Age estimation of captive Asian elephants (Elephas maximus) based on DNA methylation: An exploratory analysis using methylation-sensitive high-resolution melting (MS-HRM)

アジアゾウのDNAから年齢を推定 --メチル化解析による効率的な年齢推定法を構築--. 京都大学プレスリリース. 2023-12-27.Age is an important parameter for bettering the understanding of biodemographic trends—development, survival, reproduction and environmental effects—critical for conservation. However, current age estimation methods are challenging to apply to many species, and no standardised technique has been adopted yet. This study examined the potential use of methylation-sensitive high-resolution melting (MS-HRM), a labour-, time-, and cost-effective method to estimate chronological age from DNA methylation in Asian elephants (Elephas maximus). The objective of this study was to investigate the accuracy and validation of MS-HRM use for age determination in long-lived species, such as Asian elephants. The average lifespan of Asian elephants is between 50–70 years but some have been known to survive for more than 80 years. DNA was extracted from 53 blood samples of captive Asian elephants across 11 zoos in Japan, with known ages ranging from a few months to 65 years. Methylation rates of two candidate age-related epigenetic genes, RALYL and TET2, were significantly correlated with chronological age. Finally, we established a linear, unisex age estimation model with a mean absolute error (MAE) of 7.36 years. This exploratory study suggests an avenue to further explore MS-HRM as an alternative method to estimate the chronological age of Asian elephants

Investigation of biomarkers in a rare case of fulminant necrotizing enterocolitis in a preterm infant

We encountered a very rare case of fulminant necrotizing enterocolitis (F-NEC) in a preterm male baby. The course of NEC and sepsis in this case was clearly different from the usual course. After onset at 14 days of life, catheter-related bloodstream infection was first assumed, and antibiotics and γ-globulin administration were started. However, 12 hours after onset, the baby's abdominal distension increased remarkably, and his entire abdominal wall turned red to purple. Escherichia coli were isolated from the blood culture, but the catheter tip culture was negative. Exchange transfusion was performed 32 hours after onset, but no significant changes were observed in the baby's general condition, and he died 46 hours after onset. The acute phase reactants of CRP and α1-acid glycoprotein increased, but haptoglobin did not. Although IL-1β and TNFα increased as expected with sepsis, IL-6, IL-8, IL-10, and G-CSF however increased to a greater extent than expected. From the above, we diagnosed the development of intestinal necrosis as a result of widespread intestinal ischemia, and that sepsis was associated with this poor condition

Non-invasive age estimation based on faecal DNA using methylation-sensitive high-resolution melting for Indo-Pacific bottlenose dolphins

野生イルカのうんちから年齢を推定 --野生水生動物の糞から抽出したDNAのエピジェネティッククロックを用いた年齢推定に世界で初めて成功--. 京都大学プレスリリース. 2023-12-18.Age is necessary information for the study of life history of wild animals. A general method to estimate the age of odontocetes is counting dental growth layer groups (GLGs). However, this method is highly invasive as it requires the capture and handling of individuals to collect their teeth. Recently, the development of DNA-based age estimation methods has been actively studied as an alternative to such invasive methods, of which many have relied on used biopsy samples. However, if DNA-based age estimation can be developed from faecal samples, age estimation can be performed entirely non-invasively. We developed an age estimation model using the methylation rate of two gene regions, GRIA2 and CDKN2A, measured through methylation-sensitive high-resolution melting (MS-HRM) from faecal samples of wild Indo-Pacific bottlenose dolphins (Tursiops aduncus). The age of individuals was known through conducting longitudinal individual identification surveys underwater. Methylation rates were quantified from 36 samples collected from 30 individuals. Both gene regions showed a significant correlation between age and methylation rate. The age estimation model was constructed based on the methylation rates of both genes which achieved sufficient accuracy (after LOOCV: MAE = 5.08, R² = 0.33) for the ecological studies of the Indo-Pacific bottlenose dolphins, with a lifespan of 40–50 years. This is the first study to report the use of non-invasive faecal samples to estimate the age of marine mammals

MUTYH Gln324His gene polymorphism and genetic susceptibility for lung cancer in a Japanese population

<p>Abstract</p> <p>Background</p> <p>Genetic polymorphisms of DNA repair enzymes in the base excision repair (BER) pathway, may lead to genetic instability and lung cancer carcinogenesis. We investigated the interactions among the gene polymorphisms in DNA repair genes and lung cancer.</p> <p>Methods</p> <p>We analyzed associations among <it>OGG1 </it>Ser326Cys and <it>MUTYH </it>Gln324His gene polymorphisms in relation to lung cancer risk using PCR-RFLP. The study involved 108 lung cancer patients and 121 non-cancer controls divided into non-smokers, smokers according to pack-years smoked in Japanese.</p> <p>Results</p> <p>The results showed that the <it>MUTYH His/His </it>genotype compared with <it>Gln/Gln </it>genotype showed an increased risk for lung cancer (adjusted odds ratio [OR] 3.03, confidence interval [95%CI], 1.31–7.00, p = 0.010), whereas there was no significant increase for the <it>Gln/His </it>genotype (adjusted OR 1.35, 95%CI 0.70–2.61, p = 0.376). The <it>MUTYH His/His </it>genotype was at a borderline increased risk for both adenocarcinoma and squamous cell carcinoma (adjusted OR 2.50, 95%CI 0.95–6.62, p = 0.065 for adenocarcinoma; adjusted OR 3.20, 95%CI 0.89–11.49, p = 0.075 for squamous cell carcinoma, respectively). However, the <it>OGG1 Ser/Cys </it>or <it>Cys/Cys </it>genotypes compared with the <it>Ser/Ser </it>genotype did not have significantly increased risk for lung cancer, containing either adenocarcinoma or squamous cell carcinoma. The joint effect of tobacco exposure and the <it>MUTYH His/His </it>genotype compared with the <it>Gln/Gln </it>genotype showed a significant association with lung cancer risk in smokers, and there was not significantly increased in non-smokers (adjusted OR 3.82, 95%CI 1.22–12.00, p = 0.022 for smokers; adjusted OR 2.60, 95%CI 0.60–11.25, p = 0.200 for non-smokers, respectively). The effect of tobacco exposure and the <it>OGG1 </it>Ser326Cys showed also no significant risk for lung cancer.</p> <p>Conclusion</p> <p>Our findings suggest that the <it>MUTYH </it>Gln324His polymorphism appear to play an important role in modifying the risk for lung cancer in the Japanese population.</p

Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population

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Large Population of ALMA Galaxies at z>6 with Very High [OIII]88um to [CII]158um Flux Ratios: Evidence of Extremely High Ionization Parameter or PDR Deficit?

We present our new ALMA observations targeting [OIII]88um, [CII]158um, [NII]122um, and dust continuum emission for three Lyman break galaxies at z=6.0293-6.2037 identified in the Subaru/Hyper Suprime-Cam survey. We clearly detect [OIII] and [CII] lines from all of the galaxies at 4.3-11.8sigma levels, and identify multi-band dust continuum emission in two of the three galaxies, allowing us to estimate infrared luminosities and dust temperatures simultaneously. In conjunction with previous ALMA observations for six galaxies at z>6, we confirm that all the nine z=6-9 galaxies have high [OIII]/[CII] ratios of L[OIII]/L[CII]~3-20, ~10 times higher than z~0 galaxies. We also find a positive correlation between the [OIII]/[CII] ratio and the Lya equivalent width (EW) at the ~90% confidence level. We carefully investigate physical origins of the high [OIII]/[CII] ratios at z=6-9 using Cloudy, and find that high density of the interstellar medium, low C/O abundance ratio, and the cosmic microwave background attenuation are responsible to only a part of the z=6-9 galaxies. Instead, the observed high [OIII]/[CII] ratios are explained by 10-100 times higher ionization parameters or low photodissociation region (PDR) covering fractions of 0-10%, both of which are consistent with our [NII] observations. The latter scenario can be reproduced with a density bounded nebula with PDR deficit, which would enhance the Lya, Lyman continuum, and C+ ionizing photons escape from galaxies, consistent with the [OIII]/[CII]-Lya EW correlation we find.Comment: 20 pages, 18 figures, Accepted for publication in Ap

Wheat‐ghretropins: novel ghrelin‐releasing peptides derived from wheat protein

Ghrelin is an endogenous orexigenic hormone mainly produced by stomach cells and is reported to influence appetite, gastrointestinal motility and growth hormone secretion. We observed that enzymatic digest of wheat gluten stimulated ghrelin secretion from mouse ghrelinoma 3-1, a ghrelin-releasing cell line. Further on, we characterized the ghrelin-releasing peptides present in the digest by comprehensive peptide analysis using liquid chromatography-mass spectrometry and structure-activity relationship. Among the candidate peptides, we found that SQQQQPVLPQQPSF, LSVTSPQQVSY and YPTSL stimulated ghrelin release. We then named them wheat-ghretropin A, B and C, respectively. In addition, we observed that wheat-ghretropin A increased plasma ghrelin concentration and food intake in mice after oral administration. Thus, we demonstrated that wheat-ghretropin stimulates ghrelin release both in vitro and in vivo. To the best of our knowledge, this is the first report of a wheat-derived exogenous bioactive peptide that stimulates ghrelin secretion

Esophageal metastasis of renal cell carcinoma resected by endoscopic submucosal dissection: a case report

Background: Esophageal metastasis of renal cell carcinoma (RCC) is extremely rare. We have described herein a case of a 59-year-old man with esophageal metastasis of RCC that was endoscopically resected.Case presentation: The case was a 59-year-old man who had undergone left nephrectomy for renal clear cell carcinoma 17 years ago and splenectomy for splenic metastasis 3 years ago. Esophagogastroduodenoscopy (EGD) performed 9 years ago revealed a small reddish elevated lesion with a smooth surface in the middle esophagus; this lesion increased in size 4 years ago. However, no biopsy was performed. The lesion continued to grow in size and was found to have become nodular during the present observation. Biopsy revealed clear cell carcinoma. Endoscopic ultrasound (EUS) revealed that the lesion had not invaded the submucosa, and contrast-enhanced computed tomog-raphy did not reveal any other metastasis. The lesion was successfully removed en bloc via endoscopic submucosal dissection (ESD). Pathologically, the tumor was detected in the subepithelium with focal infiltration of the muscularis mucosa. It consisted of monotonous cells with small nuclei and a clear cytoplasm. Immunohistological findings indi-cated that the tumor was a metastasis of RCC. The lateral and vertical margins were noted to be free.Conclusions: We have presented herein a case of esophageal metastasis of RCC that had progressed over 9 years and was then resected en bloc through endoscopic submucosal dissection