Intraventricular Transplantation of Engineered Neuronal Precursors for In Vivo Neuroarchitecture Studies

Gene control of neuronal cytoarchitecture is currently the subject of intensive investigation. Described here is a simple method developed to study in vivo gene control of neocortical projection neuron morphology. This method is based on (1) in vitro lentiviral engineering of neuronal precursors as "test" and "control" cells, (2) their co-transplantation into wild-type brains, and (3) paired morphometric evaluation of their neuronal derivatives. Specifically, E12.5 pallial precursors from panneuronal, genetically labeled donors, are employed for this purpose. They are engineered to take advantage of selected promoters and tetON/OFF technology, and they are free-hand transplanted into neonatal lateral ventricles. Later, upon immunofluorescence profiling of recipient brains, silhouettes of transplanted neurons are fed into NeurphologyJ open source software, their morphometric parameters are extracted, and average length and branching index are calculated. Compared to other methods, this one offers three main advantages: it permits achieving of fine control of transgene expression at affordable costs, it only requires basic surgical skills, and it provides statistically reliable results upon analysis of a limited number of animals. Because of its design, however, it is not adequate to address non cell-autonomous control of neuroarchitecture. Moreover, it should be preferably used to investigate neurite morphology control after completion of neuronal migration. In its present formulation, this method is exquisitely tuned to investigate gene control of glutamatergic neocortical neuron architecture. Taking advantage of transgenic lines expressing EGFP in other specific neural cell types, it can be re-purposed to address gene control of their architecture

MAXIMUM MUON PRODUCTION DEPTH AND ITS FLUCTUATIONS ABOVE 15 EEV AT THE PIERRE AUGER OBSERVATORY: MASS COMPOSITION AND CONSTRAINTS ON HADRONIC INTERACTION MODELS

The surface detector array of the Pierre Auger Observatory measures the arrival time distribution of particles and it therefore provides indirect information on the longitudinal development of the muonic component of extensive air showers. In this work, the depth at which the muon production is maximum and the corresponding shower-to-shower fluctuations are reconstructed for more than 2000 events above 15 EeV (1.5X10^19 eV), in a wide range of zenith angles between 45\ub0 and 65\ub0. Both observables are analysed in terms of mass composition of ultra-high energy cosmic rays, one of the most intriguing issues of modern astrophysics. In addition, these observables are exploited to attempt to constrain the most up-to date hadronic interactions models, which are used in the simulation of extensive air showers

Multidimensional Functional Profiling of Human Neuropathogenic FOXG1 Alleles in Primary Cultures of Murine Pallial Precursors

FOXG1 is an ancient transcription factor gene mastering telencephalic development. A number of distinct structural FOXG1 mutations lead to the “FOXG1 syndrome”, a complex and heterogeneous neuropathological entity, for which no cure is presently available. Reconstruction of primary neurodevelopmental/physiological anomalies evoked by these mutations is an obvious pre-requisite for future, precision therapy of such syndrome. Here, as a proof-of-principle, we functionally scored three FOXG1 neuropathogenic alleles, FOXG1G224S, FOXG1W308X, and FOXG1N232S, against their healthy counterpart. Specifically, we delivered transgenes encoding for them to dedicated preparations of murine pallial precursors and quantified their impact on selected neurodevelopmental and physiological processes mastered by Foxg1: pallial stem cell fate choice, proliferation of neural com-mitted progenitors, neuronal architecture, neuronal activity, and their molecular correlates. Briefly, we found that FOXG1G224S and FOXG1W308X generally performed as a gain-and a loss-of-function-allele, respectively, while FOXG1N232S acted as a mild loss-of-function-allele or phenocopied FOXG1WT . These results provide valuable hints about processes misregulated in patients heterozygous for these mutations, to be re-addressed more stringently in patient iPSC-derivative neuro-organoids. Moreover, they suggest that murine pallial cultures may be employed for fast multidimensional profiling of novel, human neuropathogenic FOXG1 alleles, namely a step propedeutic to timely delivery of therapeutic precision treatments

Suprathermal particle addition to solar wind pressure: possible influence on magnetospheric transmissivity of low energy cosmic rays?

Energetic (suprathermal) solar particles, accelerated in the interplanetary medium, contribute to the solar wind pressure, in particular during high solar activity periods. We estimated the effect of the increase of solar wind pressure due to suprathermal particles on magnetospheric transmissivity of galactic cosmic rays in the case of one recent solar event

Association between Resistin Levels and All-Cause and Cardiovascular Mortality: A New Study and a Systematic Review and Meta-Analysis.

CONTEXT: Studies concerning the association between circulating resistin and mortality risk have reported, so far, conflicting results. OBJECTIVE: To investigate the association between resistin and both all-cause and cardiovascular (CV) mortality risk by 1) analyzing data from the Gargano Heart Study (GHS) prospective design (n=359 patients; 81 and 58 all-cause and CV deaths, respectively); 2) performing meta-analyses of all published studies addressing the above mentioned associations. DATA SOURCE AND STUDY SELECTION: MEDLINE and Web of Science search of studies reporting hazard ratios (HR) of circulating resistin for all-cause or CV mortality. DATA EXTRACTION: Performed independently by two investigators, using a standardized data extraction sheet. DATA SYNTHESIS: In GHS, adjusted HRs per one standard deviation (SD) increment in resistin concentration were 1.28 (95% CI: 1.07-1.54) and 1.32 (95% CI: 1.06-1.64) for all-cause and CV mortality, respectively. The meta-analyses included 7 studies (n=4016; 961 events) for all-cause mortality and 6 studies (n=4,187: 412 events) for CV mortality. Pooled HRs per one SD increment in resistin levels were 1.21 (95% CI: 1.03-1.42, Q-test p for heterogeneity<0.001) and 1.05 (95% CI: 1.01-1.10, Q-test p for heterogeneity=0.199) for all-cause and CV mortality, respectively. At meta-regression analyses, study mean age explained 9.9% of all-cause mortality studies heterogeneity. After adjusting for age, HR for all-cause mortality was 1.24 (95% CI: 1.06-1.45). CONCLUSIONS: Our results provide evidence for an association between circulating resistin and mortality risk among high-risk patients as are those with diabetes and coronary artery disease

Polychlorinated dioxins, furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in food from Italy: Estimates of dietaryintake and assessment

Dietary intake of polychlorinated dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) from various foods (fish and seafood, meat and meat-based products, milk and dairy products, hen eggs, olive oil and fats) was investigated for various sex/age groups of the Italian population. The concentrations of PCDD/Fs and dl-PCBs and their contribution to total TEQ values varied depending on food matrix. Fish (0.50 pg WHO-TEQ/g wet weight) and seafood (0.16 pg WHO-TEQ/g wet weight) showed the highest mean concentrations of PCDD/Fs plus dl-PCBs, followed by meat (1.70 pg WHO-TEQ/g lipid weight), meat based products (1.03 pg WHO-TEQ/g lipid weight), milk and dairy products (0.78 pg WHO-TEQ/g lipid weight), hen eggs (0.71 pg WHO-TEQ/g lipid weight), fats (0.27 pg WHO-TEQ/g lipid weight) and olive oil (0.09 pg WHO-TEQ/g lipid weight). In all samples WHO-TEQ PCDD/F plus dl-PCB concentrations fulfilled the European Union food law, except in pork loin samples (1.39 pg WHO-TEQ/g lipid weight). Differences in exposure depending on the sex/age groups (children&nbsp;&gt;&nbsp;teenagers&nbsp;&gt;&nbsp;adults&nbsp;&gt;&nbsp;elders) and hypotheses considered (lower bound and upper bound) were encountered. Non-cancer risk values showed a low exposure. Carcinogenicity risk results revealed that highly exposed individuals were distributed over all sex/age groups, even though the proportion of individuals exceeding the safe limit was higher in children. These data once again underline the importance of trying to control the levels of these contaminants in fishery products, particularly in fish, who represents one of the main exposure sources for consumers. PRACTICAL APPLICATION: This paper may help the consumer in making food choices to minimize the exposure risk to dioxins, furans and PCBs

Phytochemical and biological characterization of dry outer scales extract from Tropea red onion (Allium cepa L. var. Tropea)–A promising inhibitor of pancreatic lipase

Background: Allium cepa L. var. Tropea is typically cultivated in Calabria (Italy) and it is certified as “Cipolla Rossa di Tropea Calabria-PGI” (Tropea red onion). The use of clinically available anti-obesity drugs such as Orlistat is being gradually dismissed due to their side-effects and this has encouraged the search for alternative inhibitors of intestinal lipases such as phytochemicals showing less side-effects. In this study we aimed to evaluate for the first time the anti-obesity potential of the hydroalcoholic extract from the dry outer scales of Tropea red onion by the assesment of its capacity to inhibit pancreatic lipase. Its possible mechanism of action was also studied with planar lipid membranes (PLMs) surrogate of intestinal membranes. Methods: Specialized metabolites in the extract were determined by GC–MS, HPLC-DAD, HPLC-UV-DAD and HPLC-HRMS analyses. Inhibition of pancreatic lipase was studied in vitro against crude lipase Type II from porcine pancreas. PLMs used in the electrophysiology measurements were made up of DOPS:DOPE:POPC. Results: The extract contained quercetin-4′-O-glucoside, quercetin and quercetin-3,4′-O-diglucoside as the most abundant phenolics. Among apolar constituents, γ-sitosterol, linoleic and stearic acids were dominant. The lipase inhibitory effect of the extract had an IC50 value equal to 0.77±0.03 mg/mL (positive control, IC50 = 0.018 mg/mL). The electrophysiological study demonstrated that the extract is able to incorporate into PLMs and to form transient channel-like events Conclusions: Taken altogether, the results allow us to suggest that the hydroalcoholic extract from the dry outer scales of Tropea red onion could prevent lipid ester hydrolysis and it has a protective effect against phospholipase as found for interfacially active compounds

Olive tree in circular economy as a source of secondary metabolites active for human and animal health beyond oxidative stress and inflammation

none10noExtra-virgin olive oil (EVOO) contains many bioactive compounds with multiple biological activities that make it one of the most important functional foods. Both the constituents of the lipid fraction and that of the unsaponifiable fraction show a clear action in reducing oxidative stress by acting on various body components, at concentrations established by the European Food Safety Authority’s claims. In addition to the main product obtained by the mechanical pressing of the fruit, i.e., the EVOO, the residual by-products of the process also contain significant amounts of antioxidant molecules, thus potentially making the Olea europea L. an excellent example of the circular economy. In fact, the olive mill wastewaters, the leaves, the pomace, and the pits discharged from the EVOO production process are partially recycled in the nutraceutical and cosmeceutical fields also because of their antioxidant effect. This work presents an overview of the biological activities of these by-products, as shown by in vitro and in vivo assays, and also from clinical trials, as well as their main formulations currently available on the market.openMallamaci R.; Budriesi R.; Clodoveo M.L.; Biotti G.; Micucci M.; Ragusa A.; Curci F.; Muraglia M.; Corbo F.; Franchini C.Mallamaci, R.; Budriesi, R.; Clodoveo, M. L.; Biotti, G.; Micucci, M.; Ragusa, A.; Curci, F.; Muraglia, M.; Corbo, F.; Franchini, C