The bloodsucking arthropod bite as possible cofactor in the transmission of human herpesvirus-8 infection and in the expression of Kaposi's sarcoma disease

Based on a review of the literature on human herpesvirus-8 (HHV8) and Kaposi's sarcoma (KS) and on the distribution of KS in Italy (Veneto region particularly), we hypothesize that the bite of bloodsucking arthropods is a cofactor in the seroconversion to HHV8 positivity and probably in the pathogenesis of KS. The bloodsucking arthropod releases with saliva powerful antihaemostatics and immunomodulators which may favour the replication and the establishment of the pathogen. Transmission would depend on the close contact of the child with a seropositive mother (or relatives) whose infective saliva is used to relieve itching and scratching at the arthropod bite's sites. During any deregulation of the immune system (e.g. ageing), local immune responses to new insect bites may induce virus activation which could prelude KS insurgence. The pathogen is not directly transmitted by the arthropod which merely prepares the cutaneous microenvironment for the virus. We have therefore introduced a new category of medically important arthropods, "promoter arthropods", besides those already defined as biological or mechanical vectors. Promoter arthropods are species able to induce in the host long-lasting, immediate or delayed-type hypersensitivity responses as well as local immunosuppression due to substances injected with their saliva. The striking variability of ORF-K1 gene of HHV8 could be due to the adaptation of the virus to the specific microenvironments resulting from the immune response to the salivary antigens characteristic of the bloodsucking arthropod species prevalent in each geographical area. It is worth noting that other viruses (especially Hepatitis B Virus) may exploit the same non-sexual transmission route.     

A new gene-finding tool: using the Caenorhabditis elegans operons for identifying functional partner proteins in human cells

How can a large number of different phenotypes be generated by a limited number of genotypes? Promiscuity between different, structurally related and/or unrelated proteins seems to provide a plausible explanation to this pertinent question. Strategies able to predict such functional interrelations between different proteins are important to restrict the number of putative candidate proteins, which can then be subjected to time-consuming functional tests. Here we describe the use of the operon structure of the nematode genome to identify partner proteins in human cells. In this work we focus on ion channels proteins, which build an interface between the cell and the outside world and are responsible for a growing number of diseases in humans. However, the proposed strategy for the partner protein quest is not restricted to this scientific area but can be adopted in virtually every field of human biology where protein-protein interactions are assumed.     

Break the pattern: breakpoints in beta diversity of vertebrates are general across clades and suggest common historical causes

The use of correlative analyses might be insufficient to understand the processes that control biodiversity, because the variables accounting for different hypotheses (e.g. current climate, past climate change, post‐glacial dispersal limitation) are mutually correlated. We suggest here that, in order to gain insight, it could be useful to search for latitudinal thresholds that could provide information about qualitative changes in the way biodiversity varies in space. Such tipping points could inform about higher‐level processes that are not reflected in correlative analyses. We test whether similar breakpoints in latitudinal beta‐diversity patterns exist for different vertebrate groups with diverse life histories and dispersal abilities. In birds, bats and non‐volant mammals we find breakpoints similar to those of amphibians. Differences in species composition are mainly due to species replacement from the equator to the breakpoint, but are dominated by nested species losses from the breakpoint to higher latitudes. Thus, marked thresholds discriminate two world regions where different processes appear to drive biodiversity.     

Convenient preparation of L-arabino-hexos-5-ulose derivatives from lactose

2,6-di-O-benzyl- (9), 2-O-benzyl-3,4-O-isopropylidene- (19), and 2-O-benzyl-6-O-m-chlorobenzoyl-L-arabino-hexos-5-ulose (20) have been prepared using 4'-deoxy-4'-eno- and 6'-deoxy-5'-eno lactose dimethyl acetal derivatives 7 and 14 as key intermediates. The synthesis of enol ethers 7 and 14 has been performed with good yields by base-promoted elimination of acetone or p-toluenesulfonic acid from 2',6'-di-O-benzyl-, and 6'-O-p-toluenesulfonyl-2,3:5,6:3',4'-tri-O-isopropylidenelactose dimethyl acetal, respectively. The epoxidation with MCPBA of 7 and 14 in methanol or dichloromethane furnishes C-5'-methoxy and C-5'-m-chlorobenzoyloxy derivatives, easily transformed with good yields into L-arabino 5-ketoaldohexoses 9, 19 and 20.     

Multiscale modelling as a tool to prescribe realistic boundary conditions for the study of surgical procedures

This work was motivated by the problems of analysing detailed 3D models of vascular districts with complex anatomy. It suggests an approach to prescribing realistic boundary conditions to use in order to obtain information on local as well as global haemodynamics. A method was developed which simultaneously solves Navier-Stokes equations for local information and a non-linear system of ordinary differential equations for global information. This is based on the principle that an anatomically detailed 3D model of a cardiovascular district can be achieved by using the finite element method. In turn the finite element method requires a specific boundary condition set. The approach outlined in this work is to include the system of ordinary differential equations in the boundary condition set. Such a multiscale approach was first applied to two controls: (i) a 3D model of a straight tube in a simple hydraulic network and (ii) a 3D model of a straight coronary vessel in a lumped-parameter model of the cardiovascular system. The results obtained are very close to the solutions available for the pipe geometry. This paper also presents preliminary results from the application of the methodology to a particular haemodynamic problem: namely the fluid dynamics of a systemic-to-pulmonary shunt in paediatric cardiac surgery.     

Lead induced DNA strand breaks in lymphocytes of exposed workers: role of reactive oxygen species and protein kinase C

Lead and lead compounds play a significant role in modern industry; a wide variety of population is at risk of occupational exposure and lead is suspected to be a human carcinogen. The biochemical and molecular mechanisms of lead toxicity are poorly understood, but emerging data suggest that some of the effects of lead may be due to its interference with calcium in the activation of protein kinase C (PKC) and/or through production of reactive oxygen species (ROS). Many of these results are conducted in vitro on cell lines or ex vivo on human lymphocytes treated in vitro. We, therefore, performed a study on the induction of DNA damage, using the alkaline comet assay, in lymphocytes of battery plant workers. To elucidate in vivo the mechanism(s) responsible for this effect, we determined ROS production, and glutathione (GSH) levels in living cells using the fluorescent probe (2',7'-dichlorofluorescein and monochlorobimane, respectively). Subcellular fractions were obtained from sonicated lymphocytes; cytosolic and membrane expression of PKC isoforms (alpha, and zeta) was evaluated after electrophoresis by immunoblot analysis. The results indicate that lead-exposed workers have significantly elevated levels of DNA breaks compared to the unexposed group. A multivariate analysis of variance (ANOVA) shows that the most common confounding factors (smoking, drinking and age) have no synergistic effects with lead-exposure on the comet parameters or on GSH levels and ROS production. The logistic regression analysis distinguishing the exposed and non-exposed indicates that only GSH with tail moment are selected as significant risk factors. There is a significant positive correlation with ROS production and negative correlation with GSH levels. The content of PKC alpha in cytosol and membranes is decreased 40% (indicating a down-regulation of protein), whereas PKC zeta isoform is not modified in an evident manner. Our results suggest that lead-exposure induces an increase of DNA breakage with an alternate cellular redox state and a significant down-regulation of PKC alpha, suggesting that this metal may act as a tumor promoter.     

Structural properties of a collagenous heterotrimer that mimics the collagenase cleavage site of collagen type I

Collagens contain sequence- and conformation-dependent epitopes responsible for their digestion by collagenases at specific loci. A synthetic heterotrimer construct containing the collagenase cleavage site of collagen type I was found to mimic perfectly native collagen in terms of selectivity and mode of enzymatic degradation. The NMR conformational analysis of this molecule clearly revealed the presence of two structural domains, i.e. a triple helix spanning the Gly-Pro-Hyp repeats and a less ordered portion corresponding to the collagenase cleavage site where the three chains are aligned in extended conformation with loose interchain contacts. These structural properties allow for additional insights into the very particular mechanism of collagen digestion by collagenases.     

Seroprevalence of antibodies to Neospora caninum in dogs from Spain

The prevalence of Neospora caninum antibodies was determined in sera of 139 dogs from Catalonia (northeastern Spain) using the indirect immunofluorescence antibody test (IFAT). Antibodies in the IFAT were found in 17 of 139 dogs (12.2%) with titers ranging from 1:50 to 1: 1,600. Seroprevalence was higher in dogs over 1 yr old compared with dogs younger than 1 yr (P < 0.05). No statistical difference was observed when sex, breed, purpose, or modus vivendi was compared with seropositivity. Most dogs had low antibody titers, which indicated subclinical infection in the area studied. No neosporosis-related disease was reported from any dog, although a German shepherd with an antibody titer of 1:800 showed pododermatitis. All sera were also screened using a commercial direct agglutination test (DAT). The DAT showed a similar specificity but a lower sensitivity when compared with IFAT as a reference technique.