Copper chelation delays the onset of prion disease.

The prion protein (PrP) binds copper and under some conditions copper can facilitate its folding into a more protease resistant form. Hence, copper levels may influence the infectivity of the scrapie form of prion protein (PrP Sc ). To determine the feasibility of copper-targeted therapy for prion disease, we treated mice with a copper chelator, D-(؊)-penicillamine (D-PEN), starting immediately following intraperitoneal scrapie inoculation. D-PEN delayed the onset of prion disease in the mice by about 11 days (p ‫؍‬ 0.002), and reduced copper levels in brain by 29% (p < 0.01) and in blood by 22% (p ‫؍‬ 0.03) compared with control animals. Levels of other metals were not significantly altered in the blood or brain. Modest correlation was observed between incubation period and levels of copper in brain (p ‫؍‬ 0.08) or blood (p ‫؍‬ 0.04), indicating that copper levels are only one of many factors that influence the rate of progression of prion disease. In vitro, copper dose-dependently enhanced the proteinase K resistance of the prion protein, and this effect was counteracted in a dose-dependent manner by co-incubation with D-PEN. Overall, these findings indicate that copper levels can influence the conformational state of PrP, thereby enhancing its infectivity, and this effect can be attenuated by chelatorbased therapy

Spike residue 403 affects binding of coronavirus spikes to human ACE2

The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and allows VSV pseudoparticle infection of human lung cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S reduces pseudoparticle infection and viral replication. The T403R RaTG13 S is neutralized by sera from individuals vaccinated against COVID-19 indicating that vaccination might protect against future zoonoses. Our data suggest that a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2 by S proteins of bat coronaviruses. This finding could help to better predict the zoonotic potential of animal coronaviruses

Immunomodulation Targeting Abnormal Protein Conformation Reduces Pathology in a Mouse Model of Alzheimer's Disease

Many neurodegenerative diseases are characterized by the conformational change of normal self-proteins into amyloidogenic, pathological conformers, which share structural properties such as high β-sheet content and resistance to degradation. The most common is Alzheimer's disease (AD) where the normal soluble amyloid β (sAβ) peptide is converted into highly toxic oligomeric Aβ and fibrillar Aβ that deposits as neuritic plaques and congophilic angiopathy. Currently, there is no highly effective treatment for AD, but immunotherapy is emerging as a potential disease modifying intervention. A major problem with most active and passive immunization approaches for AD is that both the normal sAβ and pathogenic forms are equally targeted with the potential of autoimmune inflammation. In order to avoid this pitfall, we have developed a novel immunomodulatory method that specifically targets the pathological conformations, by immunizing with polymerized British amyloidosis (pABri) related peptide which has no sequence homology to Aβ or other human proteins. We show that the pABri peptide through conformational mimicry induces a humoral immune response not only to the toxic Aβ in APP/PS1 AD transgenic mice but also to paired helical filaments as shown on AD human tissue samples. Treated APP/PS1 mice had a cognitive benefit compared to controls (p<0.0001), associated with a reduction in the amyloid burden (p = 0.0001) and Aβ40/42 levels, as well as reduced Aβ oligomer levels. This type of immunomodulation has the potential to be a universal β-sheet disrupter, which could be useful for the prevention or treatment of a wide range of neurodegenerative diseases

Contribution à l'étude chorologique des pelouses calcicoles de la région de Cessières (Aisne)

Prelli R. Contribution à l'étude chorologique des pelouses calcicoles de la région de Cessières (Aisne) . In: Bulletin de l'Association de géographes français, N°387-388, 48e année,1971. pp. 175-178

Asplenium x sleepiae nothosubsp krameri (A-foreziense x A-obovatum subsp obovatum), a fern hybrid new for France (Aspleniaceae, Pteridophyta)

A mixed population of several Asplenium taxa was studied near Roquebrune-sur-Argens (France, Var). A. foreziense, A. obovatum subsp. obovatum and A. obovatum subsp. lanceolatum were identified in the field and then confirmed by spore measurement. The presence of two hybrids within the population was also established thanks to a cytological study, especially that of A. x sleepiae nothosubsp. krameri, a triploid hybrid new for french flora

Asplenium x sleepiae nothosubsp krameri (A. foreziense x A. obovatum subsp. obovatum), une fougère hybride nouvelle pour la flore française (Aspleniaceae, Pteridophyta)

A mixed population of several Asplenium taxa was studied near Roquebrune-sur-Argens (France, Var). A. foreziense, A. obovatum subsp. obovatum and A. obovatum subsp. lanceolatum were identified in the field and then confirmed by spore measurement. The presence of two hybrids within the population was also established thanks to a cytological study, especially that of A. x sleepiae nothosubsp. krameri, a triploid hybrid new for french flora