Morphological Changes of Reach Two of the Nile River

Sediment Transport and Morphodynamic

Nonattachment as a Mediator of the Mindfulness-Well-being Relationship: Comparing Emirati and Australian Students

ObjectivesFew studies have explored mindfulness and nonattachment in Arab populations. This study extends our understanding of mindfulness and nonattachment to Arab students in the United Arab Emirates (UAE) based on the 20-item Five Facet Mindfulness Questionnaire (FFMQ) and the 7-item Nonattachment Scale (NAS-7). This study investigated the model fit of each measure, in conjunction with examining the measurement invariance of both measures across Emirati and Australian samples. Next, this study investigated the mediating role of nonattachment.MethodsUniversity students from the UAE (N = 452) and Australia (N = 731) completed self-report measures of mindfulness, nonattachment, positive and negative affect, and depression, stress, and anxiety.ResultsFor the FFMQ, a four-factor model—excluding the facet Observe but with the addition of covariance between two items from the facet Describe—provided adequate fit in both samples. The NAS-7 provided adequate fit in the Australian sample but not the UAE. While the FFMQ model was invariant across samples, the NAS-7 was non-invariant, thus preventing sample comparison. Overall, nonattachment partially mediated the relationship between mindfulness and well-being with differences across samples.ConclusionsFindings support the use of a four-factor model of the FFMQ in Emirati samples and attest to its robustness and suitability as a measure for cross-cultural comparisons. Findings also support a partial mediating role for nonattachment and attest to the intricacies of the Emirati culture

Development of a new medium containing date syrup for production of bleomycin by Streptomyces mobaraensis ATCC 15003 using response surface methodology

A combined statistical approach of orthogonal design and polynomial regression were applied to optimize the composition and concentration of a liquid fermentation medium for the production of bleomycin (BLM) by Streptomyces mobaraensis. Optimal conditions for maximal productivity were determined based on eight parameters at three different levels. The sources of carbon and nitrogen concentration and their interactions with other precursors were found to be statistically significant factors. When date syrup was used as an additional carbon source, higher BLM amount was obtained in comparison to glucose. It was found that the optimum nitrogen source was achieved with the use of soyabean meal. The combined orthogonal design and response surface methodology predicted optimal conditions for production of BLM to be 138 mg dl-1. A confirmatory experiment of the optimal medium composition produced 142 mg dl-1 in the fifth day fermentation at 30°C. The complex medium containing 40 gml-1 date syrup as additional carbon source enhanced the production of BLM by 73%. The combined statistical approach enabled rapid identification and integration of key medium parameters for optimizing secondary metabolite production and could be very useful in pharma-ceutical screening programs.Keywords: Bleomycin, Streptomyces mobaraensis, orthogonal design, medium optimization, date syrupAfrican Journal of Biotechnology Vol. 9(33), pp. 5450-5459, 16 August, 201

The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction

Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5′ ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Conformational Analysis of Monoclonal Antibodies in Lyophilized and Spray Dried Solids

Monoclonal antibodies (mAbs) constitute a large class of therapeutic proteins that have diverse clinical uses. Like most proteins, mAbs are vulnerable to chemical and/or physical degradation, which can lead to significant losses during manufacturing and storage. To slow down such reactions, mAbs are oftentimes formulated in solid rather than liquid dosage forms. Additionally, antibody-drug conjugates, an emerging therapeutic modality that involves mAbs conjugated to cytotoxic small molecule drugs, are formulated as lyophilized solids. As such, the importance of understanding and predicting stability of mAbs in the solid-state cannot be overstated. To this end, various analytical methods are typically used to probe the structure and dynamics of proteins in the solid-state as metrics to predict stability. Recently, hydrogen-deuterium exchange with mass spectrometric analysis (HDX-MS) emerged as a useful tool for the analysis of the higher order structure and the development of stable liquid formulations of therapeutic proteins. In the solid-state (ss), HDX-MS provides a sensitive probe of the conformation of proteins as well as the extent of the interactions thereof with the components of the formulation matrix at both the intact and peptide levels, a property that cannot be measured by other analytical methods. In this vein, the overarching aim of this dissertation is to evaluate the utility of ssHDX-MS to (i) predict physical stability of mAbs in the solid-state, (ii) to probe local conformational changes of mAbs in different solid matrices, and (iii) to study the effect of different manufacturing processes on the conformation of mAbs in the solid-state. The results of these investigations demonstrate a correlation between several ssHDX parameters and the aggregation of a model mAb in lyophilized formulations, and show that local conformational changes and/or site specific interactions with excipients are evident in a histidine matrix. Following from this result, adding histidine to a lyophilized sucrose matrix is shown to decrease the aggregation of the mAb at different pH conditions. Finally, ssHDX-MS analysis indicates the presence of conformational and/or spatial heterogeneity in the spray dried formulations of the mAb with sucrose or trehalose compared to the lyophilized counterparts. Taken together, these findings demonstrate the sensitivity of ssHDX-MS analysis to conformational changes weakly indicated by or invisible to spectroscopic methods, and support the broader use of ssHDX-MS to probe formulation and process effects on protein structure, and to predict physical stability in solid formulations

Probing the Conformation of an IgG1 Monoclonal Antibody in Lyophilized Solids Using Solid-State Hydrogen–Deuterium Exchange with Mass Spectrometric Analysis (ssHDX-MS)

Therapeutic proteins are often formulated as lyophilized products to improve their stability and prolong shelf life. The stability of proteins in the solid-state has been correlated with preservation of native higher order structure and/or molecular mobility in the solid matrix, with varying success. In the studies reported here, we used solid-state hydrogen–deuterium exchange with mass spectrometric analysis (ssHDX-MS) to study the conformation of an IgG1 monoclonal antibody (mAb) in lyophilized solids and related the extent of ssHDX to aggregation during storage in the solid phase. The results demonstrate that the extent of ssHDX correlated better with aggregation rate during storage than did solid-state Fourier-transform infrared (ssFTIR) spectroscopic measurements. Interestingly, adding histidine to sucrose at different formulation pH conditions decreased aggregation of the mAb, an effect that did not correlate with structural or conformational changes as measured by ssFTIR or ssHDX-MS. Moreover, peptide-level ssHDX-MS analysis in four selected formulations demonstrated global changes across the structure of the mAb when lyophilized with sucrose, trehalose, or mannitol, whereas site-specific changes were observed when lyophilized with histidine as the sole excipient

Qualitative healthcare worker survey: Retrospective cross-sectional case study on COVID-19 in the African context

Background: Despite the presence of COVID-19 epidemiologic data in Africa, there are gaps in the understanding of healthcare workers’ concerns and fears early in the pandemic. Methods: A retrospective cross-sectional multi-country pan-African qualitative survey case study on the perceived effects of the COVID-19 pandemic on healthcare workers in the continent focused specifically on personal safety and misinformation. The survey was distributed to 13 countries via snowball sampling of practitioners between April 22 and May 15, 2020. The survey solicited free-form answers, resulting in a large spectrum of responses. Qualitative analysis included open and axial coding methods for thematic emergence. Results: A total of 489 analyzable responses were recorded. The majority of respondents (n = 273, 57%) highlighted personal safety concerns including lack of resources and training to prevent infection (33%); fear of infection and transmission (24%); lack of public awareness and compliance with regulations (12%); governmental concerns (9%) and economic insecurity (11%) amongst others. 328 respondents (67%) reported having heard misinformation about COVID-19. Responses included misinformation regarding origin of the virus (11%), false modes of transmission (6%), differential effect for specific groups (30%), unproven cures (35%), and disbelief in existence (11%). Responses for misinformation and fears revealed categorical associations between certain countries. Conclusion: Addressing fears and concerns of frontline healthcare workers facilitates their essential role in combating community misinformation, and further understanding could provide essential insight to institutions and governments to direct resource allotment and community education