Self-processing module
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The self-processing module (SPM) is an internal segment of the FrpC protein (P415-F591) secreted by the pathogenic Gram-negative bacterium Neisseria meningitidis during meningococcal infection of human upper respiratory tract. SPM mediates 'protein trans-splicing', a unique natural mechanism for editing of proteins, which involves a calcium-dependent autocatalytic cleavage of the peptide bond between D414 and P415 and covalent linkage of the cleaved fragment through its carboxy-terminal group of D414 to [Formula: see text]-amino group of lysine residue within a neighboring polypeptide chain. We present an NMR resonance assignment of the calcium-free SPM, which displays characteristic features of intrinsically disordered proteins. Non-uniformly sampled 5D HN(CA)CONH, 4D HCBCACON, and HCBCANCO spectra were recorded to resolve poorly dispersed resonance frequencies of the disordered protein and 91 % of SPM residues were unambiguously assigned. Analysis of the chemical shifts revealed that two regions of the intrinsically disordered SPM (A95-S101 and R120-I127) have a tendency to form a helical structure, whereas the residues P1-D7 and G36-A40 have the propensity to adopt a [Formula: see text]-structure.
- MeSH
- bakteriální proteiny chemie MeSH
- membránové proteiny chemie MeSH
- Neisseria meningitidis metabolismus MeSH
- nukleární magnetická rezonance biomolekulární * MeSH
- sekundární struktura proteinů MeSH
- vnitřně neuspořádané proteiny chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The posttranslational Ca2+-dependent "clip-and-link" activity of large repeat-in-toxin (RTX) proteins starts by Ca2+-dependent structural rearrangement of a highly conserved self-processing module (SPM). Subsequently, an internal aspartate-proline (Asp-Pro) peptide bond at the N-terminal end of SPM breaks, and the liberated C-terminal aspartyl residue can react with a free ε-amino group of an adjacent lysine residue to form a new isopeptide bond. Here, we report a solution structure of the calcium-loaded SPM (Ca-SPM) derived from the FrpC protein of Neisseria meningitidis The Ca-SPM structure defines a unique protein architecture and provides structural insight into the autocatalytic cleavage of the Asp-Pro peptide bond through a "twisted-amide" activation. Furthermore, in-frame deletion of the SPM domain from the ApxIVA protein of Actinobacillus pleuropneumoniae attenuated the virulence of this porcine pathogen in a pig respiratory challenge model. We hypothesize that the Ca2+-dependent clip-and-link activity represents an unconventional strategy for Gram-negative pathogens to adhere to the host target cell surface.IMPORTANCE The Ca2+-dependent clip-and-link activity of large repeat-in-toxin (RTX) proteins is an exceptional posttranslational process in which an internal domain called a self-processing module (SPM) mediates Ca2+-dependent processing of a highly specific aspartate-proline (Asp-Pro) peptide bond and covalent linkage of the released aspartyl to an adjacent lysine residue through an isopeptide bond. Here, we report the solution structures of the Ca2+-loaded SPM (Ca-SPM) defining the mechanism of the autocatalytic cleavage of the Asp414-Pro415 peptide bond of the Neisseria meningitidis FrpC exoprotein. Moreover, deletion of the SPM domain in the ApxIVA protein, the FrpC homolog of Actinobacillus pleuropneumoniae, resulted in attenuation of virulence of the bacterium in a pig infection model, indicating that the Ca2+-dependent clip-and-link activity plays a role in the virulence of Gram-negative pathogens.
- MeSH
- Actinobacillus pleuropneumoniae chemie patogenita MeSH
- bakteriální proteiny chemie genetika MeSH
- bakteriální toxiny chemie MeSH
- infekce bakteriemi rodu Actinobacillus veterinární MeSH
- membránové proteiny chemie MeSH
- Neisseria meningitidis chemie MeSH
- posttranslační úpravy proteinů * MeSH
- prasata MeSH
- vápník metabolismus MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
iv, 27 stran
- MeSH
- Betacoronavirus MeSH
- COVID-19 prevence a kontrola MeSH
- epidemický výskyt choroby MeSH
- kontrola infekce MeSH
- koronavirové infekce prevence a kontrola MeSH
- pandemie MeSH
- poskytování zdravotní péče MeSH
- zdravotnické služby - potřeby a požadavky MeSH
- Konspekt
- Veřejné zdraví a hygiena
- NLK Obory
- veřejné zdravotnictví
- hygiena
- NLK Publikační typ
- publikace WHO
Microtubules composed of tubulin heterodimers represent highly dynamic structures. These structures are essential for basic cellular functions, such as cell division. Microtubules can grow or shrink in response to environmental signals, principally chemical cues. Here, we provide an alternative-physical-strategy to modulate tubulin properties and its self-assembly process. The conformation and electrical properties of tubulin subunits are modulated by nanosecond electropulse signals. The formed structures of electrically treated tubulin are tightly linked to the degree of conformational and electrical properties changes induced by nanosecond electropulses. This strategy opens a new way for controlling the self-assembly process in biomolecules as well as in bioinspired materials.
S rozvojem a zdokonalováním technologie dialyzační léčby a lékařské péče se sice zvyšuje věk pacientů léčených dialýzou a posunuje jejich kvalitu života (QoL) na vyšší úroveň, ale přesto stále ne dostatečně blízko úrovni zdravé populace. Plošně jsme zhodnotili kvalitu života (QoL) peritoneálně dialyzovaných (PD) pacientů České republiky (n = 95; muži/ženy = 49/46, průměrný věk 56,9 ± 12,8; délka léčby PD od 0,25 do 224 měsíců, tj. průměrně 29,1 ± 32,4 měsíců). Kvalita života pacientů s konečným stadiem selhání ledvin (ESRD) léčených peritoneální dialýzou (PD) je významně snížena ve srovnání s běžnou populací, zejména v oblasti fyzického zdraví (p < 0,001). Vyšší průměrné hodnocení bylo u domény „životní podmínky“ (p < 0,001) a „DIS modul“ (p = 0,035). Kromě kvalitní zdravotní péče je vhodné do léčebného plánu zařadit i nemedicínské intervence, které by podpořily zlepšení kvality života zejména v doméně fyzických funkcí a podpořit tak u stárnoucí populace dialyzovaných pacientů zachování soběstačnosti a sebeobsluhy. Jednou z možností je aktivace pacienta prostřednictvím pravidelných cvičebních programů, v doprovodu s psychosociální intervencí a tréninkem motivace. Pohybová složka by měla být vnímána a aplikována jako prostředek pro zkvalitnění léčby, který je nízkonákladový, ve výsledku efektivní a akceptovatelný pro pacienta.
With the development of dialysing and treating process the life expectancy is extended and the patient’s need of an improved quality of life (QoL) arises as well, but still not enough close to the level of a healthy population. We performed an area assessment of quality of life (QoL) in patients on peritoneal dialysis (PD) in the Czech Republic (n = 95; male/female = 49/46, average age 56.9 ± 12.8; total time on PD from 0.25 to 224 months; average time of PD 29.1 ± 32.4 months). Rating in QoL of patients with end stage renal disease (ESRD) treated with peritoneal dialysis (PD) is significantly decreased as compared with average values of Czech standards, especially in the domain “physical health” (p < 0.001). Significantly higher average rating was found in the domain of “environment” (p < 0.001) and “DIS module” (p = 0.035). In addition to quality of the health care nonmedical interventions that support the improvement of QoL, especially in the domain of physical health, should be also included in the treatment plan, and thus support the ageing population of dialysis patients maintaining self-sufficiency and self-care. One of the possibilities is exercise intervention, which should be seen as the way to improve the treatment. It should be seen as cost effective, efficient and acceptable for patients.
Auxin is unique among plant hormones due to its directional transport that is mediated by the polarly distributed PIN auxin transporters at the plasma membrane. The canalization hypothesis proposes that the auxin feedback on its polar flow is a crucial, plant-specific mechanism mediating multiple self-organizing developmental processes. Here, we used the auxin effect on the PIN polar localization in Arabidopsis thaliana roots as a proxy for the auxin feedback on the PIN polarity during canalization. We performed microarray experiments to find regulators of this process that act downstream of auxin. We identified genes that were transcriptionally regulated by auxin in an AXR3/IAA17- and ARF7/ARF19-dependent manner. Besides the known components of the PIN polarity, such as PID and PIP5K kinases, a number of potential new regulators were detected, among which the WRKY23 transcription factor, which was characterized in more detail. Gain- and loss-of-function mutants confirmed a role for WRKY23 in mediating the auxin effect on the PIN polarity. Accordingly, processes requiring auxin-mediated PIN polarity rearrangements, such as vascular tissue development during leaf venation, showed a higher WRKY23 expression and required the WRKY23 activity. Our results provide initial insights into the auxin transcriptional network acting upstream of PIN polarization and, potentially, canalization-mediated plant development.
- MeSH
- Arabidopsis genetika růst a vývoj MeSH
- geneticky modifikované rostliny MeSH
- genové regulační sítě * účinky léků MeSH
- kořeny rostlin účinky léků genetika růst a vývoj metabolismus MeSH
- kyseliny indoloctové metabolismus farmakologie MeSH
- membránové transportní proteiny genetika metabolismus MeSH
- mikročipová analýza MeSH
- polarita buněk * genetika MeSH
- proteiny huseníčku genetika metabolismus fyziologie MeSH
- regulace genové exprese u rostlin účinky léků MeSH
- stanovení celkové genové exprese MeSH
- transkripční faktory fyziologie MeSH
- zpětná vazba fyziologická účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aging of human populations, including those in Europe, is an indisputable fact. The challenge for the future is not simply prolonging human life at any cost or by any means but rather extending self-sufficiency and quality of life. Even in the most advanced societies, the eternal questions remain. Who will take care of the older generations? Will adult children's own circumstances be sufficient to support family members as they age? For a range of complex reasons, including socioeconomic conditions, adult children are often unable or unwilling to assume responsibility for the care of older family members. For this reason, it is imperative that aging adults maintain their independence and self-care for as long as possible. Movement is an important part of self-sufficiency. Moreover, movement has been shown to improve patients' clinical status. At a time when the coronavirus pandemic is disrupting the world, older people are among the most vulnerable. Our paper explores current knowledge and offers insights into the significant benefits of movement for the elderly, including improved immunity. We discuss the biochemical processes of aging and the counteractive effects of exercise and endogenous substances, such as vitamin D.
- MeSH
- COVID-19 imunologie patologie virologie MeSH
- cvičení * MeSH
- lidé MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- obezita patologie MeSH
- psychický stres MeSH
- sarkopenie patologie MeSH
- SARS-CoV-2 izolace a purifikace MeSH
- stárnutí * MeSH
- vitamin D aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Using the remarkable overlap between brain circuits affected in Parkinson's disease (PD) and those underlying motor sequence learning, we may improve the effectiveness of motor rehabilitation interventions by identifying motor learning facilitators in PD. For instance, additional sensory stimulation and task cueing enhanced motor learning in people with PD, whereas exercising using musical rhythms or console computer games improved gait and balance, and reduced some motor symptoms, in addition to increasing task enjoyment. Yet, despite these advances, important knowledge gaps remain. Most studies investigating motor learning in PD used laboratory-specific tasks and equipment, with little resemblance to real life situations. Thus, it is unknown whether similar results could be achieved in more ecological setups and whether individual's task engagement could further improve motor learning capacity. Moreover, the role of social interaction in motor skill learning process has not yet been investigated in PD and the role of mind-set and self-regulatory mechanisms have been sporadically examined. Here, we review evidence suggesting that these psychosocial factors may be important modulators of motor learning in PD. We propose their incorporation in future research, given that it could lead to development of improved non-pharmacological interventions aimed to preserve or restore motor function in PD.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. Research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoceptive processing. AIMS: In this preregistered study, we investigated whether psilocybin microdoses alter self-reported interoceptive awareness and whether repeated microdosing over 3 weeks modulates emotion processing and reduces symptoms of anxiety and depression. METHODS: We used a double-blind, placebo-controlled, within-subject crossover design. Participants completed the Multidimensional Assessment of Interoceptive Awareness Questionnaire 11⁄2 h after self-administering their second dose (or placebo), and the emotional go/no-go task and the shortened Depression Anxiety Stress Scale 11⁄2 h after self-administering their seventh dose. RESULTS: Our confirmatory analyses revealed that psilocybin microdosing did not affect emotion processing or symptoms of anxiety and depression compared with placebo. Our exploratory analyses revealed that psilocybin microdosing did not affect self-reported interoceptive awareness, that symptoms of depression and stress were significantly reduced in the first block compared with baseline, that participants broke blind in the second block and that there was no effect of expectations. Further research in a substance-naïve population with clinical range anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing.
- MeSH
- deprese farmakoterapie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- emoce účinky léků MeSH
- halucinogeny aplikace a dávkování farmakologie MeSH
- klinické křížové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- průzkumy a dotazníky MeSH
- psilocybin aplikace a dávkování farmakologie MeSH
- úzkost farmakoterapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
