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A bstract By using integral forms we derive the superspace action of D = 3, N = 1 supergravity as an integral on a supermanifold. The construction is based on target space picture changing operators, here playing the rôle of Poincaré duals to the lower-dimensional spacetime surfaces embedded into the supermanifold. We show how the group geometrical action based on the group manifold approach interpolates between the superspace and the component supergravity actions, thus providing another proof of their equivalence.

A bstract We reconstruct the action of N = 1 , D = 4 Wess-Zumino and N = 1 , 2 , D = 4 super-Yang-Mills theories, using integral top forms on the supermanifold ℳ 4 4 . Choosing different Picture Changing Operators, we show the equivalence of their rheonomic and superspace actions. The corresponding supergeometry and integration theory are discussed in detail. This formalism is an efficient tool for building supersymmetric models in a geometrical framework.

A bstract We construct N=1 d=3 AdS supergravity within the group manifold approach and compare it with Achucarro-Townsend Chern-Simons formulation of the same theory. We clarify the relation between the off-shell super gauge transformations of the Chern- Simons theory and the off-shell worldvolume supersymmetry transformations of the group manifold action. We formulate the Achucarro-Townsend model in a double supersymmetric action where the Chern-Simons theory with a supergroup gauge symmetry is constructed on a supergroup manifold. This framework is useful to establish a correspondence of degrees of freedom and auxiliary fields between the two descriptions of d=3 supergravity.

We thank P. Fré and C. Maccaferri for fruitful discussions. This research is original and has a financial support of the Università del Piemonte Orientale (Fondi Ricerca Locale).

Serum paraoxonase (PON1) is an esterase that is associated with high-density lipoproteins (HDLs) in the plasma; it is involved in the detoxification of organophosphate insecticides such as parathion and chlorpyrifos 1 , 2 , 3 . PON1 may also confer protection against coronary artery disease by destroying pro-inflammatory oxidized lipids present in oxidized low-density lipoproteins (LDLs) 4 , 5 , 6 , 7 , 8 . To study the role of PON1 in vivo , we created PON1 -knockout mice by gene targeting. Compared with their wild-type littermates, PON1-deficient mice were extremely sensitive to the toxic effects of chlorpyrifos oxon, the activated form of chlorpyrifos, and were more sensitive to chlorpyrifos itself. HDLs isolated from PON1-deficient mice were unable to prevent LDL oxidation in a co-cultured cell model of the artery wall, and both HDLs and LDLs isolated from PON1 -knockout mice were more susceptible to oxidation by co-cultured cells than the lipoproteins from wild-type littermates. When fed on a high-fat, high-cholesterol diet, PON1 -null mice were more susceptible to atherosclerosis than their wild-type littermates.

Stapled transanal rectal resection is the most surgical procedure used for obstructed defecation syndrome, rectal prolapse, rectocele and rectal intussusception worldwide. The aim of this study is to report our experience and long time consequences and to offer a new medico-legal perspective. We retrospective review medical charts of patients treated between 2006 and 2021 ​b ​y the same team directed by the same senior surgeon. We consider major complications and long time sequelaeses as main object for the discussion. Inclusion and exclusion criteria were created. IRB approved the study. After revision a medico-legal perspective was done based on major complications. During the study period 1726 patients, ages between 18 and 71 years old, were treated with 1280 STARR procedures and 446 “Longo” [was stopped on 2012]; all procedures were performed by the senior surgeon and visited by the team at the same control visit at 7days, 30 days and 12 and 18 months after surgery. All patients had 100 ​% compliance at 30 days, while 85 ​% had long time visit (more than 18 months). During the study period 6 ​% (104 subjects) of patients had minor complications while 1 patient (42 ​yrs female) reported total fecal incontinence after 18 months (0,05 ​%). This patient had mental disorder treated with drugs unknown before surgery and long time mental disorder after surgery. We focused on this last case to discuss long time complication This survey reports some interesting clinical data; respect to standard complications minor complications such as pain, bleeding and anal discomfort represent less than 10 ​% of procedures that is a good results in this perineal surgery. For those working with rectal mucosal prolapse, obstructed defecation syndrome, rectocele or rectal intussusception is essential to distinguish these diagnosis to have a good counselling with patient before surgery (at least 1 month before). It is essential to check these patients with a close follow-up especially after surgery, to avoid any other mental discomfort related to fecal incontinence; long time fecal incontinence, without anatomical disorders as our case, could be associated and related to drugs consumption or mental disorder, or perineal insensitivity due to surgical procedure. In conclusion it is essential to have good clinical practice to suggest STARR procedure, having idea about different diseases, different surgical approaches and different long time complications. •Starr procedure is a safe technique.•Long time follow-up is important to avoid incontinence.•Surgical indications are essential to avoid long time complication such as incontinence.

Aims/hypothesis We previously used an integrative genetics approach to demonstrate that 5-lipoxygenase (5-LO) deficiency in mice (Alox5 ⁻/⁻) protects against atherosclerosis despite increasing lipid levels and fat mass. In the present study, we sought to further examine the role of 5-LO in adiposity and pancreatic function. Methods Alox5 ⁻/⁻ and wild-type (WT) mice were characterised with respect to adiposity and glucose/insulin metabolism using in vivo and in vitro approaches. The role of ALOX5 in pancreatic function in human islets was assessed through short interfering RNA (siRNA) knockdown experiments. Results Beginning at 12 weeks of age, Alox5 ⁻/⁻ mice had significantly increased fat mass, plasma leptin levels and fasting glucose levels, but lower fasting insulin levels (p < 0.05). Although Alox5 ⁻/⁻ mice did not exhibit insulin resistance, they had impaired insulin secretion in response to a bolus glucose injection. Histological analyses revealed that Alox5 ⁻/⁻ mice had increased islet area, beta cell nuclear size, and numbers of beta cells/mm² islet (p < 0.05), indicative of both hyperplasia and hypertrophy. Basal and stimulated insulin secretion in isolated Alox5 ⁻/⁻ islets were significantly lower than in WT islets (p < 0.05) and accompanied by a three- to fivefold decrease in the expression of the genes encoding insulin and pancreatic duodenal homeobox 1 (Pdx1). Direct perturbation of ALOX5 in isolated human islets with siRNA decreased insulin and PDX1 gene expression by 50% and insulin secretion by threefold (p < 0.05). Conclusions/interpretation These results provide strong evidence for pleiotropic metabolic effects of 5-LO on adiposity and pancreatic function and may have important implications for therapeutic strategies targeting this pathway for the treatment of cardiovascular disease.

The ErbB-2 interacting protein receptor-associated late transducer (RALT) was previously identified as a feedback inhibitor of ErbB-2 mitogenic signals. We now report that RALT binds to ligand-activated epidermal growth factor receptor (EGFR), ErbB-4 and ErbB-2.ErbB-3 dimers. When ectopically expressed in 32D cells reconstituted with the above ErbB receptor tyrosine kinases (RTKs) RALT behaved as a pan-ErbB inhibitor. Importantly, when tested in either cell proliferation assays or biochemical experiments measuring activation of ERK and AKT, RALT affected the signalling activity of distinct ErbB dimers with different relative potencies. RALT ΔEBR, a mutant unable to bind to ErbB RTKs, did not inhibit ErbB-dependent activation of ERK and AKT, consistent with RALT exerting its suppressive activity towards these pathways at a receptor-proximal level. Remarkably, RALT ΔEBR retained the ability to suppress largely the proliferative activity of ErbB-2.ErbB-3 dimers over a wide range of ligand concentrations, indicating that RALT can intercept ErbB-2.ErbB-3 mitogenic signals also at a receptor-distal level. A suppressive function of RALT ΔEBR towards the mitogenic activity of EGFR and ErbB-4 was detected at low levels of receptor occupancy, but was completely overcome by saturating concentrations of ligand. We propose that quantitative and qualitative aspects of RALT signalling concur in defining identity, strength and duration of signals generated by the ErbB network.