seeding competency
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Tauopathies are characterised by intracellular deposits of fibrillar tau tangles. However, the interneuronal spread of pathological tau species precedes the development of major tau burdens. Two amyloid motifs, VQIINK in repeat 2 and VQIVYK in repeat 3, of tau repeat domain, assemble into β-sheet-rich fibrils on their own but alone do not form seed-competent fibrils. In contrast, the entire R3 region self-aggregates and forms seed-competent fibrils. Our study aimed to identify the minimal regions in the tau repeat domain that define seeding and its impact on intracellular tau phosphorylation and aggregation. Using peptides of individual repeats, we show that R2, like R3, forms seed-competent fibrils when assembled in the presence of heparin. However, R3, but not R2, forms seed-competent fibrils when assembled without heparin, even though both R2 and R3 have identical N-terminal hexapeptide and cysteine residue sequences. Moreover, cysteine to alanine substitution in R3 abrogates its self-aggregation and seeding potency. Tau RD P301S biosensor cells and Tau P301L (0N4R)-expressing HEK293 cells seeded with R2 and R3 fibrils show the induction of pathological phosphorylation of tau at Ser262/Ser396/Ser404 positions and oligomerisation of native tau. Protein fractions of biosensor cells seeded with R2 and R3 fibrils reseed endogenous tau aggregation when introduced into a fresh set of biosensor cells. Our findings suggest that R3 may be the minimal region for pathological seed generation under physiological conditions, whereas R2 might need polyanionic cofactors to generate pathogenic seeds. Lastly, R2 and R3 fibrils induce template-induced misfolding and pathological hyperphosphorylation of intracellular tau, making intracellular tau seed-competent.
- MeSH
- Alzheimerova nemoc * metabolismus MeSH
- cystein MeSH
- HEK293 buňky MeSH
- heparin MeSH
- lidé MeSH
- proteiny tau genetika metabolismus MeSH
- tauopatie * metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Emerging experimental evidence suggests tau pathology spreads between neuroanatomically connected brain regions in a prion-like manner in Alzheimer's disease (AD). Tau seeding, the ability of prion-like tau to recruit and misfold naïve tau to generate new seeds, is detected early in human AD brains before the development of major tau pathology. Many antitumour drugs have been reported to confer protection against neurodegeneration, supporting the repurposing of approved and experimental or investigational oncology drugs for AD therapy. In this study, we evaluated whether antitumour drugs that abrogate the generation of seed-competent aggregates of tau Repeat 3 (R3) domain peptides can prevent tau seeding and toxicity in Tau-RD P301S FRET Biosensor cells and Caenorhabditis elegans. We demonstrate that drugs that interact with the N-terminal VQIVYK or the C-terminal region housing the Cys322 prevent R3 dimerisation, abolishing the generation of prion-like R3 seeds. Preformed R3 seeds (fibrils) capped with, or R3 seeds formed in the presence of VQIVYK- or Cys322-targeting drugs have a reduced potency to cause aggregation of naïve tau in biosensor cells and protect worms from aggregate toxicity. These findings indicate that VQIVYK- or Cys322-targeting drugs may act as prophylactic agents against tau seeding.
Vicia cracca diploids and autotetraploids are highly parapatric in Europe; tetraploids reside in western and northern part, whereas diploids occupy much drier south-eastern part. They meet together in a Central European contact zone. This distribution pattern raised questions about a transformative effect of polyploidization on plant performance and environmental tolerances. We investigated plant survival, growth, and seed production in two water regimes in a common garden experiment using seeds collected from five localities in the Central European contact zone where diploids and tetraploids occur in sympatry. Obtained data imply that tetraploids of V. cracca are not generally superior in performance to diploids. Significantly larger seeds from tetraploid mother plants collected in the field were not correlated with greater stature of the seedlings. Nonetheless, tetraploids might have a potential to out-compete diploids in the long run due to the tetraploids' ability of greater growth which manifested in the second year of cultivation. Considering the response of diploids and tetraploids to water supply, drought stressed tetraploids but not diploids produced a higher proportion of aborted seeds than watered ones, which implies that tetraploids are more drought susceptible than diploids. On the other hand, decreased plant height in drought stresses tetraploids, which simultaneously increased total seed production, may suggest that tetraploids have a greater ability to avoid local extinction under unfavourable conditions by enhancing biomass allocation into production of seeds at the cost of lower growth. The significant interaction between ploidy level and locality in several traits suggests possible polyfyletic origin of tetraploids and the necessity to clarify the history of the tetraploids in Europe.
- MeSH
- biomasa MeSH
- diploidie MeSH
- ploidie MeSH
- semena rostlinná genetika růst a vývoj MeSH
- semenáček genetika růst a vývoj MeSH
- sympatrie MeSH
- tetraploidie MeSH
- vikev genetika růst a vývoj MeSH
- zahrady MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Being a chilling-sensitive staple crop, rice (Oryza sativa L.) is vulnerable to climate change. The competence of rice to withstand chilling stress should, therefore, be enhanced through technological tools. The present study employed chemical intervention like application of sodium nitroprusside (SNP) as nitric oxide (NO) donor and elucidated the underlying morpho-physiological and biochemical mechanisms of NO-mediated chilling tolerance in rice plants. At germination stage, germination indicators were interrupted by chilling stress (5.0 ± 1.0 °C for 8 h day-1), while pretreatment with 100 μM SNP markedly improved all the indicators. At seedling stage (14-day-old), chilling stress caused stunted growth with visible toxicity along with alteration of biochemical markers, for example, increase in oxidative stress markers (superoxide, hydrogen peroxide, and malondialdehyde) and osmolytes (total soluble sugar; proline and soluble protein content, SPC), and decrease in chlorophyll (Chl), relative water content (RWC), and antioxidants. However, NO application attenuated toxicity symptoms with improving growth attributes which might be related to enhance activities of antioxidants, mineral contents, Chl, RWC and SPC. Furthermore, principal component analysis indicated that water imbalance and increased oxidative damage were the main contributors to chilling injury, whereas NO-mediated mineral homeostasis and antioxidant defense were the critical determinants for chilling tolerance in rice. Collectively, our findings revealed that NO protects against chilling stress through valorizing cellular defense mechanisms, suggesting that exogenous application of NO could be a potential tool to evolve cold tolerance as well as climate resilience in rice.
- MeSH
- donory oxidu dusnatého farmakologie MeSH
- homeostáza účinky léků MeSH
- klíčení účinky léků MeSH
- malondialdehyd metabolismus MeSH
- nitroprusid farmakologie MeSH
- nízká teplota MeSH
- ochrana úrody metody MeSH
- oxid dusnatý metabolismus MeSH
- peroxid vodíku metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- peroxidasy metabolismus MeSH
- reakce na chladový šok fyziologie MeSH
- rýže (rod) účinky léků MeSH
- semenáček účinky léků MeSH
- superoxidy metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
To better understand the effect of species traits on plant invasion, we collected comparative data on 20 reproductive and dispersal traits of 93 herbaceous alien species in the Czech Republic, central Europe, introduced after 1500 A. D. We explain plant invasion success, expressed by two measures: invasiveness, i.e. whether the species is naturalized but non-invasive, or invasive; and dominance in plant communities expressed as the mean cover in vegetation plots. We also tested how important reproductive and dispersal traits are in models including other characteristics generally known to predict invasion outcome, such as plant height, life history and residence time. By using regression/classification trees we show that the biological traits affect invasion success at all life stages, from reproduction (seed production) to dispersal (propagule properties), and the ability to compete with resident species (height). By including species traits information not usually available in multispecies analyses, we provide evidence that traits do play important role in determining the outcome of invasion and can be used to distinguish between alien species that reach the final stage of the invasion process and dominate the local communities from those that do not. No effect of taxonomy ascertained in regression and classification trees indicates that the role of traits in invasiveness should be assessed primarily at the species level.
