Distributional Change and Epidemic Introgression in Overlapping Areas of Japanese Pond Frog Species Over 30 Years

Pelophylax nigromaculatus, P. porosus porosus, and P. p. brevipoda are three pond frog species distributed in Japan. Their distributions overlap at two basins in central Japan (P. nigromaculatus and P. p. porosus in the Matsumoto basin, and P. nigromaculatus and P. p. brevipoda in the Ina basin), and hybrid descendants have been found in these areas. To clarify the distribution areas and hybrid zones of the frogs, and to understand the mode of introgressive hybridization and its impact on the frog populations, we conducted exhaustive sampling at each basin and performed allozyme and mtDNA analyses of 233 individuals. Analysis using genetic markers clearly detected nine F1 hybrids and 94 hybrid descendants of P. nigromaculatus and P. porosus from the overlapping areas of both basins. Allozyme and mtDNA data suggest directional hybridization between female P. p. porosus and male P. nigromaculatus in the Matsumoto basin. Over the past 30 years, the distribution of P. p. porosus has been narrowed and fragmented by the invasion of P. nigromaculatus, seemingly because of directional hybridization in the Matsumoto basin. In the Ina basin, the “pure” P. p. brevipoda (n = 8) population was extremely reduced by gene introgression from P. nigromaculatus, yet its distribution was barely changed compared to the Matsumoto basin. Consequently, this study shows that P. porosus populations are threatened by interspecific hybridization with P. nigromaculatus, and that introgressive hybridization damaged P. porosus populations by different means in each basin

Gastrointestinal Endoscopy for Patients with High Levels of Serum CEA and CA19-9

Serum levels of tumor markers, such as carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9）, are often measured to detect potential malignancy. When these levels are high, the presence or absence of malignancy is confirmed via a more detailed examination using gastrointestinal （GI） endoscopy and computed tomography. The rate of confirmation of malignancy upon such a follow-up is unknown. This study aimed to investigate the malignancy detection rate via GI endoscopy for patients with high levels of serum CEA and CA19-9. All patients who underwent such GI endoscopy between January 2018 and February 2019 at Showa University Hospital were included in this study. The patients were divided into a follow-up group and a screening group, depending on the purpose of measuring their serum CEA/CA19-9 levels. There were 156 patients who underwent GI endoscopy because of high CEA/CA19-9 levels within the study period. Advanced malignant lesions were detected in 10 patients （6.4％）, including seven cases of colorectal cancer and three cases of upper GI malignancies. In the screening group, six cases （5.7％） of GI malignancies were detected, none of which were found in asymptomatic patients without anemia. In the follow-up group, four cases （7.8％） of GI malignancies were detected; three patients were asymptomatic, and one patient had anemia. Our findings suggest that high serum CEA/CA19-9 levels in asymptomatic patients without anemia and without a history of malignancy do not indicate the presence of malignancy. However, high serum CEA/CA19-9 levels may indicate the potential presence of GI malignancies for patients with a history of malignant tumors, even if they are asymptomatic and do not have anemia

Irradiation by a Combination of Different Peak-Wavelength Ultraviolet-Light Emitting Diodes Enhances the Inactivation of Influenza A Viruses

Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock. This study aimed to determine the ideal irradiation by ultraviolet-light emitting diodes (UV-LEDs) for IAV disinfection. We irradiated the IAV H1N1 subtype with 4.8 mJ/cm2 UV using eight UV-LEDs [peak wavelengths (WL) = 365, 310, 300, 290, 280, 270, and 260 nm)] or a mercury low pressure (LP)-UV lamp (Peak WL = 254 nm). Inactivation was evaluated by the infection ratio of Madin–Darby canine kidney (MDCK) cells or chicken embryonated eggs. Irradiation by the 260 nm UV-LED showed the highest inactivation among all treatments. Because the irradiation-induced inactivation effects strongly correlated with damage to viral RNA, we calculated the correlation coefficient (RAE) between the irradiant spectrum and absorption of viral RNA. The RAE scores strongly correlated with the inactivation by the UV-LEDs and LP-UV lamp. To increase the RAE score, we combined three different peak WL UV-LEDs (hybrid UV-LED). The hybrid UV-LED (RAE = 86.3) significantly inactivated both H1N1 and H6N2 subtypes to a greater extent than 260 nm (RAE = 68.6) or 270 nm (RAE = 42.2) UV-LEDs. The RAE score is an important factor for increasing the virucidal effects of UV-LED irradiation

CpG Island Methylator Phenotype in Primary Gastric Carcinoma

Gastric cancers (GC) with methylation of multiple CpG islands have a CpG island methylator phenotype (CIMP) and they can have different biological features. The aim of this study was to investigate the DNA methylation status of GCs and its association with their clinicopathological features. We evaluated the methylation status of four genes (MINT1, MINT2, MINT25 and MINT31) in 105 primary GCs using bisulfite-pyrosequencing analysis. We classified tumors as CIMP-high (CIMP-H), CIMP-low (CIMP-L) or CIMP-negative (CIMP-N) based on the methylation of MINT1, MINT2, MINT25, and MINT31. Overall, the prevalence of CIMP-H, CIMP-L and CIMP-N was 22% (23/105), 52% (55/105) and 26% (27/105), respectively. We observed a significant difference in tumor stage (stages I-II vs. stages III-IV) between CIMP-H and CIMP-N tumors (P = 0.0435). No significant differences were observed in clinicopathological characteristics (gender, age, location and tumor differentiation) among the CIMP phenotypes. The prognoses of patients with a CIMP-H tumor is likely to be better than those with CIMP-L or CIMP-N tumors, but these differences are not statistically significant (P = 0.074 and P = 0.200). Our results suggest that CIMP may define a subgroup of GCs with distinct biological features

Magnifying Colonoscopy Findings for Differential Diagnosis of Sessile Serrated Adenoma/Polyps and Hyperplastic Polyps

Sessile serrated adenoma/polyps (SSA/Ps) are thought to be precursors of colorectal cancers. However, current endoscopic techniques for differentiating SSA/Ps from conventional hyperplastic polyps (HPs) have low diagnostic accuracy. The aim of the present study was to assess the ability of mucosal crypt patterns to distinguish SSA/Ps from HPs. We examined 140 lesions from 93 patients that had been diagnosed histologically as SSA/Ps or HPs at the Showa University Hospital between June 2010 and May 2012. Three experienced colonoscopists reviewed the endoscopic findings of magnifying colonoscopy. Type II open-shape (Type II-O) pit patterns and varicose microvascular vessels (VMVs) were identified according to previously proposed definitions. Although 140 lesions were initially identified for the study, 27 lesions were excluded from analysis because of insufficient endoscopic findings. Thus, endoscopic findings from a total of 113 lesions (68 SSA/Ps and 45 HPs) were evaluated. Of 113 serrated polyps, 51 lesions (44 SSA/Ps and 7 HPs; P<0.01) had Type II-O pit patterns. The inter- and intra-observer agreement for these patterns among three colonoscopists was κ=0.61 (range 0.57–0.65) and κ=0.68 (range 0.52–0.94), respectively. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of Type II-O pit patterns for differentiating between SSA/P and HP were 86%, 61%, 65%, and 84%, respectively. In contrast, the PPV, NPV, sensitivity, and specificity of VMVs were 68%, 43%, 37%, and 73%, respectively. The results indicate that Type II-O mucosal crypt patterns may be useful for the differential diagnosis of SSAPs and HPs

HDAC Inhibitors Exert Anti-Myeloma Effects through Multiple Modes of Action

HDACs are critical regulators of gene expression that function through histone modification. Non-histone proteins and histones are targeted by these proteins and the inhibition of HDACs results in various biological effects. Moreover, the aberrant expression and function of these proteins is thought to be related to the pathogenesis of multiple myeloma (MM) and several inhibitors have been introduced or clinically tested. Panobinostat, a pan-HDAC inhibitor, in combination with a proteasome inhibitor and dexamethasone has improved survival in relapsing/refractory MM patients. We revealed that panobinostat inhibits MM cell growth by degrading the protein PPP3CA, a catalytic subunit of calcineurin. This degradation was suggested to be mediated by suppression of the chaperone function of HSP90 due to HDAC6 inhibition. Cytotoxicity due to the epigenetic regulation of tumor-associated genes by HDAC inhibitors has also been reported. In addition, HDAC6 inhibition enhances tumor immunity and has been suggested to strengthen the cytotoxic effects of therapeutic antibodies against myeloma. Furthermore, therapeutic strategies to enhance the anti-myeloma effects of HDAC inhibitors through the addition of other agents has been intensely evaluated. Thus, the treatment of patients with MM using HDAC inhibitors is promising as these drugs exert their effects through multiple modes of action

Can tryptophan supplement intake at breakfast enhance melatonin secretion at night?

[Background]Tryptophan (TRP) is an essential amino acid, and it has been suggested that TRP intake at breakfast combined with daytime bright light exposure can increase nocturnal melatonin secretion. However, the mechanisms involved are not yet clear. The aim of this study was to examine the effect of TRP supplement intake at breakfast on nocturnal melatonin secretion under different daytime light intensities in humans. [Method]Twelve subjects (aged 21.3 ± 3.0 years, mean ± standard deviation) participated in a random order in experimental sessions lasting 3 days under four conditions in a laboratory setting. The four conditions were TRP*Bright, Placebo*Bright, TRP*Dim, and Placebo*Dim. A TRP capsule (1000 mg) or a placebo starch capsule (1000 mg) were taken at breakfast. In addition, during the daytime (07:00–18:00), the subjects were asked to stay under different light intensities: >5000 lx (bright) or <50 lx (dim). Saliva samples were collected for measuring the concentration of melatonin. The time courses of melatonin concentration and dim light melatonin onset (DLMO) were compared among the four conditions using repeated measurements analysis of variance (ANOVA). [Result] Nocturnal melatonin concentrations in the bright light condition tended to be higher than in the dim light condition (main effect of light: p = .099). Moreover, in the bright light condition, the change in DLMO between baseline and after the intervention was significantly higher than that in the dim light condition (main effect of light: p <.001). However, the ANOVA results indicated no significant effect of TRP intake on melatonin secretion. [Conclusion]Our findings indicated that intake of 1000 mg of TRP at breakfast on 1 day did not change nocturnal melatonin secretion, even though TRP is the precursor of melatonin. In contrast, daytime bright light exposure increased nocturnal melatonin secretion and advanced the phase of melatonin onset. Therefore, TRP supplementation, unlike exposure to daytime bright light, does not acutely affect biological rhythm and sleep in humans. [Trial registration]UMIN Clinical Trial Registry: UMIN00002412