Valproic acid neuroprotection in 6-OHDA lesioned rat, a model for parkinson's disease

Background: Valproic acid (VPA) a long standing anti-epileptic and anti-manic drug has been recently investigated as a neuroprotective molecule, in relation to its action as an inhibitor of histone deacetylases (HDACs), favoring relaxed configuration of chromatin and thus promoting gene transcription. Methods: In the present study, chronic administration of VPA added to the diet, was tested for neuroprotection in a rat model of Parkinson's disease. The model consists of multiple injections of the dopaminergic toxin, 6-hydroxydopamine (6-OHDA), unilaterally in the striatum with consequent degeneration of the dopaminergic neurons originating the nigro-striatal pathway. This model of neurodegeneration is widely used as a reliable animal model for Parkinson's disease (PD). Results: Chronic VPA administration significantly reduced degeneration of dopaminergic neurons in the substantia nigra, and of dopaminergic terminals in the striatum, in rats subjected to the unilateral lesion of the nigrostriatal pathway. VPA treatment was also able to increase α-synuclein expression in the substantia nigra and to counteract the lesion-dependent decrease of the protein in the substantia nigra itself and in the striatum. Conclusions: Present data, which follow previous results obtained in the rotenone rat model of nigrostriatal degeneration, allow to propose VPA as a treatment to be tested for its effectiveness in other animal models of parkinsonism, in view of possible translation to patients

Nitric Oxide Protects Neuroblastoma Cells from Apoptosis Induced by Serum Deprivation through cAMP-response Element-binding Protein (CREB) Activation

The transcription factor cAMP-response element-binding protein (CREB) mediates survival in many cells, including neurons. Recently, death of cerebellar granule neurons due to nitric oxide (NO) deprivation was shown to be accompanied by down-regulation of CREB activity (1). We now provide evidence that overproduction of endogenous NO or supplementation with exogenous NO renders SK-N-BE human neuroblastoma cells more resistant to apoptosis induced by serum deprivation. Parental cells underwent apoptosis after 24 h of serum deprivation, an outcome largely absent in clones overexpressing human neuronal nitric oxide synthase (nNOS). This protective effect was reversed by the inhibition of NOS itself or soluble guanylyl cyclase, pointing at cGMP as an intermediate effector of NO-mediated rescue. A slow-releasing NO donor protected parental cells to a significant extent, thus confirming the survival effect of NO. The impaired viability of serum-deprived parental cells was accompanied by a strong decrease of CREB phosphorylation and transcriptional activity, effects significantly attenuated in nNOS-overexpressing clones. To confirm the role of CREB in survival, the ectopic expression of CREB and/or protein kinase A largely counteracted serum deprivation-induced cell death of SK-N-BE cells, whereas transfection with a CREB negative mutant was ineffective. These experiments indicate that CREB activity is an important step for NO-mediated survival in neuronal cells

Development of an eco-sustainable solution for the second life of decommissioned oil and gas platforms:The mineral accretion technology

With the approaching end of the productive lives of offshore oil and gas platforms, the issue about decommissioning and what to do with existing structures arises. In this regard, this study aims to test solutions, at a preliminary level, for the eco-sustainable reuse of platforms at the end of their extraction phase. In particular, mineral accretion technology is applied by low-voltage electrolysis of seawater due to the precipitation of calcium carbonate on a cathode material in order to assess the protection capacity of the platforms against corrosion. This approach allows the extension of a platform’s “life” under a more sustainable purpose. The results, derived from laboratory and field experiments, will allow us to reduce uncertainties and define the best operating conditions to increase the efficiency of the mineral accretion technology in the marine ecosystem. The data collection on the main parameters that influence the process (i.e., temperature, salinity, and applied current) and the quantitative analysis of the collected material allowed us to acquire a better knowledge about mineral composition and deposition rate

Localisation-to-delocalisation transition of moir\'{e} excitons in WSe2_2/MoSe2_2 heterostructures

Moir\'{e} excitons (MXs) are electron-hole pairs localised by the periodic (moir\'{e}) potential forming in two-dimensional heterostructures (HSs). MXs can be exploited, $e.g.$, for creating nanoscale-ordered quantum emitters and achieving or probing strongly correlated electronic phases at relatively high temperatures. Here, we studied the exciton properties of a WSe$_2$/MoSe$_2$ HS from $T$=6 K to room temperature using time-resolved and continuous-wave micro-photoluminescence, also under magnetic field. The exciton dynamics and emission lineshape evolution with temperature show clear signatures that MXs de-trap from the moir\'{e} potential and turn into free interlayer excitons (IXs) at $T\gtrsim$120 K. The MX-to-IX transition is also apparent from the exciton magnetic moment reversing its sign when the moir\'{e} potential is not capable to localise excitons at elevated temperatures. Concomitantly, the exciton formation and decay times reduce drastically. Thus, our findings establish the conditions for a truly confined nature of the exciton states in a moir\'{e} superlattice with increasing temperature

Structural insights into the DNA recognition mechanism by the bacterial transcription factor PdxR

Specificity in protein-DNA recognition arises from the synergy of several factors that stem from the structural and chemical signatures encoded within the targeted DNA molecule. Here, we deciphered the nature of the interactions driving DNA recognition and binding by the bacterial transcription factor PdxR, a member of the MocR family responsible for the regulation of pyridoxal 5 & PRIME;-phosphate (PLP) biosynthesis. Single particle cryo-EM performed on the PLP-PdxR bound to its target DNA enabled the isolation of three conformers of the complex, which may be considered as snapshots of the binding process. Moreover, the resolution of an apo-PdxR crystallographic structure provided a detailed description of the transition of the effector domain to the holo-PdxR form triggered by the binding of the PLP effector molecule. Binding analyses of mutated DNA sequences using both wild type and PdxR variants revealed a central role of electrostatic interactions and of the intrinsic asymmetric bending of the DNA in allosterically guiding the holo-PdxR-DNA recognition process, from the first encounter through the fully bound state. Our results detail the structure and dynamics of the PdxR-DNA complex, clarifying the mechanism governing the DNA-binding mode of the holo-PdxR and the regulation features of the MocR family of transcription factors

Next generation terabit transponder

Affordable cost and power for next generation transponders is estimated. Electronics and photonics joint progress and subcarrier generation is argued to achieve 1 Tb/s with twice the power and cost of current 100 Gb/s transponders

Choline acetyltransferase activity at different ages in brain of Ts65Dn mice, an animal model for Down's syndrome and related neurodegenerative diseases.

Ts65Dn mice, trisomic for a portion of chromosome 16 segmentally homologous to human chromosome 21, are an animal model for Down's syndrome and related neurodegenerative diseases, such as dementia of Alzheimer type. In these mice, cognitive deficits and alterations in number of basal forebrain cholinergic neurons have been described. We have measured in Ts65Dn mice the catalytic activity of the cholinergic marker, choline acetyltransferase (ChAT), as well as the activity of the acetylcholine degrading enzyme acetylcholinesterase (AChE), in the hippocampus and in cortical targets of basal forebrain cholinergic neurons. In mice aged 10 months, ChAT activity was significantly higher in Ts65Dn mice, compared to 2N animals, in the hippocampus, olfactory bulb, olfactory cortex, pre-frontal cortex, but not in other neocortical regions. At 19 months of age, on the other hand, no differences in ChAT activity were found. Thus, alterations of ChAT activity in these forebrain areas seem to recapitulate those recently described in patients scored as cases of mild cognitive impairment or mild Alzheimer's disease. Other neurochemical markers putatively associated with the disease progression, such as those implicating astrocytic hyperactivity and overproduction of amyloid precursor protein family, were preferentially found altered in some brain regions at the oldest age examined (19 months)