaties. This paper seeks to discuss various challenges and resistance that the Court has faced since the adoption of the Founding Protocol to the Establishment of the African Court on Human and People’s Rights. The outcome of the paper casts shadow on the legitimacy and effectiveness of the African Court as the guarantor of human rights within the African continent.

Keywords: African Court on Human and People’s Rights, African Union, African regional human rights system, compliance

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Authors: Mostafa Najim, Alaa Rahhal, Fadi Khir, Safae Abu Yousef, Amer Aljundi, Feryal Ibrahim, Aliaa Amer, Ahmed Soliman Mohamed, Samira Saleh, Dekra Alfaridi, Ahmed Mahfouz, Sumaya Al-Yafei, Faraj Howady, Mohamad Yahya Khatib, Samar Alemadi

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Background: Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy among critically ill patients. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19 induced coagulopathy, their clinical significance among critically ill patients with COVID-19 remains uncertain. Methods: This prospective observational study included patients with COVID-19 admitted to intensive care units (ICU) to evaluate the prevalence and clinical significance of aPLs, including anticardiolipin IgG/IgM, anti-β2-glycoprotein IgG/IgM, and lupus anticoagulant. The study outcomes included the prevalence of aPLs, a primary composite outcome of all-cause mortality, and arterial or venous thrombosis among aPLs positive patients versus aPLs negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. Results: A total of 60 critically ill patients were enrolled. Of whom, 57 (95%) were male, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found to have positive aPLs; of whom 21 patients were positive for lupus anticoagulant, whereas one patient was positive for anti-β2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during ICU did not differ among patients with positive aPLs compared to those with negative aPLs (4 (18%) vs. 6 (16%), aOR= 0.98, 95% CI 0.1-6.7; p-value= 0.986). Likewise, the secondary outcomes, including all-cause mortality, venous thrombosis, arterial thrombosis, discharge from ICU, time to mortality, and time to discharge from ICU, did not differ between those with positive aPLs upon ICU admission in comparison to patients with negative aPLs. Conclusion: The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

Keywords: antiphospholipid antibodies, critically ill patients, coagulopathy, coronavirus

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Authors: A. Serap Fırat

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The aim of this study is to display conceptually the relationship and interaction between matter of human resources training and the information age. Fast development from industrial community to an information community has occurred and organizations have been seeking ways to overcome this change. Human resources policy and human capital with enhanced competence will have direct impact on work performance; therefore, this paper deals with the increased importance of human resource management due to the fact that it nurtures human capital. Researching and scanning are used as a method in this study. Both local and foreign literature and expert views are employed -as much as one could be- in the making of the theoretical framework of this study.

Keywords: human resources, information age, education, organization, occupation

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