Spectrum of disease-causing mutations in protein secondary structures

<p>Abstract</p> <p>Background</p> <p>Most genetic disorders are linked to missense mutations as even minor changes in the size or properties of an amino acid can alter or prevent the function of the protein. Further, the effect of a mutation is also dependent on the sequence and structure context of the alteration.</p> <p>Results</p> <p>We investigated the spectrum of disease-causing missense mutations in secondary structure elements in proteins with numerous known mutations and for which an experimentally defined three-dimensional structure is available. We obtained a comprehensive map of the differences in mutation frequencies, location and contact energies, and the changes in residue volume and charge – both in the mutated (original) amino acids and in the mutant amino acids in the different secondary structure types. We collected information for 44 different proteins involved in a large number of diseases. The studied proteins contained a total of 2413 mutations of which 1935 (80%) appeared in secondary structures. Differences in mutation patterns between secondary structures and whole proteins were generally not statistically significant whereas within the secondary structural elements numerous highly significant features were observed.</p> <p>Conclusion</p> <p>Numerous trends in mutated and mutant amino acids are apparent. Among the original residues, arginine clearly has the highest relative mutability. The overall relative mutability among mutant residues is highest for cysteine and tryptophan. The mutability values are higher for mutated residues than for mutant residues. Arginine and glycine are among the most mutated residues in all secondary structures whereas the other amino acids have large variations in mutability between structure types. Statistical analysis was used to reveal trends in different secondary structural elements, residue types as well as for the charge and volume changes.</p

Workplace Stress and Employee Wellbeing: Case of Health Care Staff in UAE

Workplace stress is a world-wide concern and has been a subject of researchers, academicians, authorities and decision makers’ interest. It has evidently been considered to be causing poor performance, reduced employee morale, lack of autonomy, job insecurity and to greater extent the employee's wellbeing. Employees in healthcare and hospitality sector work in 24*7 work schedule due to the demanding nature of the industry. Empirical evidences have indicated that employee experience high stress on account of work overload and long working hours taking a toll on their mental and physical well-being. The purpose of this study was to investigate the impact of workplace stress on employee well-being among staff employees in the health care sector and hospitals in UAE. A total of 150 employees working at staff level in health care centers and hospitals in UAE were surveyed. The results showed that workplace has negative impact on employee well-being and the impact was found to be weak. The findings of the study suggest that an increase in workplace stresses will reduce wellbeing of employees. The researchers recommend that in order to reduce the impact of stress on employee well-being organizational support, family support and social support is essential

Hierarchical Nanostructures of Titanium Dioxide: Synthesis and Applications

This chapter covers different routes of preparation of hierarchical nanostructures (HNS) of titanium dioxide. Keeping the interest in developing modern and sustainable methods of materials chemistry, this chapter focuses on synthesis routes for TiO2 HNSs reported by researchers from all over the world. The chapter includes the details of chemical reactions taking place during the synthesis and the effects of various process parameters like: type of surfactants, organic/inorganic titanium salts, temperature and pressure on products. The obtained TiO2 HNSs from different synthesis routes are subsequently compared in terms of their morphology, crystallite size, surface area, particle size and phase. The merits and demerits of all synthesis techniques are also added for comprehensive information. At the end, various applications of HNSs are discussed and their performance is analyzed with respect to the morphologies obtained from different synthesis techniques

Association of oxidative stress with female infertility - a case control study

Objective: To compare stress markers and reproductive hormones in fertile and infertile females, and to relate the markers with age, duration and cause of infertility, and body mass index..Methods: The case-control study was conducted at Aga Khan University Hospital, Karachi, from March 2017 to February 2018. Females aged 16-50 years regardless of ethnic background were recruited from the Australian Concept Infertility Medical Centre, Karachi, and were equally divided into infertile cases group A, and fertile controls group B. Serum follicular stimulating hormone, luteinizing hormone, estradiol, glutathione reductase and cortisol were measured using enzyme-linked innmunosorbent assay. SPSS 19 was used for statistical analysis..Results: There were 328 female subjects divided into two equal groups of 164(50%). Serum luteinizing hormone and cortisol was higher in the group A than in group B (p\u3c0.001). Serum glutathione reductase was low in group A compared to group B (p\u3c0.001). Duration of infertility, serum levels of glutathione reductase and cortisol were also significantly different among infertile females when distributed on the basis of cause of infertility (p\u3c0.05). Serum cortisol had negative correlation with glutathione reductase (p\u3c0.001). Age and body mass index had a positive correlation with serum cortisol (p=0.035; p=0.63), while there was a negative correlation with glutathione reductase (p = -0.732)..Conclusions: Prolonged duration of infertility, age of females and body mass index enhanced the production of stress hormones and decreased antioxidant activity which augmented the risk of infertility

The relationship between fake news and fake medicines: how misinformation has fuelled the sale of COVID-19 substandard and falsified medical products

As waves of COVID-19 continue to threaten public health, an increasing volume of disease-related information is widely accessible, and not all of it is accurate or reliable. The World Health Organisation (WHO) described this overabundance of information, misinformation, and disinformation as an "infodemic", making it difficult for many to distinguish fact from fiction. These definitions are complex and transitional; however, misinformation is defined as the "inadvertent sharing of false information", whereas disinformation is more sinister in origin and constitutes "the deliberate creation and sharing of information known to be false." The infodemic encapsulates both intentional and unintentional erroneous sources. Ultimately, the patient safety consequences remain the same, including amplifying vaccine hesitancy and propagating dangerous "coronavirus cures" myths, leading to higher COVID related mortality rates. Disinformation, desperation, and panic drive the production and sale of falsified medical products. The WHO estimates 1 in 10 medical products in low-and-middle-income countries (LMIC) settings are substandard or falsified (SF), which may worsen diseases, cause disability or even death.&nbsp;Ultimately, SF products undermine public trust in COVID-19 vaccines and treatments, all sectors must come together in this crisis to ensure quality covid medical products are distributed safely and fairly to end the pandemic sooner rather than later. &nbsp

Integrative omics approaches provide biological and clinical insights : examples from mitochondrial diseases

High-throughput technologies for genomics, transcriptomics, proteomics, and metabolomics, and integrative analysis of these data, enable new, systems-level insights into disease pathogenesis. Mitochondrial diseases are an excellent target for hypothesis-generating omics approaches, as the disease group is mechanistically exceptionally complex. Although the genetic background in mitochondrial diseases is in either the nuclear or the mitochondrial genome, the typical downstream effect is dysfunction of the mitochondrial respiratory chain. However, the clinical manifestations show unprecedented variability, including either systemic or tissue-specific effects across multiple organ systems, with mild to severe symptoms, and occurring at any age. So far, the omics approaches have provided mechanistic understanding of tissue-specificity and potential treatment options for mitochondrial diseases, such as metabolome remodeling. However, no curative treatments exist, suggesting that novel approaches are needed. In this Review, we discuss omics approaches and discoveries with the potential to elucidate mechanisms of and therapies for mitochondrial diseases.Peer reviewe

MRFS: A Multi-Resource Fair Scheduling Algorithm in Heterogeneous Cloud Computing

Task scheduling in cloud computing is considered as a significant issue that has attracted much attention over the last decade. In cloud environments, users expose considerable interest in submitting tasks on multiple Resource types. Subsequently, finding an optimal and most efficient server to host users’ tasks seems a fundamental concern. Several attempts have suggested various algorithms, employing Swarm optimization and heuristics methods to solve the scheduling issues associated with cloud in a multi-resource perspective. However, these approaches have not considered the equalization of dominant resources on each specific resource type. This substantial gap leads to unfair allocation, SLA degradation and resource contention. To deal with this problem, in this paper we propose a novel task scheduling mechanism called MRFS. MRFS employs Lagrangian multipliers to locate tasks in suitable servers with respect to the number of dominant resources and maximum resource availability. To evaluate MRFS, we conduct time-series experiments in the cloudsim driven by randomly generated workloads. The results show that MRFS maximizes per-user utility function by %15-20 in FFMRA compared to FFMRA in absence of MRFS. Furthermore, the mathematical proofs confirm that the sharingincentive, and Pareto-efficiency properties are improved under MRF

Potential Economic and Household Income Gains from Trade Liberalization by Using MyGTAP Model

The current study attempted to calculate the potential gains/losses to the household income in Pakistan. The study has employed MyGTAP model which was initially developed by Minor &amp; Walmsley (2012) and is extension of standard GTAP model. The standard GTAP model was linked with a representative household model by using the Social Accounting Matrix (SAM) to capture the effects of trade liberalization on economic growth and income distribution. The study used eight different simulations to calculate the impact of trade agreements with EU, SAARC, China and India and found a significant rise in economic growth. Regardless of some limitations, the model developed in this study produced significant results that may help to explain the current debate on trade liberalization. The results of the study conclude that it is manufacturing sector that may help to improve the income of all types of household and economic growth

Potential Economic and Household Income Gains from Trade Liberalization by Using MyGTAP Model

The current study attempted to calculate the potential gains/losses to the household income in Pakistan. The study has employed MyGTAP model which was initially developed by Minor &amp; Walmsley (2012) and is extension of standard GTAP model. The standard GTAP model was linked with a representative household model by using the Social Accounting Matrix (SAM) to capture the effects of trade liberalization on economic growth and income distribution. The study used eight different simulations to calculate the impact of trade agreements with EU, SAARC, China and India and found a significant rise in economic growth. Regardless of some limitations, the model developed in this study produced significant results that may help to explain the current debate on trade liberalization. The results of the study conclude that it is manufacturing sector that may help to improve the income of all types of household and economic growth