The Global Engineer : Incorporating global skills within UK higher education of engineers

Background. The Marburg virus (MARV) has a negative-sense single-stranded RNA genome, belongs to the family Filoviridae, and is responsible for several outbreaks of highly fatal hemorrhagic fever. Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. To understand the evolution of MARV at the codon level, we report a comprehensive analysis of synonymous codon usage patterns in MARV genomes. Multiple codon analysis approaches and statistical methods were performed to determine overall codon usage patterns, biases in codon usage, and influence of various factors, including mutation pressure, natural selection, and its two hosts, Homo sapiens and Rousettus aegyptiacus. Results. Nucleotide composition and relative synonymous codon usage (RSCU) analysis revealed that MARV shows mutation bias and prefers U- and A-ended codons to code amino acids. Effective number of codons analysis indicated that overall codon usage among MARV genomes is slightly biased. The Parity Rule 2 plot analysis showed that GC and AU nucleotides were not used proportionally which accounts for the presence of natural selection. Codon usage patterns of MARV were also found to be influenced by its hosts. This indicates that MARV have evolved codon usage patterns that are specific to both of its hosts. Moreover, selection pressure from R. aegyptiacus on the MARV RSCU patterns was found to be dominant compared with that from H. sapiens. Overall, mutation pressure was found to be the most important and dominant force that shapes codon usage patterns in MARV. Conclusions. To our knowledge, this is the first detailed codon usage analysis of MARV and extends our understanding of the mechanisms that contribute to codon usage and evolution of MARV

An in silico overview on the usefulness of tags and linkers in plant molecular pharming

Plant molecular pharming is a promising concept based on the large-scale production of recombinant proteins encompassing antibodies, vaccines and enzymes for human or veterinary uses and treatments. This new branch of biopharmaceutical industry offers pratcical and safety advantages over other traditional production systems. In higher plants, the complex cellular machinery makes possible synthesis and posttranslational modifications of heterologous protein macromolecules. The limiting obstacle to using this plant system at industrial scale is most often the low yield of the recombinant proteins. To improve this production level, many studies have been focusing on the choice of plant species, tissues, organs and cell suspension cultures or various upstream and downstream constituents in the expression cassettes. Likewise, new engineering technologies in plant molecular pharming have emerged relying on the usefulness of using soybean agglutinin (SBA), hydrophobin, zein and elastin-like peptide tags which are employed to extract and purify recombinant proteins in some host systems and under the control, and as a part, of different expression cassettes. Known to be very useful tools in recombinant proteins linkers separate different domains or units of the heterologous gene and thereby keep the functionality of the protein of interest. Here, we compare computationally one tag SBA as a part of fusion with a pharmaceutical human protein ADA joint directly or by the specific flexible (GGGGS)3 liker. The in silico analysis focuses on the mRNAs stability and fusions of tagged and tagged-linked ADA recombinant proteins

Drought Susceptibility Index; a Preferred Criterion in Screening for Tolerance in Soybean

Soybean (Glycine max L.) yield and yield related traits are constrained by drought. Adaptation of soybean to changing environment could be improved by exploitation and introgression of diverse germplasm in breeding program. In present study, the response to drought conditions, especially at flowering stage, was evaluated to determine the potential soybean germplasm for future soybean breeding programs in Pakistan. Field experiment was conducted under two water regimes i.e. well-water and water-limited, to assess the effect of drought in seed yield and yield related traits. Although, drought led to overall reduction of ~15 % in thousand seed weight but still some soybean genotypes performed relatively better under water-limited conditions. These genotypes were also tolerant to drought, with a drought susceptibility index of \u3c 0.5. PCA also explained the pattern of variation existing in soybean germplasm grown under given water regimes i.e. well-water and water-limited conditions. The identified soybean genotypes could be a favorable resource to introduce high yielding soybean in local environment

Une méthode basée sur l'amarrage pour la détermination d'épitopes in silico

Le développement des anticorps thérapeutiques s'est rapidement accéléré dans les 10 dernières années et concerne un nombre croissant de pathologies. La connaissance de l'épitope, à savoir la région de la cible à laquelle l'anticorps se fixe, est essentielle pour la compréhension des effets fonctionnels de ce dernier. Nous avons développé une méthode in silico, MAbTope, qui permet une prédiction précise de cet épitope, quand bien même aucune structure 3D de l'anticorps d’intérêt n'est résolue. Cette méthode se base sur une méthode d'amarrage protéine-protéine développée auparavant dans l’équipe BIOS. Le jeu d'apprentissage a été fortement enrichi en complexes anticorps-cibles, de nouvelles fonctions de score spécifiques ont été mises au point, et le plus important, l'objectif de l'apprentissage-machine a été modifié pour optimiser non plus la conformation de !'assemblage, mais la prédiction de l'épitope. Nous montrons que la méthode qui en résulte permet une prédiction précise et robuste de l'épitope, que la structure 3D de l'anticorps soit connue ou non. Nous montrons également comment les prédictions peuvent être facilement exploitées pour la validation expérimentale. Enfin, nous montrons comment la méthode peut être utilisée pour étudier à haut-débit le recouvrement d'épitopes par des anticorps ayant la même cible.The development of therapeutic antibodies has been rapidly increasing in the last 10 years, with application to an increasing number of pathologies. The knowledge of the epitope, the region of the antigen to which the antibody binds, is crucial for understanding its functional effects. We have developed an in silico method, MAbTope, which allows the accurate prediction of the epitope, regardless of the availability of the 3D structure of the antibody of interest. This method is based on a protein-protein docking method previously developed in the BIOS group. The learning dataset was enlarged in antibody-antigen complexes, new specific scoring functions have been designed, and very importantly, the objective of machine-learning was switched from the conformational perspective towards the epitope determination perspective. We show that the resulting method allows robust and accurate prediction, whether or not the 3D structure of the antibody is available. We also show how the predictions can be easily exploited for experimental validation. Finally, we show how this method can be used for high-throughput epitope binning

Natriuretic peptides appeared after their receptors in vertebrates

International audienceBackground In mammals, the natriuretic system contains three natriuretic peptides, NPPA, NPPB and NPPC, that bind to three transmembrane receptors, NPR1, NPR2 and NPR3. The natriuretic peptides are known only in vertebrates. In contrast, the receptors have orthologs in all the animal taxa and in plants. However, in non-vertebrates, these receptors do not have natriuretic properties, and most of their ligands are unknown. How was the interaction of the NP receptors and the NP established in vertebrates? Do natriuretic peptides have orthologs in non-vertebrates? If so, what was the function of the interaction? How did that function change? If not, are the NP homologous to ancestral NPR ligands? Or did the receptor's binding pocket completely change during evolution? Methods In the present study, we tried to determine if the pairs of natriuretic receptors and their ligands come from an ancestral pair, or if the interaction only appeared in vertebrates. Alignments, modeling, docking, research of positive selection, and motif research were performed in order to answer this question. Results We discovered that the binding pocket of the natriuretic peptide receptors was completely remodeled in mammals. We found several peptides in non vertebrates that could be related to human natriuretic peptides, but a set of clues, as well as modeling and docking analysis, suggest that the natriuretic peptides undoubtedly appeared later than their receptors during animal evolution. We suggest here that natriuretic peptide receptors in non vertebrates bind to other ligands. Conclusions The present study further support that vertebrate natriuretic peptides appeared after their receptors in the tree of life. We suggest the existence of peptides that resemble natriuretic peptides in non-vertebrate species, that might be the result of convergent evolution

Perceived stigma among patient with pulmonary tuberculosis at public health facilities in southwest Ethiopia: A cross-sectional study.

ObjectivesAlthough tuberculosis (TB) related stigma has a significant impact on the diagnosis, patient adherence with treatment, and recovery from the disease, there is limited evidence from Ethiopia regarding perceived stigma among patient with pulmonary tuberculosis (PTB).The purpose of this study was to assess perceived stigma and associated factors among patient with PTB on treatment in southwest Ethiopia.MethodsInstitution-based cross-sectional study was conducted from April to May 2019 among 410 patient with PTB. Data were collected by using the perceived tuberculosis stigma scale. Epi data v3.1 and SPSSv23 were used for data entry and analysis. Multivariable logistic regression models were fitted to identify factors associated with perceived stigma. Results are presented as adjusted odds ratios (AORs) with 95% confidence intervals (CIs).ResultPrevalence of perceived stigma among patient with Pulmonary tuberculosis was 57.1% (95% CI: 52.2, 61.7). Poor social support (AOR = 2.41; 95% CI: 1.06, 5.48), above a month duration of illness (AOR = 2.48; 95% CI: 1.33, 4.64), high perceived stress (AOR = 1.95; 95% CI:1.09, 3.49), current khat use (AOR = 1.88; 95% CI:1.05, 3.37), and presence of depression (AOR = 8.18; 95% CI:4.40, 15.22) were significantly associated with perceived stigma. Patient with HIV co-infection were 5.67 times (AOR = 5.67; 95% CI: 2.32, 13.87) more likely to have Perceived stigma than their counterparts.ConclusionTB related stigma was reported by more than half of the study participant. Stigma reduction measures are needed to lower TB related stigma perceived by the patient, the level of distress associated with it, and to promote the psychological wellbeing of patient with TB