Search results for: Congo red dye
5 The Role of Piceatannol in Counteracting Glyceraldehyde-3-Phosphate Dehydrogenase Aggregation and Nuclear Translocation
Authors: Joanna Gerszon, Aleksandra Rodacka
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In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation
Procedia PDF Downloads 1674 Land Rights, Policy and Cultural Identity in Uganda: Case of the Basongora Community
Authors: Edith Kamakune
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As much as Indigenous rights are presumed to be part of the broad human rights regime, members of the indigenous communities have continually suffered violations, exclusions, and threat. There are a number of steps taken from the international community in trying to bridge the gap, and this has been through the inclusion of provisions as well as the passing of conventions and declarations with specific reference to the rights of indigenous peoples. Some examples of indigenous people include theSiberian Yupik of St Lawrence Island; the Ute of Utah; the Cree of Alberta, and the Xosa andKhoiKhoi of Southern Africa. Uganda’s wide cultural heritage has played a key role in the failure to pay special attention to the needs of the rights of indigenous peoples. The 1995 Constitution and the Land Act of 1998 provide for abstract land rights without necessarily paying attention to indigenous communities’ special needs. Basongora are a pastoralist community in Western Uganda whose ancestral land is the present Queen Elizabeth National Park of Western Uganda, Virunga National Park of Eastern Democratic Republic of Congo, and the small percentage of the low lands under the Rwenzori Mountains. Their values and livelihood are embedded in their strong attachment to the land, and this has been at stake for the last about 90 Years. This research was aimed atinvestigating the relationship between land rights and the right to cultural identity among indigenous communities, looking at the policy available on land and culture, and whether the policies are sensitive of the specific issues of vulnerable ethnic groups; and largely the effect of land on the right to cultural identity. The research was guided by three objectives: to examine and contextualize the concept of land rights among the Basongora community; to assess the policy frame work available for the protection of the Basongora community; to investigate the forms of vulnerability of the Basongora community. Quantitative and qualitative methods were used. a case of Kaseseand Kampala Districts were purposefully selected .138 people were recruited through random and nonrandom techniques to participate in the study, and these were 70 questionnaire respondents; 20 face to face interviews respondents; 5 key informants, and 43 participants in focus group discussions; The study established that Land is communally held and used and thatit continues to be a central source of livelihood for the Basongora; land rights are important in multiplication of herds; preservation, development, and promotion of culture and language. Research found gaps in the policy framework since the policies are concerned with tenure issues and the general provisions areambiguous. Oftenly, the Basongora are not called upon to participate in decision making processes, even on issues that affect them. The research findings call forauthorities to allow Basongora to access Queen Elizabeth National Park land for pasture during particular seasons of the year, especially during the dry seasons; land use policy; need for a clear alignment of the description of indigenous communitiesunder the constitution (Uganda, 1995) to the international definition.Keywords: cultural identity, land rights, protection, uganda
Procedia PDF Downloads 1563 The Urgent Quest for an Alliance between the Global North and Global South to Manage the Risk of Refugees and Asylum Seekers
Authors: Mulindwa Gerald
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Forced Migration is believed to be the most pressing issue in migration studies today, it therefore makes it of paramount importance that we examine the efficacy of the prevailing laws, treaties, conventions and global policies of refugee management. It suffices to note that the existing policies are vague and ambiguous encouraging the hospitality but not assessing the social economic impact to not only the refugees but also their host communities. The commentary around the Off-shore arrangements like one of UK-Rwanda and the legal implications of the same, make it even more fascinating. These are issues that need to be amplified and captured in the Migration Policies. In Uganda, a small landlocked country in East Africa, there always appeared new faces who were refugees from the Congo and Rwanda the neighboring countries to the West and South West respectively. The refugees would migrate to Uganda with absolutely no idea whatsoever how they were going to meet the daily needs of life, no food, no shelter, no clothing. It interest’s one’s mind to conscientiously interrogate the policy issues surrounding refugee management. The 1951 convention sets a number of obligations to states and the conundrum, faced by citizens of the universe interested in Migration studies is ensuring maximum compliance to these obligations considering the resource challenges. States have a duty to protect refugees in accordance with Article 14 of the Universal Declaration for Human Rights which was adopted by the 1951 convention, these speak to rights like the most important right of refugees known as the Principle of Non-Refoulement, which prohibits expulsion or return of refugees or asylum seekers The International Organization for Migrations projection of the number of migrants globally by 2050 was overwhelmingly surpassed by 2019 due to wars, conflicts that have been experienced in different parts of the globe. This is also due natural calamities and tough economic conditions. It is a descriptive analysis that encompasses a qualitative design research based on a case study involving both desk research and field study. The use of qualitative research approaches like interview guides, document review and direct observation methods helped to bring in the experience, social, behavioral and cultural aspects of the respondents into the study, and since qualitative research uses subjective information and not limited to the rigidly definable variables, thus it helped to explore the research area of the study. it therefore verily believe that this paper is going to trigger perspectives and spark a conversation on this really pressing global issue of refugees and asylum seekers, it is suggesting viable solutions to the management challenges while making recommendations like the ensuring that no refugees or asylum seekers are closed at any borders on the globe for instance a concerted effort of all global players to ensure that refugees are protected efficiently.Keywords: management, migration, refugees, rights
Procedia PDF Downloads 532 Where do Pregnant Women Miss Out on Nutrition? Analysis of Survey Data from 22 Countries
Authors: Alexis D'Agostino, Celeste Sununtunasuk, Jack Fiedler
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Background: Iron-folic acid (IFA) supplementation during antenatal care (ANC) has existed in many countries for decades. Despite this, low national coverage persists and women do not often consume appropriate amounts during pregnancy. USAID’s SPRING Project investigated pregnant women’s access to, and consumption of, IFA tablets through ANC. Cross-country analysis provided a global picture of the state of IFA-supplementation, while country-specific results noted key contextual issues, including geography, wealth, and ANC attendance. The analysis can help countries prioritize strategies for systematic performance improvements within one of the most common micronutrient supplementation programs aimed at reducing maternal anemia. Methodology: Using falter point analysis on Demographic and Health Survey (DHS) data collected from 162,958 women across 22 countries, SPRING identified four sequential falter points (ANC attendance, IFA receipt or purchase, IFA consumption, and number of tablets taken) where pregnant women fell out of the IFA distribution structure. SPRING analyzed data on IFA intake from DHS surveys with women of reproductive age. SPRING disaggregated these data by ANC participation during the most recent pregnancy, residency, and women’s socio-economic status. Results: Average sufficient IFA tablet use across all countries was only eight percent. Even in the best performing countries, only about one-third of pregnant women consumed 180 or more IFA tablets during their most recent pregnancy. ANC attendance was an important falter point for a quarter of women across all countries (with highest falter rates in Democratic Republic of the Congo, Nigeria, and Niger). Further analysis reveals patterns, with some countries having high ANC coverage but low IFA provision during ANC (DRC and Haiti), others having high ANC coverage and IFA provision but few women taking any tablets (Nigeria and Liberia), and countries that perform well in ANC, supplies, and initial consumption but where very few women consume the recommended 180 tablets (Malawi and Cambodia). Country-level analysis identifies further patterns of supplementation. In Indonesia, for example, only 62% of women in the poorest quintile took even one IFA tablet, while 86% of the wealthiest women did. This association between socioeconomic status and IFA intake held across nearly all countries where these data are available and was also visible in rural/urban comparisons. Analysis of ANC attendance data also suggests that higher numbers of ANC visits are associated with higher tablet intake. Conclusions: While it is difficult to disentangle which specific aspects of supply or demand cause the low rates of consumption, this tool allows policy-makers to identify major bottlenecks to scaling-up IFA supplementation during ANC. In turn, each falter point provides possible explanations of program performance and helps strategically identify areas for improved IFA supplementation. For example, improving the delivery of IFA supplementation in Ethiopia relies on increasing access to ANC, but also on identifying and addressing program gaps in IFA supply management and health workers’ practices in order to provide quality ANC services. While every country requires a customized approach to improving IFA supplementation, the multi-country analysis conducted by SPRING is a helpful first step in identifying country bottlenecks and prioritizing interventions.Keywords: iron and folic acid, supplementation, antenatal care, micronutrient
Procedia PDF Downloads 3971 Virulence Factors and Drug Resistance of Enterococci Species Isolated from the Intensive Care Units of Assiut University Hospitals, Egypt
Authors: Nahla Elsherbiny, Ahmed Ahmed, Hamada Mohammed, Mohamed Ali
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Background: The enterococci may be considered as opportunistic agents particularly in immunocompromised patients. It is one of the top three pathogens causing many healthcare associated infections (HAIs). Resistance to several commonly used antimicrobial agents is a remarkable characteristic of most species which may carry various genes contributing to virulence. Objectives: to determine the prevalence of enterococci species in different intensive care units (ICUs) causing health care-associated infections (HAIs), intestinal carriage and environmental contamination. Also, to study the antimicrobial susceptibility pattern of the isolates with special reference to vancomycin resistance. In addition to phenotypic and genotypic detection of gelatinase, cytolysin and biofilm formation among isolates. Patients and Methods: This study was carried out in the infection control laboratory at Assiut University Hospitals over a period of one year. Clinical samples were collected from 285 patients with various (HAIs) acquired after admission to different ICUs. Rectal swabs were taken from 14 cases for detection of enterococci carriage. In addition, 1377 environmental samples were collected from the surroundings of the patients. Identification was done by conventional bacteriological methods and confirmed by analytical profile index (API). Antimicrobial sensitivity testing was performed by Kirby Bauer disc diffusion method and detection of vancomycin resistance was done by agar screen method. For the isolates, phenotypic detection of cytolysin, gelatinase production and detection of biofilm by tube method, Congo red method and microtiter plate. We performed polymerase chain reaction (PCR) for detection of some virulence genes (gelE, cylA, vanA, vanB and esp). Results: Enterococci caused 10.5% of the HAIs. Respiratory tract infection was the predominant type (86.7%). The commonest species were E.gallinarum (36.7%), E.casseliflavus (30%), E.faecalis (30%), and E.durans (3.4 %). Vancomycin resistance was detected in a total of 40% (12/30) of those isolates. The risk factors associated with acquiring vancomycin resistant enterococci (VRE) were immune suppression (P= 0.031) and artificial feeding (P= 0.008). For the rectal swabs, enterococci species were detected in 71.4% of samples with the predominance of E. casseliflavus (50%). Most of the isolates were vancomycin resistant (70%). Out of a total 1377 environmental samples, 577 (42%) samples were contaminated with different microorganisms. Enterococci were detected in 1.7% (10/577) of total contaminated samples, 50% of which were vancomycin resistant. All isolates were resistant to penicillin, ampicillin, oxacillin, ciprofloxacin, amikacin, erythromycin, clindamycin and trimethoprim-sulfamethaxazole. For the remaining antibiotics, variable percentages of resistance were reported. Cytolysin and gelatinase were detected phenotypically in 16% and 48 % of the isolates respectively. The microtiter plate method showed the highest percentages of detection of biofilm among all isolated species (100%). The studied virulence genes gelE, esp, vanA and vanB were detected in 62%, 12%, 2% and 12% respectively, while cylA gene was not detected in any isolates. Conclusions: A significant percentage of enterococci was isolated from patients and environments in the ICUs. Many virulence factors were detected phenotypically and genotypically among isolates. The high percentage of resistance, coupled with the risk of cross transmission to other patients make enterococci infections a significant infection control issue in hospitals.Keywords: antimicrobial resistance, enterococci, ICUs, virulence factors
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