The ability to perceive and respond to environmental stimuli emerges in the absence of sensory experience. Spontaneous retinal activity prior to eye opening guides the refinement of retinotopy and ...eye-specific segregation in mammals, but its role in the development of higher-order visual response properties remains unclear. Here, we describe a transient window in neonatal mouse development during which the spatial propagation of spontaneous retinal waves resembles the optic flow pattern generated by forward self-motion. We show that wave directionality requires the same circuit components that form the adult direction-selective retinal circuit and that chronic disruption of wave directionality alters the development of direction-selective responses of superior colliculus neurons. These data demonstrate how the developing visual system patterns spontaneous activity to simulate ethologically relevant features of the external world and thereby instruct self-organization.
Platelets are generated from the cytoplasm of megakaryocytes (MKs) via actin cytoskeleton reorganization. Zyxin is a focal adhesion protein and wildly expressed in eukaryotes to regulate actin ...remodeling. Zyxin is upregulated during megakaryocytic differentiation; however, the role of zyxin in thrombopoiesis is unknown. Here we show that zyxin ablation results in profound macrothrombocytopenia. Platelet lifespan and thrombopoietin level were comparable between wild-type and zyxin-deficient mice, but MK maturation, demarcation membrane system formation, and proplatelet generation were obviously impaired in the absence of zyxin. Differential proteomic analysis of proteins associated with macrothrombocytopenia revealed that glycoprotein (GP) Ib-IX was significantly reduced in zyxin-deficient platelets. Moreover, GPIb-IX surface level was decreased in zyxin-deficient MKs. Knockdown of zyxin in a human megakaryocytic cell line resulted in GPIbα degradation by lysosomes leading to the reduction of GPIb-IX surface level. We further found that zyxin was colocalized with vasodilator-stimulated phosphoprotein (VASP), and loss of zyxin caused diffuse distribution of VASP and actin cytoskeleton disorganization in both platelets and MKs. Reconstitution of zyxin with VASP binding site in zyxin-deficient hematopoietic progenitor cell-derived MKs restored GPIb-IX surface expression and proplatelet generation. Taken together, our findings identify zyxin as a regulator of platelet biogenesis and GPIb-IX surface expression through VASP-mediated cytoskeleton reorganization, suggesting possible pathogenesis of macrothrombocytopenia.
Large-scale functional networks have been characterized in both rodent and human brains, typically by analyzing fMRI-BOLD signals. However, the relationship between fMRI-BOLD and underlying neural ...activity is complex and incompletely understood, which poses challenges to interpreting network organization obtained using this technique. Additionally, most work has assumed a disjoint functional network organization (i.e., brain regions belong to one and only one network). Here, we employ wide-field Ca
imaging simultaneously with fMRI-BOLD in mice expressing GCaMP6f in excitatory neurons. We determine cortical networks discovered by each modality using a mixed-membership algorithm to test the hypothesis that functional networks exhibit overlapping organization. We find that there is considerable network overlap (both modalities) in addition to disjoint organization. Our results show that multiple BOLD networks are detected via Ca
signals, and networks determined by low-frequency Ca
signals are only modestly more similar to BOLD networks. In addition, the principal gradient of functional connectivity is nearly identical for BOLD and Ca
signals. Despite similarities, important differences are also detected across modalities, such as in measures of functional connectivity strength and diversity. In conclusion, Ca
imaging uncovers overlapping functional cortical organization in the mouse that reflects several, but not all, properties observed with fMRI-BOLD signals.
Recent years have witnessed a growing trend in the participation of renewable energy on the generation side and relatively high peak loads on the demand side, which makes it gradually challenging for ...traditional methods concentrating separately on the generation side to maintain system balance. Load resources, with potentialities to provide faster and more economical responses to balance signals, are able to make contributions to system balance through demand response(DR) programs in addition. With the reformation and development of the electricity market, load aggregators(LAs) pear as representatives of small-scale customers and generations to meet response limitations and participate in DR programs. The LA in this paper, which aggregates residential customers and a PV system with battery energy storage(BES) units, balances the power by optimal scheduling and bidding in Day-ahead(DA) and real-time(RT) markets based on real-time electricity price(RTP). And the objective of this paper is to maximize the profits of LA. A majority of papers use deterministic methods for the modeling of renewable generations and residential loads. However, influenced by multiple factors, the actual renewable outputs and residential responsive loads towards real-time electricity prices are unavoidably uncertain. These uncertainties bring risks to LA’s scheduling and bidding strategies, which results in the reduction of LA’s profits. A stochastic model based on the scenario generation method is adopted to reflect the uncertainties of customers’ responsive loads and the PV system’s outputs. The objective profit function turns out to be a risk function influenced by uncertain factors and the risk control method conditional risk at value(CVaR) is integrated to obtain optimal solutions for this maximization problem. Case studies have verified the effectiveness of the proposed strategy.
Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. ...Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical,in vitroandin vivoelectrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the "recurrent network" model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development.
Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic "retinal waves" are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as "readouts" of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits.
Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines. However, many patients experience minimal benefits from certain medical treatments because of poor ...compliance, short retention times in the oral cavity, and inadequate drug efficacy. Herein, we present a novel hydrogel patch (SCE2) composed of a biopolymer matrix (featuring ultraviolet-triggered adhesion properties) loaded with cuttlefish ink nanoparticles (possessing pro-healing functions). Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light. SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species. These properties contribute to the elimination of bacteria and the management of the oxidation process, thus accelerating the healing phase's progression from inflammation to proliferation. In studies involving diabetic rats with oral ulcers, the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area, facilitating rapid re-epithelialization, and fostering angiogenesis. In conclusion, this light-sensitive hydrogel patch offers a promising path to expedited wound healing, potentially transforming treatment strategies for clinical oral ulcers.
We present a hydrogel patch (SCE2) endowed with strong adhesive properties and immunomodulatory functions, designed for the treatment of oral ulcers in diabetes. Display omitted
•A hydrogel patch (SCE2) is engineered for treating oral ulcers in individuals with diabetes.•SCE2 is produced through the incorporation of cuttlefish ink nanoparticles within a biopolymer matrix.•SCE2 demonstrates potent capabilities in photothermal antibacterial and ROS scavenging.•SCE2 aids in the recovery of oral ulcers by diminishing inflammation and enhancing angiogenesis.
In a typical electricity market, the load aggregator (LA) bids in the wholesale market to purchase electricity and meet the expected demand of its customers in the retail market. However, considering ...the uncertainty of the wholesale market prices, the LA has to undertake all the risks arising from the price volatility in the wholesale market, which may make the LA suffer from financial loss under some scenarios such as price spikes. To this end, first, this article proposes an optimal bidding strategy model for the LA that implements the demand response program (DRP), which enables the LA to reduce the risk of financial loss caused by price volatility. The bidding model is a mixed integer linear programming problem, which can be solved efficiently via a commercial solver. Second, making a rational and quantitative compensation mechanism is significant for the LA to induce its customers to participate in the DRP while there are few studies investigating it, hence, this article designs a quantitative compensation mechanism for the LA. Case studies using a dataset from the Thames valley vision verify the effectiveness of the proposed bidding model. The results confirm that the implementation of DRP not only brings great profits to LA but also benefits the other entities in the electricity market.
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