Using molecular mechanics to predict bulk material properties of fibronectin fibers

The structural proteins of the extracellular matrix (ECM) form fibers with finely tuned mechanical properties matched to the time scales of cell traction forces. Several proteins such as fibronectin (Fn) and fibrin undergo molecular conformational changes that extend the proteins and are believed to be a major contributor to the extensibility of bulk fibers. The dynamics of these conformational changes have been thoroughly explored since the advent of single molecule force spectroscopy and molecular dynamics simulations but remarkably, these data have not been rigorously applied to the understanding of the time dependent mechanics of bulk ECM fibers. Using measurements of protein density within fibers, we have examined the influence of dynamic molecular conformational changes and the intermolecular arrangement of Fn within fibers on the bulk mechanical properties of Fn fibers. Fibers were simulated as molecular strands with architectures that promote either equal or disparate molecular loading under conditions of constant extension rate. Measurements of protein concentration within micron scale fibers using deep ultraviolet transmission microscopy allowed the simulations to be scaled appropriately for comparison to in vitro measurements of fiber mechanics as well as providing estimates of fiber porosity and water content, suggesting Fn fibers are approximately 75% solute. Comparing the properties predicted by single molecule measurements to in vitro measurements of Fn fibers showed that domain unfolding is sufficient to predict the high extensibility and nonlinear stiffness of Fn fibers with surprising accuracy, with disparately loaded fibers providing the best fit to experiment. This work shows the promise of this microstructural modeling approach for understanding Fn fiber properties, which is generally applicable to other ECM fibers, and could be further expanded to tissue scale by incorporating these simulated fibers into three dimensional network models

Vocal learning promotes patterned inhibitory connectivity.

Skill learning is instantiated by changes to functional connectivity within premotor circuits, but whether the specificity of learning depends on structured changes to inhibitory circuitry remains unclear. We used slice electrophysiology to measure connectivity changes associated with song learning in the avian analog of primary motor cortex (robust nucleus of the arcopallium, RA) in Bengalese Finches. Before song learning, fast-spiking interneurons (FSIs) densely innervated glutamatergic projection neurons (PNs) with apparently random connectivity. After learning, there was a profound reduction in the overall strength and number of inhibitory connections, but this was accompanied by a more than two-fold enrichment in reciprocal FSI-PN connections. Moreover, in singing birds, we found that pharmacological manipulations of RA's inhibitory circuitry drove large shifts in learned vocal features, such as pitch and amplitude, without grossly disrupting the song. Our results indicate that skill learning establishes nonrandom inhibitory connectivity, and implicates this patterning in encoding specific features of learned movements

Ultrashort Q-switched pulses from a passively mode-locked distributed Bragg reflector semiconductor laser

A compact semiconductor mode-locked laser (MLL) is presented that demonstrates strong passive Q-switched mode-locking over a wide range of drive conditions. The Q-switched frequency is tunable between 1 and 4 GHz for mode-locked pulses widths around 3.5 ps. The maximum ratio of peak to average power of the pulse-train is >120, greatly exceeding that of similarly sized passively MLLs

Theta-Modulated Gamma-Band Synchronization Among Activated Regions During a Verb Generation Task

Expressive language is complex and involves processing within a distributed network of cortical regions. Functional MRI and magnetoencephalography (MEG) have identified brain areas critical for expressive language, but how these regions communicate across the network remains poorly understood. It is thought that synchronization of oscillations between neural populations, particularly at a gamma rate (>30 Hz), underlies functional integration within cortical networks. Modulation of gamma rhythms by theta-band oscillations (4–8 Hz) has been proposed as a mechanism for the integration of local cell coalitions into large-scale networks underlying cognition and perception. The present study tested the hypothesis that these oscillatory mechanisms of functional integration were present within the expressive language network. We recorded MEG while subjects performed a covert verb generation task. We localized activated cortical regions using beamformer analysis, calculated inter-regional phase locking between activated areas, and measured modulation of inter-regional gamma synchronization by theta phase. The results show task-dependent gamma-band synchronization among regions activated during the performance of the verb generation task, and we provide evidence that these transient and periodic instances of high-frequency connectivity were modulated by the phase of cortical theta oscillations. These findings suggest that oscillatory synchronization and cross-frequency interactions are mechanisms for functional integration among distributed brain areas supporting expressive language processing

Structure of a liquid crystalline fluid around a macroparticle: Density functional theory study

The structure of a molecular liquid, in both the nematic liquid crystalline and isotropic phases, around a cylindrical macroparticle, is studied using density functional theory. In the nematic phase the structure of the fluid is highly anisotropic with respect to the director, in agreement with results from simulation and phenomenological theories. On going into the isotropic phase the structure becomes rotationally invariant around the macroparticle with an oriented layer at the surface.Comment: 10 pages, 6 figues. Submitted to Phys. Rev.

Correction to: Position statement: minimum archiving requirements for emergency medicine point‑of‑care ultrasound—a modified Delphi‑derived national consensus (Canadian Journal of Emergency Medicine, (2021), 23, 4, (450-454), 10.1007/s43678-021-00109-8)

A correction to this paper has been published: https://doi.org/10.1007/s43678-021-00117-8