Modulation Of PKR Activity During HIV Infection And Cellular Stress By PACT And TRBP

A crucial component of the cellular response to stress is the attenuation of protein synthesis to allow the cell to dedicate resources for the restoration of homeostasis or towards the induction of apoptotic cell death in case the stressors overwhelm the cell. This process is itself regulated by one of the four eIF2α kinases of which PKR (Protein Kinase R) is responsible for inhibiting general translation during viral infection, oxidative stress, ER stress, heat shock or serum withdrawal. During viral infection, PKR is transcriptionally induced by interferon but remains latent until it interacts with dsRNA. This interaction induces a conformational change that activates PKR’s catalytic activity, resulting in the phosphorylation of the eukaryotic initiation factor eIF2α and the cessation of both general and viral protein synthesis. This inhibition of viral protein synthesis is however short-lived, as several viral and host cellular factors are coopted by viruses to neutralize PKR’s catalytic activity against viral replication. One such cellular factor is PACT (Protein Activator of PKR), PKR’s protein activator during non-viral stress, which interacts strongly with PKR during HIV infection but does not activate its catalytic activity. We investigated the mechanisms behind PACT’s inability to activate PKR robustly during HIV infection. Our results show that PACT acts synergistically with the HIV trans-activator, Tat, dsRNA-containing mRNAs, as well as the adenosine deaminase, ADAR1 to form a PKR inhibitory complex to facilitate the translation of viral mRNAs during HIV infection. Most importantly, these results elucidate a pathway that could be a target of antiviral therapy to promote PKR activation and reduce viral load in infected cells. During non-viral stress, PKR’s activity is regulated negatively by the TAR RNA Binding Protein, TRBP. TRBP regulates PKR activity by interacting with PKR as well as PACT. Stress-induced phosphorylation of PACT at Serine 287 weakens its interaction with TRBP, while increasing PACT’s homomeric interactions and heteromeric interactions with PKR. The role, if any, of similar stress-induced post-translational modifications on TRBP’s ability to form homomeric interactions and heteromeric interactions with PKR as well as to inhibit PKR have remained unclear. In this light, we investigated whether TRBP is subject to stress-induced phosphorylation and how that might alter TRBP-TRBP and TRBP-PKR interactions as well as TRBP’s ability to inhibit PKR. Our results demonstrate that TRBP is phosphorylated by the Mitogen Activated Protein Kinases JNK and ERK in response to oxidative stress, and consequently forms strong homomeric interactions with PKR, resulting in increased inhibition of PKR and better cell recovery during oxidative stress. PKR, PACT, and TRBP ‘s homomeric and heteromeric interactions are primarily mediated by the evolutionarily conserved dsRNA binding motif (dsRBM) present in all three proteins as well as in several other dsRNA binding proteins. We investigated the contributions of the two copies of dsRBMs in PACT to PACT’s interactions with dsRNA, PACT, TRBP, and PKR. Our results establish that each motif contributes to a varying extent towards PACT’s interaction with its known binding partners, and highlight the importance of PACT homodimerization for PKR activation

Hypothyroxinemia in Acquired Immune Deficiency Syndrome (AIDS)

A journal article on HIV/Aids.Acquired immune deficiency syndrome (AIDS), a disease predictive of a defect in the cell-mediated immunity, is caused by the human immuno-deficiency virus (HIV).1'1 Infection with this virus results in a gradual but progressive deterioration of immune function leading to disease manifestation. The syndrome is characterised by generalised infection and lymphad- enopathy, and is often associated with multisystem disorders. Patients with AIDS have been reported to have a high frequency of endocrine abnormalities, mostly affecting the adrenal gland, but also the thyroid and other endocrine organs.4-8 These lesions may result from necrosis, infection of the organs, or malignant transformations, presenting as Kaposi sarcoma

Effects of Open Cast Quarrying Technique on Vegetation Cover and the Environment in South-Eastern Nigeria

Quarrying activities happen to cause huge losses in land and vegetation cover due to the fact that its operations are usually on a large scale and the sites are abandoned after the resources have become depleted. This study examined the open cast quarrying technique and also the spatial pattern of the quarrying activities and their locations in the study area. Direct field measurement was utilized for the study using a Surveyors tape to measure the lateral extent of degraded land. Garmin eTrex GPS receiver was used to obtain the co˗ordinates of the quarry sites. Geographical Information System and Global Positioning System were used for producing a map of the area and fixing the geographic positions of the locations of the quarry sites respectively. The data so collected were collated and analysed for 27 quarry locations selected from six local government areas where quarrying activities are heavily concentrated and currently active. The result of the study obtained from the principal component analysis showed that there is a significant pattern in the quarrying activities and their locations with explained variance of (82.91 %). The spatial pattern and locations of the quarrying activities in the study area showed: Ohaukwu (11), Ivo (2), Ishielu (1), Ezza North (5), Afikpo North (4) and Izzi (4).The parameters that described the pattern of quarrying activities were:  the area of pit covered (0.91), percentage of quarrying area (0.93), numbers of pit covered (0.83), and villages involved (0.64).  The study also revealed that the total area of vegetation cover destroyed was 402.855 hectares. Field measurements showed that the percentages of land lost in the local government areas were quarrying activities are intensified are as follows: Ohaukwu 28.7%, Ishielu 9.3%, Ivo 35.2%, Afikpo North 14. 7%, Ezza  North 8.0% and Izzi 3.7%. The study recommended that the Government and public agencies concerned should develop and enforce policies and strategies to achieve a balanced, coordinated and sustainable development in the State

Development of a Solar-Powered Integrated Wireless Soil Moisture Meter

In this study, we developed a solar-powered integrated wireless soil moisture meter that can easily measure in situ soil moisture, soil temperature, and hydrogen potential (pH) using nature\u27s solar energy. Knowledge of soil moisture content and other relevant soil-specific parameters is essential for irrigation scheduling, fertilizer selection, and fertigation. Also, considering that the electricity supply in some developing countries is either erratic or unavailable, this research aims to bridge the gap in electricity availability and ease of measurement and integrate more soil-specific parameters. The sensor system was developed using the frequency domain (FD) technique for fast response. These parameters were measured sequentially at an interval of about 5 seconds, with the readings displayed simultaneously on a Bluetooth-connected device (e.g., an Android phone) located about 50 meters away from the developed system. The different sensors are classified and adequately labeled to identify the parameter to be measured. The performance evaluation carried out indicated a reasonably functioning device that is cost-effective. The results obtained showed that the system was resourceful as it not only measured the parameters of interest (soil moisture, temperature, and pH) but also gave a prompt response in measurement and transmission. Overall, the developed wireless soil moisture meter provides instantaneous data on pH, moisture, and temperature circulation across soil layers. The system is promising as it can be integrated into large-scale automated irrigation systems for agricultural lands

PACT-mediated pkr activation acts as a hyperosmotic stress intensity sensor weakening osmoadaptation and enhancing inflammation

The inability of cells to adapt to increased environmental tonicity can lead to inflammatory gene expression and pathogenesis. The Rel family of transcription factors TonEBP and NF-κB p65 play critical roles in the switch from osmoadaptive homeostasis to inflammation, respectively. Here we identified PACT-mediated PKR kinase activation as a marker of the termination of adaptation and initiation of inflammation in Mus musculus embryonic fibroblasts. We found that high stress-induced PACT-PKR activation inhibits the interaction between NF-κB c-Rel and TonEBP essential for the increased expression of TonEBP-dependent osmoprotective genes. This resulted in enhanced formation of TonEBP/NF-κB p65 complexes and enhanced proinflammatory gene expression. These data demonstrate a novel role of c-Rel in the adaptive response to hyperosmotic stress, which is inhibited via a PACT/PKR-dependent dimer redistribution of the Rel family transcription factors. Our results suggest that inhibiting PACT-PKR signaling may prove a novel target for alleviating stress-induced inflammatory diseases

Stroke prevalence amongst sickle cell disease patients in Nigeria: a multi-centre study

Background: Stroke is a life-changing, debilitating complication of sickle cell disease (SCD). Previous studies had recorded high stroke prevalence amongst this group of patients. Nigeria has a large population of people affected by this condition and this study aims to assess the stroke prevalence in this large population.Methodology: Stroke prevalence data from 14 physicians working in 11 tertiary health centres across the country was collated by doctors using the sickle cell registers and patient case notes. This data was then collated and used to obtain the overall stroke prevalence in adult and children.Results: The stroke prevalence in sickle cell disease patients in Nigeria was observed to be 12.4 per 1000 patients. Prevalence in the adult patients was 17.7 per 1000 patients and 7.4 per 1000 patients in children. Twenty three percent of the affected patients had more than stroke episode.Conclusion: The stroke prevalence in Nigeria is lower than previously recorded rates and further studies will be required to investigate other factors which may play a role.Keywords: sickle cell, stroke, Nigeria, prevalenc

Serum Soluble Transferrin Receptor and Transferrin Levels among Regular Blood Donors

Background: The study evaluated the effects of regular blood donation on serum transferrin and soluble transferrin receptor levels at Wenchi Methodist Hospital. Methods: This was a hospital-based cross-sectional study conducted at the Medical Laboratory Department of the Wenchi Methodist Hospital in the Bono Region of Ghana. A total of eighty-nine (89) venous blood samples from apparently healthy blood donors were analyzed. Complete blood count parameters were analyzed using an automated haematology analyzer and serum transferrin and transferrin receptor using ELISA. The data were analyzed using SPSS version 22.0. Results: Haemoglobin (p<0.001) and HCT (p=0.004) were significantly lower among the regular blood donors compared with the first-time donors. Regular blood donors had relatively higher serum transferrin (p<0.001) and soluble transferrin receptor levels (p<0.001). A negative correlation was observed between Hb and serum transferrin (r=-0.552, p<0.001), as well as Hb and serum soluble transferrin receptor (r=-0.552, p<0.001). Remunerated donors had lower Hb (p=0.001) and HCT% (p=0.001) but a higher transferrin receptor (p=0.041) than non-remunerated donors. Conclusion: Regular blood donors had relatively lower erythrocyte parameters but higher serum transferrin and soluble transferrin receptors, indicating a possible reduction in serum iron and iron stores. Moderate negative correlations exist between Hb and both transferrin and soluble transferrin receptors. Again, remunerated donors had lower erythrocyte parameters but higher transferrin and soluble transferrin receptors than non-remunerated donors. Periodic assessment of iron parameters among regular blood donors is recommended. A future longitudinal study to assess the entire iron profile of regular blood donors is recommended.   Doi: 10.28991/SciMedJ-2022-04-03-01 Full Text: PD

Distance education students’ indulgence in six sharp practices: General linear modelling of predictive parameters

This study examined the degree to which students indulge in six prominent misconducts in Distance Education Institutions (DEIs). The study also quantified how class size, instructional delivery and institutional policies predict students’ indulgence in sharp practices using a general linear modelling approach. A sample of 871 participants was drawn from 1,742 final-year students across two DEIs in Nigeria. A structured questionnaire was used for data collection. The questionnaire had acceptable psychometric estimates of dimensionality, content and construct validity, as well as reliability. Sharp practices such as cheating, plagiarism, falsification, impersonation, and arm-twisting were more prevalent in large classes, whereas only inducement was higher in small classes. Class size influenced students’ indulgence in sharp practices in DEIs. Instructional delivery and institutional policies negatively predicted students’ indulgence in the six sharp practices. Almost all the six sharp practices correlated positively and significantly, except for impersonation and inducement. Therefore, distance education students who cheat, plagiarize, arm-twist, falsify records, induce lecturers, and promote impersonation are more likely to indulge in other forms of sharp practices. It was concluded that large class sizes, poor instructional delivery, and poorly implemented institutional policies promote sharp practices among distance education students. Based on this conclusion, key policy and research implications are discussed

Multitasking, but for what benefit? The dilemma facing Nigerian university students regarding part-time working.

Students working part-time while studying for a full-time university degree are commonplace in many Western countries. This paper however, examines the historically uncommon part-time working activities and career aspirations among Nigerian university students. In particular, how working is perceived to contribute to developing employability skills, and whether it is influenced by their self-efficacy. Survey data from 324 questionnaires was collected from a federal university, although the data analysis used a mixed-method. The findings indicate that despite low levels of part-time working generally among students, older, more experienced, higher level and female students, place a premium on the skills that part-time work can develop. Moreover, self-efficacy and being female, is a significant predictor in understanding part-time work and career aspirations. This study offers originality by focusing on students’ part-time work, the value working provides, and its link with career aspirations, within a relatively unexplored context of Nigeria

The practice of hepatocellular cancer surveillance in Nigeria

Background: Hepatocellular cancer is a disease of global and public health importance due to the widespread distribution of risk factors and associated high case fatality. Hepatocellular Cancer (HCC) in Sub-Saharan Africa is commonly seen among the younger age groups (&lt;45 years) who present mostly in the terminal stage, when the disease is not amenable to any curative therapy. Hepatocellular Carcinoma surveillance employs the use of simple, cheap and readily available investigations, to detect early curable cancer in individuals with risk factors for HCC.Objectives:The aim of this study is to assess the practice of hepatocellular cancer screening among physicians.Methodolgy:This is a nationwide online survey carried out among physicians who care for patients with HCC. A questionnaire was sent out via a web link to all consenting doctors in Nigeria. The responses were collated in a cloud-based application and data was analysed using Epi-info version 20.Results:Atotal of 218 respondents, 142 were males (65.1 %) with a mean age of 37.6 ± 5.7 years. The modal age group was 31-40 years 153 (69.5%). The main factors considered as a hindrance to surveillance were; the cost of the tests (57.7%), failure of return of patients (50.5%) and not being aware of a surveillance program (45.2 %). The majority of the respondents were Gastroenterologists and Family Physicians. 54% of the gastroenterologists and 64% of the family physicians have never offered HCC surveillance to their patients.Conclusion:This survey highlights a knowledge gap in HCC surveillance among physicians. There is a need to make HCCsurveillance a daily routine among patients at risk by all physicians. Keywords: Surveillance, Hepatocellular Carcinoma, HBV, HCV, Cancer screening