Body mass index and breast cancer risk in premenopausal and postmenopausal East Asian women: a pooled analysis of 13 cohort studies.

Background: It has been suggested that the association between body mass index and breast cancer risk differs between Asian women and Western women. We aimed to assess the associations between body mass index and breast cancer incidence in East Asian women.

Methods: Pooled analyses were performed using individual participant data of 319,189 women from 13 cohort studies in Japan, Korea, and China.

Identification of the growth cone as a probe and driver of neuronal migration in the injured brain.

Axonal growth cones mediate axonal guidance and growth regulation. We show that migrating neurons in mice possess a growth cone at the tip of their leading process, similar to that of axons, in terms of the cytoskeletal dynamics and functional responsivity through protein tyrosine phosphatase receptor type sigma (PTPσ). Migrating-neuron growth cones respond to chondroitin sulfate (CS) through PTPσ and collapse, which leads to inhibition of neuronal migration.

Annual improvement trends in resuscitation outcome of patients defibrillated by laypersons after out-of-hospital cardiac arrests and compression-only resuscitation of laypersons.

Aim: We aimed to investigate the effect of compression-only cardiopulmonary resuscitation (CPR) with conventional CPR in patients who were defibrillated by laypersons.

Methods: This is a population-based, nationwide observational study. Adult and children who sustained a witnessed out-of-hospital cardiac arrest and defibrillated by laypersons between 2005 to 2019 were identified on the national database.

Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine.

New neurons, continuously added in the adult olfactory bulb (OB) and hippocampus, are involved in information processing in neural circuits. Here, we show that synaptic pruning of adult-born neurons by microglia depends on phosphatidylserine (PS), whose exposure on dendritic spines is inversely correlated with their input activity. To study the role of PS in spine pruning by microglia in vivo, we developed an inducible transgenic mouse line, in which the exposed PS is masked by a dominant-negative form of milk fat globule-EGF-factor 8 (MFG-E8), MFG-E8D89E.

Visually cued fear conditioning test for memory impairment related to cortical function.

Aim: Fear conditioning tests are intended to elucidate a subject's ability to associate a conditioned stimulus with an aversive, unconditioned stimulus, such as footshock. Among these tests, a paradigm related to precise cortical functions would be increasingly important in drug screening for disorders such as schizophrenia and dementia. Therefore, we established a new fear conditioning paradigm using a visual cue in mice.

Successful correction of factor V deficiency of patient-derived iPSCs by CRISPR/Cas9-mediated gene editing.

Background: Factor V (FV) deficiency is a monogenic inherited coagulation disorder considered to be an ideal indication for gene therapy. To investigate the possibility of therapeutic application of genome editing, we generated induced pluripotent stem cells (iPSCs) from a FV-deficient patient and repaired the mutation of factor V gene (F5) using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9).

Methods: The patient's peripheral blood mononuclear cells were reprogrammed for iPSCs.

A head-to-toe dimerization has physiological relevance for ligand-induced inactivation of protein tyrosine receptor type Z.

Protein-tyrosine phosphatase (PTPase) receptor type Z (PTPRZ) has two receptor isoforms, PTPRZ-A and -B, containing tandem intracellular PTP-D1 and -D2 domains, with only D1 being active. Pleiotrophin (PTN) binding to the extracellular PTPRZ region leads to inactivation of its PTPase activity, thereby facilitating oligodendrocyte precursor cell (OPC) differentiation and myelination in the central nervous system. However, the mechanisms responsible for PTN-induced PTPRZ inactivation remain unclear.

Behavioral and neurological analyses of adult mice carrying null and distinct loss-of-receptor function mutations in protein tyrosine phosphatase receptor type Z (PTPRZ).

Protein tyrosine phosphatase receptor type Z (PTPRZ) is preferentially expressed in the central nervous system as two transmembrane receptor isoforms PTPRZ-A/B and one secretory isoform PTPRZ-S. Ptprz-knockout mice lacking the expression of all three isoforms show behavioral, learning, and neurological abnormalities, including increased exploratory activities to novelty, deficits in spatial and contextual learning, and reduced responses to methamphetamine, relative to wild-type mice. To investigate whether PTPRZ isoforms play distinct physiological roles, we herein performed behavioral studies on two knock-in mouse lines: One expresses the catalytically inactive Cys-1930 to Ser (CS) mutants of PTPRZ-A/B, while the other generated in the present study expresses catalytically active mutants of PTPRZ-A/B lacking the negative regulatory PTP-D2 domain and C-terminal PDZ-binding motif (ΔD2) instead of wild-type PTPRZ-A/-B.

The PTN-PTPRZ signal activates the AFAP1L2-dependent PI3K-AKT pathway for oligodendrocyte differentiation: Targeted inactivation of PTPRZ activity in mice.

Protein tyrosine phosphatase receptor type Z (PTPRZ) maintains oligodendrocyte precursor cells (OPCs) in an undifferentiated state. The inhibition of PTPase by its ligand pleiotrophin (PTN) promotes OPC differentiation; however, the substrate molecules of PTPRZ involved in the differentiation have not yet been elucidated in detail. We herein demonstrated that the tyrosine phosphorylation of AFAP1L2, paxillin, ERBB4, GIT1, p190RhoGAP, and NYAP2 was enhanced in OPC-like OL1 cells by a treatment with PTN.

Enhanced extinction of aversive memories in mice lacking SPARC-related protein containing immunoglobulin domains 1 (SPIG1/FSTL4).

Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity related to learning and memory. We previously reported that SPARC-related protein containing immunoglobulin domains 1 (SPIG1, also known as Follistatin-like protein 4, FSTL4) binds to pro-BDNF and negatively regulates BDNF maturation; however, its neurological functions, particularly in learning and memory, have not yet been elucidated. We herein examined the electrophysiological and behavioral phenotypes of Spig1-knockout (Spig1-KO) mice.

Protamine neutralizes chondroitin sulfate proteoglycan-mediated inhibition of oligodendrocyte differentiation.

Chondroitin sulfate proteoglycans (CSPGs), which are enriched in demyelinating plaques in neurodegenerative diseases, such as multiple sclerosis (MS), impair remyelination by inhibiting the migration and differentiation of oligodendrocyte precursor cells (OPCs) in the central nervous system (CNS). We herein show that protamine (PRM, also known as a heparin antagonist) effectively neutralizes the inhibitory activities of CSPGs, thereby enhancing OPC differentiation and (re)myelination in mice. Cell-based assays using mouse OPC-like OL1 cells revealed that the PRM treatment exerted masking effects on extracellular CSPGs and improved oligodendrocyte differentiation on inhibitory CSPG-coated substrates.

Identification of novel splicing variants of protein tyrosine phosphatase receptor type Z.

Protein tyrosine phosphatase receptor type Z (PTPRZ, also known as PTPζ or RPTPβ) is preferentially expressed in the central nervous system (CNS). PTPRZ plays important roles during development and adulthood in CNS myelination, learning and memory. Three splicing isoforms for PTPRZ have been identified to date: two receptor type isoforms, PTPRZ-A and PTPRZ-B, and one secretory isoform, PTPRZ-S.

Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells.

The R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs) comprises PTPRZ and PTPRG. A recent study on primary human glioblastomas suggested a close association between PTPRZ1 (human PTPRZ) expression and cancer stemness. However, the functional roles of PTPRZ activity in glioma stem cells have remained unclear.

Structural Changes in Poly(trimethylene adipate) and Poly(trimethylene succinate) During Melt Crystallization Studied Using In Situ Infrared Spectroscopy.

This paper investigates the structural changes occurring in poly(trimethylene adipate) (PTAd) and poly(trimethylene succinate) (PTSu) during melt crystallization using differential scanning calorimetry (DSC) and in situ Fourier transform infrared (FT-IR) spectroscopy. Cooling thermograms revealed that PTAd had a faster crystallization rate than PTSu. Infrared (IR) bands of the two polyesters were assigned by correlating with the IR bands of polymers containing the trimethylene and the diacid segments.

Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity: PLEIOTROPHIN-PTPRZ-A SIGNALING IS INVOLVED IN OLIGODENDROCYTE DIFFERENTIATION.

Protein-tyrosine phosphatase receptor type Z (PTPRZ) is predominantly expressed in the developing brain as a CS proteoglycan. PTPRZ has long (PTPRZ-A) and short type (PTPRZ-B) receptor forms by alternative splicing. The extracellular CS moiety of PTPRZ is required for high-affinity binding to inhibitory ligands, such as pleiotrophin (PTN), midkine, and interleukin-34; however, its functional significance in regulating PTPRZ activity remains obscure.

Small-molecule inhibition of PTPRZ reduces tumor growth in a rat model of glioblastoma.

Protein tyrosine phosphatase receptor-type Z (PTPRZ) is aberrantly over-expressed in glioblastoma and a causative factor for its malignancy. However, small molecules that selectively inhibit the catalytic activity of PTPRZ have not been discovered. We herein performed an in vitro screening of a chemical library, and identified SCB4380 as the first potent inhibitor for PTPRZ.

Inactivation of Protein Tyrosine Phosphatase Receptor Type Z by Pleiotrophin Promotes Remyelination through Activation of Differentiation of Oligodendrocyte Precursor Cells.

Unlabelled: Multiple sclerosis (MS) is a progressive neurological disorder associated with myelin destruction and neurodegeneration. Oligodendrocyte precursor cells (OPCs) present in demyelinated lesions gradually fail to differentiate properly, so remyelination becomes incomplete. Protein tyrosine phosphatase receptor type Z (PTPRZ), one of the most abundant protein tyrosine phosphatases expressed in OPCs, is known to suppress oligodendrocyte differentiation and maintain their precursor cell stage.

Channel properties of Nax expressed in neurons.

Nax is a sodium-concentration ([Na+])-sensitive Na channel with a gating threshold of ~150 mM for extracellular [Na+] ([Na+]o) in vitro. We previously reported that Nax was preferentially expressed in the glial cells of sensory circumventricular organs including the subfornical organ, and was involved in [Na+] sensing for the control of salt-intake behavior. Although Nax was also suggested to be expressed in the neurons of some brain regions including the amygdala and cerebral cortex, the channel properties of Nax have not yet been adequately characterized in neurons.

Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Features.

Sotos syndrome, characterized by intellectual disability and characteristic facial features, is caused by haploinsufficiency in the NSD1 gene. We conducted an etiological study on two siblings with Sotos features without mutations in NSD1 and detected a homozygous frameshift mutation in the APC2 gene by whole-exome sequencing, which resulted in the loss of function of cytoskeletal regulation in neurons. Apc2-deficient (Apc2) mice exhibited impaired learning and memory abilities along with an abnormal head shape.

Specific dephosphorylation at tyr-554 of git1 by ptprz promotes its association with paxillin and hic-5.

G protein-coupled receptor kinase-interactor 1 (Git1) is involved in cell motility control by serving as an adaptor that links signaling proteins such as Pix and PAK to focal adhesion proteins. We previously demonstrated that Git1 was a multiply tyrosine-phosphorylated protein, its primary phosphorylation site was Tyr-554 in the vicinity of the focal adhesion targeting-homology (FAH) domain, and this site was selectively dephosphorylated by protein tyrosine phosphatase receptor type Z (Ptprz). In the present study, we showed that Tyr-554 phosphorylation reduced the association of Git1 with the FAH-domain-binding proteins, paxillin and Hic-5, based on immunoprecipitation experiments using the Tyr-554 mutants of Git1.

Gastrointestinal symptoms and food/nutrition concerns after the great East Japan earthquake in March 2011: survey of evacuees in a temporary shelter.

On March 11, 2011, a 9.1 magnitude earthquake occurred in the eastern Pacific Ocean off the coast of northern Japan. A resulting tsunami struck the Japan Pacific coast, causing >20,000 deaths, injuries and missing persons.

SPIG1 negatively regulates BDNF maturation.

We previously identified SPARC-related protein-containing immunoglobulin domains 1 (SPIG1, also known as Follistatin-like protein 4) as one of the dorsal-retina-specific molecules expressed in the developing chick retina. We here demonstrated that the knockdown of SPIG1 in the retinal ganglion cells (RGCs) of developing chick embryos induced the robust ectopic branching of dorsal RGC axons and failed to form a tight terminal zone at the proper position on the tectum. The knockdown of SPIG1 in RGCs also led to enhanced axon branching in vitro.

Successful treatment of pulmonary contusion following chest trauma using poly-2-methoxyethyl acrylate, a biocompatible polymer surface coating for extracorporeal membrane oxygenation.

Case: We report a patient with life-threatening lung contusion who was rescued using poly-2-methoxyethyl acrylate, a biocompatible polymer surface coating for extracorporeal membrane oxygenation, which enabled reduction of the dose of systemic anticoagulation to prevent circuit thrombosis.

Outcome: A 56-year-old man was transferred to our hospital due to blunt chest trauma following a 30-m fall into water. Chest X-ray and computed tomography showed bilateral lung contusions with bilateral pneumothorax.

Application of a first impression triage in the Japan railway west disaster.

On April 25, 2005, a Japanese express train derailed into a building, resulting in 107 deaths and 549 injuries. We used "First Impression Triage (FIT)", our new triage strategy based on general inspection and palpation without counting pulse/respiratory rates, and determined the feasibility of FIT in the chaotic situation of treating a large number of injured people in a brief time period. The subjects included 39 patients who required hospitalization among 113 victims transferred to our hospital.