Dental microstructure and life history in subfossil Malagasy lemurs

When compared with their recently extinct relatives, living lemurs represent a mere fraction of a broad radiation that occupied unique niches in the recent past. Among living lemurs, indrids exhibit the fastest rates of dental development. This dental precocity is tightly correlated with rapid pace of postnatal dental eruption, early replacement of the deciduous teeth, high dental endowment at weaning, and relatively slow somatic growth. This pattern is in stark contrast to that seen in extant lemurids, where somatic development is highly accelerated and dental development is relatively slow. We report on the pace of dental development in one species of palaeopropithecid, the sister group to extant indrids. Like much smaller modern indrids, the chimpanzee-sized Palaeopropithecus ingens was dentally precocious at birth as evidenced by the advanced state of molar crown formation. This finding implies a pattern characteristic of Propithecus and other indrids—rapid dental development despite relatively prolonged gestation. Gestation length in this one species of subfossil lemur was likely greater than 9 months. Our results demonstrate that large body size in primates does not preclude exceedingly rapid dental development

Metabolic Cleavage and Translocation Efficiency of Selected Cell Penetrating Peptides: A Comparative Study with Epithelial Cell Cultures

We investigated the metabolic stability of four cell penetrating peptides (CPPs), namely SAP, hCT(9-32)-br, [Pα] and [Pβ], when in contact with either subconfluent HeLa, confluent MDCK or Calu-3 epithelial cell cultures. Additionally, through analysis of their cellular translocation efficiency, we evaluated possible relations between metabolic stability and translocation efficiency. Metabolic degradation kinetics and resulting metabolites were assessed using RP-HPLC and MALDI-TOF mass spectrometry. Translocation efficiencies were determined using fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM). Between HeLa, MDCK and Calu-3 we found the levels of proteolytic activities to be highly variable. However, for each peptide, the individual degradation patterns were quite similar. The metabolic stability of the investigated CPPs was in the order of CF-SAP = CF-hCT(9-32)-br > [Pβ]−IAF > [Pα] and we identified specific cleavage sites for each of the four peptides. Throughout, we observed higher translocation efficiencies into HeLa cells as compared to MDCK and Calu-3, corresponding to the lower state of differentiation of HeLa cell cultures. No direct relation between metabolic stability and translocation efficiency was found, indicating that metabolic stability in general is not a main limiting factor for efficient cellular translocation. Nevertheless, translocation of individual CPPs may be improved by structural modifications aiming at increased metabolic stability

A doubly labeled penetratin analogue as a ratiometric sensor for intracellular proteolytic stability.

Item does not contain fulltextEndocytosis has been shown to play a major role in the cellular import of cationic cell-penetrating peptides (CPPs) and CPP conjugates. Considering the presence of proteolytic activities inside the endolysosomal compartment, it is necessary to assess the consequences of the import mechanism on the intracellular integrity of the vector and the cargo. In this work, a penetratin analogue terminally labeled with two different fluorophores was synthesized and used as a sensor to quantitatively dissect the contribution of intracellular proteolytic activities on the breakdown of this specific CPP. Using a panel of lysosomal protease inhibitors, the endocytic compartment was identified as the major site of degradation. In contrast, an inhibitor of the proteasome had little effect on intracellular peptide integrity. Very remarkably, inhibitors of endolysosomal proteolysis also affected the intracellular distribution of fluorescence, leading to a reduction of fluorescein fluorescence in the cytoplasm. This change in fluorescence distribution was very similar to the one observed after incubation of cells with inhibitors of endosomal acidification. These results indicate that cytoplasmic fluorescence, typically interpreted as CPP entering the cytosol, may originate from proteolytic breakdown products.1 januari 201