ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex

The small GTPase ADP-ribosylation factor (ARF) regulates the structure and function of the Golgi complex through mechanisms that are understood only in part, and which include an ability to control the assembly of coat complexes and phospholipase D (PLD). Here we describe a new property of ARF, the ability to recruit phosphatidylinositol-4-OH kinase-beta and a still unidentified phosphatidylinositol-4-phosphate-5-OH kinase to the Golgi complex, resulting in a potent stimulation of synthesis of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate; this ability is independent of its activities on coat proteins and PLD. Phosphatidylinositol-4-OH kinase-beta is required for the structural integrity of the Golgi complex: transfection of a dominant-negative mutant of the kinase markedly alters the organization of the organelle.     

Antimicrobial and anti-pathogenic activity of some thioureides derivatives against Erwinia amylovora phytopathogenic strains

A series of N-(1-methyl-1 Hpyrazole-4-carbonyl)-thiourea derivatives were assessed for their in vitro antimicrobial and anti-pathogenic activity against twenty-two strains of Erwinia amylovora isolated from different regions in Romania. The compounds were solubilised in dimethylsulfoxide and screened for their in vitro antimicrobial activity. The qualitative screening of the susceptibility spectra of various strains to the compounds was performed by adapted diffusion techniques (distribution of the tested compound solution directly on the solid medium previously seeded with the bacterial inoculums). The quantitative assay of the minimal inhibitory concentration (MIC, microg/mL) was based on liquid medium two-fold microdilutions. The subinhibitory concentrations of the tested substances were investigated for their influence on biofilm development on inert substrata. The present study showed that six new thiourea compounds exhibited a low antibacterial activity (MIC values > 500 microg/ml), but the subinhibitory concentrations inhibited the biofilm development on inert substrata. Thus, these results could suggest the usefulness of the tested compounds as control agents for preventing the first stage (colonization) of the infection with the fire blight pathogen.     

Synaptojanin 1-mediated PI(4,5)P2 hydrolysis is modulated by membrane curvature and facilitates membrane fission

Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P?] plays a fundamental role in clathrin-mediated endocytosis. However, precisely how PI(4,5)P? metabolism is spatially and temporally regulated during membrane internalization and the functional consequences of endocytosis-coupled PI(4,5)P? dephosphorylation remain to be explored. Using cell-free assays with liposomes of varying diameters, we show that the major synaptic phosphoinositide phosphatase, synaptojanin 1 (Synj1), acts with membrane curvature generators/sensors, such as the BAR protein endophilin, to preferentially remove PI(4,5)P? from curved membranes as opposed to relatively flat ones. Moreover, in vivo recruitment of Synj1's inositol 5-phosphatase domain to endophilin-induced membrane tubules results in fragmentation and condensation of these structures largely in a dynamin-dependent fashion. Our study raises the possibility that geometry-based mechanisms may contribute to spatially restricting PI(4,5)P? elimination during membrane internalization and suggests that the PI(4,5)P?-to-PI4P conversion achieved by Synj1 at sites of high curvature may cooperate with dynamin to achieve membrane fission.     

Biologically threatened dolphins and whales

Among the several threats to which free-ranging cetaceans are exposed, a number of biological noxae are believed to represent a serious hazard to their health and conservation on a global scale, with special emphasis on the Mediterranean Sea. These pathogens include viral agents such as Morbillivirus, which during the last 25 years have caused dramatic epidemics and die-offs among several aquatic mammal species and populations worldwide, as well as Herpesvirus, protozoan agents such as Toxoplasma gondii and bacterial pathogens such as Brucella spp.     

Anti-tumor necrosis factor treatment in occult hepatitis B virus infection: a retrospective analysis of 62 patients with psoriatic disease

One of the problems possibly related to the use of biological agents targeting tumor necrosis factor (TNF)-alpha is the increased risk of infections, including the activation of hepatitis B virus (HBV). HBV activation can occur in carriers of hepatitis B surface antigen (HBsAg), but the risk may also involve the HBsAg-negative (anti-HBc ± anti-HBs) occult carriers. Precise data on the safety of anti-TNF and/or other immunosuppressive drugs in HBV occult carriers are not available. We performed a retrospective analysis of 62 psoriatic patients with occult HBV infection treated with anti-TNF biological agents over a period of approximately 4 years: 44 subjects were treated with etanercept, 8 with infliximab and 10 with adalimumab. During the observational treatment period, no signs of HBV activation were observed. Only in one patient the reappearance of HBsAg, without detectable HBV-DNA, was noted before retreatment with etanercept and after 10 months from discontinuation of the previous course. In this patient etanercept was re-administered in association with lamivudine without any adverse event. Our results suggest the overall safety of treatment with anti-TNF drugs in HBV occult carriers, although a careful and constant monitoring of virological markers is required in such patients during treatment with anti-TNF drugs in order to have an early recognition of viral reactivation.