Neurokinin 3 receptor-selective agonist, senktide, decreases core temperature in Japanese Black cattle.

Heat stress disrupts reproductive function in cattle. In summer, high ambient temperature and humidity elevate core body temperature, which is considered to be detrimental to reproductive abilities in cattle. Neurokinin B (NKB) is a factor that generates pulsatile GnRH and subsequent LH secretion in mammals. Recent studies have reported that NKB-neurokinin 3 receptor (NK3R) signaling is associated with heat-defense responses in rodents. The present study aimed to clarify the role of NKB-NK3R signaling in thermoregulation in cattle. We examined the effects of an NK3R-selective agonist, senktide, on vaginal temperature as an indicator of core body temperature in winter and summer. In both seasons, continuous infusion of senktide for 4 h immediately decreased vaginal temperature, and the mean temperature change in the senktide-treated group was significantly lower than that of both vehicle- and GnRH-treated groups. Administration of GnRH induced LH elevation, but there was no significant difference in vaginal temperature change between GnRH- and vehicle-treated groups. Moreover, we investigated the effects of senktide on ovarian temperature. Senktide treatment seemed to suppress the increase in ovarian temperature from 2 h after the beginning of administration, although the difference between groups was not statistically significant. Taken together, these results suggest that senktide infusion caused a decline in the vaginal temperature of cattle, in both winter and summer seasons, and this effect was not due to the gonadotropin-releasing action of senktide. These findings provide new therapeutic options for senktide to support both heat-defense responses and GnRH/LH pulse generation.

Neutron-induced signal on the single crystal chemical vapor deposition diamond-based neutral particle analyzer.

A diamond-based neutral particle analyzer (DNPA) array composed of single-crystal chemical vapor deposition (sCVD) diamond detectors was installed on the Large Helical Device (LHD) for measuring the helically trapped energetic particles. In high neutron flux experiments, the unwanted neutron-induced pulse counting rate should be estimated using the neutron diagnostics because a diamond detector is sensitive to neutrons as well as energetic neutral particles. In order to evaluate the quantitative neutron-induced pulse counting rate on the DNPA, the response functions of the sCVD diamond detector for mono-energetic neutrons were obtained using accelerator-based D-D and D-7Li neutron sources in Fast Neutron Laboratory (FNL). As a result of the neutron flux estimation by the Monte Carlo N-Particle code at the NPA position in the LHD and the response function obtained in the FNL experiment, the counting rate of the neutron-induced signal was predicted to be 1.1 kcps for the source neutron emission rate of Sn = 1 × 1015 n/s. In the LHD experiment, the neutron-induced signals were observed by closing the gate valve during the plasma discharges. It is found that the counting rates of the neutron-induced signals proportional to Sn reached 1.1 kcps at Sn = 1 × 1015 n/s. As a result of the quantitative estimation of the neutron-induced signals on the DNPA using other neutron measurements, it has become possible to accurately measure energetic neutral particles in the high neutron flux experiment.

Differences between primary care physicians and specialised neurotologists in the diagnosis of dizziness and vertigo in Japan.

OBJECTIVE: Vertigo and dizziness are frequent symptoms in patients at out-patient services. An accurate diagnosis for vertigo or dizziness is essential for symptom relief; however, it is often challenging. This study aimed to identify differences in diagnoses between primary-care physicians and specialised neurotologists. METHOD: In total, 217 patients were enrolled. To compare diagnoses, data was collected from the reference letters of primary-care physicians, medical questionnaires completed by patients and medical records. RESULTS: In total, 62.2 per cent and 29.5 per cent of the patients were referred by otorhinolaryngologists and internists, respectively. The cause of vertigo or dizziness and diagnosis was missing in 47.0 per cent of the reference letters. In addition, 67.3 per cent of the diagnoses by previous physicians differed from those reported by specialised neurotologists. CONCLUSION: To ensure patient satisfaction and high quality of life, an accurate diagnosis for vertigo or dizziness is required; therefore, methods or materials to improve the diagnostic accuracy are needed.

Design optimization of a fast-neutron detector with scintillating fibers for triton burnup experiments at fusion experimental devices.

Time-resolved triton burnup studies have been carried out to estimate the behavior of alpha particles in DD fusion experimental devices. In those studies, 14 MeV neutrons emitted through DT reactions in DD plasmas should be measured selectively in the backgrounds of DD neutrons and gamma rays. For this purpose, a scintillating-fiber (Sci-Fi) based fast-neutron detector has been adapted because of its advantages such as fast response, design flexibility in detection efficiency by changing the number of Sci-Fi, and discrimination property against 2.4 MeV neutrons produced through DD reactions and gamma rays. However, its length had conventionally been set to around 10 cm without an optimization study of its design parameters to meet the requirements as 14 MeV neutron detector. In the present study, we tested three types of Sci-Fi detectors with three different lengths and compared with the simulated results of energy deposition, through which we tried to understand the phenomena in the detection process of fast neutrons. From the results, it has been shown that, due to the self-shielding of neutrons by Sci-Fi and the attenuation of scintillation photons during the transmission process to the photomultiplier tube, the optimal length of Sci-Fi is concluded to be about 6 cm.

Nanofocusing of X-ray free-electron laser using wavefront-corrected multilayer focusing mirrors.

A method of fabricating multilayer focusing mirrors that can focus X-rays down to 10 nm or less was established in this study. The wavefront aberration induced by multilayer Kirkpatrick-Baez mirror optics was measured using a single grating interferometer at a photon energy of 9.1 keV at SPring-8 Angstrom Compact Free Electron Laser (SACLA), and the mirror shape was then directly corrected by employing a differential deposition method. The accuracies of these processes were carefully investigated, considering the accuracy required for diffraction-limited focusing. The wavefront produced by the corrected multilayer focusing mirrors was characterized again in the same manner, revealing that the root mean square of the wavefront aberration was improved from 2.7 (3.3) rad to 0.52 (0.82) rad in the vertical (horizontal) direction. A wave-optical simulator indicated that these wavefront-corrected multilayer focusing mirrors are capable of achieving sub-10-nm X-ray focusing.

Seven Japanese Herbals Prolonged Cardiac Allograft Survival.

Japanese herbal medicines have long been used as alternative therapy because of their immunomodulatory effects. In recent years, use herbal medicines is rapidly increasing worldwide. In this study, we investigated the effect of 17 components of traditional Japanese herbal medicines on alloimmune responses in a murine model of cardiac allograft transplantation. Fully vascularized heterotopic hearts from C57BL/6 donors were transplanted into CBA mice by using microsurgical techniques. Artemisiae capillaris herba (Inchinko) was given to CBA recipients at a dosage of 1 g/kg/day from the day of transplantation until 7 days afterward. The other 16 components were given at a dosage of 2 g/kg/day for the same time period. Naïve CBA mice rejected C57BL/6 cardiac grafts acutely (median survival time [MST] of 7 days). CBA transplant recipients given 2 g/kg/day of Glycyrrhizae radix (Kanzou), Poria sclerotium (Bukuryo), Pinellia tuber (Hange), Cnidii rhizome (Senkyu), Paeoniae radix (Shakuyaku), and Scutellariae radix (Ogon) had prolonged C57BL/6 allograft survival significantly (MSTs were 18, 18, 17, 14, 12, and 12 days, respectively). Moreover, CBA transplant recipients given 1g/kg/day of Artemisiae capillaris herba had prolonged C57BL/6 allograft survival (MST >100 days); however, none of other 10 components prolonged allograft survival. In conclusion, administration of 7 components of traditional Japanese herbal medicines might induce prolongation of fully major histocompatibility complex-mismatched cardiac allografts.

Administration of Thrombomodulin (CD141) Could Improve Cardiac Allograft Survival in Mice.

Thrombomodulin (TM) is a promising natural anti-coagulant therapeutic protein that is effective in the treatment of disseminated intravascular coagulation. However, the mechanisms by which TM on micro-vessels enable the regulation of intimal hyperplasia remain elusive. We investigated the graft-protective effects of TM in a fully major histocompatibility complex-mismatched murine cardiac allograft transplantation model. CBA recipients transplanted with a C57BL/6 heart received intraperitoneal administration of 0.2, 2.0, and 20.0 µg/day of TM for 8 days. Histological staining was conducted to assess the degree of inflammation and infiltration in the transplanted cardiac grafts. Untreated CBA recipients rejected C57BL/6 cardiac grafts acutely (median survival time [MST] was 7 days). CBA recipients exposed to the above dosages had significantly prolonged allograft survival (MSTs were 16, 21, and 37.5 days, respectively). Histologic assessments from TM-exposed recipients 2 weeks after grafting showed that the myocardium and vessel structure in their allografts were clearly preserved, and that the infiltration of inflammatory cells around coronary arteries was suppressed. TM can induce the prolongation of fully major histocompatibility complex-mismatched cardiac allograft by exerting graft protective effects within the myocardium and coronary arteries.

Acquired undescended testis and possibly associated testicular torsion in children with cerebral palsy or neuromuscular disease.

INTRODUCTION: Torsion of an undescended testis (UDT) associated with cerebral palsy (CP) and neuromuscular disease (NMD) is an uncommon condition that is not well recognized by primary care physicians or healthcare providers. OBJECTIVE: The objective of this study was to highlight the clinical importance of torsion of a UDT in children with CP and NMD. MATERIALS AND METHODS: Eleven children with testicular torsion of a UDT operated on at the study institute between 1991 and 2015 were identified. The records of seven children (63.6%) associated with CP or NMD were retrospectively reviewed. Clinical findings of testicular torsion were assessed along with the treatment outcome and testicular salvageability. RESULTS: All seven children were not identified with a UDT by public health checkup for infant and young children. No children with CP or NMD had torsion of a descended testis during the present study period. Median age at surgery was 15 years (range, 1-20 years). The testis location was at the external inguinal ring in five patients, in the inguinal canal in one, and in the superficial inguinal pouch in one. Of the contralateral testes, four were a UDT, one was a retractile testis, and two were descended testes. Orchiectomy was performed in six patients (85.7%). In the remaining patients, the testis was preserved but became atrophic. DISCUSSION: This study demonstrated that children with CP or NMD may be affected with torsion of a UDT with peak at around puberty with the poor salvage rate, even if the testes appear descended in infancy and young children. Shortcomings of this study were the retrospective design and a small series of children undergoing surgery for torsion of a UDT. CONCLUSION: Pediatric urologists need to educate primary care physicians and healthcare providers in the recognition of acquired UDTs and possibly associated testicular torsion in children with CP and NMD. Genital examination should be continued regularly until adolescence in these children to detect acquired UDT. These children should be referred to pediatric urologists to promote surgery as soon as the diagnosis of acquired UDT is carried out. It is believed that it is perhaps the best approach to prevent loss of the testis in children with CP and NMD.

Yogurt Feeding Induced the Prolongation of Fully Major Histocompatibility Complex-Mismatched Murine Cardiac Graft Survival by Induction of CD4+Foxp3+ Cells.

Yogurt is a nutrient-rich food and the beneficial effects of yogurt on both health and immunomodulatory effects are well documented. In this pilot study, we investigated the effects of commercially produced yogurt R-1 on alloimmune responses in a murine cardiac transplantation model. The R-1 is produced by Meiji Co., Ltd., and contains live and active lactic acid bacteria (lactobacillus bulgaricus OLL1073R-1) mainly. CBA (H2k) mice underwent transplantation of a C57BL/6 (H2b; B6) heart and received oral administration of 1 mL, 0.1 mL, and 0.01 mL of R-1 from the day of transplantation until 7 days afterward. Additionally, we prepared one group of CBA recipients given 1 mL of R-1 sterilized by microwave for 7 days. Histological and immunohistochemical studies were performed. Naïve CBA mice rejected B6 cardiac graft acutely (median survival time [MST]: 7 days). CBA recipients given of 1 mL of R-1 had significantly prolonged B6 allograft survival (MST, 27 days). However, other doses of 0.1 mL and 0.01 mL of R-1 did not prolonged allograft survival (MSTs, 9 days and 8.5 days, respectively). Also, CBA recipients administered microwaved R-1 had no prolongation of B6 allograft (MST, 9 days). Histological and immunohistochemical studies showed the cardiac allograft from R-1-exposed CBA recipients had preserved graft and vessel structure and the number of infiltrated CD4+, CD8+, and Foxp3+ cells in R-1-exposed CBA recipients increased, respectively. In conclusion, our findings imply that yogurt containing active lactic acid bacteria could change alloimmune responses partially and induce the prolongation of cardiac allograft survival via CD4+Foxp3+ regulatory cells.

Chemical etching of silicon carbide in pure water by using platinum catalyst.

Chemical etching of SiC was found to proceed in pure water with the assistance of a Pt catalyst. A 4H-SiC (0001) wafer was placed and slid on a polishing pad in pure water, on which a thin Pt film was deposited to give a catalytic nature. Etching of the wafer surface was observed to remove protrusions preferentially by interacting with the Pt film more frequently, thus flattening the surface. In the case of an on-axis wafer, a crystallographically ordered surface was obtained with a straight step-and-terrace structure, the height of which corresponds to that of an atomic bilayer of Si and C. The etching rate depended upon the electrochemical potential of Pt. The vicinal surface was observed at the potential at which the Pt surface was bare. The primary etching mechanism was hydrolysis with the assistance of a Pt catalyst. This method can, therefore, be used as an environmentally friendly and sustainable technology.

Development of array-type atmospheric-pressure RF plasma generator with electric on-off control for high-throughput numerically controlled processes.

An array-type atmospheric-pressure radio-frequency (RF) plasma generator is proposed for high-precision and high-throughput numerically controlled (NC) processes. We propose the use of a metal-oxide-semiconductor field-effect transistor (MOSFET) circuit for direct RF switching to achieve plasma on-off control. We confirmed that this type of circuit works correctly using a MOSFET with a small parasitic capacitance between its source and gate. We examined the design method for the distance between adjacent electrodes, which corresponds to the parasitic capacitance between adjacent electrodes and is very important in the individual on-off control of each electrode. We developed a prototype array-type plasma generator apparatus with 19 electrodes and the same number of MOSFET circuits; we then confirmed that each electrode could control its plasma on-off state individually. We also demonstrated that the thickness uniformity of the surface Si layer of a silicon-on-insulator wafer could be processed to less than 1 nm peak to valley by the NC sacrificial oxidation method using the apparatus.

Bax deficiency extends the survival of Ku70 knockout mice that develop lung and heart diseases.

Ku70 (Lupus Ku autoantigen p70) is essential in nonhomologous end joining DNA double-strand break repair, and ku70(-/-) mice age prematurely because of increased genomic instability and DNA damage responses. Previously, we found that Ku70 also inhibits Bax, a key mediator of apoptosis. We hypothesized that Bax-mediated apoptosis would be enhanced in the absence of Ku70 and contribute to premature death observed in ku70(-/-) mice. Here, we show that ku70(-/-) bax(+/-) and ku70(-/-) bax(-/-) mice have better survival, especially in females, than ku70(-/-) mice, even though Bax deficiency did not decrease the incidence of lymphoma observed in a Ku70-null background. Moreover, we found that ku70(-/-) mice develop lung diseases, like emphysema and pulmonary arterial (PA) occlusion, by 3 months of age. These lung abnormalities can trigger secondary health problems such as heart failure that may account for the poor survival of ku70(-/-) mice. Importantly, Bax deficiency appeared to delay the development of emphysema. This study suggests that enhanced Bax activity exacerbates the negative impact of Ku70 deletion. Furthermore, the underlying mechanisms of emphysema and pulmonary hypertension due to PA occlusion are not well understood, and therefore ku70(-/-) and Bax-deficient ku70(-/-) mice may be useful models to study these diseases.

Inhibition of Bax protects neuronal cells from oligomeric Aß neurotoxicity.

Although oligomeric ß-amyloid (Aß) has been suggested to have an important role in Alzheimer disease (AD), the mechanism(s) of how Aß induces neuronal cell death has not been fully identified. The balance of pro- and anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2 and Bcl-w versus Bad, Bim and Bax) has been known to have a role in neuronal cell death and, importantly, expression levels of these proteins are reportedly altered in the vulnerable neurons in AD. However, the roles of apoptotic proteins in oligomeric Aß-induced cell death remain unclear in vivo or in more physiologically relevant models. In addition, no study to date has examined whether Bax is required for the toxicity of oligomeric Aß. Here, we found that treatment with oligomeric Aß increased Bim levels but decreased Bcl-2 levels, leading to the activation of Bax and neuronal cell death in hippocampal slice culture and in vivo. Furthermore, the inhibition of Bax activity either by Bax-inhibiting peptide or bax gene knockout significantly prevented oligomeric Aß-induced neuronal cell death. These findings are first to demonstrate that Bax has an essential role in oligomeric Aß-induced neuronal cell death, and that the targeting of Bax may be a therapeutic approach for AD.

[Newly developed method of computed tomography scanning to obtain three-dimensional graphics for supporting pulmonary resection].

To acquire the pulmonary artery (PA) and pulmonary vein (PV) image separately, we scanned PA phase while X-ray source moved caudal direction, followed by continuous scan of PV phase by moving back reverse direction. We assessed some scanning conditions to shorten scanning time and determined the starting time for scanning to obtain the maximum intensity difference of radio-opaque contrast between PA and PV phase. Additional infusion of normal saline was followed after contrast medium administration. Finally, scanning could be finished almost 10 seconds with only 20 ml contrast medium for establish three-dimensional (3D) images of pulmonary vessels, and the residual contrast medium could be used for consecutive usual preoperative computed tomography (CT). Twenty-three patients who underwent lung resection were assessed their preoperative 3D-CT images using 5-point scale; 5 and 4 as good, 3 as fair, 2 and 1 as poor. As a result, 18 (78.3%) and 1 (4.3%) were categorized as good and poor, respectively. We successfully decreased the frequency of CT and contrast agent dose for 3D-CT in patients being scheduled for lung resection by the new methods reported herein. Additionally, the workload of building up 3D-CT images by medical workers was also reduced.

One-dimensional Wolter optics with a sub-50 nm spatial resolution.

We studied an imaging system consisting of an elliptical mirror and a hyperbolic mirror [i.e., one-dimensional (1D) Wolter optics] to realize an achromatic full-field hard x-ray microscopy with a resolution better than 50 nm. We report the performance of this 1D Wolter optical system when the mirrors were ultraprecisely figured by elastic emission machining. Experiments to form a demagnified image (demagnification factor of 385) of a 10 µm slit were conducted at an x-ray energy of 11.5 keV at BL29XUL of SPring-8. The system could form a demagnified image with a resolution better than 50 nm over a 12.1 µm field.

Distribution of 16 EPA-priority polycyclic aromatic hydrocarbons (PAHs) in sludges collected from nine Tunisian wastewater treatment plants.

Polycyclic aromatic hydrocarbons (PAHs) are organic compounds which may be present as contaminants in wastewater sewage sludge. Due to their toxicity and persistence in the solid phase, information should be gathered relating to their presence in sewage sludge in order to determine their contamination risks after land application. In this study, sewage sludge samples from nine Tunisian wastewater treatment plants (WWTPs) were characterized for the total content in 16 EPA-priority PAHs using an optimized extraction protocol. These WWTPs differ in the type of applied treatment and the wastewater source. Through this first assessment of PAHs in Tunisian sludges, their total concentration varied from 96 to the highest level of 7718 ng g(-1). Regardless of the source of wastewater, the highest PAH content was found in sludges deriving from untreated wastewater (natural lagooning). In addition, some correlation was found between the distribution patterns of each PAH, the type of applied treatment on one hand and the wastewater source on other hand.

Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70.

BACKGROUND: Malignant T cells in primary cutaneous T-cell lymphoma (CTCL) are genetically unstable and exhibit prolonged lifespans potentially explained by dysregulation of apoptosis, yet are responsive to apoptosis-inducing therapies. The heterodimeric protein Ku70/80 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). OBJECTIVES: To investigate the expression of Ku70/80 in CD3+ T cells derived from skin and blood in patients with CTCL and normal samples, as well as benign dermatoses. METHODS: Normal (n=10), CTCL (n=9) and benign dermatoses (n=13) skin samples were stained for confocal imaging of Ku70/80 and CD3 and analysed using imaging software. Circulating CD4+ T cells in normal and CTCL peripheral blood were analysed by flow cytometry and Western blot for Ku70/80 expression (n=6). RESULTS: Ku70 and Ku80 were significantly diminished in T cells of CTCL lesions relative to T cells of control skin. Decreased T-cell Ku70 expression was not a feature of the benign dermatoses psoriasis and contact dermatitis, suggesting that loss of Ku70/80 in CTCL is not simply the result of cutaneous inflammation. Reduced Ku70 was also noted in circulating CD4+ T cells in patients with CTCL with peripheral blood involvement. CONCLUSIONS: Deficient expression or lack of Ku70/80 may result in genomic instability and play a role in tumorigenesis, as well as account for the increased susceptibility of malignant T cells to apoptosis-inducing treatment modalities in the setting of intrinsic resistance to apoptosis.

The anti-apoptotic function of human αA-crystallin is directly related to its chaperone activity.

αA-crystallin is a molecular chaperone and an antiapoptotic protein. This study investigated the mechanism of inhibition of apoptosis by human αA-crystallin and determined if the chaperone activity of αA-crystallin is required for the antiapoptotic function. αA-crystallin inhibited chemical-induced apoptosis in Chinese hamster ovary (CHO) cells and HeLa cells by inhibiting activation of caspase-3 and -9. In CHO cells, it inhibited apoptosis induced by the overexpression of human proapoptotic proteins, Bim and Bax. αA-crystallin inhibited doxorubicin-mediated activation of human procaspase-3 in CHO cells and it activated the PI3K/Akt cell survival pathway by promoting the phosphorylation of PDK1, Akt and phosphatase tensin homologue in HeLa cells. The phosphoinositide 3 kinase (PI3K) activity was increased by αA-crystallin overexpression but the protein content was unaltered. Downregulation of PI3K by the expression of a dominant-negative mutant or inhibition by LY294002 abrogated the ability of αA-crystallin to phosphorylate Akt. These antiapoptotic functions of αA-crystallin were enhanced in a mutant protein (R21A) that shows increased chaperone activity than the wild-type (Wt) protein. Interestingly, a mutant protein (R49A) that shows decreased chaperone activity was far weaker than the Wt protein in its antiapoptotic functions. Together, our study results show that αA-crystallin inhibits apoptosis by enhancing PI3K activity and inactivating phosphatase tensin homologue and that the antiapoptotic function is directly related to its chaperone activity.

Evaluation of the state-of-the-art measurement capabilities for selected PBDEs and decaBB in plastic by the international intercomparison CCQM-P114.

An international intercomparison involving eight national metrology institutes (NMIs) was conducted to establish their current measurement capabilities for determining five selected congeners from the brominated flame retardant classes polybrominated diphenyl ethers and polybrominated biphenyls. A candidate reference material consisting of polypropylene fortified with technical mixtures of penta-, octa- and decabromo diphenyl ether and decabromo biphenyl, which was thoroughly assessed for material homogeneity and stability, was used as study material. The analytical procedures applied by the participants differed with regard to sample pre-treatment, extraction, clean-up, employed calibrants and type of calibration procedure as well as regarding analytical methods used for separation, identification and quantification of the flame retardant congeners (gas chromatography coupled to an electron capture detector (GC-ECD), gas chromatography-mass spectrometry in the electron ionisation mode (GC-EI-MS), gas chromatography-mass spectrometry in the electron capture negative ionisation mode (GC-ECNI-MS), and liquid chromatography-inductive coupled plasma-mass spectrometry (LC-ICP-MS)). The laboratory means agreed well with relative standard deviations of the mean of means of 1.9%, 4.8%, 5.5% and 5.4% for brominated diphenyl ether (BDE) 47, 183 and 209 and for the brominated biphenyl (BB) congener 209, respectively. For BDE 206, a relative standard deviation of 28.5% was obtained. For all five congeners, within-laboratory relative standard deviations of six measurements obtained under intermediate precision conditions were between 1% and 10%, and reported expanded measurements uncertainties typically ranged from 4% to 10% (8% to 14% for BDE 206). Furthermore, the results are in good agreement with those obtained in the characterization exercise for determining certified values for the flame retardant congeners in the same material. The results demonstrate the state-of-the-art measurement capabilities of NMIs for quantifying representative BDE congeners and BB 209 in a polymer. The outcome of this intercomparison (pilot study) in conjunction with possible improvements for employing exclusively calibrants with thoroughly assessed purity suggests that a key comparison aiming at underpinning calibration and measurement capability (CMC) claims of NMIs can be conducted.