substrate quality
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Although multiprotein membrane complexes play crucial roles in bacterial physiology and virulence, the mechanisms governing their quality control remain incompletely understood. In particular, it is not known how unincorporated, orphan components of protein complexes are recognised and eliminated from membranes. Rhomboids, the most widespread and largest superfamily of intramembrane proteases, are known to play key roles in eukaryotes. In contrast, the function of prokaryotic rhomboids has remained enigmatic. Here, we show that the Shigella sonnei rhomboid proteases GlpG and the newly identified Rhom7 are involved in membrane protein quality control by specifically targeting components of respiratory complexes, with the metastable transmembrane domains (TMDs) of rhomboid substrates protected when they are incorporated into a functional complex. Initial cleavage by GlpG or Rhom7 allows subsequent degradation of the orphan substrate. Given the occurrence of this strategy in an evolutionary ancient organism and the presence of rhomboids in all domains of life, it is likely that this form of quality control also mediates critical events in eukaryotes and protects cells from the damaging effects of orphan proteins.
- MeSH
- bakteriální proteiny chemie metabolismus MeSH
- endopeptidasy chemie metabolismus MeSH
- membránové proteiny metabolismus MeSH
- proteinové domény MeSH
- proteolýza MeSH
- Shigella sonnei enzymologie metabolismus MeSH
- substrátová specifita MeSH
- transport elektronů MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Larger species tend to feed on abundant resources, which nonetheless have lower quality or degradability, the so-called Jarman-Bell principle. The "eat more" hypothesis posits that larger animals compensate for lower quality diets through higher consumption rates. If so, evolutionary shifts in metabolic scaling should affect the scope for this compensation, but whether this has happened is unknown. Here, we investigated this issue using termites, major tropical detritivores that feed along a humification gradient ranging from dead plant tissue to mineral soil. Metabolic scaling is shallower in termites with pounding mandibles adapted to soil-like substrates than in termites with grinding mandibles adapted to fibrous plant tissue. Accordingly, we predicted that only larger species of the former group should have more humified, lower quality diets, given their higher scope to compensate for such a diet. Using literature data on 65 termite species, we show that diet humification does increase with body size in termites with pounding mandibles, but is weakly related to size in termites with grinding mandibles. Our findings suggest that evolution of metabolic scaling may shape the strength of the Jarman-Bell principle.
- MeSH
- biologická evoluce * MeSH
- dieta * MeSH
- Isoptera genetika metabolismus MeSH
- mandibula MeSH
- velikost těla * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Delayed enhancement magnetic resonance imaging is known for its ability to identify scarred myocardial tissue. This case report describes the use of MR imaging to define the location and transmural extent of infarcted tissue in a 45-year-old woman with an anomalous right coronary artery and hemodynamically unstable ventricular tachycardia. By demonstrating a predominantly epicardial infarct, MR imaging indicated that the pericardial approach was necessary for successful substrate-based ventricular tachycardia ablation.
- MeSH
- anomálie koronárních cév diagnóza komplikace MeSH
- elektrofyziologické techniky kardiologické metody MeSH
- financování organizované MeSH
- katetrizační ablace metody MeSH
- komorová tachykardie diagnóza etiologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- následné studie MeSH
- perikard patologie MeSH
- vylepšení obrazu MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The formation of glycoconjugates depends on nucleotide sugars, which serve as donor substrates for glycosyltransferases in the lumen of Golgi vesicles and the endoplasmic reticulum (ER). Import of nucleotide sugars from the cytosol is an important prerequisite for these reactions and is mediated by nucleotide sugar transporters. Here, we report the identification of REPRESSOR OF CYTOKININ DEFICIENCY 1 (ROCK1, At5g65000) as an ER-localized facilitator of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) transport in Arabidopsis thaliana. Mutant alleles of ROCK1 suppress phenotypes inferred by a reduced concentration of the plant hormone cytokinin. This suppression is caused by the loss of activity of cytokinin-degrading enzymes, cytokinin oxidases/dehydrogenases (CKXs). Cytokinin plays an essential role in regulating shoot apical meristem (SAM) activity and shoot architecture. We show that rock1 enhances SAM activity and organ formation rate, demonstrating an important role of ROCK1 in regulating the cytokinin signal in the meristematic cells through modulating activity of CKX proteins. Intriguingly, genetic and molecular analysis indicated that N-glycosylation of CKX1 was not affected by the lack of ROCK1-mediated supply of UDP-GlcNAc. In contrast, we show that CKX1 stability is regulated in a proteasome-dependent manner and that ROCK1 regulates the CKX1 level. The increased unfolded protein response in rock1 plants and suppression of phenotypes caused by the defective brassinosteroid receptor bri1-9 strongly suggest that the ROCK1 activity is an important part of the ER quality control system, which determines the fate of aberrant proteins in the secretory pathway.
- MeSH
- Arabidopsis metabolismus ultrastruktura MeSH
- biologický transport MeSH
- cytokininy metabolismus MeSH
- endoplazmatické retikulum metabolismus MeSH
- fenotyp MeSH
- meristém metabolismus ultrastruktura MeSH
- proteiny huseníčku metabolismus MeSH
- transportní proteiny metabolismus MeSH
- uridindifosfát-N-acetylgalaktosamin metabolismus MeSH
- uridindifosfát-N-acetylglukosamin metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Magnesium homeostasis is essential for life and depends on magnesium transporters, whose activity and ion selectivity need to be tightly controlled. Rhomboid intramembrane proteases pervade the prokaryotic kingdom, but their functions are largely elusive. Using proteomics, we find that Bacillus subtilis rhomboid protease YqgP interacts with the membrane-bound ATP-dependent processive metalloprotease FtsH and cleaves MgtE, the major high-affinity magnesium transporter in B. subtilis. MgtE cleavage by YqgP is potentiated in conditions of low magnesium and high manganese or zinc, thereby protecting B. subtilis from Mn2+ /Zn2+ toxicity. The N-terminal cytosolic domain of YqgP binds Mn2+ and Zn2+ ions and facilitates MgtE cleavage. Independently of its intrinsic protease activity, YqgP acts as a substrate adaptor for FtsH, a function that is necessary for degradation of MgtE. YqgP thus unites protease and pseudoprotease function, hinting at the evolutionary origin of rhomboid pseudoproteases such as Derlins that are intimately involved in eukaryotic ER-associated degradation (ERAD). Conceptually, the YqgP-FtsH system we describe here is analogous to a primordial form of "ERAD" in bacteria and exemplifies an ancestral function of rhomboid-superfamily proteins.
- MeSH
- ATPázy spojené s různými buněčnými aktivitami metabolismus MeSH
- Bacillus subtilis růst a vývoj metabolismus MeSH
- bakteriální proteiny metabolismus MeSH
- endopeptidasy metabolismus MeSH
- membránové proteiny metabolismus MeSH
- proteomika metody MeSH
- regulace genové exprese u bakterií MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering the pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including aetiology-specific aspects and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before the expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.
- MeSH
- akční potenciály MeSH
- kardiologie * normy MeSH
- komorová tachykardie * patofyziologie chirurgie diagnóza MeSH
- konsensus MeSH
- lidé MeSH
- radiochirurgie * škodlivé účinky normy metody MeSH
- rizikové faktory MeSH
- výběr pacientů * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Evropa MeSH
Pozitivní vliv pohybu na délku i kvalitu života je znám už od starověku. Po dlouhou dobu však nebylo toto poznání možno podložit moderními exaktními medicínskými argumenty. Bylo zcela zřejmé, že vývoj jedinců se sedavým způsobem života je odlišný od vývoje jedinců fyzicky aktivních. Až po roce 2000 v souvislosti s odhalením spojitosti mezi interleukinem 6 a pohybem svalu započalo intenzivní studium této problematiky. V současné době je těchto svalových působků (myokinů) známo přibližně šest set. Podobně jsou nacházeny u tkáně tukové (adipokiny) a kostní (osteokiny). Svalová tkáň tak s ostatními souvisí nejen mechanisticky, ale tvoří s nimi humorální soulad. Tento jev má význam v patofyziologii chronického, tzv. nízkoprahového zánětu, při úbytku svaloviny, vzniku a rozvoji chronických onemocnění, na něž umírá zhruba 75 % populace. Řešení problému výrazně zatěžuje nákladovou efektivitu zdravotnictví i státní ekonomiku. Daným poznatkům je nutné přizpůsobit terapeutická doporučení a celou strategii zdravotnické péče. Doposud nejsou známy vhodné léky, které by problematiku úbytku svaloviny řešily. Z tohoto důvodu je o to více nutno dbát doporučení pohybového a dietního režimu. Na základě poznatků jsme pro naše pacienty sestavili komplexní diagnostický a léčebný program, který byl prezentován na světovém kongresu IOF‐ESCEO 2020 v Barceloně i na celostátním kongresu v Bratislavě a který představujeme včetně předběžných výsledků.
The positive effect of movement on the length and quality of life is known since the prehistoric times. For a long time, it was not possible to support this claim with modern exact medical arguments. It was quite evident that the development of individuals with a sedentary lifestyle is different from the development of physically active ones. Only after 2000 when the connection between interleukin 6 and muscle movement was discovered, intensive study of this problem was initiated. Currently, approximately 600 of these muscle substrates (myokines) are known. Similarly, they have been discovered in adipose (adipokines) and skeletal (osteokines) tissues. So muscle tissue is related to other tissues not only mechanistically, but it also creates a humoral homeostasis. This phenomenon is significant in pathophysiology of a low‐grade chronic inflammation, during muscle atrophy, the origin and the development of chronic diseases, deadly to approximately 75% of the population. Solving the problem markedly burdens the cost efficiency of health care and state economics. Current knowledge needs to influence the therapeutical recommendations and the whole strategy of health care. No appropriate drugs that would solve the problem of muscle atrophy currently exist. For this reason, it is pertinent to rely even more on recommendations of the movement and diet regimen. Based on the accumulated knowledge, we created a complex diagnostic and treatment programme for our patients that was presented on the world IOF‐ESCEO 2020 congress in Barcelona and on the statewide congress in Bratislava, including preliminary results.
Cell function is highly dependent on membrane structure, organization, and fluidity. Therefore, methods to probe the biophysical properties of biological membranes are required. Determination of generalized polarization (GP) values using Laurdan in fluorescence microscopy studies is one of the most widely-used methods to investigate changes in membrane fluidity in vitro and in vivo. In the last couple of decades, there has been a major increase in the number of studies using Laurdan GP, where several different methodological approaches are used. Such differences interfere with data interpretation inasmuch as it is difficult to validate if Laurdan GP variations actually reflect changes in membrane organization or arise from biased experimental approaches. To address this, we evaluated the influence of different methodological details of experimental data acquisition and analysis on Laurdan GP. Our results showed that absolute GP values are highly dependent on several of the parameters analyzed, showing that incorrect data can result from technical and methodological inconsistencies. Considering these differences, we further analyzed the impact of cell variability on GP determination, focusing on basic cell culture conditions, such as cell confluency, number of passages and media composition. Our results show that GP values can report alterations in the biophysical properties of cell membranes caused by cellular adaptation to the culture conditions. In summary, this study provides thorough analysis of the factors that can lead to Laurdan GP variability and suggests approaches to improve data quality, which would generate more precise interpretation and comparison within individual studies and among the literature on Laurdan GP.
Fluorescence emission spectra of yeast cell suspensions stained with calcofluor have recently been identified as promising markers of variations in the quality of yeast cell wall. It is shown in this paper how the raw fluorescence spectra of calcofluor can be transformed to reliable spectral signatures of cell wall quality, which are independent of actual dye-to-cell concentrations of examined cell suspensions. Moreover, the presented approach makes it possible to assess basis fluorescence spectra that allows for the spectral unmixing of raw fluorescence spectra in terms of respective fluorescence contributions of calcofluor solvated in the suspension medium and bound to yeast cell walls.
- MeSH
- barvení a značení MeSH
- benzensulfonáty metabolismus MeSH
- buněčná stěna chemie metabolismus MeSH
- fluorescenční barviva metabolismus MeSH
- fluorescenční spektrometrie MeSH
- glukosa farmakologie MeSH
- Saccharomyces cerevisiae chemie cytologie účinky léků metabolismus MeSH
- suspenze MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
