Biased movement of monomeric kinesin-3 KLP-6 explained by a symmetric Brownian ratchet model.

Most kinesin molecular motors dimerize to move processively and efficiently along microtubules; however, some can maintain processivity even in a monomeric state. Previous studies have suggested that asymmetric potentials between the motor domain and microtubules underlie this motility. In this study, we demonstrate that the kinesin-3 family motor protein KLP-6 can move forward along microtubules as a monomer upon release of autoinhibition.

Modeling the motion of disease-associated KIF1A heterodimers.

KIF1A is a member of the kinesin-3 motor protein family that transports synaptic vesicle precursors in axons. Mutations in the Kif1a gene cause neuronal diseases. Most patients are heterozygous and have both mutated and intact KIF1A alleles, suggesting that heterodimers composed of wild-type KIF1A and mutant KIF1A are likely involved in pathogenesis.

Number of kinesins engaged in axonal cargo transport: A novel biomarker for neurological disorders.

Kinesin motor proteins play crucial roles in anterograde transport of cargo vesicles in neurons, moving them along axons from the cell body towards the synaptic region. Not only the transport force and velocity of single motor protein, but also the number of kinesin molecules involved in transporting a specific cargo, is pivotal for synapse formation. This collective transport by multiple kinesins ensures stable and efficient cargo transport in neurons.

Fast backward steps and detachment of single kinesin molecules measured under a wide range of loads.

To understand force generation under a wide range of loads, the stepping of single kinesin molecules was measured at loads from -20 to 42 pN by optical tweezers with high temporal resolution. The optical trap has been improved to halve positional noise and increase bandwidth by using 200-nm beads. The step size of the forward and backward steps was 8.

6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) from Wasabia japonica alleviates inflammatory bowel disease (IBD) by potential inhibition of glycogen synthase kinase 3 beta (GSK-3β).

Inflammatory bowel disease (IBD) describes a set of disorders involving alterations to gastrointestinal physiology and mucosal immunity. Unravelling its complex pathophysiology is important since many IBD patients are refractory to or suffer adverse side effects from current treatments. Isothiocyanates (ITCs), such as 6-(methylsulfinyl)hexyl ITC (6-MITC) in Wasabia japonica, have potential anti-inflammatory activity.

A Unified Walking Model for Dimeric Motor Proteins.

Dimeric motor proteins, kinesin-1, cytoplasmic dynein-1, and myosin-V, move stepwise along microtubules and actin filaments with a regular step size. The motors take backward as well as forward steps. The step ratio r and dwell time τ, which are the ratio of the number of backward steps to the number of forward steps and the time between consecutive steps, respectively, were observed to change with the load.

Bone regeneration by freeze-dried composite of octacalcium phosphate collagen and teriparatide.

Objective: Octacalcium phosphate (OCP) and collagen (col) composite (OCPcol) demonstrated superior bone regeneration properties, and its commercialization appears to be forthcoming. As a practical medical material for new combination products, we developed a freeze-dried composite with OCPcol and teriparatide (TPTD) (OCPcolTPTDf), and investigated its bone regenerative properties.

Materials And Methods: A disk of OCPcol was made by mixing OCP granules and atelocollagen for medical use.

A biological study establishing the endotoxin limit of biomaterials for bone regeneration in cranial and femoral implantation of rats.

The purpose of this study was to accurately quantify the risk of endotoxin contamination in biomaterials for bone regeneration in order to establish the acceptable endotoxin limit. Collagen sheets containing varying amounts of purified endotoxin from Escherichia coli and dried, heat-killed E. coli or Staphylococcus aureus cells were implanted into cranial or femoral defects in rats.

Giant Acceleration of Diffusion Observed in a Single-Molecule Experiment on F(1)-ATPase.

The giant acceleration (GA) of diffusion is a universal phenomenon predicted by the theoretical analysis given by Reimann et al. [Phys. Rev.

Possible involvement of Hcn1 ion channel in learning and memory dysfunction in SAMP8 mice.

The senescence-accelerated mouse prone 8 (SAMP8) strain exhibits age-related learning and memory deficits (LMD) at 2 months of age. Combined linkage analysis of 264 F2 intercross SAMP8 × JF1 mice and RNA-seq analysis identified Hcn1 gene out of 29 genes in the LMD region on chromosome 13. Hcn1 in SAMP8 strain showed 15 times less polyglutamine repetition compared to Japanese fancy mouse 1 (JF1).

Energetics of the single-headed kinesin KIF1A.

KIF1A is a single-headed molecular motor that moves processively and unidirectionally along a microtubule by using the chemical energy released by hydrolyzing adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and inorganic phosphate (P(i)). Although the movement of KIF1A seems to have successfully been explained by a simple Brownian motor model of the flashing ratchet type, this model is not suited to discuss the energetics of KIF1A. We introduce an elaborated model of the ratchet type to investigate how the chemical free energy is converted into mechanical work by taking account of the binding and release of reactant (ATP) and product (ADP and P(i)) molecules to and from the motor.

Ghrelin postsynaptically depolarizes dorsal raphe neurons in rats in vitro.

Ghrelin promotes growth hormone (GH) secretion and feeding. Recent studies further showed that ghrelin displayed a defending effect against the depressive-like symptoms and affected sleep in animals and humans. Serotonergic system is considered to be implicated in feeding, depression and other mood disorders, and sleep.

Detection of respiratory waveforms using non-contact electrodes during bathing.

The aim of this study is to develop a method for measuring the respiratory waveform using non-contact electrodes during bathing. To determine the most appropriate electrode arrangement, we modeled a composite system consisting of a body submerged in bath water. We calculated the frequency dependence of the impedance amplitude using a three-dimensional finite difference method (3D-FDM).

Electrophysiological effects of orexin-B and dopamine on rat nucleus accumbens shell neurons in vitro.

Orexin (ORX) plays a critical role in reward-seeking behavior for natural rewards and drugs of abuse. The mesolimbic dopamine (DA) pathway that projects into the nucleus accumbens (NAc) from the ventral tegmental area is deeply involved in the neural mechanisms underlying reward, drug abuse and motivation. A recent study demonstrated that ORX-immunopositive fibers densely project into the shell of the NAc (NAcSh), suggesting that the NAcSh might be a site of the interaction between the ORXergic and DAergic systems for reward-seeking behavior.

Cytosolic calcium elevation induced by orexin/hypocretin in granule cell domain cells of the rat cochlear nucleus in vitro.

Using rat brain slice preparations, we examined the effect of orexin on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) in the granule cell domain (GCD) cells of the cochlear nucleus that carry non-auditory information to the dorsal cochlear nucleus. Application of orexin concentration-dependently increased [Ca(2+)](i), and in two thirds of GCD cells these increases persisted in the presence of tetrodotoxin. There was no significant difference between the dose-response curve for orexin-A and that for orexin-B.

Electrophysiological effect of ghrelin and somatostatin on rat hypothalamic arcuate neurons in vitro.

Growth hormone (GH) secretion from the pituitary gland is partly regulated by GH releasing hormone (GHRH)-containing neurons located in the hypothalamic arcuate nucleus (ARC). GHRH-containing neurons express the GH secretagogue (GHS) receptor (GHS-R) and the somatostatin (SRIF) receptor. Recently, an endogenous ligand for the GHS-R named ghrelin was found.

Microinjection of neuropeptide S into the rat ventral tegmental area induces hyperactivity and increases extracellular levels of dopamine metabolites in the nucleus accumbens shell.

The newly identified neuropeptide S (NPS) is mainly expressed in a group of neurons located between the locus coeruleus and Barrington's nucleus in the brainstem. Central administration of NPS increases motor activity and wakefulness, and it decreases anxiety-like behavior and feeding. The NPS receptor (NPSR) is widely distributed in various brain regions including the ventral tegmental area (VTA).

Prandial increases of leptin and orexin in the brain modulate spatial learning and memory.

Leptin is well known to be involved in the inhibition of feeding, hermogenesis, reproduction and neuroendocrine functions through its actions on the rodents hypothalamic receptors. Leptin facilitated the presynaptic transmitter release and postsynaptic sensitivity to the transmitters in the hippocampal CA1 neurons. Thus long-term potentiation (LTP) and the phosphorylation of Ca2+/calmodulin protein kinase II (CaMK II) were facilitated in the CA1 neurons.

Theta oscillations in primate prefrontal and anterior cingulate cortices in forewarned reaction time tasks.

Previously, we introduced a monkey model for human frontal midline theta oscillations as a possible neural correlate of attention. It was based on homologous theta oscillations found in the monkey's prefrontal and anterior cingulate cortices (areas 9 and 32) in a self-initiated hand-movement task. However, it has not been confirmed whether theta activity in the monkey model consistently appears in other situations demanding attention.

Electrophysiological effects of neuropeptide S on rat ventromedial hypothalamic neurons in vitro.

The newly identified neuropeptide S (NPS) is a ligand for a previously orphan G protein-coupled GPR 154 receptor, now named the NPS receptor (NPSR). Previous studies have shown that NPS induces hyperlocomotion, increases arousal and suppresses anxiety-like behaviors via NPSR. Although NPS also inhibits food intake, nothing is known about the neuronal mechanisms underlying this action.

Electrophysiological effects of ghrelin on laterodorsal tegmental neurons in rats: an in vitro study.

Ghrelin, a gut and brain peptide, is a potent stimulant for growth hormone (GH) secretion and feeding. Recent studies further show a critical role of ghrelin in the regulation of sleep-wakefulness. Laterodorsal tegmental nucleus (LDT), that regulates waking and rapid eye movement (REM) sleep, expresses GH secretagogue receptors (GHS-Rs).

Orexin-A and ghrelin depolarize the same pedunculopontine tegmental neurons in rats: an in vitro study.

Orexin (ORX), also called hypocretin, and ghrelin are newly identified peptides in the brain and/or peripheral organs, and they are involved in the regulation of sleep-wakefulness as well as feeding. In our previous studies we have found that ORX and ghrelin each depolarizes more than half of the cholinergic neurons recorded in the pedunculopontine tegmental nucleus (PPT) via a dual ionic mechanism including a decrease of K(+) conductance and an increase of nonselective cationic conductance. Thus, the present study was carried out to investigate whether ORX-A and ghrelin both depolarize the same PPT neuron.

Reconstruction of critical-sized bone defect in dog skull by octacalcium phosphate combined with collagen.

Purpose: The present study was designed to investigate whether synthetic octacalcium phosphate (OCP) combined with collagen (OCP/collagen) can repair a critical-sized defect in dog skull. OCP/collagen has been shown to biodegrade and to tend to be replaced by newly formed bone if implanted in rat calvaria defects.

Materials And Methods: An OCP/collagen disk was prepared from pepsin-digested atelocollagen isolated from porcine dermis and synthetic OCP.

Electrophysiological effects of orexin/hypocretin on nucleus accumbens shell neurons in rats: an in vitro study.

Orexin-A (ORX-A) and orexin-B (ORX-B) play critical roles in the regulation of sleep-wakefulness, energy homeostasis, neuroendocrine system and autonomic functions. Although ORXs are also implicated in the reward process, their electrophysiological effects on neurons in the shell of nucleus accumbems (NAcSh) have not been described thoroughly. Therefore we examined the electrophysiological effects of ORXs on rat NAcSh neurons.

Electrophysiological effects of ghrelin on pedunculopontine tegmental neurons in rats: An in vitro study.

Ghrelin is a potent stimulant for growth hormone (GH) secretion and feeding. Recent studies further show a critical role of ghrelin in the regulation of sleep-wakefulness. Pedunculopontine tegmental nucleus (PPT), which regulates waking and rapid eye movement (REM) sleep, expresses GH secretagogue receptors (GHS-Rs).