The scheme of liftings and applications

We study the locus of the liftings of a homogeneous ideal $H$ in a polynomial ring over any field. We prove that this locus can be endowed with a structure of scheme $\mathrm L_H$ by applying the constructive methods of Gr\"obner bases, for any given term order. Indeed, this structure does not depend on the term order, since it can be defined as the scheme representing the functor of liftings of $H$. We also provide an explicit isomorphism between the schemes corresponding to two different term orders. Our approach allows to embed $\mathrm L_H$ in a Hilbert scheme as a locally closed subscheme, and, over an infinite field, leads to find interesting topological properties, as for instance that $\mathrm L_H$ is connected and that its locus of radical liftings is open. Moreover, we show that every ideal defining an arithmetically Cohen-Macaulay scheme of codimension two has a radical lifting, giving in particular an answer to an open question posed by L. G. Roberts in 1989.Comment: the presentation of the results has been improved, new section (Section 6 of this version) concerning the torus action on the scheme of liftings, more detailed proofs in Section 7 of this version (Section 6 in the previous version), new example added (Example 8.5 of this version

Pharmacological effects of palmitoylethanolamide on hypertension, insulin-resistance and obesity in murine models

N-Palmitoylethanolamide (PEA) is an endogenous N-acylethanolamine, first identified in lipid extracts from brain, liver, and muscle of rat and guinea pig. PEA is formed “on demand” from membrane phospholipids and it is gaining ever-increasing interest not only for its anti-inflammatory and analgesic effects mediated by peroxisome-proliferator activated receptor (PPAR)-α, but also for its novel metabolic effects. Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health. Main consequence of obesity is cardiovascular disease (CVD). The sum of the risk factors that predisposes to CVD goes by the name of “metabolic syndrome” (MetS). Hypertension is an important hallmark of MetS and a common cause of kidney disease. In the first part of this thesis, we investigated the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids (EETs), CYP-dependent arachidonic acid (AA) metabolites, as endothelium derived hyperpolarizing factors (EDHF), and renin-angiotensin system (RAS) modulation. To achieve this aim, SHR and Wistar-Kyoto normotensive (WKY) rats were treated with PEA (30 mg/kg/day, s.c.) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure the soluble epoxide hydrolase (sEH), which is the enzyme responsible for EETs degradation in their corresponding inactive diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme (ACE) and angiotensin receptor (AT)1 expression. We showed that EDHF-mediated dilation in response to acetylcholine (Ach) was increased in mesenteric beds of PEA-treated SHR. Interestingly, in both vascular tissues, PEA significantly decreased the sEH protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid (DHET), implying a reduction in EET hydrolysis. Moreover, PEA treatment down-regulated AT1 and ACE expression, indicating a reduction in Ang II-mediated effects. Our data clearly demonstrate the involvement of EETs and RAS in the blood pressure lowering effect of PEA. The relationship between obesity, insulin-resistance (IR) type 2 diabetes mellitus (T2DM) and MetS is well known. IR is defined as an inefficient glucose uptake and utilization in peripheral tissues in response to insulin stimulation. IR in the prediabetes stage is a feature of glucose intolerance, which includes impaired fasting glucose and/or impaired glucose tolerance. When insulin binds to its transmembrane receptor (InsR), promotes its autophosphorylation (pInsR). Activated pInsR recruits insulin receptor substrate (IRS), leading to insulin signaling cascade. A potential link between inflammation and IR has been shown. Indeed, obesity is characterized by chronic low grade inflammation, where the release of adipose tissue-derived cytokines can block insulin action and cause systemic IR. In fact, serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 are significantly increased in serum from obese patients. All cytokines induce IRS1 protein degradation, which suppresses insulin signaling pathway and subsequently suppresses glucose transporter (GLUT) translocation and glycogen synthesis, contributing to IR and hyperglycemia. Our study was focused on the pharmacological effect of PEA in an animal model of diet-induced obesity (DIO), feeding mice with a high-fat diet (HFD), and on the mechanisms by which this lipid mediator could modulate the storage and availability of energy sources, restoring lipid/glucose homeostasis. To achieve this aim, mice were fed a standard chow diet (STD group) or HFD (DIO group). After twelve weeks, both STD or HFD mice were treated with PEA (30 mg/kg/day, o.s.) for ten weeks. At the end of the experimental period, body parameters were determined, and serum and tissues collected for following determinations. Interestingly, PEA caused a reduction in body weight and fat mass, improved glucose tolerance and prevented IR, induced by HFD feeding. Moreover, PEA restored the alterations of serum biochemical and inflammatory parameters, inducing a marked reduction of ALT, AST, cholesterol, and pro-inflammatory cytokines, such as TNF-α, IL-1 and monocyte chemoattractant protein (MCP)-1. PEA also normalized metabolic hormone levels and restored insulin sensitivity. At hepatic level, PEA treatment significantly induced an increase in the activation AMPK/ACC pathway, stimulating fatty acid oxidation, compromised in obese mice. To evaluate tissue insulin-sensitivity, we determined the hepatic expression of the InsR, whose expression decreased in liver of DIO mice compared to that of STD animals, and increased in PEA-treated mice. Then, we evaluated the effectiveness of hepatic insulin signaling through the evaluation of InsR and Akt phosphorylated state and the expression of GLUT-2. PEA treatment restored insulin signaling. The protective effect of PEA was strengthened by the evaluation of hepatic IL-6 and TNF-α, whose transcription, upregulated by HFD feeding, was reduced. To address the direct effect of PEA on hepatic insulin-sensitivity, we evaluated the restoration of insulin signaling, altered by the induction of IR, in HepG2 cells, a human hepatocarcinoma cell line. Therefore, we demonstrated in vitro that PEA increased the phosphorylation of Akt in insulin resistant cells, following insulin stimulation. PEA was also able to modulate glucose homeostasis at hypothalamic level. Therefore, we examined neuronal activation at the arcuate (ARC) and ventromedial (VMH) nuclei, evaluating c-fos immunostaining. In the ARC nucleus of DIO mice, a decrease in c-fos labeling was found. Interestingly, in the PEA-treated DIO group, a trend of c-fos labeling increase was evidenced. Consistently, in the VHM of DIO mice a significant decrease in the neuronal activation was shown compared to STD mice, although, no differences were found between DIO and PEA-treated DIO mice. The involvement of the hypothalamic control of glucose homeostasis by PEA was confirmed in in vitro experiments, using human SH-SY5Y neuroblastoma cell line. When insulin-resistant cells were treated with PEA, the re-stimulation with insulin showed a restoration of Akt phosphorylation, and therefore of insulin-sensitivity. These findings show that this acylethanolamide also displays a central effect on glucose homeostasis, reducing neuronal IR. Our data strengthened evidence on the metabolic activity of PEA, through the involvement of central and peripheral mechanisms. PEA clearly ameliorates glucose-tolerance and insulin-sensitivity, indicating its therapeutic potential for the treatment of metabolic dysfunctions associated to obesity, such as IR and T2DM

Neuronutraceuticals Modulate Lipopolysaccharide- or Amyloid-β 1-42 Peptide-Induced Transglutaminase 2 Overexpression as a Marker of Neuroinflammation in Mouse Microglial Cells

Background: Tissue type 2 Transglutaminase (TG2, E.C. 2.3.2,13) is reported to be involved in phagocytosis of apoptotic cells in mouse microglial BV2 cells and peripheral macrophages. In this study, by using Lipopolysaccharide (LPS)- or Amyloid-beta 1-42 (Abeta 1-42) peptide-stimulated mi-croglial cell line BV2 and mouse primary microglial cells, we examined the effects of different neuronutraceutical compounds, such as Curcumin (Cu) and N-Palmitoylethanolamine (PEA), known for their anti-inflammatory activity, on TG2 and several inflammatory or neuroprotective biomarkers expressions. Methods: Mouse BV2 cells were treated with LPS or Abeta1-42 in presence of Curcumin or PEA, in order to evaluate the expression of TG2 and other inflammatory or neuro-protective markers by RealTime PCR and Western Blot analyses. Results: Curcumin and PEA were capable to reduce TG2 expression in mouse microglial cells during co-treatment with LPS or Abeta 1-42. Conclusions: The results show the role of TG2 as an important marker of neuroinflamma-tion and suggest a possible use of Curcumin and PEA, in order to reduce LPS- or Abeta1-42-induced TG2 overexpression in mouse microglial cells

Role of hepatocyte growth factor in the immunomodulation potential of amniotic fluid stem cells

Human amniotic fluid stem cells (hAFSCs) may be useful for regenerative medicine because of their potential to differentiate into all three germ layers and to modulate immune response with different types of secretion molecules. This last issue has not been completely elucidated. The aim of this study was to investigate the secretome profile of the hAFSC, focusing on the role of hepatocyte growth factor (HGF) in immunoregulation through short and long cocultures with human peripheral blood mononuclear cells. We found that HGF produced by hAFSCs exerts a cytoprotective role, inducing an increase in caspase-dependent apoptosis in human immune cells. This study provides evidence supporting the hypothesis that amniotic fluid is an ideal source of stem cells for expansion and banking properties for therapeutic use. hAFSCs not only are less immunogenic but also can secrete immunoregulatory factors that may be useful in autoimmune diseases or allogenic implants. SIGNIFICANCE: New information about the secretome pattern is reported in this paper. Human amniotic fluid stem cells (hAFSCs) possess immunomodulatory properties involving hepatocyte growth factor production. hAFSCs could be used in immunotherapies and might be able to avoid allogenic rejectio

Hypervariability of Ascidian Mitochondrial Gene Order: Exposing the Myth of Deuterostome Organelle Genome Stability

The few sequenced mitochondrial (mt) genomes of the class Ascidiacea (Chordata, Tunicata), mostly belonging to congeneric species of the Phlebobranchia order, show extraordinary gene order rearrangements. In order to assess if this hypervariability in gene order is a general feature of Ascidiacea, we report here the gene arrangement of five ascidians belonging to the Aplousobranchia and Stolidobranchia orders. Our data show that Ascidiacea are characterized by: 1) extensive gene order rearrangements both within and between the three major lineages; 2) lack of significant similarities to the gene order of other deuterostomes; and 3) an extent of rearrangements comparable with that of Mollusca (especially the Gastropoda, Bivalvia, and Scaphopoda classes), a phylum with highly rearranged mtDNAs. The only conserved feature is the location of all genes on the same strand, which suggests that selective constraints are related to the mt transcription. Finally, a higher mobility of the tRNA genes is undetectable because of saturation effect, and only the partially conserved cox2-cob gene block seems to retain some phylogenetic signals

Skin above the knees: treatments for a difficult area

INTRODUCTION, OBJECTIVES, PURPOSE OF THE STUDY The interest for non-invasive techniques for skin rejuvenation is increasing. However, lax skin above the knee is often forgotten. As a matter of fact, there were not so many options for its treatment. The aim of our study is to present the application of selected rejuvenation techniques and to define their efficacy and safety. MATERIALS AND METHODS Clinical evaluation of the patient. Classification and selection of the patient and targeted therapies: from calcium hydroxyapatite to microfocused ultrasound. Inclusion criteria: people aged >18 years old; skin laxity. Exclusion criteria: severe diseases and severe skin laxity. Treatment in single or multiple sessions. Controls at T0 + T30 + T90. Measurement and analysis: standard digital photo. Evaluation of results and satisfaction of patients. RESULTS The targeted approach focused on the correction of specific morphologic variations of the skin above the knee, showing a variable grading, is effective and able to satisfy patient expectations. The treatment was well tolerated; we reported only a few adverse events: local reactions (erythema, oedema, swelling). All these effects last few days. CONCLUSIONS The treatment of the skin above the knee is challenging. Our protocols have shown good results in this difficult area and a good tolerability profile. A good selection of patients is mandatory in order to achieve the best result

Occurrence of Legionella spp. in thermal environments: Virulence factors and biofilm formation in isolates from a spa☆ , ☆☆

Abstract The aim of the study was to evaluate the occurrence of Legionella spp. in the water system of a spa in the city of Naples by analyzing water, air and surface samples. On the whole, 312 samples were collected and analyzed in the course of 10 months. Legionella CYE Agar Base and Legionella Latex Test (Oxoid©) were used to identify and serotype presumptive Legionella pneumophila strains. A further identification was carried out by rDNA16S and ITS region amplification followed by a sequence analysis by DNA Sequencing Analysis software (Applied Biosystems). Similarity search was performed using BLAST algorithm against the GenBank database (NCBI GenBank). Specific in-vitro tests aimed to evaluate the production of esoenzymes (hemolysins, collagenases, mucinases, lipases, proteinases, DNAses, elastases) on GC-FC Agar were also carried out. Finally, a crystal violet staining method (absorbance at 570 nm) was used to evaluate the ability of the strains to produce biofilm in a 96-multiwell polyethylene plate. All samples were negative for L. pneumophila. Six different Legionella strains were isolated from water samples and identified as Legionella londiniensis and Legionella spp. A significant (from 1000 to 10,000 CFU/L) and a low to moderate (from 100 to 1000 CFU/L) contamination were detected respectively in the 5% and 4% of samples; 91% of water samples showed a Legionella spp. amount less than 100 CFU/L. Two Legionella londiniensis isolates showed collagenases, caseinases, proteinases and gelatinases activities, being classified as potentially pathogenic bacteria. None of the isolates were classified as strong biofilm producer but they showed a moderate to weak ability to form biofilm on polyethylene. This result is significant because large part of the spa pipelines is plastic-coated. The highest frequency of isolation of Legionella spp. was detected in the unit for Thermal Mud Therapy, which showed a relative risk value equal to 1.69 (CI 95% 0.60–4.70). Although our results proved a moderate contamination in different water samples, the presence of potentially pathogenic environmental strains of Legionella spp. should not be underestimated because most part of costumers attending the spa are old and sick people, and Legionella strains can represent a real risk

Improving the aging of the neck: combined treatments

INTRODUCTION, OBJECTIVES, PURPOSE OF THE STUDY The request for less aggressive procedures to treat skin laxity of face and neck is increasing. Only a few approaches are available for aesthetic treatments of the neck. Several factors are known to be involved in aging process: skin laxity and photodamage, fat tissue deposition, variation of muscle tone. MATERIALS AND METHODS Clinical evaluation of the patient. Classification and selection of the patient and targeted therapies: from microbotox, bio-stimulation, high intensity focused ultrasound to traction thread. Inclusion criteria: people aged >18 years old; moderate skin laxity and horizontal wrinkles of the neck. Exclusion criteria: severe diseases; skin laxity showing a high grade of severity and severe fat tissue deposition. Different treatments in multiple sessions. Controls at T0 + T30 + T90. Measurement and analysis: standard digital photo. Evaluation of results and satisfaction of patients. RESULTS The targeted approach focused on the correction of specific expressions of the ageing of the neck, showing a variable grading, is effective. The association of target therapy results to satisfy patient expectations. CONCLUSIONS In the field of aesthetic medicine we have available various techniques such as microbotox, bio-stimulation, high intensity focused ultrasound and traction thread. One treatment does not exclude the others. The combination of the two treatment it is possible to optimize the results. The targeted treatment and an appropriate selection of patients are essential to reach satisfactory results in the treatment of imperfections related to the process of ageing of the neck

Permanent implants for lip augmentation: Results from a retrospective study and presentation of tips and tricks

Introduction: Lip augmentation request is increasing. Nowadays, several techniques to obtain temporary effects are available. On the other hand, permanent results can be reached through lip prosthesis implantation. This procedure represents an innovation in the field of aesthetic medicine and surgery. Material & Methods: A total of 110 women with atrophic or hypoplastic lips were treated with lip implants. The treatment was performed in a single session and controls were scheduled at fixed time intervals. A standard digital photo was used for measurement and analysis. Data concerning patient satisfaction and complications of the technique were collected and analysed. Variations to the original technique were also considered. Results: Patient evaluation revealed that a permanent and natural result without discomfort for the patient and/or the partner was reached with the implantation of silicone prosthesis in the upper and/or lower lip. Swelling, bruising, and malpositions were the most frequent adverse events. A case of severe edema was reported. Practical tricks acquired through experience were analysed to prevent complications. Conclusions: The request of permanent results for lip augmentation allowed the development of silicone prosthesis. Advantages of this prosthesis are: safety, definitive result, and reversibility considering the possibility to remove the implanted prosthesis in case of request