Tissue geometry drives deterministic organoid patterning Gjorevski, N; Nikolaev, M; Brown, T E ...
Science (American Association for the Advancement of Science),
2022-Jan-07, 2022-01-07, 20220107, Volume:
375, Issue:
6576
Journal Article
Peer reviewed
Open access
Epithelial organoids are stem cell–derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they ...self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.
The paper deals with the analysis of a system of nonlinear integral equations resulting from the three-parameter closure of the third spatial moment in the Dieckmann–Law model in the case of an
...-species community in an
-dimensional space. For the analysis of its solvability, this system is represented as an operator equation in a Banach space of a special form. Sufficient conditions for the existence of a nontrivial solution are stated using a generalized fixed point principle.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
genus of Asteraceae family is a source of medicinal plants known worldwide and used as ethnopharmacological remedies for the treatment of diabetes in Northern Asia (Siberia). The aim of this study ...was to determine the phenolic profile of 12 Siberian
species (
) and to test the efficacy of plant extracts and pure compounds for antidiabetic potential. Finally, by HPLC-DAD-ESI-TQ-MS/MS technique, 112 individual phenolic compounds were detected in
extracts in a wide range of concentrations. Some species accumulated rare plant phenolics, such as coumarin-hemiterpene ethers (lacarol derivatives) from
and
; melilotoside from
; dihydrochalcones (davidigenin analogs) from
; chrysoeriol glucosides from
, and
; eriodictyol glycosides from
; and some uncommon flavones and flavonols. The predominant phenolic group from
species herb was caffeoylquinic acid (CQAs), and in all species, the major CQAs were 5-
-CQA (20.28-127.99 μg/g) and 3,5-di-
-CQA (7.35-243.61 μg/g). In a series of
bioassays, all studied
extracts showed inhibitory activity against principal enzymes of carbohydrate metabolism, such as α-amylase (IC
= 150.24-384.14 μg/mL) and α-glucosidase (IC
= 214.42-754.12 μg/mL). Although many phenolic compounds can be inhibitors, experimental evidence suggests that the CQAs were key to the biological response of
extracts. Mono-, di- and tri-substituted CQAs were assayed and showed inhibition of α-amylase and α-glucosidase, with IC
values of 40.57-172.47 μM and 61.08-1240.35 μM, respectively, and they were more effective than acarbose, a well-known enzyme inhibitor. The results obtained in this study reveal that Siberian
species and CQAs possess a pronounced inhibitory activity against α-amylase and α-glucosidase and could become a complement to synthetic antidiabetic drugs for controlling blood glucose level.
Despite the extensive pharmacology of NMDA receptors, the use of drugs able to decrease their overactivation in CNS pathologies is limited. One reason for this may be lack of knowledge of the effects ...of NMDA receptor antagonists on the functional properties of neurons, as a significant quantity of data has been obtained in in vitro models, which do not completely reproduce real pathophysiological processes. The present study addressed the effects of NMDA receptor antagonists with different mechanisms of action on the properties of pyramidal neuron responses in the prefrontal cortex of the rat brain. The competitive antagonist APV (50 μM) and the ion channel blocker memantine (100 μM) were inactive against evoked EPSP. In conditions of suppression of inhibitory transmission with picrotoxin (50 μM), extracellular stimulation evoked epileptiform responses with prolonged membrane depolarization and generation of a burst of action potentials. APV limited the duration and amplitude of these responses. Memantine acquired activity only when magnesium was excluded from the extracellular medium. Memantine’s lack of effect can be explained in terms of competition for the magnesium ion binding site in the channel cavity. These studies show that prediction of the systemic effects of blockers on neuron function and excitability requires use of in vitro models in which NMDA receptors are activated in the presence of a physiological magnesium concentration and without clamping of the membrane potential.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Membrane potential is a fundamental property of biological cells. Changes in membrane potential characterize a vast number of vital biological processes, such as the activity of neurons and ...cardiomyocytes, tumorogenesis, cell-cycle progression, etc. A common strategy to record membrane potential changes that occur in the process of interest is to utilize organic dyes or genetically-encoded voltage indicators with voltage-dependent fluorescence. Sensors are introduced into target cells, and alterations of fluorescence intensity are recorded with optical methods. Techniques that allow recording relative changes of membrane potential and do not take into account fluorescence alterations due to factors other than membrane voltage are already widely used in modern biological and biomedical studies. Such techniques have been reviewed previously in many works. However, in order to investigate a number of processes, especially long-term processes, the measured signal must be corrected to exclude the contribution from voltage-independent factors or even absolute values of cell membrane potential have to be evaluated. Techniques that enable such measurements are the subject of this review.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction
There is no consensus about whether late-onset schizophrenia(LOS) is a type of schizophrenia or a secondary psychotic disorder. One of the theories of the occurrence of late-onset ...psychoses is neurodegeneration caused by the imbalance of proteostasis.
Objectives
To study the concentration and expression of alpha-synuclein in patients with LOS compared with controls.
Methods
The study involved 42 patients with the ICD-10 criteria of schizophrenia with the onset of the disease after 45 years and 104 controls with no dementia and severe somatic pathology, comparable in age and gender. The alpha-synuclein level was estimated in a lymphocytic cell fraction from patients with LOS N=42 and controls N=104 using the Human alpha-synuclein ELISA kit. The expression of the SNCA gene was studied in 22 LOS patients and 22 controls and determined by PCR using the SYBR Green Supermix kit and the CFX96 instrument in comparison with the referent genes using previously developed primers. LOS group underwent psychopathological examination including scales. Statistics: SPSS 12.0; the Mann–Whitney test; exponential regression analysis; data is given as median (min–max). The level of significance was set at p<0.05.
Results
The alpha-synuclein level is higher in patients with LOS (9.21 (0.78-29.52)) compared to control (6,355 (0.46-35.44)), p=0.024. The mRNA level of the SNCA gene is higher in the LOS group (0.533 (0.089-1.406)) compared to controls (0.087 (0.016-0.266) , p<0.001.
Conclusions
Our study shows the relationship of alpha-synuclein with the manifestations of LOS. Obtained novel data can open up new targets for therapy and bring it closer to understanding the phenomenon.
Disclosure
No significant relationships.
This paper presents a developed ontology of emergent properties characterizing the emergent behavior of complex engineering systems, which is the emergence of greater functionality of the overall ...system compared to the sum of the functionalities of system components. The ontology is based on the systems thinking approach used in systems architecture, one of the key points to consider in the conceptual design of engineering systems and used to manage the complexity of systems. Firstly, in the paper, research attributes and the adaptation of the term "ontology" for systems thinking are given. Secondly, the coverage of analyzed literature sources in the description of the literature search is demonstrated. Thirdly, the developed ontology consisting of semantics and relationships of systems emergent properties is presented. The proposed ontology is followed by highlighting its possible systems engineering applications. Finally, in conclusion, the benefits of the developed ontology are mentioned. Overall, the current paper combines aspects of systems engineering with key elements of the design of complex systems.
Uncertainties in the neutron data and correlations between them—covariances—are necessary both for estimating the errors of neutronic characteristics of reactors and shielding and for reducing these ...errors to an acceptable level by adjusting them on the basis of the analysis of the results of macro experiments. Up-to-date information on the uncertainties of neutron data is contained in three relatively independent libraries of evaluated neutron data: American ENDF/B-VII, Japanese JENDL-4.0, and Russian BROND-3.1. In this study, the covariance data from these libraries for the most studied fuel material—uranium-235— are compared among themselves and with the spread of the evaluated cross sections recommended in these libraries. It was found that, in the fast neutron region, the uncertainties attributed to the important characteristics such as the number of secondary fission neutrons and the fission cross section are comparable in their magnitudes with the spread of the evaluated values of these characteristics. Since the evaluations of neutron data in all the libraries are based on nearly the same set of experimental results, only differently averaged, this is evidence that the uncertainties assigned to them are too optimistic. It was also revealed that, in all the considered data, the balance of dispersions attributed to the total cross section and to its components—partial cross sections—is roughly disturbed. A method for data correction which eliminates the noted inconsistency is proposed. The revision concerns the uncertainties of the components of the scattering cross section—elastic, inelastic, the reaction (
n
, 2
n
)— and leads to a decrease in the errors attributed to the cross sections of these reactions. The proposed technique can be used to correct the covariance data for other reactor materials.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Fluorescence of the vast majority of natural opsin-based photoactive proteins is extremely low, in accordance with their functions that depend on efficient transduction of absorbed light energy. ...However, several recently proposed classes of engineered rhodopsins with enhanced fluorescence, along with the discovery of a new natural highly fluorescent rhodopsin, NeoR, opened a way to exploit these transmembrane proteins as fluorescent sensors and draw more attention to studies on this untypical rhodopsin property. Here, we review the available data on the fluorescence of the retinal chromophore in microbial and animal rhodopsins and their photocycle intermediates, as well as different isomers of the protonated retinal Schiff base in various solvents and the gas phase.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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