Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS

The present study was aimed at characterizing the effects of Withania somnifera (Wse) and Mucuna pruriens (Mpe) on a Drosophila melanogaster model for Amyotrophic Lateral Sclerosis (ALS). In particular, the effects of Wse and Mpe were assessed following feeding the flies selectively overexpressing the wild human copper, zinc-superoxide dismutase (hSOD1-gain-of-function) in Drosophila motoneurons. Although ALS-hSOD1 mutants showed no impairment in life span, with respect to GAL4 controls, the results revealed impairment of climbing behaviour, muscle electrophysiological parameters (latency and amplitude of ePSPs) as well as thoracic ganglia mitochondrial functions. Interestingly, Wse treatment significantly increased lifespan of hSDO1 while Mpe had not effect. Conversely, both Wse and Mpe significantly rescued climbing impairment, and also latency and amplitude of ePSPs as well as failure responses to high frequency DLM stimulation. Finally, mitochondrial alterations were any more present in Wse-but not in Mpe-Treated hSOD1 mutants. Hence, given the role of inflammation in the development of ALS, the high translational impact of the model, the known anti-inflammatory properties of these extracts, and the viability of their clinical use, these results suggest that the application of Wse and Mpe might represent a valuable pharmacological strategy to counteract the progression of ALS and related symptom

(1)H-NMR analysis provides a metabolomic profile of patients with multiple sclerosis

OBJECTIVE: To investigate the metabolomic profiles of patients with multiple sclerosis (MS) and to define the metabolic pathways potentially related to MS pathogenesis. METHODS: Plasma samples from 73 patients with MS (therapy-free for at least 90 days) and 88 healthy controls (HC) were analyzed by (1)H-NMR spectroscopy. Data analysis was conducted with principal components analysis followed by a supervised analysis (orthogonal partial least squares discriminant analysis [OPLS-DA]). The metabolites were identified and quantified using Chenomx software, and the receiver operating characteristic (ROC) curves were calculated. RESULTS: The model obtained with the OPLS-DA identified predictive metabolic differences between the patients with MS and HC (R2X = 0.615, R2Y = 0.619, Q2 = 0.476; p < 0.001). The differential metabolites included glucose, 5-OH-tryptophan, and tryptophan, which were lower in the MS group, and 3-OH-butyrate, acetoacetate, acetone, alanine, and choline, which were higher in the MS group. The suitability of the model was evaluated using an external set of samples. The values returned by the model were used to build the corresponding ROC curve (area under the curve of 0.98). CONCLUSION: NMR metabolomic analysis was able to discriminate different metabolic profiles in patients with MS compared with HC. With the exception of choline, the main metabolic changes could be connected to 2 different metabolic pathways: tryptophan metabolism and energy metabolism. Metabolomics appears to represent a promising noninvasive approach for the study of M

Sardinia Radio Telescope wide-band spectral-polarimetric observations of the galaxy cluster 3C 129

We present new observations of the galaxy cluster 3C 129 obtained with the Sardinia Radio Telescope in the frequency range 6000-7200 MHz, with the aim to image the large-angular-scale emission at high-frequency of the radio sources located in this cluster of galaxies. The data were acquired using the recently-commissioned ROACH2-based backend to produce full-Stokes image cubes of an area of 1 deg x 1 deg centered on the radio source 3C 129. We modeled and deconvolved the telescope beam pattern from the data. We also measured the instrumental polarization beam patterns to correct the polarization images for off-axis instrumental polarization. Total intensity images at an angular resolution of 2.9 arcmin were obtained for the tailed radio galaxy 3C 129 and for 13 more sources in the field, including 3C 129.1 at the galaxy cluster center. These data were used, in combination with literature data at lower frequencies, to derive the variation of the synchrotron spectrum of 3C 129 along the tail of the radio source. If the magnetic field is at the equipartition value, we showed that the lifetimes of radiating electrons result in a radiative age for 3C 129 of t_syn = 267 +/- 26 Myrs. Assuming a linear projected length of 488 kpc for the tail, we deduced that 3C 129 is moving supersonically with a Mach number of M=v_gal/c_s=1.47. Linearly polarized emission was clearly detected for both 3C 129 and 3C 129.1. The linear polarization measured for 3C 129 reaches levels as high as 70% in the faintest region of the source where the magnetic field is aligned with the direction of the tail.Comment: 19 pages, 17 figures, accepted for publication in MNRA

BDNF, trkB and PSA-NCAM in the hippocampus of Roman rats after forced swimming

The selective breeding of Roman High- (RHA) and Low-Avoidance (RLA) rats are considered as a genetic model of resilience to stress-induced depression and of vulnerability to that trait, respectively1. There is evidence that alterations in neuronal plasticity in the hippocampus and other brain areas are critically involved in the pathophysiology of mood disorders. Here, we investigated on immunochemical occurrence of Brain-derived neurotrophic factor (BDNF), tyrosine-kinase receptor trkB and polysialilated form of the neural cell adhesion molecule (PSANCAM) in the hippocampus of the Roman rat lines under baseline conditions and after acute forced swimming (FS). Western blot (WB) analyses showed that, in basal conditions, the relative levels of BDNF, trkB and PSA-NCAM markedly differed, appearing lower by 48%, 25% and 65%, respectively, in RLA vs RHA rats. WB analyses carried out after FST showed no differences between baseline and FST rats. In tissue sections, BDNF-, trkB- and PSA-NCAM-like immunoreactivity (LI) showed a distinctive labelling, mainly localized to proximal neuronal processes and nerve fibers distributed in the Ammon’s horn and dentate gyrus (DG). A number of PSA-NCAM-positive neurons in the subgranular layer of dentate gyrus also occurred. Densitometric analysis further showed differences in the hippocampal subregions. Thus, upon FST, BDNF-LI was less abundant in the CA3 sector of the Ammon’s horn of FST vs control RLA rats (-24%), whereas PSA-NCAM-LI was more abundant in the DG of RHA than RLA rats (+26%). Our findings suggest that an altered neuronal availability of and/or responsiveness to BDNF and inadequate dynamic events related to neuroplasticity may contribute to outline the molecular and morphological basis for the distinct vulnerability to stress-induced depression in the two rat lines

A digital beamformer for the PHAROS2 phased array feed

PHased Arrays for Re°ector Observing Systems (PHAROS) is a C-band (4–8 GHz) Phased Array Feed (PAF) receiver designed to operate from the primary focus of a large single-dish radio astronomy antenna. It consists of an array of 220-element Vivaldi antennas (10 11 2 polarization), cryogenically cooled at roughly 20K along with low noise ampli¯ers (LNAs), and of analogue beamformers cryogenically cooled at roughly 80 K. PHAROS2, the upgrade of PHAROS, is a PAF demonstrator developed in the framework of the Square Kilometer Array Advanced Instrumentation Program (SKA AIP) with the goal of investigating the potential of the PAF technologies at high frequencies in view of their possible application on the SKA dish telescopes. The PHAROS2 design includes new cryogenically cooled LNAs with state-of-the-art performance, a digital beamformer capable of synthesizing four beams from a sub-array of 24 single-polarization antenna elements, and a C-band multi-channel Warm Section receiver capable of analogue ¯ltering and down-converting the signals from the antennas to a suitable frequency range at the input of the digital backend, providing an instantaneous bandwidth of 275MHz for each signal. In this paper, we describe the design and performance of the PHAROS2 digital backend/beamformer, based on the Italian Tile Processing Module (ITPM) hardware, which was initially developed for the SKA Low Frequency Aperture Array (LFAA). The backend was adapted to perform the beamforming for our PAF application. We describe the implementation of the beamformer on the Field Programmable Gate Arrays (FPGAs) of the ITPM and how the backend was successfully used to synthesize four independent beams, both in the laboratory (across the entire 275MHz instantaneous bandwidth) and during on-¯eld observations at the BEST-2 array (across 16MHz instantaneous bandwidth), which is a subset of the Northern Cross Radio Telescope (located in the district of Bologna, Italy). The beamformer design allows re-scaling to a greater number of beams and wider bandwidths.peer-reviewe

Transient receptor potential vanilloid type 1 (TRPV1) and neuropeptides in the dorsal root ganglia and spinal cord in a rat model of Bortezomib-induced neuropathy

Bortezomib (BTZ) is an effective antineoplastic drug that acts by inhibiting the ubiquitin-proteasome cellular pathways. In clinical practice, its chronic administration triggers a significant neurotoxicity, which has been associated with impairment of Aβ, Aδ, and C type primary afferent fibers, though the mechanism underlying its harmful effects remains still to be fully clarified. In order to mimic the clinical use of the drug, we have recently designed an experimental model based on the use of 0,20 mg/kg drug concentration for 8 weeks followed by a follow-up period of 4 weeks. We have previously shown that, in these conditions, a hallmark of neurotoxicity is represented by a small fiber neuropathy, whereas dorsal root ganglia (DRG) neurons did not show any morphological alterations. In order to provide data regarding the mechanism underlying BTZ harmful effects, here we characterize the spinal primary sensory neurons on the basis of their expression of the transient receptor potential vanilloid type-1 (TRPV1) and sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). In fact, TRPV1 is expressed by sensory neurons where it functions as a molecular integrator for nociception. Its activation causes depolarisation leading to burning pain and release of CGRP and SP which, in turn, activate their effector cell receptors and enhance the sensitization of nociceptors. With this aim, lumbar DRG and spinal cord of BTZ-treated model rats were processed for avidine-biotin-peroxidase complex or fluorescence immunohistochemistry. In the DRG, the immunolabelling for TRPV1 revealed a subpopulation of predominantly small- to medium-sized neurons which appeared more extensive in BTZ-treated rats. Centrally, TRPV1-LI labelled fiber tracts and terminal-like elements distributed in laminae I and II of the dorsal horn where they appeared widely codistributed with both CGRP-LI and SP-LI. With the exception of a slight more intense TRPV1 staining in lamina I of the dorsal horn of BTZ-treated vs control rats, no clear-cut differences in the distribution and amount of immunoreactivity for the three markers could be observed

Effect of acute administration of dietary Pistacia lentiscus L. essential oil on the ischemia-reperfusion-induced changes in rat frontal cortex and plasma

In this study Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, was tested for its protective effects in cerebral ischemia/reperfusion-induced injury in Wistar rat frontal cortex and plasma. Cerebral ischemia was produced by a 20 min bilateral common carotid artery occlusion followed by 30 min reperfusion. Pistacia lentiscus L. essential oil (E.O.) (200 mg/0, 45 ml of sunflower oil as vehicle) was administered via gavage 6 hours prior to ischemia. Rats were randomly assigned to four groups, ischemic/reperfused (I/R) and sham-operated rats treated with the vehicle or with E.O.. Different brain areas were analysed for fatty acid changes and expression of the enzyme cyclooxygenase-2 (COX-2). Ischemia/reperfusion triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid (HPUFA) most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of COX-2, as assessed by Western Blot. In plasma of ischemic/reperfused rats, E.O. administration increased both the DHA-to-eicosapentaenoic acid (EPA) ratio and levels of the endocannabinoid congeners palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). The results obtained suggest that ischemia/reperfusion triggers a cerebral insult sufficient to cause a a region specific lipid peroxidation as evidenced by the detectable, significant decrease in the tissue level of DHA, the most abundant essential fatty acid of neuronal membrane phospholipids. Acute dietary pre-treatment with E.O. triggers modifications both in the frontal cortex, where COX-2 expression decreases and the decrease of DHA is apparently prevented, and in plasma, where PEA and OEA levels increase. We suggest that the activity of PEA and OEA, as endogenous ligands of the peroxisome proliferator-activated receptor (PPAR)-alpha, by inducing the peroxisomal beta oxidation, may explain the observed increase in the DHA/EPA ratio. The latter, in fact, might account for an increased metabolism of n-3 aimed at restoring DHA within damaged brain tissue. The possibility that changes in fatty acid metabolism and plasmatic availability of PEA and OEA are correlated events represents an issue worth future investigations