Giving Is Nicer than Taking: Preschoolers Reciprocate Based on the Social Intentions of the Distributor

Recent research has found that even preschoolers give more resources to others who have previously given resources to them, but the psychological bases of this reciprocity are unknown. In our study, a puppet distributed resources between herself and a child by taking some from a pile in front of the child or else by giving some from a pile in front of herself. Although the resulting distributions were identical, three- and five-year-olds reciprocated less generously when the puppet had taken rather than given resources. This suggests that children’s judgments about resource distribution are more about the social intentions of the distributor and the social framing of the distributional act than about the amount of resources obtained. In order to rule out that the differences in the children’s reciprocal behavior were merely due to experiencing gains and losses, we conducted a follow-up study. Here, three- and-five year olds won or lost resources in a lottery draw and could then freely give or take resources to/from a puppet, respectively. In this study, they did not respond differently after winning vs. losing resources.     

Controlling nucleic acid secondary structure by intercalation: effects of DNA strand length on coralyne-driven duplex disproportionation

Small molecules that intercalate in DNA and RNA are powerful agents for controlling nucleic acid structural transitions. We recently demonstrated that coralyne, a small crescent-shaped molecule, can cause the complete and irreversible disproportionation of duplex poly(dA)·poly(dT) into triplex poly(dA)·poly(dT)·poly(dT) and a poly(dA) self- structure. Both DNA secondary structures that result from duplex disproportionation are stabilized by coralyne intercalation. In the present study, we show that the kinetics and thermodynamics of coralyne-driven duplex disproportionation strongly depend on oligonucleotide length. For example, disproportionation of duplex (dA)₁₆·(dT)₁₆ by coralyne reverts over the course of hours if the sample is maintained at 4°C. Coralyne-disproportioned (dA)₃₂· (dT)₃₂, on the other hand, only partially reverts to the duplex state over the course of days at the same temperature. Furthermore, the equilibrium state of a (dA)₁₆·(dT)₁₆ sample in the presence of coralyne at room temperature contains three different secondary structures [i.e. duplex, triplex and the (dA)₁₆ self-structure]. Even the well-studied process of triplex stabilization by coralyne binding is found to be a length-dependent phenomenon and more complicated than previously appreciated. Together these observations indicate that at least one secondary structure in our nucleic acid system [i.e. duplex, triplex or (dA)_n self-structure] binds coralyne in a length-dependent manner.     

Tuning of conformational preorganization in model 2',5'- and 3',5'-linked oligonucleotides by 3'- and 2'-O-methoxyethyl modification

Conformational properties of trimeric and tetrameric 2′,5′-linked oligonucleotides, 3′-MOE-A₃^2′,5′ (1) and 3′-MOE-A₄^2′,5′ (2), and their 3′,5′-linked analogs, 2′-MOE-A₃^3′,5′ (3) and 2′-MOE-A₄^3′,5′ (4), were examined with the use of heteronuclear NMR spectroscopy. The temperature-dependent ³J_HH, ³J_HP and ³J_CP coupling constants, acquired in the range of 273–343 K, gave insight into the conformation of sugar rings in terms of a two-state North ↔ South (N ↔ S) pseudorotational equilibrium and into the conformation of the sugar–phosphate backbone in the model antisense oligonucleotides 1–4. 2′,5′-linked oligomers 3′-MOE-A₃^2′,5′ (1) and 3′-MOE-A₄^2′,5′ (2) show preference for N-type conformers and indication of A-type conformational features, which is prerequisite for antisense hybridization. The drive of N ↔ S equilibrium in 1–4 has been rationalized with the competing gauche effects of 2′/3′-phosphodiester and 3′/2′-MOE groups, anomeric and steric effects. Furthermore, the pairwise comparisons of 3′-MOE with 3′-OH and 3′-deoxy 2′,5′-linked adenine trimers emphasized the fine tuning of N ↔ S equilibrium in 3′-MOE-A₃^2′,5′ (1) and 3′-MOE-A₄^2′,5′ (2) by the steric effects of 3′-MOE group and the possibility of water-mediated H-bonds with vicinal phosphodiester functionality. In full correspondence, the drive of N ↔ S equilibrium towards N by 2′-MOE in 3′,5′-linked analogs 2′-MOE-A₃^3′,5′ (3) and 2′-MOE-A₄^3′,5′ (4) is weaker in comparison with 3′-OH group in the corresponding ribo analogs. β^t, γ⁺ and ε^– rotamers are preferred in both 2′,5′- and in 3′,5′-linked oligonucleotides 1–4.     

Different role of intracellular loops of glucagon-like peptide-1 receptor in G-protein coupling

Previous studies revealed the importance of the third intracellular loop of glucagon-like peptide-1 receptor (GLP-1R) in coupling to G(s) and G(i1) proteins. In order to further study the signaling mechanisms of GLP-1R, we tested three peptides, corresponding to the sequences of the first (IC(1)), the second (IC(2)), and the third (IC(3)) intracellular loop of GLP-1R, for their interactions with heterotrimeric G-proteins of different types (G(alphas), G(alphao), G(alphai1), and G(alpha11) plus G(beta1gamma2)) overexpressed in sf9 cells. IC(3) peptide powerfully stimulates all types of tested G-proteins, whereas IC(1) and IC(2) peptides show differential effects on G-proteins. Both IC(1) and IC(2) peptides activate G(s) and cooperate with IC(3) peptide in its stimulation. G(o) is not affected by IC(1) and IC(2). G(i1) and G(11) are not affected by IC(1), but are activated by IC(2), which in activation cooperates with IC(3). We suggest that GLP-1R is not coupled only to G(s) and G(i1), as shown previously, but also to G(o) and G(11). IC(3) loop is the main switch that mediates signaling via GLP-1R to G-proteins, while IC(1) and IC(2) loops are important in discrimination between different types of G-proteins.     

Phytochelatin synthase catalyzes key step in turnover of glutathione conjugates

Conjugation of xenobiotic compounds and endogenous metabolites to glutathione is an ubiquitous process in eukaryotes. In animals, the first and rate-limiting step of glutathione-S-conjugate metabolism is characterized by the removal of the aminoterminal glutamic acid residue of glutathione. In plants, however, glutathione-S-conjugates are generally metabolized by removal of the carboxylterminal glycine residue of the tripeptide glutathione to give rise to the S-glutamylcysteinyl-derivative. Purification of the glutathione-conjugate catabolizing activity from cell suspension cultures of the plant Silene cucubalus indicated that phytochelatin synthase catalyzes the first step of the pathway. Heterologously expressed phytochelatin synthase from Arabidopsis efficiently converted S-bima ne-glutathione to S-bimane-glutamylcysteine, the formation of which was unequivocally identified by mass spectrometry. No further products, such as S-derivatives of phytochelatins, were observed. Several different glutathione-S-conjugates served as substrates for the enzyme and were processed to the corresponding glutamylcysteinyl-adducts. Affinity-purified phytochelatin synthase preparations required divalent heavy metal ions such as Cd(2+), Zn(2+) or Cu(2+) for detectable turnover of glutathione-S-conjugates. Characterization of the enzymatic properties of phytochelatin synthase argues for both cellular functions of the gamma-glutamylcysteinyl-dipeptidyltransferase: (1) formation of heavy-metal binding peptides and (2) degradation of glutathione-S-conjugates. Mechanistically, the former role is the result of gamma-glutamylcysteinyl transpeptidation onto glutathione or derivatives thereof, while the catabolic function reflects transpeptidation of S-glutamylcysteinyl-adducts onto the acceptor molecule water. Thus, phytochelatin synthase seems to fulfil a second crucial role in glutathione metabolism.     

The outcome of autologous chondrocyte transplantation treatment of cartilage lesions in the knee

Recent results of the clinical outcome of autologous chondrocyte transplantation (ACT) treatment in a group of 28 patients with focal femoral condyle cartilage lesions revealed a correlation trend with the quality of the in vitro cell culture matrix-protein synthesis. No impact of the patients' age and chondrocyte cryopreservation prior to implantation was observed. Further studies are needed to confirm the preliminary results.     

Sensitivity and flexibility of regular and chaotic calcium oscillations

Sensitivity and flexibility are important properties of biological systems. These properties are here investigated for intracellular calcium oscillations. For a particular model, we comparatively investigate sensitivity and flexibility of regular and chaotic Ca(2+) oscillations. For this model, we obtain two main results. First, sensitivity of the model system to parameter shifting does not depend on the complexity of Ca(2+) oscillations. We observe, however, that both regular and chaotic Ca(2+) oscillations are highly sensitive in regions close to bifurcation points. Second, also flexibility of Ca(2+) oscillations does not significantly depend on the type of Ca(2+) oscillations. Our results show that regular as well as chaotic Ca(2+) oscillations in the studied model are highly flexible in regimes with weak dissipation. Both results are discussed in the sense of possible biological importance.     

Exocytotic release of ATP from cultured astrocytes

Astrocytes appear to communicate with each other as well as with neurons via ATP. However, the mechanisms of ATP release are controversial. To explore whether stimuli that increase [Ca(2+)](i) also trigger vesicular ATP release from astrocytes, we labeled ATP-containing vesicles with the fluorescent dye quinacrine, which exhibited a significant co-localization with atrial natriuretic peptide. The confocal microscopy study revealed that quinacrine-loaded vesicles displayed mainly non-directional spontaneous mobility with relatively short track lengths and small maximal displacements, whereas 4% of vesicles exhibited directional mobility. After ionomycin stimulation only non-directional vesicle mobility could be observed, indicating that an increase in [Ca(2+)](i) attenuated vesicle mobility. Total internal reflection fluorescence (TIRF) imaging in combination with epifluorescence showed that a high percentage of fluorescently labeled vesicles underwent fusion with the plasma membrane after stimulation with glutamate or ionomycin and that this event was Ca(2+)-dependent. This was confirmed by patch-clamp studies on HEK-293T cells transfected with P2X(3) receptor, used as sniffers for ATP release from astrocytes. Glutamate stimulation of astrocytes was followed by an increase in the incidence of small transient inward currents in sniffers, reminiscent of postsynaptic quantal events observed at synapses. Their incidence was highly dependent on extracellular Ca(2+). Collectively, these findings indicate that glutamate-stimulated ATP release from astrocytes was most likely exocytotic and that after stimulation the fraction of quinacrine-loaded vesicles, spontaneously exhibiting directional mobility, disappeared.     

Thyroid hormone analog, diiodothyropropionic acid (DITPA), exerts beneficial effects on chamber and cellular remodeling in cardiomyopathic hamsters

Diiodothyropropionic acid (DITPA) is a thyroid hormone analog that is currently in phase II clinical trials. However, there have not been any studies to comprehensively analyze its effect on myocyte morphology. In addition, long-term studies with DITPA have not been done. This study compares the effects of DITPA with L-thyroxine (T4) on chamber remodeling, cardiac function, cellular morphology, cardiac blood flow, and protein expression. Normal and cardiomyopathic hamsters were treated with T4 or DITPA for 2 months. At the end of the treatment, echos, hemodynamics, coronary blood flow, cell morphology, and protein expression data were collected. Both T4 and DITPA treatment reduced chamber diameter during diastole, suggesting attenuated chamber dilatation in cardiomyopathic hamsters. Wall thickness also tended to increase, which was supported by cell morphology data in which DITPA significantly increased cross-sectional growth of myocytes specifically in the minor dimension, which is oriented transmurally. T4 and DITPA also increased myocardial blood flow both at baseline and after maximal dilation. This suggests there was increased angiogenesis or reduced loss of arterioles. Both T4 and DITPA had beneficial effects on chamber remodeling, which was most likely due to beneficial changes in cell shape and improved vascular supply.