Schrifttumsberichte

Ohne Zusammenfassung     

Schrifttumsberichte

Ohne Zusammenfassung     

CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity

Extracellular vesicles (EV) are released by virtually all cells and they transport biologically important molecules from the release site to target cells. Colorectal cancer (CRC) is a leading cause of cancer-related death cases, thus, it represents a major health issue. Although the EV cargo may reflect the molecular composition of the releasing cells and thus, EVs may hold a great promise for tumor diagnostics, the impact of intratumoral heterogeneity on the intensity of EV release is still largely unknown. By using CRC patient-derived organoids that maintain the cellular and molecular heterogeneity of the original epithelial tumor tissue, we proved that CD44^high cells produce more organoids with a higher proliferation intensity, as compared to CD44^low cells. Interestingly, we detected an increased EV release by CD44^high CRC cells. In addition, we found that the miRNA cargos of CD44^high and CD44^low cell derived EVs largely overlapped and only four miRNAs were specific for one of the above subpopulations. We observed that EVs released by CD44^high cells induced the proliferation and activation of colon fibroblasts more strongly than CD44^low cells. However, this effect was due to the higher EV number rather than to the miRNA cargo of EVs. Collectively, we identified CRC subpopulations with different EV releasing capabilities and we proved that CRC cell-released EVs have a miRNA-independent effect on fibroblast proliferation and activation.     

Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium,Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models

Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich-type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long-term cytostatic activity. These structure-activity relationship studies revealed that: (1) osmium(II) p-cymene complexes were active in all models, while rhodium(III) and iridium(III) Cp* complexes proved largely inactive; (2) the biological effect was influenced by the nature of the central azole ring of the ligands—1,2,3-triazole was the most effective, followed by 1,3,4-oxadiazole, while the isomeric 1,2,4-oxadiazole abolished the cytostatic activity; (3) we found a correlation between the hydrophobic character of the complexes and their cytostatic activity: compounds with O-benzoyl protective groups on the carbohydrate moiety were active, compared to O-deprotected ones. The best compound, an osmium(II) complex, had an IC₅₀ value of 0.70 µM. Furthermore, the steepness of the inhibitory curve of the active complexes suggested cooperative binding; cooperative molecules were better inhibitors than non-cooperative ones. The cytostatic activity of the active complexes was abolished by a lipid-soluble antioxidant, vitamin E, suggesting that oxidative stress plays a major role in the biological activity of the complexes. The complexes were active on ovarian cancer, pancreatic adenocarcinoma, osteosarcoma and Hodgkin’s lymphoma cells, but were inactive on primary, non-transformed human fibroblasts, indicating their applicability as potential anticancer agents.     

Resource changes: exogenous or endogenous,gradual or abrupt. Experimental evidence

The paper reports a laboratory experiment in which groups of participants managed a Common-Pool Resource (CPR). The goal was to observe if different types of resource change, whether exogenous or endogenous, and gradual or sudden, would lead to different behaviour, and if the participants would adapt easily to any one of these changes. The experiment used a time continuous, dynamic tool. Endogenous resource changes, when compared with exogenous changes, led to higher cooperation, and a better management of the resource, thus reducing the risk of extinction through overharvesting. Abrupt changes appear to induce users to modify their behaviour according to what happens to the resource, but gradual changes do not seem to lead to behavioural change. In line with previous research, our results suggest that, when the users are aware of the threat of potential disasters, they can adapt their behaviour and move toward a solution which can avoid the tragedy of the commons.     

Coordinating Self-interested Planning Agents

We consider planning problems where a number of non-cooperative agents have to work on a joint problem. Such problems consist in completing a set of interdependent, hierarchically ordered tasks. Each agent is assigned a subset of tasks to perform for which it has to construct a plan. Since the agents are non-cooperative, they insist on planning independently and do not want to revise their individual plans when the joint plan has to be assembled from the individual plans. We present a general formal framework to study some computational aspects of this non-cooperative coordination problem and we establish some complexity results to identify some of the factors that contribute to the complexity of this problem. Finally, we illustrate our approach with an application to coordination in multi-modal logistic planning.     

Predictors of self-assessed work ability among subjects with recent-onset asthma

Novel reversed micellar solutions formulated with a mixture of AOT (dioctyl sulfosuccinate) and DOLPA (dioleyl phosphoric acid) show good potential for use in reversed micellar protein extraction operations. Chymotrypsin is easily extracted from an aqueous phase into organic isooctane containing 10 mM AOT and DOLPA in a 4:1 ratio. The extraction ability of the mixed reversed micelles of 10 mM was higher than that of 200 mM AOT alone. The results of extraction indicated that the AOT-DOLPA mixed reversed micelles are very useful for separating and enriching chymotrypsin. Back-extraction of chymotrypsin from the organic phase to a fresh aqueous phase is also accomplished by adding an alcohol to the organic phase. Although the back-transfer of chymotrypsin from the reversed micelles formed by AOT alone is very slow and difficult, in the AOT-DOLPA mixed reversed micelles, the back-extraction can be achieved completely by addition of 10% (v/v) isobutyl alcohol to the reversed micellar phase. The time to attain to the equilibrium of back-extraction was reduced from more than 24 to 2 h by adding the alcohol. On the basis of the activity data, the best composition of AOT and DOLPA was a 4:1 ratio and the total surfactant concentration was 10 mM. The activity of chymotrypsin recovered from the mixed reversed micelles was higher than that of the initial protein before the forward-transfer. This result means that the novel mixed reversed micellar solutions are useful not only in separation but also in purification of proteins.     

Mechanisms of catalysis and allosteric regulation of yeast chorismate mutase from crystal structures

BACKGROUND: Chorismate mutase (CM) catalyzes the Claisen rearrangement of chorismate to prephenate, notably the only known enzymatically catalyzed pericyclic reaction in primary metabolism. Structures of the enzyme in complex with an endo-oxabicyclic transition state analogue inhibitor, previously determined for Bacillus subtilis and Escherichia coli CM, provide structural insight into the enzyme mechanism. In contrast to these bacterial CMs, yeast CM is allosterically regulated in two ways: activation by tryptophan and inhibition by tyrosine. Yeast CM exists in two allosteric states, R (active) and t (inactive). RESULTS: We have determined crystal structures of wild-type yeast CM cocrystallized with tryptophan and an endo-oxabicyclic transition state analogue inhibitor, of wild-type yeast CM co-crystallized with tyrosine and the endo-oxabicyclic transition state analogue inhibitor and of the Thr226-->Ser mutant of yeast CM in complex with tryptophan. Binding of the transition state analogue inhibitor to CM keeps the enzyme in a 'super R' state, even if the inhibitory effector tyrosine is bound to the regulatory site. CONCLUSIONS: The endo-oxabicyclic inhibitor binds to yeast CM in a similar way as it does to the distantly related CM from E. coli. The inhibitor-binding mode supports a mechanism by which polar sidechains of the enzyme bind the substrate in the pseudo-diaxial conformation, which is required for catalytic turnover. A lysine and a protonated glutamate sidechain have a critical role in the stabilization of the transition state of the pericyclic reaction. The allosteric transition from T-->R state is accompanied by a 15 degrees rotation of one of the two subunits relative to the other (where 0 degrees rotation defines the T state). This rotation causes conformational changes at the dimer interface which are transmitted to the active site. An allosteric pathway is proposed to include residues Phe28, Asp24 and Glu23, which move toward the activesite cavity in the T state. In the presence of the transition-state analogue a super R state is formed, which is characterised by a 22 degrees rotation of one subunit relative to the other.     

Capsaicin and capsiate could be appropriate agents for treatment of obesity: A meta-analysis of human studies

Consumption of capsaicin or its nonpungent analogues, capsinoids has been reported to affect energy expenditure and fat oxidation, although available data are still controversial. The aim of the present study was to conduct a meta-analysis regarding the effects of these substances on energy expenditure and respiratory quotient, with special emphasis on the role of body mass index (BMI) of the participants. Medical databases were systematically searched for papers. Of the 627 trials identified, 9 provided results suitable to be included in analysis. Data analysis showed that after ingestion of capsaicin or capsinoids the energy expenditure increased (245 kJ/day, 58.56 kcal/day, p = 0.030) and the respiratory quotient decreased (by 0.216; p = 0.031) indicating a rise in fat oxidation. Studies with mean BMI of the participants below 25 kg/m² failed to report any effect of capsaicin or capsinoids on the energy expenditure (p = 0.718) or on the respiratory quotient (p = 0.444), but studies with mean BMI exceeding 25 kg/m² demonstrated an increase in energy expenditure (292 kJ/day, 69.79 kcal/day, p = 0.023) and a marked decrease in respiratory quotient (?0.257, p = 0.036). Our data clearly suggest that capsaicin or capsiate could be a new therapeutic approach in obesity promoting a negative energy balance and increased fat oxidation.     

Fine Bubble‐based CO2 Capture Mediated by Triethanolamine Coupled to Whole Cell Biotransformation

Carbon capture technology can be set up in combination with biocatalysis to utilize the bound CO₂ as substrate in the Kolbe‐Schmitt like enzymatic reaction. The exemplary whole cell biotransformation of catechol to 2,3‐dihydroxybenzoic acid in a triethanolamine‐mediated multiphase system shows increased equilibrium conversion. Apart from the beneficial thermodynamics, the inherent fluid properties of triethanolamine is enabling easy application of CO₂ fine bubbles as highly efficient gassing method to minimize the CO₂ demand and CO₂ emissions.