Tau aggregation into neurofibrillary tangles is a defining feature of Alzheimer's disease and other tauopathies. Although aggregation depends largely on specific amyloidogenic motifs (particularly VQIINK and VQIVYK) in repeated regions of tau microtubule-binding domains, how the primary sequence of adjacent repeats intrinsically influences aggregation and prion-like propagation remains unclear. This study systematically characterized three unmodified, physiologically relevant tau peptide constructs-R1R3, R2R3, and R3R4-to define their intrinsic aggregation kinetics, structural features, and prion-like seeding activity. Among these constructs, we found that R2R3 showed rapid aggregation, distinct β-sheet formation, and potent seeding capable of sustained secondary propagation in cellular biosensor assays. Whereas recent studies have highlighted chemically modified peptides (e.g., acetylated and phosphomimic peptides), our study emphasizes the importance of native, unmodified sequences as fundamental determinants in tau aggregation. Furthermore, these findings establish R2R3 as a robust minimal tau model, providing a valuable tool for mechanistic research and therapeutic screening in tau-related neurodegeneration.
- MeSH
- kinetika MeSH
- lidé MeSH
- proteinové agregáty * MeSH
- proteiny tau * chemie metabolismus MeSH
- sekvence aminokyselin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- proteinové agregáty * MeSH
- proteiny tau * MeSH
Cultivar Désirée is an important model for potato functional genomics studies to assist breeding strategies. Here, we present a haplotype-resolved genome assembly of Désirée, achieved by assembling PacBio HiFi reads and Hi-C scaffolding, resulting in a high-contiguity chromosome-level assembly. We implemented a comprehensive annotation pipeline incorporating gene models and functional annotations from the Solanum tuberosum Phureja DM reference genome alongside RNA-seq reads to provide high-quality gene and transcript annotations. Additionally, we provide a genome-wide DNA methylation profile using Oxford Nanopore reads, enabling insights into potato epigenetics. The assembled genome, annotations, methylation and expression data are visualised in a publicly accessible genome browser, providing a valuable resource for the potato research community.
Parabasalid hindgut symbionts of the xylophagous Isoptera/Cryptocercus lineage (Blattodea: Blattoidea) have been attracting the interest of biologists for decades. However, the parabasalids from other cockroaches (Blattodea excluding Isoptera) remain largely unstudied. The genus Hypotrichomonas, along with genus Trichomitus, belongs to the small parabasalid order Hypotrichomonadida. So far, ten valid Hypotrichomonas species have been described from animals, both vertebrates and invertebrates. Here we have uncovered an extensive diversity of this genus in cockroaches. We have obtained 72 isolates from 41 cockroach species and one from a water-filled tree hole. Using a combination of light-microscopic morphology of protargol-stained cells, scanning electron microscopy, and a phylogenetic analysis of SSU rRNA gene, we show that our strains represent multiple novel Hypotrichomonas species, and we formally describe seven of them. Our data show that the evolutionary center of the genus likely lies in cockroaches. Moreover, the new evolutionary lineages of Hypotrichomonas from cockroaches show a high degree of host specificity.
- Klíčová slova
- Morphology, Phylogeny, SEM, Taxonomy, Trichomonads,
- MeSH
- biodiverzita * MeSH
- fylogeneze MeSH
- molekulární sekvence - údaje MeSH
- Parabasalidea * klasifikace genetika izolace a purifikace ultrastruktura MeSH
- protozoální DNA genetika chemie MeSH
- ribozomální DNA genetika chemie MeSH
- RNA ribozomální 18S genetika MeSH
- sekvenční analýza DNA MeSH
- švábi * parazitologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- protozoální DNA MeSH
- ribozomální DNA MeSH
- RNA ribozomální 18S MeSH
Aptamers are short DNA or RNA sequences that can fold into unique three-dimensional structures, enabling them to bind specifically to target molecules with high affinity, similar to antibodies. A distinctive feature of many aptamers is their ability to adopt a G-quadruplex (G4) fold, a four-stranded structure formed by guanine-rich sequences. While G4 formation has been proposed or demonstrated for some aptamers, we aimed to investigate how frequently quadruplex-prone motifs emerge from the SELEX process. To achieve this, we examined quadruplex candidate sequences from the UTexas Aptamer Database, which contains over 1400 aptamer sequences extracted from 400 publications spanning several decades. We analyzed the G4 and i-motif propensity of these sequences. While no likely i-motif forming candidates were found, nearly 1/4 of DNA aptamers and 1/6 of RNA aptamers were predicted to form G4 structures. Interestingly, many motifs capable of forming G4 structures were not previously reported or suspected. Out of 311 sequences containing a potential stable G4 motif, only 53 of them (17%) reported the word "quadruplex" in the corresponding article. We experimentally tested G4 formation for 30 aptamer sequences and were able to confirm G4 formation for all the sequences with a G4Hunter score of 1.31 or more. These observations suggest the need to reevaluate G4 propensity among aptamer sequences.
- MeSH
- aptamerová technika SELEX MeSH
- aptamery nukleotidové * chemie MeSH
- G-kvadruplexy * MeSH
- guanin chemie MeSH
- nukleotidové motivy MeSH
- sekvence nukleotidů MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aptamery nukleotidové * MeSH
- guanin MeSH
BACKGROUND: In hospitals, decisions are often made under time pressure. There is, however, little evidence on how time pressure affects the quality of treatment and the documentation behaviour of physicians. SETTING: We implemented a controlled laboratory experiment with a healthcare framing in which international medical students in the Czech Republic treated patients in the role of hospital physicians. We varied the presence of time pressure and a documentation task. RESULTS: We observed worse treatment quality when individuals were faced with a combination of a documentation task and time pressure. In line with the concept of the speed-accuracy trade-off, we showed that quality changes are likely driven by less accuracy. Finally, we showed that while documentation quality was relatively high overall, time pressure significantly lowered the latter leading to a higher hypothetical profit loss for the hospital. CONCLUSIONS: Our results suggest that policy reforms aimed at increasing staffing and promoting novel technologies that facilitate physicians' treatment decisions and support their documentation work in the hospital sector might be promising means of improving the treatment quality and reducing inefficiencies potentially caused by documentation errors.
- Klíčová slova
- Laboratory experiment, Physician incentives, Time pressure, Work motivation,
- MeSH
- časové faktory MeSH
- dokumentace * normy MeSH
- kvalita zdravotní péče * MeSH
- lékaři * psychologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
The description and delineation of trematode species is a major ongoing task. Across the field there has been, and currently still is, great variation in the standard of this work and in the sophistication of the proposal of taxonomic hypotheses. Although most species are relatively unambiguously distinct from their congeners, many are either morphologically very similar, including the major and rapidly growing component of cryptic species, or are highly variable morphologically despite little to no molecular variation for standard DNA markers. Here we review challenges in species delineation in the context provided to us by the historical literature, and the use of morphological, geographical, host, and molecular data. We observe that there are potential challenges associated with all these information sources. As a result, we encourage careful proposal of taxonomic hypotheses with consideration for underlying species concepts and frank acknowledgement of weaknesses or conflict in the data. It seems clear that there is no single source of data that provides a wholly reliable answer to our taxonomic challenges but that nuanced consideration of information from multiple sources (the 'integrated approach') provides the best possibility of developing hypotheses that will stand the test of time.
- Klíčová slova
- cryptic species, hypotheses, species concept, synonymy, taxonomy,
- MeSH
- fylogeneze MeSH
- infekce červy třídy Trematoda parazitologie MeSH
- klasifikace * metody MeSH
- Trematoda * klasifikace genetika anatomie a histologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
We designed a minimalistic zinc(II)-binding peptide featuring the Cys2His2 zinc-finger motif. To this aim, several tens of thousands of (His/Cys)-Xn-(His/Cys) protein fragments (n=2-20) were first extracted from the 3D protein structures deposited in Protein Data Bank (PDB). Based on geometrical constraints positioning two Cys (C) and two His (H) side chains at the vertices of a tetrahedron, approximately 22 000 sequences of the (H/C)-Xi-(H/C)-Xj-(H/C)-Xk-(H/C) type, satisfying Nmetal-binding H=Nmetal-binding C=2, were processed. Several other criteria, such as the secondary structure content and predicted fold stability, were then used to select the best candidates. To prove the viability of the computational design experimentally, three peptides were synthesized and subjected to isothermal calorimetry (ITC) measurements to determine the binding constants with Zn2+, including the entropy and enthalpy terms. For the strongest Zn2+ ions binding peptide, P1, the dissociation constant was shown to be in the nanomolar range (KD=~220 nM; corresponding to ΔGbind=-9.1 kcal mol-1). In addition, ITC showed that the [P1 : Zn2+] complex forms in 1 : 1 stoichiometry and two protons are released upon binding, which suggests that the zinc coordination involves both cysteines. NMR experiments also indicated that the structure of the [P1 : Zn2+] complex might be quite similar to the computationally predicted one. In summary, our proof-of-principle study highlights the usefulness of our computational protocol for designing novel metal-binding peptides.
- Klíčová slova
- Computer design, Isothermal calorimetry, Metal-binding peptide, NMR, QM modeling, Zinc(II),
- MeSH
- molekulární modely MeSH
- peptidy * chemie metabolismus chemická syntéza MeSH
- sekvence aminokyselin MeSH
- termodynamika MeSH
- vazba proteinů MeSH
- zinek * chemie metabolismus MeSH
- zinkové prsty MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- peptidy * MeSH
- zinek * MeSH
Mutations in CACNA1C, the gene encoding Cav1.2 voltage-gated calcium channels, are associated with a spectrum of disorders, including Timothy syndrome and other neurodevelopmental and cardiac conditions. In this study, we report a child with a de novo heterozygous missense variant (c.1973T > C; L658P) in CACNA1C, presenting with refractory epilepsy, global developmental delay, hypotonia, and multiple systemic abnormalities, but without overt cardiac dysfunction. Electrophysiological analysis of the recombinant Cav1.2 L658P variant revealed profound gating alterations, most notably a significant hyperpolarizing shift in the voltage dependence of activation and inactivation. Additionally, molecular modeling suggested that the L658P mutation disrupts interactions within the IIS5 transmembrane segment, reducing the energy barrier for state transitions and facilitating channel opening at more negative voltages. These findings establish L658P as a pathogenic CACNA1C variant primarily associated with severe neurological dysfunction and expands the phenotypic spectrum of CACNA1C-related disorders.
- Klíčová slova
- CACNA1C, Calcium channel, Cav1.2, Channelopathies, Electrophysiology, L658P,
- MeSH
- dítě MeSH
- gating iontového kanálu MeSH
- HEK293 buňky MeSH
- lidé MeSH
- missense mutace genetika MeSH
- molekulární modely MeSH
- mutace * genetika MeSH
- neurovývojové poruchy * genetika patofyziologie MeSH
- sekvence aminokyselin MeSH
- vápníkové kanály - typ L * genetika chemie metabolismus MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- CACNA1C protein, human MeSH Prohlížeč
- vápníkové kanály - typ L * MeSH
Taxonomy provides a general foundation for research on insects. Using stored product pest (SPP) arthropods as a model group, this article overviews the historical impacts of taxonomy on applied entomology. The article surveys the dynamics of historical descriptions of new species in various SPP taxa; the majority of all species (90%) were described prior to 1925, while the key pests were described prior to 1866. The review shows that process of describing new SPP species is not random but is influenced by following factors: (i) larger species tend to be described earlier than smaller and SPP moths and beetles are described earlier than psocids and mites; (ii) key economic pests are on average described earlier than less significant ones. Considering a species name as a "password" to unique information resources, this review also assesses the historical number of synonymous or duplicate names of SPP species. Pests belonging to some higher taxa Lepidoptera and Coleoptera has accumulated more scientific synonyms than those others belonging to Psocoptera and Acari. Number of synonyms positively correlated with the economic importance of SPP species. The review summarized semantic origin of SPP names showing minor proportion of names (17.6%) are toponyms (geography) or eponyms (people), while the majority (82.4%) fall into other categories (descriptive, etc.). It is concluded that awareness of taxonomic advances, including changes to species and higher taxa names, should be effectively communicated to pest control practitioners and applied entomology students, and specifically addressed in relevant textbooks, web media, and databases.
- Klíčová slova
- Acari, insects, stored commodities, synonyms, taxonomy,
- MeSH
- entomologie * dějiny MeSH
- hmyz * klasifikace MeSH
- klasifikace * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Micropterigidae is regarded as the sister group of all the other Lepidoptera, providing important insights into the evolution of Lepidoptera. However, the gene and protein profiles of silk from Micropterigidae have not yet been identified. In this study, we investigate the components of silk cocoons of the micropterigid species Neomicropteryx cornuta. Here we show that the protein fibroin heavy chain (FibH) is absent in the silk of N. cornuta and that the putative homolog of fibroin light chain (FibL) is also absent or severely altered. This is confirmed by transcriptome and genome analyses of the conserved regions in this species. The examination of the synteny around the fibH genes in several Lepidoptera and Trichoptera species shows that the genomic region containing this gene is absent in another micropterigid species, Micropterix aruncella. In contrast, we found putative orthologs of fibH and fibL in the representative transcripts of another distinct clade, Eriocraniidae. This study shows that the loss of FibH and the loss or severe divergence of FibL occurrs specifically in the family Micropterigidae and reveals dynamic evolutionary changes in silk composition during the early evolution of Lepidoptera. It also shows that silk proteins without FibH can form a solid cocoon.
- MeSH
- fibroiny * genetika chemie metabolismus MeSH
- fylogeneze MeSH
- hedvábí * genetika chemie metabolismus MeSH
- hmyzí proteiny * genetika metabolismus MeSH
- Lepidoptera * genetika metabolismus MeSH
- molekulární evoluce MeSH
- můry * genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fibroiny * MeSH
- hedvábí * MeSH
- hmyzí proteiny * MeSH
