Search bioRxiv⌕ Search

Biology subjects

Francois, N.

Publications and source records attributed to Francois, N..

4 recordsLinked to original sources

Dynamics of a mixed beech (Fagus silvatica L.) and hornbeam (Carpinus betulus L.) natural regeneration in North-East France: evolution of stand density and species composition with an insight into tree mortality factors.

ContextMixed beech and hornbeam regenerations are quite common in the east of France but their management is based more on general principles linked to ecosystem functions or services than on silvicultural practices. This is why it is so useful to establish stand trajectories to characterizing the evolution of density during stand development, as well as individual tree mortality models to predict how each species may react, particularly in a changing environment. AimsThis study was conducted to establish size-density trajectories of mixed even-aged beech and hornbeam natural regenerations, using an already tested piecewise polynomial function, and develop an individual tree mortality model based on a logit function. Material and methodsThe study took place in a mixed beech-hornbeam naturally regenerated stand in Hesse forest (NE of France), where a square design 42*42m comprising 64 square plots of 5.25m side was inventoried each year since 2001 until 2012. Measurements included tree species and status (dead or alive), girth at breast height for all trees and total height for a sample of living trees (beech and hornbeam). The size-density trajectories of the 64 plots describing the course of the number of living trees in relation with the mean stand girth, in logarithmic scales, were modeled with a piecewise polynomial function fitted with a mixed-effects model. On the other hand, the individual tree mortality model was fitted with a logit function including several independent variables defined at tree, plot and stand levels. ResultsThe size-density trajectory of mixed beech-hornbeam naturally regenerated stands was successfully fitted using the same function as for pure stands, with a plot-level random component that appeared linearly related to site fertility, initial density of trees (N0) and relative initial proportion of beech trees. The mortality onset appeared to occur at a higher density (RDI = 0.5) in mixed beech-hornbeam naturally regenerated stands than in pure beech even-aged stands (RDI = 0.29), while the maximum density (RDI = 1) was reached at a comparable relative number of surviving trees (N/N0). An individual tree mortality model could also be fitted using a logit function. The probability of mortality of trees appeared linked to individual (social status, species), collective (relative density) and site (fertility, water stress) factors. ConclusionThe size-density trajectory model first developed for pure even-aged stands appeared well adapted to mixed beech and hornbeam natural regenerations, and the individual tree mortality model constructed at the same time for these stands revealed that water stress induced mortality was relatively comparable for beech and hornbeam. These two models give the opportunity to simulate the development of mixed beech and hornbeam regenerations with the addition of a growth model.

ecology↗

Discovery of Isobavachin, a natural flavonoid, as an Apolipoprotein E4 (ApoE4) structure corrector for Alzheimer's disease

Alzheimers disease (AD) is a progressive neurodegenerative disease characterized by extensive neurodegeneration and consequent severe memory loss. Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for AD, with its pathological effects linked to structural instability and altered interactions with lipids and other important disease proteins including amyloid beta (A{beta}) and tau ({tau}). Therefore, correcting and stabilizing the ApoE4 structure has emerged as a promising therapeutic strategy for mitigating its detrimental effects. In this study, we investigated naturally occurring bioavailable flavonoids as ApoE4 stabilizers, focusing on their potential to modulate ApoE4 structure and function. Comprehensive investigation of a focused database using our integrated computational and experimental screening protocol led to the identification of Isobavachin as a potential corrector and stabilizer of ApoE4 structure. In addition, a few other bioavailable flavonoids with similar stabilizing properties were identified, albeit to a much lesser extent as compared to Isobavachin. The findings support the therapeutic potential of flavonoids as ApoE4 modulators and highlight Isobavachin as a lead candidate for further preclinical evaluation. These results provide new insights into the pharmacological targeting of ApoE4 and open avenues for the development of flavonoid-based, ApoE-directed therapies for AD.

neuroscience↗

MAJOR METABOLITES FROM HYPERICUM PERFORATUM L., HYPERFORIN AND HYPERICIN, ARE BOTH ACTIVE AGAINST HUMAN CORONAVIRUSES

COVID-19 pandemic has highlighted the need of antiviral molecules against coronaviruses. Plants are an endless source of active compounds. In the current study, we investigated the potential antiviral effects of Hypericum perforatum L.. Its extract contained two major metabolites belonging to distinct chemical classes, hypericin (HC) and hyperforin (HF). First, we demonstrated that HC inhibited HCoV-229E at the entry step by directly targeting the viral particle in a light-dependent manner. While antiviral properties have already been described for HC, the study here showed for the first time that HF has pan-coronavirus antiviral capacity. Indeed, HF was highly active against Alphacoronavirus HCoV-229E (IC50 value of 1.10 {micro}M), and Betacoronaviruses SARS-CoV-2 (IC50 value of of 0.24 to 0.98 {micro}M), SARS-CoV (IC50 value of 1.01 {micro}M) and MERS-CoV (IC50 value of 2.55 {micro}M). Unlike HC, HF was active at a post-entry step, most likely the replication step. Antiviral activity of HF on HCoV-229E and SARS-CoV-2 was confirmed in primary human respiratory epithelial cells. Furthermore, in vitro combination assay of HF with remdesivir showed that their association was additive, which was encouraging for a potential therapeutical association. As HF was active on both Alpha- and Betacoronaviruses, a cellular target was hypothesized. Heme oxygenase 1 (HO-1) pathway, a potential target of HF, has been investigated but the results showed that HF antiviral activity against HCoV-229E was not dependent on HO-1. Collectively, HF is a promising antiviral candidate in view of our results and pharmacokinetics studies already published in animal models or in human.

microbiology↗

A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses

The SARS-CoV-2 outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against HCoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and MERS-CoV, and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane as demonstrated by cryo-electron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses, and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2 contaminated surfaces.

microbiology↗