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Landiolol, an ultra-short-acting β1-selective blocker, is more effective in controlling heart rate compared with digoxin in patients with atrial tachyarrhythmias and left ventricular dysfunction. However, the effect of atrial tachyarrhythmia type on the effectiveness of landiolol remains unknown. Hence, this study aimed to evaluate the effectiveness of landiolol in patients with atrial fibrillation (AF) and atrial tachycardia (AT), not limited to those with heart failure with a reduced ejection fraction. To this end, we evaluated the efficacy and safety of landiolol in managing tachycardiac AF and tachycardiac atrial flutter/AT in 44 patients with reduced left ventricular function. We found that while landiolol was effective in managing patients with AF and heart failure with a preserved or mid-range ejection fraction, however, it might be more challenging to control heart rate in patients with AT using a similar dosage of landiolol.

Neurally mediated syncope (NMS) is associated with a sudden loss of consciousness. However, the diagnostic tools and measures for prognosis management are limited. To overcome these limitations, the differences in the binding energies of Giα-protein-coupled receptors to the Glu9 and Glu12 residues on the α2B-AR gene were elucidated through the analysis of α2B-AR gene polymorphism. The suppression of the activity of adenylate cyclase (AC), which is involved in vasoconstriction, may be related to the onset of NMS. The head-up tilt (HUT) test results indicated differences in systolic blood pressure (SBP) and AC activity between patients with vasodepressor (VT)-NMS and healthy volunteers. Patients with VT-NMS had increased AC activity and decreased SBP. Conversely, in healthy volunteers, no changes in AC activity or SBP were found. These findings suggest that a high SBP and elevated AC activity at rest are likely to cause syncope. A high incidence of cardiovascular events is found in patients with negative HUT test results, highlighting the importance of investigating the cause of syncope in cases where the HUT test results are negative. Overall, our results may provide a means of assessing the risk of NMS development within healthy populations and underscore the importance of subsequent treatments for NMS.

Precise and sequential motor tasks that require strenuous and fine force control involve distinct, complex neural mechanisms without which they would be difficult to perform. A previous study showed that strenuous force exertion gives rise to potentiation of active muscles (post-contraction potentiation, PCP). However, the mechanisms underlying PCP remain unclear. We investigated the neural mechanisms underlying PCP using spectral analyses of surface EMG activity. Fourteen healthy participants were asked to perform an EMG matching task (2% of maximum voluntary contraction, MVC) before (Test 1) and after (Test 2) they exerted a brief 50% MVC (conditioning contraction, CC). The exerted force was significantly lower during Test 2 than Test 1, indicating that PCP did occur. In addition, spike-like EMG responses with a mean frequency of ~10 Hz were frequently observed during Test 2. Power spectrum analysis demonstrated that the peak power of both α and β bands increased after CC, and that changes in the peak power of both bands during Test 2 negatively correlated with changes in force. These findings suggest that the synchronization of active motor units accounted for PCP.

Abstract Background Takotsubo syndrome is a stress-induced disease that makes up 2–3% of acute coronary syndrome cases. However, its onset mechanism remains unclear. Although females are overwhelmingly affected, males end up having more cardiac complications. Case presentation We examined the differences in stress responses in the myocardium between sexes in patients with takotsubo syndrome. We biopsied samples from an over 70-year-old Japanese male and an over 80-year-old Japanese female. Tissues from the left ventricle apex in the acute phase and the apical ballooning-type were examined using histopathology and deoxyribonucleic acid (DNA) microarray analysis. Our data showed that left ventricular ejection fractions were 38% and 56%, and peak creatinine kinase concentrations during hospitalization were 629 U/L and 361 U/L, for the male and female patient, respectively. The pulmonary capillary wedge pressure was 26 mmHg and 11 mmHg for the male and female patient, respectively. Negative T did not return to normal in the male subject after 6 months. Histopathology results indicated that contraction band necrosis and lymphocyte infiltration were more common in the male subject. Conclusions We noticed that possible differences may exist between male and female patients using pathological examination and some DNA analyses. In particular, it may help treat acute severity in males. We will elucidate the mechanism of takotsubo syndrome development by increasing the number of samples to support the reliability of the data in the future.

Surface electromyographic activity (sEMG) of the biceps brachii (BB) during weak elbow flexion has been reported to immediately increase after strong elbow flexion even while exerting consistent force; this phenomenon is called “post-contraction potentiation” (PCP). To determine whether the central nervous system is involved in PCP, we investigated the effect of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) during PCP. Initially, the participants were instructed to perform successive muscle contraction tasks with different forces: 2% (Test 1); then 25%, 50%, or 100% (conditioning contraction [CC]); and again 2% (Test 2) of maximum voluntary contraction (MVC). In subsequent experiments, the CC intensity was set at 50% MVC, and tDCS (anodal, cathodal, and sham) was applied to the M1 before the task. In the last experiment, TMS was applied to M1 to evaluate the excitability of the corticospinal tract during Tests 1 and 2. The CC intensity at 50% or 100% MVC generated PCP, but didn’t at 25% MVC. Anodal tDCS significantly decreased the magnitude of PCP, while cathodal tDCS showed an increase in magnitude compared to sham tDCS. The BB motor-evoked potential amplitude during Test 2 was lower compared to that during Test 1. These findings suggest that changes in the excitability of the corticospinal tract and resultant changes in the activation pattern of motor unit activity play a role in generating PCP.

Associations between neurotransmitters, adrenergic receptor (ADR) mutations, and behaviors in chickens produced and domesticated by artificial selection remain unclear. This study investigates the association of neurotransmitters and ADR mutations with egg laying and cockfighting—behaviors associated with significantly different breeding backgrounds—in Shaver Brown and Shamo chickens. Accordingly, the whole sequences of nine ADR genes were determined, and nine amino acid-specific mutation sites from five genes (ADRα1A: S365G, ADRα1D: T440N, ADRα2A: D273E, ADRβ1: N443S, S445N, ADRβ3: R342C, Q404L, and P406S) were extracted. Evolutionary analysis showed that these mutations were not ancestrally derived. These results confirm that the mutations at these sites were artificially selected for domestication and are breed specific. NST population analysis confirmed a difference in the degree of genetic differentiation between the two populations in seven genes. The results further confirm differences in the degree of genetic differentiation between the two populations in Shaver Brown (ADRA1B and ADRA1D) and Shamo (ADRA1A and ADRA2B) chickens, indicating that the ADR gene differs between the two breeds. The effects of artificial selection, guided by the human-driven selection of desirable traits, are reflected in adrenaline gene mutations. Furthermore, certain gene mutations may affect domestication, while others may affect other traits in populations or individuals.

The authors would like to make the following correction to the published paper [...]

We investigated circulatory dynamics in patients with vasodepressor type neurally mediated syncope (VT-NMS) by performing high-resolution Holter electrocardiography and a correlation analysis of changes in adenylate cyclase activity, blood pressure, and pulse during the head-up tilt test. Holter electrocardiography was performed for 30 patients. Adenylate cyclase activity was evaluated in lymphocytes from blood samples taken at rest and during the head-up tilt test. There was no change in autonomic nerve fluctuation during electrocardiography in VT-NMS patients, but our results showed a significant difference in blood pressure and adenylate cyclase activity between VT-NMS patients and healthy volunteers; the systolic blood pressure of VT-NMS patients decreased after 5 min, while at 10 min, the adenylate cyclase activity was the highest (0.53%) and the systolic blood pressure was the lowest (111.8 mm Hg). Pulse rates increased after 10 min. VT-NMS patients showed higher blood pressure, pulse rate, and adenylate cyclase activity during the tilt test than did healthy volunteers. In patients with syncope, standing for longer than 10 minutes may increase the risk of VT-NMS. From our results, we consider it likely that high systolic blood pressure and adenylate cyclase activity at rest cause fainting in VT-NMS patients. Our findings may be helpful for identifying individuals with a high risk of developing NMS in the healthy population.

Most patients with Takotsubo Syndrome (TTS) are postmenopausal females. TTS in males is rare and gender differences have not been sufficiently investigated. Therefore, we investigated gender differences in TTS. TTS in males and females is often triggered by physical and emotional stress, respectively. Heart failure, a severe in-hospital complication, requires greater mechanical respiratory support in males. Fatal arrhythmias such as ventricular tachycardia and ventricular fibrillation and in-hospital mortality rates are higher in males. The white blood cell (WBC) count has been shown to be higher in males than in females with cardiovascular death compared with non-cardiovascular death. Therefore, the WBC count, a simple marker, may reflect severe TTS. Decreased estrogen levels, common in postmenopausal females, are a pathogenic mechanism of TTS. Females have a more significant increase in the extracellular matrix-receptor interaction than males. Moreover, the pathological findings after hematoxylin–eosin staining were different in males and females. Males had more severe complications than females in the acute phase of TTS; thus, more careful observations and interventions are likely required. From these results, it can be considered that the mechanism of the onset of TTS may be different between males and females. Therefore, it is necessary to fully understand the gender differences in order to more effectively manage TTS.

This study aimed to clarify whether genetic mutations participate in renal cell carcinoma (RCC) metastasis to the adrenal gland (AG). Our study analyzed whole mitochondrial gene and ribonucleic acid sequencing (RNA-seq) data from a male patient in his 60s with metastatic RCC. We confirmed common mutation sites in the mitochondrial gene and carried out Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using RNA-seq data for RCC and adrenal carcinoma. Furthermore, we confirmed the common mutation sites of mitochondrial genes in which the T3394Y (p.H30Y) site transitioned from histidine (His.; H) to tyrosine (Tyr.; Y) in the NADH dehydrogenase subunit 1 (ND1) gene. The R11,807G (p.T350A) site transitioned from threonine (Thr.; T) to alanine (Ala.; A). Additionally, the G15,438R or A (p.G231D) site transitioned from glycine (Gly.; G) to aspartic acid (Asp.; D) in cytochrome b (CYTB). Furthermore, pathway analysis, using RNA-seq, confirmed the common mutant pathway between RCC and adrenal carcinoma as cytokine–cytokine receptor (CCR) interaction. Confirmation of the original mutation sites suggests that transfer to AG may be related to the CCR interaction. Thus, during metastasis to the AG, mitochondria DNA mutation may represent the initial origin of the metastasis, followed by the likely mutation of the nuclear genes.

ABSTRACT: Background: Alopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a genome region known to be associated with AA as compared to other regions. Methods: We engineered mice carrying AA risk allele identified by haplotype sequencing for the MHC region using allele-specific genome editing with the CRISPR/Cas9 system. Finally, we performed functional evaluations in the mice and AA patients with and without the risk allele. Findings: We identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Furthermore, mice engineered to carry the risk allele displayed a hair loss phenotype. Transcriptomics further identified CCHCR1 as a novel component interacting with hair cortex keratin in hair shafts. Both, these alopecic mice and AA patients with the risk allele displayed morphologically impaired hair and comparable differential expression of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Interpretation: Our results implicate CCHCR1 with the risk allele in a previously unidentified subtype of AA based on aberrant keratinization in addition to autoimmune events. Funding: This work was supported by JSPS KAKENHI (JP16K10177) and the NIHR UCLH Biomedical Research center (BRC84/CN/SB/5984).

Syncope is commonly encountered in daily clinical practice. Depending on its etiology (benign or life-threatening conditions or environmental triggers), syncope can be neurally mediated (reflex), cardiac, or orthostatic. Furthermore, neurologic disease can cause symptoms that mimic syncope. However, there is limited research on neurally mediated syncope (NMS), which is considered a benign disorder, and close follow-ups are rarely performed. NMS can cause serious clinical events, including severe trauma and car accidents. The head-up tilt test (HUTT) is the gold standard for diagnosing NMS; however, its clinical significance remains unknown, and its relevance to NMS prognosis requires further research. This retrospective study aimed to assess the clinical significance of the HUTT for NMS. We reviewed the charts of 101 patients who underwent HUTT at Tokai University Hospital in Japan between January 2016 and March 2019. During the HUTT, 72 patients (69.2%) experienced syncope. Patients were followed up for 886.1 ± 457.7 days (interquartile range: 518–1293 days). The syncope recurrence rate was 16.9%; however, no significant difference was observed between the two groups (HUTT positive vs. negative) (13.8% vs. 18.1%, p = 0.772). Four of 29 (13.9%) and two of 72 (2.8%) patients in the negative and positive HUTT groups, respectively, experienced cardiac events (p = 0.019). Negative HUTT results may assist in anticipating unexpected clinical events within a few years. A negative HUTT result may allow us to reconsider the NMS diagnosis based on clinical information. Close outpatient follow-up of patients with negative HUTT results is warranted.

The enteric protozoa Entamoeba histolytica is the causative agent of amebiasis, which is one of the most common parasitic diseases in developed and developing countries. Entamoeba nuttalli is the genetically closest species to E. histolytica in current phylogenetic analyses of Entamoeba species, and is prevalent in wild macaques. Therefore, E. nuttalli may be a key organism in which to investigate molecules required for infection of human or non-human primates. To explore the molecular signatures of host-parasite interactions, we conducted de novo assembly of the E. nuttalli genome, utilizing self-correction of PacBio long reads and polishing corrected reads using Illumina short reads, followed by comparative genomic analysis with two other mammalian and a reptilian Entamoeba species. The final draft assembly of E. nuttalli included 395 contigs with a total length of approximately 23 Mb, and 9,647 predicted genes, of which 6,940 were conserved with E. histolytica. In addition, we found an E. histolytica-specific repeat known as ERE2 in the E. nuttalli genome. GO-term enrichment analysis of mammalian host-related molecules indicated diversification of transmembrane proteins, including AIG1 family and BspA-like proteins that may be involved in the host-parasite interaction. Furthermore, we identified an E. nuttalli-specific protein that contained 42 repeats of an octapeptide ([G,E]KPTDTPS). This protein was shown to be localized on the cell surface using immunofluorescence. Since many repeat-containing proteins in parasites play important roles in interactions with host cells, this unique octapeptide repeat-containing protein may be involved in colonization of E. nuttalli in the intestine of macaques. Overall, our draft assembly provides a valuable resource for studying Entamoeba evolution and host-parasite selection.

The study aims to clarify the mechanism in patients with neurally mediated syncope (NMS), focusing on the adenylate cyclase (AC) activity level in lymphocytes. This study included 40 subjects: 22 healthy volunteers and 18 NMS patients. We investigated the changes in AC activity that occur during of syncope at rest and during the head-up tilt (HUT) test. We obtained 8 mL of blood at rest time and four times during the HUT test. Then, we measured the AC activity and the test reagent was added to the lymphocytes (10,000) and reacted for 30 min at room temperature. We were able to determine the standard value of AC activity when adrenaline (AD) and isoproterenol (IP) were added to lymphocytes. The results of our study showed one of the causes of NMS has a difference in AC activity level and classification of the patients into two different types of NMS was possible: either the vasodepressor type (VT) or mixed type (MT). At rest time, VT patients showed significantly higher AC activity (AD; 100 μM: p = 0.005, IP; 50 μM: p = 0.02) and MT patients showed significantly lower AC activity (AD; 10 μM: p = 0.02, IP; 50 μM: p = 0.004) than the average AC activity in healthy volunteers. Moreover, VT patients had significantly higher AC activity than healthy volunteers at the four points of the HUT test. MT patients had significantly lower AC activity (AD: p = 0.04 and IP: p = 0.04) than healthy volunteers at the rest time of HUT. Our study showed a significant difference in AC activities between NMS patients and healthy volunteers at rest. Therefore, a detailed NMS diagnosis can be made by examining AC activity levels in blood taken at rest time.

Neural output from the locomotor system for each arm and leg influences the spinal motoneuronal pools directly and indirectly through interneuronal (IN) reflex networks. This review article mainly describes the recent findings concerning the existence, features and functions of common IN systems on spinal reflex pathways induced by multisensory inputs during human locomotion. In particular, we focus on regulation of polysynaptic cutaneous reflex pathways assessed by spatial facilitation. Furthermore, we provide evidence for activation of common presynaptic inhibitory INs that integrate locomotor-related commands and antagonist group Ia inputs. The experimental results are discussed in light of recent advances in motor control in humans and other animals with implications for locomotor rehabilitation.

It is unclear how descending inputs from the vestibular system affect the excitability of cervical interneurons in humans. To elucidate this, we investigated the effects of galvanic vestibular stimulation (GVS) on the spatial facilitation of motor-evoked potentials (MEPs) induced by combined pyramidal tract and peripheral nerve stimulation. To assess the spatial facilitation, electromyograms were recorded from the biceps brachii muscles (BB) of healthy subjects. Transcranial magnetic stimulation (TMS) over the contralateral primary motor cortex and electrical stimulation of the ipsilateral ulnar nerve at the wrist were delivered either separately or together, with interstimulus intervals of 10 ms (TMS behind). Anodal/cathodal GVS was randomly delivered with TMS and/or ulnar nerve stimulation. The combination of TMS and ulnar nerve stimulation facilitated BB MEPs significantly more than the algebraic summation of responses induced separately by TMS and ulnar nerve stimulation (i.e., spatial facilitation). MEP facilitation significantly increased when combined stimulation was delivered with GVS (p < 0.01). No significant differences were found between anodal and cathodal GVS. Furthermore, single motor unit recordings showed that the short-latency excitatory peak in peri-stimulus time histograms during combined stimulation increased significantly with GVS. The spatial facilitatory effects of combined stimulation with short interstimulus intervals (i.e., 10 ms) indicate that facilitation occurred at the premotoneuronal level in the cervical cord. The present findings therefore suggest that GVS facilitates the cervical interneuron system that integrates inputs from the pyramidal tract and peripheral nerves and excites motoneurons innervating the arm muscles.

Corticospinal excitability is known to be modulated during voluntary muscle contraction of distal limbs. Although a large number of studies have demonstrated the variety of modulations in corticospinal excitability during distal limb movement, those interlimb neural interactions in corticospinal excitability have not been fully understood. Here, we mainly review previous studies that used transcranial magnetic stimulation (TMS) to report the modulation of corticospinal excitability during distal limb movement, and discuss related neural mechanisms and functional implications. Corticospinal modulation, produced across the limbs, was observed regardless of the combination of limbs (i.e., upper limbs, upper and lower limbs, and lower limbs). The pattern of modulation depended on the strength and the modality of muscle contraction in the active limb. Discrete forceful isometric contraction tended to facilitate corticospinal excitability in the tested muscle of the opposite limb. However, isotonic muscle contraction tended to show suppression or movement phase-locked specific facilitation. In association with the involvement of modulation in spinal motoneuronal and intracortical motor circuitry, it was suggested that different neural mechanisms mediate each pattern of corticospinal modulation.

In the present study, the aim was to determine whether a history of ankle sprain during the junior (JUN; age < 12 years) playing years of soccer players could predict the occurrence of ankle sprain in their junior youth (JY; age < 13, 14, and 15 years) playing years. Therefore, we administered a questionnaire survey to 1,361 players belonging to 28 JY soccer teams. Analyses of the participants’ answers indicated that 57.0% of the players sustained ankle sprains during their JUN playing years and 64.0% of the players sustained ankle sprains during their JUN and JY playing years. Players with a history of ≥5 ankle sprains had a higher occurrence rate of sprains in their JY years as compared to players with no history of ankle sprains. The odds ratio (OR), calculated using logistic regression analysis based on the number of ankle sprains sustained during the JUN playing years, was highest for players with ≥5 sprains compared to those with 2 or 3 sprains during the JUN playing years. To reduce the occurrence rate of ankle sprains for players in the JY category, effective screening processes, prevention measures, and rehabilitation programs for ankle sprains during the JUN playing years should be established.

The Hoffmann (H-) reflex can be depressed when elicited repetitively at a frequency of ~1 Hz. This H-reflex depression is termed homosynaptic depression (HD) and is attributed to impaired neurotransmitter release from the presynaptic Ia terminal. In the present study, we systematically evaluated the extent to which HD in the soleus was modulated by the level of homonymous muscle contraction and the size of the test H-reflex. Changes in HD were also assessed while the target muscle was subjected to fatigue. The participants were 11 healthy male volunteers aged 20−25 years. HD was induced by delivering a percutaneous electrical stimulus at 1 Hz to the right posterior peroneal nerve. HD was proportional to the size of the test reflex size up to 60% of the maximum size of the direct motor response (Mmax), at which point values plateaued. HD decreased significantly during voluntary contraction of the homonymous muscle (range,

Both active and passive rhythmic limb movements reduce the amplitude of spinal cord Hoffmann (H-) reflexes in muscles of moving and distant limbs. This could have clinical utility in remote modulation of the pathologically hyperactive reflexes found in spasticity after stroke or spinal cord injury. However, such clinical translation is currently hampered by a lack of critical information regarding the minimum or effective duration of passive movement needed for modulating spinal cord excitability. We therefore investigated the H-reflex modulation in the flexor carpi radialis (FCR) muscle during and after various durations (5, 10, 15, and 30 min) of passive stepping in 11 neurologically normal subjects. Passive stepping was performed by a robotic gait trainer system (Lokomat®) while a single pulse of electrical stimulation to the median nerve elicited H-reflexes in the FCR. The amplitude of the FCR H-reflex was significantly suppressed during passive stepping. Although 30 minutes of passive stepping was sufficient to elicit a persistent H-reflex suppression that lasted up to 15 minutes, 5 minutes of passive stepping was not. The duration of H-reflex suppression correlated with that of the stepping. These findings suggest that the accumulation of stepping-related afferent feedback from the leg plays a role in generating short-term interlimb plasticity in the circuitry of the FCR H-reflex.

For many locomotor behaviors, such as walking or running, we count on subliminal somatosensory information to smoothly maintain on-going movement and avoid falling down when disturbances are presented to the stability of the body. Reflex responses induced by disturbances to stability play important roles in generating quick corrective responses. Reflex outputs to the arm and leg muscles generated by muscle and cutaneous afferents during locomotor movement show quite different features compared to those generated by simple voluntary contraction during sitting or standing, irrespective of the similar background activity of motoneurons. In particular, the excitability of cutaneous reflex pathways elicited by the electrical stimulation of low threshold mechanoreceptors on the skin is strongly modulated in a phase-, nerve-, task-dependent manner during locomotor movement. The pattern generating system in the spinal cord, which has been studied intensively in quadrupedal animals, may be responsible for both generating locomotor movement and reflex modulation even in humans. However, due to methodological difficulties, the accumulated evidence derived from human experiments is indirect. In this review, we will outline these unique features of the cutaneous reflexes during locomotor and rhythmic movements in humans.

The objective of this study was to clarify the effects of disease on neurally mediated syncope (NMS) during an acute stress reaction. We analyzed the mechanism of the molecular interaction and the polymorphisms of the alpha-2 adrenoreceptor (α2B-AR) gene as the potential psychiatric cause of incentive stress. We focused on the following three genotypes of the repeat polymorphism site at Glu 301-303 in the α2B-AR gene: Glu12/12, Glu12/9, and Glu9/9. On the basis of our clinical research, NMS is likely to occur in people with the Glu12/9 heterotype. To verify this, we assessed this relationship with the interaction of Gi protein and adenylate cyclase by in silico analysis of the Glu12/9 heterotype. By measuring the difference in the dissociation time of the Gi-α subunit twice, we found that the Glu12/9 heterotype suppressed the action of adenylate cyclase longer than the Glu homotypes. As this difference in the Glu repeat number effect is thought to be one of the causes of NMS, we investigated the evolutionary significance of the Glu repeat number. Glu8 was originally repeated in simians, while the Glu12 repeats occurred over time during the evolution of bipedalism in humans. Taken with the Glu12 numbers, NMS would likely become a defensive measure to prevent significant blood flow to the human brain.

The chicken domestication process represents a typical model of artificial selection, and gives significant insight into the general understanding of the influence of artificial selection on recognizable phenotypes. Two Japanese domesticated chicken varieties, the fighting cock (Shamo) and the long-crowing chicken (Naganakidori), have been selectively bred for dramatically different phenotypes. The former has been selected exclusively for aggressiveness and the latter for long crowing with an obedient sitting posture. To understand the particular mechanism behind these genetic changes during domestication, we investigated the degree of genetic differentiation in the aforementioned chickens, focusing on dopamine receptor D2, D3, and D4 genes. We studied other ornamental chickens such as Chabo chickens as a reference for comparison. When genetic differentiation was measured by an index of nucleotide differentiation (NST) newly devised in this study, we found that the NST value of DRD4 for Shamo (0.072) was distinctively larger than those of the other genes among the three populations, suggesting that aggressiveness has been selected for in Shamo by collecting a variety of single nucleotide polymorphisms. In addition, we found that in DRD4 in Naganakidori, there is a deletion variant of one proline at the 24th residue in the repeat of nine prolines of exon 1. We thus conclude that artificial selection has operated on these different kinds of genetic variation in the DRD4 genes of Shamo and Naganakidori so strongly that the two domesticated varieties have differentiated to obtain their present opposite features in a relatively short period of time.

Neural output from the locomotor system for each arm and leg influences the spinal motoneuronal pools directly and indirectly through interneuronal (IN) reflex networks. While well documented in other species, less is known about the functions and features of convergence in common IN reflex system from cutaneous afferents innervating different foot regions during remote arm and leg movement in humans. The purpose of the present study was to use spatial facilitation to examine possible convergence in common reflex pathways during rhythmic locomotor limb movements. Cutaneous reflexes were evoked in ipsilateral tibialis anterior muscle by stimulating (in random order) the sural nerve (SUR), the distal tibial nerve (TIB), and combined simultaneous stimulation of both nerves (TIB&SUR). Reflexes were evoked while participants performed rhythmic stepping and arm swinging movement with both arms and the leg contralateral to stimulation (ARM&LEG), with just arm movement (ARM) and with just contralateral leg movement (LEG). Stimulation intensities were just below threshold for evoking early latency (

Presynaptic inhibition of transmission between Ia afferent terminals and alpha motoneurons (Ia PSI) is a major control mechanism associated with soleus H-reflex modulation during human locomotion. Rhythmic arm cycling suppresses soleus H-reflex amplitude by increasing segmental Ia PSI. There is a reciprocal organization in the human nervous system such that arm cycling modulates H-reflexes in leg muscles and leg cycling modulates H-reflexes in forearm muscles. However, comparatively little is known about mechanisms subserving the effects from leg to arm. Using a conditioning-test (C-T) stimulation paradigm, the purpose of this study was to test the hypothesis that changes in Ia PSI underlie the modulation of H-reflexes in forearm flexor muscles during leg cycling. Subjects performed leg cycling and static activation while H-reflexes were evoked in forearm flexor muscles. H-reflexes were conditioned with either electrical stimuli to the radial nerve (to increase Ia PSI; C-T interval = 20 ms) or to the superficial radial (SR) nerve (to reduce Ia PSI; C-T interval = 37-47 ms). While stationary, H-reflex amplitudes were significantly suppressed by radial nerve conditioning and facilitated by SR nerve conditioning. Leg cycling suppressed H-reflex amplitudes and the amount of this suppression was increased with radial nerve conditioning. SR conditioning stimulation removed the suppression of H-reflex amplitude resulting from leg cycling. Interestingly, these effects and interactions on H-reflex amplitudes were observed with subthreshold conditioning stimulus intensities (radial n., ∼0.6×MT; SR n., ∼ perceptual threshold) that did not have clear post synaptic effects. That is, did not evoke reflexes in the surface EMG of forearm flexor muscles. We conclude that the interaction between leg cycling and somatosensory conditioning of forearm H-reflex amplitudes is mediated by modulation of Ia PSI pathways. Overall our results support a conservation of neural control mechanisms between the arms and legs during locomotor behaviors in humans.