323,150 research outputs found
Multiple S-Layer Proteins of Brevibacillus laterosporus as Virulence Factors against Insects
No full textS-layers are involved in the adaptation of bacteria to the outside environment and in pathogenesis, often representing special virulence factors. Vegetative cells of the entomopathogenic bacterium Brevibacillus laterosporus are characterized by an overproduction of extracellular surface layers that are released in the medium during growth. The purpose of this study was to characterize cell wall proteins of this bacterium and to investigate their involvement in pathogenesis. Electron microscopy observations documented the presence of multiple S-layers, including an outermost (OW) and a middle (MW) layer, in addition to the peptidoglycan layer covering the plasma membrane. After identifying these proteins (OWP and MWP) by mass spectrometry analyses, and determining their gene sequences, the cell wall multilayer-released fraction was successfully isolated and used in insect bioassays alone and in combination with bacterial spores. This study confirmed a central role of spores in bacterial pathogenicity to insects but also detected a significant virulence associated with fractions containing released cell wall multilayer proteins. Taken together, S-layer proteins appear to be part of the toxins and virulence factors complex of this microbial control agent of invertebrate pests
Forensic Biometrics: Challenges, Innovation and Opportunities. In: Francese, S., S. P. King, R. (eds) Driving Forensic Innovation in the 21st Century. Springer, Cham.
No full textForensic science has always benefited from the adoption and exploitation of novel technologies to perform and analyze measurements at a crime scene and in the laboratory. Modern information technologies boosted many forensic procedures, such as accelerating and automating the comparison of fingerprints and fingermarks, and, recently, the analysis and comparison of images from human faces. Moreover, the recent advent of fast and performant Machine Learning (often dubbed AI) models, greatly improved the applicability of automatic face recognition to operational scenarios. However, even though technology has enabled the development of such systems, there are several hindering factors which must be taken into account. In this chapter the technological, legal and societal factors potentially enabling and fostering the development and application of automatic face recognition in forensic procedures are described and discussed. Also, the current issues and main concerns, restricting the mass-adoption of automatic face recognition technologies in forensic cases are presented. This chapter attempts not only to document both enablers and roadblockers of forensic face recognition, but also provides some promising research avenues and suggestions for a better application of these technologies in today’s society
Tricyclic pyrazoles. Part 3. Synthesis, biological evaluation and molecular modelling of analogues of the cannabinoid antagonist NESS 0327
No full textA series of analogues of 8-chloro-1-(2′,4′-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo- [6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide 4a (NESS 0327) (Ruiu, S.; Pinna, G. A.; Marchese, G.; Mussinu, J. M.; Saba, P.; Tambaro, S.; Casti, P.; Vargiu, R.; Pani, L. Synthesis and Characterization of NESS 0327: A Novel Putative Antagonist of CB1 Cannabinoid Receptor. J. Pharmacol. Exp. Ther. 2003, 306, 363-370) was synthesized and evaluated for their affinity to cannabinoid receptors. Depending on the chemical modification of the lead structure that was chosen, compounds 4b, 4c, 4i, 4l, and 4m still proved to be potent binders of the CB1 receptor. Moreover, several analogues (4c, 4d, 4e, and 4m) demonstrated superior CB2 receptor binding affinities compared to the parent ligand. Compounds 4b, 4c, 4i, and 4l displayed the most promising pharmacological profiles, having the highest selectivity for CB1 receptors with Ki(CB2) to Ki(CB1) ratios of 11 250, 2000, 3330 and 4625, respectively. Compound 4c increased the intestinal propulsion in mice and antagonized the effect induced by the CB1 receptor agonist WIN 55,212-2. Finally, molecular modeling studies were carried out on a set of tricyclic pyrazoles (2a-4a) and on rimonabant 1 (SR141716A), indicating that high CB1 receptors affinities were consistent for the tricyclic derivatives, both with a nonplanar geometry of the tricyclic cores and with a precise orientation of the substituent (chlorine) on this ring system
Tricyclic Pyrazoles. 3. Synthesis, biological evaluation, and molecular modeling of analogues of the cannabinoid antagonist 8-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide
No full textA series of analogues of 8-chloro-1-(2′,4′-dichlorophenyl)-AT- piperidin-1-yl-1,4,5,6-tetrahydrobenzo-[6,7]cyclohepta[1,2-c] pyrazole-3-carboxamide 4a (NESS 0327) (Ruiu, S.; Pinna, G. A.; Marchese, G.; Mussinu, J. M.; Saba, P.; Tambaro, S.; Casti, P.; Vargiu, R.; Pani, L. Synthesis and Characterization of NESS 0327: A Novel Putative Antagonist of CB 1 Cannabinoid Receptor. J. Pharmacol. Exp. Ther. 2003, 306, 363-370) was synthesized and evaluated for their affinity to cannabinoid receptors. Depending on the chemical modification of the lead structure that was chosen, compounds 4b, 4c, 4i, 4l, and 4m still proved to be potent binders of the CB1 receptor. Moreover, several analogues (4c, 4d, 4e, and 4m) demonstrated superior CB2 receptor binding affinities compared to the parent ligand. Compounds 4b, 4c, 4i, and 4l displayed the most promising pharmacological profiles, having the highest selectivity for CB1 receptors with Ki(CB2) to Ki(CB1) ratios of 11 250, 2000, 3330 and 4625, respectively. Compound 4c increased the intestinal propulsion in mice and antagonized the effect induced by the CB 1 receptor agonist WIN 55,212-2. Finally, molecular modeling studies were carried out on a set of tricyclic pyrazoles (2a-4a) and on rimonabant 1 (SR141716A), indicating that high CB1 receptors affinities were consistent for the tricyclic derivatives, both with a nonplanar geometry of the tricyclic cores and with a precise orientation of the substituent (chlorine) on this ring system. © 2005 American Chemical Society
Receptorial and pharmacological characterization of the new cannabinoid agonist NESS040C5
No full textA number of studies indicate that cannabinoids can reduce intraocular pressure (IOP) both in animals and humans, suggesting a putative efficacy of these compounds in the treatment of glaucoma.
Among the cannabinoid derivatives encompassed by Patent US 7,485,730 assigned to PharmaNess Scarl, different compounds characterized by low or absent permeability toward blood brain barrier evidenced agonism activity on both CB1 and CB2 sub-type cannabinoid receptors.
In this study we report the synthesis and pharmacological profile of a new compounds claimed by the above mentioned Patent: N-menthyl-6-methyl-1-(4''-methylbenzyl)-1,4dihydrothieno[2',3':4,5]cyclopenta[1,2-c]pyrazol-3-carboxamide (NESS040C5).
The affinity towards both CB1 and CB2 receptors was determined through radioreceptor binding assays according to the procedure reported by Ruiu et al. in J.P.E.T., 2003, 306, 363−370, while the activity at those receptors was evaluated using an in vitro cell culture model.
To evaluate the pharmacological application of the compound in glaucoma treatment, a validated animal model based on the IOP determination in aged glaucomatous DBA/2J mice was adopted.
NESS040C5 showed high affinity at both CB1 and CB2 receptors, which were positively modulated suggesting an agonistic activity of the derivative. In addiction, the compound reduced IOP in DBA/2J glaucomatous mice suggesting a potential efficacy of NESS040C5 in the treatment of glaucoma
Evaluation of water depth - damage functions in built-up areas in Sardinia (Italy)
No full textFlood events occurring in the Mediterranean area lead to investigate on relevant damages caused by flooding in urbanized areas. The EU Flood Directive 2007/60, requiring a cost-benefit analysis for the definition of mitigation measures, should be supported by appraisals of flood damages. Recent studies recognise the use of water depth- damage functions as key elements in the decision-making process of mitigation measures and should be developed specifically considering regional territory features. This paper confirmed application of the Joint Research Centre (JRC) model approach considering studies developed for the Sardinian region and providing water depth-damage functions for direct tangible damage assessment in this region. Historical data on flood damages were collected considering two recent flood events and relations between water depth and expected damage are proposed using a Pearson III probability distribution. The obtained water depth-damage functions show different trends due to building types in the two studied areas. The procedure was subsequently implemented considering synthetically generated flood events in order to estimate the expected mean annual damage values due to flooding in prone areas and to verify the economic efficiency in planning mitigation measures. Aiming to confirm the study results reliability, the case study of Olbia town was accurately analysed. In particular, Olbia water depth-damage function was applied for synthetic floodplain scenarios generated with occurrence of 50, 100, 200 and 500 years to observe potential damages and to conduct a comparison with the occurred case
Room-Temperature Hydrodehalogenation of Halogenated Heteropentalenes with One or Two Heteroatoms
No full textEffect of the amisulpride isomers on rat prolactinemia
No full textThe effects on rat serum prolactin level of the two isomers constituting the racemic form of amisulpride were compared. (S-)-amisulpride induced hyperprolactinemia at lower doses (ED50=0.09±0.01 mg/kg) than racemic- (ED50=0.24±0.03 mg/kg) and (R+)-amisulpride (ED50=4.13±0.05 mg/kg), in accord with their affinities for pituitary dopamine D2 receptor (Ki=3.8±0.2, 6.4±0.2 and 143.3±2.3 nM, respectively). At doses twice the ED50, (S-)-amisulpride produced a maximal increase in prolactin level similar to that of the racemic form (403±21% and 425±15%, respectively), but higher than that of (R+)-amisulpride (198±8%). These results suggest that the hyperprolactinemia induced by the racemic-amisulpride is mostly due to its (S-)-isomer. © 2002 Elsevier Science B.V. All rights reserved
The standardized Withania somnifera Dunal root extract alters basal and morphine-induced opioid receptor gene expression changes in neuroblastoma cells.
No full textBACKGROUND:
Behavioral studies demonstrated that the administration of Withania somnifera Dunal roots extract (WSE), prolongs morphine-elicited analgesia and reduces the development of tolerance to the morphine's analgesic effect; however, little is known about the underpinning molecular mechanism(s). In order to shed light on this issue in the present paper we explored whether WSE promotes alterations of μ (MOP) and nociceptin (NOP) opioid receptors gene expression in neuroblastoma SH-SY5Y cells.
METHODS:
A range of WSE concentrations was preliminarily tested to evaluate their effects on cell viability. Subsequently, the effects of 5 h exposure to WSE (0.25, 0.50 and 1.00 mg/ml), applied alone and in combination with morphine or naloxone, on MOP and NOP mRNA levels were investigated.
RESULTS:
Data analysis revealed that morphine decreased MOP and NOP receptor gene expression, whereas naloxone elicited their up-regulation. In addition, pre-treatment with naloxone prevented the morphine-elicited gene expression alterations. Interestingly, WSE was able to: a) alter MOP but not NOP gene expression; b) counteract, at its highest concentration, morphine-induced MOP down-regulation, and c) hamper naloxone-induced MOP and NOP up-regulation.
CONCLUSION:
Present in-vitro data disclose novel evidence about the ability of WSE to influence MOP and NOP opioid receptors gene expression in SH-SY5Y cells. Moreover, our findings suggest that the in-vivo modulation of morphine-mediated analgesia by WSE could be related to the hindering of morphine-elicited opioid receptors down-regulation here observed following WSE pre-treatment at its highest concentration
Blockade of neurotensin receptors affects differently hypo-locomotion and catalepsy induced by haloperidol in mice
No full textAntipsychotic drug treatment increases neurotensin (NT) neurotransmission, and the exogenous administration of NT produces antipsychotic-like effects in rodents. In order to investigate whether "endogenous" NT may act as a natural occurring antipsychotic or may mediate antipsychotic drug activity, the effects of the selective NT receptor antagonists SR 48692 and SR 142948A were analyzed in different behavioural tests of locomotor activity using vehicle, amphetamine, or haloperidol in mice. SR 48692 (0.1-1 mg/kg, i.p.) and SR 142948A (0.03-0.1 mg/kg, i.p.) failed to affect mouse spontaneous locomotor activity and amphetamine-induced (2.5 mg/kg, i.p.) hyper-locomotion. However, SR 48692 (0.1 and 0.3 mg/kg, i.p.) and SR 142948A (0.03 and 0.05 mg/kg, i.p.) significantly alleviated the reduction of locomotor activity elicited by haloperidol (0.01 and 0.04 mg/kg, s.c.) in vehicle- or amphetamine-treated mice. Finally, SR 48692 (0.3 mg/kg, i.p.) and SR 142948A (0.05 and 0.1 mg/kg, i.p.) increased mouse catalepsy produced by haloperidol (0.3 mg/kg, s.c.). The present results indicate that while endogenous NT is not involved in the modulation of either mouse spontaneous locomotor activity or amphetamine-induced hyper-locomotion, it might act by enhancing the therapeutic effects of haloperidol and by attenuating the extrapyramidal side effects elicited by this antipsychotic. © 2004 Elsevier Ltd. All rights reserved
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