A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices in C. elegans.

Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. The C. elegans PVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells. LECT-2 functions in a multi-protein receptor-ligand complex that also contains two transmembrane ligands on the skin, SAX-7/L1CAM and MNR-1, and the neuronal transmembrane receptor DMA-1. LECT-2 greatly enhances the binding between SAX-7, MNR-1 and DMA-1. The activation of DMA-1 strictly requires all three ligands, which establishes a combinatorial code to precisely target and pattern dendritic arbors

Sarcomeres Pattern Proprioceptive Sensory Dendritic Endings through UNC-52/Perlecan in C. elegans

SummarySensory dendrites innervate peripheral tissues through cell-cell interactions that are poorly understood. The proprioceptive neuron PVD in C. elegans extends regular terminal dendritic branches between muscle and hypodermis. We found that the PVD branch pattern was instructed by adhesion molecule SAX-7/L1CAM, which formed regularly spaced stripes on the hypodermal cell. The regularity of the SAX-7 pattern originated from the repeated and regularly spaced dense body of the sarcomeres in the muscle. The extracellular proteoglycan UNC-52/Perlecan linked the dense body to the hemidesmosome on the hypodermal cells, which in turn instructed the SAX-7 stripes and PVD dendrites. Both UNC-52 and hemidesmosome components exhibited highly regular stripes that interdigitated with the SAX-7 stripe and PVD dendrites, reflecting the striking precision of subcellular patterning between muscle, hypodermis, and dendrites. Hence, the muscular contractile apparatus provides the instructive cues to pattern proprioceptive dendrites

Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions

Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis

Precise regulation of the guidance receptor DMA-1 by KPC-1/furin instructs dendritic branching decisions

Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis

Multi-scale interactive network in the application of DAS seismic data processing

Distributed acoustic sensing (DAS) is regarded as a novel acquisition technology for seismic data. Compared with conventional electrical geophones, DAS has a series of obvious advantages including low-cost, high spatial resolution, good coverage, and strong resistance to the harsh environment. Noise attenuation is an essential step in seismic data processing. However, there are two main difficulties faced by the denoising task of DAS seismic data. On the one hand, some background noise in DAS seismic data, such as optical low-frequency noise, horizontal noise, and fading noise, is unique and not presented in the conventional seismic data; on the other hand, the signal-to-noise ratio (SNR) of DAS seismic data is relatively low. Recently, a convolutional neural network (CNN) has shown superior denoising performance compared to the traditional method. To follow this promising trend, we propose a multi-scale interactive convolutional neural network (MSI-Net) and apply it to denoise the challenging DAS seismic data. Different from most of the existing CNN architecture used in seismic data denoising, the MSI-Net considers both coarse-scale and fine-scale features by improving the inherent serial convolution to multi-scale parallel convolution, which is beneficial to recover detailed information. Moreover, we utilize some connections to achieve the information interaction between different scales, which promotes the flow of information and enables the network to extract more informative multi-scale features from the DAS seismic data. Moreover, both synthetic and real examples demonstrate that the proposed MSI-Net can effectively attenuate a variety of unique DAS background noise and also completely recover the weak signals. Compared with conventional CNN architecture, MSI-Net exhibits better performance in global SNR and local details

Visualizing the Zhang-Rice singlet, molecular orbitals and pair formation in cuprate

The parent compound of cuprates is a charge-transfer-type Mott insulator with strong hybridization between the Cu $3d_{\mathrm x^2-y^2}$ and O $2p$ orbitals. A key question concerning the pairing mechanism is the behavior of doped holes in the antiferromagnetic (AF) Mott insulator background, which is a prototypical quantum many-body problem. It was proposed that doped hole on the O site tends to form a singlet, known as Zhang-Rice singlet (ZRS), with the unpaired Cu spin. But experimentally little is known about the properties of a single hole and the interplay between them that leads to superconductivity. Here we use scanning tunneling microscopy to visualize the electronic states in hole-doped $\mathrm{Ca_2CuO_2Cl_2}$, aiming to establish the atomic-scale local basis for pair formation. A single doped hole is shown to have an in-gap state and a clover-shaped spatial distribution that can be attributed to a localized ZRS. When the dopants are close enough, they develop delocalized molecular orbitals with characteristic stripe- and ladder-shaped patterns, accompanied by the opening of a small gap around the Fermi level ($E_{\mathrm F}$). With increasing doping, the molecular orbitals proliferate in space and gradually form densely packed plaquettes, but the stripe and ladder patterns remain nearly the same. The low-energy electronic states of the molecular orbitals are intimately related to the local pairing properties, thus play a vitally important role in the emergence of superconductivity. We propose that the Cooper pair is formed by two holes occupying the stripe-like molecular orbital, while the attractive interaction is mediated by the AF spin background

Study on the accessibility and affordability of 50 drugs in Wuhan based on the WHO/HAI standardization method

ObjectiveTo understand the availability and affordability of essential drugs in Wuhan since the implementation of the national essential medicine system, and to provide a basis for the subsequent formulation and improvement of related policies.MethodsUsing the standard survey method jointly developed by the WHO and Health Action International (HAI), a sample of 50 essential drugs was selected to investigate and evaluate their availability and affordability in public medical and health institutions and social retail pharmacies in Wuhan, using six diseases with high clinical morbidity as the targets.ResultsThe availability of the original drug and the lowest-priced generic drug in public hospitals is 26.4 and 42.47% respectively, and that in retail pharmacies is 26.8 and 54.4% respectively. The median price ratio of the original drug and the lowest-priced generic drug is 28.71 and 2.23 respectively in public hospitals, and 29.24 and 3.59 respectively in retail pharmacies; In addition to individual drugs, such as omeprazole, others are affordable. The availability of essential drugs in public hospitals in Wuhan is lower than that in social retail pharmacies, and the availability of the lowest-priced generic drugs is much higher than that of original drugs.ConclusionThe availability of essential drugs in public hospitals in Wuhan is lower than that in social retail pharmacies, and the availability of the lowest-priced generic drugs is much higher than that of original drugs. The price of the original drug is much higher than the international reference price; The price of medicines in public hospitals is lower than that in retail pharmacies;the overall condition of affordability is good, but there is a big gap between the affordability levels of original drugs and generic drugs, and the affordability of original drugs is relatively poor. It is recommended to adjust the relevant policies according to the actual situation of Wuhan city itself, moderately ensure the supply of original drugs, improve the price transparency of retail pharmacies, and ensure that the basic drug needs of the public are met

A Dendritic Guidance Receptor Complex Brings Together Distinct Actin Regulators to Drive Efficient F-Actin Assembly and Branching

Proper morphogenesis of dendrites plays a fundamental role in the establishment of neural circuits. The molecular mechanism by which dendrites grow highly complex branches is not well understood. Here, using the C. elegans PVD neuron, we demonstrate that high-order dendritic branching requires actin polymerization driven by coordinated interactions between two membrane proteins, DMA-1 and HPO-30, and with their cytoplasmic interactors, the RacGEF TIAM-1 and the actin nucleation promotion factor WAVE Regulatory Complex (WRC). The dendrite branching receptor DMA-1 directly binds to the PDZ domain of TIAM-1, while the claudin-like protein HPO-30 directly interacts with the WRC. On dendrites, DMA-1 and HPO-30 form a receptor-associated signaling complex to bring TIAM-1 and the WRC to close proximity, leading to elevated assembly of F-actin needed to drive high-order dendrite branching. The synergistic activation of F-actin assembly by scaffolding distinct actin regulators might represent a general mechanism in promoting complex dendrite arborization

A Retrospective Analysis of the Clinical Features of Inpatients With Epilepsy in the Ganzi Tibetan Autonomous Prefecture

Background: There is limited detailed clinical information for patients with epilepsy in Tibet. This study sought to provide data about the clinical features of epilepsy in the Ganzi Tibetan Autonomous Prefecture to improve strategies for epilepsy prevention and management in this region.Methods: We reviewed the clinical record of patients with epilepsy in the Neurology Department, Ganzi Tibetan Autonomous Prefecture People's Hospital and compared the clinical features and compared it with control, from West China Hospital in Chengdu.Results: This retrospective study included 165 patients with epilepsy admitted between January 2015 and February 2018. Majority of patients (97%) in this study had active epilepsy; 28.5% had generalized onset seizures and 68.5% had focal onset seizures. Fifty-four patients had received anti-epileptic drug (AED) treatment prior to hospitalization, however, 38 (70.4%) patients took the medication irregularly. The leading etiology of this cohort was head trauma (20.6%), followed by stroke (10.9%), neurocysticercosis (7.9%), brain hydatidosis (6.7%) and tuberculous infection (5.5%). Compared with in-patients in Chengdu, epilepsy in Ganzi was more frequently caused by infection (OR = 4.216, 95% CI, 2.124–8.367), including neurocysticercosis (OR = 29.301, 95% CI, 1.727–497.167) and brain hydatidosis (OR = 24.637, 95% CI, 1.439–421.670).Conclusions: These data suggest that the control of cerebral infections, especially parasite infection, is essential for the prevention of epilepsy in the Ganzi Tibetan Autonomous Prefecture. Education of local primary doctors and patients about the literacy of epilepsy will enable better management of epilepsy in this population