Collagen VI Regulates Motor Circuit Plasticity and Motor Performance by Cannabinoid Modulation.

Collagen VI is a key component of muscle basement membranes, and genetic variants can cause monogenic muscular dystrophies. Conversely, human genetic studies recently implicated collagen VI in central nervous system function, with variants causing the movement disorder dystonia. To elucidate the neurophysiological role of collagen VI, we generated mice with a truncation of the dystonia-related collagen α3 VI (COL6A3) C-terminal domain (CTD). These Col6a3CTT mice showed a recessive dystonia-like phenotype in both sexes. We found that COL6A3 interacts with the cannabinoid receptor 1 (CB1R) complex in a CTD-dependent manner. Col6a3CTT mice of both sexes have impaired homeostasis of excitatory input to the basal pontine nuclei (BPN), a motor control hub with dense COL6A3 expression, consistent with deficient endocannabinoid (eCB) signaling. Aberrant synaptic input in the BPN was normalized by a CB1R agonist, and motor performance in Col6a3CTT mice of both sexes was improved by CB1R agonist treatment. Our findings identify a readily therapeutically addressable synaptic mechanism for motor control.SIGNIFICANCE STATEMENT Dystonia is a movement disorder characterized by involuntary movements. We previously identified genetic variants affecting a specific domain of the COL6A3 protein as a cause of dystonia. Here, we created mice lacking the affected domain and observed an analogous movement disorder. Using a protein interaction screen, we found that the affected COL6A3 domain mediates an interaction with the cannabinoid receptor 1 (CB1R). Concordantly, our COL6A3-deficient mice showed a deficit in synaptic plasticity linked to a deficit in cannabinoid signaling. Pharmacological cannabinoid augmentation rescued the motor impairment of the mice. Thus, cannabinoid augmentation could be a promising avenue for treating dystonia, and we have identified a possible molecular mechanism mediating this.

Determining the composition and microstructure of ethylene-propylene copolymers by pyrolysis-gas chromatography.

The average composition and detailed microstructure of copolymers of ethylene and propylene have been studied by pyrolysis-gas chromatography (Py-GC), using a statistical modeling approach to analyze the data. The trimer distribution obtained from Py-GC is used to infer monomer arrangement information, which is quantified in terms of a number-average sequence length for each monomer. These values are used to define the microstructure and to calculate the average composition. Compared with other available techniques, Py-GC provides a simple, quick and reliable approach to study the microstructure and composition of polyolefin copolymers. Details of this Py-GC method are discussed, including an examination of its advantages and disadvantages, and a summary of the qualitative and quantitative analysis aspects of this approach is presented. The combination of a statistical modeling approach with Py-GC to study copolymer composition and microstructure allows one to investigate the complex problem of monomer arrangement in copolymers using a widely available analytical technique. We expect that with further advances in separation technology, especially two-dimensional gas chromatography (GC x GC), research of this type will be become increasingly accurate and reproducible in the near future.

Relative strengths of competition for space and food in a sessile filter feeder.

Previous workers have demonstrated that sessile filter feeders compete for food and space, but little is known about the relative strengths of these two processes. To determine this, the density and position of barnacles (Balanus improvisus) in a unidirectional current were manipulated to alter the amount of competition for space and food, respectively. Results indicated that competition for space significantly reduced growth, and marginally reduced survivorship. Competition for food was also detected, but only among uncrowded individuals; thus, it appears to be the weaker of the two interactions. However, under crowded conditions, downstream individuals actually grew more than those upstream. The most likely explanation for this result is that downstream individuals fed more efficiently because they were not exposed to the full force of the current. The results also suggest that since natural densities started high but continually decreased throughout the study, barnacles undergo an ontogenetic shift in the relative importance of these processes.