Effectiveness of individualized training based on force–velocity profiling on physical function in older men

The study aimed to investigate the effectiveness of an individualized power training program based on force–velocity (FV) profiling on physical function, muscle morphology, and neuromuscular adaptations in older men. Forty-nine healthy men (68 ± 5 years) completed a 10-week training period to enhance muscular power. They were randomized to either a generic power training group (GPT) or an individualized power training group (IPT). Unlike generic training, individualized training was based on low- or high-resistance exercises, from an initial force–velocity profile. Lower-limb FV profile was measured in a pneumatic leg-press, and physical function was assessed as timed up-and-go time (TUG), sit-to-stand power, grip strength, and stair-climbing time (loaded [20kg] and unloaded). Vastus lateralis morphology was measured with ultrasonography. Rate of force development (RFD) and rate of myoelectric activity (RMA) were measured during an isometric knee extension. The GPT group improved loaded stair-climbing time (6.3 ± 3.8 vs. 2.3% ± 7.3%, p = 0.04) more than IPT. Both groups improved stair-climbing time, sit to stand, and leg press power, grip strength, muscle thickness, pennation angle, fascicle length, and RMA from baseline (p < 0.05). Only GPT increased loaded stair-climbing time and RFD (p < 0.05). An individualized power training program based on FV profiling did not improve physical function to a greater degree than generic power training. A generic power training approach combining both heavy and low loads might be advantageous through eliciting both force- and velocity-related neuromuscular adaptions with a concomitant increase in muscular power and physical function in older men.publishedVersio

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway