Reproducibility of scientific results is a key element of science and credibility. The lack of reproducibility across many scientific fields has emerged as an important concern. In this piece, we assess mathematical model reproducibility and propose a scorecard for improving reproducibility in this field.
Plants need to maintain a low Na+/K+ ratio for their survival and growth when there is high sodium concentration in soil. Under these circumstances, the high affinity K+ transporter (HKT) and its homologs are known to perform a critical role with HKT1;5 as a major player in maintaining Na+ concentration. Preferential expression of HKT1;5 in roots compared to shoots was observed in rice and rice-like genotypes from real time PCR, microarray, and RNAseq experiments and data. Its expression trend was generally higher under increasing salt stress in sensitive IR29, tolerant Pokkali, both glycophytes; as well as the distant wild rice halophyte, Porteresia coarctata, indicative of its importance during salt stress. These results were supported by a low Na+/K+ ratio in Pokkali, but a much lower one in P. coarctata. HKT1;5 has functional variability among salt sensitive and tolerant varieties and multiple sequence alignment of sequences of HKT1;5 from Oryza species and P. coarctata showed 4 major amino acid substitutions (140 P/A/T/I, 184 H/R, D332H, V395L), with similarity amongst the tolerant genotypes and the halophyte but in variance with sensitive ones. The best predicted 3D structure of HKT1;5 was generated using Ktrab potassium transporter as template. Among the four substitutions, conserved presence of aspartate (332) and valine (395) in opposite faces of the membrane along the Na+/K+ channel was observed only for the tolerant and halophytic genotypes. A model based on above, as well as molecular dynamics simulation study showed that valine is unable to generate strong hydrophobic network with its surroundings in comparison to leucine due to reduced side chain length. The resultant alteration in pore rigidity increases the likelihood of Na+ transport from xylem sap to parenchyma and further to soil. The model also proposes that the presence of aspartate at the 332 position possibly leads to frequent polar interactions with the extracellular loop polar residues which may shift the loop away from the opening of the constriction at the pore and therefore permit easy efflux of the Na+. These two substitutions of the HKT1;5 transporter probably help tolerant varieties maintain better Na+/K+ ratio for survival under salt stress.
The reproducibility crisis has emerged as an important concern across many fields of science including life science, since many published results failed to reproduce. Systems biology modelling, which involves mathematical representation of biological processes to study complex system behaviour, was expected to be least affected by this crisis. While lack of reproducibility of experimental results and computational analysis could be a repercussion of several compounded factors, it was not fully understood why systems biology models with well defined mathematical expressions fail to reproduce and how prevalent it is. Hence, we systematically attempted to reproduce 455 kinetic models of biological processes published in peer-reviewed research articles from 152 journals; which is collectively a work of about 1400 scientists from 49 countries. Our investigation revealed that about half (49%) of the models could not be reproduced using the information provided in the published manuscripts. With further effort, an additional 12% of the models could be reproduced either by empirical correction or support from authors. The other 37% remained non-reproducible models due to missing parameter values, missing initial concentration, inconsistent model structure, or a combination of these factors. Among the corresponding authors of the non-reproducible model we contacted, less than 30% responded. Our analysis revealed that models published in journals across several fields of life science failed to reproduce, revealing a common problem in the peer-review process. Hence, we propose an 8-point reproducibility scorecard that can be used by authors, reviewers and journal editors to assess each model and address the reproducibility crisis.
Objectives: This study aimed to analyse the epidemiological and clinical characteristics of critical COVID-19 cases and investigate risk factors including comorbidities and age in relation with the clinical aftermath of COVID-19 in critical cases in Bangladesh. Methods: In this retrospective study, epidemiological and clinical characteristics, complications, laboratory results, and clinical management of the patients were studied from data obtained from 168 individuals diagnosed with an advanced prognosis of COVID-19 admitted in two hospitals in Bangladesh. Results: Individuals in the study sample contracted COVID-19 through community transmission. 56.5% (n = 95) cases died in intensive care units (ICU) during the study period. The median age was 56 years and 79.2% (n=134) were male. Typical clinical manifestation included Acute respiratory distress syndrome (ARDS) related complications (79.2%), fever (54.2%) and cough (25.6%) while diabetes mellitus (52.4%), hypertension (41.1%) and heart diseases (16.7%) were the conventional comorbidities. Clinical outcomes were detrimental due to comorbidities rather than age and comorbid individuals over 50 were at more risk. In the sample, oxygen saturation was low (< 95% SpO2) in 135 patients (80.4%) and 158 (93.4%) patients received supplemental oxygen. Identical biochemical parameters were found in both deceased and surviving cases. Administration of antiviral drug Remdesivir and the glucocorticoid, Dexamethasone increased the proportion of surviving patients slightly. Conclusions: Susceptibility to developing critical illness due to COVID-19 was found more in comorbid males. These atypical patients require more clinical attention from the prospect of controlling mortality rate in Bangladesh.
Mohammad Ali Moni) 14 15 ABSTRACT 16 17 An outbreak, caused by a RNA virus, SARS-CoV-2 named COVID-19 has become pandemic with a 18 magnitude which is daunting to all public health institutions in the absence of specific antiviral 19 treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two important proteins of this 20 virus facilitating its entry into host cell and genome replication. Small interfering RNA (siRNA) is a 21 prospective tool of the RNA interference (RNAi) pathway for the control of human viral infections 22 by suppressing viral gene expression through hybridization and neutralization of target 23 complementary mRNA. So, in this study, the power of RNA interference technology was harnessed 24 to develop siRNA molecules against specific target genes namely, nucleocapsid phosphoprotein 25 gene and surface glycoprotein gene. Conserved sequence from 139 SARS-CoV-2 strains from 26 around the globe was collected to construct 78 siRNA that can inactivate nucleocapsid 27 phosphoprotein and surface glycoprotein genes. Finally, based on GC content, free energy of 28folding, free energy of binding, melting temperature and efficacy prediction process 8 siRNA 29molecules were selected which are proposed to exerts the best action. These predicted siRNAs 30 should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in 31 the response against SARS-CoV-2 32 33
Aim: Rabies virus infections are a global threat to human and animal health, yet no progressive curative therapy has been developed. In this study, the nucleoprotein gene of rabies virus which is responsible for viral infection was used as a target to design our desired siRNA. Methods: The conserved regions were analyzed by doing alignment of sequences from different strains. Subsequently, different computational tools were used for designing and validation of siRNA molecules. Results: We identified four probable siRNA molecules from twelve different strains of rabies virus which may silence the nucleoprotein gene and inhibit the multiplication of the virus. Conclusion: Our study may help to take an effective therapeutic approach against rabies virus and lead to better control of rabies in humans.
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