A functional alternative splicing mutation in human tryptophan hydroxylase-2

The brain serotonergic system has an essential role in the physiological functions of the central nervous system and dysregulation of serotonin (5-HT) homeostasis has been implicated in many neuropsychiatric disorders. The tryptophan hydroxylase-2 (TPH2) gene is the rate-limiting enzyme in brain 5-HT synthesis, and thus is an ideal candidate gene for understanding the role of dysregulation of brain serotonergic homeostasis. Here, we characterized a common, but functional single-nucleotide polymorphism (SNP rs1386493) in the TPH2 gene, which decreases efficiency of normal RNA splicing, resulting in a truncated TPH2 protein (TPH2-TR) by alternative splicing. TPH2-TR, which lacks TPH2 enzyme activity, dominant-negatively affects full-length TPH2 function, causing reduced 5-HT production. The predicted mRNA for TPH2-TR is present in postmortem brain of rs1386493 carriers. The rs13864923 variant does not appear to be overrepresented in either global or multiplex depression cohorts. However, in combination with other gene variants linked to 5-HT homeostasis, this variant may exhibit important epistatic influences

Evidence generation and reproducibility in cell and gene therapy research: A call to action

Stem cells & developmental biolog

Monitoring upper limbs during exoskeleton-assisted gait outdoors

Powered exoskeleton can restore locomotion to spinal cord injury subjects but measuring their impact on the upper limbs is critical, since repeated excessive loads are strongly correlated to chronic pain at shoulder level. This paper presents a novel set of instrumented crutches, able to measure force exerted on the ground during walking sessions, thanks to embedded time-of-flight cameras and force sensors. The force sensors, along with an inertial module, assess the force acting on the upper limbs, while the time-of-flight cameras detects the gait phases looking at the feet position. The aim is to provide an affordable measuring system, without requiring a fully instrumented gait-lab, allowing the user-robot interaction to be measured in a more natural setting, closer to the foreseen working condition. The instrumented crutches are fully independent of any other instrumentation to allow a comparison of different exoskeleton models in terms of upper limb involvement