Microbial Ecology and Geo-electrical Responses across a Groundwater Plume

We have used geophysics, microbiology, and geochemistry to link large-scale (30+ m) geophysical self-potential (SP) responses at a groundwater contaminant plume with its chemistry and microbial ecology of groundwater and soil from in and around it. We have found that microbially mediated transformation of ammonia to nitrite, nitrate, and nitrogen gas was likely to have promoted a well-defined electrochemical gradient at the edge of the plume, which dominated the SP response. Phylogenetic analysis demonstrated that the plume fringe or anode of the geobattery was dominated by electrogens and biodegradative microorganisms including Proteobacteria alongside Geobacteraceae, Desulfobulbaceae, and Nitrosomonadaceae. The uncultivated candidate phylum OD1 dominated uncontaminated areas of the site. We defined the redox boundary at the plume edge using the calculated and observed electric SP geophysical measurements. Conductive soils and waste acted as an electronic conductor, which was dominated by abiotic iron cycling processes that sequester electrons generated at the plume fringe. We have suggested that such geoelectric phenomena can act as indicators of natural attenuation processes that control groundwater plumes. Further work is required to monitor electron transfer across the geoelectric dipole to fully define this phenomenon as a geobattery. This approach can be used as a novel way of monitoring microbial activity around the degradation of contaminated groundwater plumes or to monitor in situ bioelectric systems designed to manage groundwater plumes

Positive allosteric modulation of GABAB receptors ameliorates sensorimotor gating in rodent models

This is the peer reviewed version of the following article: Frau, R., Bini, V., Pillolla, G., Malherbe, P., Pardu, A., Thomas, A. W., Devoto, P. and Bortolato, M. (2014), Positive Allosteric Modulation of GABAB Receptors Ameliorates Sensorimotor Gating in Rodent Models. CNS Neurosci Ther, 20: 679–684. doi:10.1111/cns.12261, which has been published in final form at http://doi.org/10.1111/cns.12261. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.BACKGROUND: Converging evidence points to the involvement of γ-amino-butyric acid B receptors (GABABRs) in the regulation of information processing. We previously showed that GABABR agonists exhibit antipsychotic-like properties in rodent models of sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. The therapeutic potential of these agents, however, is limited by their neuromuscular side effects; thus, in the present study we analyzed whether rac-BHFF, a potent GABABR positive allosteric modulator (PAM), could counter spontaneous and pharmacologically induced PPI deficits across various rodent models. METHODS: We tested the antipsychotic effects of rac-BHFF on the PPI deficits caused by the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine, in Sprague-Dawley rats and C57BL/6 mice. Furthermore, we verified whether rac-BHFF ameliorated the spontaneous PPI impairments in DBA/2J mice. RESULTS: rac-BHFF dose-dependently countered the PPI deficits across all three models, in a fashion akin to the GABABR agonist baclofen and the atypical antipsychotic clozapine; in contrast with these compounds, however, rac-BHFF did not affect startle magnitude. CONCLUSIONS: The present data further support the implication of GABABRs in the modulation of sensorimotor gating, and point to their PAMs as a novel promising tool for antipsychotic treatment, with fewer side effects than GABABR agonists

NGR Tumor-Homing Peptides : Structural Requirements for Effective APN (CD13) Targeting

Acknowledgements We thank The Development Trust, University of Aberdeen, for financial support and a fellowship to M.P.Peer reviewedPublisher PD

Ethanol-Dependent Synthesis of Salsolinol in the Posterior Ventral Tegmental Area as Key Mechanism of Ethanol’s Action on Mesolimbic Dopamine

Abnormal consumption of ethanol, the ingredient responsible for alcoholic drinks’ addictive liability, causes millions of deaths yearly. Ethanol’s addictive potential is triggered through activation, by a still unknown mechanism, of the mesolimbic dopamine (DA) system, part of a key motivation circuit, DA neurons in the posterior ventral tegmental area (pVTA) projecting to the ipsilateral nucleus accumbens shell (AcbSh). The present in vivo brain microdialysis study, in dually-implanted rats with one probe in the pVTA and another in the ipsilateral or contralateral AcbSh, demonstrates this mechanism. As a consequence of the oral administration of a pharmacologically relevant dose of ethanol, we simultaneously detect a) in the pVTA, a substance, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), untraceable under control conditions, product of condensation between DA and ethanol’s first by-product, acetaldehyde; and b) in the AcbSh, a significant increase of DA release. Moreover, such newly generated salsolinol in the pVTA is responsible for increasing AcbSh DA release via m opioid receptor (mOR) stimulation. In fact, inhibition of salsolinol’s generation in the pVTA or blockade of pVTA mORs prevents ethanol-increased ipsilateral, but not contralateral, AcbSh DA release. This evidence discloses the long-sought key mechanism of ethanol’s addictive potential and suggests the grounds for developing preventive and therapeutic strategies against abnormal consumption

Biological Assays and Chemical Composition of Volatile Oils of Bupleurum fruticosum L. (Apiaceae)

The composition of supercritical CO 2 extracts and essential oils obtained by hydrodistillation of Bupleurum fruticosum L., growing spontaneously in Italy and Portugal, and its antifungal activity is reported. The collected extracts were analyzed by GC-FID and GC-MS methods. The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oils against Candida albicans, C. tropicalis, C. krusei, C. guillermondii, C. parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, T. mentagrophytes, Microsporum canis, M. gypseum, Epidermophyton floccosum, Aspergillus niger, A. fumigatus and A. flavus

Decision trees to evaluate the risk of developing multiple sclerosis

Introduction: Multiple sclerosis (MS) is a persistent neurological condition impacting the central nervous system (CNS). The precise cause of multiple sclerosis is still uncertain; however, it is thought to arise from a blend of genetic and environmental factors. MS diagnosis includes assessing medical history, conducting neurological exams, performing magnetic resonance imaging (MRI) scans, and analyzing cerebrospinal fluid. While there is currently no cure for MS, numerous treatments exist to address symptoms, decelerate disease progression, and enhance the quality of life for individuals with MS. Methods: This paper introduces a novel machine learning (ML) algorithm utilizing decision trees to address a key objective: creating a predictive tool for assessing the likelihood of MS development. It achieves this by combining prevalent demographic risk factors, specifically gender, with crucial immunogenetic risk markers, such as the alleles responsible for human leukocyte antigen (HLA) class I molecules and the killer immunoglobulin-like receptors (KIR) genes responsible for natural killer lymphocyte receptors. Results: The study included 619 healthy controls and 299 patients affected by MS, all of whom originated from Sardinia. The gender feature has been disregarded due to its substantial bias in influencing the classification outcomes. By solely considering immunogenetic risk markers, the algorithm demonstrates an ability to accurately identify 73.24% of MS patients and 66.07% of individuals without the disease. Discussion: Given its notable performance, this system has the potential to support clinicians in monitoring the relatives of MS patients and identifying individuals who are at an increased risk of developing the disease

High-density lipoprotein contribute to G0-G1/S transition in Swiss NIH/3T3 fibroblasts

High density lipoproteins (HDLs) play a crucial role in removing excess cholesterol from peripheral tissues. Although their concentration is lower during conditions of high cell growth rate (cancer and infections), their involvement during cell proliferation is not known. To this aim, we investigated the replicative cycles in synchronized Swiss 3T3 fibroblasts in different experimental conditions: i) contact-inhibited fibroblasts re-entering cell cycle after dilution; ii) scratch-wound assay; iii) serum deprived cells induced to re-enter G1 by FCS, HDL or PDGF. Analyses were performed during each cell cycle up to quiescence. Cholesterol synthesis increased remarkably during the replicative cycles, decreasing only after cells reached confluence. In contrast, cholesteryl ester (CE) synthesis and content were high at 24h after dilution and then decreased steeply in the successive cycles. Flow cytometry analysis of DiO-HDL, as well as radiolabeled HDL pulse, demonstrated a significant uptake of CE-HDL in 24h. DiI-HDL uptake, lipid droplets (LDs) and SR-BI immunostaining and expression followed the same trend. Addition of HDL or PDGF partially restore the proliferation rate and significantly increase SR-BI and pAKT expression in serum-deprived cells. In conclusion, cell transition from G0 to G1/S requires CE-HDL uptake, leading to CE-HDL/SR-BI pathway activation and CEs increase into LDs

Isolation of the Volatile Oil from Satureja thymbra by Supercritical Carbon Dioxide Extraction: Chemical Composition and Biological Activity:

Satureja thymbra L. is well known in Italy by the popular name of "Santoreggia sarda". It grows only in Sardinia and nowadays it is restricted to the slope of the Colle San Michele in Cagliari. The composition of the aromatic extracts obtained by supercritical CO2 and by hydrodistillation and their antifungal activity is reported. The collected extracts were analyzed by GC-FID and GC-MS methods. No significant differences were observed in the composition of the volatile extracts depending on the extraction method. The results showed the presence of thymol, γ-terpinene, β-caryophyllene, p-cymene, carvacrol and borneol as main components. The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oils against Candida albicans, C. tropicalis, C. krusei, C. guillermondii, C. parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, T. mentagrophytes, T. mentagrophytes var. interdigitale, Trichophyton rubrum, T. verrucosum, Microsporum canis, M. gypseum, Epidermophyton floccosum, Aspergillus niger, A. fumigatus and A. flavus. The volatile extracts revealed a wide-spectrum antifungal activity. They were fungicidal and similarly potent against yeasts, dermatophyte and Aspergillus stains, with MICs ranging from 0.16 to 0.32 μL.mL−1