Esbl/ampc-producing escherichia coli in wild boar: Epidemiology and risk factors

The complex health problem of antimicrobial resistance (AMR) involves many host species, numerous bacteria and several routes of transmission. Extended-spectrum β-lactamase and AmpC (ESBL/AmpC)-producing Escherichia coli are among the most important strains. Moreover, wildlife hosts are of interest as they are likely antibiotics free and are assumed as environmental indicators of AMR contamination. Particularly, wild boar (Sus scrofa) deserves attention because of its increased population densities, with consequent health risks at the wildlife–domestic–human interface, and the limited data available on AMR. Here, 1504 wild boar fecal samples were microbiologically and molecularly analyzed to investigate ESBL/AmpC-producing E. coli and, through generalized linear models, the effects of host-related factors and of human population density on their spread. A prevalence of 15.96% of ESBL/AmpC-producing E. coli, supported by blaCTX-M (12.3%), blaTEM (6.98%), blaCMY (0.86%) and blaSHV (0.47%) gene detection, emerged. Young animals were more colonized by ESBL/AmpC strains than older subjects, as observed in domestic animals. Increased human population density leads to increased blaTEM prevalence in wild boar, suggesting that spatial overlap may favor this transmission. Our results show a high level of AMR contamination in the study area that should be further investigated. However, a role of wild boar as a maintenance host of AMR strains emerged

Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice

The sphingolipid ceramide is intimately involved in the growth, differentiation, senescence, and death of normal and cancerous cells. Mitochondria are increasingly appreciated to play a key role in ceramide-induced cell death. Recent work showed the C16-pyridinium ceramide analogue LCL-30 to induce cell death in vitro by mitochondrial targeting. The aim of the current study was to translate these results to an in vivo model. We found that LCL-30 accumulated in mitochondria in the murine colorectal cancer cell line CT-26 and reduced cellular ATP content, leading to dose- and time-dependent cytotoxicity. Although the mitochondrial levels of sphingosine-1-phosphate (S1P) became elevated, transcription levels of ceramide-metabolising enzymes were not affected. In mice, LCL-30 was rapidly absorbed from the peritoneal cavity and cleared from the circulation within 24 h, but local peritoneal toxicity was dose-limiting. In a model of subcutaneous tumour inoculation, LCL-30 significantly reduced the proliferative activity and the growth rate of established tumours. Sphingolipid profiles in tumour tissue also showed increased levels of S1P. In summary, we present the first in vivo application of a long-chain pyridinium ceramide for the treatment of experimental metastatic colorectal cancer, together with its pharmacokinetic parameters. LCL-30 was an efficacious and safe agent. Future studies should identify an improved application route and effective partners for combination treatment

Ceramides bind VDAC2 to trigger mitochondrial apoptosis

Ceramides draw wide attention as tumor suppressor lipids that act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are largely unknown. Using a photoactivatable ceramide probe, we here identify the voltage-dependent anion channels VDAC1 and VDAC2 as mitochondrial ceramide binding proteins. Coarse-grain molecular dynamics simulations reveal that both channels harbor a ceramide binding site on one side of the barrel wall. This site includes a membrane-buried glutamate that mediates direct contact with the ceramide head group. Substitution or chemical modification of this residue abolishes photolabeling of both channels with the ceramide probe. Unlike VDAC1 removal, loss of VDAC2 or replacing its membrane-facing glutamate with glutamine renders human colon cancer cells largely resistant to ceramide-induced apoptosis. Collectively, our data support a role of VDAC2 as direct effector of ceramide-mediated cell death, providing a molecular framework for how ceramides exert their anti-neoplastic activity

Identification and Characterization of Murine Mitochondria-associated Neutral Sphingomyelinase (MA-nSMase), the Mammalian Sphingomyelin Phosphodiesterase 5*

Sphingolipids play important roles in regulating cellular responses. Although mitochondria contain sphingolipids, direct regulation of their levels in mitochondria or mitochondria-associated membranes is mostly unclear. Neutral SMase (N-SMase) isoforms, which catalyze hydrolysis of sphingomyelin (SM) to ceramide and phosphocholine, have been found in the mitochondria of yeast and zebrafish, yet their existence in mammalian mitochondria remains unknown. Here, we have identified and cloned a cDNA based on nSMase homologous sequences. This cDNA encodes a novel protein of 483 amino acids that displays significant homology to nSMase2 and possesses the same catalytic core residues as members of the extended N-SMase family. A transiently expressed V5-tagged protein co-localized with both mitochondria and endoplasmic reticulum markers in MCF-7 and HEK293 cells; accordingly, the enzyme is referred to as mitochondria-associated nSMase (MA-nSMase). MA-nSMase was highly expressed in testis, pancreas, epididymis, and brain. MA-nSMase had an absolute requirement for cations such as Mg2+ and Mn2+ and activation by the anionic phospholipids, especially phosphatidylserine and the mitochondrial cardiolipin. Importantly, overexpression of MA-nSMase in HEK293 cells significantly increased in vitro N-SMase activity and also modulated the levels of SM and ceramide, indicating that the identified cDNA encodes a functional SMase. Thus, these studies identify and characterize, for the first time, a mammalian MA-nSMase. The characterization of MA-nSMase described here will contribute to our understanding of pathways regulated by sphingolipid metabolites, particularly with reference to the mitochondria and associated organelles

Scuola Lavoro Famiglia Universit\ue0. Per un sistema formativo alleato e competente

In uno scenario contrassegnato dall\u2019accelerazione dei cambiamenti socioeconomici e dalla complessit\ue0 delle dinamiche geopolitiche, la sfida della collaborazione tra scuola e lavoro permane centrata sulla formazione delle persone. Chiama in causa famiglie e universit\ue0, la coscienza e l\u2019intenzionalit\ue0 dell\u2019impegno profuso nelle relazioni educative. Gli autori dei saggi indicano le potenzialit\ue0 di un\u2019alleanza sistemica e competente tra istituzioni formative, professioni e realt\ue0 associative. Senza celare ambiguit\ue0 e difficolt\ue0 nei percorsi di alternanza scuola lavoro, il volume accredita l\u2019ipotesi che per favorirne il successo sia essenziale la progettazione e il coordinamento pedagogico. Nel curricolo del secondo ciclo di istruzione, includere moduli in cui gli allievi svolgono esperienze in contesti lavorativi pu\uf2 dare vita ad un inedito processo di cross fertilisation, tra saperi e organizzazioni, generi e generazioni. Scuola lavoro universit\ue0 famiglia. Per un sistema formativo alleato e competente. Nell\u2019intelligenza delle nostre mani, lo sviluppo umano come libert\ue

Pedagogia dell'ambiente 2017 Tra sviluppo umano e responsabilit\ue0 sociale

Tra controversie e ambiguit\ue0 di diverso genere, la cultura della sostenibilit\ue0 rappresenta una forma di capitale sociale che indica il grado di coesione civica, la natura dei rapporti di collaborazione istituzionale, l'ampiezza e la profondit\ue0 dei legami di solidariet\ue0. Le questioni ambientali hanno assunto negli ultimi anni crescente rilevanza pubblica e occupazionale. Non sorprende che un gruppo della Societ\ue0 Italiana di Pedagogia sia dedicato ai temi della Pedagogia dell'Ambiente, dello Sviluppo Umano, della Responsabilit\ue0 sociale. Pedagogia dell'ambiente 2017 designa un'area di aspettative pubbliche e un luogo di partecipazione, di responsabilit\ue0 sociale ed economica, di intrapresa tecnologica. Apprendere ed insegnare, innovare e competere richiedono orientamenti valoriali ed azioni responsabili. \uc8 in gioco una pedagogia militante ed emancipativa, per vivere il benessere ed educare alla qualit\ue0 della vita