A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways.

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl)-induced fibrosis with chronic intra-gastric alcohol feeding.

Kinematic Origins of Motor Inconsistency in Expert Pianists.

For top performers, including athletes and musicians, even subtle inconsistencies in rhythm and force during movement production decrease the quality of performance. However, extensive training over many years beginning in childhood is unable to perfect dexterous motor performance so that it is without any error. To gain insight into the biological mechanisms underlying the subtle defects of motor actions, the present study sought to identify the kinematic origins of inconsistency of dexterous finger movements in musical performance.

A label-free impedance-based whole cell assay revealed a new G protein-coupled receptor ligand for mouse microglial cell migration.

We report the usefulness of an impedance-based label-free whole cell assay to identify new ligands for G protein-coupled receptors (GPCRs) involved in microglial cell migration. Authentic GPCR ligands were subjected to the impedance-based cell assay in order to examine the responses of ligands for MG5 mouse microglial cells. Complement component 5 (C5a), adenosine 5'-diphosphate (ADP), uridine 5'-triphosphate (UTP), lysophosphatidic acid (LPA), and lysophosphatidylserine (LysoPS) were found to elicit different cellular impedance patterns, i.

Adaptive response to l-serine deficiency is mediated by p38 MAPK activation via 1-deoxysphinganine in normal fibroblasts.

Unlabelled: Reduced availability of l-serine limits cell proliferation and leads to an adaptation to l-serine-deficient environment, the underlying molecular mechanism of which remain largely unexplored. Genetic ablation of 3-phosphoglycerate dehydrogenase (Phgdh), which catalyzes the first step of de novo l-serine synthesis, led to diminished cell proliferation and the activation of p38 MAPK and stress-activated protein kinase/Jun amino-terminal kinase in mouse embryonic fibroblasts under l-serine depletion. The resultant l-serine deficiency induced cyclin-dependent kinase inhibitor 1a (Cdkn1a; p21) expression, which was mediated by p38 MAPK.

The impact of stress on motor performance in skilled musicians suffering from focal dystonia: Physiological and psychological characteristics.

Recent investigations have suggested that stress can modulate motor function. However, the impact of stress on motor performance of musicians suffering from focal dystonia (FDM) remains unknown. The current study assessed motor performance in 20 FDM patients and 16 healthy musicians (HM) before and under stress.

Quantification of sound instability in embouchure tremor based on the time-varying fundamental frequency.

Task-specific tremor in musicians is an involuntary oscillating muscular activity mostly of the hand or the embouchure, which predominantly occurs while playing the instrument. In contrast to arm or hand tremors, which have been examined and objectified based on movement kinematics and muscular activity, embouchure tremor has not yet been investigated. To quantify and describe embouchure tremor we analysed sound production and investigated the fluctuation of the time-varying fundamental frequency of sustained notes.

The Dipeptides Ile-Tyr and Ser-Tyr Exert Distinct Effects on Catecholamine Metabolism in the Mouse Brainstem.

Catecholamine synthesis and transmission in the brain are influenced by the availability of Tyr in the body. In this study, we compared the effects of oral administration of Tyr-containing dipeptides Ile-Tyr, Ser-Tyr, and Tyr-Pro with Tyr alone on catecholamine metabolism in the mouse brainstem. Among these dipeptides, Ile-Tyr administration led to increases in dopamine, the dopamine metabolites homovanillic acid, and 3,4-dihydroxyphenylacetic acid, compared to administration of Ser-Tyr, Tyr-Pro, or Tyr alone.

Duration of Prehospital Resuscitation Efforts After Out-of-Hospital Cardiac Arrest.

Background: During out-of-hospital cardiac arrest, it is unclear how long prehospital resuscitation efforts should be continued to maximize lives saved.

Methods And Results: Between 2005 and 2012, we enrolled 282 183 adult patients with bystander-witnessed out-of-hospital cardiac arrest from the All-Japan Utstein Registry. Prehospital resuscitation duration was calculated as the time interval from call receipt to return of spontaneous circulation in cases achieving prehospital return of spontaneous circulation or from call receipt to hospital arrival in cases not achieving prehospital return of spontaneous circulation.

Complete occlusion of the left main trunk coronary artery by a cardiac papillary fibroelastoma in a hemodynamically unstable patient.

Papillary fibroelastomas are benign cardiac tumors with high embolic potential. The majority of cases of complete obstruction of the left main trunk (LMT) of the coronary artery are diagnosed via autopsy following sudden death; survival is rare in this setting. We present the case of a 60-year-old woman who underwent stent placement in the LMT three years prior to developing chest pain and cold sweats.

The curse of motor expertise: Use-dependent focal dystonia as a manifestation of maladaptive changes in body representation.

Focal task-specific dystonia (FTSD) impairs not only motor dexterity, but also somatosensory perception involved in well-trained behavioral tasks. Occupations that carry a risk of developing FTSD include musician, writer, painter, surgeon, and golfer, which are characterized by repetitive and precise motor actions over a prolonged period. Behavioral studies have uncovered various undesirable effects of FTSD on sensorimotor functions, such as a loss of independent movement control, unintended muscular co-activation, awkward limb posture, and impairment of fine discrimination of tactile and proprioceptive sensations.

Secrets of virtuoso: neuromuscular attributes of motor virtuosity in expert musicians.

Musical performance requires extremely fast and dexterous limb movements. The underlying biological mechanisms have been an object of interest among scientists and non-scientists for centuries. Numerous studies of musicians and non-musicians have demonstrated that neuroplastic adaptations through early and deliberate musical training endowed superior motor skill.

Interleukin-17A Plays a Pivotal Role in Chemically Induced Hepatocellular Carcinoma in Mice.

Aim: The aim of the present study was to investigate the role of interleukin (IL)-17A in the initiation and progression of hepatocellular carcinoma.

Methods: IL-17A deficient (KO) and wild-type (WT) mice were intraperitoneal injected with diethyl nitrosamine (DEN) to induce hepatocellular carcinoma, and the incidence of tumours was assessed 38 weeks later. In order to investigate the effects of DEN on hepatocytes in the acute phase of DEN administration, DEN-treated mice were sacrificed at designated time points.

Novel insight for midline cyst formation in prostate: The involvement of decreased prenatal testosterone suggested by second-to-fourth digit ratio study.

Objectives: To clarify the relationship between midline cyst formation and second to fourth finger length ratio.

Methods: The present study included 95 benign prostatic hyperplasia patients and 61 healthy male college students. All midline cysts were identified by transrectal ultrasonography.

Losing dexterity: patterns of impaired coordination of finger movements in musician's dystonia.

Extensive training can bring about highly-skilled action, but may also impair motor dexterity by producing involuntary movements and muscular cramping, as seen in focal dystonia (FD) and tremor. To elucidate the underlying neuroplastic mechanisms of FD, the present study addressed the organization of finger movements during piano performance in pianists suffering from the condition. Principal component (PC) analysis identified three patterns of fundamental joint coordination constituting finger movements in both patients and controls.

Interleukin 17A plays a role in lipopolysaccharide/D-galactosamine-induced fulminant hepatic injury in mice.

Background: Lipopolysaccharide/d-galactosamine (LPS/GalN)-induced hepatic injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor alpha (TNF-α) plays a pivotal role. Moreover, it was reported from our laboratory that interleukin (IL) 17A enhanced production of TNF-α by the Kupffer cell.

Objective: The purpose of this study was to determine the role of IL-17A in LPS/GalN-induced hepatic injury in mice.

Orally administrated dipeptide Ser-Tyr efficiently stimulates noradrenergic turnover in the mouse brain.

In this study, we examined the effect of orally administrated dipeptides containing Tyr (Y) on the metabolism of catecholamines in mouse brains. We found that among eight synthetic dipeptides whose sequences are present frequently in soy proteins, Ser-Tyr (SY), Ile-Tyr, and Tyr-Pro had the highest apparent permeability coefficients in monolayers of human intestinal epithelial Caco-2 cells. When administrated orally, SY markedly increased tyrosine content in the cerebral cortex compared to the vehicle control, Ile-Tyr, Tyr-Pro, and Y alone.

STAT3 integrates cooperative Ras and TGF-β signals that induce Snail expression.

The epithelial-mesenchymal transition (EMT) is a crucial morphological event that occurs during the progression of epithelial tumors. EMT can be induced by transforming growth factor β (TGF-β) in certain kinds of cancer cells through the induction of Snail, a key regulator of EMT. We have previously found that TGF-β remarkably induces Snail expression in cooperation with Ras signals; however, the underlying mechanism of this synergism has not yet been determined.

Takotsubo cardiomyopathy in two patients with microvascular angina.

We present two cases in which takotsubo cardiomyopathy (TC) developed immediately after a diagnosis of microvascular angina had been established. One patient who had been diagnosed as having endothelium-dependent microvascular angina (microvascular spasm) developed TC three weeks after the initial admission. The other patient was diagnosed as having endothelium-independent microvascular angina (decreased coronary flow reserve) and subsequently developed TC after the discontinuation of nicorandil treatment.

L-Serine Deficiency Elicits Intracellular Accumulation of Cytotoxic Deoxysphingolipids and Lipid Body Formation.

L-serine is required to synthesize membrane lipids such as phosphatidylserine and sphingolipids. Nevertheless, it remains largely unknown how a diminished capacity to synthesize L-serine affects lipid homeostasis in cells and tissues. Here, we show that deprivation of external L-serine leads to the generation of 1-deoxysphingolipids (doxSLs), including 1-deoxysphinganine, in mouse embryonic fibroblasts (KO-MEFs) lacking D-3-phosphoglycerate dehydrogenase (Phgdh), which catalyzes the first step in the de novo synthesis of L-serine.

Acquisition and reacquisition of motor coordination in musicians.

Precise control of movement timing plays a key role in musical performance. This motor skill requires coordination across multiple joints and muscles, which is acquired through extensive musical training from childhood. However, extensive training has a potential risk of causing neurological disorders that impair fine motor control, such as task-specific tremor and focal dystonia.

Distinct digit kinematics by professional and amateur pianists.

Many everyday tasks such as typing, grasping, and object manipulation require coordination of dynamic movement across multiple joints and digits. Playing a musical instrument is also one such task where the precise movement of multiple digits is transformed into specific sounds defined by the instrument. Through extensive practice musicians are able to produce precisely controlled movements to interact with the instrument and produce specific sequences of sounds.