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The binary system η Carinae is a unique laboratory that facilitates the study of particle acceleration to high energies under a wide range of conditions, including extremely high densities around periastron. To date, no consensus has emerged as to the origin of the gigaelectronvolt γ-ray emission in this important system. With a re-analysis of the full Fermi-LAT data set for η Carinae, we show that the spectrum is consistent with a pion decay origin. A single population leptonic model connecting X-ray to -ray emission can be ruled out. We revisit our physical model from 2015, based on two acceleration zones associated with the termination shocks in the winds of both stars. We conclude that inverse Compton emission from in-situ accelerated electrons dominates the hard X-ray emission detected with NuSTAR at all phases away from periastron and that pion-decay from shock accelerated protons is the source of -ray emission. Very close to periastron there is a pronounced dip in hard X-ray emission, concomitant with the repeated disappearance of the thermal X-ray emission, which we interpret as due to the suppression of significant electron acceleration in the system. Within our model, the residual emission seen by NuSTAR at this phase can be accounted for with secondary electrons produced in interactions of accelerated protons, which agrees with the variation in pion-decay -ray emission. Future observations with H.E.S.S., CTA, and NuSTAR should confirm or refute this scenario. [ABSTRACT FROM AUTHOR]

Study Question: Does spontaneous endometriosis in cynomolgus monkeys have the characteristics required of a good experimental model?Summary Answer: Spontaneous endometriosis in cynomolgus monkeys exhibited similar clinicopathological characteristics to the human disease and was useful as an experimental model.What Is Known Already: The prevalence of endometriosis in autopsied cynomolgus monkeys (Macaca fascicularis) in a breeding colony was reported to be 28.7% in 1993. The histopathological findings we reported recently showed that components of spontaneous endometriosis were not only endometriotic epithelium and stromal cells (CD10-positive) with hemorrhage and inflammation, but also smooth muscle metaplasia and nerve fibers.Study Design, Size, Duration: During routine medical examinations at a research facility from 2008 to 2012, 614 female cynomolgus monkeys of reproductive age (6-25 years) were screened for endometriosis by the presence of regular menstrual bleeding, serum CA125 levels and palpation of the abdomen. In total, 29 monkeys were selected as subjects for the following study.Participants/materials, Setting, Methods: Of the 29 monkeys selected, 15 were diagnosed with endometriosis by laparoscopy and/or open surgery. The monkeys were monitored by observing their general condition, and eight of these were monitored using laparoscopy and MRI. In addition, to investigate appropriate screening parameters and endometriosis-associated biological parameters in monkeys, we retrospectively examined general laboratory parameters that correlate to the menstrual cycle and disease status.Main Results and the Role Of Chance: The combination of CA125 serum levels (this was a useful marker for chocolate cysts), palpation of the abdomen, and fecal abnormalities was the most efficient screening method for diagnosing monkeys with endometriosis. Each animal could be diagnosed and assigned a disease stage by laparoscopy. While monitoring the disease stage by laparoscopy and/or MRI, disease status in individual monkeys was mainly stable or was progressive for 2-7 months. The detection rate by screening was low (15/614) but age-specific analysis suggests that screening would be more efficient if a colony for an endometriosis model is maintained with 11-20-year olds. As an endometriosis-associated biological parameter, the decrease in food consumption that coincided with menstruation was selected and correlated well (R2 value = 0.8239) with disease status (according to a modified adhesion revised American Fertility Society score).Large Scale Data: N/A.Limitations, Reasons For Caution: Peritoneal fluid was not analyzed because a smaller amount is produced in cynomolgus monkeys than in baboons. Although clinical endometriosis-associated pain is evaluated in women using a visual analog scale, pain could not be directly evaluated in this non-human primate model.Wider Implications Of the Findings: Although cynomolgus monkeys are relatively small (2-5 kg) primates, laparoscopy and MRI make it possible to evaluate spontaneous endometriosis in these monkeys and to monitor its development over time. Spontaneous endometriosis in cynomolgus monkeys is a useful model for evaluating disease progress and drug efficacy because they have similar lesions to those in humans, and conventional laboratory methods and parameters for assessment are well established.Study Funding/competing Interest(s): No external funds were used for this study. A.N.-K., K.T., H.T., A.K. and M.S. are full-time employees of Chugai Pharmaceutical Co., Ltd. R.K. received a consultancy fee from Chugai Pharmaceutical Co., Ltd. and lecture fees from Chugai Pharmaceuticals, Japan Vaccine Co. Ltd., Merck & Co., Mochida Co. Ltd., Roche Diagnostics, and BD, unrelated to the submitted work. S.N., S.O. and T.S. have nothing to declare. [ABSTRACT FROM AUTHOR]

Study Question: What are the characteristics of spontaneous endometriosis in cynomolgus monkeys?Summary Answer: Spontaneous endometriosis in cynomolgus monkeys exhibited similar characteristics to the human disease.What Is Known Already: One previous report described the prevalence and the basic histopathology of spontaneous endometriosis in cynomolgus monkeys.Study Design, Size, Duration: Endometriotic lesions that had been histologically confirmed in 8 female cynomolgus monkeys between 5 and 21 years old were subjected to study.Participants/materials, Setting, Methods: The monkeys died of, or were sacrificed because of, sickness consequent on endometriosis. Specimens were evaluated histopathologically with haematoxylin and eosin staining, iron staining and immunohistochemistry (CD10, CD31, α-SMA and PGP9.5), and by observing them under a microscope.Main Results and the Role Of Chance: Endometriotic and stromal cells (CD10-positive) with haemorrhage and inflammation were observed. Smooth muscle metaplasia and nerve fibres were also noted in the endometriotic lesions. Endometriotic lesions in lymph nodes were incidentally found.Limitations and Reasons For Caution: Since laparoscopic analysis for monitoring the disease state was not set as a parameter of the current study, time course changes (progression) of the disease were not assessed.Wider Implications Of the Findings: Further investigation of spontaneous endometriosis in cynomolgus monkeys may contribute to better understanding of the disease pathobiology.Study Funding/competing Interests: No external funds were used for this study. A.N.K., S.M., S.H., T.I., O.K., A.K. and M.S. are full-time employees of Chugai Pharmaceutical Co., Ltd. R.K. received lecture fees from Chugai Pharmaceutical Co., Ltd., unrelated to the submitted work. S.N., S. O., L.Y., K.Y. and T.S. have nothing to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Human epithelial ovarian carcinoma is well-known as a sex steroid-dependent neoplasm, but the possible biological significance of progesterone receptor (PR) in this cancer remains controversial. Recently, two isoforms of human PR, PRA and PRB, have been characterized and different functional characteristics have been reported for these two isoforms. We therefore examined immunohistochemistry (107 cases) and reverse transcription-polymerase chain reaction (RT-PCR) (16 cases) for PRA, PRB, and oestrogen receptor-a (ER-a). Labeling indices (LI) for PRA and PRB were 2.4 and 43.6, respectively, and the difference was statistically significant. PRB LI, but not PRA LI, as well as performance status, stage, and residual tumour turned out to be independent prognostic factors following multivariate analysis. There was also a significant correlation between ER-a LI and PRB LI (r = 0.595, P < 0.0001), suggestive of a possible interaction between these two receptors. RT-PCR also detected the expression of PR isoform transcripts in the same pattern as was observed with immunohistochemistry. Results of these studies indicate that PRA and PRB both mediate distinct pathways of progesterone action in ovarian carcinoma. Moreover, it is important to examine PRB LI as a prognostic factor in the cases of human epithelial ovarian carcinoma. [ABSTRACT FROM AUTHOR]

Urine of ddY/DAO mice lacking d-amino-acid oxidase contained 5.7 times more serine than that of normal ddY/DAO+ mice. Most of the serine was d-isomer. The origin of thisd-serine was examined. Oral administration of 0.02% amoxicillin and 0.004% minocycline to the ddY/ DAO- mice for 7 days did not reduce the urinary d-serine, indicating that the d-serine was not of intestinal bacterial origin. When the mouse diet was changed to one with different compositions, the urinary d-serine was considerably reduced. Furthermore, starvation of the ddY/DAO- mice for 24 hours reduced the urinary d-serine to 33% of the original level. These results indicate that most of the urinary d-serine comes from the diet. However, the urine of the starved ddY/DAO- mice still contained 4.6 times more d-serine than that of the ddY/DAO+ mice, suggesting a part of the D-serine have an endogenous origin. [ABSTRACT FROM AUTHOR]

Genomic DNA was extracted from mice of 15 strains (A/J, AKR, BALB/c, C3H/He, C57BL/6, CBA/J, CD-1, CF#1, DBA/2, ddY/DAO, ddY/DAO, ICR, NC, NZB and NZW) for the examination of the difference in the structure of the d-amino-acid oxidase gene among the mouse strains. The DNAs were digested with restriction endonucleases and analyzed by Southern hybridization using d-amino-acid oxidase cDNA as a probe. The 15 strains showed the same hybridization patterns in the EcoRV, BamHI or BglII digestion. In the EcoRI digestion, the DBA/2 strain showed a different hybridization pattern from the other 14 strains. In the PvuII and XbaI digestion, C3H/He, CBA/J, ddY/DAO and NC strains were different from the other 11 strains. In the PstI and HindIII digestion, restriction fragment length polymorphisms were observed, and the 15 strains were classified into four groups according to their hybridization patterns. These results indicate that the 15 strains of mice carry a structurally similar d-amino-acid oxidase gene, but there is a variation in its inside sequence among the groups of the strains. [ABSTRACT FROM AUTHOR]

d-Amino acid oxidase cDNA was amplified by a polymerase chain reaction using RNA extracted from the mouse kidney. When digested with HindIII, the cDNAs of the BALB/c and ddY/DAO mice were cleaved into two fragments whereas the cDNA of the ddY/DAO mice was not. Sequencing revealed that nucleotide-471 of the cDNAs was G in the BALB/c and ddY/DAO mice whereas it was substituted for C in the ddY/DAO mice. This base substitution was the cause of the failure of the cleavage of the cDNA of the ddY/DAO mice. Examination of other strains of inbred mice showed that d-amino-acid oxidase cDNAs of A/J, AKR, C57BL/6, CD-1, CF#1, ICR, DBA/2, NZB and NZW mice were cleaved with HindIII into two fragments whereas those of C3H/He, CBA/J and NC mice were not. Genomic DNAs extracted from the mice of these 15 strains were digested with HindIII and hybridized with d-amino-acid oxidase cDNA. A 18.2-kb fragment hybridized with the probe in the C3H/He, CBA/J, ddY/DAO and NC mice whereas two fragments of 12 kb and 6.2 kb hybridized in the other mice. These results are consistent with those of the cDNAs, confirming the loss of the HindIII cleavage site in the C3H/He, CBA/J, ddY/DAO and NC mice. The Southern hybridization revealed a loss of a different HindIII cleavage site in the A/J, AKR, C57BL/6, DBA/2, ICR and NZB mice. The substitution at nucleotide-471 should cause a substitution of an amino acid residue. However, this substitution did not affect catalytic activity of d-amino acid oxidase. [ABSTRACT FROM AUTHOR]

Urine of mutant ddY/DAO mice lacking d-amino-acid oxidase activity contained more serine and proline than that of normal ddY/DAO mice. d-Amino-acid oxidase treatment of urinary amino acids decreased the serine and proline, suggesting that they contained d-isomers. An HPLC analysis confirmed the presence of d-serine. Urinary serine and proline contents were not decreased when the ddY/DAO mice were fed a diet which did not contain supplementary d-methionine or when they were given water containing antibiotics. These results suggest that the d-serine and d-proline do not derive from the d-methionine supplemented in the diet or from intestinal bacteria. In urine of the ddY/DAO mice, a substance which seemed to be d-methionine sulfoxide and/or d-methionine sulfone was present. It is probably a metabolite of the d-methionine supplemented in the diet. The d-aminoaciduria in the mutant mice lacking d-amino-acid oxidase activity indicates that this enzyme is involved in the metabolism of the d-amino acids in normal mice. [ABSTRACT FROM AUTHOR]

An abstract for the article "Antibiotics and Antiseptics for Venous Leg Ulcers," by S. O'Meara, D. Al-Kurdi and L.G. Ovington is presented.

Investigates the expression of survivin in the endometria of women with regular menstrual cycles using reverse transcription-polymerase chain reaction and immunohistochemistry. Comparison with apoptosis inhibitor Bcl-2; Relationship between survivin and Bcl-2; Survivin expression during embryonic and fetal development; Relationship between survivin and apoptosis; Location of survivin in the endometrial glandular epithelium.