Systemic administrations of protamine heal subacute spinal cord injury in mice.

Spinal cord injury (SCI) results in damage to neural circuits that cause long-term locomotor and sensory disability. The objective of the present study is to evaluate whether a clinical drug, protamine, can be employed as a therapeutic agent for SCI. First, we examined the rescue effect of protamine on dystrophic endballs (DEs) cultured on a chondroitin sulfate (CS) gradient coating.

Identification of APBB1 as a substrate for anaplastic lymphoma kinase.

Anaplastic lymphoma kinase (ALK) is a well-known oncogene involved in various malignancies such as anaplastic large cell lymphoma, lung cancer and neuroblastoma. Several substrates for fused ALK have been identified and their biological functions have been described. However, the lack of a comprehensive identification of ALK substrates limits our understanding of the biological roles of receptor ALK.

Integrated Systems Analysis Deciphers Transcriptome and Glycoproteome Links in Alzheimer's Disease.

Glycosylation is increasingly recognized as a potential therapeutic target in Alzheimer's disease. In recent years, evidence of Alzheimer's disease-specific glycoproteins has been established. However, the mechanisms underlying their dysregulation, including tissue- and cell-type specificity, are not fully understood.

Towards the in vivo identification of protein-protein interactions.

Protein-protein interactions (PPIs) play crucial roles in biological processes. The conventional methods based on affinity purification of a protein of interest (POI) have been widely used to identify unknown PPIs. Recently, proximity-dependent biotin identification (BioID) has been used increasingly to investigate PPIs.

Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis.

Objective: Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients older than 50 years of age. sIBM is hardly responds to any immunosuppressing theraphies, and its pathophysiology remains elusive. This study aims to explore pathogenic pathways underlying sIBM and identify novel therapeutic targets using metabolomic and transcriptomic analyses.

The impact of clarifying the long-term solution picture through solution-focused interventions on positive attitude towards life.

Solution-focused brief therapy is a psychotherapeutic model. The purpose of this study was to examine the effects of clarity of long-term solutions on positive attitude towards life. In order to examine the effects of the long-term solution image, the conditions for clarifying the long-term and short-term solution images, and not seeking clarification of the solution image were set and randomly assigned.

The mammalian-type thioredoxin reductase 1 confers a high-light tolerance to the green alga Chlamydomonas reinhardtii.

Reactive oxygen species (ROS) can both act as a poison causing cell death and important signaling molecules among various organisms. Photosynthetic organisms inevitably produce ROS, making the appropriate elimination of ROS an essential strategy for survival. Interestingly, the unicellular green alga Chlamydomonas reinhardtii expresses a mammalian form of thioredoxin reductase, TR1, which functions as a ROS scavenger in animal cells.

Screening of novel Midkine binding protein by BioID2-based proximity labeling.

Midkine (MK), a heparin-binding growth factor, is associated with the poor prognosis of the pediatric tumor, neuroblastoma. MK would be a druggable target as many studies showed inhibition of its function in various cancers suppressed tumor developments. To establish the therapy targeting MK, identification of its binding partners, and elucidation of its intracellular signaling are needed.

Dermatan sulphate is an activating ligand of anaplastic lymphoma kinase.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that harbours a tyrosine kinase domain in its intracellular region and is expressed in both central and peripheral nervous systems. RTKs are activated upon ligand binding and receptor clustering; however, ALK remains an orphan receptor despite its pathological significance, especially in malignancy. Recent biochemical work showed that heparan sulphate (HS), an unbranched sulphated glycan, acts as a ligand for and activates ALK.

Axonal Regeneration by Glycosaminoglycan.

Like other biomolecules including nucleic acid and protein, glycan plays pivotal roles in various cellular processes. For instance, it modulates protein folding and stability, organizes extracellular matrix and tissue elasticity, and regulates membrane trafficking. In addition, cell-surface glycans are often utilized as entry receptors for viruses, including SARS-CoV-2.

Forward and backward locomotion patterns in C. elegans generated by a connectome-based model simulation.

Caenorhabditis elegans (C. elegans) can produce various motion patterns despite having only 69 motor neurons and 95 muscle cells. Previous studies successfully elucidate the connectome and role of the respective motor neuron classes related to movement.

Midkine Interaction with Chondroitin Sulfate Model Synthetic Tetrasaccharides and Their Mimetics: The Role of Aromatic Interactions.

Midkine (MK) is a neurotrophic factor that participates in the embryonic central nervous system (CNS) development and neural stem cell regulation, interacting with sulfated glycosaminoglycans (GAGs). Chondroitin sulfate (CS) is the natural ligand in the CNS. In this work, we describe the interactions between a library of synthetic models of CS-types and mimics.

Type IIa RPTPs and Glycans: Roles in Axon Regeneration and Synaptogenesis.

Type IIa receptor tyrosine phosphatases (RPTPs) play pivotal roles in neuronal network formation. It is emerging that the interactions of RPTPs with glycans, i.e.

Enoxaparin promotes functional recovery after spinal cord injury by antagonizing PTPRσ.

The receptor-type protein tyrosine phosphatase sigma (PTPRσ) regulates axonal regeneration/sprouting as a molecular switch in response to glycan ligands. Cell surface heparan sulfate oligomerizes PTPRσ and inactivates its enzymatic activity, which in turn promotes axonal growth. In contrast, matrix-associated chondroitin sulfate monomerizes PTPRσ and activates it.

Identification of PTPRσ-interacting proteins by proximity-labelling assay.

Receptor protein tyrosine phosphatases (RPTPs) are type-I transmembrane proteins and involved in various biological and pathological processes. Their functions are supposed to be exerted through tyrosine dephosphorylation of their specific substrates. However, our comprehensive understanding of specific substrates or interacting proteins for RPTPs is poor.

Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis.

Chondroitin sulfate (CS) and heparan sulfate (HS) are glycosaminoglycans that both bind the receptor-type protein tyrosine phosphatase PTPRσ, affecting axonal regeneration. CS inhibits axonal growth, while HS promotes it. Here, we have prepared a library of HS octasaccharides and, together with synthetic CS oligomers, we found that PTPRσ preferentially interacts with CS-E-a rare sulfation pattern in natural CS-and most HS oligomers bearing sulfate and sulfamate groups.

Generation and characterization of antagonistic anti-human interleukin (IL)-18 monoclonal antibodies with high affinity: Two types of monoclonal antibodies against full-length IL-18 and the neoepitope of inflammatory caspase-cleaved active IL-18.

Interleukin-18 (IL-18) is a pro-inflammatory cytokine that evokes both innate and acquired immune responses. IL-18 is initially synthesized as an inactive precursor and the cleavage for processing into a mature, active molecule is mediated by pro-inflammatory caspases following the activation of inflammasomes. Two types of monoclonal antibodies were raised: anti-IL-18 antibodies which recognize full-length and cleaved IL-18; and anti-IL-18 neoepitope antibodies which specifically recognize the new N-terminal YFGKLESK of IL-18 cleaved by pro-inflammatory caspase-1/4.

A computational model of internal representations of chemical gradients in environments for chemotaxis of Caenorhabditis elegans.

The small roundworm Caenorhabditis elegans employs two strategies, termed pirouette and weathervane, which are closely related to the internal representation of chemical gradients parallel and perpendicular to the travelling direction, respectively, to perform chemotaxis. These gradients must be calculated from the chemical information obtained at a single point, because the sensory neurons are located close to each other at the nose tip. To formulate the relationship between this sensory input and internal representations of the chemical gradient, this study proposes a simple computational model derived from the directional decomposition of the chemical concentration at the nose tip that can generate internal representations of the chemical gradient.

Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes.

Neurocan (NCAN), a secreted chondroitin sulfate proteoglycan, is one of the major inhibitory molecules for axon regeneration in nervous injury. However, its role in cancer is not clear. Here we observed that high NCAN expression was closely associated with the unfavorable outcome of neuroblastoma (NB).

Midkine Promotes Atherosclerotic Plaque Formation Through Its Pro-Inflammatory, Angiogenic and Anti-Apoptotic Functions in Apolipoprotein E-Knockout Mice.

Background: A recent study suggested that midkine (MK), a heparin-binding growth factor, is associated with atherosclerosis progression in patients with artery disease. It has previously been reported that MK plays a critical role in neointima formation in a restenosis model, whereas the role of MK in the development of atherosclerosis has not been investigated. The present study assessed the effect of MK administration on the process of atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE) mice.

Mechanisms of axon regeneration: The significance of proteoglycans.

Background: Therapeutics specific to neural injury have long been anticipated but remain unavailable. Axons in the central nervous system do not readily regenerate after injury, leading to dysfunction of the nervous system. This failure of regeneration is due to both the low intrinsic capacity of axons for regeneration and the various inhibitors emerging upon injury.

Dissecting the interaction between tissue inhibitor of metalloproteinases-3 (TIMP-3) and low density lipoprotein receptor-related protein-1 (LRP-1): Development of a "TRAP" to increase levels of TIMP-3 in the tissue.

Tissue inhibitor of metalloproteinases 3 (TIMP-3) is a key regulator of extracellular matrix turnover for its ability to inhibit matrix metalloproteinases (MMPs), adamalysin-like metalloproteinases (ADAMs) and ADAMs with thrombospondin motifs (ADAMTSs). TIMP-3 is a secreted protein whose extracellular levels are regulated by endocytosis via the low-density-lipoprotein receptor-related protein-1 (LRP-1). In this study we developed a molecule able to "trap" TIMP-3 extracellularly, thereby increasing its tissue bioavailability.