Interactions between C-type lectin-like NK cell receptors and their protein ligands form one of the key recognition mechanisms of the innate immune system that is involved in the elimination of cells that have been malignantly transformed, virally infected, or stressed by chemotherapy or other factors. We determined an x-ray structure for the extracellular domain of mouse C-type lectin related (Clr) protein g, a ligand for the activation receptor NKR-P1F. Clr-g forms dimers in the crystal structure resembling those of human CD69. This newly reported structure, together with the previously determined structure of mouse receptor NKR-P1A, allowed the modeling and calculations of electrostatic profiles for other closely related receptors and ligands. Despite the high similarity among Clr-g, Clr-b, and human CD69, these molecules have fundamentally different electrostatics, with distinct polarization of Clr-g. The electrostatic profile of NKR-P1F is complementary to that of Clr-g, which suggests a plausible interaction mechanism based on contacts between surface sites of opposite potential.

• MeSH
• CD antigeny chemie   imunologie   MeSH
• diferenciační antigeny T-lymfocytů chemie   imunologie   MeSH
• krystalografie rentgenová MeSH
• lektiny typu C chemie   imunologie   MeSH
• lidé MeSH
• ligandy MeSH
• membránové proteiny chemie   imunologie   MeSH
• myši MeSH
• receptory imunologické chemie   imunologie   MeSH
• statická elektřina MeSH
• strukturní homologie proteinů MeSH
• terciární struktura proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CD antigeny MeSH
• CD69 antigen MeSH Prohlížeč
• Dcl1 protein, mouse MeSH Prohlížeč
• diferenciační antigeny T-lymfocytů MeSH
• lektiny typu C MeSH
• ligandy MeSH
• membránové proteiny MeSH
• Nkrp1f protein, mouse MeSH Prohlížeč
• receptory imunologické MeSH

Human resources and labor force participation in China are discussed, with consideration given to policies affecting employment and trends in urbanization. (SUMMARY IN ENG AND RUS)

• Klíčová slova
• Asia, China, Developing Countries, Eastern Asia, Economic Factors, Employment Status *, Geographic Factors, Human Resources *, Labor Force *, Policy *, Population, Socioeconomic Factors, Socioeconomic Status, Spatial Distribution, Urban Spatial Distribution, Urbanization *,
• MeSH
• demografie MeSH
• ekonomika MeSH
• městské obyvatelstvo MeSH
• populace MeSH
• rozvojové země MeSH
• socioekonomické faktory MeSH
• společenská třída MeSH
• urbanizace * MeSH
• veřejná politika * MeSH
• zaměstnanost * MeSH
• zdravotničtí pracovníci * MeSH
• zeměpis MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Asie MeSH
• Čína MeSH
• Dálný východ MeSH

The authors elaborated a method for assessment of the renal lithium clearance, CLr, the results of which correlate well with the plasmatic clearance (CLp] (r = 0.785, p less than 0.05). This correlation improved substantially after correction of CLr to the clearance of endogenous creatinine, CLcr (r = 0.945; p less than 0.05). The mean values of CLr of the investigated group--26.4 ml/min are in agreement with the results published by other authors. A significant correlation between CLr and CLcr (r = 0.826, p less than 0.05) along with comparison of the intraindividual variability of assessed results indicates that it is better to use as a parameter of sodium absorption from the proximal tubule the fractional lithium clearance rather than absolute values of CLr.

• MeSH
• dospělí MeSH
• ledviny metabolismus   MeSH
• lidé MeSH
• lithium krev   farmakokinetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• lithium MeSH

A data table arranged according to two factors can often be considered a compositional table. An example is the number of unemployed people, split according to gender and age classes. Analyzed as compositions, the relevant information consists of ratios between different cells of such a table. This is particularly useful when analyzing several compositional tables jointly, where the absolute numbers are in very different ranges, e.g. if unemployment data are considered from different countries. Within the framework of the logratio methodology, compositional tables can be decomposed into independent and interactive parts, and orthonormal coordinates can be assigned to these parts. However, these coordinates usually require some prior knowledge about the data, and they are not easy to handle for exploring the relationships between the given factors. Here we propose a special choice of coordinates with direct relation to centered logratio (clr) coefficients, which are particularly useful for an interpretation in terms of the original cells of the tables. With these coordinates, robust principal component analysis (rPCA) is performed for dimension reduction, allowing to investigate relationships between the factors. The link between orthonormal coordinates and clr coefficients enables to apply rPCA, which would otherwise suffer from the singularity of clr coefficients.

• Klíčová slova
• Compositional data, compositional table, independence table, interaction table, pivot coordinates, robust principal component analysis,
• Publikační typ
• časopisecké články MeSH

The common approach for regression analysis with compositional variables is to express compositions in log-ratio coordinates (coefficients) and then perform standard statistical processing in real space. Similar to working in real space, the problem is that the standard least squares regression fails when the number of parts of all compositional covariates is higher than the number of observations. The aim of this study is to analyze in detail the partial least squares (PLS) regression which can deal with this problem. In this paper, we focus on the PLS regression between more than one compositional response variable and more than one compositional covariate. First, we give the PLS regression model with log-ratio coordinates of compositional variables, then we express the PLS model directly in the simplex. We also prove that the PLS model is invariant under the change of coordinate system, such as the ilr coordinates with a different contrast matrix or the clr coefficients. Moreover, we give the estimation and inference for parameters in PLS model. Finally, the PLS model with clr coefficients is used to analyze the relationship between the chemical metabolites of Astragali Radix and the plasma metabolites of rat after giving Astragali Radix.

• Klíčová slova
• 62H12, 62H86, 62J05, Compositional data, centered log-ratio coefficients, coordinates, linear regression model, partial least squares,
• Publikační typ
• časopisecké články MeSH

Working at the border between innate and adaptive immunity, natural killer (NK) cells play a key role in the immune system by protecting healthy cells and by eliminating malignantly transformed, stressed or virally infected cells. NK cell recognition of a target cell is mediated by a receptor "zipper" consisting of various activating and inhibitory receptors, including C-type lectin-like receptors. Among this major group of receptors, two of the largest rodent receptor families are the NKR-P1 and the Clr receptor families. Although these families have been shown to encode receptor-ligand pairs involved in MHC-independent self-nonself discrimination and are a target for immune evasion by tumour cells and viruses, structural mechanisms of their mutual recognition remain less well characterized. Therefore, we developed a non-viral eukaryotic expression system based on transient transfection of suspension-adapted human embryonic kidney 293 cells to produce soluble native disulphide dimers of NK cell C-type lectin-like receptor ectodomains. The expression system was optimized using green fluorescent protein and secreted alkaline phosphatase, easily quantifiable markers of recombinant protein production. We describe an application of this approach to the recombinant protein production and characterization of native rat NKR-P1B and Clr-11 proteins suitable for further structural and functional studies.

• MeSH
• HEK293 buňky MeSH
• krysa rodu Rattus MeSH
• lektinové receptory NK-buněk - podrodina B chemie   genetika   metabolismus   MeSH
• lidé MeSH
• multimerizace proteinu MeSH
• protein podobný kalcitoninovému receptoru chemie   genetika   metabolismus   MeSH
• proteinové domény MeSH
• proteinové inženýrství metody   MeSH
• rekombinantní proteiny chemie   genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Calcrl protein, rat MeSH Prohlížeč
• lektinové receptory NK-buněk - podrodina B MeSH
• protein podobný kalcitoninovému receptoru MeSH
• rekombinantní proteiny MeSH

The effect of lipophilicity on the renal clearance for a group of weak organic acids (benzoic, phenylacetic and hippuric acid derivatives) was studied in rabbits, rats and mice. These compounds are eliminated in the kidney by glomerular filtration and undergo both tubular secretion and tubular reabsorption. For quantification of the effect of lipophilicity, an equation [formula: see text] was employed, where CLR represents renal clearance of the parent drug, ERPF is effective renal plasma flow, D is the partition coefficient of the acids between octanol and water, and a and b are constants. In interspecies comparison, the values of parameters a and b are similar indicating no significant interspecies differences in this route of elimination.

• MeSH
• činčila MeSH
• inbrední kmeny potkanů MeSH
• králíci MeSH
• krevní proteiny metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyseliny chemie   moč   MeSH
• ledviny metabolismus   MeSH
• lipidy chemie   moč   MeSH
• myši MeSH
• renální oběh MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• krevní proteiny MeSH
• kyseliny MeSH
• lipidy MeSH

The distribution of time that people spend in physical activity of various intensities has important health implications. Physical activity (commonly categorised by the intensity into light, moderate and vigorous physical activity), sedentary behaviour and sleep, should not be analysed separately, because they are parts of a time-use composition with a natural constraint of 24 h/day. To find out how are relative reallocations of time between physical activity of various intensities associated with health, herewith we describe compositional scalar-on-function regression and a newly developed compositional functional isotemporal substitution analysis. Physical activity intensity data can be considered as probability density functions, which better reflects the continuous character of their measurement using accelerometers. These probability density functions are characterised by specific properties, such as scale invariance and relative scale, and they are geometrically represented using Bayes spaces with the Hilbert space structure. This makes possible to process them using standard methods of functional data analysis in the L2 space, via centred logratio (clr) transformation. The scalar-on-function regression with clr transformation of the explanatory probability density functions and compositional functional isotemporal substitution analysis were applied to a dataset from a cross-sectional study on adiposity conducted among school-aged children in the Czech Republic. Theoretical reallocations of time to physical activity of higher intensities were found to be associated with larger and more progressive expected decreases in adiposity. We obtained a detailed insight into the dose-response relationship between physical activity intensity and adiposity, which was enabled by using the compositional functional approach.

• Klíčová slova
• Compositional scalar-on-function regression, isotemporal substitution, physical activity, probability density functions, sedentary behaviour, sleep,
• MeSH
• adipozita * MeSH
• Bayesova věta MeSH
• časové faktory MeSH
• cvičení * fyziologie   MeSH
• dítě MeSH
• lidé MeSH
• obezita * MeSH
• průřezové studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: In critically ill patients, multi-trauma and intensive therapy can influence the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics with time-dependent bacterial killing. Consequently, PK/PD targets (%fT>MIC) - crucial for antimicrobial effects -may not be attained. METHODS: Two patients admitted to the surgical ICU of the University Hospital in Hradec Králove for multiple-trauma were given piperacillin/tazobactam by 1-hour IV infusion 4/0.5 g every 8h. PK variables: total and renal clearance (CLtot, CLR), volume of distribution (Vd), and elimination half-life (T1/2) were calculated, followed by glomerular filtration rate (MDRD) and cumulative fluid balance (CFB-total fluid volume based on 24-h registered fluid intake minus output). The PK/PD target attainment (100%fT>MIC) was defined as free (f) piperacillin plasma concentrations that remain, during the entire dosing interval (T), above the minimum inhibitory concentration (100%fT>MIC) within days 4-8 (when CFB culminates and disappears). Piperacillin concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and corrected for unbound fraction (22%). RESULTS: CFB culminated over days 2-5 reaching 15-30 L and was associated with a large Vd (29-42 L). While MDRD in patient 1 was low (0.3-0.4 mL s⁻¹ 1.7 m⁻²), that of patient 2 was increasing (> 3.1 mL s⁻¹ 1.7 m⁻²), which was associated with augmented CLR. In patient 2, the fT reached only 62, 52, and 44% on days 4, 6, and 8, respectively. In patient 1, the %fT was much higher, attaining values four to fivefold greater than that targeted. CONCLUSIONS: Critically ill patients are at risk of drug under- or overdosing without dose up-titration with regard to covariate effects and individual drug pharmacokinetics.

• Klíčová slova
• PK/PD target attainment, body fluid retention, critically ill patients, personalised therapy, pharmacodynamics, pharmacokinetics, piperacillin,
• MeSH
• antibakteriální látky farmakokinetika   farmakologie   MeSH
• dospělí MeSH
• inhibitory beta-laktamasy farmakokinetika   farmakologie   MeSH
• kombinace léků piperacilin a tazobactam MeSH
• kritický stav * MeSH
• kyselina penicilanová analogy a deriváty   farmakokinetika   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• pilotní projekty MeSH
• piperacilin farmakokinetika   farmakologie   MeSH
• prospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• inhibitory beta-laktamasy MeSH
• kombinace léků piperacilin a tazobactam MeSH
• kyselina penicilanová MeSH
• piperacilin MeSH

Receptors belonging to NKR-P1 family and their specific Clr ligands form an alternative missing self recognition system critical in immunity against tumors and viruses, elimination of tumor cells subjected to genotoxic stress, activation of T cell dependent immune response, and hypertension. The three-dimensional structure of the extracellular domain of the mouse natural killer (NK) cell receptor mNKR-P1Aex has been determined by X-ray diffraction. The core of the C-type lectin domain (CTLD) is homologous to the other CTLD receptors whereas one quarter of the domain forms an extended loop interacting tightly with a neighboring loop in the crystal. This domain swapping mechanism results in a compact interaction interface. A second dimerization interface resembles the known arrangement of other CTLD NK receptors. A functional dimeric form of the receptor is suggested, with the loop, evolutionarily conserved within this family, proposed to participate in interactions with ligands.

• MeSH
• buňky NK metabolismus   MeSH
• difrakce rentgenového záření MeSH
• lektinové receptory NK-buněk - podrodina B chemie   metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• myši MeSH
• Ramanova spektroskopie MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lektinové receptory NK-buněk - podrodina B MeSH