Stability of cooperation under image scoring in group interactions

Image scoring sustains cooperation in the repeated two-player prisoner's dilemma through indirect reciprocity, even though defection is the uniquely dominant selfish behaviour in the one-shot game. Many real-world dilemma situations, however, firstly, take place in groups and, secondly, lack the necessary transparency to inform subjects reliably of others' individual past actions. Instead, there is revelation of information regarding groups, which allows for `group scoring' but not for image scoring. Here, we study how sensitive the positive results related to image scoring are to information based on group scoring. We combine analytic results and computer simulations to specify the conditions for the emergence of cooperation. We show that under pure group scoring, that is, under the complete absence of image-scoring information, cooperation is unsustainable. Away from this extreme case, however, the necessary degree of image scoring relative to group scoring depends on the population size and is generally very small. We thus conclude that the positive results based on image scoring apply to a much broader range of informational settings that are relevant in the real world than previously assumed.Comment: 6 two-column pages, 4 figures; accepted for publication in Scientific Report

Központi idegrendszeri kannabinoid receptorok farmakológiai és funkcionális feltérképezése = Pharmacological and functional mapping central nervous system cannabinoid receptors

Kimutattuk, hogy bár a kannabinoidok GABA felszabadulásra gyakorolt hatását a hippokampuszban a CB1 receptorok közvetítik, ezek a hatások részben fennmaradnak a CB1 receptor genetikai törlése esetén is, valószínűleg egy "tartalék" kannabinoid receptor feldúsulása révén. Elsőként írtuk le és jellemeztük a kannabinoidok gátló hatását a szerotonin felszabadulásra a hippokampuszban. A kannabinoidok hatását a CB1-receptorok közvetítik, és az a szerotonerg terminálisoknak elsősorban egy szubpopulációjára terjed ki. Kimutattuk, hogy az endokannabinoidok a hippokampuszban a bazális IL-1beta produkció szabályozásában is szerepet játszanak, mégpedig stimuláló jelleggel és a P2X7 receptorok közvetítésével. Eredményeink elsőként igazolják, hogy a nucleus accumbens drog addikcióban kiemelten fontos szerepet játszó dopaminerg végződéseiből a kannabinoidok nemcsak a dopaminerg neuronok ventralis tegmentum-ban elhelyezkedő sejttestjeinek stimulálásával, hanem a nucleus accumbensen belüli hatással, dizinhibíciós mechanizmussal is képesek dopamint felszabadítani. Leírtuk a noradrenalin és acetilkolin felszabadulás frekvenciafüggő kannabinerg modulációját a prefrontális kéregben. Kimutattuk, hogy GPR3 receptor genetikai törlése az agyi monoamin tartalmak csökkenéséhez és ezzel korreláló magatartásváltozásokkal jár a szorongás és a depresszió állatkísérletes modelljeiben. | We showed that the effect of cannabinoids on GABA release in the hippocampus is mediated by CB1-cannabinoid receptors. However, these effects are partly maintained after genetic deletion of CB1 receptors, and probably due to a residual, 'backup' cannabinoid receptor, which is overexpressed in CB1 knockouts. We reported for the first time the inhibitory effect of cannabinoids on serotonin release from the hippocampus. The action of cannabinoids is mediated by CB1 receptors, but affects only one subpopulation of serotonergic nerve terminals. We showed that endocannabinoids stimulate basal IL-1beta production in the hippocampus, partly with the participation of P2X7 receptors. We provided the first neurochemical evidence that the activation of CB1 cannabinoid receptors leads to the augmentation of [3H]dopamine efflux via a local GABAA receptor-mediated disinhibitory mechanism in the rat nucleus accumbens. In addition, the frequency dependent modulation of noradrenaline and acetylcholine release by cannabinoids is characterized in the prefrontal cortex. We also showed that genetical deletion of GPR3 receptor leads to the depletion of monoamine content in the brain and consistent alterations of behavior in animal models of anxiety and depression

Myb-binding Protein 1a (Mybbp1a) Regulates Levels and Processing of Pre-ribosomal RNA

Ribosomal RNA gene transcription, co-transcriptional processing, and ribosome biogenesis are highly coordinated processes that are tightly regulated during cell growth. In this study we discovered that Mybbp1a is associated with both the RNA polymerase I complex and the ribosome biogenesis machinery. Using a reporter assay that uncouples transcription and RNA processing, we show that Mybbp1a represses rRNA gene transcription. In addition, overexpression of the protein reduces RNA polymerase I loading on endogenous rRNA genes as revealed by chromatin immunoprecipitation experiments. Accordingly, depletion of Mybbp1a results in an accumulation of the rRNA precursor in vivo but surprisingly also causes growth arrest of the cells. This effect can be explained by the observation that the modulation of Mybbp1a protein levels results in defects in pre-rRNA processing within the cell. Therefore, the protein may play a dual role in the rRNA metabolism, potentially linking and coordinating ribosomal DNA transcription and pre-rRNA processing to allow for the efficient synthesis of ribosomes

Nemszinaptikus transmisszió: egy új megközelítés az alapvető agy funkciók megértéséhez = Nonsynaptic transmission: a new pathway to understand major brain functions

A két-foton mikroszkópia használata új információkat szolgáltatott a nemszinaptikus kölcsönhatásokról szubmikronos anatómiai struktúrákban. Feltérképeztük a technika felhasználásának lehetőségeit a különböző szövetpreparátumok, idegsejttípusok esetében. A membrán Na+/Ca2+ cserélő gátlása elsősorban a dendrittörzsben befolyásolja a szinaptikus Ca2+ tranzienseket, és szabályozza a tüske-dendrit kapcsolatot. A dendritikus Ca2+ válaszok szintjén a noradrenalin pozitív hatású a dendritikus integráció kapacitásaira nézve, elősegíti a dendritikus potenciálok keletkezését, előnyös a munkamemóriára nézve. Kísérleteink feltárták a nikotin sokrétű serkentő hatásait a dendritek funkcióira nézve, így az akciós potenciálok terjedésének erősítését, spontán válaszok kialakulását a piramissejtek tüskéiben, illetve az interneuronok dendrittörzsében. A farmakológiai alkalmazások közül az antidepresszánsok hatásait vizsgáltuk. Elképzelhető, hogy az antidepresszánsok a lassú inaktivált állapot stabilizálásának keresztül gátolják a Na+ csatorna funkciót úgy, hogy segítsék a depressziós neurális "körök" oldódását. A terápia során kialakuló koncentráció viszonyokban a fluoxetin és a dezipramin az NMDA receptorok működését hatékonyan gátolhatják, ami fontos eleme lehet a depresszió oldásának. | The use of two-photon microscopy yielded novel information about the nonsynaptic interactions in submicron anatomical structures. We mapped the applicational possibilities of this technique using various tissue preparations and neuron types. The inhibition of the membrane Na+/Ca2+ exchanger primarily influenced the synaptic Ca2+ transients in the dendrite shaft and regulate locally the dendrite/spine connectivity. At the level of the dendritic Ca2+ responses, noradrenaline has a positive effect on the capacity of dendritic integration, promotes the initiation of dendritic spikes, and enhances working memory. Our experiments revealed that nicotine has multiple effects on dendritic functions including the strengthening the propagation of action potentials in the dendrite and inducing spontaneous responses in dendritic spines of the pyramidal neurons and dendrites of interneurons. Among the pharmacological applications, we studied the effects of antidepressants. It is possible that the antidepressants block the function of the Na+ channel through the stabilization of the inactivated state in a way that helps unbound the depressive "circuits". At therapeutically relevant concentrations fluoxetine and desipramine can efficiently inhibit the function of the NMDA receptor that might be an important element of antidepressive mechanisms

Circulating miRNA Expression Profiling in Primary Aldosteronism

Objective: Primary aldosteronism is a major cause of secondary hypertension. Its two principal forms are bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA) whose differentiation is clinically pivotal. There is a major clinical need for a reliable and easily accessible diagnostic biomarker for case identification and subtyping. Circulating microRNAs were shown to be useful as minimally invasive diagnostic markers. Our aim was to determine and compare the circulating microRNA expression profiles of adenoma and hyperplasia plasma samples, and to evaluate their applicability as minimally invasive markers. Methods: One hundred and twenty-three samples from primary aldosteronism patients were included. Next-generation sequencing was performed on 30 EDTA-anticoagulated plasma samples (discovery cohort). Significantly differently expressed miRNAs were validated by real-time reverse transcription-qPCR in an independent validation cohort (93 samples). Results: We have found relative overexpression of miR-30e-5p, miR-30d-5p, miR-223-3p, and miR-7-5p in hyperplasia compared to adenoma by next-generation sequencing. Validation by qRT-PCR confirmed significant overexpression of hsa-miR-30e-5p, hsa-miR-30d-5p, and hsa-miR-7-5p in hyperplasia samples. Regarding the microRNA expressional variations, adenoma is more heterogeneous at the miRNA level compared to hyperplasia. Conclusion: Three microRNAs were significantly overexpressed in hyperplasia samples compared to adenoma samples, but their sensitivity and specificity values are not good enough for introduction to clinical practice

Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins

Demonstration of Metabolic and Cellular Effects of Portal Vein Ligation Using Multi-Modal PET/MRI Measurements in Healthy Rat Liver.

OBJECTIVES: In the early recognition of portal vein ligation (PVL) induced tumor progression, positron emission tomography and magnetic resonance imaging (PET/MRI) could improve diagnostic accuracy of conventionally used methods. It is unknown how PVL affects metabolic patterns of tumor free hepatic tissues. The aim of this preliminary study is to evaluate the effect of PVL on glucose metabolism, using PET/MRI imaging in healthy rat liver. MATERIALS AND METHODS: Male Wistar rats (n = 30) underwent PVL. 2-deoxy-2-(18F)fluoro-D-glucose (FDG) PET/MRI imaging (nanoScan PET/MRI) and morphological/histological examination were performed before (Day 0) and 1, 2, 3, and 7 days after PVL. Dynamic PET data were collected and the standardized uptake values (SUV) for ligated and non-ligated liver lobes were calculated in relation to cardiac left ventricle (SUVVOI/SUVCLV) and mean liver SUV (SUVVOI/SUVLiver). RESULTS: PVL induced atrophy of ligated lobes, while non-ligated liver tissue showed compensatory hypertrophy. Dynamic PET scan revealed altered FDG kinetics in both ligated and non-ligated liver lobes. SUVVOI/SUVCLV significantly increased in both groups of lobes, with a maximal value at the 2nd postoperative day and returned near to the baseline 7 days after the ligation. After PVL, ligated liver lobes showed significantly higher tracer uptake compared to the non-ligated lobes (significantly higher SUVVOI/SUVLiver values were observed at postoperative day 1, 2 and 3). The homogenous tracer biodistribution observed before PVL reappeared by 7th postoperative day. CONCLUSION: The observed alterations in FDG uptake dynamics should be taken into account during the assessment of PET data until the PVL induced atrophic and regenerative processes are completed

Chronic hyperglycemia induces trans-differentiation of human pancreatic stellate cells and enhances the malignant molecular communication with human pancreatic cancer cells

BACKGROUND: Diabetes mellitus is linked to pancreatic cancer. We hypothesized a role for pancreatic stellate cells (PSC) in the hyperglycemia induced deterioration of pancreatic cancer and therefore studied two human cell lines (RLT-PSC, T3M4) in hyperglycemic environment. METHODOLOGY/PRINCIPAL FINDINGS: The effect of chronic hyperglycemia (CHG) on PSCs was studied using mRNA expression array with real-time PCR validation and bioinformatic pathway analysis, and confirmatory protein studies. The stress fiber formation (IC: αSMA) indicated that PSCs tend to transdifferentiate to a myofibroblast-like state after exposure to CHG. The phosphorylation of p38 and ERK1/2 was increased with a consecutive upregulation of CDC25, SP1, cFOS and p21, and with downregulation of PPARγ after PSCs were exposed to chronic hyperglycemia. CXCL12 levels increased significantly in PSC supernatant after CHG exposure independently from TGF-β1 treatment (3.09-fold with a 2.73-fold without TGF-β1, p<0.05). The upregualtion of the SP1 transcription factor in PSCs after CHG exposure may be implicated in the increased CXCL12 and IGFBP2 production. In cancer cells, hyperglycemia induced an increased expression of CXCR4, a CXCL12 receptor that was also induced by PSC's conditioned medium. The receptor-ligand interaction increased the phosphorylation of ERK1/2 and p38 resulting in activation of MAP kinase pathway, one of the most powerful stimuli for cell proliferation. Certainly, conditioned medium of PSC increased pancreatic cancer cell proliferation and this effect could be partially inhibited by a CXCR4 inhibitor. As the PSC conditioned medium (normal glucose concentration) increased the ERK1/2 and p38 phosphorylation, we concluded that PSCs produce other factor(s) that influence(s) pancreatic cancer behaviour. CONCLUSIONS: Hyperglycemia induces increased CXCL12 production by the PSCs, and its receptor, CXCR4 on cancer cells. The ligand-receptor interaction activates MAP kinase signaling that causes increased cancer cell proliferation and migration

The German MultiCare-study: Patterns of multimorbidity in primary health care – protocol of a prospective cohort study

Background Multimorbidity is a highly frequent condition in older people, but well designed longitudinal studies on the impact of multimorbidity on patients and the health care system have been remarkably scarce in numbers until today. Little is known about the long term impact of multimorbidity on the patients' life expectancy, functional status and quality of life as well as health care utilization over time. As a consequence, there is little help for GPs in adjusting care for these patients, even though studies suggest that adhering to present clinical practice guidelines in the care of patients with multimorbidity may have adverse effects. Methods The study is designed as a multicentre prospective, observational cohort study of 3.050 patients aged 65 to 85 at baseline with at least three different diagnoses out of a list of 29 illnesses and syndromes. The patients will be recruited in approx. 120 to 150 GP surgeries in 8 study centres distributed across Germany. Information about the patients' morbidity will be collected mainly in GP interviews and from chart reviews. Functional status, resources/risk factors, health care utilization and additional morbidity data will be assessed in patient interviews, in which a multitude of well established standardized questionnaires and tests will be performed. Discussion The main aim of the cohort study is to monitor the course of the illness process and to analyse for which reasons medical conditions are stable, deteriorating or only temporarily present. First, clusters of combinations of diseases/disorders (multimorbidity patterns) with a comparable impact (e.g. on quality of life and/or functional status) will be identified. Then the development of these clusters over time will be analysed, especially with regard to prognostic variables and the somatic, psychological and social consequences as well as the utilization of health care resources. The results will allow the development of an instrument for prediction of the deterioration of the illness process and point at possibilities of prevention. The practical consequences of the study results for primary care will be analysed in expert focus groups in order to develop strategies for the inclusion of the aspects of multimorbidity in primary care guidelines