Neural Functions of Matrix Metalloproteinases: Plasticity, Neurogenesis, and Disease

The brain changes in response to experience and altered environment. To do that, the nervous system often remodels the structures of neuronal circuits. This structural plasticity of the neuronal circuits appears to be controlled not only by intrinsic factors, but also by extrinsic mechanisms including modification of the extracellular matrix. Recent studies employing a range of animal models implicate that matrix metalloproteinases regulate multiple aspects of the neuronal development and remodeling in the brain. This paper aims to summarize recent advances of our knowledge on the neuronal functions of matrix metalloproteinases and discuss how they might relate in neuronal disease

Wide-bandgap GaN-based watt-class photonic-crystal lasers

青色GaN系フォトニック結晶レーザーの高出力・高ビーム品質動作に成功 --次世代の高品位レーザー加工、高輝度照明、水中LiDAR等の実現に向けて--. 京都大学プレスリリース. 2022-11-04.Short-wavelength (blue-violet-to-green) lasers with high power and high beam quality are required for various applications including the machining of difficult-to-process materials and high-brightness illuminations and displays. Promising light sources for such applications are wide-bandgap GaN-based photonic-crystal surface-emitting lasers (PCSELs), which are based on two-dimensional resonance in the photonic crystal. Developments of these devices have lagged behind those of longer-wavelength GaAs-based PCSELs, because device designs for achieving robust two-dimensional resonance and a nanofabrication process that avoids introducing disorders have remained elusive for wide-bandgap GaN-based materials. Here, we address these issues and successfully realize GaN-based PCSELs with high, watt-class (>1 W) output power and a circular, single-lobed beam with a very narrow (~0.2°) divergence angle at blue wavelengths. In addition, we demonstrate continuous-wave operation with a high output power (~320 mW) and a high beam quality (M²~1). Our results will enable the use of GaN-based PCSELs in the above-mentioned applications

Integrated Lipidomics in the Secreted Phospholipase A2 Biology

Mammalian genomes encode genes for more than 30 phospholipase A2s (PLA2s) or related enzymes, which are subdivided into several subgroups based on their structures, catalytic mechanisms, localizations and evolutionary relationships. More than one third of the PLA2 enzymes belong to the secreted PLA2 (sPLA2) family, which consists of low-molecular-weight, Ca2+-requiring extracellular enzymes, with a His-Asp catalytic dyad. Individual sPLA2 isoforms exhibit unique tissue and cellular localizations and enzymatic properties, suggesting their distinct pathophysiological roles. Recent studies using transgenic and knockout mice for several sPLA2 isoforms, in combination with lipidomics approaches, have revealed their distinct contributions to various biological events. Herein, we will describe several examples of sPLA2-mediated phospholipid metabolism in vivo, as revealed by integrated analysis of sPLA2 transgenic/knockout mice and lipid mass spectrometry. Knowledge obtained from this approach greatly contributes to expanding our understanding of the sPLA2 biology and pathophysiology

Dendrite Reshaping of Adult Drosophila Sensory Neurons Requires Matrix Metalloproteinase-Mediated Modification of the Basement Membranes

SummaryIn response to changes in the environment, dendrites from certain neurons change their shape, yet the mechanism remains largely unknown. Here we show that dendritic arbors of adult Drosophila sensory neurons are rapidly reshaped from a radial shape to a lattice-like shape within 24 hr after eclosion. This radial-to-lattice reshaping arises from rearrangement of the existing radial branches into the lattice-like pattern, rather than extensive dendrite pruning followed by regrowth of the lattice-shaped arbors over the period. We also find that the dendrite reshaping is completely blocked in mutants for the matrix metalloproteinase (Mmp) 2. Further genetic analysis indicates that Mmp2 promotes the dendrite reshaping through local degradation of the basement membrane upon which dendrites of the sensory neurons innervate. These findings suggest that regulated proteolytic alteration of the extracellular matrix microenvironment might be a fundamental mechanism to drive a large-scale change of dendritic structures during reorganization of neuronal circuits

Prediction of Prehospital Change of the Cardiac Rhythm From Nonshockable to Shockable in Out‐of‐Hospital Patients With Cardiac Arrest: A Post Hoc Analysis of a Nationwide, Multicenter, Prospective Registry

Background Predicting a spontaneous rhythm change from nonshockable to shockable before hospital arrival in patients with out‐of‐hospital cardiac arrest can help emergency medical services develop better strategies for prehospital treatment. The aim of this study was to identify predictors of spontaneous rhythm change before hospital arrival in patients with out‐of‐hospital cardiac arrest and develop a predictive scoring system. Methods and Results We retrospectively reviewed data of eligible patients with out‐of‐hospital cardiac arrest with an initial nonshockable rhythm registered in a nationwide registry between June 2014 and December 2017. We performed a multivariable analysis using a Cox proportional hazards model to identify predictors of a spontaneous rhythm change, and a ridge regression model for predicting it. The data of 25 804 patients were analyzed (derivation cohort, n=17 743; validation cohort, n=8061). The rhythm change event rate was 4.1% (724/17 743) in the derivation cohort, and 4.0% (326/8061) in the validation cohorts. Age, sex, presence of a witness, initial rhythm, chest compression by a bystander, shock with an automated external defibrillator by a bystander, and cause of the cardiac arrest were all found to be independently associated with spontaneous rhythm change before hospital arrival. Based on this finding, we developed and validated the Rhythm Change Before Hospital Arrival for Nonshockable score. The Harrell’s concordance index values of the score were 0.71 and 0.67 in the internal and external validations, respectively. Conclusions Seven factors were identified as predictors of a spontaneous rhythm change from nonshockable to shockable before hospital arrival. We developed and validated a score to predict rhythm change before hospital arrival