Homodimerization as a molecular switch between low and high efficiency PrPC cell surface delivery and neuroprotective activity

PrP^C is associated with a variety of functions, and its ability to interact with a multitude of partners, including itself, may largely explain PrP multifunctionality and the lack of consensus on the genuine physiological function of the protein in vivo. In contrast, there is a consensus in the literature that alterations in PrP^C trafficking and intracellular retention result in neuronal degeneration. In addition, a proteolytic modification in the late secretory pathway termed the α-cleavage induces the secretion of PrPN1, a PrP^C-derived metabolite with fascinating neuroprotective activity against toxic oligomeric Aβ molecules implicated in Alzheimer disease. Thus, studies focusing on understanding the regulation of PrP^C trafficking to the cell surface and the modulation of α-cleavage are essential. The objective of this commentary is to highlight recent evidences that PrP^C homodimerization stimulates trafficking of the protein to the cell surface and results in high levels of PrPN1 secretion. We also discuss a hypothetical model for these results and comment on future challenges and opportunities.     

Widespread formation of intracellular calcium carbonates by the bloom-forming cyanobacterium Microcystis

The formation of intracellular amorphous calcium carbonates (iACC) has been recently observed in a few cultured strains of Microcystis, a potentially toxic bloom-forming cyanobacterium found worldwide in freshwater ecosystems. If iACC-forming Microcystis are abundant within blooms, they may represent a significant amount of particulate Ca. Here, we investigate the significance of iACC biomineralization by Microcystis. First, the presence of iACC-forming Microcystis cells has been detected in several eutrophic lakes, indicating that this phenomenon occurs under environmental conditions. Second, some genotypic (presence/absence of ccyA, a marker gene of iACC biomineralization) and phenotypic (presence/absence of iACC) diversity have been detected within a collection of strains isolated from one single lake. This illustrates that this trait is frequent but also variable within Microcystis even at a single locality. Finally, one-third of publicly available genomes of Microcystis were shown to contain the ccyA gene, revealing a wide geographic and phylogenetic distribution within the genus. Overall, the present work shows that the formation of iACC by Microcystis is common under environmental conditions. While its biological function remains undetermined, this process should be further considered regarding the biology of Microcystis and implications on the Ca geochemical cycle in freshwater environments.     

Bioguided Fractionation and Isolation of an Antiplasmodial Saponin from the Roots of Nauclea xanthoxylon (A.Chev.) Aubrév. (Rubiaceae)

The root extract of Nauclea xanthoxylon (A.Chev.) Aubrév. displayed significant 50 % inhibition concentration (IC₅₀s) of 0.57 and 1.26 μg/mL against chloroquine resistant and sensitive Plasmodium falciparum (Pf) Dd2 and 3D7 strains, respectively. Bio-guided fractionation led to an ethyl acetate fraction with IC₅₀s of 2.68 and 1.85 μg/mL and subsequently, to the new quinovic acid saponin named xanthoxyloside ( 1 ) with IC₅₀s of 0.33 and 1.30 μM, respectively against the tested strains. Further compounds obtained from ethyl acetate and hexane fractions were the known clethric acid ( 2 ), ursolic acid ( 3 ), quafrinoic acid ( 4 ), quinovic acid ( 5 ), quinovic acid 3-O-β-D-fucopyranoside ( 6 ), oleanolic acid ( 7 ), oleanolic acid 3-acetate ( 8 ), friedelin ( 9 ), β-sitosterol ( 10a ), stigmasterol ( 10b ) and stigmasterol 3-O-β-D-glucopyranoside ( 11 ). Their structures were characterised with the aid of comprehensive spectroscopic methods (1 and 2D NMR, Mass). Bio-assays were performed using nucleic acid gel stain (SYBR green I)-based fluorescence assay with chloroquine as reference. Extracts and compounds exhibited good selectivity indices (SIs) of >10. Significant antiplasmodial activities measured for the crude extract, the ethyl acetate fraction and xanthoxyloside ( 1 ) from that fraction can justify the use of the root of N. xanthoxylon in ethnomedicine to treat malaria.     

Expression pattern of the homeotic gene Bapx1 during early chick gastrointestinal tract development

Regulation of the Bone Morphogenetic Protein (BMP) signaling pathway is essential for the normal development of vertebrate gastrointestinal (GI) tract, but also for the differentiation of the digestive mesenchymal layer into smooth muscles and submucosal layer. Different studies demonstrated that Bapx1 (for bagpipe homeobox homolog 1) negatively regulates the BMP pathway, but its precise expression pattern during the development and the differentiation of the GI tract mesenchyme actually remains to be examined. Here, we present the spatio-temporal expression profile of Bapx1 in the chick GI tract. We show that Bapx1 is first expressed in the undifferentiated mesenchyme of the gizzard and the colon. After the differentiation of the digestive mesenchyme, we found Bapx1 strongly expressed in the gizzard smooth muscle and in the submucosa layer of the colon. This expression pattern provides new insights into the roles of Bapx1 during the regionalization of the GI tract and the differentiation of the digestive mesenchyme of the colon and the stomach.     

Assessing the response of forest productivity to climate extremes in Switzerland using model–data fusion

The response of forest productivity to climate extremes strongly depends on ambient environmental and site conditions. To better understand these relationships at a regional scale, we used nearly 800 observation years from 271 permanent long‐term forest monitoring plots across Switzerland, obtained between 1980 and 2017. We assimilated these data into the 3‐PG forest ecosystem model using Bayesian inference, reducing the bias of model predictions from 14% to 5% for forest stem carbon stocks and from 45% to 9% for stem carbon stock changes. We then estimated the productivity of forests dominated by Picea abies and Fagus sylvatica for the period of 1960–2018, and tested for productivity shifts in response to climate along elevational gradient and in extreme years. Simulated net primary productivity (NPP) decreased with elevation (2.86 ± 0.006 Mg C ha^?1 year^?1 km^?1 for P. abies and 0.93 ± 0.010 Mg C ha^?1 year^?1 km^?1 for F. sylvatica). During warm–dry extremes, simulated NPP for both species increased at higher and decreased at lower elevations, with reductions in NPP of more than 25% for up to 21% of the potential species distribution range in Switzerland. Reduced plant water availability had a stronger effect on NPP than temperature during warm‐dry extremes. Importantly, cold–dry extremes had negative impacts on regional forest NPP comparable to warm–dry extremes. Overall, our calibrated model suggests that the response of forest productivity to climate extremes is more complex than simple shift toward higher elevation. Such robust estimates of NPP are key for increasing our understanding of forests ecosystems carbon dynamics under climate extremes.     

Cell-Size Homeostasis and the Incremental Rule in a Bacterial Pathogen

How populations of growing cells achieve cell-size homeostasis remains a major question in cell biology. Recent studies in rod-shaped bacteria support the “incremental rule” where each cell adds a constant length before dividing. Although this rule explains narrow cell-size distributions, its mechanism is still unknown. We show that the opportunistic pathogen Pseudomonas aeruginosa obeys the incremental rule to achieve cell-length homeostasis during exponential growth but shortens its cells when entering the stationary phase. We identify a mutant, called frik, which has increased antibiotic sensitivity, cells that are on average longer, and a fraction of filamentous cells longer than 10 μm. When growth slows due to entry in stationary phase, the distribution of frik cell sizes decreases and approaches wild-type length distribution. The rare filamentous cells have abnormally large nucleoids, suggesting that a deficiency in DNA segregation prevents cell division without slowing the exponential elongation rate.