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Proper assembly of the spindle apparatus is crucially important for faithful chromosome segregation during anaphase. Thanks to the effort over the last decades, we have very detailed information about many events leading to spindle assembly and chromosome segregation, however we still do not understand certain aspects, including, for example, spindle length control. When tight regulation of spindle size is lost, chromosome segregation errors emerge. Currently, there are several hypotheses trying to explain the molecular mechanism of spindle length control. The number of kinetochores, activity of molecular rulers, intracellular gradients, cell size, limiting spindle components, and the balance of the spindle forces seem to contribute to spindle size regulation, however some of these mechanisms are likely specific to a particular cell type. In search for a general regulatory mechanism, in our study we focused on the role of cell size and nuclear to cytoplasmic ratio in this process. To this end, we used relatively large cells isolated from 2-cell mouse embryos. Our results showed that the spindle size upper limit is not reached in these cells and suggest that accurate control of spindle length requires balanced ratio between nuclear and cytoplasmic volumes.

Proper assembly of the spindle apparatus is crucially important for faithful chromosome segregation during anaphase. Thanks to the effort over the last decades, we have very detailed information about many events leading to spindle assembly and chromosome segregation, however we still do not understand certain aspects, including, for example, spindle length control. When tight regulation of spindle size is lost, chromosome segregation errors emerge. Currently, there are several hypotheses trying to explain the molecular mechanism of spindle length control. The number of kinetochores, activity of molecular rulers, intracellular gradients, cell size, limiting spindle components, and the balance of the spindle forces seem to contribute to spindle size regulation, however some of these mechanisms are likely specific to a particular cell type. In search for a general regulatory mechanism, in our study we focused on the role of cell size and nuclear to cytoplasmic ratio in this process. To this end, we used relatively large cells isolated from 2-cell mouse embryos. Our results showed that the spindle size upper limit is not reached in these cells and suggest that accurate control of spindle length requires balanced ratio between nuclear and cytoplasmic volumes.

Lymphatic transport of drugs after oral administration is an important physiological process in highly lipophilic compounds, such as cannabidiol (CBD). The majority of lymphatic transport studies have been historically conducted in anesthetized rats. However, this animal model differs significantly from the humans regarding both anatomical and physiological features. The aim of this study was therefore to develop a novel animal model using pigs and to provide an interspecies comparison for the lymphatic transport of CBD. The thoracic lymph duct was cannulated via thoracotomy in three pigs and lymph and blood were sampled from conscious animals to assess the lymphatic transport parameters and basic pharmacokinetic parameters of CBD administered in two distinct drug formulations (sesame oil-based solution and nanoemulsion) using a two-period cross-over study design. The mean ± SD oral bioavailability (F) was 6.1 ± 0.9% for the oil solution and 9.2 ± 6.6% for the nanoemulsion. The relative bioavailability via lymph (F ), i.e. the percentage of the systemically available drug that has been transported through the mesenteric lymph, was 20 ± 10% and 11 ± 13%, respectively. Whereas the F for the oil solution was 2.3-fold lower in pigs compared to rats, the F for the nanoemulsion was almost identical for both species. In conclusion, the lymphatic transport of CBD plays an important role after its oral administration. The particular parameters differed significantly between the rodent and higher non-rodent species. The use of higher species models is therefore warranted for the lymphatic transport assessment in settings close to humans.