Regulation of TrkB receptor translocation to lipid rafts by adenosine A2A receptors and its functional implications for BDNF-induced regulation of synaptic plasticity

Brain-derived neurotrophic factor (BDNF) signalling is critical for neuronal development and transmission. Recruitment of TrkB receptors to lipid rafts has been shown to be necessary for the activation of specific signalling pathways and modulation of neurotransmitter release by BDNF. Since TrkB receptors are known to be modulated by adenosine A_2A receptor activation, we hypothesized that activation of A_2A receptors could influence TrkB receptor localization among different membrane microdomains. We found that adenosine A_2A receptor agonists increased the levels of TrkB receptors in the lipid raft fraction of cortical membranes and potentiated BDNF-induced augmentation of phosphorylated TrkB levels in lipid rafts. Blockade of the clathrin-mediated endocytosis with monodansyl cadaverine (100 μM) did not modify the effects of the A_2A receptor agonists, but significantly impaired BDNF effects on TrkB recruitment to lipid rafts. The effect of A_2A receptor activation in TrkB localization was mimicked by 5 μM forskolin, an adenylyl cyclase activator. Also, it was blocked by the PKA inhibitors Rp-cAMPs and PKI-(14-22) and by the Src-family kinase inhibitor PP2. Moreover, removal of endogenous adenosine or disruption of lipid rafts reduced BDNF stimulatory effects on glutamate release from cortical synaptosomes. Lipid raft integrity was also required for the effects of BDNF upon hippocampal long-term potentiation at CA1 synapses. Our data demonstrate, for the first time, a BDNF-independent recruitment of TrkB receptors to lipid rafts, induced by the activation of adenosine A_2A receptors, with functional consequences for TrkB phosphorylation and BDNF-induced modulation of neurotransmitter release and hippocampal plasticity.     

Mechanisms of phosphate solubilization by fungal isolates when exposed to different P sources

The use of phosphate-solubilizing fungi is a promising biotechnological strategy in the management of phosphorus (P) fertilization, as it enables the utilization of rock phosphates (RP) or the recovery of P fixed in soil particles. The objective of our study was to evaluate fungal isolates for mechanisms of solubilization of P-bearing compounds, such as AlPO₄, FePO₄, Ca₃(PO₄)₂, Araxá RP, and Catalão RP. Four fungal isolates obtained from Brazilian soils were characterized in liquid media: Aspergillus niger FS1, Penicillium canescens FS23, Eupenicillium ludwigii FS27, and Penicillium islandicum FS30. A. niger FS1 was the only isolate able to solubilize all of the P sources, solubilizing 71, 36, 100, and 14 % of the P from AlPO₄, FePO₄, Ca₃(PO₄)₂, and RPs, respectively. Medium acidification was an effective solubilization mechanism, particularly for Ca₃(PO₄)₂. The other P sources were mainly solubilized through organic acids produced by the fungi. Oxalic acid, produced exclusively by A. niger FS1, and citric acid were decisive factors in the solubilization of AlPO₄ and FePO₄. Penicillium isolates produced more gluconic acid than A. niger FS1 in all treatments. However, this higher production did not result in higher solubilization for any of the P sources, showing that gluconic acid contributes little to the solubilization of the P sources evaluated. The higher capacity of medium acidification and the production of organic acids with stronger metal-complexation activity are characteristics that confer to A. niger FS1 a wider action on insoluble P sources. Consequently, this isolate qualifies as a promising candidate for application in the management of P fertilization.     

Growth impairment after TBI of leukemia survivors children: a model- based investigation

Background

Children receiving Total Body Irradiation (TBI) in preparation for Hematopoietic Stem Cell Transplantation (HSCT) are at risk for Growth Hormone Deficiency (GHD), which sometimes severely compromises their Final Height (FH). To better represent the impact of such therapies on growth we apply a mathematical model, which accounts both for the gompertzian-like growth trend and the hormone-related ‘spurts’, and evaluate how the parameter values estimated on the children undergoing TBI differ from those of the matched normal population.

Methods

25 patients long-term childhood lymphoblastic and myeloid acute leukaemia survivors followed at Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children’s Hospital (Turin, Italy) were retrospectively analysed for assessing the influence of TBI on their longitudinal growth and for validating a new method to estimate the GH therapy effects. Six were treated with GH therapy after a GHD diagnosis.

Results

We show that when TBI was performed before puberty overall growth and pubertal duration were significantly impaired, but such growth limitations were completely reverted in the small sample (6 over 25) of children who underwent GH replacement therapies.

Conclusion

Since in principle the model could account for any additional growth ‘spurt’ induced by therapy, it may become a useful ‘simulation’ tool for paediatricians for comparing the predicted therapy effectiveness depending on its timing and dosage.

     

Grey squirrels in central Italy: a new threat for endemic red squirrel subspecies

A new population of the invasive American Eastern grey squirrel (Sciurus carolinensis) has recently settled in central Italy from an accidental release in Perugia, Umbria in the early 2000s. The grey squirrel is known to compete with and exclude native red squirrels (S. vulgaris) in the British Isles and Northern Italy, so it represents a potentially important new conservation threat to the red squirrel subspecies of south and central Italy, S. vulgaris italicus and S. v. meridionalis, which are endemic to peninsular Italy. The grey squirrel population range in Perugia is currently expanding at a rate of about 0.29 km/year (SD 0.19), slower than grey squirrel invasions elsewhere in Europe. Nuclear DNA analysed at 12 different microsatellite loci revealed that the grey squirrels in Perugia have extremely low genetic diversity, consistent with a small founder size. Genetic assignment tests indicate that the Perugia population was founded by translocations from an established population in Piedmont, Italy. No genetic substructure is evident yet in the Perugia population. These results together have serious consequences for the management of the grey squirrel invasion in Perugia and the conservation of the red squirrel subspecies: the Perugia grey squirrel population should be eradicated if politically feasible; otherwise new releases of grey squirrels, especially from sources other than the Piedmont population, should be prevented because such introductions could increase genetic diversity, thereby potentially increasing population range expansion rate to the much higher levels seen for more diverse grey squirrel populations elsewhere in Europe.     

Co-management and Spatial Features Contribute to Secure Fish Abundance and Fishing Yields in Tropical Floodplain Lakes

Empirical data are needed to show the efficacy of co-management, which is regarded as a promising approach to achieve conservation goals. In this study, we addressed the potential influence of fisheries co-management to increase fish abundance and fishing yields in the lower Tocantins River Basin (Brazilian Amazon), downstream from a large dam. We analyzed 590 fish landings (6.7 t of fish) from five fishing villages and 48 fish samples obtained using gillnets (10,378 fish from 101 species) in 12 floodplain lakes in four regions: two with incipient co-management and two unmanaged. The fish species richness did not differ among the regions, but the lakes in the regions that were co-managed had higher fish abundance (biomass and number of individuals) and a higher mean proportion of fish reproducing during the high water season. Fishers had higher catches per unit of effort in the co-managed regions than fishers in the non-managed regions. These results were also influenced by geographic factors (distance and accessibility of lakes), as fish biomass was higher in lakes that were distant from the main river and from the main city in the region. Managers should thus consider strategic selection of the geographic locations of managed sites, even in remote areas. However, the fish biomass sampled in lakes was more related to region than to the lakes’ geographical location. Therefore, co-management has at least partially contributed to increased fish abundance and fishing yields in the studied region, through the protection of an important fish habitat (lakes). We provide empirical evidence that co-management can contribute to the maintenance of fish abundance, sustainability of fisheries, and food security in large tropical rivers impacted by damming.     

Interactions between a seed‐eating neotropical rodent,the Azara's agouti (Dasyprocta azarae), and the Brazilian ‘pine’ Araucaria angustifolia

We studied the seed predation and scatter‐hoarding behaviour of Azara's agoutis Dasyprocta azarae (Rodentia: Dasyproctidae) in relation to the seeds of the Brazilian ‘pine’, Araucaria angustifolia (Araucariaceae), the rodent's main winter food source. We compared seed‐removal rates, seed‐caching rates, cache distances and recovery rates between a summer period of food abundance (with a low demand for A. angustifolia seeds and no such seeds naturally available) and a winter period of food scarcity (with a high demand for A. angustifolia seeds). We investigated whether the relative seed value affected the rodent's seed‐handling behaviour. We predicted that during the high seed‐demand period (winter): (1) cache distances would be greater; (2) fewer seeds would be stored; (3) more seeds would be recovered and the seed‐recovery time would be lower. In support of our first two predictions, the caching distances were greater in winter (mean ± SE = 15.67 ± 5.11 m) than in summer (9.40 ± 1.59 m), and agoutis hoarded >9 times more seeds in summer (55) than in winter (6). Our third prediction was not supported, and the proportion of unrecovered caches and buried seed recovery times did not differ between winter (mean ± SE = 3.00 ± 0.00 days, n = 5 seeds) and summer (11.05 ± 3.68 days, n = 20 seeds). The high resource density (during summer) rather than the density of A. angustifolia seeds likely influenced seed fate. Agoutis acted mainly as predators, leaving few intact seeds, caching a low proportion of handled seeds (? 8%) and rapidly consuming the caches. Agoutis may cache seeds to keep them safe from competitors on a short‐term basis rather than maintaining medium‐ or long‐term reserves for use during food‐scarcity periods.     

Potential Role of IL-17-Producing iNKT Cells in Type 1 Diabetes

We explored in this study the status and potential role of IL-17-producing iNKT cells (iNKT17) in type 1 diabetes (T1D) by analyzing these cells in patients with T1D, and in NOD mice, a mouse model for T1D. Our analysis in mice showed an increase of iNKT17 cells in NOD vs control C57BL/6 mice, partly due to a better survival of these cells in the periphery. We also found a higher frequency of these cells in autoimmune-targeted organs with the occurrence of diabetes, suggesting their implication in the disease development. In humans, though absent in fresh PMBCs, iNKT17 cells are detected in vitro with a higher frequency in T1D patients compared to control subjects in the presence of the proinflammatory cytokine IL-1β, known to contribute to diabetes occurrence. These IL-1β-stimulated iNKT cells from T1D patients keep their potential to produce IFN-γ, a cytokine that drives islet β-cell destruction, but not IL-4, with a reverse picture observed in healthy volunteers. On the whole, our results argue in favour of a potential role of IL-17-producing iNKT cells in T1D and suggest that inflammation in T1D patients could induce a Th1/Th17 cytokine secretion profile in iNKT cells promoting disease development.     

Left and Right Amygdala - Mediofrontal Cortical Functional Connectivity Is Differentially Modulated by Harm Avoidance

Background

The left and right amygdalae are key regions distinctly involved in emotion-regulation processes. Individual differences, such as personality features, may affect the implicated neurocircuits. The lateralized amygdala affective processing linked with the temperament dimension Harm Avoidance (HA) remains poorly understood. Resting state functional connectivity imaging (rsFC) may provide more insight into these neuronal processes.

Methods

In 56 drug-naive healthy female subjects, we have examined the relationship between the personality dimension HA on lateralized amygdala rsFC.

Results

Across all subjects, left and right amygdalae were connected with distinct regions mainly within the ipsilateral hemisphere. Females scoring higher on HA displayed stronger left amygdala rsFC with ventromedial prefrontal cortical (vmPFC) regions involved in affective disturbances. In high HA scorers, we also observed stronger right amygdala rsFC with the dorsomedial prefrontal cortex (dmPFC), which is implicated in negative affect regulation.

Conclusions

In healthy females, left and right amygdalae seem implicated in distinct mPFC brain networks related to HA and may represent a vulnerability marker for sensitivity to stress and anxiety (disorders).     

Female Sexual Function of Overweight Women with Gestational Diabetes Mellitus – A Cross-Sectional Study

Obesity and gestational diabetes mellitus (GDM) are increasing worldwide and may compromise female sexual function. We hypothesize that among GDM patients in the third trimester of pregnancy, those with excess body fat would have worse female sexual function scores than normal weight women. Our aim was to assess the sexual function of overweight compared to normal weight women with GDM. This was a cross-sectional survey involving 143 Brazilian women with GDM in the third trimester of pregnancy: 76 were overweight (pre-pregnancy body mass index-BMI≥25.0 Kg/m²) and 67 were normal weight (BMI 18.5–24.9 Kg/m²). Participants were recruited from March 2010 to April 2013 at the antenatal clinic of a single public tertiary teaching institution. The Female Sexual Function Index (FSFI) questionnaire was used to assess sexual function. Overall, 51.7% of the 143 participants were at risk for sexual dysfunction symptoms (FSFI scores ≤26); this rate was significantly higher among overweight compared to normal weight women (60.5% versus 41.8%, p = 0.038). Mean total FSFI scores were significantly lower in overweight compared to normal weight women (21.7±9.2 versus 24.9±8.0, p = 0.029). Compared to normal weight women, overweight participants had lower mean scores in desire (3.4±1.2 versus 4.0±1.4, p = 0.007) and lubrication (3.8±2.0 versus 4.5±1.6, p = 0.023). According to these results, overweight women with GDM in the third trimester of pregnancy have lower female sexual function scores than normal weight women with the same disorder.     

Information Transfer and Criticality in the Ising Model on the Human Connectome

We implement the Ising model on a structural connectivity matrix describing the brain at two different resolutions. Tuning the model temperature to its critical value, i.e. at the susceptibility peak, we find a maximal amount of total information transfer between the spin variables. At this point the amount of information that can be redistributed by some nodes reaches a limit and the net dynamics exhibits signature of the law of diminishing marginal returns, a fundamental principle connected to saturated levels of production. Our results extend the recent analysis of dynamical oscillators models on the connectome structure, taking into account lagged and directional influences, focusing only on the nodes that are more prone to became bottlenecks of information. The ratio between the outgoing and the incoming information at each node is related to the the sum of the weights to that node and to the average time between consecutive time flips of spins. The results for the connectome of 66 nodes and for that of 998 nodes are similar, thus suggesting that these properties are scale-independent. Finally, we also find that the brain dynamics at criticality is organized maximally to a rich-club w.r.t. the network of information flows.