Simulating Epstein-Barr virus infection with C-ImmSim

MOTIVATION: Epstein-Barr virus (EBV) infects greater than 90% of humans benignly for life but can be associated with tumors. It is a uniquely human pathogen that is amenable to quantitative analysis; however, there is no applicable animal model. Computer models may provide a virtual environment to perform experiments not possible in human volunteers. RESULTS: We report the application of a relatively simple stochastic cellular automaton (C-ImmSim) to the modeling of EBV infection. Infected B-cell dynamics in the acute and chronic phases of infection correspond well to clinical data including the establishment of a long term persistent infection (up to 10 years) that is absolutely dependent on access of latently infected B cells to the peripheral pool where they are not subject to immunosurveillance. In the absence of this compartment the infection is cleared. AVAILABILITY: The latest version 6 of C-ImmSim is available under the GNU General Public License and is downloadable from www.iac.cnr.it/~filippo/cimmsim.html     

Infections requiring hospitalization in the abatacept clinical development program: an epidemiological assessment

Introduction  

Patients with rheumatoid arthritis (RA) have an increased risk of infection and this risk appears to be higher with anti-TNF (tumor necrosis factor) agents. We pooled data from the cumulative abatacept RA clinical development program, both double-blind and open-label periods, to estimate the incidence rates (IRs) of infections requiring hospitalization including pneumonia and opportunistic infections, in comparison with RA patients treated with non-biologic disease-modifying antirheumatic drugs (DMARDs) from several reference cohorts.     

Acanthodasys caribbeanensis sp. n., a new species of Thaumastodermatidae (Gastrotricha, Macrodasyida) from Belize and Panama

We describe one new species of Acanthodasys (Gastrotricha, Macrodasyida, Thaumastodermatidae) collected from sublittoral sites around Carrie Bow Cay, Belize and Isla Colón in the Bocas del Toro archipelago, Panama. Though eight species of Acanthodasys are currently recognized, no species has yet been reported from the Caribbean. Acanthodasys caribbeanensissp. n. is characterized by the lack of lateral adhesive tubes, the presence of ventrolateral adhesive tubes, and with cuticular armature in the form of both spineless and spined scales. The spineless scales are not elliptical as in other species of Acanthodasys, but are instead variable in shape and closely resemble the spineless scales of species of Diplodasys. Spined scales bear uniancres up to 50 μm long and are the largest reported in the genus. Uniancres are arranged dorsally around the mouth rim and distributed in five distinguishable columns. Adult size varies from 325-625 μm long.     

Fine structure of the retrocerebral organ in the rotifer Trichocerca similis (Monogononta)

The retrocerebral organ (RCO) is a complex glandular system that is widely distributed across species of phylum Rotifera (sensu stricto). This system is hypothesized to secrete mucus that aids in benthic locomotion, adhesion, and/or reproduction. Unfortunately, the ultrastructure of the RCO is mostly unknown, having only been partially examined in one species. We used transmission electron microscopy and confocal laser scanning microscopy to describe the RCO in the planktonic freshwater rotifer Trichocerca similis. Results reveal the RCO to be a singular syncytial organ composed of a posterior glandular region, an expansive reservoir, and an anterior duct. The glandular portion has an active synthetic cytoplasm with paired nuclei, abundant rER, ribosomes, Golgi, and mitochondria. Electron-dense secretion granules accumulate at the anterior end of the gland and undergo homotypic fusion to create larger, more electron-lucent granules with numerous mesh-like contents that gradually fuse into tubular secretions that accumulate in the reservoir. Ultrastructure of these secretions suggests they may be hydrated glycoproteins. Cross-striated longitudinal muscles form a partial sleeve around the reservoir and may function to squeeze the secretions through the single cytoplasmic duct that penetrates the cerebral ganglion. A review of the RCOs from other rotifers suggests that further ultrastructural analyses are required before attempting to discern their functions and homologies.     

Androgen therapy in constitutional delay of growth

BACKGROUND/AIMS: Two modalities of androgen therapy prevail in the treatment of constitutional delay of growth (CDG): monthly injections of testosterone or daily tablets of the non-aromatizable oxandrolone. The present study was undertaken to prospectively compare both compounds and dose. METHODS: Thirty patients with CDG were the subjects of this study. The protocol required that they all be at age 12-14 years with a bone age delay of more than 2 'years', height less than -2 SDS and growth velocity less than -0.5 SDS. The subjects were at a Tanner stage 1 or 2 and testicular volume were no larger than 4 ml. They were randomly assigned into 3 treatment groups: group 1 patients received monthly injections of 25 mg testosterone propionate-enanthate; group 2 patients received monthly injections of 50 mg testosterone propionate-enanthate; group 3 patients received oral oxandrolone at a weekly dose of 0.7 mg/kg. Treatment was given for a period of 6 months and follow-up commenced 6 months later and yearly thereafter for 2 years. RESULTS: Height velocity and height increased significantly only in groups 2 and 3. Bone age advanced most in group 2. Puberty progressed faster in that group as compared with group 3. The predicted adult height before and 2 years after completion of treatment remained unchanged in the two testosterone groups. It increased significantly in the oxandrolone group from a mean 169.8 cm before therapy to a mean 177.5 cm 2 years after completion of therapy. Peak GH levels were significantly higher on both testosterone 50 mg and oxandrolone, as compared to pretreatment levels. The increment was significantly greater in group 2 as was the increment in serum IGF-1 and IGFBP3. CONCLUSIONS: These results imply that 6 months of testosterone injections at a dose of 50 mg, but not 25 mg, is an effective and safe treatment for patients with CDG, with no considerable impact on final height prediction. On the other hand, daily oxandrolone treatment, starting at age 12-14 years, may increase the predicted final adult height.     

Modelling the spatial configuration of refuges for a sustainable control of pests: a case study of Bt cotton

The 'high-dose-refuge' (HDR) strategy is widely recommended by the biotechnology industry and regulatory authorities to delay pest adaptation to transgenic crops that produce Bacillus thuringiensis (Bt) toxins. This involves cultivating nontoxic plants (refuges) in close proximity to crops producing a high dose of Bt toxin. The principal cost associated with this strategy is due to yield losses suffered by farmers growing unprotected, refuge plants. Using a population genetic model of selection in a spatially heterogeneous environment, we show the existence of an optimal spatial configuration of refuges that could prevent the evolution of resistance whilst reducing the use of costly refuges. In particular, the sustainable control of pests is achievable with the use of more aggregated distributions of nontransgenic plants and transgenic plants producing lower doses of toxin. The HDR strategy is thus suboptimal within the context of sustainable agricultural development.     

ESTABLISHING GENETIC CORRELATIONS INVOLVING PARASITE VIRULENCE

For many host-parasite interactions, virulence is necessarily affected by population densities, transmission biology of the parasite, and proliferation of the parasite at the expense of its host. Attempts to experimentally demonstrate genetic correlations involving virulence therefore need to employ protocols controlling for variation in the number of successful infections (i.e., the end-point of transmissibility). If protocols are not controlled, then correlations may be spurious, as appears to be the case in recent experimental studies by Ebert (1994) and Ebert and Magnin (1997). There is a need to explore the modes of the evolution of each of the many sequential steps in nonsymbiotic and symbiotic phases of host-parasite associations and the implication of such evolution for overall virulence. I argue that it is the interdependence of these sequential steps (and not overall virulence) that should be at the center of attempts to establish genetic correlations.