Gradual onset of the Maunder Minimum revealed by high-precision carbon-14 analyses.

The Sun exhibits centennial-scale activity variations and sometimes encounters grand solar minimum when solar activity becomes extremely weak and sunspots disappear for several decades. Such an extreme weakening of solar activity could cause severe climate, causing massive reductions in crop yields in some regions. During the past decade, the Sun's activity has tended to decline, raising concerns that the Sun might be heading for the next grand minimum. However, we still have an underdeveloped understanding of solar dynamo mechanisms and hence precise prediction of near-future solar activity is not attained. Here we show that the 11-year solar cycles were significantly lengthened before the onset of the Maunder Minimum (1645-1715 CE) based on unprecedentedly high-precision data of carbon-14 content in tree rings. It implies that flow speed in the convection zone is an essential parameter to determine long-term solar activity variations. We find that a 16 year-long cycle had occurred three solar cycles before the onset of prolonged sunspot disappearance, suggesting a longer-than-expected preparatory period for the grand minimum. As the Sun has shown a tendency of cycle lengthening since Solar Cycle 23 (1996-2008 CE), the behavior of Solar Cycle 25 can be critically important to the later solar activity.

Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora.

Fish oil-derived long-chain monounsaturated fatty acids (LCMUFAs) with a carbon chain length longer than 18 units ameliorate cardiovascular risk in mice. In this study, we investigated whether LCMUFAs could improve endothelial functions in mice and humans. In a double-blind, randomized, placebo-controlled, parallel-group, multi-center study, healthy subjects were randomly assigned to either an LCMUFA oil (saury oil) or a control oil (olive and tuna oils) group. Sixty subjects were enrolled and administrated each oil for 4 weeks. For the animal study, ApoE-/- mice were fed a Western diet supplemented with 3% of either gadoleic acid (C20:1) or cetoleic acid (C22:1) for 12 weeks. Participants from the LCMUFA group showed improvements in endothelial function and a lower trimethylamine-N-oxide level, which is a predictor of coronary artery disease. C20:1 and C22:1 oils significantly improved atherosclerotic lesions and plasma levels of several inflammatory cytokines, including IL-6 and TNF-α. These beneficial effects were consistent with an improvement in the gut microbiota environment, as evident from the decreased ratio of Firmicutes and/ or Bacteroidetes, increase in the abundance of Akkermansia, and upregulation of short-chain fatty acid (SCFA)-induced glucagon-like peptide-1 (GLP-1) expression and serum GLP-1 level. These data suggest that LCMUFAs alter the microbiota environment that stimulate the production of SCFAs, resulting in the induction of GLP-1 secretion. Fish oil-derived long-chain monounsaturated fatty acids might thus help to protect against cardiovascular disease.

Prolonged production of 14C during the ~660 BCE solar proton event from Japanese tree rings.

Annual rings record the intensity of cosmic rays (CRs) that had entered into the Earth's atmosphere. Several rapid 14C increases in the past, such as the 775 CE and 994CE 14C spikes, have been reported to originate from extreme solar proton events (SPEs). Another rapid 14C increase, also known as the ca. 660 BCE event in German oak tree rings as well as increases of 10Be and 36Cl in ice cores, was presumed similar to the 775 CE event; however, as the 14C increase of approximately 10‰ in 660 BCE had taken a rather longer rise time of 3-4 years as compared to that of the 775 CE event, the occurrence could not be simply associated to an extreme SPE. In this study, to elucidate the rapid increase in 14C concentrations in tree rings around 660 BCE, we have precisely measured the 14C concentrations of earlywoods and latewoods inside the annual rings of Japanese cedar for the period 669-633 BCE. Based on the feature of 14C production rate calculated from the fine measured profile of the 14C concentrations, we found that the 14C rapid increase occurred within 665-663.5 BCE, and that duration of 14C production describing the event is distributed from one month to 41 months. The possibility of occurrence of consecutive SPEs over up to three years is offered.

Earliest datable records of aurora-like phenomena in the astronomical diaries from Babylonia.

The astronomical diaries from Babylonia (ADB) are excellent sources of information of natural phenomena, including astronomical ones, in pre-Christ era because it contains the record of highly continuous and systematic observations. In this article, we present results of a survey of aurora-like phenomena in ADB, spanning from BCE 652 to BCE 61. We have found nine records of aurora-like phenomena. Philological and scientific examinations suggest that five of them can be considered as likely candidate for aurora observations. They provide unique information about the solar and aurora activities in the first millennium BCE. Graphical abstract.

Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models.

SCOPE: Fish oil-derived long-chain monounsaturated fatty acids (LCMUFA) containing chain lengths longer than 18 were previously shown to improve cardiovascular disease risk factors in mice. However, it is not known if LCMUFA also exerts anti-atherogenic effects. The main objective of the present study was to investigate the effect of LCMUFA on the development of atherosclerosis in mouse models. METHODS AND RESULTS: LDLR-KO mice were fed Western diet supplemented with 2% (w/w) of either LCMUFA concentrate, olive oil, or not (control) for 12 wk. LCMUFA, but not olive oil, significantly suppressed the development of atherosclerotic lesions and several plasma inflammatory cytokine levels, although there were no major differences in plasma lipids between the three groups. At higher doses 5% (w/w) LCMUFA supplementation was observed to reduce pro-atherogenic plasma lipoproteins and to also reduce atherosclerosis in ApoE-KO mice fed a Western diet. RNA sequencing and subsequent qPCR analyses revealed that LCMUFA upregulated PPAR signaling pathways in liver. In cell culture studies, apoB-depleted plasma from LDLR-K mice fed LCMUFA showed greater cholesterol efflux from macrophage-like THP-1 cells and ABCA1-overexpressing BHK cells. CONCLUSION: Our research showed for the first time that LCMUFA consumption protects against diet-induced atherosclerosis, possibly by upregulating the PPAR signaling pathway.

Long-term dietary supplementation with saury oil attenuates metabolic abnormalities in mice fed a high-fat diet: combined beneficial effect of omega-3 fatty acids and long-chain monounsaturated fatty acids.

BACKGROUND: Pacific saury is a common dietary component in East Asia. Saury oil contains considerable levels of n-3 unsaturated fatty acids (PUFA) and long-chain monounsaturated fatty acids (LCMUFA) with aliphatic tails longer than 18 carbons. In our previous study, consumption of saury oil for 4 to 6 wk improved insulin sensitivity and the plasma lipid profile in mice. However, the long-term effects of saury oil on metabolic syndrome (MetS) risk factors remain to be demonstrated. In the current study, we examined the long-term effects of saury oil on mice fed a high-fat diet, and compared the effect of n-3 PUFA EPA and LCMUFA on MetS risk factor in diet-induced obese mice. METHODS AND RESULTS: In Experiment 1, male C57BL/6 J mice were fed either a 32% lard diet (control) or a diet containing 22% lard plus 10% saury oil (saury oil group) for 18 weeks. Although no differences were found in body weight and energy expenditure between the control and saury oil groups, the saury oil diet decreased plasma insulin, non-HDL cholesterol, hepatic steatosis, and adipocyte size, and altered levels of mRNA transcribed from genes involved in insulin signaling and inflammation in adipose tissue. Organ and plasma fatty acid profile analysis revealed that consumption of saury oil increased n-3 PUFA and LCMUFA (especially n-11 LCMUFA) levels in multiple organs, and decreased the fatty acid desaturation index (C16:1/C16:0; C18:1/C18:0) in liver and adipose tissue. In Experiment 2, male C57BL/6 J mice were fed a 32% lard diet (control), a diet containing 28% lard plus 4% EPA (EPA group), or a diet containing 20% lard plus 12% LCMUFA concentrate (LCMUFA group) for 8 weeks. EPA or LCMUFA intake increased organ levels of EPA and LCMUFA, respectively. Consumption of EPA reduced plasma lipid levels and hepatic lipid deposition, and decreased the fatty acid desaturation index in liver and adipose tissue. Consumption of LCMUFA decreased plasma non-HDL cholesterol, improved hyperinsulinemia, and decreased the fatty acid desaturation index in adipose tissue. EPA accumulated mainly in liver, and LCMUFA (especially n-11 LCMUFA) accumulated mainly in white adipose tissue, suggesting their possible individual biological effects for improving MetS. CONCLUSION: Our results suggest that saury oil-mediated improvement of metabolic syndrome in diet-induced obese mice may possibly be due to a combined effect of n-3 PUFA and LCMUFA.

Dietary supplementation with long-chain monounsaturated fatty acids attenuates obesity-related metabolic dysfunction and increases expression of PPAR gamma in adipose tissue in type 2 diabetic KK-Ay mice.

The objective of present study was to examine the effect of long-chain monounsaturated fatty acids (LC-MUFAs) with chain lengths longer than 18 (i.e., C20:1 and C22:1 isomers combined) on obesity-related metabolic dysfunction and its molecular mechanisms. Type-2 diabetic KK-Ay mice (n = 20) were randomly assigned to the 7% soybean oil-diet group (control group) and 4% LC-MUFA concentrate-supplemented-diet group (LC-MUFA group). At 8 weeks on the diet, the results showed that plasma, liver and adipose tissue levels of C20:1 and C22:1 isomers increased significantly with LC-MUFA treatment. Supplementation with LC-MUFAs markedly reduced white fat pad weight as well as adipocyte size in the mice. The levels of plasma free fatty acids, insulin, and leptin concentration in the obese diabetic mice of the LC-MUFA group were also decreased as compared with the mice in the soybean oil-diet control group. Dietary LC-MUFAs significantly increased the mRNA expression of peroxisome proliferator-activated receptor gamma (Pparg), lipoprotein lipase (Lpl), fatty acid transport protein (Fatp), fatty acid translocase/CD36 (Cd36), as well as mRNA expression of genes involved in lipid oxidation such as carnitine palmitoyltransferase-1A (Cpt1a) and citrate synthase (Cs), and decreased the mRNA expression of inflammatory marker serum amyloid A 3 (Saa3) in the adipose tissues of diabetic mice. The results suggest that LC-MUFAs may ameliorate obesity-related metabolic dysfunction partly through increased expression of Pparg as well as its target genes, and decreased inflammatory marker expression in white adipose tissue.

Ingestion of a single serving of saury alters postprandial levels of plasma n-3 polyunsaturated fatty acids and long-chain monounsaturated fatty acids in healthy human adults.

BACKGROUND: Saury oil contains considerable amounts of n-3 polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) with long aliphatic tails (>18C atoms). Ingestion of saury oil reduces the risk of developing metabolic syndrome concomitant with increases in n-3 PUFA and long-chain MUFA in plasma and organs of mice. We therefore evaluated changes in postprandial plasma fatty acid levels and plasma parameters in healthy human subjects after ingestion of a single meal of saury. FINDINGS: Five healthy human adults ingested 150 g of grilled saury. Blood was collected before the meal and at 2, 6, and 24 hr after the meal, and plasma was prepared. Plasma levels of eicosapentaenoic acid, docosahexaenoic acid, and long-chain MUFA (C20:1 and C22:1 isomers combined) increased significantly throughout the postprandial period compared with the pre-meal baseline. Postprandial plasma insulin concentration increased notably, and plasma levels of glucose and free fatty acids decreased significantly and subsequently returned to the pre-meal levels. CONCLUSIONS: Our study suggests that a single saury meal may alter the postprandial plasma levels of n-3 PUFA and long-chain MUFA in healthy human subjects.

Diet high in fat and sucrose induces rapid onset of obesity-related metabolic syndrome partly through rapid response of genes involved in lipogenesis, insulin signalling and inflammation in mice.

BACKGROUND: Frequent consumption of a diet high in fat and sucrose contributes to lifestyle-related diseases. However, limited information is available regarding the short-term effects of such a diet on the onset of obesity-associated metabolic abnormalities. METHODS: Male C57BL/6 J mice were divided into two groups and fed a standard chow diet (control group) or a high fat-high sucrose diet containing 21% fat and 34% sucrose (HF-HS diet group) for 2 or 4 weeks. RESULTS: The HF-HS diet significantly induced body weight gain beginning at week 1 and similarly increased mesenteric white adipose tissue weight and plasma insulin levels at weeks 2 and 4. Plasma resistin levels were notably elevated after feeding with the HF-HS diet for 4 weeks. Measurement of hepatic triglycerides and Oil Red O staining clearly indicated increased hepatic lipid accumulation in response to the HF-HS diet as early as 2 weeks. Quantitative PCR analysis of liver and white adipose tissue indicated that, starting at week 2, the HF-HS diet upregulated mRNA expression from genes involved in lipid metabolism and inflammation and downregulated genes involved in insulin signalling. Although plasma cholesterol levels were also rapidly increased by the HF-HS diet, no differences were found between the control and HF-HS diet-fed animals in the expression of key genes involved in cholesterol biosynthesis. CONCLUSIONS: Our study demonstrates that the rapid onset of hepatosteatosis, adipose tissue hypertrophy and hyperinsulinemia by ingestion of a diet high in fat and sucrose may possibly be due to the rapid response of lipogenic, insulin signalling and inflammatory genes.

Comparison between famciclovir and valacyclovir for acute pain in adult Japanese immunocompetent patients with herpes zoster.

Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster-associated pain including post-herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2-3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3-4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.

9,400 years of cosmic radiation and solar activity from ice cores and tree rings.

Understanding the temporal variation of cosmic radiation and solar activity during the Holocene is essential for studies of the solar-terrestrial relationship. Cosmic-ray produced radionuclides, such as (10)Be and (14)C which are stored in polar ice cores and tree rings, offer the unique opportunity to reconstruct the history of cosmic radiation and solar activity over many millennia. Although records from different archives basically agree, they also show some deviations during certain periods. So far most reconstructions were based on only one single radionuclide record, which makes detection and correction of these deviations impossible. Here we combine different (10)Be ice core records from Greenland and Antarctica with the global (14)C tree ring record using principal component analysis. This approach is only possible due to a new high-resolution (10)Be record from Dronning Maud Land obtained within the European Project for Ice Coring in Antarctica in Antarctica. The new cosmic radiation record enables us to derive total solar irradiance, which is then used as a proxy of solar activity to identify the solar imprint in an Asian climate record. Though generally the agreement between solar forcing and Asian climate is good, there are also periods without any coherence, pointing to other forcings like volcanoes and greenhouse gases and their corresponding feedbacks. The newly derived records have the potential to improve our understanding of the solar dynamics and to quantify the solar influence on climate.

Pollock oil supplementation modulates hyperlipidemia and ameliorates hepatic steatosis in mice fed a high-fat diet.

BACKGROUND: Hyperlipidemia associated with obesity is closely related to the development of atherosclerosis. Both n-3 polyunsaturated fatty acids (PUFAs) and long-chain monounsaturated fatty acids (MUFAs; i.e., C20:1 and C22:1 isomers) supplementation modulate risk factors for metabolic syndrome via multiple mechanisms, including the restoration of impaired lipid metabolism. We therefore examined the effects of pollock oil, which contains a considerable amount of n-3 PUFAs as well as long-chain MUFAs, on plasma hyperlipidemia and hepatic steatosis in diet-induced obese mice. METHODS: Male C57BL/6J mice (24-26 g) were divided into two groups (n = 10/group) and were fed a high-fat diet containing 32% lard (control group) or 17% lard plus 15% pollock oil (experimental group) for 6 weeks. For both groups, fat comprised 60% of the total caloric intake. RESULTS: Although body and liver masses for the two groups did not differ significantly, hepatic lipids concentrations (triglycerides and total cholesterols) were lower (P < 0.05) after pollock oil ingestion. After 2 weeks on the specified diets, plasma lipid levels (total cholesterol, LDL cholesterol, and triglycerides) significantly decreased (P < 0.05) in the experimental group compared with the control group, although plasma HDL cholesterol levels did not differ. At the end of 6 weeks, plasma adiponectin levels increased (P < 0.05), whereas plasma resistin and leptin levels decreased (P < 0.05) in the experimental mice. Increased levels of long-chain MUFAs and n-3 PUFAs in plasma, liver and adipose tissue by ingesting pollock oil were possibly correlated to these favorable changes. Expression of hepatic genes involved in cholesterol metabolism (SREBP2, HMGCR, and ApoB) and lipogenesis (SREPB1c, SCD-1, FAS, and Acacα) was suppressed in the experimental group, and may have favorably affected hyperlipidemia and hepatic steatosis induced by the high-fat diet. CONCLUSIONS: We demonstrated that pollock oil supplementation effectively improved hyperlipidemia, attenuated hepatic steatosis, and downregulated the express of hepatic genes involved in cholesterol and lipid metabolism in mice with diet-induced obesity.

Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-Ay Mice with genetic type 2 diabetes.

BACKGROUND: Studies have demonstrated the beneficial effect of palmitoleic acid (C16:1 n-7) on reducing muscle insulin resistance and preventing beta-cell apoptosis. However, the effect of palmitoleic acid on diabetes remains to be elucidated. The aim of this study was to examine the antidiabetic effect of palmitoleic acid in KK-Ay mice, a spontaneous model for studies of obese type 2 diabetes with low insulin sensitivity. METHODS: KK-Ay mice were orally administered vehicle, 300 mg/kg of palmitoleic acid, or 300 mg/kg of palmitic acid (C16:0) on a daily basis for 4 weeks. RESULTS: Palmitoleic acid reduced body weight increase, ameliorated the development of hyperglycemia and hypertriglyceridemia, and improved insulin sensitivity. In addition, hepatic characteristics were significantly affected, as weight of the liver and hepatic triglyceride levels were lower in the palmitoleic acid group when compared to the control (vehicle and palmitic acid groups). Oil red O staining clearly indicated reduced hepatic lipid accumulation in response to palmitoleic acid. Furthermore, palmitoleic acid down-regulated mRNA expressions of proinflammatory adipocytokine genes (TNFα and resistin) in white adipose tissue and lipogenic genes (SREBP-1, FAS, and SCD-1) in liver. CONCLUSIONS: These results suggest that palmitoleic acid improves hyperglycemia and hypertriglyceridemia by increasing insulin sensitivity, in part owing to suppressing proinflammatory gene expressions and improving hepatic lipid metabolism in diabetic mice.

Beneficial effects of dietary fish-oil-derived monounsaturated fatty acids on metabolic syndrome risk factors and insulin resistance in mice.

The aim of this study was to elucidate the effect of fish-oil-derived monounsaturated fatty acids (MUFAs) containing large amounts of C20:1 and C22:1 isomers on metabolic disorders in mice. Male C57BL/6J mice were fed a 32% lard diet (control) or a 27% lard plus 5% saury-oil-derived MUFA diet for 6 weeks. Dietary MUFA improved insulin resistance and alleviated metabolic syndrome risk factors by reducing blood glucose and lipids. These favorable changes may be attributed to an improved adipocytokine profile. MUFA ingestion resulted in favorable changes in mRNA expression of genes involved in glucose/lipid metabolism (SCD-1, CPT1a, UCPs, and CS) as well as inflammation (MAC1, MMP3, and SAA3) and alterations in fatty acid composition. Our data suggest that marine MUFA improved glucose/lipid homeostasis and hindered the development of metabolic syndrome in obese mice.

Dietary saury oil reduces hyperglycemia and hyperlipidemia in diabetic KKAy mice and in diet-induced obese C57BL/6J mice by altering gene expression.

We investigated the effect of saury oil on the alleviation of metabolic syndrome in mice. Saury oil contains 18% (w/w/) n-3 polyunsaturated fatty acids (n-3 PUFA) and 35% (w/w) monounsaturated fatty acids (MUFA). Diabetic KKAy mice were fed a 10% soybean oil diet (control) or a 10% saury oil diet for 4 weeks, and diet-induced obese C57BL/6J mice were fed a high-fat diet containing 32% lard (control) or 22% lard plus 10% saury oil for 6 weeks. After the intervention periods, the levels of glucose, insulin and lipids in plasma had decreased significantly for the saury oil diet group, and insulin sensitivity had improved. These favorable changes may be attributed to the increased adiponectin and decreased TNFα and resistin levels in plasma. The saury oil diet also resulted in downregulated expression of the lipogenic genes (SREBP-1, SCD-1, FAS, and ACC) as well as upregulation of the fatty acid oxidative gene, CPT-1, and the energy expenditure-related genes (PGC1α and PGC1ß) in white adipose tissue for the diet-induced obese C57BL/6J mice. An increase in n-3 PUFA levels and the concomitant decrease in the n-6/n-3 PUFA level ratio in serum, white adipose tissue, and liver with a saury oil diet are likely to be involved in the beneficial changes to the metabolic indicators. MUFA may also play a positive role in remodeling lipid composition. Based on these mice models, our results suggest a potential use for saury oil for improving metabolic abnormalities.

Synchronized Northern Hemisphere climate change and solar magnetic cycles during the Maunder Minimum.

The Maunder Minimum (A.D. 1645-1715) is a useful period to investigate possible sun-climate linkages as sunspots became exceedingly rare and the characteristics of solar cycles were different from those of today. Here, we report annual variations in the oxygen isotopic composition (δ(18)O) of tree-ring cellulose in central Japan during the Maunder Minimum. We were able to explore possible sun-climate connections through high-temporal resolution solar activity (radiocarbon contents; Δ(14)C) and climate (δ(18)O) isotope records derived from annual tree rings. The tree-ring δ(18)O record in Japan shows distinct negative δ(18)O spikes (wetter rainy seasons) coinciding with rapid cooling in Greenland and with decreases in Northern Hemisphere mean temperature at around minima of decadal solar cycles. We have determined that the climate signals in all three records strongly correlate with changes in the polarity of solar dipole magnetic field, suggesting a causal link to galactic cosmic rays (GCRs). These findings are further supported by a comparison between the interannual patterns of tree-ring δ(18)O record and the GCR flux reconstructed by an ice-core (10)Be record. Therefore, the variation of GCR flux associated with the multidecadal cycles of solar magnetic field seem to be causally related to the significant and widespread climate changes at least during the Maunder Minimum.

Isolation and identification of antihypertensive peptides from antarctic krill tail meat hydrolysate.

Antarctic krill (Euphausia superba) obtained from the huge biomass in Antarctic waters is an important food product in Japan. Antarctic krill peptide powder (AKPP) prepared from the tail meat by enzymatic hydrolysis significantly decreased the systolic blood pressure in spontaneously hypertensive rats by a single oral administration (1, 10, or 100 mg). Presumably, the effect of AKPP was through inhibition of the conversion of angiotensin, which mediates blood pressure elevation, from its inactive propeptide to the mature angiotensin. Two potent angiotensin I-converting enzyme (ACE) inhibitory peptides were isolated from AKPP by high-performance liquid chromatography (HPLC) and identified as Val-Trp (IC(50)= 2.75 microg/mL; 12.9 microM) and Leu-Lys-Tyr (IC(50)= 4.26 microg/mL; 10.1 microM). Val-Trp and Leu-Lys-Tyr comprised 0.025%+/- 0.0023% (w/w) and 0.018%+/- 0.0023% (w/w) of AKPP, respectively, as measured by electrospray ionization mass spectrometry (ESI-MS). The contributions of Val-Trp and Leu-Lys-Tyr to the ACE inhibitor activity of AKPP were 17.7%+/- 1.60% and 8.04%+/- 1.03%, respectively, suggesting that these 2 peptides constitute a substantial portion of the overall ACE inhibitor potential of AKPP.