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Copyright of Rehabilitation & Physical Medicine / Rehabilitace a Fyzikální Lékařství is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The present study is designed to find out if sesquiterpenes, α-humulene (HUM), valencene (VAL), β-caryphyllene-oxide (CAO) and trans-nerolidol (NER), are able to improve the antiproliferative effect of classical cytostatic drugs, 5-fluorouracil (FU) and oxaliplatin (1,2-diaminocyclohexaneoxalato-platinum, OxPt), in colon cancer cell lines Caco-2 and SW-620. In addition, the possible mechanisms of sesquiterpene action are studied. The results show significant ability of HUM and especially of CAO to enhance the anti-proliferative effects of FU and OxPt in cancer cell lines Caco-2 and SW-620. On the other hand, VAL and NER are ineffective. The action of CAO could be partly based on its ability to disrupt the mitochondrial membrane potential and to activate initiator caspases, but other mechanisms are probably also involved. Based on these results, CAO seems to have the potential for combination therapy of colon cancers and deserves further study.

This study explores the capabilities of large language models to replicate the behavior of individuals with underdeveloped cognitive and language skills. Specifically, we investigate whether these models can simulate child-like language and cognitive development while solving false-belief tasks, namely, change-of-location and unexpected-content tasks. GPT-3.5-turbo and GPT-4 models by OpenAI were prompted to simulate children (N = 1296) aged one to six years. This simulation was instantiated through three types of prompts: plain zero-shot, chain-of-thoughts, and primed-by-corpus. We evaluated the correctness of responses to assess the models' capacity to mimic the cognitive skills of the simulated children. Both models displayed a pattern of increasing correctness in their responses and rising language complexity. That is in correspondence with a gradual enhancement in linguistic and cognitive abilities during child development, which is described in the vast body of research literature on child development. GPT-4 generally exhibited a closer alignment with the developmental curve observed in 'real' children. However, it displayed hyper-accuracy under certain conditions, notably in the primed-by-corpus prompt type. Task type, prompt type, and the choice of language model influenced developmental patterns, while temperature and the gender of the simulated parent and child did not consistently impact results. We conducted analyses of linguistic complexity, examining utterance length and Kolmogorov complexity. These analyses revealed a gradual increase in linguistic complexity corresponding to the age of the simulated children, regardless of other variables. These findings show that the language models are capable of downplaying their abilities to achieve a faithful simulation of prompted personas., Competing Interests: NO., (Copyright: © 2024 Milička et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The popularity and rapid spread of new psychoactive substances is why there is an urgent need for their fast monitoring in saliva in the field with electrodes modified with a selective receptor. Oligomers of electrochemically oxidized 3-aminobenzoic acid that are deposited on the surface of a graphite screen-printed electrode (o-3ABA/G/SPE) is proposed as a selector for the analyte of forensic interest. The oligomeric structure and existence of the zwitterionic form of o-3ABA on the G/SPE surface was confirmed using scanning electron microscopy, Raman spectroscopy and cyclic voltammetry techniques. The equilibrium adsorption constants between o-3ABA and 2-aminoindane (primary amine: K ads (2-AI) = 5.31 × 10 4 ) and selected synthetic cathinones (secondary amine: K ads (butylone) = 6.12 × 10 5 , tertiary amines: K ads (MDPV) = 3.41 × 10 4 and K ads (naphyrone) = 1.01 × 10 4 ) were estimated using the electrochemical impedance spectroscopy (EIS) technique. The EIS technique was applied for determining a 1.0 μM concentration of 2-AI (RSD 3.5-4.0%) and butylone (RSD 4.9-6.4%) in the model and oral fluid samples.

Background: Basal cell carcinoma (BCC) is the most frequent skin cancer worldwide, however, its metastatic spreading is extremely rare., Case: We present a case of advanced BCC with rapid growth of new tumor lesions in a patient who was later diagnosed with Gorlin syndrome. Due to the advanced disease stage, the patient was examined for circulating tumor cells (CTCs), which are used as a prognostic marker in some metastatic malignancies. To date, no studies have been found that could assess the BCC tumor and the presence of CTCs in peripheral blood. CTCs were obtained after each surgical excision and during systemic oncological therapy from the peripheral venous blood by size-based isolation method (Metacell®) and cultured in vitro for 7 days. CTCs were enriched by size-based separation and examined using vital fluorescence microscopy. Cytomorphological comparison of CTCs with cells from the tumor lesions was provided. In the course of the treatment, the CTCs count in the blood decreased after surgical removal of the tumorous mass, but finally, the sustained and persisting decrease in CTCs was achieved with a hedgehog pathway inhibitor treatment., Conclusion: The detection of CTCs points a systematic disease behavior in this case.

We consider the symmetric two-state 16-vertex model on the square lattice whose vertex weights are invariant under any permutation of adjacent edge states. The vertex-weight parameters are restricted to a critical manifold which is self-dual under the gauge transformation. The critical properties of the model are studied numerically with the Corner Transfer Matrix Renormalization Group method. Accuracy of the method is tested on two exactly solvable cases: the Ising model and a specific version of the Baxter eight-vertex model in a zero field that belong to different universality classes. Numerical results show that the two exactly solvable cases are connected by a line of critical points with the polarization as the order parameter. There are numerical indications that critical exponents vary continuously along this line in such a way that the weak universality hypothesis is violated.

Insight into the structure-function relationship of membrane proteins is important to understand basic cell function and inform drug development, as these are common targets for drugs. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) is an established technique for the study of protein conformational dynamics and has shown compatibility with membrane proteins. However, the digestion and mass analysis of peptides from membrane proteins can be challenging, severely limiting the HDX-MS experiment. Here we compare the digestion of four integral membrane proteins-Cl - /H + exchange transporter (ClC-ec1), leucine transporter (LeuT), dopamine transporter (DAT), and serotonin transporter (SERT)-by the use of porcine pepsin and three alternative aspartic proteases either in-solution or immobilized on-column in an optimized HDX-MS-compatible workflow. Pepsin was the most favorable for the digestion of ClC-ec1 and LeuT, providing coverage of 82.2 and 33.2% of the respective protein sequence; however, the alternative proteases surpassed pepsin for the digestion of DAT and SERT. By also screening quench solution additives, we observe that the denaturant urea was beneficial, resulting in improved sequence coverage of all membrane proteins, in contrast to guanidine hydrochloride. Furthermore, significant improvements in sequence coverage were achieved by tailoring the chromatography to handle hydrophobic peptides. Overall, we demonstrate that the susceptibility of membrane proteins to proteolytic digestion during HDX-MS is highly protein-specific. Our results highlight the importance of having multiple proteases and different quench buffer additives in the HDX-MS toolbox and the need to carefully screen a range of digestion conditions to successfully optimize the HDX-MS analysis of integral membrane proteins.

Mouse Nkrp1a receptor is a C-type lectin-like receptor expressed on the surface of natural killer cells that play an important role against virally infected and tumor cells. The recently solved crystal structure of Nkrp1a raises questions about a long loop region which was uniquely extended from the central region in the crystal. To understand the functional significance of the loop, the solution structure of Nkrp1a using nuclear magnetic resonance (NMR) spectroscopy was determined. A notable difference between the crystal and NMR structure of Nkrp1a appears in the conformation of the long loop region. While the extended loop points away from the central core and mediates formation of a domain swapped dimer in the crystal, the solution structure is monomeric with the loop tightly anchored to the central region. The findings described the first solution structure in the Nkrp1 family and revealed intriguing similarities and differences to the crystal structure. Proteins 2016; 84:1304-1311. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

DCL-1 (CD302) is a single-pass type one transmembrane protein which is predominantly expressed on myeloid cell lines. It possess the ability of endocytosis and is assumed to play a role in cell adhesion and migration. It has been also connected to several illnesses but more on the level of mRNA than on the protein expression level. More interestingly it is alternatively expressed in the form of a fusion protein with another single-pass type one transmembrane protein DEC205 (CD205) which is normally involved in antigen-uptake and endocytosis. The fusion protein has been assigned to have altered function compared to the wild type proteins. We have performed NMR structural analysis of the 16.2 kDa extracellular domain of DCL-1 to get a better insight onto this molecule. We have been able to assign nearly 97 % of resonance frequencies for the (15)N and (13)C labeled recombinant protein. The assignments have been deposited into Biological Magnetic Resonance Data Bank under the accession number 25802.