Peer E Kamil Part 2 Pdf Free Download
Lyn Goeppinger
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As you can see from the attached reviews, every reviewer recognized your study as important to the field and clearly appreciated the work you invested into writing and preparing this manuscript. Nevertheless, while all reviewers showed excitement over the novel BAC and CCMV model system you have created, some issues were raised that need to be addressed. There are two points in particular that were brought up during the review process that I would like to highlight. First, while all reviewers recognized the importance of a CCMV BAC, the question was raised as to how far this BAC actually reflects circulating WT CCMV isolates as multiple genes were lost during the cloning process. Furthermore, the BAC additionally acquired an unusual amount of sequence differences compared to the original viral sequence, either potentially indicating genome instability or sequencing errors. Reviewer 1 also raised additional concerns arising from the sequences differences between the generated BAC and the original parental virus, hence the authors should re-evaluate their identified mutations and examine potential effect these adaptations could have on the resulting BAC derived virus for viral genes identified as possibly affected by the reviewer. Secondly, both reviewer 1 and reviewer 3 noted that the experiments performed to characterize the CCMV BAC derived virus were actually performed on human cells, hence in cross-species infections. As explained in the reviews, this can be suboptimal as this could make the interpretation of the generated results more complicated as the virus is not adapted to this host species. Reviewer 3 suggested potentially useful approaches that authors could attempt to address this issue.
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Co-evolution of CMV with their host species over millions of years has led to some unique interactions between viral proteins and host intracellular/extracellular proteins (of various cell types). In the past, primate CMVs (chimpanzee, baboon, rhesus macaques) were isolated and adapted in cell cultures using human fibroblasts due to their readily availability. Chimpanzee fibroblasts are now possible to obtain and have been shown to have unique gene expressing profiles than their human counterparts. The authors should consider including some comparative analyses of CCMV infection in chimpanzee fibroblasts. Otherwise, one may suspect the discrepancies of temporal profiles (of viral gene expression) and their impacts on host cells (at both RNA and protein levels) between HCMV and CCMV are experimental artifacts resulting from CCMV replicating in cells not from its natural host.
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Further studies using markers and tissue-processing methods were also used to show the presence of drug in the certain regions of the inner ear (3). But they do not give any details regarding the drug concentration. Computer simulations have been developed based on the limited data for the estimation of drug amount in different parts of cochlea (7).
Finding high concentrations in the basal region was consistent with other studies showing that cellular effects were more prominent in the basal turn than in the apex of cochlea (14, 15). We also found dexamethasone in all parts of the inner ear. The basal turn and vestibule were found to have higher concentrations in a short time. But after two hours, the apex was the prominent instead of the basal turn, while vestibule preserved its concentration. But our calculations did not match the concentration gradients calculated by Plontke et al. (7, 13) The question about the difference between the basal and apical region still remains.
The interesting part is that the control ear also showed slightly elevated drug levels in the vestibule after two hours. The most probable explanation for this situation is the contamination via Eustachian tube.
BackgroundExtensive population growth and climate change accelerate the search for alternative ways of plant-based biomass, biofuel and feed production. Here, we focus on hitherto unknow, new promising cold-stimulated function of phospholipid:diacylglycerol acyltransferase1 (PDAT1) - an enzyme catalyzing the last step of triacylglycerol (TAG) biosynthesis.ResultOverexpression of AtPDAT1 boosted seed yield by 160% in Arabidopsis plants exposed to long-term cold compared to standard conditions. Such seeds increased both their weight and acyl-lipids content. This work also elucidates PDAT1's role in leaves, which was previously unclear. Aerial parts of AtPDAT1-overexpressing plants were characterized by accelerated growth at early and vegetative stages of development and by biomass weighing three times more than control. Overexpression of PDAT1 increased the expression of SUGAR-DEPENDENT1 (SDP1) TAG lipase and enhanced lipid remodeling, driving lipid turnover and influencing biomass increment. This effect was especially pronounced in cold conditions, where the elevated synergistic expression of PDAT1 and SDP1 resulted in double biomass increase compared to standard conditions. Elevated phospholipid remodeling also enhanced autophagy flux in AtPDAT1-overexpresing lines subjected to cold, despite the overall diminished autophagy intensity in cold conditions.ConclusionsOur data suggest that PDAT1 promotes greater vitality in cold-exposed plants, stimulates their longevity and boosts oilseed oil production at low temperature.
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