The tower of London (tol) in Italy. standardization of the tol test in an Italian population

Deficit in planning and problem-solving, affecting a wide range of neuropsychological patients, has been widely investigated using the Tower of London (ToL) test, as developed by Shallice (Philos Trans R Soc Lond Ser B Biol Sci 298:199-209, 1). The ToL taps on several executive functions (EF), such as planning, time for planning or rule breaks, which may be usefully indexed by different ToL measurements. However, in its original version, the different aspects involved in ToL are not evaluated in a specific way.Here, we report the standardization of the ToL, on 896 individuals aged 15-86 years, taking in account individual factors (i.e. gender, age, years of education) which may affect performances on ToL. We computed several indexes on the ToL including score, planning and execution times, perseverations, rule breaks and self-monitoring. We found that these indexes were affected by individual factors such as gender, age and education. Present results not only provide extensive normative data according to gender, as well as different age and education ranges, but also represent a very useful instrument for a more fine-grained diagnosis of EF deficits in a wide range of neuropsychological patients, including traumatic brain injury and brain-damaged patients, as well as Alzheimer's disease and Parkinson's disease patients

Blockade of in vitro ictogenesis by low-frequency stimulation coincides with increased epileptiform response latency

Low-frequency stimulation, delivered through transcranial magnetic or deep-brain electrical procedures, reduces seizures in patients with pharmacoresistant epilepsy. A similar control of ictallike discharges is exerted by low-frequency electrical stimulation in rodent brain slices maintained in vitro during convulsant treatment. By employing field and “sharp” intracellular recordings, we analyzed here the effects of stimuli delivered at 0.1 or 1 Hz in the lateral nucleus of the amygdala on ictallike epileptiform discharges induced by the K+ channel blocker 4-aminopyridine in the perirhinal cortex, in a rat brain slice preparation. We found that 1) ictal events were nominally abolished when the stimulus rate was brought from 0.1 to 1 Hz; 2) this effect was associated with an increased latency of the epileptiform responses recorded in perirhinal cortex following each stimulus; and 3) both changes recovered to control values following arrest of the 1-Hz stimulation protocol. The control of ictal activity by 1-Hz stimulation and the concomitant latency increase were significantly reduced by GABAB receptor antagonism. We propose that this frequency-dependent increase in latency represents a short-lasting, GABAB receptor-dependent adaptive mechanism that contributes to decrease epileptiform synchronization, thus blocking seizures in epileptic patients and animal models

Diminished presynaptic GABA(B) receptor function in the neocortex of a genetic model of absence epilepsy

Changes in GABA(B) receptor subunit expression have been recently reported in the neocortexof epileptic WAG/Rij rats that are genetically prone to experience absence seizures.These alterations may lead to hyperexcitability by downregulating the function of presynapticGABA(B) receptors in neocortical networks as suggested by a reduction in paired-pulsedepression. Here, we tested further this hypothesis by analyzing the effects induced by theGABA(B) receptor agonist baclofen (0.1-10 μM) on the inhibitory events recorded in vitro fromneocortical slices obtained from epileptic (>180 day-old) WAG/Rij and age-matched, nonepilepticcontrol (NEC) rats. We found that higher doses of baclofen were required todepress pharmacologically isolated, stimulus-induced IPSPs generated by WAG/Rij neuronsas compared to NEC. We also obtained similar evidence by comparing the effects ofbaclofen on the rate of occurrence of synchronous GABAergic events recorded by WAG/Rijand NEC neocortical slices treated with 4-aminopyridine+glutamatergic receptor antagonists.In conclusion, these data highlight a decreased function of presynaptic GABA(B) receptorsin the WAG/Rij rat neocortex. We propose that this alteration may contribute toneocortical hyperexcitability and thus to absence seizures

Reduced GABA(B) receptor subunit expression and paired-pulse depression in a genetic model of absence seizures

Neocortical networks play a major role in the genesis of generalized spike-and-wave (SW) discharges associated with absence seizures in humans and in animal models, including genetically predisposed WAG/Rij rats. Here, we tested the hypothesis that alterations in GABAB receptors contribute to neocortical hyperexcitability in these animals. By using Real-Time PCR we found that mRNA levels for most GABAB(1) subunits are diminished in epileptic WAG/Rij neocortex as compared with age-matched non-epileptic controls (NEC), whereas GABAB(2) mRNA is unchanged. Next, we investigated the cellular distribution of GABAB(1) and GABAB(2) subunits by confocal microscopy and discovered that GABAB(1) subunits fail to localize in the distal dendrites of WAG/Rij neocortical pyramidal cells. Intracellular recordings from neocortical cells in an in vitro slice preparation demonstrated reduced paired-pulse depression of pharmacologically isolated excitatory and inhibitory responses in epileptic WAG/Rij rats as compared with NECs; moreover, paired-pulse depression in NEC slices was diminished by a GABAB receptor antagonist to a greater extent than in WAG/Rij rats further suggesting GABAB receptor dysfunction. In conclusion, our data identify changes in GABAB receptor subunit expression and distribution along with decreased paired-pulse depression in epileptic WAG/Rij rat neocortex. We propose that these alterations may contribute to neocorticalhyperexcitability and thus to SW generation in absence epilepsy

Quantum Technologies with 2D-materials

In the recent years, the continuous advancements in oxide thin films epitaxial growth and characterization techniques led to the possibility of design and control complex oxide heterointerfaces and characterize their crystal and electronic structure with atomic precision. These advancements brought to light a wealth of properties for oxide heterointerfaces and opened to new opportunities for oxide electronics and spintronics. Now the research on oxide interfaces is expanding outside the pure material science realm, entering the field of application-oriented devices. In this thesis, the innovative and intriguing functionalities arising in an oxide system where Rashba spin-orbit coupling, magnetism, superconductivity and high-mobility are combined in the same two dimensional electron gas (2DEG) have been reported. The focus of my work has two main aspects: on one side, to study the interplay between the several ground states in the 2DEG at the LaAlO3/EuTiO3/SrTiO3 interface; on the other, to realize nanodevices which will make these phenomena functional for new quantum electronics with advantages like scalability, easy top-down processing and possibility to manipulate the 2DEG system with unprecedented control

Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence.

Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression of ADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, we demonstrate that Pten-deficient prostate tumours are addicted to the NOTCH signalling. Importantly, we find that pharmacological inhibition of γ-secretase promotes growth arrest in both Pten-null and Pten/Trp53-null prostate tumours by triggering cellular senescence. Altogether, our findings describe a novel pro-tumorigenic network that links PTEN loss to ADAM17 and NOTCH signalling, thus providing the rational for the use of γ-secretase inhibitors in advanced prostate cancer patients

Application of different analytical methods for the determination of phenolics and antioxidant activity in hawthorn (Crataegus spp.) bud and sprout herbal extracts

Hawthorn (Crataegus spp., family: Rosaceae) extracts have been used as pharmaceutical preparations owing to positive effects on cardiovascular system. The AlCl3-based official method employed for the determination of pharmacologically active compounds was compared with other techniques such as Folin-Ciocalteau method and HPLC-DAD. Antioxidant activity was determined by ABTS radical cation assay. Methods were applied on extracts from buds and sprouts collected from common hawthorn (C. monogyna Jacq., C. laevigata (Poir.) DC.) located in Northeastern Italy. Phenolic content determined by AlCl3-based method, Folin-Ciocalteau method, and HPLC-DAD was in the range 23,534-27,728, 75,284-100,616 and 57,317-58,639 mg kg-1 of dry matter (DM), respectively, in buds, and 17,280-19,330, 27,653-38,590, and 30,635-32,185 mg kg-1 DM, respectively, in sprouts. Antioxidant activity ranged from 119,864 to 174,640 and 31,484 to 52,584 mg Trolox eq. kg-1 DM in buds and sprouts, respectively. Phenolic amount and profile were significantly affected by phenological stage and sampling location. Antioxidant activity was related to flavan-3-ol and hydroxycinnamic acid amount, and to non-phenolic substances. AlCl3-based method underestimated total phenolic content owing to lack of selectivity to important phenolic classes whereas Folin-Ciocalteau method was affected by non-phenolic interfering substances. HPLC-DAD proved to be more effective in determining hawthorn phenolics