- MeSH
- Cats MeSH
- Cerebral Cortex cytology physiology MeSH
- Neurophysiology MeSH
- Neurons physiology MeSH
- Check Tag
- Cats MeSH
Článek se zabývá možnostmi funkčního zobrazování metodou MR (fMRI). V úvodu jsou uvedeny principy této nové metody, založené na změně toku krve a krevního objemu (Cerebrař Blood Flow CBF a Cerebral Blood Volume - CBV) a změně oxygenace krve při aktivaci vybraného mozkového centra. Velikost změn MR signálu během aktivace je relativně malá (jednotky procent) a je ruswe ovlivněna fyziologickou pulzaci mozku. Proto klade metoda značné nároky na výběr správné měřicí sekvence, ale také na způsob vyhodnocení naměřených dat. Rychlé sekvence typu Echo-planar imaging (EPI) mají výrazně lepší časové rozlišení než sekvence typu FLASH, ale jejich použití vyžaduje speciální gradientní systém a obrazy jsou velmi náchylné ke geometrickým poškozením díky susceptibility efektům. Uvedeny jsou příklady využití obou technik. Změny signálu mohou být vyhodnoceny různými statistickými metodami (např. t-testem) nebo může být využita korelace s časovým programem stimulace během měření. V článkuje porovnáno několik možných metod vyhodnocení, pro vyhodnocení převážné většiny našich měření byl využit výpočet korelačního koeficientu a relativní změny signálu pro každý voxel obrazu. Přibližně 50 dobrovolníků a 8 pacientů bylo začleněno do studia motorické a senzomotorické aktivity mozku pomocí fMRI. Motorická stimulace byla prováděna pohybem prstů určené ruky ve zvolených intervalech a podávala téměř vždy jasné změny signálu v oblasti primárního motorického kortexu (MK), někdy také sekundárního MK. Velikost aktivované oblasti a změny signálu byly značně závislé na subjektu. Objektivněji proveditelné možnosti stimulace senzomotorického systému jsou např. stimulace elektrickými impulzy (metoda zavedená pro měření EEG) nebo vibrace s optimalizovanou frekvencí a amplitudou. Obě tyto metody byly testovány. V obou případech byla aktivace v senzomotorické oblasti detekována, ale jak velikost aktivovaných oblastí, tak hlavně změny signálu byly výrazně menší než u motorické stimulace.
The authors discuss possibilities of functional imaging by the MR method (fMRI). In the int ntroduction the principles of this new method are given, based on a change of the cerebral blood flow (CBF) and cerebral blood volume (CBV) and change of blood oxygenation during activation of a selected brain centre. The magnitude of changes of the MR signal during activation is relatively small (several per cent) and the physiological pulsation of the brain interferes with it. Therefore the method puts great demands on the selection of the correct sequence of measurements and also on the method of evaluation of assessed data. Rapid sequences of the Echo-planar imaging (EPI) type have a much better time resolution than sequences of the FLASH type but their use calls for a special gradient system and the pictures are very liable to suffer geometrical damage due to the susceptibility effect. Examples of the application of both techniques are given. Changes of the signal can be evaluated by different statistical methods (e.g. the t-test) or correlation with the time programme of stimulation during measurement can be used. The authors compare several possible methods of evaluation. For evaluation of the majority of measurements the authors used calculation of the correlation coefficient and relative changes of the signal for every voxel of the image. About 50 volunteers and 8 patients were included in the group where motor and sensomotor brain activity was studied by means of fMRI. Motor stimulation involved movements of the fingers of the hand at selected intervals and produced almost always clear changes of the signal in the area of the primary motor cortex (MC), sometimes also the secondary MC and very frequently also the MC area of the contralateral hemisphere was activated. The size of the activated area and changes of the signal depended to a great extent on the subject. More objective ways of stimulation of the sensomotor system are e.g. stimulation with electric impulses (the method used for assessment of EEG) or vibrations with an optimal frequency and amplitude. Both these methods were tested. In both instances activation in the sensomotor area was detected but the size of activated areas as well as the change of signal was much smaller than in motor stimulation.
The seven-transmembrane-spanning receptors of the FZD1-10 class are bound and activated by the WNT family of lipoglycoproteins, thereby inducing a complex network of signaling pathways. However, the specificity of the interaction between mammalian WNT and FZD proteins and the subsequent signaling cascade downstream of the different WNT-FZD pairs have not been systematically addressed to date. In this study, we determined the binding affinities of various WNTs for different members of the FZD family by using bio-layer interferometry and characterized their functional selectivity in a cell system. Using purified WNTs, we show that different FZD cysteine-rich domains prefer to bind to distinct WNTs with fast on-rates and slow off-rates. In a 32D cell-based system engineered to overexpress FZD2, FZD4, or FZD5, we found that WNT-3A (but not WNT-4, -5A, or -9B) activated the WNT-β-catenin pathway through FZD2/4/5 as measured by phosphorylation of LRP6 and β-catenin stabilization. Surprisingly, different WNT-FZD pairs showed differential effects on phosphorylation of DVL2 and DVL3, revealing a previously unappreciated DVL isoform selectivity by different WNT-FZD pairs in 32D cells. In summary, we present extensive mapping of WNT-FZD cysteine-rich domain interactions complemented by analysis of WNT-FZD pair functionality in a unique cell system expressing individual FZD isoforms. Differential WNT-FZD binding and selective functional readouts suggest that endogenous WNT ligands evolved with an intrinsic natural bias toward different downstream signaling pathways, a phenomenon that could be of great importance in the design of FZD-targeting drugs.
- MeSH
- beta Catenin metabolism MeSH
- Cell Line MeSH
- Phosphorylation MeSH
- Frizzled Receptors metabolism MeSH
- Protein Interaction Mapping MeSH
- Protein Interaction Maps * MeSH
- Mice MeSH
- Protein Isoforms metabolism MeSH
- Wnt Proteins metabolism MeSH
- Wnt Signaling Pathway * MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Intramural MeSH
3rd ed. 407 s. : obr. ; 25 cm
In Saccharomyces cerevisiae, K+-uptake under K+-limiting conditions is largely mediated by the cation translocation systems Trk1 and Trk2 belonging to the family of SKT proteins. They are related to two-transmembrane-domain (inward rectifying K-) channels but unlike the symmetrical tetrameric structure of K-channels, a single Trk contains four pore-forming domains (A-D) encoded on one polypeptide chain. Between domains A and B Trks contain large cytosolic regions dubbed "long hydrophilic loop" (LHL). LHLs are not homologous/similar to any other identified protein (domain) and also show little similarity between Trk1 and Trk2. Here we demonstrate that Trk1 is functional without LHL. However, in growth experiments NaCl sensitivity of Trk1[ΔLHL] expressing cells is increased under K+-limiting conditions compared to full-length Trk1. Non-invasive ion flux measurements showed that K+-influx through Trk1 and Trk1[ΔLHL] is decreased in the presence of surplus Na+ due to permeability of the proteins for both cations and competition between them. Trk1[ΔLHL] is less affected than full-length Trk1 because it is more selective for K+ over Na+. Furthermore, K+ re-uptake after starvation is delayed and decreased in Trk1[ΔLHL]. Thus, a role of LHL is regulating cation fluxes through Trk1 by (i) allowing also Na+ to pass if monovalent cations (mainly K+) are limiting and (ii) by accelerating/enhancing a switch from low to high affinity ion translocation. We propose that LHL could modulate Trk1 transport properties via direct influence on a transmembrane helix (M2A) which can switch between bent and straight conformation, thereby directly modifying the radius of the pore and selectivity filter.
- MeSH
- Dimerization MeSH
- Potassium metabolism MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Ion Transport MeSH
- Cations metabolism MeSH
- Cation Transport Proteins chemistry metabolism MeSH
- Saccharomyces cerevisiae Proteins chemistry metabolism MeSH
- Saccharomyces cerevisiae metabolism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Anthropometry methods MeSH
- Adolescent MeSH
- Pulse MeSH
- Heart Rate MeSH
- Physical Fitness MeSH
- Efficiency MeSH
- Check Tag
- Adolescent MeSH
Autoři informují o zkušenostech s vyšetřením téměř 3000 vedlejších nosních dutin CT a kolem 700 endoskopických endonazálních operací, při nichž postupovali podle obrazů CT, jež velmi dobře korelovaly s peroperačními nálezy. S rozvojem fyziologických poznatků, prakticky ověřených při funkční endonazální endoskopické chirurgii (FEECH) je získán nový pohled na diagnostiku a indikaci konzervativní i chirurgické léčby horních dýchacích cest. Klíčovou oblastí a centrem patologie VDN jsou delikátní struktury čichového labyrintu a ostiomeatální jednotky. Vznik těchto moderních přístupů je neodmyslitelný od rozvoje CT, které umožnilo detailní zobrazení kostních i měkkotkánových struktur. Práce popisuje koncepci FEECH, postup a indikace vyšetření CT vedlejších nosních dutin (VDN) v koronárni, axiální a sagitální rovině, limitované CT, HRCT, pooperační CT, CT-cisternografii a 3D CT. S rostoucí dosažitelnosti CT klesá význam konvenční skiagrafie, spolu s růstem nároků kliniků na diagnostickou hodnotu zobrazovacích metod. Diskutuje se klinický význam kostních anatomických variací a slizničních změn, včetně tzv. rizikových oblastí VDN, orbity a rinobáze, na něž upozorňují vyšetření CT. Cílenou individuální volbou vyšetření CT v úzké spolupráci radiodiagnostika a klinika se dosahuje optimální diagnostické výtěžnosti při minimální radiační zátěži nemocného a snížení ekonomických nákladů.
The authors inform on their experience with the CT examination of almost 3000 paranasal sinuses and cca 700 endoscopic endonasal operations where they proceeded according to CT images which correlated very well with peroperative findings. The expansion of physiological findings, verified on endonasal endoscopic surgery (FEES) opens new vistas as regards diagnosis and indication of conservative and surgical treatment of the upper airways. The crucial area and focal point of the pathology of paranasal sinuses are delicate structures of the ethmoidal labyrinth and ostiomeatal unit. The development of these modern approaches is closely linked to the development of CT which made detailed imaging of osseous and soft tissue structures possible. The authors describe the concept of FEES, the procedure and indications for CT examination of the paranasal sinuses in the coronary, axial and sagital plane, limited CT, HRCT, postoperative CT, CT cisternography and 3D CT. With the expanding availability of CT the importance of conventional skiagraphy declines, along with the clinicians' demands on the diagnostic value of imaging methods. The authors discuss the clinical importance of anatomical bone variations and mucosal changes, incl. so-called risk areas of the paranasal sinuses, the orbit and rhinobase to which attention is drawn by CT examinations. Aimed individual selection of CT examination in close collaboration of the radiodiagnostician and clinician achieves an optimal diagnostic yield with a minimum radiation exposure of the patient and reduction of financial costs.
