Search Our Scientific Publications & Authors

JCI Insight 2021 Apr 8. Epub 2021 Apr 8.

Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.

Extensive activation of glial cells during a latent period has been well documented in various animal models of epilepsy. However, it remains unclear whether activated glial cells contribute to epileptogenesis; i.e. Read More

EMBO Rep 2021 Apr 6:e51532. Epub 2021 Apr 6.

Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.

Ferroptosis has recently attracted much interest because of its relevance to human diseases such as cancer and ischemia-reperfusion injury. We have reported that prolonged severe cold stress induces lipid peroxidation-dependent ferroptosis, but the upstream mechanism remains unknown. Here, using genome-wide CRISPR screening, we found that a mitochondrial Ca uptake regulator, mitochondrial calcium uptake 1 (MICU1), is required for generating lipid peroxide and subsequent ferroptosis under cold stress. Read More

Int J Mol Sci 2021 Mar 26;22(7). Epub 2021 Mar 26.

Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Korányi fasor 9, 6720 Szeged, Hungary.

Spreading depolarization (SD) is a wave of mass depolarization that causes profound perfusion changes in acute cerebrovascular diseases. Although the astrocyte response is secondary to the neuronal depolarization with SD, it remains to be explored how glial activity is altered after the passage of SD. Here, we describe post-SD high frequency astrocyte Ca oscillations in the mouse somatosensory cortex. Read More

FASEB J 2021 May;35(5):e21400

IGF, Université de Montpellier, CNRS, INSERM, Montpellier, France.

Anterior pituitary endocrine cells that release hormones such as growth hormone and prolactin are excitable and fire action potentials. In these cells, several studies previously showed that extracellular sodium (Na ) removal resulted in a negative shift of the resting membrane potential (RMP) and a subsequent inhibition of the spontaneous firing of action potentials, suggesting the contribution of a Na background conductance. Here, we show that the Na leak channel NALCN conducts a Ca - Gd -sensitive and TTX-resistant Na background conductance in the GH cell line, a cell model of pituitary endocrine cells. Read More

Cryst Growth Des 2021 Mar 28;21(3):1576-1590. Epub 2021 Jan 28.

Department of Earth Sciences, Utrecht University, Princetonlaan 8A, 3584 CB Utrecht, The Netherlands.

The effect of stoichiometry on the new formation and subsequent growth of CaCO was investigated over a large range of solution stoichiometries (10 < < 10, where = {Ca}:{CO}) at various, initially constant degrees of supersaturation (30 < Ω < 200, where Ω = {Ca}{CO}/), pH of 10.5 ± 0.27, and ambient temperature and pressure. Read More

Eur J Obstet Gynecol Reprod Biol X 2021 Apr 2;10:100124. Epub 2021 Mar 2.

Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Centre de Recherche du CHUS, Sherbrooke, QC, Canada.

Background: Human myometrium is a therapeutic target for labor induction and preterm labor.

Objective: This study aimed to assess the physiological role of alternative calcium conductance on contractions triggered by uterotonic drugs in human myometrium. Membrane conductances, supported by TRPV channels, may provide alternative pathways to control either free intracellular and/or submembrane Ca-concentration, which in turn will modulate membrane polarization and contractile responses. Read More

Int J Mol Sci 2021 Feb 25;22(5). Epub 2021 Feb 25.

Department of Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.

Oxidative stress and inflammation play important roles in the pathophysiology of acute kidney injury (AKI). Transient receptor potential ankyrin 1 (TRPA1) is a Ca2+-permeable ion channel that is sensitive to reactive oxygen species (ROS). The role of TRPA1 in AKI remains unclear. Read More

Bio Protoc 2020 Jul 20;10(14):e3681. Epub 2020 Jul 20.

Department of Biological Sciences, Tokyo Metropolitan University, Hachioji, Tokyo, 192-0397, Japan.

Polyethylene glycol calcium (PEG-Ca)-mediated transfection allows rapid and efficient examination to analyze diverse cellular functions of genes of interest. In plant cells, macromolecules, such as DNA, RNA and protein, are delivered into protoplasts derived from somatic tissues or calli via PEG-Ca transfection. To broaden and develop the scope of investigations using plant gametes and zygotes, a procedure for direct delivery of macromolecules into these cells has recently been established using PEG-Ca transfection. Read More

Cell Biol Toxicol 2021 Mar 2. Epub 2021 Mar 2.

College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, Shaanxi, China.

3-Chloro-1, 2-propanediol (3-MCPD) is a food-borne toxic substance well-known for more than 40 years that is mainly associated with nephrotoxicity. A better understanding of 3-MCPD nephrotoxicity is required to devise efficacious strategies to counteract its toxicity. In the present work, the role of endoplasmic reticulum (ER) stress along with its underlying regulatory mechanism in 3-MCPD-mediated renal cytotoxicity was investigated in vivo and in vitro. Read More

J Cell Physiol 2021 Mar 1. Epub 2021 Mar 1.

Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

Vascular stiffening, an early and common characteristic of cardiovascular diseases (CVDs), stimulates vascular smooth muscle cell (VSMC) proliferation which reciprocally accelerates the progression of CVDs. However, the mechanisms by which extracellular matrix stiffness accompanying vascular stiffening regulates VSMC proliferation remain largely unknown. In the present study, we examined the role of the intermediate-conductance Ca -activated K  (IK ) channel in the matrix stiffness regulation of VSMC proliferation by growing A7r5 cells on soft and stiff polydimethylsiloxane substrates with stiffness close to these of arteries under physiological and pathological conditions, respectively. Read More

Oxid Med Cell Longev 2021 4;2021:1246491. Epub 2021 Feb 4.

Department of Marine Life Science, Jeju National University, Jeju 63243, Republic of Korea.

Anthocyanins from the petals of L. (PS) possess anti-inflammatory, antioxidant, and antimelanogenic activities. However, it remains unclear whether PS inhibit the NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation and assembly. Read More

Fungal Genet Biol 2021 Apr 16;149:103540. Epub 2021 Feb 16.

Department of Plant Pathology & Environmental Microbiology, The Pennsylvania State University, University Park, PA 16802, United States. Electronic address:

Genetically encoded Ca indicators (GECIs) enable long-term monitoring of cellular and subcellular dynamics of this second messenger in response to environmental and developmental cues without relying on exogenous dyes. Continued development and optimization in GECIs, combined with advances in gene manipulation, offer new opportunities for investigating the mechanism of Ca signaling in fungi, ranging from documenting Ca signatures under diverse conditions and genetic backgrounds to evaluating how changes in Ca signature impact calcium-binding proteins and subsequent cellular changes. Here, we attempted to express multi-color (green, yellow, blue, cyan, and red) circularly permuted fluorescent protein (FP)-based Ca indicators driven by multiple fungal promoters in Fusarium oxysporum, F. Read More

Macromolecules 2021 Feb 19;54(3):1137-1146. Epub 2021 Jan 19.

AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.

The biological functions of natural polyelectrolytes are strongly influenced by the presence of ions, which bind to the polymer chains and thereby modify their properties. Although the biological impact of such modifications is well recognized, a detailed molecular picture of the binding process and of the mechanisms that drive the subsequent structural changes in the polymer is lacking. Here, we study the molecular mechanism of the condensation of calcium, a divalent cation, on hyaluronan, a ubiquitous polymer in human tissues. Read More

Front Pharmacol 2020 25;11:561956. Epub 2021 Jan 25.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, China.

Aloperine (ALO), a quinolizidine alkaloid isolated from L. used in the traditional Uygur medicine, induced a significant increase in cellular glucose uptake of L6 cells, suggesting it has the potential to relieve hyperglycemia. Therefore, we investigated the effects of ALO on type 2 diabetes mellitus (T2DM) through and studies. Read More

PLoS One 2021 10;16(2):e0244556. Epub 2021 Feb 10.

Mary Anne McPhail Equine Performance Center, Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States of America.

Recurrent exertional rhabdomyolysis (RER) is a chronic muscle disorder of unknown etiology in racehorses. A potential role of intramuscular calcium (Ca2+) dysregulation in RER has led to the use of dantrolene to prevent episodes of rhabdomyolysis. We examined differentially expressed proteins (DEP) and gene transcripts (DEG) in gluteal muscle of Thoroughbred race-trained mares after exercise among three groups of 5 horses each; 1) horses susceptible to, but not currently experiencing rhabdomyolysis, 2) healthy horses with no history of RER (control), 3) RER-susceptible horses treated with dantrolene pre-exercise (RER-D). Read More

J Gen Physiol 2021 Mar;153(3)

Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, and the University of Wisconsin Cardiovascular Research Center, Madison, WI.

In myocardium, phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) is thought to modulate the cooperative activation of the thin filament by binding to myosin and/or actin, thereby regulating the probability of cross-bridge binding to actin. At low levels of Ca2+ activation, unloaded shortening velocity (Vo) in permeabilized cardiac muscle is comprised of an initial high-velocity phase and a subsequent low-velocity phase. The velocities in these phases scale with the level of activation, culminating in a single high-velocity phase (Vmax) at saturating Ca2+. Read More

Int J Orthop Trauma Nurs 2020 Nov 12:100833. Epub 2020 Nov 12.

North Cumbria Integrated Care NHS Foundation Trust, Carlisle, CA2 7HY, UK. Electronic address:

Purpose: To assess if application of dual-layer compression bandage to osteotomy patients post-surgery can positively influence levels of post-operative pain and swelling.

Patients & Methods: Prospective, single-centre, randomised controlled trial comparing standard care, non-compression bandaging, versus Coban™ 2 (3M). Seven day application of the latter to index leg of osteotomy patients. Read More

Blood 2021 02;137(8):1061-1071

Department of Anesthesiology and Intensive Care Medicine, University Hospital of Tuebingen, Tuebingen, Germany.

The pathophysiology of COVID-19-associated thrombosis seems to be multifactorial. We hypothesized that COVID-19 is accompanied by procoagulant platelets with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization. Read More

Biochem J 2021 01;478(1):197-215

Department of Biochemistry, The University of Western Ontario, London, Ontario, Canada N6A 5C1.

The membrane protein dysferlin (DYSF) is important for calcium-activated plasma membrane repair, especially in muscle fibre cells. Nearly 600 mutations in the DYSF gene have been identified that are causative for rare genetic forms of muscular dystrophy. The dysferlin protein consists of seven C2 domains (C2A-C2G, 13%-33% identity) used to recruit calcium ions and traffic accessory proteins and vesicles to injured membrane sites needed to reseal a wound. Read More

J Ethnopharmacol 2021 Apr 12;270:113815. Epub 2021 Jan 12.

Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, PR China. Electronic address:

Ethnopharmacological Relevance: Erzhi formula (EZF) consists of Ecliptae herba (EH) and Fructus Ligustri Lucidi (FLL) at a ratio 1:1, and constitutes a well-known formula in China that is commonly used for treating menopausal diseases.

Aim Of The Study: In this study, we explored the pharmacologic actions and potential molecular mechanisms underlying EZF's action in preventing and treating osteoporosis.

Materials And Methods: The active components and related targets of EZF's anti-osteoporotic effects were predicted by network pharmacology, and functional enrichment analysis was also performed. Read More

Proc Natl Acad Sci U S A 2021 Jan;118(3)

RIKEN-MIT Laboratory for Neural Circuit Genetics, The Picower Institute for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;

There is considerable evidence for hippocampal time cells that briefly activate in succession to represent the temporal structure of memories. Previous studies have shown that time cells can be disrupted while leaving place cells intact, indicating that spatial and temporal information can be coded in parallel. However, the circuits in which spatial and temporal information are coded have not been clearly identified. Read More

Pancreas 2021 Jan;50(1):3-11

From the Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.

Abstract: Acute pancreatitis (AP) is one of the most common gastroenterological disorders leading to hospitalization. It has long been debated whether biliary AP, about 30% to 50% of all cases, is induced by bile acids (BAs) when they reach the pancreas via reflux or via the systemic blood circulation.Besides their classical function in digestion, BAs have become an attractive research target because of their recently discovered property as signaling molecules. Read More

Mitochondrion 2021 03 17;57:37-46. Epub 2020 Dec 17.

Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, Gautam Buddha Nagar, Uttar Pradesh 201314, India; Academy of Scientific and Innovative Research, CSIR-HRDG, Ghaziabad, Uttar Pradesh 201002, India. Electronic address:

Background: Biogenesis and function of mitochondria is profoundly dependent on cytosolic translation of mitochondrial pre-proteins and its subsequent translocation and folding inside the organelle. Continuous exposure of non-native precursor proteins, exposure to damaging by-products of oxidative phosphorylation, load of mis-targeted or misfolded proteins from neighbouring compartments and unremitting demand of communication between mitochondrial and nuclear genomes, continuously pose proteotoxic threats to the organelle. Our knowledge of cellular mechanisms to cope up with such impending threat of proteotoxicity to mitochondria, is currently evolving. Read More

Front Cell Dev Biol 2020 1;8:596879. Epub 2020 Dec 1.

Physiological Institute, University of Regensburg, Regensburg, Germany.

All vertebrate cells activate Cl currents (I) when swollen by hypotonic bath solution. The volume-regulated anion channel VRAC has now been identified as LRRC8/SWELL1. However, apart from VRAC, the Ca-activated Cl channel (CaCC) TMEM16A and the phospholipid scramblase and ion channel TMEM16F were suggested to contribute to cell swelling-activated whole-cell currents. Read More

BMJ Open 2020 12 10;10(12):e043403. Epub 2020 Dec 10.

Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.

Introduction: Early empiric treatment with broad-spectrum antimicrobials is common in neonatal intensive care units (NICU) due to the non-specific clinical presentation of infection. However, excessive and inappropriate antimicrobial use can lead to the emergence of drug-resistant organisms and adverse neonatal outcomes. This study aims to develop and implement a nationwide NICU-specific antimicrobial stewardship programme (ASP) to promote judicious antimicrobial use and control the emergence of multidrug-resistant organisms (MDROs) in Canada. Read More

Elife 2020 12 10;9. Epub 2020 Dec 10.

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.

Synaptic vesicle (SV) endocytosis is coupled to exocytosis to maintain SV pool size and thus neurotransmitter release. Intense stimulation induces activity-dependent bulk endocytosis (ADBE) to recapture large quantities of SV constituents in large endosomes from which SVs reform. How these consecutive processes are spatiotemporally coordinated remains unknown. Read More

Psychiatry Res 2021 Jan 24;295:113588. Epub 2020 Nov 24.

Jiangsu Provincial Key Laboratory of Special Children's Impairment and Intervention, Nanjing Normal University of Special Education, Nanjing, China; State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China. Electronic address:

Cannabis exposure is related to neuroanatomical changes in brain regions rich in cannabinoid receptors, such as the hippocampus. However, researchers have not clearly determined whether persistent heavy cannabis use leads to morphological changes in the hippocampus or whether an earlier age of onset of first cannabis use and/or higher doses of cannabis exposure exacerbate these alterations. In this longitudinal study, we investigated whether continued heavy cannabis use in young adults is associated with an altered hippocampal volume. Read More

J Cell Mol Med 2021 Jan 23;25(1):473-483. Epub 2020 Nov 23.

Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.

Osteoporosis is a disease in which bone mineral density decreases due to abnormal activity of osteoclasts, and is commonly found in post-menopausal women who have decreased levels of female hormones. Sphingosylphosphorylcholine (SPC) is an important biological lipid that can be converted to sphingosine-1-phosphate (S1P) by autotaxin. S1P is known to be involved in osteoclast activation by stimulating osteoblasts, but bone regulation by SPC is not well understood. Read More

J Vis Exp 2020 11 3(165). Epub 2020 Nov 3.

Institute of Pharmacology and Toxicology, University Medical Center Göttingen; Partner Site Göttingen, DZHK (German Centre for Cardiovascular Research); Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen.

Mouse models play a crucial role in arrhythmia research and allow studying key mechanisms of arrhythmogenesis including altered ion channel function and calcium handling. For this purpose, atrial or ventricular cardiomyocytes of high quality are necessary to perform patch-clamp measurements or to explore calcium handling abnormalities. However, the limited yield of high-quality cardiomyocytes obtained by current isolation protocols does not allow both measurements in the same mouse. Read More

Am J Physiol Regul Integr Comp Physiol 2021 02 18;320(2):R129-R137. Epub 2020 Nov 18.

Graduate School of Informatics and Engineering, University of Electro-Communications, Tokyo, Japan.

The effect of cooling on in vivo intracellular calcium ion concentration [Ca] after eccentric contractions (ECs) remains to be determined. We tested the hypothesis that cryotherapy following ECs promotes an increased [Ca] and induces greater muscle damage in two muscles with substantial IIb and IIx fiber populations. The thin spinotrapezius (SPINO) muscles of Wistar rats were used for in vivo [Ca] imaging, and tibialis anterior (TA) muscles provided greater fidelity and repeatability of contractile function measurements. Read More