Altered mitochondrial response to activation of T-cells in neonate

Mitochondrial functions have a major impact on T-cell functionality. In this study we characterized whether mitochondrial function in the neonatal T-cells differs from that in the adult T-cells during short T-cell activation. METHODS: We used fow cytometry methods to test mitochondrial mass and to monitor mitochondrial Ca(2+) levels, mitochondrial potential and superoxide generation in parallel with cytoplasmic Ca(2+) levels during phythohaemagglutinine-induced activation of CD4+ and CD8+ T-cells of 12 term neonates and 11 healthy adults. RESULTS: Baseline mitochondrial mass of CD4+ and CD8+ cells was lower in the neonate than in the adult. In comparison with the adult, neonatal resting CD4+ T-cells had lower cytoplasmic Ca(2+) levels and this was associated with normal activation induced Ca(2+)-response. During short-term activation cytoplasmic Ca(2+)-response was lower in neonatal than in adult CD8+ T-cells. Mitochondrial Ca(2+) uptake was increased in CD4+ neonatal T cells while it decreased in CD8+ T-cells. Mitochondrial depolarization was increased in CD4+ and decreased in CD8+ neonatal T-cells compared to adults. Superoxide generation was higher and equal in neonatal CD4+ and CD8+ cells, respectively, compared to the adult ones. CONCLUSION: Our data suggest that neonatal T-cells exhibit marked differences in mitochondrial function and superoxide generation compared to adult T-cells

Fabry-betegség – terápiás útmutató

A Fabry-kór a lizoszomális tárolási betegségek csoportjába tartozó, X-kromoszómához kötötten, recesszív módon öröklődő betegség, amely a globotriaozilceramid felhalmozódásához vezet a szervezet legkülönbözőbb szöveteiben. A betegség első tünetei többnyire gyermekkorban jelentkeznek, a progresszió során a betegek súlyos szervi károsodásokkal és korai halálozással számolhatnak. Elsősorban férfiak érintettek, azonban a betegség tüneteit heterozigóta nők esetében is megfigyelhetjük, de náluk a kórkép súlyossága változó, általában enyhébb lefolyású. Az enzimpótló kezelések megjelenése szükségessé tette, hogy részletes diagnosztikus és terápiás protokollt dolgozzunk ki. A jelen dolgozatban megjelenő ajánlásokat egy, a magyarországi Fabry-kóros betegek kezelésében részt vevő orvosokból, a diagnosztika területén dolgozó biológosukból és egyéb szakemberekből álló multidiszciplináris munkacsoport foglalta össze. A munkacsoport áttekintette a korábbi klinikai tanulmányokat, a publikált vizsgálatokat és a közelmúltban megjelent nemzetközi és nemzeti útmutatókat. | Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive and the first symptoms usually present in childhood. Consequences of the disease are disability and premature death. The disease in females could be as severe as in males although women may be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline has been summarized by a Hungarian multi-disciplinary working group consisting of physicians who are involved in diagnosis and care of Fabry patients. Previous clinical studies, published articles, and recently established international treatment guidelines were reviewed by the group

From Encoding to Recognition: Exploring the Shared Neural Signatures of Visual Memory

This study investigated the shared neural dynamics underlying encoding and recognition processes across diverse visual object stimulus types in short term experimental familiarization, using EEG-based representational similarity analysis and multivariate cross-classification. Building upon previous research, we extended our exploration to the encoding phase. We show early visual stimulus category effects around 150 ms post-stimulus onset and old/new effects around 400 to 600 ms. Notably, a divergence in neural responses for encoding, old, and new stimuli emerged around 300 ms, with items encountered during the study phase showing the highest differentiation from old items during the test phase. Cross-category classification demonstrated discernible memory-related effects as early as 150 ms. Anterior regions of interest, particularly in the right hemisphere, did not exhibit differentiation between experimental phases or between study and new items, hinting at similar processing for items first encountered, irrespective of experiment phase. While short-term experimental familiarity did not consistently adhere to the old >new pattern observed in long-term personal familiarity, statistically significant effects are observed specifically for experimentally familiarized faces, suggesting a potential unique phenomenon specific to facial stimuli. Further investigation is warranted to elucidate underlying mechanisms and determine the extent of face-specific effects. Lastly, our findings underscore the utility of multivariate cross-classification and cross-dataset classification as promising tools for probing abstraction and shared neural signatures of cognitive processing

Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis.

Whereas many phagocytosis steps involve ionic fluxes, the underlying ion channels remain poorly defined. As reported in mice, the calcium conducting TRPV2 channel impacts the phagocytic process. Macrophage phagocytosis is critical for defense against pathogens. In cystic fibrosis (CF), macrophages have lost their capacity to act as suppressor cells and thus play a significant role in the initiating stages leading to chronic inflammation/infection. In a previous study, we demonstrated that impaired function of CF macrophages is due to a deficient phagocytosis. The aim of the present study was to investigate TRPV2 role in the phagocytosis capacity of healthy primary human macrophage by studying its activity, its membrane localization and its recruitment in lipid rafts. In primary human macrophages, we showed that P. aeruginosa recruits TRPV2 channels at the cell surface and induced a calcium influx required for bacterial phagocytosis. We presently demonstrate that to be functional and play a role in phagocytosis, TRPV2 might require a preferential localization in lipid rafts. Furthermore, CF macrophage displays a perturbed calcium homeostasis due to a defect in TRPV2. In this context, deregulated TRPV2-signaling in CF macrophages could explain their defective phagocytosis capacity that contribute to the maintenance of chronic infection

Financial Structure and Economic Welfare: Applied General Equilibrium Development Economics

This review provides a common framework for researchers thinking about the next generation of micro-founded macro models of growth, inequality, and financial deepening, as well as direction for policy makers targeting microfinance programs to alleviate poverty. Topics include treatment of financial structure general equilibrium models: testing for as-if-complete markets or other financial underpinnings; examining dual-sector models with both a perfectly intermediated sector and a sector in financial autarky, as well as a second generation of these models that embeds information problems and other obstacles to trade; designing surveys to capture measures of income, investment/savings, and flow of funds; and aggregating individuals and households to the level of network, village, or national economy. The review concludes with new directions that overcome conceptual and computational limitations.National Science Foundation (U.S.)National Institutes of Health (U.S.)Templeton FoundationBill & Melinda Gates Foundatio

Characterization of a K+-induced conformational switch in a human telomeric DNA oligonucleotide using 2-aminopurine fluorescence

Human telomeric DNA consists of tandem repeats of the DNA sequence d(GGGTTA). Oligodeoxynucletotide telomere models such as d[A(GGGTTA)(3)GGG] (Tel22) fold in a cation-dependent manner into quadruplex structures consisting of stacked G-quartets linked by d(TTA) loops. NMR has shown that in Na(+) solutions Tel22 forms a ‘basket’ topology of four antiparallel strands; in contrast, Tel22 in K(+) solutions consists of a mixture of unknown topologies. Our previous studies on the mechanism of folding of Tel22 and similar telomere analogs utilized changes in UV absorption between 270 and 325 nm that report primarily on G-quartet formation and stacking showed that quadruplex formation occurs within milliseconds upon mixing with an appropriate cation. In the current study, we assessed the dynamics and equilibria of folding of specific loops by using Tel22 derivatives in which the dA residues were serially substituted with the fluorescent reporter base, 2-aminopurine (2-AP). Tel22 folding induced by Na(+) or K(+) assessed by changes in 2-AP fluorescence consists of at least three kinetic steps with time constants spanning a range of ms to several hundred seconds. Na(+)-dependent equilibrium titrations of Tel22 folding could be approximated as a cooperative two-state process. In contrast, K(+)-dependent folding curves were biphasic, revealing that different conformational ensembles are present in 1 mM and 30 mM K(+). This conclusion was confirmed by (1)H NMR. Molecular dynamics simulations revealed a K(+) binding pocket in Tel22 located near dA1 that is specific for the so-called hybrid-1 conformation in which strand 1 is in a parallel arrangement. The possible presence of this topologically specific binding site suggests that K(+) may play an allosteric role in regulating telomere conformation and function by modulating quadruplex tertiary structure

Strong, bold, and kind : Self-control and cooperation in social dilemmas

Financial support from the Swedish Research Council (Vetenskapsrådet), from Formas through the program Human Cooperation to Manage Natural Resources (COMMONS), and the Ideenfonds of the University of Munich is gratefully acknowledged.We develop a model that relates self-control to cooperation patterns in social dilemmas, and we test the model in a laboratory public goods experiment. As predicted, we find a robust association between stronger self-control and higher levels of cooperation, and the association is at its strongest when the decision maker’s risk aversion is low and the cooperation levels of others high. We interpret the pattern as evidence for the notion that individuals may experience an impulse to act in self-interest—and that cooperative behavior benefits from self-control. Free-riders differ from other contributor types only in their tendency not to have identified a self-control conflict in the first place.PostprintPeer reviewe

Understanding time-inconsistent heterogeneous preferences in economics and finance:A practice theory approach

This paper introduces an innovative framework for decision making by individuals with inconsistent preferences. Practices, associations of individuals with a preference set shared by its members, provide context and unify preferences across an economy so that decision-makers are situated in social and economic structures. Our framework models the time evolution of certain attributes, emerging from the practice framework, that govern individuals’ decisions and their intertemporal variation. A novel feature is that preferences are able to rank other preference sets without the need to aggregate them. Instead, the selection of a preference set is treated as a decision in its own right. Our framework explains decision making paradoxes such as the disposition effect and agency cost considerations that are frequently encountered in the behavioural finance and economics literature

Robot-Assisted Hybrid Esophagectomy Is Associated with a Shorter Length of Stay Compared to Conventional Transthoracic Esophagectomy:A Retrospective Study

Aim. To compare the peri- and postoperative data between a hybrid minimally invasive esophagectomy (HMIE) and the conventional Ivor Lewis esophagectomy. Methods. Retrospective comparison of perioperative characteristics, postoperative complications, and survival between HMIE and Ivor Lewis esophagectomy. Results. 216 patients were included, with 160 procedures performed with the conventional and 56 with the HMIE approach. Lower perioperative blood loss was found in the HMIE group (600 ml versus 200 ml, p<0.001). Also, a higher median number of lymph nodes were harvested in the HMIE group (median 28) than in the conventional group (median 23) (p=0.002). The median length of stay was longer in the conventional group compared to the HMIE group (11.5 days versus 10.0 days, p=0.03). Patients in the HMIE group experienced fewer grade 2 or higher complications than the conventional group (39% versus 57%, p=0.03). The rate of all pulmonary (51% versus 43%, p=0.32) and severe pulmonary complications (38% versus 18%, p = 0.23) was not statistically different between the groups. Conclusions. The HMIE was associated with lower intraoperative blood loss, a higher lymph node harvest, and a shorter hospital stay. However, the inborn limitations with the retrospective design stress a need for prospective randomized studies. Registration number is DRKS00013023