Establishment of a patient-derived xenograft mouse model of pleomorphic leiomyosarcoma

Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately evaluate their efficacy, as well as the lack of an adequate technical protocol for efficient transplantation and engraftment of sarcoma specimens in patient-derived xenograft (PDX) models. Accordingly, in this study, we sought to identify the optimal type of sarcoma and develop a protocol for generating a PDX model. We characterized a PDX mouse model using histopathological and immunohistochemical analyses to determine whether it would show pathological characteristics similar to those of human sarcomas. We achieved engraftment of one of the 10 transplanted sarcoma specimens, the xenografted tumor of which exhibited massive proliferation. Histologically, the engrafted sarcoma foci resembled a primary tumor of pleomorphic leiomyosarcoma and maintained their histological structure in all passages. Moreover, immunohistochemical analysis revealed the expression of specific markers of differentiation to smooth muscle, which is consistent with the features of leiomyosarcoma. We thus demonstrated that our pleomorphic leiomyosarcoma PDX mouse model mimics at least one aspect of human sarcomas, and we believe that this model will facilitate the development of novel therapies for sarcomas.     

Natural occurrence of neoplastic lesions in young sprague-dawley rats

It is important for the assessment of toxicological effects of chemicals to know what kinds of neoplasms naturally occur in the early life of experimental animals. In the present study, we demonstrated spontaneous neoplasms in Sprague-Dawley rats used in 4-, 13- and 26-week toxicity studies conducted at Bozo Research Center in the last decade. The tumors, which were first observed in 19-week-old animals, included anterior adenoma of the pituitary, follicular cell adenocarcinoma and C cell adenoma of the thyroids, nephroblastoma of the kidneys, basal cell tumor of the skin and malignant lymphoma. Thereafter, hemangiosarcoma of the tongue, adenocarcinoma of the submandibular glands, histiocytic sarcoma of the spleen, oligodendroglioma of the brain and adenocarcinoma and fibroadenoma of the mammary glands were detected in 32-week-old animals. The incidences of mammary adenocarcinoma and pituitary anterior adenoma were higher than those of other tumors. The present results showed that the same tumors as reported in aged rats could also develop in younger rats.     

Insulin responses to administrations of amino acids and fatty acids in healthy cats

In order to compare the stimulation ability of insulin secretion, we determined changes in plasma glucose and insulin concentrations after intravenous administration of various amino acids and essential fatty acids in clinically healthy adult cats. Plasma glucose concentrations were within the normal ranges after injection of amino acids and fatty acids. Plasma insulin concentrations increased rapidly 2 to 4 min after injection of arginine, then decreased to the basal levels at 20 min in all five cats. Insulin peak responses were significantly greater in arginine injections than in normal saline (P<0.01). Areas under the curve (AUC) of plasma insulin concentrations from 0 to 10 min after injection of arginine were significantly larger than after injection of normal saline (P<0.01) and glucose (P<0.05). Increases in AUC of plasma insulin concentration from 0 to 60 min were observed after injection of arginine, leucine, alanine, and fat emulsion. Arginine had a strong insulinotropic effect, and leucine, alanine, and fatty acids had weak ones. Besides, valine, methionine, taurine and glutamine had no stimulant activity of insulin. Given the risk of glucose toxication and required time for testing, the intravenous arginine tolerance test may be useful for estimation of insulin responses in cats.     

An intrinsic bond-centered electronic glass with unidirectional domains in underdoped cuprates

Removing electrons from the CuO2 plane of cuprates alters the electronic correlations sufficiently to produce high-temperature superconductivity. Associated with these changes are spectral-weight transfers from the high-energy states of the insulator to low energies. In theory, these should be detectable as an imbalance between the tunneling rate for electron injection and extraction-a tunneling asymmetry. We introduce atomic-resolution tunneling-asymmetry imaging, finding virtually identical phenomena in two lightly hole-doped cuprates: Ca(1.88)Na(0.12)CuO(2)Cl2 and Bi2Sr2Dy(0.2)Ca(0.8)Cu2O(8+delta). Intense spatial variations in tunneling asymmetry occur primarily at the planar oxygen sites; their spatial arrangement forms a Cu-O-Cu bond-centered electronic pattern without long-range order but with 4a(0)-wide unidirectional electronic domains dispersed throughout (a(0): the Cu-O-Cu distance). The emerging picture is then of a partial hole localization within an intrinsic electronic glass evolving, at higher hole densities, into complete delocalization and highest-temperature superconductivity.     

Aluminum-26 and beryllium-10 in marine sediment

Activities of aluminum-26 and beryllium-10 in marine sediment were measured at 0.01 +/- 0.13 and 4.4 +/- 0.9 disintegrations per minute, per kilogram dry weight, respectively. Only an upper limit of 0.03 could be determined for the ratio of aluminum-26 to beryllium-10 in the sediment. The ratio is probably explained by production by cosmic rays in the atmosphere.     

Detection of the regions of phytosiderophore release from barley roots

Abstract

We devised a method to detect regions of phytosiderophore release from barley (Hordeum vulgare cv. Minorimugi) roots. Plants were grown in Fe-sufficient (+Fe) or Fe-deficient (?-Fe) water cultures for 14 d in a phytotron. Intact or excised roots were sampled and put between two sheets of filter papers just after the onset of the light period. The filter papers with roots were wrapped with vinyl film to avoid drying out and covered with aluminum foil to shade. The roots between the filter paper were kept in the phytotron for 4 h and phytosiderophores (PS) released from roots were absorbed by the filter paper. Then, the shape of the roots was preserved by photocopy and PS released on the filter paper were visualized by the method employed for detecting PS on thin layer chromatography (TLC). Gelatinous Fe solubilizing activity was employed for detecting PS on the filter paper. Released PS were detected as white spots on the orange-colored background and the regions of PS release from the roots were visible on the filter paper. It was evident that the apical zones of roots were the main regions of PS release. It was apparent that a distinct primary root newly formed on the basal parts had higher activity to release PS than the other roots of ?Fe plants. It was also shown that apical root zones of +Fe plants released PS.     

Genetic and environmental variances of body size and morphological traits in communally reared clonal lines from gynogenetic diploid ayu, Plecoglossus altivelis

Four clonal lines of ayu, Plecoglossus altivelis, were produced from mitotic-gynogenetic diploids, mixed before hatching and reared communally. After 9 months, the clonal fish were sacrificed for measurement of body size, morphometric relationships, and meristic counts. DNA fingerprinting was used to confirm the clonal nature of the fish and to identify the clonal line of origin for each fish.

Significant differences were observed among clonal lines for almost all body size, morphometric and meristic measures. Such differences are suggested to represent genotypic difference among clonal lines given the common environmental conditions provided to all the experimental groups, assuming that the genotype-environment interaction was negligible.

By applying the human twin model, genetic and environmental variances in the clonal population was estimated after the clonal lines were separated by DNA fingerprinting. Heritability estimates for data collected at 9 months were relatively high for body size and varied from low to high in meristic and morphometric traits. These results suggest the possible usage of clonal lines as a control fish for estimation of heritability of traits important to aquaculture.     

Retrospective surveillance of metabolic parameters affecting reproductive performance of Japanese Black breeding cows

This retrospective study was conducted to confirm the relationship between pre- and postpartum metabolic parameters and postpartum reproductive performance and to clarify seasonal characteristics of the metabolic parameters by using our metabolic profile test (MPT) database of Japanese Black breeding herds. In evaluation 1, MPT databases of blood samples from multiparous cows collected prepartum and postpartum were divided into two groups according to calving interval, and each MPT parameter was compared. In evaluation 2, the same MPT databases used in evaluation 1 were divided into two groups according to the sampling period. Significant differences were found in the prepartal total protein and postpartal γ-glutamyltransferase in evaluation 1. In evaluation 2, significant differences were found in the prepartal and postpartal total protein, albumin/globulin ratio, and glucose. Clear seasonal differences in MPT results emphasized the usefulness of the MPT in breeding cattle herds fed home-pasture roughage and suggest that unsatisfactory reproductive performance during hot periods reflects inadequate nutritional content of the diet and possible reduced feed intake due to heat stress.     

Dataset of CarboEastAsia and uncertainties in the CO2 budget evaluation caused by different data processing

The datasets of net ecosystem CO₂ exchange (NEE) were acquired from 21 forests, 3 grasslands, and 3 croplands in the eastern part of Asia based on the eddy covariance measurements of the international joint program, CarboEastAsia. The program was conducted by three networks in Asia, ChinaFLUX, JapanFlux, and KoFlux, to quantify, synthesize, and understand the carbon budget of the eastern part of Asia. An intercomparison was conducted for NEE estimated by three gap-filling procedures adopted by ChinaFLUX, JapanFlux, and KoFlux to test the range of uncertainty in the estimation of NEE. The overall comparison indicated good agreement among the procedures in the seasonal patterns of NEE, although a bias was observed in dormant seasons depending on the different criteria of data screening. Based on the gap-filled datasets, the magnitude and seasonality of the carbon budget were compared among various biome types, phenology, and stress conditions throughout Asia. The annual values of gross primary production and ecosystem respiration were almost proportional to the annual air temperature. Forest management, including clear-cutting, plantation, and artificial drainage, was significant and obviously affected the annual carbon uptake within the forests. Agricultural management resulted in notable seasonal patterns in the crop sites. The dataset obtained from a variety of biome types would be an essential source of knowledge for ecosystem science as well as a valuable validation dataset for modeling and remote sensing to upscale the carbon budget estimations in Asia.