The thalamus is the hub through which neural signals are transmitted from the basal ganglia and cerebellum to the neocortex. However, thalamocortical axonal activity during motor learning remains ...largely undescribed. We conducted two-photon calcium imaging of thalamocortical axonal activity in the motor cortex of mice learning a self-initiated lever-pull task. Layer 1 (L1) axons came to exhibit activity at lever-pull initiation and termination, while layer 3 (L3) axons did so at lever-pull initiation. L1 population activity had a sequence structure related to both lever-pull duration and reproducibility. Stimulation of the substantia nigra pars reticulata activated more L1 than L3 axons, whereas deep cerebellar nuclei (DCN) stimulation did the opposite. Lesions to either the dorsal striatum or the DCN impaired motor learning and disrupted temporal dynamics in both layers. Thus, layer-specific thalamocortical signals evolve with the progression of learning, which requires both the basal ganglia and cerebellar activities.
•Thalamocortical (TC) axon activity reflects motor representations during learning•TC axon activation induces movement and their inactivation impairs motor learning•TC axons in layers 1 and 3 diverge to show distinct movement-locked activities•Evolving TC axon activity in each layer requires the basal ganglia and cerebellum
Tanaka et al. show that patterns of layer-specific thalamocortical axon activity involving signals from the basal ganglia and cerebellum evolve during learning of a self-initiated motor task. The progression of this activity is impaired by lesions to either region.
Synaptic plasticity is the cellular basis of learning and memory. When animals learn a novel motor skill, synaptic modifications are induced in the primary motor cortex (M1), and new postsynaptic ...dendritic spines relevant to motor memory are formed in the early stage of learning. However, it is poorly understood how presynaptic axonal boutons are formed, eliminated, and maintained during motor learning, and whether long-range corticocortical and thalamocortical axonal boutons show distinct structural changes during learning. In this study, we conducted two-photon imaging of presynaptic boutons of long-range axons in layer 1 (L1) of the mouse M1 during the 7-day learning of an accelerating rotarod task. The training-period-averaged rate of formation of boutons on axons projecting from the secondary motor cortical area increased, while the average rate of elimination of those from the motor thalamus (thalamic boutons) decreased. In particular, the elimination rate of thalamic boutons during days 4-7 was lower than that in untrained mice, and the fraction of pre-existing thalamic boutons that survived until day 7 was higher than that in untrained mice. Our results suggest that the late stabilization of thalamic boutons in M1 contributes to motor skill learning.
The primary motor cortex (M1) possesses two intermediate layers upstream of the motor-output layer: layer 2/3 (L2/3) and layer 5a (L5a). Although repetitive training often improves motor performance ...and movement coding by M1 neuronal ensembles, it is unclear how neuronal activities in L2/3 and L5a are reorganized during motor task learning. We conducted two-photon calcium imaging in mouse M1 during 14 training sessions of a self-initiated lever-pull task. In L2/3, the accuracy of neuronal ensemble prediction of lever trajectory remained unchanged globally, with a subset of individual neurons retaining high prediction accuracy throughout the training period. However, in L5a, the ensemble prediction accuracy steadily improved, and one-third of neurons, including subcortical projection neurons, evolved to contribute substantially to ensemble prediction in the late stage of learning. The L2/3 network may represent coordination of signals from other areas throughout learning, whereas L5a may participate in the evolving network representing well-learned movements.
Siderophores are low molecular weight organic compounds produced by various microorganisms, especially pathogenic bacteria including rhizobacteria, and have a high affinity for iron. Although most ...microorganisms are thought to secrete siderophores under iron-depleted conditions, it is unclear how many microorganisms produce siderophores in the natural environment. Also, the chrome azurol sulfonate (CAS) assay, which is widely used for the detection of siderophores, needs to be improved for wider applicability. We developed a simple, high-throughput CAS assay in a 96-well microplate with a concentrated CAS reagent and commonly used diluted growth media in the absence of artificial iron depletion. The improved microplate CAS shuttle assay revealed that it could easily detect siderophores released from Pseudomonas (P.) fluorescence, P. putida, Burlkholderia stabilis, and Ottowia oryzae, as models of siderophore-producing bacteria. This CAS shuttle assay employed along with diluted growth media is a promising tool to screen new siderophore-producing bacteria.
•Diluted growth media without iron-depleting treatment induce siderophore production of microbe.•Developed a simple, high-throughput CAS assay in a 96-well microplate with a CAS reagent and used diluted growth media•Confirmed that diluted growth media in the absence of artificial iron depletion induce siderophore production of microbe•We demonstrated that the diluted media can be applied to measure low concentrations of fluorescent siderophores.•Fluorescent siderophores were observed in new specie by our assay.
Tetrapyrroles are well-known photosensitizers. In plants, various intermediate molecules of tetrapyrrole metabolism have been reported to induce cell death in a light-dependent manner. In contrast to ...these reports, we found that pheophorbide a, a key intermediate of chlorophyll catabolism, causes cell death in complete darkness in a transgenic Arabidopsis plant, As-ACD1. In this plant, expression of mRNA for pheophorbide a oxygenase was suppressed by expression of Acd1 antisense RNA; thus, As-ACD1 accumulated an excessive amount of pheophorbide a when chlorophyll breakdown occurred. We observed that when senescence was induced by a continuous dark period, leaves of As-ACD1 plants became dehydrated. By measuring electrolyte leakage, we estimated that >50% of the leaf cells underwent cell death within a 5 d period of darkness. Light and electron microscopic observations indicated that the cellular structure had collapsed in a large population of cells. Partially covering a leaf with aluminum foil resulted in light-independent cell death in the covered region and induced bleaching in the uncovered regions. These results indicate that accumulation of pheophorbide a induces cell death under both darkness and illumination, but the mechanisms of cell death under these conditions may differ. We discuss the possible mechanism of light-independent cell death and the involvement of pheophorbide a in the signaling pathway for programmed cell death.
A prototype MgB 2 bulk with a diameter of 20 mm and a thickness of 2 mm was synthesized using the MVT (Magnesium Vapor Transport) method, which can realize dense and high-purity MgB 2 bulks by ...transporting and diffusing pure magnesium vapor into boron pellets. Owing to its superior J c - B characteristic, the obtained bulk by the MVT method exhibited, compared to similar bulks synthesized by the conventional in-situ method, a comparable trapped magnetic field at only one-tenth the thickness. Using the measured J c ( B ) data, the influence of the geometry and the size of the bulk synthesized by the MVT method on the trapped magnetic field was investigated by numerical simulation. The simulation results suggest that a bulk fabricated by the MVT method can efficiently achieve a large trapped magnetic field with a thinner thickness for a fixed diameter than a bulk fabricated by the in-situ method.
Summary
Background
Biomarkers of atopic dermatitis (AD) are largely lacking, especially in infant AD. Those that have been examined to date have focused mostly on serum cytokines, with few on ...noninvasive biomarkers in the skin.
Objectives
We aimed to explore biomarkers obtainable from noninvasive sampling of infant skin. We compared these with plasma biomarkers and structural and functional measures of the skin barrier.
Methods
We recruited 100 infants at first presentation with AD, who were treatment naive to topical or systemic anti‐inflammatory therapies, and 20 healthy children. We sampled clinically unaffected skin by tape stripping the stratum corneum (SC). Multiple cytokines and chemokines and natural moisturizing factor were measured in the SC and plasma. We recorded disease severity and skin barrier function.
Results
Nineteen SC and 12 plasma biomarkers showed significant differences between healthy and AD skin. Some biomarkers were common to both the SC and plasma, and others were compartment specific. Identified biomarkers of AD severity included T helper 2‐skewed markers interleukin (IL)‐13, CCL17, CCL22, IL‐5; markers of innate activation (IL‐18, IL‐1α, IL1β, CXCL8) and angiogenesis (Flt‐1, vascular endothelial growth factor); and others (soluble intercellular adhesion molecule‐1, soluble vascular cell adhesion molecule‐1, IL‐16, IL‐17A).
Conclusions
We identified clinically relevant biomarkers of AD, including novel markers, easily sampled and typed in infants. These markers may provide objective assessment of disease severity and suggest new therapeutic targets, or response measurement targets for AD. Future studies will be required to determine whether these biomarkers, seen in very early AD, can predict disease outcomes or comorbidities.
What's already known about this topic?
Atopic dermatitis is a clinically heterogeneous condition with multiple clinical manifestations and a complex pathogenesis.
Systemic biomarkers of severity have been identified in adults, but are less well defined in children.
Biomarkers from the skin compartment have been based on biopsies to date.
What does this study add?
Noninvasive sampling can detect clinically relevant biomarkers in AD skin.
These biomarkers may be useful for disease stratification, and provide insights into the pathogenesis of infant AD.
Innate immune activation is important in the epidermis in infantile AD.
What is the translational message?
Noninvasive biomarkers can yield significant insights into infantile AD.
They identify innate activation, the T helper 2 pathway and angiogenesis as important pathways in this condition.
Respond to this article
Linked Comment: Hijnen. Br J Dermatol 2019; 180:455–456.
Plain language summary available online
Ceramic restorations with resin-based adhesive systems have been the focus of recent attention in clinical dentistry. Yttrium-oxide-partially-stabilized zirconia (YPSZ) ceramics have optimized ...physical properties and exhibit favorable fracture toughness, though their bonding properties are problematic. Although functional phosphate monomers and silica-coating by tribochemical modification were expected to improve the bonding properties between YPSZ ceramics and resin-based adhesives, these two methods remain controversial. This study evaluated the efficiency of silica-coating by tribochemical modification of YPSZ ceramics. The application of phosphate monomer and a silane coupling agent on silica-coated YPSZ was also investigated. The silica-coating of YPSZ ceramics by tribochemical modification was not efficient, given the higher mechanical toughness of the densely sintered ceramics. Stable shear bond strength was achieved on silica-coated YPSZ ceramics with the cooperative interaction of phosphate monomer and silane coupling.
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