Biophysical studies of the intracellular domains of the EGFR family of Receptor Tyrosine Kinases

The epidermal growth factor receptor and its three orthologues, HER2, HER3 and HER4 have been the subject of intensive basic, clinical and translational research due to their involvement in cancers. These proteins are part of elaborate networks that interact with a myriad of other molecules to effect diverse signaling pathways and affect cellular processes such as migration, apoptosis, cell differentiation and so on. In addition to the formation of preformed dimers, it is well established that ligand engagement leads to receptor dimerization in all family members, except HER2. In the past decade, it has been shown that their intracellular domains dimerize in an asymmetric fashion where the C-lobe of the donor kinase interacts extensively with the Nlobe of the receiver kinase. This structural model is critical for activation of the receiver kinase and subsequent phosphorylation of the C-terminal tail. While the structures of the different domains have been solved, minimum structural and biophysical studies have been performed on the C-terminal tails. In this thesis, we use multiple approaches to characterize the C-terminal tails of EGFR and HER3, and show that they are intrinsically disordered regions of these receptors. We also developed a strategy that has been employed to site-specifically fluorophore-label the EGFR kinase domain, and would serve as a biological probe to directly measure EGFR kinase domain dimerization on lipid surfaces

Biophysical evidence for intrinsic disorder in the C-terminal tails of the epidermal growth factor receptor (EGFR) and HER3 receptor tyrosine kinases

The epidermal growth factor receptor (EGFR)/ErbB family of receptor tyrosine kinases includes oncogenes important in the progression of breast and other cancers, and they are targets for many drug development strategies. Each member of the ErbB family possesses a unique, structurally uncharacterized C-terminal tail that plays an important role in autophosphorylation and signal propagation. To determine whether these C-terminal tails are intrinsically disordered regions, we conducted a battery of biophysical experiments on the EGFR and HER3 tails. Using hydrogen/deuterium exchange mass spectrometry, we measured the conformational dynamics of intracellular half constructs and compared the tails with the ordered kinase domains. The C-terminal tails demonstrate more rapid deuterium exchange behavior when compared with the kinase domains. Next, we expressed and purified EGFR and HER3 tail-only constructs. Results from circular dichroism spectroscopy, size exclusion chromatography with multiangle light scattering, dynamic light scattering, analytical ultracentrifugation, and small angle X-ray scattering each provide evidence that the EGFR and HER3 C-terminal tails are intrinsically disordered with extended, non-globular structure in solution. The intrinsic disorder and extended conformation of these tails may be important for their function by increasing the capture radius and reducing the thermodynamic barriers for binding of downstream signaling proteins

COVID-19 in Africa : rethinking the tools to manage future pandemics

Corona virus disease 2019 (COVID-19) remains an incurable, progressive pneumonia-like illness characterized by fever, dry cough, fatigue, and headache during its early stages. COVID-19 has ultimately resulted in mortality in at least 2 million people worldwide. Millions of people globally have already been affected by this disease, and the numbers are expected to increase, perhaps until an effective cure or vaccine is identified. Although Africa was initially purported by the World Health Organization (WHO) to be severely hit by the pandemic, Africa recorded the least number of cases during the first wave, with lowest rates of infections, compared to Asia, Europe, and the Americas. This statistic might be attributed to the low testing capacity, existing public health awareness and lessons learnt during Ebola epidemic. Nonetheless, the relatively low rate of infection should be an opportunity for Africa to be better prepared to overcome this and future epidemics. In this paper, the authors provide insights into the dynamics and transmission of the severe acute respiratory syndrome corona virus (SARS-CoV-2) during the first wave of the pandemic; possible explanations into the relatively low rates of infection recorded in Africa; with recommendations for Africa to continue to fight Covid-19; and position itself to effectively manage future pandemics. © 2021 Emahi I et al

Bacteriological Quality Assessment of swimming pools in the Osu-Labadi Area, Accra

Bacterial contamination of swimming pool water poses public health risks to swimmers and others who come into direct contact with such pools. There has been an increase in the patronage of swimming pools in Ghana for sports and recreation and therefore the need to investigate the pools compliance with sanitary standards. This study examined the bacteriological and physicochemical (pH, temperature and residual chlorine) levels of swimming pool water in Osu-Labadi, Accra, Ghana to determine the levels of bacterial pollution. Six outdoor swimming pools were randomly selected for this cross-sectional study. Microbiological examination was conducted on a total of 18 samples collected monthly in the evening after the pools had been used. This took place over a 3 month period, from March to May 2014, using standard microbiological and analytical methods. The results of the study indicated that the total viable bacteria count of all the pool water exceeded the acceptable limits. All 6 pools were contaminated by E. coli, Enterobacter faecalis and Klebsiella pneumonia, as well, 5 out of the 6 pools were contaminated by Enterobacter cloacae, Staphylococcus aureus, and Streptococcus agalactiae. The residual chlorine level in all the pools was below the recommended level of 1.0 mg/liter. Statistical analysis showed significant association between water contamination with microbial indicators and physicochemical aspects such as pH, temperature and residual chlorine (p<0.05). The high microbial load count and the isolation of pathogenic bacteria from the pools is an indication of the need to improve monitoring by pool health authorities, improve pool disinfection standards and educate swimmers on hygiene before entering pools. Key words: swimming pool, microbial load, residual chlorine, bacterial contaminant

Empirical Research on the Downturn in Church Attendance in Australia: The youth without Religion

The church has played a significant role in the lives of Australia’s people since the European settlement. It used to provide several welfare services such as educational, health, and orphanages, even more than the government. Australian churches played a significant role in shaping the culture of Australians. Australia was the only country with no newspaper on Sunday as they kept Sunday as a regular holiday and kept everything closed. Indeed, for Australia’s farmers, religion was so important that they decided to remain clear of their religion and, in 1901, to lead up the Federation. As the years passed, church attendance reduced, and others chose no religion. Few considered religion as least important, resulting in an overall decline in Australia’s churches. The paper reiterated the downturn in church attendance in Australia, found reasons for the downturn, and how the youth can be driven to attend the church. Innovation, discipleship, evangelism, oneness, care, hospitality, service to the community, and social media presence were discovered to be strategies for motivating the younger generation, first-time worshippers and new converts to the church

A Survey of Information Literacy (IL) Programmes in Technical University (Tu) Libraries in Ghana

A quantitative study of the libraries of 7 Technical Universities (TUs) of Ghana was conducted to evaluate information literacy programmes at such universities in Ghana. The study employed a descriptive survey research strategy. A sample of 7 librarians out of the 8 TU libraries in Ghana was collected using purposive sampling. A questionnaire served as the instrument to collect data relating to the objectives of the study. The study gathered mostly quantitative data which were analyzed using the Statistical Package for Social Sciences (SPSS). The findings showed that the majority of the examined libraries included information literacy classes as part of their information literacy programmes. These were mostly widely delivered through face to face and online tutorial methods. Furthermore, the study identified the barriers to the successful implementation and running of information literacy programmes in Ghana. It identified lack of integration of information literacy into the curricula of tertiary institutions as a barrier to effective information literacy programmes. From this barrier many other barriers that are typically rectified when information literacy is properly integrated into school curricul

Influence of Brand Equity on Brand Trust: Mediation of Brand Reputation and Moderation of Social Media

The Present study aims to investigate the brand equity of the local as well as international fast food restaurants in the country of Ghana. Furthermore, the study investigates the particular brand association (B Ass.) and brand awareness (B Aw.) dimensions of the brand equity (BE). Moreover, the mediating role of the brand reputation (BR) examined in between dimensions of brand equity and brand trust (BT). In addition the moderating effect of social media also investigated. Study adopted the partial least square 3.0 for inferential statistics as well as structural equation modelling. The results of the study exhibited, that   brand equity has positive and significant influence on brand reputation. Moreover the positive and significant effects of social media on brand trust also notified in the study. In addition, the effect of brand awareness on brand trust partially mediated by brand reputation, while the association between brand association and brand trust is fully mediated. Furthermore, the moderating effect of social media (SM) on brand trust noted negative and significant. The outcomes of the scholarship add to advance indulgent of the multifaceted psychosomatic procedures tangled in purchaser selection standards for a fast food restaurants and service industry. Keywords: Brand Equity (BE); Brand Awareness (B Aw.); Brand Association (B Ass.); Brand Reputation (BR); Brand Trust (BT); Social Media (SM) DOI: 10.7176/EJBM/11-21-02 Publication date:July 31st 201

Temperature, microwave power and pomace thickness impact on the drying kinetics and quality of carrot pomace

This study investigated the effect of air temperature, microwave power, and pomace thickness on the drying kinetics and quality of dried carrot pomace. The study established that the drying of carrot pomace occurs in the falling rate period, suggesting that drying was driven by molecular diffusion. The microwave-drying moisture diffusivity increased with microwave power and ranged between 1.57×10–8 and 2.61×10–8 m2/s. As regards convective air-drying, the moisture diffusivity values were between 3.38×10–10 and 8.27×10–10 m2/s. The microwave powerto-mass activation energy was 15.079 W/g for 5 mm, 7.599 W/g for 10 mm and 9.542 W/g for 15 mm dried samples. Meanwhile, the temperature-dependent activation energy for carrot pomace was found to be 27.637 kJ/mol for 5 mm, 17.92 kJ/mol for 10 mm and 38.76 kJ/mol for 15 mm thickness pomace. Generally, drying time decreased with increasing microwave power or air temperature. The ascorbic acid content of the fresh carrot pomace reduced after both microwave and convective air-drying. However, microwave power, and sample thickness had significant effect on the β-carotene content of dried products but air temperature did not have a significant effect. The effect of temperature and sample thickness on brown pigment formation was substantial with air temperature compared to microwave. The study has demonstrated that microwave drying, compared to conventional drying, enhances moisture removal, drying time, and preservation of carotenoids and ascorbic acid. Therefore, microwave drying can be considered as an alternative method for obtaining quality dried carrot pomace

Effect of inherent innovativeness and consumer readiness on attitudes to mobile banking

Despite the strong evidence that many consumers relish their experience with mobile banking, others indicate that some segments may not be comfortable with these emerging digitized platforms due to certain inherent personal traits. Drawing insights from the socio-psychology and innovation/SSTs adoption literature, this paper tested a structural model with inherent innovativeness as an antecedent variable, and consumers' attitude to M-banking, as a mediator to their future usage intention. The moderating effect of consumer readiness on the hypothesized relationship between consumers' attitudes and intention to use mobile banking was also examined. The model was tested on survey data from 720 respondents from the United Kingdom (UK). Findings show that inherent innovativeness significantly explain attitudes to mobile banking. There was, however, mixed outcomes concerning the effects of three dimensions of consumer readiness on the link between attitudes and intention to use mobile banking. The results show that only ability exert a positive and a significant effect on the examined relationship. The effects of motivation and role clarity seemed insignificant. The findings from this paper can help retail bank managers improve their channel and promotional decisions in order to enhance the service experience of relevant segments