Distribution pathways
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- MeSH
- biologické modely MeSH
- buněčná imunita MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- ligandy MeSH
- mezibuněčné signální peptidy a proteiny chemie imunologie metabolismus MeSH
- přirozená imunita MeSH
- receptory cytokinové chemie imunologie metabolismus MeSH
- signální transdukce MeSH
- transkripční faktory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
The ubiquitin-proteasome pathway fulfills major biological functions, but its physiologic tissue distribution and the interrelationship between pathway component activities and ubiquitin pools are unknown. Therefore, we analyzed free and conjugated ubiquitin, ubiquitin-protein ligation rates (UbPL) and chymotryptic- and tryptic-like proteasome peptidase activities in porcine skeletal muscle, heart, lung, liver, spleen and kidney (n=5 each). There were considerable differences between tissues (p<0.05 for all parameters). Lung and spleen showed high levels of free and conjugated ubiquitin and high UbPL. Proteasome activities were highest in kidney and heart. There were linear relationships between tryptic-like and chymotryptic-like proteasome peptidase activities (r2 = 0.624, p<0.001) and between free and conjugated ubiquitin tissue levels (r2 = 0.623, p<0.001). Tissue levels of free and conjugated ubiquitin correlated linear with UbPL (p<0.005), but they were not correlated with proteasome peptidase activities. The results suggest that tissue ubiquitin pools are tightly regulated and indicate a constant proportion of conjugated ubiquitin. They further support the hypothesis that ubiquitin-protein ligase systems, and probably deubiquitylating enzymes, are key regulators of ubiquitin homeostasis. The detected differences are suggestive of tissue-specific roles of ubiquitin-proteasome pathway components. Besides the known importance of the ubiquitin proteasome pathway in heart, kidney and the immune system, the results suggest the lung as another organ in which ubiquitin proteasome pathway components may also significantly contribute to disease processes.
- MeSH
- finanční podpora výzkumu jako téma MeSH
- interpretace statistických dat MeSH
- komplexy ubikvitinligas biosyntéza chemie MeSH
- prasata fyziologie MeSH
- tkáňová distribuce fyziologie účinky léků MeSH
- tkáňové extrakty chemie izolace a purifikace MeSH
- ubikvitin konjugující enzymy biosyntéza chemie MeSH
- ubikvitin chemie MeSH
- western blotting metody využití MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
Cytokinins are a class of phytohormones, signalling molecules specific to plants. They act as regulators of diverse physiological processes in complex signalling pathways. It is necessary for plants to continuously regulate cytokinin distribution among different organs, tissues, cells, and compartments. Such regulatory mechanisms include cytokinin biosynthesis, metabolic conversions and degradation, as well as cytokinin membrane transport. In our review, we aim to provide a thorough picture of the latter. We begin by summarizing cytokinin structures and physicochemical properties. Then, we revise the elementary thermodynamic and kinetic aspects of cytokinin membrane transport. Next, we review which membrane-bound carrier proteins and protein families recognize cytokinins as their substrates. Namely, we discuss the families of "equilibrative nucleoside transporters" and "purine permeases", which translocate diverse purine-related compounds, and proteins AtPUP14, AtABCG14, AtAZG1, and AtAZG2, which are specific to cytokinins. We also address long-distance cytokinin transport. Putting all these pieces together, we finally discuss cytokinin distribution as a net result of these processes, diverse in their physicochemical nature but acting together to promote plant fitness.
- MeSH
- Arabidopsis metabolismus MeSH
- biologický transport MeSH
- buněčná membrána metabolismus MeSH
- cytokininy metabolismus MeSH
- homeostáza MeSH
- hydrofobní a hydrofilní interakce MeSH
- kinetika MeSH
- kořeny rostlin metabolismus MeSH
- membránové transportní proteiny metabolismus MeSH
- proteiny huseníčku genetika MeSH
- regulace genové exprese u rostlin MeSH
- regulátory růstu rostlin metabolismus MeSH
- signální transdukce fyziologie MeSH
- termodynamika MeSH
- výhonky rostlin metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The sarcolemmal Ca2+ efflux pathways, Na+-Ca2+-exchanger (NCX) and Ca2+-ATPase (PMCA), play a crucial role in the regulation of intracellular Ca2+ load and Ca2+ transient in cardiomyocytes. The distribution of these pathways between the t-tubular and surface membrane of ventricular cardiomyocytes varies between species and is not clear in human. Moreover, several studies suggest that this distribution changes during the development and heart diseases. However, the consequences of NCX and PMCA redistribution in human ventricular cardiomyocytes have not yet been elucidated. In this study, we aimed to address this point by using a mathematical model of the human ventricular myocyte incorporating t-tubules, dyadic spaces, and subsarcolemmal spaces. Effects of various combinations of t-tubular fractions of NCX and PMCA were explored, using values between 0.2 and 1 as reported in animal experiments under normal and pathological conditions. Small variations in the action potential duration (≤ 2%), but significant changes in the peak value of cytosolic Ca2+ transient (up to 17%) were observed at stimulation frequencies corresponding to the human heart rate at rest and during activity. The analysis of model results revealed that the changes in Ca2+ transient induced by redistribution of NCX and PMCA were mainly caused by alterations in Ca2+ concentrations in the subsarcolemmal spaces and cytosol during the diastolic phase of the stimulation cycle. The results suggest that redistribution of both transporters between the t-tubular and surface membranes contributes to changes in contractility in human ventricular cardiomyocytes during their development and heart disease and may promote arrhythmogenesis.
- MeSH
- akční potenciály MeSH
- biologické modely MeSH
- buněčná membrána metabolismus MeSH
- kardiomyocyty * metabolismus MeSH
- lidé MeSH
- modely kardiovaskulární MeSH
- pumpa pro výměnu sodíku a vápníku * metabolismus MeSH
- sarkolema * metabolismus MeSH
- srdeční komory * metabolismus MeSH
- vápník * metabolismus MeSH
- vápníková signalizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Acylový zvyšok mastnej kyseliny je hlavnou štrukturálnou zložkou prakticky všetkých lipidov, čím predstavuje jednu zo základných funkčných skupín týchto molekúl. Mastné kyseliny (FAs) sa vzájomne líšia dĺžkou reťazca, počtom násobných väzieb a pozíciou násobnej väzby v reťazci. Podľa počtu násobných väzieb v polynenasýtenej FA (PUFAs) možno rozlíšiť mononenasýtené FAs (MUFAs) a polynenasýtené FAs (PUFAs). V živých bunkách predstavujú PUFAs dominantný substrát pre tvorbu biologicky aktívnych zlúčenín – oktadekanoidov, eikosanoidov a dokosanoidov – klasifikovaných ako oxylipíny alebo PUFAnoidy. Predložená prehľadová práca sa sústreďuje len na skupinu PUFAnoidov, ktorých biologické účinky zahŕňajú “pozitívny efekt” pre bunku. Skupina omega-3 PUFAnoidov pozostáva z lipoxínov, resolvínov a protektínov. Všetky tieto biologicky aktívne lipidy sú prednostne formované metabolickou cestou prostredníctvom LOX. Predstavujú časť bunkových mechanizmov, ktoré prispievajú k odstráneniu zápalových buniek a k obnove integrity tkanív. Nový prístup k protizápalovým modelom je orientovaný na duálnu COX/LOX-inhibíciu a stimuláciu tvorby ochranných eikosanoidov a dokosanoidov, a na ich dôležitý terapeutický potenciál pri riadení molekulárnych mechanizmov v rámci chronických zápalových procesov.
The fatty acyl structure represents the major lipid building block of practically all lipids and therefore is one of the most fundamental categories of these molecules. Fatty acids (FAs) differ particularly in their chain length, number of double bonds and position of the bonds in the chain. The number of double bonds in the unsaturated molecule of FA distinguishes monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs). In the living cell PUFAs represent the dominant substrates for the formation of biologically active compounds – octadecanoids, eicosanoids and docosanoids – classified as oxylipins or as PUFAnoids. The present review focuses only on the groups of PUFAnoids which biological activities comprise a “positive effect” for the cell. This group of omega-3 PUFAnoids consists of lipoxins, resolvins and protectins. All these biologically active lipids are formed mainly in the LOX-pathway. They are part of the cell mechanisms that contribute to the removal of inflammatory cells and restoration of tissue integrity. A new approach to an optimal anti-inflammatory model shows orientation to the dual COX/LOX-inhibition and the stimulation of the protective eicosanoids and docosanoids formation and its considerable therapeutic potential in managing of molecular mechanisms of chronic inflammatory processes.
- Klíčová slova
- resolvins, protectins,
- MeSH
- aktivní transport MeSH
- chronická nemoc farmakoterapie MeSH
- farmakokinetika MeSH
- ikosanoidy * terapeutické užití MeSH
- inhibitory cyklooxygenasy 2 metabolismus MeSH
- inhibitory lipoxygenas metabolismus MeSH
- lidé MeSH
- lipoxiny * metabolismus MeSH
- membránové lipidy MeSH
- omega-3 mastné kyseliny metabolismus MeSH
- zánět * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
PURPOSE: Using the International Standard Classification of Education (ISCED), we examined the educational and vocational pathways of two comparable, parental cohorts: childhood cancer survivors (CCS) and their siblings. Both cohorts had previously entered parenthood. The aim of the study was to elucidate whether childhood cancer and treatment affect the educational pathways chosen by parents who are former patients. METHODS: We analysed data that was collected from childhood cancer survivors and their siblings regarding their offspring's health within the FeCt Multicentre Offspring Study (conducted 2013-2016). We evaluated and compared the professional pathways of (i) all participating survivors and all participating siblings and those of (ii) survivors and their biological siblings. RESULTS: Overall information on parental gender, age, and education were available from 1077 survivors and 246 siblings (group (i)). The majority of participants were female with a mean age of 35.2 (survivor) and 37.9 (sibling) years at time of survey. For subgroup (ii), analysis information was available on 191 survivors and 210 siblings. Fathers achieved university degrees significantly more often than mothers (p = 0.003 (i), p < 0.001 (ii)). The distribution of professional education was not significantly different between cancer survivors and siblings in either cohort (i) or (ii). CONCLUSIONS: Regarding our research on the educational and vocational trajectory of CCS, patients can be reassured that family planning and vocational education are well compatible. Inequalities regarding gender-specific educational pathways remain to be addressed. IMPLICATIONS FOR CANCER SURVIVORS: CCS should monitor their fertility status regularly and, if necessary, cryopreserve germ cells or tissue in order to optimize their family planning. Educational opportunities should be pursued as desired and with confidence. Local as well as European aftercare programs can assist with family planning and education.
- MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- nádory * terapie MeSH
- přežívající onkologičtí pacienti * MeSH
- přežívající MeSH
- rodiče MeSH
- sourozenci MeSH
- stupeň vzdělání MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.
- MeSH
- adherence k farmakoterapii MeSH
- alergická rýma diagnóza farmakoterapie epidemiologie imunologie MeSH
- farmaceuti MeSH
- kritické cesty * MeSH
- lékárny * MeSH
- lidé MeSH
- management nemoci MeSH
- ochrana veřejného zdraví MeSH
- role odborníka MeSH
- systémy pro podporu klinického rozhodování MeSH
- telemedicína MeSH
- určení symptomu MeSH
- veřejné zdravotnické služby * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Inverted repeats (IR) play important roles in specific DNA-dependent processes in simple prokaryotes to complex eukaryotes. They are recognized by a variety of proteins including restriction enzymes, helicases and transcription factors. We evaluate the presence and localization of IRs in all validated human promoter sequences within 1000 bp upstream and downstream of the transcription start site (TSS). The occurrence of 7 bp and longer IRs is located non-randomly in promoter regions, with enrichment within 200 bp upstream of the TSS. The highest frequency of IRs is just before TSS for repeats of 8 bp or longer. A comparison of promoters divided according to the occurrence of five individual promoter motifs shows unique location patterns of IRs. Principal component analyses and hierarchical clustering of IRs abundance demonstrated that they are depleted and/or not enriched in the promoters of stably expressed genes, but show significant enrichments for specific dynamically regulated biological pathways.
