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This correlation between the in vitro models described here and observations of DCIS clinical samples supports the validity of these co-units as models of normal and DCIS-like breast.
The behavior of other RS preparations in the two in vitro models described here can not be deduced from the obtained results and has to be examined case by case.
There are already several in vitro models described in the literature which, although they are characterised by additional techniques (eg cell number and viability, immunohistochemistry, qRT-PCR) to those used in this study, many involve small species, for example mouse [ 8], rat [ 9, 10] or rabbit [ 11].
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However, two recent in vitro models describe insulin receptor dynamics in more detail [ 37, 38].
To determine accurately these transport parameters, particularly biliary efflux, the intracellular concentration of compound must be estimated, hence in vitro models describing the dynamics of the hepatocyte system have been adopted to calculate precisely these in vitro uptake parameters.
Therefore, the physiology of mycobacteria grown in the sudden anaerobiosis in vitro model described by Sohaskey and in ours is likely to be very different, which may not allow direct comparison of the data obtained in both models.
We also used the in vitro model (described above) to verify the therapeutic efficacy of salubrinal (a selective inhibitor of eIF2α de-phosphorylation) in controlling protein folding and processing based on its ability to reduce the accumulation of ubiquitinated proteins.
We used the in vitro model described by Gotoh and colleagues [ 16].
While detailed in vivo studies of the host response are now required, the in vitro model described here will allow responses to specific modulators (such as therapeutics) to be investigated.
Implications and future directions The iPSC-based in vitro model described here allows the evaluation of the effects of patient-specific ALS-associated FUS mutations on ALS-relevant cell types, e.g. motoneurons.
As a future perspective, the iPSC-based in vitro model described here, derived from patients by reprogramming or generated by site-directed mutagenesis, might greatly improve our understanding of the molecular basis of MN death and possibly help finding new therapeutic targets for ALS.
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