Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45

Skeletal muscle constitutes approximately 40% of the human body mass, and alterations in muscle mass and strength may result in physical disability. Therefore, the elucidation of the factors responsible for muscle force development is of paramount importance. Excitation-contraction coupling (ECC) is a process during which the skeletal muscle surface membrane is depolarized, causing a transient release of calcium from the sarcoplasmic reticulum that activates the contractile proteins. The ECC machinery is complex, and the functional role of many of its protein components remains elusive. This study demonstrates that deletion of the gene encoding the sarcoplasmic reticulum protein JP45 results in decreased muscle strength in young mice. Specifically, this loss of muscle strength in JP45 knockout mice is caused by decreased functional expression of the voltage-dependent Ca(2+) channel Ca(v)1.1, which is the molecule that couples membrane depolarization and calcium release from the sarcoplasmic reticulum. These results point to JP45 as one of the molecules involved in the development or maintenance of skeletal muscle strength.     

Functional Crosstalk Between Cell-Surface and Intracellular Channels Mediated by Junctophilins Essential for Neuronal Functions

Junctophilins (JPs) contribute to the formation of junctional membrane complexes between the plasma membrane and the endoplasmic/sarcoplasmic reticulum, and provide a structural platform for channel communication during excitation–contraction coupling in muscle cells. In the brain, two neuronal JP subtypes are widely expressed in neurons. Recent studies have defined the essential role of neural JPs in the communication between cell-surface and intracellular channels, which modulates the excitability and synaptic plasticity of neurons in the cerebellum and hippocampus.     

Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

Junctional membrane complexes (JMCs) composed of the plasma membrane and endoplasmic/sarcoplasmic reticulum seem to be a structural platform for channel crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the sarcoplasmic reticulum membrane and binding with the plasma membrane in muscle cells. In this article, we report that mutant JP double-knockout (JP-DKO) mice lacking neural JP subtypes exhibited an irregular hindlimb reflex and impaired memory. Electrophysiological experiments indicated that the activation of small-conductance Ca(2+)-activated K(+) channels responsible for afterhyperpolarization in hippocampal neurons requires endoplasmic reticulum Ca(2+) release through ryanodine receptors, triggered by NMDA receptor-mediated Ca(2+) influx. We propose that in JP-DKO neurons lacking afterhyperpolarization, the functional communications between NMDA receptors, ryanodine receptors, and small-conductance Ca(2+)-activated K(+) channels are disconnected because of JMC disassembly. Moreover, JP-DKO neurons showed an impaired long-term potentiation and hyperactivation of Ca(2+)/calmodulin-dependent protein kinase II. Therefore, JPs seem to have an essential role in neural excitability fundamental to plasticity and integrated functions.     

Enhancement of spatial attention in nociceptin/orphanin FQ receptor-knockout mice

We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-knockout mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-knockout mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-knockout mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic acid-induced writhing tests compared to those of wild-type mice. The nociceptin receptor-knockout mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-knockout mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-knockout mice than wild-type mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.     

Prevention and management of hypertrophic scars after laparoscopic surgery using silicone gel sheets: a pilot study

ObjectiveTo assess the effectiveness and safety of modified silicone gel sheets applied to hypertrophic scars and keloids following laparoscopic surgery.MethodsPatients who had undergone laparoscopic surgery and who had either conventional or modified silicone gel sheets affixed to their surgical lesions for 6 months postoperatively (treatment groups), and control patients who had not received postsurgical treatment involving silicone gel sheets, were enrolled. The surgical wounds were assessed visually and using the Japan Scar Workshop (JSW) Scar Scale. Patients were interviewed before, 3 months after, and 6 months after sheet affixation.ResultsA total of 45 patients were included, comprising 15 patients per group. Both silicone gel-sheet groups had significantly lower JSW Scar Scale scores at 3 and 6 months after affixation compared with controls. The scores were not significantly different between the conventional and modified treatment groups and no adverse events were observed in the latter.ConclusionsModified silicone gel sheets were more effective than controls and comparable to conventional gel sheets, and there were no adverse events related to laparoscopic surgical wounds in the improved silicone gel sheet group, demonstrating the safety and effectiveness of the modified silicone gel sheets.     

Deep Learning and Its Application to Function Approximation for MR in Medicine: An Overview

This article presents an overview of deep learning (DL) and its applications to function approximation for MR in medicine. The aim of this article is to help readers develop various applications of DL. DL has made a large impact on the literature of many medical sciences, including MR. However, its technical details are not easily understandable for non-experts of machine learning (ML).The first part of this article presents an overview of DL and its related technologies, such as artificial intelligence (AI) and ML. AI is explained as a function that can receive many inputs and produce many outputs. ML is a process of fitting the function to training data. DL is a kind of ML, which uses a composite of many functions to approximate the function of interest. This composite function is called a deep neural network (DNN), and the functions composited into a DNN are called layers. This first part also covers the underlying technologies required for DL, such as loss functions, optimization, initialization, linear layers, non-linearities, normalization, recurrent neural networks, regularization, data augmentation, residual connections, autoencoders, generative adversarial networks, model and data sizes, and complex-valued neural networks.The second part of this article presents an overview of the applications of DL in MR and explains how functions represented as DNNs are applied to various applications, such as RF pulse, pulse sequence, reconstruction, motion correction, spectroscopy, parameter mapping, image synthesis, and segmentation.