A protein kinase a-independent pathway controlling aquaporin 2 trafficking as a possible cause for the syndrome of inappropriate antidiuresis associated with polycystic kidney disease 1 haploinsufficiency.

Renal water reabsorption is controlled by vasopressin (AVP) which binds to V2 receptors resulting in PKA activation, phosphorylation of AQP2 at serine 256 (pS256) and translocation to the plasma membrane. Besides S256, AVP causes dephosphorylation of S261. Recent studies showed that cyclin-dependent kinases can phosphorylate S261 AQP2 peptides in vitro. In an attempt to investigate the possible role of cdks on AQP2 phosphorylation, we identified a new PKA-independent pathway regulating AQP2 trafficking. In ex-vivo kidney slices and MDCK-AQP2 cells, R-roscovitine, a specific cdks inhibitor, increased pS256 and decreased pS261. The changes in AQP2 phosphorylation were paralleled by an increase in cell surface AQP2 expression and osmotic water permeability in the absence of forskolin stimulation. Of note, R-roscovitine didn’t alter cAMP-dependent PKA activity. Because phosphorylation results from the balance between kinase and phosphatase activity, we evaluated the possible contribution of protein phosphatases PP1, PP2A and PP2B. Of these, R-roscovitine treatment specifically reduced PP2A protein expression and activity in MDCK cells. Interestingly, in PKD1+/- mice displaying a syndrome of inappropriate antidiuresis with high level of pS256 despite unchanged AVP and cAMP, we found a reduced PP2A expression and activity and reduced pS261. Similarly to what previously found in PKD1+/- mice, R-roscovitine treatment caused a significant decrease in intracellular calcium in MDCK cells. Our data indicate that a reduced activity of PP2A, secondary to reduced intracellular Ca2+ levels, promotes AQP2 trafficking independently of the AVP-PKA axis. This pathway may be relevant for explaining pathological states characterized by inappropriate AVP secretion and positive water balance

Filippo Juvarra regista di corti e capitali dalla Sicilia al Piemonte all'Europa

Il complesso degli album che formano il cosiddetto corpus juvarrianum fu acquisito sul mercato antiquario tra il 1762 e il 1763 dall’allora prefetto della Biblioteca Giuseppe Pasini con il duplice intento di offrire a docenti e studenti dell’Ateneo torinese un importante fondo di disegni e incisioni e di dotare la Biblioteca di gran parte della produzione grafica di Filippo Juvarra, architetto di origine siciliana, ma fortemente inserito nel contesto culturale torinese. A questa prima serie si aggiunge il dono nel 1857 di un ulteriore volume, l’unico espressamente ideato da Juvarra, la raccolta dei «Penzieri diversi p. studio d’architettura fatti da me D. Filippo Juvarra a 9 luglio 1707 in Roma». La Biblioteca Nazionale Universitaria di Torino, in concomitanza con i trecento anni della sua fondazione da parte di Vittorio Amedeo II – di fatto il vero trait-d’union tra la biblioteca e l’architetto – e l’ ABNUT (Associazione Amici della Biblioteca Nazionale Universitaria) hanno voluto con tenacia riportare all’attenzione del pubblico, da quello più vasto agli specialisti, nell’ambito della straordinaria ricchezza dei fondi, l’eccezionalità di questo corpus juvarrianum, presentato per la prima volta nella sua compiutezza in occasione della mostra e offerto, con aggiornamenti critici, in questo volume. Alla pubblicazione dell’intero repertorio degli album si associa una selezionata serie di saggi d’occasione, che mettono in luce la ricchezza non soltanto della figura di Juvarra, ma innanzitutto del milieu culturale juvarriano con le sue ricadute evidenti sul panorama torinese ed europeo. Autori saggi e schede: Clelia Arnaldi di Balme, Nicola Badolato, Giulia Bergamo, Paola Bianchi, Giosuè Bronzino, Maria Vittoria Cattaneo, Paolo Cornaglia, Annerita Colturato, Chiara Devoti, Enrico Genta, Elena Gianasso, Andrea Merlotti, Gustavo Mola di Nomaglio, Franca Porticelli, Giuseppina Raggi, Costanza Roggero, José Luis Sancho Gaspar, Cristina Scalon, Fabio Uliana, Franca Varallo

Regulated Salinity Eustress in a Floating Hydroponic Module of Sequentially Harvested Lettuce Modulates Phytochemical Constitution, Plant Resilience, and Post-Harvest Nutraceutical Quality

A mild salinity stress (eustress) may modulate the induction of the plant defense system in horticultural crops and the synthesis of phytochemical components able to enhance plant resilience, post-harvest performance, and the nutraceutical quality of produce. However, the choice of the correct eustress type and dose to induce the synthesis of these protective phytochemicals is pivotal to avoid potential interference with plant growth and productivity. In order to study how green and red lettuce (Lactuca sativa L.) plants equilibrate the nutritional and nutraceutical components of quality with yield components, we applied iso-osmotic concentrations of three different salts (20 mM NaCl, 20 mM KCl, and 13.3 mM CaCl2, with a final total ionic concentration of 40 mM) in combination with two successive harvests in a floating raft system. The biometric parameters, mineral composition, bioactive compounds, and antioxidant activity of both cultivars were analyzed. The green cultivar had a superior response concerning biometric traits and productivity compared to the red one during the first cut but lower phytochemical content (e.g., ascorbic acid). The effect of cut order, independently of cultivar and salinity treatments, demonstrated that at the first harvest plants could redirect metabolism by increasing the lipophilic antioxidant content (LAA) at the expense of plant yield, therefore increasing plant resilience and post-harvest nutraceutical quality; whereas, at the second harvest, plants reverted principally to tissue expansion. The treatments with iso-osmotic salt concentrations did not affect K and Mg ion contents but further increased LAA and resulted only in a moderate decrease of fresh yield. The lettuce nitrate content was reduced during the second cut only when lettuce plants were treated with NaCl and especially CaCl

Plant-based protein hydrolysate improves salinity tolerance in hemp: Agronomical and physiological aspects

Hemp (Cannabis sativa L.) is a multipurpose plant attracting increasing interest as a source for the production of natural fibers, paper, bio-building material and food. In this research we studied the agronomical performance of Cannabis sativa cv. Eletta Campana irrigated with saline water. Under those conditions, we tested the effect of protein hydrolysate (PH) biostimulant application in overcoming and/or balancing deleterious salinity effects. The results of the diverse treatments were also investigated at the physiological level, focusing on photosynthesis by means of a chlorophyll a fluorescence technique, which give an insight into the plant primary photochemical reactions. Four salinity levels of the irrigation solution (fresh water-EC0, and NaCl solutions at EC 2.0, 4.0 or 6.0 dS m−1, EC2, EC4 and EC6, respectively) were combined with 2 biostimulant treatments (untreated (control) or treated with a commercial legume-derived protein hydrolysate (LDPH)). The increasing salinity affected plant photochemistry resulting in lower plant growth and seed production, while the LDPH biostimulant showed a protective effect, which improved crop performance both in control and in salinity conditions. The LDPH treatment improved seeds yield (+38.6% on average of all treated plants respect to untreated plants), as well as residual biomass, relevant in fiber production

Human inflammatory bowel disease does not associate with Lawsonia intracellularis infection

BACKGROUND: There is increasing evidence that bacterial infection of the intestinal mucosa may contribute to the pathogenesis of inflammatory bowel diseases (IBD). In pigs, an obligate intracellular bacterium, Lawsonia intracellularis (LI), was shown to cause proliferative enteropathy (PE) of which some forms display histological and clinical similarities to human IBD. Since LI-similar Desulfovibrio spp. may infect human cells, we hypothesized that LI might be associated with the development of human IBD. RESULTS: In human intestinal tissue samples, PCR using LLG, 50SL27, LSA and strictly LI-specific 16SII primers, yielded either no amplicons or products with weak homology to human genomic sequences. Sequencing of these amplicons revealed no specificity for LI. However, amplification of DNA with less specific 16SI primers resulted in products bearing homology to certain Streptococcus species. These 16SI-amplified products were present in healthy and diseased specimens, without obvious prevalence. CONCLUSION: LI is not associated with the pathogenesis of UC or CD. Whether an immunologic response to commensal bacteria such as streptococci may contribute to the chronic inflammatory condition in IBD, remained to be determined

Plant-Derived Biostimulants Differentially Modulate Primary and Secondary Metabolites and Improve the Yield Potential of Red and Green Lettuce Cultivars

The use of biostimulants in modern agriculture has rapidly expanded in recent years, owing to their beneficial effects on crop yield and product quality, which have come under the scope of intensive research. Accordingly, in the present study we appraised the efficacy of two plantderived biostimulants, the legume-derived protein hydrolysates Trainer®® (PH), and the tropical plant extract Auxym®® (TPE) on two lettuce cultivars (green and red salanova®®) in terms of morpho-physiological and biochemical traits (primary and secondary metabolites). The two cultivars differed in their acquisition capacity for nitrate and other beneficial ions, their photosynthetic and transpiration rates, and their ability to synthetize and accumulate organic acids and protective metabolites. The biostimulant effect was significant for almost all the parameters examined but it was subjected to significant cultivar × biostimulant interactions, denoting a cultivardependent response to biostimulant type. Notwithstanding this interaction, biostimulant application could potentially improve the yield and quality of lettuce by stimulating plant physiological processes, as indicated by the SPAD index (leaf chlorophyll index), ACO2 (assimilation rate), E (transpiration), and WUEi (intrinsic water use efficiency), and by increasing concurrently the plant mineral content (total N, K, Ca, Mg) and the biosynthesis of organic acids (malate, citrate), phenols (caffeic acid, coumaroyl quinic acid isomer 1, dicaffeoylquinic acid isomer 1), and flavonoids (quercetin-3-O-glucuronide, quercetin-3-O-glucoside). Biostimulant action may facilitate the bio-enhancement of certain lettuce cultivars that are otherwise limited by their genetic potential, for the accumulation of specific compounds beneficial to human health

dDAVP Downregulates the AQP3-Mediated Glycerol Transport via V1aR in Human Colon HCT8 Cells

Vasopressin (AVP) plays a key function in controlling body water and salt balance through the activation of the vasopressin receptors V1aR and V2R. Abnormal secretion of AVP can cause the syndrome of inappropriate antidiuresis that leads to hyponatremia, which is an electrolyte disorder often observed in the elderly hospitalized and oncologic patients. Beyond kidneys, the colonic epithelium modulates water and salt homeostasis. The water channel AQP3, expressed in villus epithelial cells is implicated in water absorption across human colonic surface cells. Here, the action of dDAVP, a stable vasopressin analog, was evaluated on the AQP3 expression and function using human colon HCT8 cells as an experimental model. Confocal and Western Blotting analysis revealed that HCT8 cells express both V1aR and V2R. Long-term (72 h) treatment with dDAVP reduced glycerol uptake and cell viability. These effects were prevented by SR49059, a synthetic antagonist of V1aR, but not by tolvaptan, a specific V2R antagonist. Of note, the SR49059 action was impaired by DFP00173, a selective inhibitor of AQP3. Interestingly, compared to the normal colonic mucosa, in the colon of patients with adenocarcinoma, the expression of V1aR was significantly decreased. These findings were confirmed by gene expression analysis with RNA-Seq data. Overall, data suggest that dDAVP, through the V1aR dependent pathway, reduces AQP3 mediated glycerol uptake, a process that is reversed in adenocarcinoma, suggesting that the AVP-dependent AQP3 pathway may represent a novel target in colon diseases associated with abnormal cell growth

Clinical-cytological-grading and phenotyping in patients with chronic rhinosinusitis with nasal polyps: The relevance in clinical practice

Chronic rhinosinusitis (CRS) includes two main phenotypes: without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP). CRSwNP may be associated with comorbidity, mainly concerning asthma, aspirin intolerance, and allergy. CRSwNP patients may also be evaluated by clinical-cytological grading (CCG). The current study investigated the prevalence and characteristics of the different CCG and phenotypes in CRSwNP outpatients examined in clinical practice. This retrospective cross-sectional study enrolled 791 consecutive CRSwNP outpatients (424 males, mean age 48.8 years). In the total population, asthma was a common comorbidity (30.8%) as well as aspirin intolerance (24.8%), and allergy (50.8%). As concerns CCG-grading, 210 (26.5%) outpatients had low-grade, 366 (46.3%) medium, and 215 (27.2%) high. As regards cytological phenotypes, 87 (11%) had neutrophilic type, 371 (46.3%) eosinophilic, 112 (14.2%) mast cell, and 221 (27.9%) mixed. High-grade CCG was significantly associated with more frequent asthma, aspirin intolerance, allergy, recurrent surgery, and mixed cytological phenotype. Low-grade CCG was characterized by fewer comorbidities and operations, and neutrophilic phenotype. Therefore, the present study confirmed that CCG is a useful tool in the management of outpatients with CRSwNP. CRSwNP is frequently associated with asthma, aspirin intolerance, and allergy comorbidity. High-grade CCG is frequently characterized by a mixed cytological phenotype, thus, by more severe progress. These real-world outcomes underline that CRSwNP deserves adequate attention for careful management and optimal identification of the best-tailored therapy; CCG and cytological phenotyping could be fruitful tools in clinical practice. Asthma and aspirin intolerance should be adequately investigated in all CRS patients

Pain in patients with pancreatic cancer: prevalence, mechanisms, management and future developments

Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients’ quality of life and survival