Effective lattice actions for correlated electrons

We present an exact, unconstrained representation of the electron operators in terms of operators of opposite statistics. We propose a path--integral representation for the $t$-$J$ model and introduce a parameter controlling the semiclassical behaviour. We extend the functional approach to the Hubbard model and show that the mean--field theory is equivalent to considering, at Hamiltonian level, the Falikov--Kimball model. Connections with a bond-charge model are also discussed.Comment: 12 pages, REVTeX 3.0, no figure

Laparoscopic lymph node biopsy for lymphoma with a novel use of indocyanine green fluorescence in a 66-year-old male patient

Introduction: Indocyanine green (ICG) near-infrared fluorescence is primarily employed in detecting Intraoperative sentinel lymph node (SLN) mapping or to evaluate the extent of radical lymphadenectomy mainly in colo-rectal and gastric cancer. To date there are no reports indicating the use of this dye to detect pathologic lymphatic tissue when a lymph node biopsy for suspected lymphoproliferative disease is performed. Presentation of case: A 66-year-old male patient was admitted to the hospital for severe pain of left renal colic type. A computed tomography (CT) scan and a positron emission tomography (PET) showed a left hydroureteronephrosis due to ureter compression by paraortic solid tissue of lymphomatous aspect with a standardized uptake value (SUV) of 15. Multiple lymphadenopathies on paracaval, para-aortic and common iliac sites were present as well. Discussion: A laparoscopic lymph node biopsy (LLB) was planned for diagnostic purposes. After induction of anesthesia a ICG solution was injected Intradermally at both inguinal regions. At laparoscopy a complete visualization of the pathologic lymphnodes was achieved, enabling incisional biopsies of the lymphomatous mass. Histopathological examination showed an extranodal localization of an aggressive B-cell non-Hodgkin lymphoma. Conclusion: ICG-fluorescence seems to offer a simple and safe method for pathologic lymph node detection. LLB in the suspicion of intra abdominal lymphoma can largely take advantage by this novel opportunity not yet tested to date. More studies with large case series are needed to confirm the efficacy of ICG-fluorescence for detecting pathologic lymph nodes

How Merchant Towns Shaped Parliaments: From the Norman Conquest of England to the Great Reform Act

This is the final version. Available from the American Economic Association via the DOI in this recordWe study the emergence of urban self-governance in the late medieval period. We focus on England after the Norman Conquest of 1066, building a novel comprehensive dataset of 554 medieval towns. During the Commercial Revolution (twelfth to thirteenth centuries), many merchant towns obtained Farm Grants: the right of self-governed tax collection and law enforcement. Self-governance, in turn, was a stepping stone for parliamentary representation: Farm Grant towns were much more likely to be summoned directly to the medieval English Parliament than otherwise similar towns. We also show that self-governed towns strengthened the role of Parliament and shaped national institutions over the subsequent centuries

Sulodexide counteracts endothelial dysfunction induced by metabolic or non-metabolic stresses through activation of the autophagic program

OBJECTIVE: Endothelial dysfunction (ED) predisposes to venous thrombosis (VT) and post-thrombotic syndrome (PTS), a long-term VT-related complication. Sulodexide (SDX) is a highly purified glycosaminoglycan with antithrombotic, pro-fibrinolytic and anti-inflammatory activity used in the treatment of chronic venous disease (CVD), including patients with PTS. SDX has recently obtained clinical evidence in the “extension therapy” after initial-standard anticoagulant treatment for the secondary prevention of recurrent deep vein thrombosis (DVT). Herein, we investigated how SDX counteracts ED. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used. Metabolic and non metabolic-induced ED was induced by treating with methylglyoxal (MGO) or irradiation (IR), respectively. Bafilomycin A1 was used to inhibit autophagy. The production of reactive oxygen species (ROS), tetrazolium bromide (MTT) assay for cell viability, terminal de-oxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for cell apoptosis, Real-time PCR and Western blot analysis for gene and protein expression were used. RESULTS: SDX protected HUVEC from MGO- or IR-induced apoptosis by counteracting the activation of the intrinsic and extrinsic caspase cascades. The cytoprotective effects of SDX resulted from a reduction in a) ROS production, b) neo-synthesis and release of pro-inflammatory cytokines (TNFα, IL1, IL6, IL8), c) DNA damage induced by MGO or IR. These effects were reduced when autophagy was inhibited. CONCLUSIONS: Data herein collected indicate the ability of SDX to counteract ED induced by metabolic or non-metabolic stresses by involving the intracellular autophagy pathway. Our experience significantly increases the knowledge of the mechanisms of action of SDX against ED and supports the use of SDX in the treatment of CVD, PTS and in the secondary prevention of recurrent DVT

AMPK Activators as Novel Drug Candidates for the Treatment of Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs), mainly represented by ulcerative colitis and Crohn’s disease, are chronic and idiopathic diseases of the digestive tract. They incidence and prevalence is raising significantly in both developed and developing countries, thus representing a major challenge for the worldwide healthcare systems. The pharmacological armamentarium for the treatment of IBDs is far from being satisfactory, as the therapeutic success of the available drugs is still limited. Accordingly, the development of novel and effective compounds is highly requested. In this context, the serine/threonine heterotrimeric kinase AMPK (adenosine monophosphate-activated protein kinase) seems a sound target to strike. Known as the central hub of energy homeostasis in eukaryotic cells, AMPK contributes also to the modulation of immune/inflammatory cell functions. Actually, alterations in AMPK expression and/or activity play a key role in the pathophysiology of immune-mediated inflammatory diseases characterized by abnormal immune cell functions, like IBDs. Moreover, AMPK is able to improve intestinal health by enhancing para-cellular junctions, nutrient transporters, autophagy and apoptosis. Accordingly, AMPK activation represents a promising therapeutic strategy for the treatment of intestinal inflammatory disorders. Here we describe a novel heterocyclic derivative, developed as AMPK activator. Tested in C2C12 myoblast cell lines, our compound significantly increased AMPK activity, in a concentration-dependent manner, turning out to be more effective than the well-known activator acadesine (ACA). Moreover, assayed in a mouse model of acute DNBS-induced colitis, the novel heterocycle displayed a relevant anti-inflammatory efficacy, proving to ameliorate both systemic- and tissue-related inflammatory parameters like body and spleen weight, colon length, macroscopic damage, TNF and MDA levels. Also in this case, our compound turned out to be significantly more active that the known reference ACA, thus imposing itself as a novel and valuable drug candidate for the treatment of IBDs

Resistance Patterns, mcr-4 and OXA-48 Genes, and Virulence Factors of Escherichia coli from Apennine Chamois Living in Sympatry with Domestic Species, Italy

The aim of this study was to determine and characterize potential resistance mechanisms against selected Critically Important Antibiotics in Escherichia coli isolates collected from wild and domestic ruminants living in the Maiella National Park, in Central Italy. A total of 38 isolates were obtained from red deer, Apennine chamois, cattle, sheep, and goats grazing in lands with different levels of anthropic pressure. Antimicrobial susceptibility was determined by Minimal Inhibitory Concentration testing, showing phenotypic resistance to colistin, meropenem, or ceftazidime in 9 isolates along with one bacterial strain being resistant to three of the tested antibiotics. In addition, the biomolecular assays allowed the amplification of the genes conferring the colistin (mcr-4), the carbapenems (OXA-48), penicillins and cephalosporins (TEM, SHV, CMY-1, CMY-2) resistance. In order to describe the potential pathogenicity of isolates under study, virulence genes related to Shiga toxin-producing (STEC) and enteropathogenic (EPEC) pathovars were identified. This study is the first report of mcr-4 and OXA-48 genes in resistant E. coli harboring virulence genes in Italian wildlife, with special regard to Apennine chamois and red deer species. The multidisciplinary approach used in this study can improve the early detection of emerging antibiotic resistance determinants in human-animal-environment interfaces by means of wildlife monitoring

Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes

The decriminalization and legalization of cannabis has paved the way for investigations into the potential of the use of phytocannabinoids (pCBs) as natural therapeutics for the treatment of human diseases. This growing interest has recently focused on rare (less abundant) pCBs that are non-psychotropic compounds, such as cannabigerol (CBG), cannabichromene (CBC), Δ9-tetrahydrocannabivarin (THCV) and cannabigerolic acid (CBGA). Notably, pCBs can act via the endocannabinoid system (ECS), which is involved in the regulation of key pathophysiological processes, and also in the skin. In this study, we used human keratinocytes (HaCaT cells) as an in vitro model that expresses all major ECS elements in order to systematically investigate the effects of CBG, CBC, THCV and CBGA. To this end, we analyzed the gene and protein expression of ECS components (receptors: CB1, CB2, GPR55, TRPV1 and PPARα/γ/δ; enzymes: NAPE-PLD, FAAH, DAGLα/β and MAGL) using qRT-PCR and Western blotting, along with assessments of their functionality using radioligand binding and activity assays. In addition, we quantified the content of endocannabinoid(-like) compounds (AEA, 2-AG, PEA, etc.) using UHPLC-MS/MS. Our results demonstrated that rare pCBs modulate the gene and protein expression of distinct ECS elements differently, as well as the content of endocannabinoid(-like) compounds. Notably, they all increased CB1/2 binding, TRPV1 channel stimulation and FAAH and MAGL catalytic activity. These unprecedented observations should be considered when exploring the therapeutic potential of cannabis extracts for the treatment of human skin diseases

Double-pruning of ‘Syrah’ grapevines: a management strategy to harvest wine grapes during the winter in the Brazilian Southeast

Grape harvest in the major grapevine growing regions of Brazil occurs during the summer; a period with excessive rainfall. The climatic conditions during the Brazilian summer can have an adverse effect on fruit maturation and wine quality. This study compared the performance of 'Syrah' grapevines cultivated in two growing seasons. A double pruning management system was employed as a technique in the vineyard and the grapevines were cultivated in summer, a cycle normally adopted in the South and Southeast of Brazil and winter during 2005 and 2006 in a non-irrigated vineyard. Vine water stress was minimal for both growing seasons and photosynthetic rates were found to be lower in the winter than the summer. However, no differences in vegetative vigor were observed. The growing season was shorter in summer than in winter. This was predominately due to a faster ripening period in the summer. During the winter harvests, grapevines had a higher yield, accumulation of sugar, anthocyanins and total phenolic compounds, and the lowest rot incidence. Double-pruning proved to be a powerful tool to improve wine grape composition in the Brazilian Southeast. This management will allow the production of quality raw materials for the production of good wines, allowing Southeastern Brazil to enter the competitive globalized wine market.

Integrated Trigger and Data Acquisition system for the NA62 experiment at CERN

The main goal of the NA62 experiment is to measure the branching ratio of the K+decay, collecting O(100) events in two years of data taking. Efficient online selection of interesting events and loss-less readout at high rate will be key issues for such experiment. An integrated trigger and data acquisition system has been designed. Only the very first trigger stage will be implemented in hardware, in order to reduce the total rate for the software levels on PC farms. Readout uniformity among different subdetectors and scalability were taken into account in the architecture design

Iron-dependent trafficking of 5-lipoxygenase and impact on human macrophage activation

5-lipoxygenase (5-LOX) is a non-heme iron-containing dioxygenase expressed in immune cells that catalyzes the two initial steps in the biosynthesis of leukotrienes. It is well known that 5-LOX activation in innate immunity cells is related to different iron-associated proinflammatory disorders, including cancer, neurodegenerative diseases, and atherosclerosis. However, the molecular and cellular mechanism(s) underlying the interplay between iron and 5-LOX activation are largely unexplored. In this study, we investigated whether iron (in the form of Fe3+ and hemin) might modulate 5-LOX influencing its membrane binding, subcellular distribution, and functional activity. We proved by fluorescence resonance energy transfer approach that metal removal from the recombinant human 5-LOX, not only altered the catalytic activity of the enzyme, but also impaired its membrane-binding. To ascertain whether iron can modulate the subcellular distribution of 5-LOX in immune cells, we exposed THP-1 macrophages and human primary macrophages to exogenous iron. Cells exposed to increasing amounts of Fe3+ showed a redistribution (ranging from ~45 to 75%) of the cytosolic 5-LOX to the nuclear fraction. Accordingly, confocal microscopy revealed that acute exposure to extracellular Fe3+, as well as hemin, caused an overt increase in the nuclear fluorescence of 5-LOX, accompanied by a co-localization with the 5-LOX activating protein (FLAP) both in THP-1 macrophages and human macrophages. The functional relevance of iron overloading was demonstrated by a marked induction of the expression of interleukin-6 in iron-treated macrophages. Importantly, pre-treatment of cells with the iron-chelating agent deferoxamine completely abolished the hemin-dependent translocation of 5-LOX to the nuclear fraction, and significantly reverted its effect on interleukin-6 overexpression. These results suggest that exogenous iron modulates the biological activity of 5-LOX in macrophages by increasing its ability to bind to nuclear membranes, further supporting a role for iron in inflammation-based diseases where its homeostasis is altered and suggesting further evidence of risks related to iron overload