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An open compartmental model for describing aluminium biokinetics is presented with a central compartment consisting of transferrinand citrate-bound aluminium in blood plasma and interstitial fluid, and three peripheral compartments for organs, muscles and bones and the gastro-intestinal tract. The rate constants describing the transport of aluminium are normalized to an estimated plasma volume and do not depend on the size of the individual. Effects due to changes in compartmental sizes or to transport characteristics are described. The model is applied to biokinetics studies of a volunteer after i.v. administration and of Sprague-Dawley rats with different iron status and with nephrectomization after p.o. administration of 26Al.

Expression of exon-specific isoforms from alternatively spliced mRNA is a fundamental mechanism that substantially expands the proteome of a cell. However, conventional methods to assess alternative splicing are either consumptive and work-intensive or do not quantify isoform expression longitudinally at the protein level. Here, we therefore developed an exon-specific isoform expression reporter system (EXSISERS), which non-invasively reports the translation of exon-containing isoforms of endogenous genes by scarlessly excising reporter proteins from the nascent polypeptide chain through highly efficient, intein-mediated protein splicing. We applied EXSISERS to quantify the inclusion of the disease-associated exon 10 in microtubule-associated protein tau (MAPT) in patient-derived induced pluripotent stem cells and screened Cas13-based RNA-targeting effectors for isoform specificity. We also coupled cell survival to the inclusion of exon 18b of FOXP1, which is involved in maintaining pluripotency of embryonic stem cells, and confirmed that MBNL1 is a dominant factor for exon 18b exclusion. EXSISERS enables non-disruptive and multimodal monitoring of exon-specific isoform expression with high sensitivity and cellular resolution, and empowers high-throughput screening of exon-specific therapeutic interventions.

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