The ribosome lowers the entropic penalty of protein folding.

Most proteins fold during biosynthesis on the ribosome1, and co-translational folding energetics, pathways and outcomes of many proteins have been found to differ considerably from those in refolding studies2-10. The origin of this folding modulation by the ribosome has remained unknown. Here we have determined atomistic structures of the unfolded state of a model protein on and off the ribosome, which reveal that the ribosome structurally expands the unfolded nascent chain and increases its solvation, resulting in its entropic destabilization relative to the peptide chain in isolation. Quantitative 19F NMR experiments confirm that this destabilization reduces the entropic penalty of folding by up to 30 kcal mol-1 and promotes formation of partially folded intermediates on the ribosome, an observation that extends to other protein domains and is obligate for some proteins to acquire their active conformation. The thermodynamic effects also contribute to the ribosome protecting the nascent chain from mutation-induced unfolding, which suggests a crucial role of the ribosome in supporting protein evolution. By correlating nascent chain structure and dynamics to their folding energetics and post-translational outcomes, our findings establish the physical basis of the distinct thermodynamics of co-translational protein folding.

A novel approach to assessing the antioxidant and anti-diabetic potential of synthesized calcium carbonate nanoparticles using various extracts of Ailanthus altissima.

Calcium carbonate nanoparticles (CaCO3) have been found to exhibit unique properties that show their potential to be used in various therapies. Green synthesis of CaCO3 has been progressively gaining ac-ceptance due to its cost-effectiveness and energy-efficient nature. In the current study, different extracts of Ailanthus altissima were used to synthesize the calcium carbonate nanoparticles the synthesis and characterization of CCNPs were confirmed by using Fourier Transform Infra-Red spectroscopy, UV-Vis spectroscopy, and Scanning Electron Microscopy (SEM). The antioxidant activities (hydrogen peroxide, phosphomolydbenum, and ferric reducing) of calcium carbonate nanoparticles were affirmed by a good range of percentages of inhibition against free radical scavenging. The antidebate assays of CCNPs were observed by in-vitro and in silico approaches in a range at various concentrations while maximum inhibition occurred. In conclusion, the current study depicted that conjugated CaCO3 with A. altissima has a good potential to cure oxidative stress and Type II diabetes and could be used in the future as biogenic nanomedicine for the treatment of other metabolic diseases.

Effectiveness of implementation of standard clinical pathway through healthcare professionals among acute myocardial infarction patients undergoing angiography / angioplasty in a public tertiary care hospital, Karachi.

OBJECTIVE: To assess the effect of acute myocardial infarction standard clinical pathway among acute myocardial infarction patients on length of stay in public tertiary care setting. METHODS: The quasi-experimental non-randomised study was conducted at the Department of Cardiology, Dr Ruth Pfau Civil Hospital, Karachi, from September to December 2018, and comprised acute myocardial infarction patients. Those admitted before the implementation of acute myocardial infarction standard clinical pathway formed the control group, while those admitted after the implementation were in the intervention group. Acute myocardial infarction standard clinical pathway was implemented and the interventional clinical practices of healthcare professionals, including cardiologists, postgraduates, residents, nurses and critical care technicians, were assessed using a standard checklist. Data was analysed using SPSS 21. RESULTS: Of the 100 participants, 50(50%) were in the control group; 31(62%) males and 19(38%) females. The intervention group also had 50(50%) patients; 35(70%) males and 15(30%) females. Regarding effectiveness of the implementation of standard clinical pathway, length of hospital stay reduced significantly in the intervention group compared to the control group (p=0.003). CONCLUSIONS: The implementation of acute myocardial infarction standard clinical pathway reduced the length of hospital stay of acute myocardial infarction patients.

Genetic transformation of Sr22 gene in a high yielding susceptible cultivar of commercial wheat (Triticum aestivum L.).

In this study, the Sr22 gene was isolated and prepared for transformation in disease-susceptible commercial high-yielding wheat (Triticum aestivum L.) cultivar Lasani-2008. The Sr22 fragment was initially inserted in plasmid pUC57 for sequence confirmation before performing further experiments. After confirmation, Sr22 was subcloned in pGreen0029 which helped in further cloning and ligation. pUC57-Sr22 was restricted with Nru1 and BamH1, while pGreen0029 was restricted with EcoRV and BamH1 and ligated. From pGreen0029, Sr22 was eluted and ligated in pJIT163 to insert the 2 × 35S promoter and CaMV terminator using Xho1 and BamH1 and Sal1. At this stage, the expression cassette was completed. The 2 × 35Sp-Sr22-CaMVt was then ligated in pGreen0029 and transferred to Agrobacterium along with pSOUP. pSOUP helped pGreen0029 to insert 2X35Sp-Sr22-CaMVt in the callus of Lasani-2008, along with kanamycin-resistant gene. Transgenic callus was used for regeneration of the whole plant by tissue culture. Transgenic plants were further tested by PCR, qPCR and SDS-PAGE. The transgenic Lasani-2008 showed substantial resistance against stem rust in both seedling and adult plant stages. The results also showed that transgenic Lasani-2008 has increased average yield of grains (i.e., 4893 ± 148 kg/ha) as compared to non-transgenic Lasani-2008 (i.e., with average yield of gains 4762 ± 103 kg/ha). Sr22 containing lines and the transgenic developed in this study can be used in breeding systems. Transgenic seeds developed will be shared with breeding institutes and breeders should use this information to develop new varieties.