exploration types
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The advent of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), coupled with computational modeling, has enabled the creation of integrative 3D models of viruses, bacteria, and cellular organelles. These models, composed of thousands of macromolecules and billions of atoms, have historically posed significant challenges for manipulation and visualization without specialized molecular graphics tools and hardware. With the recent advancements in GPU rendering power and web browser capabilities, it is now feasible to render interactively large molecular scenes directly on the web. In this work, we introduce Mesoscale Explorer, a web application built using the Mol* framework, dedicated to the visualization of large-scale molecular models ranging from viruses to cell organelles. Mesoscale Explorer provides unprecedented access and insight into the molecular fabric of life, enhancing perception, streamlining exploration, and simplifying visualization of diverse data types, showcasing the intricate details of these models with unparalleled clarity.
- MeSH
- elektronová kryomikroskopie * metody MeSH
- molekulární modely * MeSH
- software * MeSH
- viry chemie ultrastruktura MeSH
- Publikační typ
- časopisecké články MeSH
Computational exploration of chemical space is crucial in modern cheminformatics research for accelerating the discovery of new biologically active compounds. In this study, we present a detailed analysis of the chemical library of potential glucocorticoid receptor (GR) ligands generated by the molecular generator, Molpher. To generate the targeted GR library and construct the classification models, structures from the ChEMBL database as well as from the internal IMG library, which was experimentally screened for biological activity in the primary luciferase reporter cell assay, were utilized. The composition of the targeted GR ligand library was compared with a reference library that randomly samples chemical space. A random forest model was used to determine the biological activity of ligands, incorporating its applicability domain using conformal prediction. It was demonstrated that the GR library is significantly enriched with GR ligands compared to the random library. Furthermore, a prospective analysis demonstrated that Molpher successfully designed compounds, which were subsequently experimentally confirmed to be active on the GR. A collection of 34 potential new GR ligands was also identified. Moreover, an important contribution of this study is the establishment of a comprehensive workflow for evaluating computationally generated ligands, particularly those with potential activity against targets that are challenging to dock.
- MeSH
- knihovny malých molekul * farmakologie chemie MeSH
- lidé MeSH
- ligandy MeSH
- receptory glukokortikoidů * metabolismus chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Příspěvek je věnován problematice strategií vztahové údržby v rámci partnerství a manželství. Studie využívá tvrzení populární knihy Garyho Chapmana Pět jazyků lásky aneb naučte se mluvit jazykem lásky toho druhého (2002). Autor zdůrazňuje, že v intimním vztahu je důležité vyjadřovat náklonnost a lásku způsobem, kterému partner rozumí. Tento typ partnerské komunikace je v jeho koncepci nazýván jako „pět jazyků lásky“: slova ujištění, soustředěná pozornost, dárky, skutky služby a fyzický kontakt. Zkoumaný soubor tvořilo 111 nesezdaných respondentů (vysokoškolských studentů) a 61 manželských párů (122 respondentů). Studie sleduje genderové rozdíly a prediktory v užívání strategií vztahové údržby. Rozdíly mezi muži a ženami byly nalezeny u kategorií „dárky“ a „soustředěná pozornost“. Zatímco muži častěji zmiňovali kategorii „dárky“, ženy uváděly častěji kategorii „soustředěná pozornost“. V logistické regresní analýze se pro „slova ujištění“ a „fyzický kontakt“ jako signifikantní prediktor uplatnila délka vztahu, pro „soustředěnou pozornost“ stav (sezdaný/nesezdaný), pro „dárky“ a „skutky služby“ stav a pohlaví.
The current study contributes to the topic of relational maintenance strategies. The study uses Gary Chapman's claims published in his popular book The Five Love Languages: How to Express Heartfelt Commitment to Your Mate (2002). The author underscores the importance of being able to express love to one's spouse in a way the spouse can understand. Chapman refers to this type of communication as the five love languages i.e. words of affirmation, quality time, gifts, acts of service and physical touch. Survey data were collected from 111 unmarried individuals (college students) and 61 married couples (122 individuals). The aim of the study was to explore differences and predictors in how married and unmarried men and women use various strategies of relational maintenance. Findings reveal that men use „gifts“ more frequently while women are more likely to use „quality time“ as strategy of relational maintenance. The predictor of „words of affirmation“ and “physical touch” was length of relationship, predictor of „quality time“ was marital status. Marital status and sex served as predictors of „gifts“ and „acts of service“.
In a fluctuating environment, the optimal level of exploratory behavior depends on the proportion of current risks and benefits. The exploratory behavior is, therefore, often subjected to heterogenous selection. In populations of commensal rodents living in close proximity of humans, this pressure is further increased by pest management. We hypothesize that the black rat (Rattus rattus) responds to this pressure by either high behavioral flexibility or by development of personality types. The aim of this study was to analyze exploratory behavior and boldness of wild black rats and its changes over time to determine whether exploratory behavior is a personality trait in black rats. Studies on animals with unreduced variability are necessary for determination of normal range of behaviors. The behavior in the open field and hole board tests yielded 1 multivariate variable representing exploratory behavior and 1 representing boldness. The hole board test additionally provided an axis representing exploratory behavior. Exploratory behavior showed moderate to high repeatability, even though we observed a considerable effect of habituation. Exploratory behavior was also strongly correlated across contexts; therefore, our results suggest that the black rat responds to heterogenous selection pressure by developing personality types. We also found a strong effect of litter identity on some aspects of the exploratory behavior. Boldness was less repeatable, which we interpret as high behavioral flexibility in this behavioral trait. In concordance with our hypothesis, the personality types in exploratory behavior, but not in boldness, are possibly maintained by heterogenous selection pressure created by human pest management. (PsycINFO Database Record
- MeSH
- chování zvířat * MeSH
- fenotyp MeSH
- individualita * MeSH
- krysa rodu rattus MeSH
- pátrací chování * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Východiska. Jednou z nejčastějších psychických poruch vyskytujících se u drogově závislých je porucha osobnosti. Jedno z možných vysvětlení je předpoklad existence osobnostní psychopatologie, která zvyšuje riziko vzniku závislosti. Východiskem pro naši práci je Kernbergův koncept hraniční organizace osobnosti, podle kterého můžeme hodnocením dimenzí obranné mechanismy, integrace identity a schopnosti testování reality zjistit závažnost osobnostní psychopatologie a tím i možný výskyt poruchy osobnosti. Cíle. Cílem práce bylo popsat osobnostní organizaci podle Kernberga u jednotlivých typů závislostí, na jejímž základě bychom mohli předpokládat míru závažnosti osobnostní psychopatologie. Nad rámec výzkumných hypotéz jsme se zabývali také analýzou vztahů mezi dotazníky, které by podpořily Kernbergův koncept. Metody. Výzkum byl proveden pomocí dotazníkového šetření. Pro zjištění daných dimenzí jsme použili Kernbergovu metodu IPO, která byla doplněna testy IPDE, DSQ-40 a BPQ. Soubor | Celkem je do výzkumu zahrnuto 211 probandů, které jsme rozdělili podle primární závislosti na alkoholovou závislost, drogovou závislost, patologické hráčství a kombinovanou závislost. Výsledky. Z výsledků můžeme pozorovat u různých typů závislosti rozdíly ve struktuře osobnosti podle Kernbergovy koncepce. Nejnižší úroveň osobnostní organizace se objevuje u kombinovaných závislostí. Nejvyšší úroveň osobnostní organizace se objevuje naopak u alkoholové závislosti. Sledujeme také signifikantní korelace mezi metodou IPO a ostatními metodami. Závěry. Na základě výsledků můžeme uvažovat nad větší závažností osobnostní psychopatologie u kombinované závislosti a u patologického hráčství a v nižší míře také u drogové závislosti oproti alkoholové závislosti.
Background. Personality disorders are common mental health conditions among drug-dependent individuals. This may be due to an underlying personality psychopathology which increases the risk of the development of addiction. Our work was based on Kernberg's concept of borderline personality organisation, which proposes that the severity of the personality psychopathology and, accordingly, the possible presence of a personality disorder can be established by means of the evaluation of the Defence Mechanisms, Identity Integration, and Reality Testing Ability dimensions. Aims. The objective of this research project was to describe the personality organisation according to Kernberg for different types of addiction for potential use in estimating the severity of the personality psychopathology. In addition to research hypotheses, we examined whether Kernberg's concept may be supported by relationships between the questionnaires used. Methods. The research involved a questionnaire survey. The measures of the dimensions were obtained using Kernberg's IPO method, complemented with the administration of the IPDE, DSQ-40, and BPQ tests. Sample | The research sample included a total of 211 participants. According to their primary addiction, the participants were divided into four categories: alcohol addiction, drug addiction, pathological gambling, and multiple addiction. Results. The results suggest differences in the personality structure according to Kernberg for each type of addiction. The lowest level of personality organisation was found in multiple addictions. Conversely, the highest level of personality organisation was shown for alcohol addiction. We also identified significant correlations between the IPO questionnaire and other psychometric instruments which support Kernberg's theory. Conclusions. The results suggest a higher rate of borderline signs and a greater severity of personality psychopathology in people with multiple addiction, pathological gambling, and, to a lesser degree, drug addiction in comparison with alcohol-dependent individuals
- Klíčová slova
- Kernbergova metoda IPO, hraniční organizace,
- MeSH
- hráčství komplikace psychologie MeSH
- lidé MeSH
- poruchy osobnosti * diagnóza komplikace MeSH
- poruchy spojené s užíváním psychoaktivních látek * klasifikace komplikace psychologie MeSH
- průzkumy a dotazníky MeSH
- výzkum MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. METHODS: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. RESULTS: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. LIMITATIONS: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. CONCLUSIONS: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD.
- MeSH
- adaptorový protein GRB2 genetika metabolismus MeSH
- algoritmy MeSH
- bipolární porucha genetika metabolismus patofyziologie MeSH
- celogenomová asociační studie MeSH
- exprese genu MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- geny erbB-2 fyziologie MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- mozek růst a vývoj metabolismus MeSH
- receptor erbB-2 metabolismus MeSH
- RNA metabolismus MeSH
- signální transdukce * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pro osoby s amputací, je použití protetické pomůcky nezbytným předpokladem pro provádění základních pohybových aktivit. S rozvojem technické protetiky se objevují nové typy protéz, které mění podmínky při pohybové činnosti. Proto je důležité porovnat případné změny v zatížení dolních končetin při chůzi u osob, které tyto protézy využívají. To nám mimo jiné umožňují biomechanické metody. V našem výzkumu jsme využili kinematickou analýzu, měření na tenzometrických (silových) plošinách, analýzu rozloženítlakových sil na kontaktu chodidla s podložkou a povrchovou elektromyografii. Zkoumali jsme chůzi u 11 probandů s bércovými protézami typu Sach a SureFlex. Při vyhodnocení záznamů jsme nalezli rozdí1yv silovém působení reakční síly při chůzi na různém typu protézy a v základních kinematických parametrech. Tyto diference se objevují na postižené i na zdravé končetině.
For amputees, the use of prosthetic instruments is an essential assumption for the pursuit of basic motion activities. With technical prosthetics development, new types of prostheses have appeared, which change motion activity conditions. It is important to compare changes in lower limb loading in gait for persons who use prostheses. It is made possible by biomechanical methods, among other things. In our research, we used kinematic analysis, force plate measuring, pressure distribution analysis of the contact foot with pad and surface electromyography. We explored the gait of 11 probands with Sach and Sureflex transtibial prostheses. In record evaluation we found differences in the force activity of the reaction force while walking on the various prosthesis types and within basic kinematic parameters. These differences occur in both prosthetic and sound limbs.
- MeSH
- biomechanika MeSH
- chůze MeSH
- Publikační typ
- abstrakt z konference MeSH
Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of renal neoplasm predominantly affecting younger individuals. It is characterized by germline mutations in SDHx genes, particularly type B. Histologically, SDH-deficient RCC features eosinophilic cytoplasmic cells forming solid nests or microcysts, sometimes entrapping normal tubules. We present three SDH-deficient RCC cases with overlapping morphological features with fumarate hydratase-deficient RCC and TFEB-rearranged RCC, an appearance that has not been previously described. All tumors lacked SDHB expression and harbored pathogenic SDHB mutations, with the germline nature confirmed in two cases. Metastasis developed in two patients. Our case set highlights the diagnostic challenges of molecularly defined renal tumors and expands the morphological spectrum of SDH-deficient RCC with unusual histological features. Clinically, these tumors appear to be aggressive.
- MeSH
- dediferenciace buněk MeSH
- dospělí MeSH
- fumarasa nedostatek genetika MeSH
- karcinom z renálních buněk * genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika analýza MeSH
- nádory ledvin * patologie genetika MeSH
- sukcinátdehydrogenasa * nedostatek genetika MeSH
- transkripční faktory BHLH-Zip genetika MeSH
- zárodečné mutace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Ambelline, an alkaloid from the Amaryllidaceae family with a crinane-type skeleton, has not yet demonstrated any outstanding biological activity. However, its analogues prepared by derivatization of the C-11 hydroxyl group show different interesting effects. Continuing our earlier work, twelve novel aromatic esters were developed (10, 14, 16, 17, 22-25, 30-33) and studied, together with previously synthesized derivatives (2-9, 11-13, 15, 18-21, 26-29) in terms of their cytotoxic activity. The cytotoxic potential was determined on a panel of nine human cancer cell lines and one noncancerous cell line to characterize their biological activity spectrum. To describe and foresee the structure-activity relationship for further research, substances synthesized and described in our previous work were also included in this cytotoxicity study. The most significant activity was associated with analogues having methyl (10), methoxy (14-17), or ethoxy (18) substitution on the phenyl condensed to ambelline. However, the 4-chloro-3-nitrobenzoyl derivative (32) showed the most promising IC50 values, ranging from 0.6 ± 0.1 μM to 9.9 ± 0.2 μM. In vitro cytotoxicity studies indicated the most potent antiproliferative activity of 32 in a dose-dependent and time-dependent manner. Besides, 32 was found to be effective in decreasing viability and triggering apoptosis of MOLT-4 T-lymphoblastic leukemia cells.
- Publikační typ
- časopisecké články MeSH
