Low-Dose Bisphenol-A Impairs Adipogenesis and Generates Dysfunctional 3T3-L1 Adipocytes

Environmental endocrine disruptors (EDCs), including bisphenol-A (BPA), have been recently involved in obesity and diabetes by dysregulating adipose tissue function. Our aim was to examine whether prolonged exposure to low doses of BPA could affect adipogenesis and adipocyte metabolic functions. Therefore, 3T3-L1 pre-adipocytes were cultured for three weeks with BPA 1nM to mimic human environmental exposure. We evaluated BPA effect on cell proliferation, differentiation, gene expression and adipocyte metabolic function. BPA significantly increased pre-adipocyte proliferation (p<0.01). In 3T3-L1 adipocytes differentiated in the presence of BPA, the expression of Peroxisome proliferator-activated receptor gamma (PPARγ), Fatty Acid Binding Protein 4/Adipocyte Protein 2 (FABP4/AP2) and CCAAT/enhancer binding protein (C/EBPα) was increased by 3.5, 1.5 and 3 folds, respectively. Mature adipocytes also showed a significant increase in lipid accumulation (p<0.05) and alterations of insulin action, with significant reduction in insulin-stimulated glucose utilization (p<0.001). Moreover, in mature adipocytes, mRNA levels of Leptin, interleukin-6 (IL6) and interferon-γ (IFNγ) were significantly increased (p<0.05). In conclusion, BPA prolonged exposure at low doses, consistent with those found in the environment, may affect adipocyte differentiation program, enhancing pre-adipocyte proliferation and anticipating the expression of the master genes involved in lipid/glucose metabolism. The resulting adipocytes are hypertrophic, with impaired insulin signaling, reduced glucose utilization and increased pro-inflammatory cytokine expression. Thus, these data supported the hypothesis that BPA exposure, during critical stages of adipose tissue development, may cause adipocyte metabolic dysfunction and inflammation, thereby increasing the risk of developing obesity-related diseases.     

Application of anhydrobiosis and dehydration of yeasts for non-conventional biotechnological goals

Dehydration of yeast cells causes them to enter a state of anhydrobiosis in which their metabolism is temporarily and reversibly suspended. This unique state among organisms is currently used in the production of active dry yeasts, mainly used in baking and winemaking. In recent decades non-conventional applications of yeast dehydration have been proposed for various modern biotechnologies. This mini-review briefly summarises current information on the application of dry yeasts in traditional and innovative fields. It has been shown that dry yeast preparations can be used for the efficient protection, purification and bioremediation of the environment from heavy metals. The high sorption activity of dehydrated yeasts can be used as an interesting tool in winemaking due to their effects on quality and taste. Dry yeasts are also used in agricultural animal feed. Another interesting application of yeast dehydration is as an additional stage in new methods for the stable immobilisation of microorganisms, especially in cases when biotechnologically important strains have no affinity with the carrier. Such immobilisation methods also provide a new approach for the successful conservation of yeast strains that are very sensitive to dehydration. In addition, the application of dehydration procedures opens up new possibilities for the use of yeast as a model system. Separate sections of this review also discuss possible uses of dry yeasts in biocontrol, bioprotection and biotransformations, in analytical methods as well as in some other areas.     

Better up,worse down: bidirectional consequences of three decades of climate change on a relict population of Erebia cassioides

Orophilous species are often unable to escape the consequences of climate change because mountains are surrounded by unsuitable habitats. Among them, several endemic species belonging to the genus Erebia Dalman (Lepidoptera, Nymphalidae, Satyrinae) can be considered as key species to assess the risk of biodiversity loss of mountain habitats. The aim of this paper is to measure changes that have occurred in the altitudinal distribution of Erebia cassioides on the Pollino Massif (Southern Italy) during the last 37 years. Sixteen sites sampled in 1975 have been resampled after about three decades (2004, 2012). In 1975 56 % of the sampled population inhabited sites above and 44 % sites below the treeline, while in 2004 and 2012 99 % of the population were observed above the treeline. Furthermore, we observed an uphill shift of 180 m in the barycentre altitude of the species distribution and an unexpected increased density of the population above the treeline which led to a range reduction coupled to population increase of E. cassioides. This pattern contrasts with the usually observed one that couples habitat reduction to population decreasing. The reason for the observed pattern is unclear, but the implication for conservation strategies could be important if confirmed for other species. In fact, during coming decades local extinctions as a consequence of climate change might be fewer and more delayed than expected, and relict populations of cold adapted species could be preserved for a longer time span within optimal habitat refugia.     

Sequencing Biological and Physical Events Affects Specific Frequency Bands within the Human Premotor Cortex: An Intracerebral EEG Study

Evidence that the human premotor cortex (PMC) is activated by cognitive functions involving the motor domain is classically explained as the reactivation of a motor program decoupled from its executive functions, and exploited for different purposes by means of a motor simulation. In contrast, the evidence that PMC contributes to the sequencing of non-biological events cannot be explained by the simulationist theory. Here we investigated how motor simulation and event sequencing coexist within the PMC and how these mechanisms interact when both functions are executed. We asked patients with depth electrodes implanted in the PMC to passively observe a randomized arrangement of images depicting biological actions and physical events and, in a second block, to sequence them in the correct order. This task allowed us to disambiguate between the simple observation of actions, their sequencing (recruiting different motor simulation processes), as well as the sequencing of non-biological events (recruiting a sequencer mechanism non dependant on motor simulation). We analysed the response of the gamma, alpha and beta frequency bands to evaluate the contribution of each brain rhythm to the observation and sequencing of both biological and non-biological stimuli. We found that motor simulation (biological>physical) and event sequencing (sequencing>observation) differently affect the three investigated frequency bands: motor simulation was reflected on the gamma and, partially, in the beta, but not in the alpha band. In contrast, event sequencing was also reflected on the alpha band.     

Jatrophane diterpenes from Euphorbia spp. as modulators of multidrug resistance in cancer therapy

A phytochemical investigation of the aerial parts of Euphorbia spp., considered one of the most common elements of Mediterranean landascape, led to the isolation of a large number of bioactive plant metabolites, belonging to the diterpenes family. Above all, over seventy jatrophane, modified jatrophane, segetane, pepluane, and paraliane diterpenoids, fifty of them reported for the first time, were extracted, purified and characterized from Euphorbia dendroides, Euphorbia characias, Euphorbia peplus, Euphorbia paralias and Euphorbia helioscopia. These compounds showed interesting pharmacological activities. In particular, jatrophanes, modified jatrophanes and lathyranes exhibited a potent inhibitory activity against P-glycoprotein (Pgp), a membrane protein that confers cellular ability to resist lethal doses of certain cytotoxic drugs by pumping them to the outside, thus resulting in a reduced cytotoxicity. Among the others, our chemical survey led to isolation of the most powerful inhibitors of daunomycin-efflux activity isolated to date for this class of inhibitors, named euphodendroidin D and pepluanin A. Their efficiency was found to be at least two-fold higher than the conventional modulator cyclosporin A, taken as a reference. In addition, the isolation of a high number of natural structurally-related analogues allowed us to perform Structure Activity Relationship (SAR) studies, without any chemical modification, which gave information on the key pharmacophoric elements of these new class of promising drugs. A further set of diterpene analogues, very recently isolated from sun spurge, E. helioscopia, individually investigated for their Pgp- and BCRP-inhibiting properties, appeared to be specific inhibitors of Pgp since they showed no significant activity against BCRP, thus resembling to the third-generation class of specific MDR inhibitors.     

Speed rate (SR) as a new dynamic index of melanoma behavior

Melanomas are skin tumors that show a variety of biological behavior. Some develop very fast and some other grow extremely slow, with metastasis appearing, eventually, many years after the diagnosis. The number of mitoses in primary melanoma has been related to a more aggressive tumor and may have a potential as predictive factor for cutaneous melanoma survival. However, tumor mitotic rate is a static measure and in multivariate analysis on tumor survival, it has scored less than other tumor characteristics. We tried to evolve tumor mitotic rate from a static parameter to a time‐dependent one. Similar to the already described growth rate (GR), we propose the speed rate (SR). SR is defined as the ratio of tumor mitotic rate to time to melanoma development. A prospective series of 345 patients with melanoma was investigated for the role of SR as predictive factor for sentinel lymph node (SLN) positivity and tumor progression. We calculated the best threshold for SR and GR to predict the risk of recurrence. Melanoma clinical and histological characteristics as well as GR were correlated in a multivariated analysis with SR. SR values >0.2 mitoses/month were associated with negative prognostic factors such as ulceration (82.8%), SLN positivity (80%), progression (82.8%), and death (85.7%). The association of GR > 0.3 mm/months and SR > 0.2 mitoses/month had a significant predictive value in terms of SLN positivity, progression, and recurrence‐free survival. We propose SR as a new “dynamic” predictor of histological SLN positivity and melanoma recurrence risk. We think that he association with this new feature with GR may be helpful in improving the accuracy of predicted clinical outcome of patient especially with thin melanomas.