The spermidine analogue GC7 (N1-guanyl-1,7-diamineoheptane) induces autophagy through a mechanism not involving the hypusination of eIF5A

The exogenous administration of spermidine promotes longevity in many model organisms. It has been proposed that this anti-age activity of spermidine is related to this polyamine's ability to promote autophagy. Since spermidine is the substrate for the eIF5A post-translational modification by hypusination, we asked ourselves whether mature eIF5A may represent the link between spermidine and autophagy induction. To test this hypothesis, we inhibited the conversion of native eIF5A by a pharmacological approach, using the N1-guanyl-1,7-diamineoheptane (GC7), a spermidine analogue which competitively and reversibly inhibits deoxyhypusine synthase (DHS). In addition, we also employed genetic approaches by ablating both the eIF5A protein itself and DHS, the rate limiting enzyme catalyzing the conversion of lysine to hypusine. Collectively the data presented in this study demonstrate that the mature eIF5A (hypusinated form) is not involved in the autophagic pathway and that the inhibitor of DHS, GC7, produces off-target effect(s) resulting in marked induction of basal autophagy. These data are relevant in light of the fact that GC7 is considered a potent and selective inhibitor of DHS and is a potential candidate drug for cancer, diabetes and HIV therapy

Resolving cryptic species complexes in marine protists: phylogenetic haplotype networks meet global DNA metabarcoding datasets

Marine protists have traditionally been assumed to be lowly diverse and cosmopolitan. Yet, several recent studies have shown that many protist species actually consist of cryptic complexes of species whose members are often restricted to particular biogeographic regions. Nonetheless, detection of cryptic species is usually hampered by sampling coverage and application of methods (e.g. phylogenetic trees) that are not well suited to identify relatively recent divergence and ongoing gene flow. In this paper, we show how these issues can be overcome by inferring phylogenetic haplotype networks from global metabarcoding datasets. We use the Chaetoceros curvisetus (Bacillariophyta) species complex as study case. Using two complementary metabarcoding datasets (Ocean Sampling Day and Tara Oceans), we equally resolve the cryptic complex in terms of number of inferred species. We detect new hypothetical species in both datasets. Gene flow between most of species is absent, but no barcoding gap exists. Some species have restricted distribution patterns whereas others are widely distributed. Closely related taxa occupy contrasting biogeographic regions, suggesting that geographic and ecological differentiation drive speciation. In conclusion, we show the potential of the analysis of metabarcoding data with evolutionary approaches for systematic and phylogeographic studies of marine protists

Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma

Continuity of Care During End of Life: An Evolutionary Concept Analysis

PURPOSE: The purpose of this study was to clarify the concept of continuity of care during the end of life with a focus on the patient’s perspective. METHODS: Rodgers’ method of evolutionary concept analysis was used. The analysis was based on literature published in English in the databases Cumulative Index for Nursing and Allied Health Literature, Medline, and PsycINFO. FINDINGS: Analysis revealed that the continuity at life’s end is a dynamic process that depends on the interaction among patients, families, and providers, and is strictly interwoven with the patient’s time perception. CONCLUSION: This analysis showed the complexities surrounding the patient’s experience of continuity at life’s end. IMPLICATION FOR NURSING: Nurses can benefit from a deeper understanding of the patient’s experience, both theoretically and in practice

Pharmacological treatment of ceftriaxone-related cholelithiasis in children: is it worthwhile?

Ceftriaxone treatment of bacterial infections can be associated with biliary complications, more commonly in children than adults, in a dosedependent manner. This study describes a clinical case series of children with ceftriaxone-related cholelithiasis. We performed a retrospective analysis of cases of ceftriaxone-related biliary complications admitted to the Pediatric Clinic, Department of Clinical and Experimental Medicine, University of Sassari, Italy, during the period 2005-2015. Four children with cholelithiasis occurring during, or soon after, the treatment with ceftriaxone are reported. Case 1 (6-month-old), case 2 (9-yearold) and case 4 (10-year-old) were symptomatic, while case 3 (3-year-old) was asymptomatic. After the ultrasonographic diagnosis of gallstones (cases 1 and 2) or biliary sludge (cases 3 and 4), ceftriaxone treatment was withdrawn, and ursodeoxycholic acid (UDCA) was started in cases 1 and 2. A complete recovery was observed in all but case 1, in whom cholelithiasis was still detectable at one-year follow-up by ultrasonography. This case underwent a triple antibiotic protocol for bacterial meningitis. The protocol included rifampicin, which is known to have an effect in decreasing hepatic concentration of bile salts. Therefore, in this case, both rifampicin and UDCA were of no benefit in preventing or treating ceftriaxone biliary complications. The current pharmacological approach for the treatment of ceftriaxonerelated cholelithiasis seems to be ineffective, likely due to the high calcium content of gallstones. Therefore, the best strategy of intervention for ceftriaxone biliary complications in children remains the prevention of the risk factors

Single-hit resolution measurement with MEG II drift chamber prototypes

Drift chambers operated with helium-based gas mixtures represent a common solution for tracking charged particles keeping the material budget in the sensitive volume to a minimum. The drawback of this solution is the worsening of the spatial resolution due to primary ionisation fluctuations, which is a limiting factor for high granularity drift chambers like the MEG II tracker. We report on the measurements performed on three different prototypes of the MEG II drift chamber aimed at determining the achievable single-hit resolution. The prototypes were operated with helium/isobutane gas mixtures and exposed to cosmic rays, electron beams and radioactive sources. Direct measurements of the single hit resolution performed with an external tracker returned a value of 110 $\mu$m, consistent with the values obtained with indirect measurements performed with the other prototypes.Comment: 18 pages, 18 figure

Un processo innovativo per la produzione di un piatto tradizionale della Sardegna: il maialetto (Porcheddu) arrosto

Il suinetto arrosto (Porcheddu) è uno dei piatti tradizionali della Sardegna più apprezzati, questo

Predicting candidemia in internal medicine departments: are we chasing the Holy Grail?

Candidemia is a challenging clinical condition with high rates of morbidity and mortality.1 Key requirements for its prompt management include early identification and timely initiation of appropriate systemic antifungal therapy, consistently reported as a major determinant of survival. However, the diagnosis of candidemia can be challenging and is often delayed as there are no specific clinical signs, blood cultures have low sensitivity, and detection of fungal blood cultures takes a long time. In addition, there is evidence that a significant percentage of such infections occurs in patients admitted to internal medicine departments. This is not particularly surprising given the advanced age of many inpatients at internal medicine departments and multiple complex comorbidities. Moreover, related therapies and healthcare system contacts often involve the use of central venous catheters and other indwelling devices, potentially entailing high risk of candidemia.2 Therefore, optimization of the diagnostic and therapeutic approach is an important and still unfulfilled need for the management of candidemia in internal medicine department