Semaphorin signalling in GnRH neurons: from development to disease

In mammals, fertility critically depends on the pulsatile secretion of gonadotropin-releasing hormone (GnRH) by scattered hypothalamic neurons (GnRH neurons). During development, GnRH neurons originate in the nasal placode and migrate first in the nasal compartment and then through the nasal/forebrain junction, before reaching their final positions in the hypothalamus. This neurodevelopmental process, which has been extensively studied in mouse models, is regulated by a plethora of factors that might control GnRH neuron migration or survival as well as the fasciculation/targeting of the olfactory/vomeronasal axons along which the GnRH neurons migrate. Defects in GnRH neuron development or release can lead to Isolated GnRH Deficiency (IGD), whose underlying genetic causes are still partially unknown. Recently, semaphorins and their receptors neuropilins and plexins, a large family of molecules implicated in neuronal developmental and plasticity processes, are emerging as key regulators of GnRH neuron biology and deficiency. Specifically, semaphorins have been shown to play different roles in GnRH neuron biology, by regulating migration and survival during embryonic development as well as secretion in adulthood

Nuovi dati sul Bronzo medio iniziale di Belverde di Cetona: gli scavi al Riparo del Capriolo e alla Buca del Leccio

Gli scavi a Belverde di Cetona condotti dall'Università di Siena dopo il 1985 hanno evidenziato una serie di insediamenti sul Monte Cetona e chiarito molti aspetti non chiari delle ricerche di U. calzoni. Le AA. illustrano i primi riusltati degli studi pluridisciplinari su due nuovi siti, evidenziandone le connessioni e le diversità con i contesti già not

Protein kinase CK2 subunits differentially perturb the adhesion and migration of GN11 cells: A model of immature migrating neurons

Protein kinase CK2 (CK2) is a highly conserved and ubiquitous kinase is involved in crucial biological processes, including proliferation, migration, and differentiation. CK2 holoenzyme is a tetramer composed by two catalytically active (\u3b1/\u3b1') and two regulatory (\u3b2) subunits and exerts its function on a broad range of targets. In the brain, it regulates different steps of neurodevelopment, such as neural differentiation, neuritogenesis, and synaptic plasticity. Interestingly, CK2 mutations have been recently linked to neurodevelopmental disorders; however, the functional requirements of the individual CK2 subunits in neurodevelopment have not been yet investigated. Here, we disclose the role of CK2 on the migration and adhesion properties of GN11 cells, an established model of mouse immortalized neurons, by different in vitro experimental approaches. Specifically, the cellular requirement of this kinase has been assessed pharmacologically and genetically by exploiting CK2 inhibitors and by generating subunit-specific CK2 knockout GN11 cells (with a CRISPR/Cas9-based approach). We show that CK2\u3b1' subunit has a primary role in increasing cell adhesion and reducing migration properties of GN11 cells by activating the Akt-GSK3\u3b2 axis, whereas CK2\u3b1 subunit is dispensable. Further, the knockout of the CK2\u3b2 regulatory subunits counteracts cell migration, inducing dramatic alterations in the cytoskeleton not observed in CK2\u3b1' knockout cells. Collectively taken, our data support the view that the individual subunits of CK2 play different roles in cell migration and adhesion properties of GN11 cells, supporting independent roles of the different subunits in these processes

Qualità microbiologica delle acque per emodialisi: quali i fattori di rischio? [Microbiological quality of hemodialysis water: what are the risk factors?]

Introduzione Un paziente in dialisi entra in contatto settimanalmente con un’ingente quantità d’acqua tramite il bagno di dialisi, in media 350 litri. È pertanto essenziale che questa soluzione abbia un’elevata qualità e purezza. Scopo del nostro studio è stato monitorare nel tempo la qualità microbiologica delle acque dell’emodialisi, al fine di individuare eventuali fattori che possano influenzarla. Metodi Abbiamo effettuato da Gennaio 2015 a Ottobre 2017 uno studio cross-sectional raccogliendo le acque delle apparecchiature dialitiche presso l’AOU Careggi. I campioni raccolti in maniera asettica e da tecnici specializzati, sono stati trasportati sotto ghiaccio a 4°C al Laboratorio di Rischio Biologico dell’Azienda USL Toscana Centro per le analisi di laboratorio. Risultati Sono stati raccolti 126 campioni di acqua. Coliformi, E. coli, Staphylococcus aureus, enterococchi sono risultati negativi in tutti i campioni. Pseudomonas aeruginosa è risultata positiva in un solo campione. Sia per le CFU a 37°C che a 22°C la tipologia di macchinario rappresenta l’unico fattore di rischio statisticamente significativo (OR 15.21 e OR 10.25 rispettivamente): i macchinari SDS hanno un rischio decisamente più alto di risultare positivi per le CFU a 37°C e 22°C. Conclusioni È necessario monitorare costantemente il sistema di trattamento delle acque di dialisi e questo ancor più nel caso di dispositivi con sistema SDS che, a causa del loro utilizzo discontinuo, possono essere soggetti più frequentemente, come dimostrato nel nostro studio, a maggiore contaminazione. PAROLE CHIAVE: sorveglianza, emodialisi, infezioniBACKGROUND: A dialyzed patient weekly gets in touch with a large amount of water (on average 350 liters) through the dialysis bath. It is therefore essential that this solution would have a high quality and purity. The aim of our study was to monitor the microbiological quality of the hemodialysis water in order to identify possible factors that could affect it. METHODS: We conducted a cross-sectional study from January 2015 to October 2017 collecting the dialysis water in AOU Careggi. Samples were aseptically collected by specialized technicians and then transported under ice at 4° C to the Laboratory of Biological Hazards of USL Toscana Centro for laboratory analyses. RESULTS: 126 water samples were collected. Coliforms, E. coli, Staphylococcus aureus, enterococci were not detected. Pseudomonas aeruginosa was found in only one sample. Both for CFU at 37° C and at 22° C, the type of device represented the only statistically significant risk factor (OR 15.21 and OR 10.25 respectively): SDS devices had a significantly higher risk of being positive for CFU at 37° C and 22° C. CONCLUSIONS: As our study demonstrated, the system producing dialysis water must be constantly monitored, especially in cases of SDS devices which may be subjected more frequently to a higher contamination, due to their discontinuous use. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy

hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colon cancer

Angiogenesis is a potential target for cancer therapy. We identified a novel signaling pathway that sustains angiogenesis and progression in colorectal cancer (CRC). This pathway is triggered by b1 integrin-mediated adhesion and leads to VEGF-A secretion. The effect is modulated by the human ether-a`-go-go related gene 1 (hERG1) K1 channel. hERG1 recruits and activates PI3K and Akt. This in turn increases the Hypoxia Inducible Factor (HIF)-dependent transcription of VEGF-A and other tumour progression genes. This signaling pathway has novel features in that the integrin- and hERG1-dependent activation of HIF (i) is triggered in normoxia, especially after CRC cells have experienced a hypoxic stage, (ii) involves NF-kB and (iii) is counteracted by an active p53. Blocking hERG1 switches this pathway off also in vivo, by inhibiting cell growth, angiogenesis and metastatic spread. This suggests that non-cardiotoxic anti-hERG1 drugs might be a fruitful therapeutic strategy to prevent the failure of anti-VEGF therapy