Investigation on the occurrence of Echinococcus multilocularis in Central Italy

Background  

Feed contaminated with Salmonella spp. constitutes a risk of Salmonella infections in animals, and subsequently in the consumers of animal products. Salmonella are occasionally isolated from the feed factory environment and some clones of Salmonella persist in the factory environment for several years. One hypothesis is that biofilm formation facilitates persistence by protecting bacteria against environmental stress, e.g. disinfection. The aim of this study was to investigate the biofilm forming potential of Salmonella strains from feed- and fishmeal factories. The study included 111 Salmonella strains isolated from Norwegian feed and fish meal factories in the period 1991–2006 of serovar Agona, serovar Montevideo, serovar Senftenberg and serovar Typhimurium.     

A Comparative Study of the Spatial Distribution of Schistosomiasis in Mali in 1984–1989 and 2004–2006

Background

We investigated changes in the spatial distribution of schistosomiasis in Mali following a decade of donor-funded control and a further 12 years without control.

Methodology/Principal Findings

National pre-intervention cross-sectional schistosomiasis surveys were conducted in Mali in 1984–1989 (in communities) and again in 2004–2006 (in schools). Bayesian geostatistical models were built separately for each time period and on the datasets combined across time periods. In the former, data from one period were used to predict prevalence of schistosome infections for the other period, and in the latter, the models were used to determine whether spatial autocorrelation and covariate effects were consistent across periods. Schistosoma haematobium prevalence was 25.7% in 1984–1989 and 38.3% in 2004–2006; S. mansoni prevalence was 7.4% in 1984–1989 and 6.7% in 2004–2006 (note the models showed no significant difference in mean prevalence of either infection between time periods). Prevalence of both infections showed a focal spatial pattern and negative associations with distance from perennial waterbodies, which was consistent across time periods. Spatial models developed using 1984–1989 data were able to predict the distributions of both schistosome species in 2004–2006 (area under the receiver operating characteristic curve was typically >0.7) and vice versa.

Conclusions/Significance

A decade after the apparently successful conclusion of a donor-funded schistosomiasis control programme from 1982–1992, national prevalence of schistosomiasis had rebounded to pre-intervention levels. Clusters of schistosome infections occurred in generally the same areas accross time periods, although the precise locations varied. To achieve long-term control, it is essential to plan for sustainability of ongoing interventions, including stengthening endemic country health systems.     

Mitotic Phosphorylation of Cdc25B Ser321 Disrupts 14-3-3 Binding to the High Affinity Ser323 Site

Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated by binding of the 14-3-3 dimer. There are three 14-3-3 binding sites on Cdc25B, with Ser³²³ being the highest affinity binding and is highly homologous to the Ser²¹⁶ 14-3-3 binding site on Cdc25C. Loss of 14-3-3 binding to Ser³²³ increases cyclin/Cdk substrate access to the catalytic site, thereby increasing its activity. It also affects the localization of Cdc25B. Thus, phosphorylation and 14-3-3 binding to this site is essential for down-regulating Cdc25B activity, blocking its mitosis promoting function. The question of how this inhibitory signal is relieved to allow Cdc25B activation and entry into mitosis is yet to be resolved. Here, we show that Ser³²³ phosphorylation is maintained into mitosis, but phosphorylation of Ser³²¹ disrupts 14-3-3 binding to Ser³²³, mimicking the effect of inhibiting Ser³²³ phosphorylation on both Cdc25B activity and localization. The unphosphorylated Ser³²¹ appears to have a role in stabilizing 14-3-3 binding to Ser³²³, and loss of the Ser hydroxyl group appears to be sufficient to significantly reduce 14-3-3 binding. A consequence of loss of 14-3-3 binding is dephosphorylation of Ser³²³. Ser³²¹ is phosphorylated in mitosis by Cdk1. The mitotic phosphorylation of Ser³²¹ acts to maintain full activation of Cdc25B by disrupting 14-3-3 binding to Ser³²³ and enhancing the dephosphorylation of Ser³²³ to block 14-3-3 binding to this site.     

Enfuvirtide administration in HIV-positive transgender patient with soft tissue augmentation: US evaluation

Enfuvirtide is a large protein that should be injected subcutaneously to ensure an appropriate absorption. Here we report the case of a transgender HIV-positive patient receiving enfuvirtide with an individualized background regimen of antiretroviral drugs, who had previously undergone liquid silicone oil injections. We performed US scan to detect silicone-free areas for following enfuvirtide injections. US can be useful in the correct management of those patients with liquid silicone oil soft tissue augmentation who require subcutaneously injected drugs.     

Identification of cells secreting a thymostimulin-like substance and examination of some histoenzymatic pathways in aging avian primary lymphatic organs: II. Bursa of Fabricius

The Bursa of Fabricius of 15 day, 1-, 3-, and 6 month-old adult chickens (White Leghorn strain) were studied by histological and histochemical staining, histoenzymatic reactions (LDH, SDH, a-GPDH, NAD, NADPH, Ca++-dependent ATP-ase, pH 8.5) and by anti-thymostimulin immunoreaction. Positive reactions for mucopolysaccharides and enzymatic activities were located in the epithelia of the follicles, i.e. in follicle-associated-epithelium (FAE), inter-follicle-epithelium (IFE) and in different epithelial compartments of cortical and medullary zones. Positive reaction for thymostimulin-like (TS-like) substance was restricted to FAE cells and weakly to the basal lamina of IFE. In 6-month-old chickens, the FAE cells disappeared; the phenomenon of bursal regression was evident, although not all the follicles were involved. In the few still normal follicles, the good reactivity to the enzymes tested suggests that residual physiological activity is still present, even if reduced.     

The phosphorylation of nuclear proteins in normal and transformed cells.

Normal (Rat 1) and transformed cells (middle T antigen-transformed derivative 3C3) were grown in the presence of 32P-orthophosphate. 32P-labelled nuclear proteins were fractionated by means of two-dimensional gel electrophoresis and detected by autoradiography. The comparative analysis of the autoradiographs of the normal and transformed cells revealed differences in the phosphorylation patterns of histone and low-molecular-mass high mobility group proteins (HMG). Three of the HMG proteins were highly phosphorylated in the transformed cells, and the analysis of their phosphorylation sites showed that these HMG proteins were phosphorylated on serine and threonine but not on tyrosine residues.     

A cyclin D-Cdk4 activity required for G2 phase cell cycle progression is inhibited in ultraviolet radiation-induced G2 phase delay.

Cyclin D-Cdk4 complexes have a demonstrated role in G1 phase, regulating the function of the retinoblastoma susceptibility gene product (Rb). Previously, we have shown that following treatment with low doses of UV radiation, cell lines that express wild-type p16 and Cdk4 responded with a G2 phase cell cycle delay. The UV-responsive lines contained elevated levels of p16 post-treatment, and the accumulation of p16 correlated with the G2 delay. Here we report that in UV-irradiated HeLa and A2058 cells, p16 bound Cdk4 and Cdk6 complexes with increased avidity and inhibited a cyclin D3-Cdk4 complex normally activated in late S/early G2 phase. Activation of this complex was correlated with the caffeine-induced release from the UV-induced G2 delay and a decrease in the level of p16 bound to Cdk4. Finally, overexpression of a dominant-negative mutant of Cdk4 blocked cells in G2 phase. These data indicate that the cyclin D3-Cdk4 activity is necessary for cell cycle progression through G2 phase into mitosis and that the increased binding of p16 blocks this activity and G2 phase progression after UV exposure.     

Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells

Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic integrity. An increasing number of tumor suppressors are being demonstrated to have roles in checkpoint mechanisms, implying that checkpoint dysfunction is likely to be a common feature of cancers. Here we report that histone deacetylase inhibitors, in particular azelaic bishydroxamic acid, triggers a G2 phase cell cycle checkpoint response in normal human cells, and this checkpoint is defective in a range of tumor cell lines. Loss of this G2 checkpoint results in the tumor cells undergoing an aberrant mitosis resulting in fractured multinuclei and micronuclei and eventually cell death. This histone deacetylase inhibitor-sensitive checkpoint appears to be distinct from G2/M checkpoints activated by genotoxins and microtubule poisons and may be the human homologue of a yeast G2 checkpoint, which responds to aberrant histone acetylation states. Azelaic bishydroxamic acid may represent a new class of anticancer drugs with selective toxicity based on its ability to target a dysfunctional checkpoint mechanism in tumor cells.