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Motor skill learning relies on the plasticity of the primary motor cortex as task acquisition drives cortical motor network remodeling. Large-scale cortical remodeling of evoked motor outputs occurs during the learning of corticospinal-dependent prehension behavior, but not simple, non-dexterous tasks. Here we determine the response of corticospinal neurons to two distinct motor training paradigms and assess the role of corticospinal neurons in the execution of a task requiring precise modulation of forelimb movement and one that does not. In vivo calcium imaging in mice revealed temporal coding of corticospinal activity coincident with the development of precise prehension movements, but not more simplistic movement patterns. Transection of the corticospinal tract and optogenetic regulation of corticospinal activity show the necessity for patterned corticospinal network activity in the execution of precise movements but not simplistic ones. Our findings reveal a critical role for corticospinal network modulation in the learning and execution of precise motor movements., (© 2023. The Author(s).)

Neural injury in mammals often leads to persistent functional deficits as spontaneous repair in the peripheral nervous system (PNS) is often incomplete, while endogenous repair mechanisms in the central nervous system (CNS) are negligible. Peripheral axotomy elicits growth-associated gene programs in sensory and motor neurons that can support reinnervation of peripheral targets given sufficient levels of debris clearance and proximity to nerve targets. In contrast, while damaged CNS circuitry can undergo a limited amount of sprouting and reorganization, this innate plasticity does not re-establish the original connectivity. The utility of novel CNS circuitry will depend on effective connectivity and appropriate training to strengthen these circuits. One method of enhancing novel circuit connectivity is through the use of electrical stimulation, which supports axon growth in both central and peripheral neurons. This review will focus on the effects of CNS and PNS electrical stimulation in activating axon growth-associated gene programs and supporting the recovery of motor and sensory circuits. Electrical stimulation-mediated neuroplasticity represents a therapeutically viable approach to support neural repair and recovery. Development of appropriate clinical strategies employing electrical stimulation will depend upon determining the underlying mechanisms of activity-dependent axon regeneration and the heterogeneity of neuronal subtype responses to stimulation., (Copyright © 2020 Jara, Agger and Hollis II.)

Objective: To investigate if attention to additional sensory information from the fingertip can improve postural stability during pain, which is known to impair balance., Methods: In 16 healthy volunteers, experimental pain was induced by intramuscular injection of hypertonic saline in the right vastus medialis muscle (isotonic saline used as nonpainful control, intramuscular injection in the same location). Pain intensity was assessed on an 11-point numeric rating scale (NRS; 0 representing "no pain" and 10 "maximum pain"). Subjects were asked to stand as still as possible on a force plate for 40 seconds with their eyes closed. Their postural stability was quantified by the area and velocity of center of pressure (CoP) displacement. The CoP was recorded with and without pain during two different conditions: 1) no touch and 2) the subjects were asked to lightly touch a curtain with their right index finger and focus their attention on keeping it as still as possible., Results: Hypertonic injections induced higher NRS scores compared with control injections (P < 0.05). During the hypertonic injection condition, the CoP area and velocity in both directions increased during no touch compared with the light touch condition (P < 0.05). No differences were found during light touch between the hypertonic and isotonic injection conditions. Although experimental knee-related pain impaired postural stability, lightly touching a curtain with the fingertip decreased postural sway during painful conditions., Conclusions: Providing additional sensory information while pain patients are performing balance exercises may improve postural stability and increase the quality of exercise, consequent rehabilitation protocols, and clinical outcomes.

Fungi are a rich source of bioactive secondary metabolites, and mushroom-forming fungi (Agaricomycetes) are especially known for the synthesis of numerous bioactive and often cytotoxic sesquiterpenoid secondary metabolites. Compared with the large number of sesquiterpene synthases identified in plants, less than a handful of unique sesquiterpene synthases have been described from fungi. Here we describe the functional characterization of six sesquiterpene synthases (Cop1 to Cop6) and two terpene-oxidizing cytochrome P450 monooxygenases (Cox1 and Cox2) from Coprinus cinereus. The genes were cloned and, except for cop5, functionally expressed in Escherichia coli and/or Saccharomyces cerevisiae. Cop1 and Cop2 each synthesize germacrene A as the major product. Cop3 was identified as an alpha-muurolene synthase, an enzyme that has not been described previously, while Cop4 synthesizes delta-cadinene as its major product. Cop6 was originally annotated as a trichodiene synthase homologue but instead was found to catalyse the highly specific synthesis of alpha-cuprenene. Coexpression of cop6 and the two monooxygenase genes next to it yields oxygenated alpha-cuprenene derivatives, including cuparophenol, suggesting that these genes encode the enzymes for the biosynthesis of antimicrobial quinone sesquiterpenoids (known as lagopodins) that were previously isolated from C. cinereus and other Coprinus species.

Proteus species are second only to Escherichia coli as the most common causative agent of Gram-negative bacteria-based urinary-tract infections and many harbor several virulence factors that provide inherent uropathogenicity. One virulence factor stems from a two-partner secretion pathway comprised of hemolysin A and hemolysin B; upon hemolysin B-dependent secretion, hemolysin A becomes activated. This system is distinct from the classic type I secretion pathway exemplified by the hemolysin system within Escherichia coli. In order to describe the mechanism by which hemolysin A is activated for pore formation, an amino-terminal truncated form capable of complementing the non-secreted full-length hemolysin A and thereby restoring hemolytic activity has been constructed, expressed and purified. A room-temperature data set has been collected to 2.5 A resolution. The crystal belongs to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 34.47, b = 58.40, c = 119.74 A. The asymmetric unit is expected to contain a single monomer, which equates to a Matthews coefficient of 1.72 A3 Da(-1) and a solvent content of 28.3%.

We have successfully demonstrated a single-frequency distributed-feedback (DFB) thulium-doped silica fiber laser emitting at a wavelength of 1735 nm. The laser cavity is less than 5 cm long and is formed by intracore UV-written Bragg gratings with a phase shift. The laser is pumped at 790 nm from a Ti:sapphire laser and has a threshold pump power of 59 mW. The laser has a maximum output power of 1 mW in a single-frequency, single-polarization radiation mode and is tunable over a few nanometers. To the best of the authors' knowledge, this is the first report of a single-frequency DFB fiber laser that uses thulium as the amplifying medium. The lasing wavelength is the longest demonstrated with DFB fiber lasers and yet is among the shortest obtained for thulium-doped silica fiber lasers.