Stomach and colonic microbiome of wild Japanese macaques

Within the gastrointestinal tract, the physiochemical microenvironments are highly diversified among the different stages of food digestion. Accordingly, gut microbiome composition and function vary at different gut sites. In this study, we examine and compare the compositional and functional potential between the stomach and colonic microbiome of wild Japanese macaques (Macaca fuscata yakui) living in the evergreen forest of Yakushima Island. We find a significantly lower microbial diversity in the stomach than in the colon, possibly due to the stomach's acidic and aerobic environment, which is suboptimal for microbial survival. According to past studies, the microbial taxa enriched in the stomach are aero- and acid-tolerant. By functional prediction through PICRUSt2, we reveal that the stomach microbiome is more enriched in pathways relating to the metabolism of simple sugars. On the contrary, the colonic microbiota is more enriched with fiber-degrading microbes, such as those from Lachnospiracea, Ruminococcaceae, and Prevotella. Our study shows a clear difference in the microbiome between the stomach and colon of Japanese macaques in both composition and function. This study provides a preliminary look at the alpha diversity and taxonomic composition within the stomach microbiome of Japanese macaques, a hindgut-fermenting nonhuman primate

Host selection of hematophagous leeches (Haemadipsa japonica): Implications for iDNA studies

The development of an efficient and cost‐effective method for monitoring animal populations or biodiversity is urgently needed, and invertebrate‐derived DNA (iDNA) may offer a promising tool for assessing the diversity and other ecological information of vertebrates. We studied the host species of a hematophagous leech (Haemadipsa japonica) in Yakushima by genetic barcoding and compared the results with those for mammal composition revealed by camera trapping. We analyzed 119 samples using two sets of primers by Sanger sequencing and one set of primer by next generation sequencing. The proportion of the samples that were successfully sequenced and identified to at least one species was 11.8–24.3%, depending on the three different methods. In all of these three methods, most of the samples were identified as sika deer (18/20, 6/15 and 16/29) or human (2/20, 7/15 and 21/29). The nonhuman mammal host species composition was significantly different from that estimated by camera trapping. Sika deer was the main host, which may be related with their high abundance, large body size and terrestriality. Ten samples included DNA derived from multiple species of vertebrates. This may be due to the contamination of human DNA, but we also found DNA from deer, Japanese macaque and a frog in the same samples, suggesting the mixture of the two meals in the gut of the leech. Using H. japonica‐derived iDNA would not be suitable to make an inventory of species, but it may be useful to collect genetic information on the targeted species, due to their high host selectivity

Protective Effects of Olmesartan and Azelnidipine against Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

In the treatment of hypertension, care should be taken for preventing of hypertensive organ injuries as well as lowering blood pressure to the adequate level in order to reduce the risk of cardiovascular diseases. The purpose of this study is to examine the effects of angiotensin II receptor blockers (ARB), calcium channel blockers (CCB) and their combination on the development of cardiovascular organ injuries in spontaneously hypertensive rats (SHR). Four groups of male 8-week-old SHR (n=9 each) were given vehicle(control), 10 mg/kg azelnidipine (AZL), 10 mg/kg olmesartan (OLM, n=9), or the combination of AZL and OLM(5 mg/kg each)for 12 weeks, and their effects on cardiovascular organ injuries were evaluated. Tail-cuff blood at 12 weeks was similarly lowered by AML, OLM and the combination therapy(148, 143 and 143 mmHg, respectively)as compared with the control SHR (198 mmHg). Pulse rate was significantly less in the AZL group but not in the OLM group or the combination therapy group than in the untreated control group (-27, -12, +6 bpm, respectively). The cardiac ventricular weight (AZL -12%, OLM -15%, combination -18% vs. control) and aortic thickness (AZL -17%, OLM -16%, combination -19% vs. control) were reduced by similar extents in the three groups given antihypertensive treatments. Regarding the myocardial fibrosis, left ventricular hydroxyproline content was reduced in the OLM and the combination groups but the change was not significant in the AZL group (AZL -14%,OLM -30%, combination -27% vs. control). In the echocardiographic evaluation of cardiac function, the index of left ventricular diastolic function is significantly improved in the OLM and the combination groups but not in the AZL group, while the index of systolic function was not different between the four groups. It is suggested that the antihypertensive therapy including ARB is superior to the monotherapy by CCB in preventing the myocardial fibrosis and preserving the left ventricular diastolic function

Synchronization of Circadian Per2 Rhythms and HSF1-BMAL1:CLOCK Interaction in Mouse Fibroblasts after Short-Term Heat Shock Pulse

Circadian rhythms are the general physiological processes of adaptation to daily environmental changes, such as the temperature cycle. A change in temperature is a resetting cue for mammalian circadian oscillators, which are possibly regulated by the heat shock (HS) pathway. The HS response (HSR) is a universal process that provides protection against stressful conditions, which promote protein-denaturation. Heat shock factor 1 (HSF1) is essential for HSR. In the study presented here, we investigated whether a short-term HS pulse can reset circadian rhythms. Circadian Per2 rhythm and HSF1-mediated gene expression were monitored by a real-time bioluminescence assay for mPer2 promoter-driven luciferase and HS element (HSE; HSF1-binding site)-driven luciferase activity, respectively. By an optimal duration HS pulse (43°C for approximately 30 minutes), circadian Per2 rhythm was observed in the whole mouse fibroblast culture, probably indicating the synchronization of the phases of each cell. This rhythm was preceded by an acute elevation in mPer2 and HSF1-mediated gene expression. Mutations in the two predicted HSE sites adjacent (one of them proximally) to the E-box in the mPer2 promoter dramatically abolished circadian mPer2 rhythm. Circadian Per2 gene/protein expression was not observed in HSF1-deficient cells. These findings demonstrate that HSF1 is essential to the synchronization of circadian rhythms by the HS pulse. Importantly, the interaction between HSF1 and BMAL1:CLOCK heterodimer, a central circadian transcription factor, was observed after the HS pulse. These findings reveal that even a short-term HS pulse can reset circadian rhythms and cause the HSF1-BMAL1:CLOCK interaction, suggesting the pivotal role of crosstalk between the mammalian circadian and HSR systems

Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study

BACKGROUND AND AIMS: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. METHODS: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. RESULTS: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. CONCLUSIONS: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (\u3e91%)

Activity of wild Japanese macaques in Yakushima revealed by camera trapping: Patterns with respect to season, daily period and rainfall

Animals are subject to various scales of temporal environmental fluctuations, among which daily and seasonal variations are two of the most widespread and significant ones. Many biotic and abiotic factors change temporally, and climatic factors are particularly important because they directly affect the cost of thermoregulation. The purpose of the present study was to determine the activity patterns of wild Japanese macaques (Macaca fuscata) with a special emphasis on the effect of thermal conditions. We set 30 camera traps in the coniferous forest of Yakushima and monitored them for a total of 8658 camera-days between July 2014 and July 2015. Over the one-year period, temperature had a positive effect, and rainfall had a negative effect on the activity of macaques during the day. Capture rate was significantly higher during the time period of one hour after sunrise and during midday. During winter days, macaques concentrated their activity around noon, and activity shifted from the morning toward the afternoon. This could be interpreted as macaques shifting their activity to warmer time periods within a single day. Japanese macaques decreased their activity during the time before sunrise in seasons with lower temperatures. It was beneficial for macaques to be less active during cooler time periods in a cold season. Even small amounts of rainfall negatively affected the activity of Japanese macaques, with capture rates decreasing significantly even when rainfall was only 0.5–1 mm/min. In conclusion, thermal conditions significantly affected the activity of wild Japanese macaques at various time scales