Gonadotropin-inhibiting hormone (GnIH), observed in quail as a member of the RFamide neuropeptide family, suppresses luteinizing hormone (LH) secretion from the avian pituitary. Rats and cattle have ...an active gene of another member of the RFamide neuropeptide family, termed RFamide-related peptide-3 (RFRP-3), although bovine RFRP-3 is different from that of rats in both length and amino-acid sequence. A single injection of GnIH or RFRP-3 inhibited LH secretion in rodents, which continued for various periods. This study was conducted to evaluate the effects of bovine C-terminal octapeptide of RFRP-3 (RFRP-3-8) on LH secretion from cultured anterior pituitary (AP) cells of cattle, and the effects of RFRP-3-8 injections on pulsatile LH secretion in castrated male calves. The suppressive effect of RFRP-3-8 on LH secretion from AP cells was observed in the presence of gonadotropin-releasing hormone (GnRH), but not in the absence of GnRH in culture media. In another experiment collecting blood samples serially from castrated male calves with repeated intravenous injections of RFRP-3-8 (
n
=
6) or saline (
n
=
6), the RFRP-3-8 group showed suppressed LH pulse frequency during the injection period (
P
<
0.05); however, the RFRP-3-8 group showed no difference from the saline group in all measures of LH secretion in the postinjection period. In conclusion, our results suggested that RFRP-3-8 suppresses LH secretion from cultured AP cells, as well as LH pulse frequency in cattle.
Abstract
The Hitachi and Takahagi 32 m radio telescopes (former satellite communication antennas) were so upgraded as to work at 6, 8, and 22 GHz. We developed the receiver systems, IF systems, ...back-end systems (including samplers and recorders), and reference systems. We measured the performance of the antennas. The system temperature including the atmosphere toward the zenith,
$T_{\rm sys}^{\ast }$
, is measured to be ∼30–40 K for 6 GHz and ∼25–35 K for 8 GHz.
$T_{\rm sys}^{\ast }$
for 22 GHz is measured to be ∼40–100 K in winter and ∼150–500 K in summer seasons, respectively. The aperture efficiency is 55%–75% for Hitachi at 6 GHz and 8 GHz, and 55%–65% for Takahagi at 8 GHz. The beam sizes at 6 GHz and 8 GHz are ∼4
${^{\circ}_{.}}$
6 and ∼3
${^{\circ}_{.}}$
8, respectively. The side-lobe level is less than 3%–4% at 6 and 8 GHz. Pointing accuracy was measured to be better than ∼0
${^{\circ}_{.}}$
3 for Hitachi and ∼0
${^{\circ}_{.}}$
6 for Takahagi. We succeeded in VLBI observations in 2010 August, indicating good performance of the antenna. We started single-dish monitoring observations of 6.7 GHz methanol maser sources in 2012 December, and found several new sources showing short-term periodic variation of the flux density.
The human visual and somatosensory systems are interdependent. Using a visual subjective body-midline (SM) judgment task, we previously confirmed that pathologic pain and deafferentation can modify ...visuospatial perception, indicating that altered somatosensory experience can modify visual perception. Conversely, in the present study we investigated whether a change in visual experience can modify perception of pathologic pain.
We used prism adaptation (PA) to modify subjects' visual experience. Five patients with complex regional pain syndrome (CRPS) adapted to wedge prisms, producing a 20-degree visual displacement toward the unaffected side. Further, we used several types of prisms in a longitudinal single-case study. Wearing prismatic goggles, the subjects performed a target-pointing task once a day for 2 weeks. We evaluated pain intensity and visual SM judgment to measure the adaptive aftereffects at three time points: before PA (pre-test), immediately after the first PA exposure (IA-test), and after a 14-day sequence of PA exposure (post-test).
PA toward the unaffected side alleviated pathologic pain and other CRPS pathologic features, when measured at post-test. None of the IA-test results showed an analgesic effect. In the longitudinal study, sham PA and 5-degree PA did not produce any effects, and PA toward the affected side actually exacerbated the subjective pain.
Our findings suggest that vision can influence pathologic pain, and preliminarily suggest that prism adaptation has a direction-specific and reproducible effect on not only pathologic pain but also other CRPS pathologic features. Thus, prism adaptation may be a viable cognitive treatment for CRPS.
As an extension of our previous work, we investigate the dynamical instability against non-axisymmetric bar-mode deformations of differentially rotating stars in Newtonian gravity by varying the ...equations of state and velocity profiles. We performed the numerical simulation and the follow-up linear stability analysis by adopting polytropic equations of state with polytropic indices n= 1, 3/2 and 5/2, and with two types of angular velocity profiles (the so-called j-constant-like and Kepler-like laws). It is confirmed that rotating stars with a high degree of differential rotation are dynamically unstable against bar-mode deformation, even when the ratio of the kinetic energy to the gravitational potential energy β is of order 0.01. The criterion for the onset of bar-mode dynamical instability depends weakly on the polytropic index n and the angular velocity profile, as long as the degree of differential rotation is high. Gravitational waves from the final non-axisymmetric quasi-stationary states are calculated using the quadrupole formula. For proto-neutron stars of mass 1.4 M⊙, radius ∼30 km and β≲ 0.1, such gravitational waves have a frequency of ∼600–1400 Hz, and the effective amplitude is larger than 10−22 at a distance of about 100 Mpc, irrespective of n and the angular velocity profile.
Multiepoch phase-referencing VLBI (Very Long Baseline Interferometry) observations with VERA (VLBI Exploration of Radio Astrometry) were performed for the symbiotic star R Aquarii (R Aqr) from 2005 ...September to 2006 October. Tracing one of the v = 2, J = 1–0 SiO maser spots, we measured an annual parallax of π = 4.59 ± 0.24 mas, corresponding to a distance of
$218_{-11}^{+12}\:$
pc. Our result is consistent with earlier distance measurements, but yields the highest accuracy of ∼ 5% level. Applying our distance, we derived an absolute K-band magnitude of M
K = −7.71 ± 0.11, which is consistent with the recent period–luminosity relation by VLBI parallax measurements for five OH-Mira variables. In addition, the expansion age of an inner nebula around R Aqr is found to be ∼ 240 yr, corresponding to about the year 1773.
Abstract l -glutamate, an umami taste substance, is a key molecule coupled to a food intake signaling pathway. Furthermore, recent studies have unveiled new roles for dietary glutamate on gut-brain ...axis communication via activation of gut glutamate receptors and subsequent vagus nerve. In the present study, we mapped activation sites of the rat forebrain after intragastric load of 60 mM monosodium l- glutamate (MSG) by measurement of Fos protein, a functional marker of neuronal activation. The same concentration of d -glucose (sweet) and NaCl (salty) was used as controls. MSG administration exclusively produced enhanced Fos expression in four hypothalamic regions (the medial preoptic area, lateral hypothalamic area, dorsomedial nucleus, and arcuate nucleus). On the other hand, glucose administration exclusively enhanced Fos induction in the nucleus accumbens. Both MSG and glucose enhanced Fos induction in three brain regions (the habenular nucleus, paraventricular nucleus, and central nucleus of the amygdala). However, MSG induced Fos inductions were more potent than those of glucose in the habenular nucleus and paraventricular nucleus. Importantly, the present study identified for the first time two brain areas (the paraventricular and arcuate hypothalamic nuclei) that are more potently activated by intragastric MSG loads compared with glucose and NaCl. Overall, our results suggest significant activation of a neural network comprising the habenular nucleus, amygdala, and the hypothalamic subnuclei following intragastric load with glutamate.
The 5' flanking region of the C3(1) component of the rat prostate steroid binding protein (PSBP) has been used to successfully target the expression of the SV40 large T-antigen (Tag) to the ...epithelium of both the mammary and prostate glands resulting in models of mammary and prostate cancers which histologically resemble the human diseases. Atypia of the mammary ductal epithelium develops at about 8 weeks of age, progressing to mammary intraepithelial neoplasia (resembling human ductal carcinoma in situ DCIS) at about 12 weeks of age with the development of invasive carcinomas at about 16 weeks of age in 100% of female mice. The carcinomas share features to what has been classified in human breast cancer as infiltrating ductal carcinomas. All FVB/N female mice carrying the transgene develop mammary cancer with about a 15% incidence of lung metastases. Approximately 10% of older male mice develop anaplastic mammary carcinomas. Unlike many other transgenic models in which hormones and pregnancy are used to induce a mammary phenotype, C3(1)/Tag mice develop mammary tumors in the mammary epithelium of virgin animals without hormone supplementation or pregnancy. Although mammary tumor development appears hormone-responsive at early stages, invasive carcinomas are hormone-independent, which corresponds to the loss of estrogen receptor-alpha expression during tumor progression. Molecular and biologic factors related to mammary tumor progression can be studied in this model since lesions evolve over a predictable time course. Genomic alterations have been identified during tumor progression, including an amplification of the distal portion of chromosome 6 containing ki-ras and loss of heterozygosity (LOH) in other chromosomal regions. We have demonstrated that stage specific alterations in the expression of genes which are critical regulators of the cell cycle and apoptosis are functionally important in vivo. C3(1)/Tag mice appear useful for testing particular therapies since growth of the mammary tumors can be reduced using chemopreventive agents, cytokines, and an anti-angiogenesis agent.
Wilson disease (WD) is characterized by hepatic copper accumulation with progressive liver damage to cirrhosis. This study aimed to characterize the toxic milk mouse from The Jackson Laboratory (Bar ...Harbor, ME, USA) (tx-j) mouse model of WD according to changes over time in hepatic copper concentrations, methionine metabolism, global DNA methylation, and gene expression from gestational day 17 (fetal) to adulthood (28 weeks).
Included liver histology and relevant biochemical analyses including hepatic copper quantification, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) liver levels, qPCR for transcript levels of genes relevant to methionine metabolism and liver damage, and DNA dot blot for global DNA methylation.
Hepatic copper was lower in tx-j fetuses but higher in weanling (three weeks) and adult tx-j mice compared to controls. S-adenosylhomocysteinase transcript levels were significantly lower at all time points, except at three weeks, correlating negatively with copper levels and with consequent changes in the SAM:SAH methylation ratio and global DNA methylation.
Compared to controls, methionine metabolism including S-adenosylhomocysteinase gene expression is persistently different in the tx-j mice with consequent alterations in global DNA methylation in more advanced stages of liver disease. The inhibitory effect of copper accumulation on S-adenosylhomocysteinase expression is associated with progressively abnormal methionine metabolism and decreased methylation capacity and DNA global methylation.
Evaluate changes from baseline in health-related quality of life (QoL) in Japanese patients with episodic migraine receiving preventive treatment with galcanezumab (GMB).
Preventive treatments for ...migraine have been shown to improve QoL, but few clinical trials have examined QoL outcomes in Japanese patients. This phase 2, randomized, double-blind, placebo-controlled study was conducted at 40 centers in Japan. Patients aged 18-65 years with episodic migraine (4-14 monthly migraine headache days) received GMB 120 mg (n=115), 240 mg (n=114), or placebo (PBO, n=230) as monthly subcutaneous injections for 6 months. QoL was measured monthly using the Migraine-Specific Quality-of-Life Questionnaire (MSQ) version 2.1. Prespecified analyses were differences between GMB and PBO for change from baseline in all 3 domains of the MSQ and MSQ-Total, for each month and the average over Months 4-6.
Treatment with GMB significantly increased MSQ scores from baseline vs PBO. Average change ± SE from baseline across Months 4-6 was 10.12±0.72 (PBO), 17.13±1.03 (GMB 120 mg;
<0.001), and 15.91±1.03 (GMB 240 mg;
<0.001) for MSQ Role Function-Restrictive; 4.80±0.65 (PBO), 9.64±0.93 (GMB 120 mg;
<0.001), and 8.35±0.93 (GMB 240 mg;
<0.05) for MSQ Role Function-Preventive (MSQ-RFP); 3.46±0.77 (PBO), 10.04±1.10 (GMB 120 mg;
<0.001), and 7.73±1.10 (GMB 240 mg;
<0.05) for MSQ Emotional Function, and 7.14±0.67 (PBO), 13.46±0.95 (GMB 120 mg;
<0.001), and 11.98±0.95 (GMB 240 mg;
<0.001) for MSQ-Total. Significantly greater improvement in scores in all MSQ domains and MSQ-Total was observed for both GMB doses vs PBO at Month 1 and was maintained for Months 1-6 (excluding Month 5 for MSQ-RFP).
Preventive treatment with GMB 120 mg/240 mg improves MSQ scores in Japanese patients with episodic migraine. Improvements were seen within the first month and maintained for 6 months and are similar to those seen in global studies enrolling primarily Caucasian patients.
ClinicalTrials.gov, NCT02959177 (registered November 7, 2016).
Summary
Insulin‐like factor 3 (INSL3), previously called relaxin‐like factor, is essential for foetal testis descent and has been implicated in sperm production in adult males. This study ...investigated the role of INSL3 in sperm production by examining the effect of neutralising INSL3 by passive immunisation on testicular function and sperm output in boars. Six male Duroc boars were randomly assigned to passive immunisation and control groups (n = 3 each). The immunisation group was intravenously injected with an IgG fraction of anti‐INSL3 antibody developed against the B domain of INSL3 at 2‐week intervals from 21‐40 weeks of age. The control group was treated with normal IgG in the same manner. Antibody administration reduced testis weight and caused a fourfold increase in the frequency of apoptotic germ cells, which was associated with upregulation of the pro‐apoptotic caspase 3 and BAX, and downregulation of the anti‐apoptotic XIAP and BCL2, and a substantial marked reduction in sperm concentration. Neutralising INSL3 delivered by passive immunisation reduced testis weight and sperm concentration by inducing germ cell apoptosis, suggesting that INSL3 acts as a germ cell survival/anti‐apoptotic factor in the maintenance of sperm production.