Early and transient reverse transcription during primary deltaretroviral infection of sheep

<p>Abstract</p> <p>Background</p> <p>Intraindividual genetic variability plays a central role in deltaretrovirus replication and associated leukemogenesis in animals as in humans. To date, the replication of these viruses has only been investigated during the chronic phase of the infection when they mainly spread through the clonal expansion of their host cells, vary through a somatic mutation process without evidence for reverse transcriptase (RT)-associated substitution. Primary infection of a new organism necessary involves allogenic cell infection and thus reverse transcription.</p> <p>Results</p> <p>Here we demonstrate that the primary experimental bovine leukemia virus (BLV) infection of sheep displays an early and intense burst of horizontal replicative dissemination of the virus generating frequent RT-associated substitutions that account for 69% of the in vivo BLV genetic variability during the first 8 months of the infection. During this period, evidence has been found of a cell-to-cell passage of a mutated sequence and of a sequence having undergone both RT-associated and somatic mutations. The detection of RT-dependent proviral substitution was restricted to a narrow window encompassing the first 250 days following seroconversion.</p> <p>Conclusion</p> <p>In contrast to lentiviruses, deltaretroviruses display two time-dependent mechanisms of genetic variation that parallel their two-step nature of replication <it>in vivo</it>. We propose that the early and transient RT-based horizontal replication helps the virus escape the first wave of host immune response whereas somatic-dependent genetic variability during persistent clonal expansion helps infected clones escape the persistent and intense immune pressure that characterizes the chronic phase of deltaretrovirus infection.</p

A dose-effect relationship for deltaretrovirus-dependent leukemogenesis in sheep

<p>Abstract</p> <p>Background</p> <p>Retrovirus-induced tumors develop in a broad range of frequencies and after extremely variable periods of time, from only a few days to several decades, depending mainly on virus type. For hitherto unexplained reasons, deltaretroviruses cause hematological malignancies only in a minority of naturally infected organisms and after a very prolonged period of clinical latency.</p> <p>Results</p> <p>Here we demonstrate that the development of malignancies in sheep experimentally infected with the deltaretrovirus bovine leukemia virus (BLV) depends only on the level of BLV replication. Animals were experimentally infected with leukemogenic or attenuated, but infectious, BLV molecular clones and monitored prospectively through 8 months for viral replication. As early as 2 weeks after infection and subsequently at any time during follow-up, leukemogenic viruses produced significantly higher absolute levels of reverse transcription (RT), clonal expansion of infected cells, and circulating proviruses with RT- and somatic-dependent mutations than attenuated viruses. These differences were only quantitative, and both kinds of viruses triggered parallel temporal fluctuations of host lymphoid cells, viral loads, infected cell clonality and proliferation.</p> <p>Conclusion</p> <p>Deltaretrovirus-associated leukemogenesis in sheep appears to be a two-hit process over time depending on the amounts of first horizontally and then vertically expanded viruses.</p

Invited Lecture 'SAXS studies of mesoporous materials'

status: publishe

Effect of ankle-foot orthoses on gait in typically developing children: Developmental trend in segmental coordination

Objective: As orthoses, and particularly ankle-foot orthoses, are widely used in the management of children with motor disorders, including cerebral palsy, we aimed to study their effect in normal children in order to add to normative gait data, which are essential for diagnosing, understanding and treating abnormal gait patterns. Design: We analyzed the effect of ankle-foot orthoses on classical gait parameters and lower limb segments coordination patterns in typically developing children in two age groups reflecting different neuromaturational/developmental situations. We recorded 3D kinematic gait patterns in 9 children (4-5 years) and 11 children (9-10 years) walking barefoot or wearing bilateral solid ankle-foot orthoses maintaining the ankle joint angle at a neutral position. Results: Ankle-foot orthoses induced little change in cadence, step length, step width or walking velocity in younger children, though they altered intralimb coordination through the gait cycle. In older children, walking velocity was reduced, shank elevation amplitude increased, while lower limb coordination changed less significantly. In this age group, ankle-foot orthoses significantly reduced the variability of coordinative strategies. Conclusion: Ankle-foot orthoses affect the gait pattern in children with a typical development at different levels in younger and older subjects, but the resulting changes are minimal. © 2010 IOS Press and the authors. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Decreased basal and stimulated thyrotropin secretion in healthy elderly men

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Self-Assembly of Pluronic F127-Silica Spherical Core-Shell Nanoparticles in Cubic Close-Packed Structures

A new ordered mesoporous silica material (COK-19) with cubic symmetry is synthesized by silicate polycondensation in a citric acid/citrate buffered micellar solution of Pluronic F127 triblock copolymer near neutral pH. SAXS, nitrogen adsorption, TEM and electron tomography reveal the final material has a cubic close packed symmetry (Fm-3m) with isolated spherical mesopores interconnected through micropores. Heating of the synthesis medium from room temperature to 70 °C results in a mesopore size increase from 7.0 to 11.2 nm. Stepwise addition of the silicate source allows to isolate a sequence of intermediates that upon characterization with small angle X-ray scattering, uncovers the formation process via formation and aggregation of individual silica-covered Pluronic micelles.status: publishe

Fate of premalignant clones during the asymptomatic phase preceding lymphoid malignancy.

peer reviewedAlmost all cancers are preceded by a prolonged period of clinical latency during which a combination of cellular events helps move carcinogen-exposed cells towards a malignant phenotype. Hitherto, investigating the fate of premalignant cells in vivo remained strongly hampered by the fact that these cells are usually indistinguishable from their normal counterparts. Here, for the first time, we have designed a strategy able to reconstitute the replicative history of the bona fide premalignant clone in an animal model, the sheep experimentally infected with the lymphotropic bovine leukemia virus. We have shown that premalignant clones are early and clearly distinguished from other virus-exposed cells on the basis of their degree of clonal expansion and genetic instability. Detectable as early as 0.5 month after the beginning of virus exposure, premalignant cells displayed a two-step pattern of extensive clonal expansion together with a mutation load approximately 6 times higher than that of other virus-exposed cells that remained untransformed during the life span of investigated animals. There was no fixation of somatic mutations over time, suggesting that they regularly lead to cellular death, partly contributing to maintain a normal lymphocyte count during the prolonged premalignant stage. This equilibrium was finally broken after a period of 18.5 to 60 months of clinical latency, when a dramatic decrease in the genetic instability of premalignant cells coincided with a rapid increase in lymphocyte count and lymphoma onset

Alteration with aging of the circadian prolactin secretory pattern in man

info:eu-repo/semantics/publishe

Deux protocoles d'hyperimmunisation au moyen de vaccins marqués réduisent l'incidence de séroconversion envers l'herpèsvirus bovin 1 en cheptels laitiers: Résultats d'une étude sur le terrain

SCOPUS: ar.jinfo:eu-repo/semantics/publishe