The Down syndrome critical region protein TTC3 inhibits neuronal differentiation via RhoA and Citron kinase.

The Down syndrome critical region (DSCR) on Chromosome 21 contains many genes whose duplication may lead to the major phenotypic features of Down syndrome and especially the associated mental retardation. However, the functions of DSCR genes are mostly unknown and their possible involvement in key brain developmental events still largely unexplored. In this report we show that the protein TTC3, encoded by one of the main DSCR candidate genes, physically interacts with Citron kinase (CIT-K) and Citron N (CIT-N), two effectors of the RhoA small GTPase that have previously been involved in neuronal proliferation and differentiation. More importantly, we found that TTC3 levels can strongly affect the NGF-induced differentiation of PC12 cells, by a CIT-K-dependent mechanism. Indeed, TTC3 overexpression leads to strong inhibition of neurite extension, which can be reverted by CIT-K RNAi. Conversely, TTC3 knockdown stimulates neurite extension in the same cells. Finally, we find that Rho, but not Rho kinase, is required for TTC3 differentiation-inhibiting activity. Our results suggest that the TTC3–RhoA–CIT-K pathway could be a crucial determinant of in vivo neuronal development, whose hyperactivity may result in detrimental effects on the normal differentiation program

Volcanic CO2 tracks the incubation period of basaltic paroxysms

The ordinarily benign activity of basaltic volcanoes is periodically interrupted by violent paroxysmal explosions ranging in size from Hawaiian to Plinian in the most extreme examples. These paroxysms often occur suddenly and with limited or no precursors, leaving their causal mechanisms still incompletely understood. Two such events took place in summer 2019 at Stromboli, a volcano otherwise known for its persistent mild open-vent activity, resulting in one fatality and damage to infrastructure. Here, we use a post hoc analysis and reinterpretation of volcanic gas compositions and fluxes acquired at Stromboli to show that the two paroxysms were preceded by detectable escalations in volcanic plume CO2 degassing weeks to months beforehand. Our results demonstrate that volcanic gas CO2 is a key driver of explosions and that the preparatory periods ahead of explosions in basaltic systems can be captured by precursory CO2 leakage from deeply stored mafic magma

Helicobacter species sequences in liver samples from patients with and without hepatocellular carcinoma

AIM: Only a minority of patients carrying a defined viral aetiologic agent develop cirrhosis and ultimately hepatocellular carcinoma (HCC), the mechanism underlying the worsening is still undefined. Experimental infection by Helicobacter hepaticus in mice causes chronic hepatitis and HCC and recently, more Helicobacter species (Helicobacter spp.) have been detected in the liver of patients suffering from cholestatic diseases and HCC arising from non-cirrhotic liver. We investigated whether Helicobacter spp. sequences could be detected in the liver of patients with cirrhosis and HCC compared to subjects with metastasis to liver from colon cancer. METHODS: Twenty-three liver samples from patients operated upon for HCC superimposed on hepatitis C virus (HCV)-related cirrhosis and 6 from patients with resected metastases from colorectal cancer, were tested by polymerase chain reaction for presence of genomic 16S rRNA of Helicobacter genus using specific primers. DNA sequencing and cag A gene analysis were also performed. RESULTS: Genomic sequences of Helicobacter spp. were found in 17 of 20 (85%) liver samples from patients with HCC and in 2 of 6 samples from patients with liver metastasis. In three samples of the first group the result was uncertain. H pylori was revealed in 16 out of 17 positive samples and Helicobacter pullorum in the other. CONCLUSION: Helicobacter spp., carcinogenic in mice, were found at a higher frequency in the liver of patients with HCV-related cirrhosis and HCC than those in patients without primary liver disease