Search results for: human transmembrane transporter proteins

Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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Authors: Sri Poedjiastoeti

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One of the traits of living beings is eating. As the living beings, people must provide their life by taking material. They must assimilate for themselves with substances. They grow and develop themselves by changing what they eat and digest into their own substance. This happened in the so-called eating. This article aims to analyze distinction between human beings and other infrahumans when facing and eating food. It uses the analytical description with metaphysical anthropology approach. As a result, to give the expression that eating is not simply to put food in mouth, chew and swallow it. Eating constitutes a sacred ceremonial if it is done in accordance with human dignity. They face food with distance and moderation as well as civilize or make their behaviour better for it. Accordingly, they are being to be human.

Keywords: human beings, behaviour, eating, dignity

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Authors: Alhaji Modu Bukar, Faez Firdaus Abdullah Jesse, Che Azurahanim Che Abdullah, Mustapha M. Noordin, Mohd-Lila Mohd Azmia

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Orf virus (ORFV) is the causative agent of a proliferative skin lesion known as contagious ecthyma in sheep and goats. Currently used live attenuated vaccines against ORFV infection have been reported to cause severe outbreaks in vaccinated animals. In this study, we investigated the immunogenicity of the B2L and F1L proteins of the virus, which are thought to elicit a protective immune response The 6-week-old 50 female mice were divided into 8 groups: seven experimental groups and one control group. Each animal in the experimental group received an initial immunisation with the nanoparticles or proteins coated with the nanoparticles, followed by two booster immunizations with the same products 14 days apart. Ten days after the last booster inoculation, the mice were either humanely killed or lethally challenged with UPM /HSN-2-ORFV at a dose of 106 TCID50/mL in a volume of 50 μl. The spleen was examined for histopathological changes and quantification of T cells by flow cytometry. On the other hand, the degree of protection of mice from the lethal virus was evaluated by lesion size, weight loss, and histopathological examination of skin and liver. The results showed that mice immunised with rB2L alone, rB2L-Al₂O₃-NPs, rB2L/rF1L, and rB2L/rF1L-Al₂O₃-NPs elicited statistically higher levels of anti-rB2L and/or rF1L-specific IgA/IgG and CD4/CD8 cell immune responses than mice in the control groups (p < 0.01). The vaccine candidate did not exhibit severe skin damage after monitoring histopathology, morbidity, and mortality. Overall, the results suggest that recombinant rB2L and rF1L antigens may be useful universal vaccine candidates against ORFV infections.

Keywords: orf virus, antigen nanoparticles, virus, nanoparticles

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Authors: Michael Augustus Akagbor

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When discussing human rights, the philosophical underpinnings of discussions about African realities are controversial, often hinging on whether human rights existed in pre-colonial Africa as not just a philosophy of thought but also a way of imagining the individual's place in society. Critics have often fixated on what many argue is the lack of socio-political structures that could have fostered the emergence and development of human rights contraptions in “mechanical” solidarities such as pre-colonial agrarian African societies. This paper debunks the notion that the perceived ‘absence’ of an ‘advanced’ and differentiated social system where the philosophical imaginaries of Hobbes and Locke could have emerged is not grounds to deny the imagined place of the human rights of the ‘individual’ in pre-colonial Africa. The paper adopts the qualitative methodology by reviewing and analyzing secondary data from various sources to advance the view that the concepts of human rights are not alien to indigenous Africa’s legal and political processes.

Keywords: human rights, reality, philosophical, Africa, individual

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Authors: E. L. Queiroz, S. M. A. Souza, R. T. S. Santos

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The cereal bars have emerged as a healthy alternative in the food sector, by presenting a remarkable functional appeal, being a product of high nutritional value. Cereals have an important function in feeding because they have features that particularize them as their variety, smooth flavour and aroma and easy digestion and absorption in the body. Brazil is the largest producer of cassava in the world, and the flour produced from this raw material is a source of nutrients for much of the low-income population, however it is little explored industrially. The northeast region of Brazil has great potential for honey production, which is a source of vitamins, proteins, minerals and organic acids but it is much used as a medicine. Aiming to combine the production of healthy food with the sustainable utilization and enhancement of family farming products, was created a cereal bar using regional raw materials of desirable nutritional characteristics: honey, umbu pulp and cassava flour. The cereal bar was characterized by physicochemical analyzes quantifying the content of lipids, proteins, moisture and ashes, microbiological and sensory evaluation showed that the cereal bar is a safe, and nutritious food with good sensory properties.

Keywords: cassava flour, cereal bar, honey, insoluble fibre

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Authors: S. A. Sadegh Zadeh, C. Kambhampati

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Mathematical and computational modellings are the necessary tools for reviewing, analysing, and predicting processes and events in the wide spectrum range of scientific fields. Therefore, in a field as rapidly developing as neuroscience, the combination of these two modellings can have a significant role in helping to guide the direction the field takes. The paper combined mathematical and computational modelling to prove a weakness in a very precious model in neuroscience. This paper is intended to analyse all-or-none principle in Hodgkin-Huxley mathematical model. By implementation the computational model of Hodgkin-Huxley model and applying the concept of all-or-none principle, an investigation on this mathematical model has been performed. The results clearly showed that the mathematical model of Hodgkin-Huxley does not observe this fundamental law in neurophysiology to generating action potentials. This study shows that further mathematical studies on the Hodgkin-Huxley model are needed in order to create a model without this weakness.

Keywords: all-or-none, computational modelling, mathematical model, transmembrane voltage, action potential

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Zhen Cao, Yu Zhu, Junxue Fu

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Immunoassay, i.e., antigen-antibody reaction, is crucial for disease diagnostics. To achieve the adequate signal of the antigen protein detection, a large amount of sample and long incubation time is needed. However, the amount of protein is usually small at the early stage, which makes it difficult to detect. Unlike cells and DNAs, no valid chemical method exists for protein amplification. Thus, an alternative way to improve the signal is through particle manipulation techniques to concentrate proteins, among which dielectrophoresis (DEP) is an effective one. DEP is a technique that concentrates particles to the designated region through a force created by the gradient in a non-uniform electric field. Since DEP force is proportional to the cube of particle size and square of electric field gradient, it is relatively easy to capture larger particles such as cells. For smaller ones like proteins, a super high gradient is then required. In this work, three-dimensional Ag/SiO2 nanorods arrays, fabricated by an easy physical vapor deposition technique called as oblique angle deposition, have been integrated with a DEP device and created the field gradient as high as of 2.6×10²⁴ V²/m³. The nanorods based DEP device is able to enrich bovine serum albumin (BSA) protein by 1800-fold and the rate has reached 180-fold/s when only applying 5 V electric potential. Based on the above nanorods integrated DEP platform, an immunoassay of mouse immunoglobulin G (IgG) proteins has been performed. Briefly, specific antibodies are immobilized onto nanorods, then IgG proteins are concentrated and captured, and finally, the signal from fluorescence-labelled antibodies are detected. The limit of detection (LoD) is measured as 275.3 fg/mL (~1.8 fM), which is a 20,000-fold enhancement compared with identical assays performed on blank glass plates. Further, prostate-specific antigen (PSA), which is a cancer biomarker for diagnosis of prostate cancer after radical prostatectomy, is also quantified with a LoD as low as 2.6 pg/mL. The time to signal saturation has been significantly reduced to one minute. In summary, together with an easy nanorod fabrication and integration method, this nanorods based DEP platform has demonstrated highly sensitive immunoassay performance and thus poses great potentials in applications for early point-of-care diagnostics.

Keywords: dielectrophoresis, immunoassay, oblique angle deposition, protein concentration

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Authors: Febi Eka Putri, Prabowo Anggorono

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Human Trafficking has become a threat in the global phenomenon, including Indonesia as a country adopting democracy to uphold the human rights value. Indonesia is classified as a source of trafficking in persons which dominate by women and children for sexual exploitation and forced labor purposes. In this case, Indonesia has committed to combat trafficking in persons by enacted domestic law to criminalize all types of human trafficking in domestic and international level. Tracing to the efforts, we cannot just simplify it, however, in 2016 Indonesia has placed as a tier 2 country because the government does not fully achieve the minimum standard by U. S. Trafficking Victims Protection Act due to only making efforts as progress. While as a part of ASEAN member, Indonesia has signed ASEAN Human Rights Declaration but when it comes to Human Trafficking issue, there is only few ASEAN member who has ratified ASEAN Convention on Trafficking in Persons, in particular Women and Children such as Singapore, Cambodia, and Thailand. This brings the evidence to structuring the role of Indonesia to combat human trafficking.

Keywords: Indonesia, Association of Southeast Asian Nations (ASEAN), human trafficking, Tier 2 country

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Authors: Kawinphat Lertpongmanee

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The problems of trafficking human beings were continuously violent in Thailand. The problems occurred from a variety of factors such as unemployment, agricultural workers’ urban immigration, sex tour, attitude of materialism society, divorced family, unsavourily effected law, and officers’ ignorance. The purposes of this study were to study the structure, connection, a number of trafficking human beings in Thailand. Qualitative and quantitative and results of previous research were used in this research. The previous procurers, interested persons, experienced people, human beings-aiding organization, and women-children rights organization were interviewed in depth. The field was used in a variety of regions. The findings showed that the structure and connection of trafficking human beings and their values are $8,750 million. There are 240,000 people in trafficked human beings. The trend of trafficking human beings grows continuously. It is changed according to economic circumstance, society and culture, and law. The state must be aware of its problem. The law is enacted by adding high penalty for serious fear.

Keywords: human trade, prostitution trafficking, trafficking in women and children, Thailand

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Authors: Mara Varelaki

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In response to the challenge of the environmental crisis the discipline of environmental ethics examines the relation of human beings towards the environment and the value of the non-human constituents of the surrounding world. In the face of this crisis, assumptions regarding human and nature relations ought to be traced and reexamined because they can cause difficulties in diagnosing problematic attitudes towards the environment and non-human animals. This paper presents the claims that European and the Judea-Christian cosmogonic myths place the human figure in the core of the creation of the cosmos, thus verifying a hierarchical structure where humans occupy the top, and they establish a perception of nature as a non-human other. By doing so, these narratives provide some justification to the notion of the human-nature dichotomy and the human domination over other life forms and ecosystems. These anthropocentric assumptions evolved into what Hilde Lindemann terms master narratives and their influence extents to ecocentric ethical theories which attempt, and often fail, to shed the anthropocentrism of the western ethical tradition. The goal of this paper is (1) to trace the anthropocentric assumptions embedded in western thought and (2) articulate how they maintain their grip on our contemporary understanding of the human relation to and position within the environment, thus showing the need for a method of detecting and bracketing anthropocentric assumptions in social narratives and ethical frameworks.

Keywords: cosmogonies, anthropocentrism, human/nature dichotomy, master narratives, ecocentrism

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Authors: Amita Barik, Ranjit Prasad Bahadur

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We investigate the role of water molecules in 89 protein-RNA complexes taken from the Protein Data Bank. Those with tRNA and single-stranded RNA are less hydrated than with duplex or ribosomal proteins. Protein-RNA interfaces are hydrated less than protein-DNA interfaces, but more than protein-protein interfaces. Majority of the waters at protein-RNA interfaces makes multiple H-bonds; however, a fraction does not make any. Those making Hbonds have preferences for the polar groups of RNA than its partner protein. The spatial distribution of waters makes interfaces with ribosomal proteins and single-stranded RNA relatively ‘dry’ than interfaces with tRNA and duplex RNA. In contrast to protein-DNA interfaces, mainly due to the presence of the 2’OH, the ribose in protein-RNA interfaces is hydrated more than the phosphate or the bases. The minor groove in protein-RNA interfaces is hydrated more than the major groove, while in protein-DNA interfaces it is reverse. The strands make the highest number of water-mediated H-bonds per unit interface area followed by the helices and the non-regular structures. The preserved waters at protein-RNA interfaces make higher number of H-bonds than the other waters. Preserved waters contribute toward the affinity in protein-RNA recognition and should be carefully treated while engineering protein-RNA interfaces.

Keywords: h-bonds, minor-major grooves, preserved water, protein-RNA interfaces

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Authors: Qinghua Xing, Xinyi Tao, Haisheng Wang, Baisuo Zhao

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The first true anaerobic, halophilic alkali thermophile, Natranaerobius thermophilus DSM 18059T, serves as a valuable model for studying cellular adaptations to saline, alkaline and thermal extremes. To uncover the adaptive strategies employed by N. thermophilus in coping with these challenges, we conducted a comprehensive iTRAQ-based quantitative proteomic analysis under different conditions of salinity (3.5 M vs. 2.5 M Na+), pH (pH 9.6 vs. pH 8.6), and temperature (52°C vs. 42°C). The increased intracellular accumulation of glycine betaine, through both synthesis and transport, plays a critical role in N. thermophilus' adaptation to these combined stresses. Under all three stress conditions, the up-regulation of Trk family proteins responsible for K+ transport is observed. Intracellular K+ concentration rises in response to salt and pH levels. Multiple types of Na+/H+ antiporter (NhaC family, Mrp family and CPA family) and a diverse range of FOF1-ATP synthase are identified as vital components for maintaining ionic balance under different stress conditions. Importantly, proteins involved in amino acid metabolism, carbohydrate metabolism, ABC transporters, signaling and chemotaxis, as well as biological macromolecule repair and protection, exhibited significant up-regulation in response to these extreme conditions. These metabolic pathways emerge as critical factors in N. thermophilus' adaptation mechanisms under extreme environmental stress. To validate the proteomic data, ddPCR analysis confirmed changes in mRNA expression, thereby corroborating the up-regulation and down-regulation patterns of 19 co-up-regulated and 36 key proteins under saline, alkaline and thermal stresses. This research enriches our understanding of the complex regulatory systems that enable polyextremophiles to survive in combined extreme conditions.

Keywords: polyextremophiles, natranaerobius thermophilus, saline- alkaline- thermal stresses, combined extremes

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Authors: Lynamata Chhun

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Human Rights enforcement in the newly independent countries like Asian and African has always been penetrating issues. In spite, the existing of the Universal Declaration of Human Rights (UDHR), regions like Africa and Asia where values and cultural norms far differ from the concept had formed their own Human Rights instruments to tackle Human Rights issues in their regions instead of embracing the concept of UDHR completely. ASEAN Human Rights Declaration is one of the examples. This paper aims to examine the enforcement of Human Rights in South East Asia in the context of ASEAN regional integration. Precisely, the author attempts to analyse the effectiveness in undertaking Human Rights issues in the region by applying both the existing international and regional frameworks using the Myanmar Rohingya Crisis as the case study. The methodology of the paper is qualitative analysis where cross-impact analysis is employed to examine the case study. It is anticipated that the main findings of this paper will illuminate how applicable the international instruments are in comparison to the regional instruments in apprehending the human rights issues and will shed light on how ASEAN and dialogue partners should cooperate in the future regarding with the challenging issues of Human Rights in the region.

Keywords: ASEAN Human Rights Declaration, ASEAN integration, ASEAN way, international and regional instruments, Universal Declaration of Human Rights

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

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Authors: Abishek Poudel

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Human-tiger conflicts are serious issues of conflicts between local people and park authority and the conflicting situation potentially play negative role in park management. The study aimed (1) To determine the trend and nature of human-tiger conflicts (2) To understand people's perception and mitigation measures towards tiger conservation. Both primary and secondary information were used to determine human- tiger conflicts in Chitwan National Park. Systematic random sampling with 5% intensity was done to collect the perception of the villagers regarding human-tiger conflicts. The study sites were selected based on frequencies of incidences of human attacks and livestock depredation viz. Rajahar and Ayodhyapuri VDCs respectively. The trend of human casualties by tiger has increased in last five year whereas the trend of livestock has decreased. Reportedly, between 2008 and 2012, tigers killed 22 people, injured 10 and killed at least 213 livestock. Conflict was less common in the park and more intense in the sub-optimal habitats of Buffer Zone. Goat was the most vulnerable livestock followed by cattle. The livestock grazing and human intrusion into tiger habitat were the causes of conflicts. Developing local stewardship and support for tiger conservation, livestock insurance, and compensation policy simplification may help reduce human-tiger conflicts.

Keywords: livestock depredation, sub optimal habitat, human-tiger, local stewardship

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Authors: Amal Hussain Alkhaiwani, Ghadah Abdullah Almalki

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Recently human errors have increasingly become a very high factor in security breaches that may affect confidential data, and most of the cyber data breaches are caused by human errors. With one individual mistake, the attacker will gain access to the entire network and bypass the implemented access controls without any immediate detection. Unaware employees will be vulnerable to any social engineering cyber-attacks. Providing security awareness to People is part of the company protection process; the cyber risks cannot be reduced by just implementing technology; the human awareness of security will significantly reduce the risks, which encourage changes in staff cyber-awareness. In this paper, we will focus on Human Awareness, human needs to continue the required security education level; we will review human errors and introduce a proposed solution to avoid the breach from occurring again. Recently Saudi Arabia faced many attacks with different methods of social engineering. As Saudi Arabia has become a target to many countries and individuals, we needed to initiate a defense mechanism that begins with awareness to keep our privacy and protect the confidential data against possible intended attacks.

Keywords: cybersecurity, human aspects, human errors, human mistakes, security awareness, Saudi Arabia, security program, security education, social engineering

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Authors: Rauan Sakenov, Peter Bukovics, Peter Gaszler, Veronika Tokacs-Kollar, Beata Bugyi

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FH2 (formin homology-2) domains of several proteins, collectively known as formins, including DAAM, DAAM1 and mDia1, promote G-actin nucleation and elongation. FH2 domains of these formins exist as oligomers. Chain dimerization by ring structure formation serves as a structural basis for actin polymerization function of FH2 domain. Proper single chain configuration and specific interactions between its various regions are necessary for individual chains to form a dimer functional in G-actin nucleation and elongation. FH1 and WH2 domain-containing formins were shown to behave as intrinsically disordered proteins. Thus, the aim of this research was to study structural dynamics of FH2 domain of DAAM. To investigate structural features of FH2 domain of DAAM, molecular dynamics simulation of chain A of FH2 domain of DAAM solvated in water box in 50 mM NaCl was conducted at temperatures from 293.15 to 353.15K, with VMD 1.9.2, NAMD 2.14 and Amber Tools 21 using 2z6e and 1v9d PDB structures of DAAM was obtained on I-TASSER webserver. Calcium and ATP bound G-actin 3hbt PDB structure was used as a reference protein with well-described structural dynamics of denaturation. Topology and parameter information of CHARMM 2012 additive all-atom force fields for proteins, carbohydrate derivatives, water and ions were used in NAMD 2.14 and ff19SB force field for proteins in Amber Tools 21. The systems were energy minimized for the first 1000 steps, equilibrated and produced in NPT ensemble for 1ns using stochastic Langevin dynamics and the particle mesh Ewald method. Our root-mean square deviation (RMSD) analysis of molecular dynamics of chain A of FH2 domains of DAAM revealed similar insignificant changes of total molecular average RMSD values of FH2 domain of these formins at temperatures from 293.15 to 353.15K. In contrast, total molecular average RMSD values of G-actin showed considerable increase at 328K, which corresponds to the denaturation of G-actin molecule at this temperature and its transition from native, ordered, to denatured, disordered, state which is well-described in the literature. RMSD values of lasso and tail regions of chain A of FH2 domain of DAAM exhibited higher than total molecular average RMSD at temperatures from 293.15 to 353.15K. These regions are functional in intra- and interchain interactions and contain highly conserved tryptophan residues of lasso region, highly conserved GNYMN sequence of post region and amino acids of the shell of hydrophobic pocket of the salt bridge between Arg171 and Asp321, which are important for structural stability and ordered state of FH2 domain of DAAM and its functions in FH2 domain dimerization. In conclusion, higher than total molecular average RMSD values of lasso and post regions of chain A of FH2 domain of DAAM may explain disordered state of FH2 domain of DAAM at temperatures from 293.15 to 353.15K. Finally, absence of marked transition, in terms of significant changes in average molecular RMSD values between native and denatured states of FH2 domain of DAAM at temperatures from 293.15 to 353.15K, can make it possible to attribute these formins to the group of intrinsically disordered proteins rather than to the group of intrinsically ordered proteins such as G-actin.

Keywords: FH2 domain, DAAM, formins, molecular modelling, computational biophysics

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Authors: Daria Grechishnikova, Maria Poptsova

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Transposable elements play an important role in the evolution of various species from bacteria to human. Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs) are two major classes of retrotransposons that occupy a considerable part of any genome and their copy numbers can range form several hundreds to a million. Both LINEs and SINEs multiply through a copy-and-paste mechanism. LINEs encode proteins, which make them capable of self-propagation while SINEs are parasitic and require the machinery of LINEs to multiply. The mechanisms how LINE and SINE RNA is recognized by the LINE-encoded reverse transcriptase (RT) remain unclear. For some SINE-LINE pairs, it was shown that they share a common 3’-end with a stem-loop structure. Majority of the SINE-LINE pairs do not have a common 3’-end. Recently we have shown that in the human genome Alu-L1 pairs have structurally similar stem-loop structure at the 3’-end. Here we extended our analysis to a wide range of species and analyzed LINEs from 161 different species from Repbase and 217 SINE sequences from SINEBase. It appeared that all of the analyzed sequences contained stem-loop structures at the 3’-end. Here we conclude that it is very likely that a common evolutionary mechanism of transposon RNA recognition requires the presence of stem-loop structures at their 3’-end.

Keywords: LINE, SINE, mechanisms of retrotransposition, retrotransposons, stem-loop, stem-loop structures, transposons

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Authors: Blen Telayneh Melese

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Rural development, the unending quest of a developing country, cannot be succeeded in deprived of human capital development. Human capital, the economic pillars of a country's development, appeals a policy-based supports while fulfilling what is expected. Ethiopia, one of the rural countries with untouched and forgotten land and human force, owes historical experiences of educational policy intending for mobilization of its citizen for the advancement of the overall economy. Rural Ethiopia as well has been the focus of those educational policies, considering the economic resources entrenched with in. In this literature review paper, Ethiopian educational policy and its contribution to human capital development, as well as its role in generating quality human labor force, is assessed concisely. The author argues that the foundation of rural development such as technology, knowledge, infrastructure, market chain, communication and etc., can only be achieved through enhanced education policy that conciliates the existing reality of rural communities. Ethiopia still needs an education policy that enables it to generate a human capital that is oriented with the rural areas economic opportunities and challenges.

Keywords: Ethiopia, rural development, human capital development, education policy

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Authors: Qamar Raza

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This paper deals with the human concern and onus which every person should provide to his/her society. Especially the rules and regulations described in constitution or traditions which we have inherited from ancestors should be followed, and also our lives should be led in accordance with them. The main concern of paper would be personal behavior with others in a good manner especially what he/she should exercise for society’s welfare. As human beings are the fundamental organ of society, who play a crucial role in reforming the society, they should try their best to develop it as well as maintain harmony, peace, we-feeling and mutual contact in the society. Focusing on how the modern society and its elements keep society successful. Regulations of our constitution and tradition are essential for reforming the society. In a nutshell, a human has to mingle in his society and keep mutual respect and understand the value of others as well as for himself.

Keywords: constitution, human beings, society, traditions

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Authors: Nusrat Praween, Krishna Thej Pammi Guru, Palash Kumar Basu

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Designing non-invasive biosensors for cancer diagnosis is essential for developing an affordable and specific tool to measure cancer-related exosome biomarkers. Exosomes, released by healthy as well as cancer cells, contain valuable information about the biomarkers of various diseases, including cancer. Despite the availability of various isolation techniques, ultracentrifugation is the standard technique that is being employed. Post isolation, exosomes are traditionally exposed to detergents for extracting their proteins, which can often lead to protein degradation. Further to this, it is very essential to develop a sensing platform for the quantification of clinically relevant proteins in a wider range to ensure practicality. In this study, exosomes were immobilized on the Au Screen Printed Electrode (SPE) using EDC/NHS chemistry to facilitate binding. After immobilizing the exosomes on the screen-printed electrode (SPE), we investigated the impact of the electric field by applying various voltages to induce exosome lysis and release their contents. The lysed solution was used for sensing TSG101, a crucial biomarker associated with various cancers, using both faradaic and non-faradaic electrochemical impedance spectroscopy (EIS) methods. The results of non-faradaic and faradaic EIS were comparable and showed good consistency, indicating that non-faradaic sensing can be a reliable alternative. Hence, the non-faradaic sensing technique was used for label-free quantification of the TSG101 biomarker. The results were validated using ELISA. Our electrochemical immunosensor demonstrated a consistent response of TSG101 from 125 pg/mL to 8000 pg/mL, with a detection limit of 0.125 pg/mL at room temperature. Additionally, since non-faradic sensing is label-free, the ease of usage and cost of the final sensor developed can be reduced. The proposed immunosensor is capable of detecting the TSG101 protein at low levels in healthy serum with good sensitivity and specificity, making it a promising platform for biomarker detection.

Keywords: biosensor, exosomes isolation on SPE, electric field lysis of exosome, EIS sensing of TSG101

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Authors: E. Akdur Öztürk, F. İrvasa Bilgiç, A. Ludovisi , O. Gülbahar, D. Dirim Erdoğan, M. Korkmaz, M. Á. Gómez Morales

Abstract:

Anisakidosis is a zoonotic human fish-borne parasitic disease caused by accidental ingestion of anisakid third-stage larvae (L3) of members of the Anisakidae family present in infected marine fish or cephalopods. Infection with anisakid larvae can lead to gastric, intestinal, extra-gastrointestinal and gastroallergic forms of the disease. Anisakid parasites have been reported in almost all seas, particularly in the Mediterranean Sea. There is a remarkably high level of risk exposure to these zoonotic parasites as they are present in economically and ecologically important fish of Europe. Anisakid L3 larvae have been also detected in several fish species from the Aegean Sea. Turkey is a peninsular country surrounded by Black, Aegean and the Mediterranean Sea. In this country, fishing habit and fishery product consumption are highly common. In recent years, there was also an increase in the consumption of raw fish due to the increasing interest in the cuisine of the Far East countries. In different regions of Turkey, A. simplex (inMerluccius Merluccius Scomber japonicus, Trachurus mediterraneus, Sardina pilchardus, Engraulis encrasicolus, etc.), Anisakis spp., Contraceucum spp., Pseudoterronova spp. and, C. aduncum were identified as well. Although it is accepted both the presence of anisakid parasites in fish and fishery products in Turkey and the presence of Turkish people with allergic manifestations after fish consumption, there are no reports of human anisakiasis in this country. Given the high prevalence of anisakid parasites in the country, the absence of reports is likely not due to the absence of clinical cases rather to the unavailability of diagnostic tools and the low awareness of the presence of this infection. The aim of the study was to set up an IgE-Western Blot (WB) based test to detect the anisakidosis sensitization among Turkish people with a history of allergic manifestation related to fish consumption. To this end, crude worm antigens (CWA) and allergen enriched fraction (50-66% ) were prepared from L3 of A. simplex (s.l.) collected from Lepidopus caudatus fished in the Mediterranean Sea. These proteins were electrophoretically separated and transferred into the nitrocellulose membranes. By WB, specific proteins recognized by positive control serum samples from sensitized patients were visualized on nitrocellulose membranes by a colorimetric reaction. The CWA and 50–66% fraction showed specific bands, mainly due to Ani s 1 (20-22 kD) and Ani s 4 (9-10 kD). So far, a total of 7 serum samples from people with allergic manifestation and positive skin prick test (SPT) after fish consumption, have been tested and all of them resulted negative by WB, indicating the lack of sensitization to anisakids. This preliminary study allowed to set up a specific test and evidence the lack of correlation between both tests, SPT and WB. However, the sample size should be increased to estimate the anisakidosis burden in Turkish people.

Keywords: anisakidosis, fish parasite, serodiagnosis, Turkey

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Authors: Sadiq Nasir

Abstract:

The need for strong cybersecurity measures has been brought to light by society's growing reliance on technology. Cybersecurity breaches continue, with the human aspect playing a crucial role, despite the availability of technology remedies. By analyzing the most recent findings in this area of research on awareness, attitudes, and behaviour, this literature review seeks to comprehend the human element in cybersecurity. A thorough overview of the most recent studies and gaps in the body of knowledge will be determined through a systematic examination of the literature. The paper indicates that in order to address the human component in cybersecurity, a socio-technical strategy is required, and it advocates for additional study in order to fully comprehend the consequences of various interventions. The findings of this study will increase our understanding of cybersecurity and have useful ramifications for companies wanting to strengthen their cybersecurity posture.

Keywords: cybersecurity, cybersecurity awareness, human factor in security, human security

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Authors: Sara Franco Ortega, Alina Goldberg Cavalleri, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

Abstract:

Safeners are agrochemicals that enhance the selective chemical control of wild grasses by increasing the ability of the crop to metabolise the herbicide. Although these compounds are widely used, their mode of action is not well understood. It is known that safeners enhance the metabolism of herbicides, by up-regulating the associated detoxification system we have termed the xenome. The xenome proteins involved in herbicide metabolism have been previously divided into four different phases, with cytochrome P450s (CYPs) playing a key role in phase I metabolism by catalysing hydroxylation and dealkylation reactions. Subsequently, glutathione S-transferases (GSTs) and UDP-glucosyltransferases lead to the formation of Phase II conjugates prior to their transport into the vacuole by ABCs transporters (Phase III). Maize (Zea mays), was been treated with different safeners to explore the selective induction of xenome proteins, with a special interest in the regulation of the CYP superfamily. Transcriptome analysis enabled the identification of key safener-inducible CYPs that were then functionally assessed to determine their role in herbicide detoxification. In order to do that, CYP’s were codon optimised, synthesised and inserted into the yeast expression vector pYES3 using in-fusion cloning. CYP’s expressed as recombinant proteins in a strain of yeast engineered to contain the P450 co-enzyme (cytochrome P450 reductase) from Arabidopsis. Microsomes were extracted and treated with herbicides of different chemical classes in the presence of the cofactor NADPH. The reaction products were then analysed by LCMS to identify any herbicide metabolites. The results of these studies will be presented with the key CYPs identified in maize used as the starting point to find orthologs in other crops and weeds to better understand their roles in herbicide selectivity and safening.

Keywords: CYPs, herbicide detoxification, LCMS, RNA-Seq, safeners

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Authors: Valencia Fernandes, Dharmendra Kumar Khatri, Shashi Bala Singh

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Background and Aim: Epigenetics are the inaudible signatures of several pathological processes in the brain. This study understands the influence of DNA methylation, a major epigenetic modification, in the prefrontal cortex and hippocampus of the diabetic brain and its notable effect on the cellular chaperones and synaptic proteins. Method: Chronic high fat diet and STZ-induced diabetic mice were studied for cognitive dysfunction, and global DNA methylation, as well as DNA methyltransferase (DNMT) activity, were assessed. Further, the cellular chaperones and synaptic proteins were examined using DNMT inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC)-via intracerebroventricular injection. Moreover, % methylation of these synaptic proteins were also studied so as to correlate its epigenetic involvement. Computationally, its interaction with the DNMT enzyme were also studied using bioinformatic tools. Histological studies for morphological alterations and neuronal degeneration were also studied. Neurogenesis, a characteristic marker for new learning and memory formation, was also assessed via the BrdU staining. Finally, the most important behavioral studies, including the Morris water maze, Y maze, passive avoidance, and Novel object recognition test, were performed to study its cognitive functions. Results: Altered global DNA methylation and increased levels of DNMTs within the nucleus were confirmed in the cortex and hippocampus of the diseased mice, suggesting hypermethylation at a genetic level. Treatment with AzadC, a global DNA demethylating agent, ameliorated the protein and gene expression of the cellular chaperones and synaptic fidelity. Furthermore, the methylation analysis profile showed hypermethylation of the hsf1 protein, a master regulator for chaperones and thus, confirmed the epigenetic involvement in the diseased brain. Morphological improvements and decreased neurodegeneration, along with enhanced neurogenesis in the treatment group, suggest that epigenetic modulations do participate in learning and memory. This is supported by the improved behavioral test battery seen in the treatment group. Conclusion: DNA methylation could possibly accord in dysregulating the memory-associated proteins at chronic stages in type 2 diabetes. This could suggest a substantial contribution to the underlying pathophysiology of several metabolic syndromes like insulin resistance, obesity and also participate in transitioning this damage centrally, such as cognitive dysfunction.

Keywords: epigenetics, cognition, chaperones, DNA methylation

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Authors: Faith G. Ehiemua, Chandra E. Ulinfun

Abstract:

This work presents two approaches that use competing models to combat criminality in human trafficking. It argues that oath-taking is an approach used to combat and repress crime by natives of African descent. Therefore, certain value choices reflected explicitly or implicitly in its habitual functioning are features of crime control, a model of the criminal process used to repress and prevent crime. By pitting the approaches against each other, the work examines the utility of the purpose of each approach with the aim of assessing moral worthiness. The approaches adopted are descriptive, normative, and theoretical. The findings reveal that oath-taking is effective in human trafficking mainly because Africans believe that the African traditional system is efficient. However, the utilitarian ethical theory applied to the use of oath-taking in human trafficking shows oath-taking as protecting the interest of human traffickers against the general good of society.

Keywords: human rights, human trafficking, oath taking, utilitarianism, victim-centered approach

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Authors: Miftahuddin Khilji

Abstract:

The concept of human right is not alien to Islam. The Shari‘ah requires all its followers the sense of responsibility to perform their duties first and then claim their rights. This eventually guarantees the protection of human rights and ensures a peaceful society. The ultimate goal of Shari‘ah is to preserve five basic necessities which are also known as Maqasid ul Shari‘ah or Objectives of Islamic Law. This goal ensures for the members of society their rights without harming public welfare. Despite of the fact that human rights have been fully guaranteed by Islam and their compliance is required by Allah Almighty; not by any legislative body or other sovereign such as kings etc. However, many western writers, organizations and so called liberal thinkers try to create concerns, doubts and misconceptions in minds of the society members. A number of issues are pointed out and people are misguided about the concept of human rights in Islam. This paper aims to discuss main the concept of human rights in the light of perfect and balanced system of laws and principles of Shari‘ah and address those misconceptions and doubts by analyzing them and answering to questions raised about the subject. It would be an effort to prove that human rights are much more significant to Shari‘ah more than any other national or international legislative body.

Keywords: human rights, Islamic law, law, Shariah

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Authors: Mayada Mazher, Ahmed Moustafa, Ahmed Abdellatif

Abstract:

Background: Autophagy is a eukaryotic, highly conserved catabolic process implicated in many pathophysiologies such as wound healing. Autophagy-associated genes serve as a scaffolding platform for signal transduction of macrophage polarization during the inflammatory phase of wound healing and tissue repair process. In the current study, we report a model for the interplay between autophagy-associated genes and macrophages polarization associated genes. Methods: In silico analysis was performed on 249 autophagy-related genes retrieved from the public autophagy database and gene expression data retrieved from Gene Expression Omnibus (GEO); GSE81922 and GSE69607 microarray data macrophages polarization 199 DEGS. An integrated protein-protein interaction network was constructed for autophagy and macrophage gene sets. The gene sets were then used for GO terms pathway enrichment analysis. Common transcription factors for autophagy and macrophages' polarization were identified. Finally, microRNAs enriched in both autophagy and macrophages were predicated. Results: In silico prediction of common transcription factors in DEGs macrophages and autophagy gene sets revealed a new role for the transcription factors, HOMEZ, GABPA, ELK1 and REL, that commonly regulate macrophages associated genes: IL6,IL1M, IL1B, NOS1, SOC3 and autophagy-related genes: Atg12, Rictor, Rb1cc1, Gaparab1, Atg16l1. Conclusions: Autophagy and macrophages' polarization are interdependent cellular processes, and both autophagy-related proteins and macrophages' polarization related proteins coordinate in tissue remodelling via transcription factors and microRNAs regulatory network. The current work highlights a potential new role for transcription factors HOMEZ, GABPA, ELK1 and REL in wound healing.

Keywords: autophagy related proteins, integrated network analysis, macrophages polarization M1 and M2, tissue remodelling

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Authors: Najm Alotaibi

Abstract:

Human motion capture has become one of the major area of interest in the field of computer vision. Some of the major application areas that have been rapidly evolving include the advanced human interfaces, virtual reality and security/surveillance systems. This study provides a brief overview of the techniques and applications used for the markerless human motion capture, which deals with analyzing the human motion in the form of mathematical formulations. The major contribution of this research is that it classifies the computer vision based techniques of human motion capture based on the taxonomy, and then breaks its down into four systematically different categories of tracking, initialization, pose estimation and recognition. The detailed descriptions and the relationships descriptions are given for the techniques of tracking and pose estimation. The subcategories of each process are further described. Various hypotheses have been used by the researchers in this domain are surveyed and the evolution of these techniques have been explained. It has been concluded in the survey that most researchers have focused on using the mathematical body models for the markerless motion capture.

Keywords: human motion capture, computer vision, vision-based, tracking

Procedia PDF Downloads 312