The human hand has so many degrees of freedom that it may seem impossible to control. A potential solution to this problem is “synergy control” which combines dimensionality reduction with great flexibility. With applicability to a wide range of tasks, this has become a very popular concept. In this review, we describe the evolution of the modern concept using studies of kinematic and force synergies in human hand control, neurophysiology of cortical and spinal neurons, and electromyographic (EMG) activity of hand muscles. We go beyond the often purely descriptive usage of synergy by reviewing the organization of the underlying neuronal circuitry in order to propose mechanistic explanations for various observed synergy phenomena. Finally, we propose a theoretical framework to reconcile important and still debated concepts such as the definitions of “fixed” vs. “flexible” synergies and mechanisms underlying the combination of synergies for hand control.

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m²) and lean (BMI, 22±1 kg/m²) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h^-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = – 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish impaired β-F1-ATPase translation as an important consequence of obesity.

Pure coconut oil, lanolin, and acetaminophen were vaporized at rates of 1–50 mg/min, using a porous network exhibiting a temperature gradient from 5000 to 5500 K/mm, without incurring noticeable chemical changes due to combustion, oxidation, or other thermally-induced chemical structural changes. The newly coined term “ereptiospiration” is used here to describe this combination of thermal transpiration at high temperature gradients since the process can force the creation of thermal aerosols by rapid heating in a localized zone. Experimental data were generated for these materials using two different supports for metering the materials to the battery powered coil: namely, a stainless steel fiber bundle and a 3-D printed steel cartridge. Heating coconut oil, lanolin, or acetaminophen in a beaker to lower temperatures than those achieved at the surface of the coil showed noticeable and rapid degradation in the samples, while visual and olfactory observations for ereptiospiration showed no noticeable degradation in lanolin and coconut oil while HPLC chromatograms along with visual observation confirm that within the limit of detection, acetaminophen remains chemically unaltered by ereptiospiration.