Prospective cohort study of Torque Teno Virus (TTV) viral load kinetics and the association with graft rejection in renal transplant patients.

INTRODUCTION: Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. MATERIALS AND METHODS: Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. RESULTS: Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881-0.9149, p < 0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p < 0.0001). Between (181-270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log10 copies/mL (by Home-Brew PCR) and 3.10 Log10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log10 copies/mL, respectively). CONCLUSIONS: Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period.

Genetic and activity dependent-mechanisms wiring the cortex: Two sides of the same coin.

The cerebral cortex is responsible for the higher-order functions of the brain such as planning, cognition, or social behaviour. It provides us with the capacity to interact with and transform our world. The substrates of cortical functions are complex neural circuits that arise during development from the dynamic remodelling and progressive specialization of immature undefined networks. Here, we review the genetic and activity-dependent mechanisms of cortical wiring focussing on the importance of their interaction. Cortical circuits emerge from an initial set of neuronal types that engage in sequential forms of embryonic and postnatal activity. Such activities further complement the cells' genetic programs, increasing neuronal diversity and modifying the electrical properties while promoting selective connectivity. After a temporal window of enhanced plasticity, the main features of mature circuits are established. Failures in these processes can lead to neurodevelopmental disorders whose treatment remains elusive. However, a deeper dissection of cortical wiring will pave the way for innovative therapies.

Transient callosal projections of L4 neurons are eliminated for the acquisition of local connectivity.

Interhemispheric axons of the corpus callosum (CC) facilitate the higher order functions of the cerebral cortex. According to current views, callosal and non-callosal fates are determined early after a neuron's birth, and certain populations, such as cortical layer (L) 4 excitatory neurons of the primary somatosensory (S1) barrel, project only ipsilaterally. Using a novel axonal-retrotracing strategy and GFP-targeted visualization of Rorb+ neurons, we instead demonstrate that L4 neurons develop transient interhemispheric axons. Locally restricted L4 connectivity emerges when exuberant contralateral axons are refined in an area- and layer-specific manner during postnatal development. Surgical and genetic interventions of sensory circuits demonstrate that refinement rates depend on distinct inputs from sensory-specific thalamic nuclei. Reductions in input-dependent refinement result in mature functional interhemispheric hyperconnectivity, demonstrating the plasticity and bona fide callosal potential of L4 neurons. Thus, L4 neurons discard alternative interhemispheric circuits as instructed by thalamic input. This may ensure optimal wiring.