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BMC Physiology
Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity
Alexandre Dal-Pan1,
Stéphane Blanc2 &
Fabienne Aujard1
BMC Physiology volume 10, Article number: 11 (2010) Cite this article
Resveratrol, a natural polyphenolic compound, was shown to protect rodents against high-fat-diet induced diabesity by boosting energy metabolism. To the best of our knowledge, no data is yet available on the effects of resveratrol in non-human primates. Six non-human heterotherm primates (grey mouse lemurs, Microcebus murinus) were studied during four weeks of dietary supplementation with resveratrol (200 mg/kg/day) during their winter body-mass gain period. Body mass, spontaneous energy intake, resting metabolic rate, spontaneous locomotor activity and daily variations in body temperature were measured. In addition, the plasma levels of several gut hormones involved in satiety control were evaluated.
Resveratrol reduced the seasonal body-mass gain by concomitantly decreasing energy intake by 13% and increasing resting metabolic rate by 29%. Resveratrol supplementation inhibited the depth of daily torpor, an important energy-saving process in this primate. The daily amount of locomotor activity remained unchanged. Except for an increase in the glucose-dependent insulinotropic polypeptide, a gut hormone known to promote mobilization of fat stores, no major change in satiety hormone plasma levels was observed under resveratrol supplementation.
These results suggest that in a non-human primate, resveratrol reduces body-mass gain by increasing satiety and resting metabolic rate, and by inhibiting torpor expression. The measured anorectic gut hormones did not seem to play a major role in these observations.
Obesity stems from a prolonged imbalance between the level of energy intake and energy expenditure, with the resultant surplus being stored as lipids predominantly in adipose tissue, but also in muscle and liver tissue, triggering features of the metabolic syndrome. Understanding the factors which regulate both energy intake and expenditure, such as environmental/lifestyle manipulations or pharmaceuticals, is an important step towards developing obesity treatments.
The physiological benefits of resveratrol (3,4',5-trihydroxystilbene or RSV), a natural polyphenol, are currently under intensive investigation. Resveratrol is produced by plants in response to infection by the pathogen Botrytis cinerea [1]. It is also induced in response to a variety of stress conditions (climate, exposure to ozone, sunlight and heavy metals) [2]. Presently, it has been detected in more than 70 plant species, including grapes, peanuts, berries and pines [2]. Resveratrol is able to activate nicotinamide adenosine dinucleotide-dependent deacetylase SIRT1 (Silent mating type Information Regulation 2 homologue Type 1), one of the seven mammalian sirtuins [3, 4] involved in glucose homeostasis and lipid metabolism. This activation of SIRT1 by RSV seems to prevent obesity by inducing oxidative mitochondrial metabolism [5] and reduced insulin resistance [6] in mice on a high-caloric diet. In the same way, RSV minimizes hyperglycaemia in diet-induced obese and diabetic mice [7], and dyslipidemia in the experimental model of obese Zucker rats. These rodent models are widely used as animal models of obesity and type 2 diabetes which present many features of the human metabolic syndrome [8]. The validity of information obtained in primates, particularly in humans, is still under debate because the experimental protocols used in the preliminary studies were quite different from each other [9]. Moreover, recent works have demonstrated that RSV supplementation mimics caloric restriction in mice [10], suggesting that RSV could be a good candidate for the development of obesity therapies.
However, most RSV studies focused on changes in energy expenditure and its related cellular mechanisms [11, 12] and were mainly obtained from genetically modified mouse models of obesity [13] or in the context of a high-fat diet [14, 11]. The effects of RSV on spontaneous food intake and its regulation are still unclear and still unknown in primates.
The aim of the present study was thus to determine the effects of a four-week RSV supplementation on energy metabolism and spontaneous food intake in a non-human primate, the grey mouse lemur (Microcebus murinus), which demonstrates seasonal spontaneous obesity. Grey mouse lemurs present high photoperiod-dependent variations in body mass associated with energy saving mechanisms, in particular a phase of heterothermia during their daily resting period. When exposed to a short photoperiod, mouse lemurs display a fast and linear body-mass gain (about 6-8 g/week) associated with a high caloric intake. In just a few weeks, a near 100% increase in body mass is observed due to high levels of fat storage, while the duration and depth of daily hypothermia bouts increase [15, 16].
The effect of RSV supplementation on body mass, resting metabolic rate (RMR), daily body temperature (Tb) variations and spontaneous food intake in the grey mouse lemur was explored to investigate of the hypothesis that RSV supplementation will affect the time courses of pre-wintering fattening mechanisms in this primate. Because previous studies on mouse lemurs have suggested that several gut hormones may be related to the pre-wintering fattening phase and to the daily heterothermia expression [17], we also tested the effects of RSV supplementation on several gut-derived peptide hormones that are involved in numerous aspects of fuel homeostasis [18]. We measured glucagon-like peptide 1 (GLP-1), pancreatic polypeptide (PP), peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP). Glucagon-like peptide 1 and PYY were shown to decrease energy expenditure and food intake [19]. Conversely, PP and GIP induced an increase in energy expenditure, motor activity and mobilization of fat stores [20]. Consequently, possible relationships between the key parameters involved in energy balance regulation and gut hormones in grey mouse lemurs were also investigated.
During the control week prior to RSV supplementation, the studied animals presented an average body-mass gain of 6.2 ± 1.3% (1.2 g/d) from their initial mass (133 ± 4 g). At the end of the four weeks of RSV supplementation, the body-mass gain was gradually suppressed to 1.0 ± 0.3% (0.5 g/d, F = 14.0, df = 4, p = 0.007, Figure 1A). A 13% decrease in spontaneous food intake was noted from the third week of RSV treatment (from 121.4 kJ/d to 104.7 kJ/d, F = 10.4, df = 4, p = 0.035, Figure 1B). The RMR increased by 29% after four weeks of RSV treatment compared to the control period (F = 12.7, df = 4, p = 0.013, Figure 1C). Total daily locomotor activity (LA) was not modified by RSV treatment (164 ± 23 a.u. in the control week vs. 168 ± 12 a.u. in the fourth week of treatment, F = 0.4, df = 4, p = 0.980, Figure 1D). A representative profile of the weekly average of variations in Tb of one mouse lemur is represented in Figure 2A. The mouse lemurs exhibited a significant increase in their mean Tb during the diurnal phase (Tb day) with a gain of 1.0 ± 0.3°C between the control and the fourth week of treatment (34.7 ± 0.5°C vs. 35.6 ± 0.1°C, F = 14.3, df = 4, p = 0.006). The minimal Tb value (Tb min) of the animals increased by 1.5 ± 0.6°C between the control and the fourth week of treatment (32.4 ± 0.8°C vs. 33.9 ± 0.4°C, F = 11.1, df = 4, p = 0.026). The amplitude of the phase of daily hypothermia was greatly reduced in response to RSV supplementation. On the other hand, no significant change in the mean Tb during the active nocturnal phase (Tb night) was found in response to RSV supplementation (36.4 ± 0.1°C vs. 36.6 ± 0.1°C, F = 3.3, df = 4, p = 0.504) (Figure 2B).
Resveratrol effects on parameters of energy balance. Six male mouse lemurs were observed during one week of ad libitum feeding (Control), followed by four weeks of RSV supplementation to the ad libitum feeding (RSV1, 2, 3 and 4). The curves represent the evolution with time of food intake (A), body-mass gain (B), resting metabolic rate (RMR) (C) and daily amount of locomotor activity (LA) (D). Values are given as mean ± SEM. Resveratrol supplementation induced a significant decrease in food intake and body-mass gain associated with an increase in RMR. The amount of LA was not modified by the treatment.
Resveratrol effects on body temperature of the animals. Six male mouse lemurs were observed during one week of ad libitum feeding (Control), followed by four weeks of RSV supplementation to the ad libitum feeding (RSV1, 2, 3 and 4). Panel (A) represents the average daily profiles of the Tb of one representative mouse lemur during the control week and during each week of RSV supplementation. Panel (B) illustrates the evolution of the diurnal (Tb day), nocturnal (Tb night) and minimal (Tb min) body temperatures according to the duration of treatment. Values are given as mean ± SEM. Resveratrol supplementation induced a clear reduction of the phase of daily torpor revealed by the significant increase in Tb day and Tb min values over the course of treatment.
No significant time-course change was reported for GLP-1, PP and PYY levels. Only the GIP level was significantly increased by RSV after four weeks of supplementation (104 ± 14 pg/ml in the control week vs. 175 ± 39 pg/ml in the fourth week, F = 11.6, df = 4, p = 0.021) (Table 1). Although trends are visible, the increased inter-individual variability observed during the treatment (from 21% to 61%, F = 14.3, df = 4, p = 0.002) did not allow any significant conclusion to be reached. Lastly, no significant correlation could be found between the variations in gut hormones and the variations in body-mass gain, food intake or RMR (Table 2).
Table 1 Resveratrol effects on the levels of the different gut hormones tested during the four weeks of treatment.
Table 2 Correlations between the variations in gut hormone levels and the variations in energy parameters.
The main findings of this study were: 1) a four-week resveratrol supplementation had significant effects on energy metabolism in the mouse lemur, characterized by a reduction in seasonal body-mass gain associated with an increase in resting metabolic rate and a decrease in food intake; 2) the response to resveratrol supplementation mainly involved a strong reduction of daily heterothermia expression with no change in the daily amount of locomotor activity; 3) despite the fact that glucose-dependent insulinotropic polypeptide (GIP) values increased during resveratrol supplementation, no correlation was evidenced between the other tested gut hormones and changes in energy balance parameters.
Resveratrol supplementation was given to mouse lemurs at the very time of seasonal fattening induced by exposure to short day lengths. This period corresponds to an increase in both spontaneous food intake and frequency of deep torpor, leading to fast body mass gain through fat accumulation. Moreover, the resting metabolic rate and locomotor activity decrease, reinforcing the energy saving processes. Resveratrol supplementation appeared to limit all these energy saving mechanisms by acting more specifically on food intake and daily hypothermia bouts without change in locomotor activity.
The observed decrease in food intake in mouse lemurs cannot be related to the palatability of resveratrol as the mouse lemurs were not found to be averse to resveratrol prior to the experiment. It is more likely that an aversive palatability of resveratrol would have led to an immediate reduction in food intake which was not observed. However, the effects on food intake might have been related to the dose of resveratrol given. The dosage level administered in this study (200 mg/kg) was selected from studies in the literature on rodents, and was intermediate between the 40 mg/kg of Baur et al. [14] and the 400 mg/kg of Lagouge et al. [12]. This dose was carefully mixed in the food and, since the animals tended to eat less than provided, the actual ingested dose of resveratrol was below 200 mg/kg. The amount of resveratrol ingested by the animals was 96.1% in the first week and 84% in the fourth week (corresponding to an equivalent of 192 mg/kg/day and 168 mg/kg/day, respectively). These amounts, based on the existing literature, appeared sufficiently high to be effective in mammals [21–23]. However, the observed satiety in resveratrol-supplemented mouse lemurs may be a sensibility response specific to this species or to primates.
Although the change in food intake could explain the reduction of seasonal body-mass gain, resveratrol supplementation significantly affected the body temperature patterns in the mouse lemur. Average values of energy savings by daily torpor in this species have been estimated to be about 40-70% as compared to the maintenance of normothermia [24, 25]. Under resveratrol supplementation, the depth and the duration of daily torpor decreased and were associated with an increase in both body temperature and resting metabolic rate during the daily resting period. In contrast, body temperature values during the night active phase were not modified, and nor was locomotor activity. The decrease in energy savings during the daily diurnal rest would thus contribute to the reduction in body-mass gain under resveratrol supplementation.
No such effect of resveratrol has been shown in mice, for which no change in food intake or body temperature was observed [11, 13]. However, these data originate from experimentally-induced obesity and it is likely that the responses observed in mouse lemurs rely on specific life-history traits of this primate, which has developed high seasonal energy saving mechanisms and exhibits pre-wintering spontaneous obesity.
Resveratrol activates mammalian sirtuins, more specifically SIRT1, which is involved in glucose homeostasis and lipid metabolism. In mice exposed to a high-fat diet or in ob/ob mice, resveratrol was shown to protect mice from diet-induced metabolic disorders [12, 13, 26] by mimicking some effects of caloric restriction. Likewise, resveratrol and assimilated SIRT1 activators have been proposed as potential treatments for type 2 diabetes in mice models [14, 12, 27, 28]. The effects of resveratrol have been suggested to depend on an increase in oxidative mitochondrial metabolism [14] and on enhanced fat oxidation [11], leading to an increase in energy expenditure. Interestingly, SRT1720, which activates SIRT1 by four fold in comparison to resveratrol, induces a significant decrease in fat mass without a change in food intake in mice [11]. In the mouse lemur, concomitantly to an increase in energy expenditure through decreasing hypothermia bouts and increasing metabolism, resveratrol might have a direct negative effect on fat storage.
Due to their involvement in satiety and satiation processes [18, 29, 30], several gut hormones have been measured in resveratrol-supplemented mouse lemurs. No significant change was recorded after four weeks for the glucagon-like peptide 1 and the peptide YY, two gut hormones involved in the reduction of food intake and energy expenditure [31–34]. Conversely, the two other gut hormones are known to induce an increase in energy expenditure. The pancreatic polypeptide increases satiety, thus leading to a loss in body mass [20] and the glucose-dependent insulinotropic polypeptide (GIP) was shown to induce an increase in exploratory behaviour and performance in some motor function tests in a transgenic mouse that over-expressed GIP [35]. Only GIP significantly increased with resveratrol supplementation. Data emerging from studies in animal models and cultured human fat cells support a physiological role for GIP in fat cell metabolism, leading to the mobilization of fat stores [17, 36]. Such effects might have contributed to the reduction in body-mass gain by limiting fat storage in supplemented mouse lemurs. The observed effect of resveratrol on food intake in the mouse lemur appears to be independent of changes in anorexic gut hormones, but the high observed inter-individual variability in our study does not allow definite conclusions to be reached. Moreover, because sampling was performed at a single point in fasted animals during the diurnal rest, changes may have been missed.
Resveratrol has been studied as a potential mimetic of caloric restriction [4]. However, caloric restriction decreases the metabolic rate [37], whereas resveratrol had the opposite effect [12]. From previous studies using moderate caloric restriction in wintering mouse lemurs [17], the effects of resveratrol significantly differed from changes observed in caloric-restricted animals. In the mouse lemurs, caloric restriction led to an increase in the duration and depth of daily torpor bouts. These body temperature adjustments were efficient at preventing body-mass loss and were not associated with changes in gut hormones [17].
In conclusion, we demonstrated for the first time the short-term effects of resveratrol on the metabolism of an heterothermic primate. Resveratrol activates energy expenditure by inducing an increase in resting metabolic rate and a decrease in torpor patterns that play key roles in energy saving in this primate. Moreover, resveratrol had a satiety effect in this primate that reduced their spontaneous food intake. All of these changes participated in the limitation of pre-wintering fattening processes in which the increase in the glucose-dependent insulinotropic polypeptide levels would play an additive role. These results provide novel information on the potential effects of resveratrol on energy metabolism and control of body mass in a primate.
Animals and animal care
We used six male grey mouse lemurs (Microcebus murinus, Cheirogaleidae, primates) born in a laboratory breeding colony in Brunoy, France (Agreement # 962773) from a population originally caught 40 years ago on the southwest coast of Madagascar. The animals were 3-year-old adults and presented a mean ± standard error of the mean (SEM) body mass of 133 ± 4 g. Conditions were constant in respect to ambient temperature (25°C), relative humidity (55%), and ad libitum food availability. Behavioural and physiological seasonal changes in mouse lemurs are dependent on the photoperiod and are reproduced in captivity using an artificial photoperiodic regimen. In the breeding colony, animals were exposed to an artificial photoperiodic regimen consisting of alternating six-month periods of Malagasy winter-like short-day lengths (light:dark 10:14) and Malagasy summer-like long-day lengths (light:dark 14:10). Animals were studied during the five weeks following the shift from long to short day lengths corresponding to the pre-wintering fattening period. To minimize social influences, the animals were housed individually in cages (0.4 × 0.4 × 0.6 m) provided with nesting materials, and were separated from each other by wooden partitions. Each week and just before the daily food allotment, animals were weighed inside their nest box, to avoid any stress, using a balance accurate to 1 g.
All animals were fed ad libitum during one week, with fresh fruit (bananas and apples) and a mixture of cereals, milk and eggs, providing them with a total of 126 kJ per day. The cereals were composed of 60% carbohydrates, 10% proteins and 30% lipids. The cereals were primarily wheat flour (96%). The mixture was introduced 1 h before the beginning of the animal's nocturnal active phase (Figure 3A). Water was always given ad libitum. During the following four weeks (RSV1, RSV2, RSV3 and RSV4), the animals were fed the same as above but 200 mg/kg of RSV (Sequoia Research Products, United Kingdom) per day was added to the mixture. Prior to the study, we monitored the food intake of the six animals presented with a choice between a bowl of control food and a bowl of food supplemented with 200 mg/kg/day of RSV. Food was provided ad libitum in both bowls. Food intake was assessed by weighing the daily leftovers and correcting for water evaporation (calculated previously with the control mixture under the same environmental conditions). The average daily amounts of food eaten were similar between control and RSV supplemented groups (t = 1.738, df = 5, p = 0.143), evidencing no significant difference in the palatability of the mixtures. To determine the exact quantity of food ingested by the animals, daily leftovers were weighed and corrected for water evaporation as with the palatability control. All the procedures were carried out in accordance with the European Communities Council Directive (86/609/EEC). All the experiments were done under personal licence to experiment on mouse lemurs, delivered by the Ministry of Education and Science after approval of a local Ethics Committee (n° 91-305, issued 20 July, 2006).
Experimental timetable. A) The activity phase (17h-7h) and the resting phase (7h-17h) are represented in this schematic profile of body temperature variations of one animal during one day. The animals were followed for five weeks: one control week and four weeks with RSV supplementation (200 mg/kg/day). The mouse lemurs were fed daily one hour before the beginning of their active phase during the five-week study. Blood sampling and measurement of the resting metabolic rate (RMR) were carried out once a week (each one on a different day) during the control period and each week of RSV treatment during their daily resting period, 4-6 h after the beginning of the light period to minimize the influence of circadian variations. B) This long-term experimental time line shows when the telemetry surgery, acclimation and first experiments were performed. The telemetry surgery was performed two weeks before the beginning of the short day period to allow animals to recover before beginning the experiment. The white arrows represent the moment when blood sampling, measurement of resting metabolic rate (RMR) and body weight were undertaken (once a week). The body temperature (Tb) and locomotor activity (LA) were continuously recorded during the five weeks from the shift to short day period.
Resting metabolic rate
Oxygen consumption was measured in a closed indirect calorimetry system. Measurements on post-absorptive animals were made daily during their resting period, 4-6 h after the beginning of the light period to minimize the influence of circadian variations (Figure 3A). The animals were trained to nest in 2.5 l opaque respiratory chambers with a woven floor to absorb any urine. The respiratory chamber was placed in a cabinet at a controlled ambient temperature of 25.0 ± 0.5°C, a value within the thermoneutral zone defined for the mouse lemur [38]. After a 20 min habituation phase with a constant air flow (2 l/min) drawn through the respirometry chamber from bottom to top, the chamber was closed for a 40-min period. The air was dried prior to analysis using a silica gel. The VO2 consumed by the animal was calculated from initial and final concentrations of O2 in the chamber which were measured from dried gas using a SERVOMEX 570A paramagnetic gas analyser (Servomex Ltd., England) (accuracy 0.01% O2). Calculations were made in Standard Temperature and Pressure, Dry and, the daily atmospheric humidity was accounted for. The oxygen analyser was routinely calibrated with N2 and atmospheric air assuming 21.00% O2 as recommended by the manufacturer. Oxygen consumption was expressed as ml O2/h. The animals were weighed before each measurement. Oxygen consumption was corrected for the body weight of the animal [39]. Body temperature was not measured before the experiment to avoid disturbing sleeping animals but males never enter deep torpor at an ambient temperature of 25°C [40]. However, O2 consumption at 25°C cannot be defined as basal because the body temperature varies in the grey mouse lemur, thus values were referred to as resting metabolic rate (RMR) [15]. The values are given as mean ± SEM.
Recording of locomotor activity and body temperature
The grey mouse lemur is a nocturnal species exhibiting high levels of locomotor activity (LA) during the dark period and complete rest during the light period. Under exposure to short days, the daily rhythm of body temperature (Tb) in the mouse lemur is characterized by high Tb values during the active period and, before the onset of the light phase, a rapid and linear drop in Tb reaching minimal values after 3-4 hours. This hypothermia bout is followed by a spontaneous re-warming to normothermic Tb levels until the following dark phase (Figure 3A).
The recording of LA and Tb was obtained by telemetry at a constant ambient temperature of 25°C. A small telemetric transmitter weighing 2.5 g (model TA10TA-F20, DataScience Co. Ltd, Minnesota, USA) was implanted into the visceral cavity under ketamine anaesthesia (Imalgene, 100 mg/kg ip, Merial, France). Telemetry surgeries were performed 15 days before the beginning of the short day period. After surgery, the animals were returned to their home cage and allowed to recover for 15 days before starting the experiment and the continuous recording of Tb from the beginning of the short day period. Total recovery was checked by visual inspection to ensure complete healing of the surgical incision and by verification of a stable daily pattern of Tb variations. Recording began in the first week following the shift to the short photoperiod (Figure 3B). A receiver board was positioned in the cage and LA (expressed in arbitrary units, a.u.) was continuously recorded during this interval by two antennas located in the receiver board which detected vertical and horizontal movements (X-Y coordinate system, Dataquest Lab Pro v. 3.0, Data Science Co. Ltd, Minnesota, USA). The Tb (in°C) of the animals was recorded every 10 min. The following parameters were analysed: daily amount of LA, mean Tb during the active nocturnal phase (Tb night), mean Tb during the resting diurnal phase (Tb day) and the minimal Tb value (Tb min).
Hormonal assays
Blood sampling was carried out once a week during the control period and in each week of RSV treatment 4-6 h after the beginning of the light period to minimize the influence of circadian variations (Figure 3A). The blood samples were taken via the saphenous vein, without anaesthesia, before food allotment. The volume of blood sampled was 100 μl and that represented less than 2% of the total blood volume of the animals. The blood samples were centrifuged at 7000 rpm at 4°C for 30 min. The plasma was stored at -20°C according to the assay procedure. Levels of glucagon-like peptide 1 (GPL-1), pancreatic polypeptide (PP), peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP) were measured in duplicate using the human gut hormones multiplex panel (LincoplexTM Multiplex Assays, Bioscience) and Luminex technology at the Saint Antoine Hospital in Paris dedicated to micro-assays in small animals (IRSSA, INSERM, IFR65, France), as previously described [17]. The average recoveries of known quantities of standard peptides (taken at the low, medium and high concentrations given in the assay) added to mouse lemur plasma were 89% for GIP, 83% for GLP1, 88% for PP and 107% for PYY. Inter-assay and intra-assay coefficients of variation were < 19% and < 11%, respectively.
All values are expressed as mean ± SEM. We used the Friedman test to assess significant variations in all of the studied parameters. Comparisons were considered to differ significantly when p < 0.05. Possible correlations between the energy balance parameters and gut hormone levels were assessed by Spearman's correlation test. All statistical computations were performed using SYSTAT for Windows (V9, SPSS Inc., Illinois, USA).
a.u.:
arbitrary unit
GIP:
glucose-dependent insulinotropic polypeptide
GLP-1:
glucagon-like peptide 1
locomotor activity
pancreatic polypeptide
PYY:
peptide YY
RMR:
RSV:
RSV1:
first week of RSV supplementation
second week of RSV supplementation
third week of RSV supplementation
fourth week of RSV supplementation
SEM:
standard error of the mean
SIRT1:
Silent mating type Information Regulation 2 homologue Type 1
Tb:
Tb night:
mean Tb during the active nocturnal phase
Tb day:
mean Tb during the resting diurnal phase
Tb min:
minimal Tb value.
Delmas D, Lancon A, Colin D, Jannin B, Latruffe N: Resveratrol as a Chemopreventive Agent: A Promising Molecule for Fighting Cancer. Curr Drug Targets. 2006, 7: 423-442. 10.2174/138945006776359331.
Bavaresco L: Role of viticultural factors on stilbene concentrations of grapes and wine. Drugs Exp Clin Res. 2003, 29: 181-7.
Baur JA, Sinclair DA: Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006, 5 (6): 493-506. 10.1038/nrd2060.
Baur JA: Resveratrol, Sirtuins, and the Promise of a DR Mimetic. Mech Ageing Dev. 2010, 131 (4): 261-269. 10.1016/j.mad.2010.02.007.
Article PubMed Central CAS PubMed Google Scholar
Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado de Oliveira R, Leid M, McBurney MW, Guarente L: Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-[gamma]. Nature. 2004, 429 (6993): 771-776. 10.1038/nature02583.
Sadruddin S, Arora R: Resveratrol: biologic and therapeutic implications. J Cardiometab Synd. 2009, 4 (2): 102-6. 10.1111/j.1559-4572.2008.00039.x.
Ramadori G, Gautron L, Fujikawa T, Vianna CR, Elmquist JK, Coppari R: Central administration of resveratrol improves diet-induced diabetes. Endocrinology. 2009, 150 (12): 5326-33. 10.1210/en.2009-0528.
Rivera L, Morón R, Zarzuelo A, Galisteo M: Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol. 2009, 77 (6): 1053-63. 10.1016/j.bcp.2008.11.027.
Cottart CH, Nivet-Antoine V, Laguillier-Morizot C, Beaudeux JL: Resveratrol bioavailability and toxicity in humans. Mol Nutr Food Res. 2010, 54: 1-10. 10.1002/mnfr.200900437.
Swindell WR: Comparative analysis of microarray data identifies common responses to caloric restriction among mouse tissues. Mech Ageing Dev. 2008, 129 (3): 138-53. 10.1016/j.mad.2007.11.003.
Feige JN, Lagouge M, Canto C, Strehle A, Houten S, Milne JC, Lambert PD, Mataki C, Elliott PJ, Auwerx J: Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab. 2008, 8: 347-358. 10.1016/j.cmet.2008.08.017.
Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J: Resveratrol Improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1[alpha]. Cell. 2006, 127 (6): 1109-1122. 10.1016/j.cell.2006.11.013.
Mayers JR, Iliff BW, Swoap SJ: Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction. FASEB Journal. 2009, 23: 1032-1040. 10.1096/fj.08-115923.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang MY, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA: Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006, 444 (7117): 337-342. 10.1038/nature05354.
Génin F, Perret M: Photoperiod-induced changes in energy balance in gray mouse lemurs. Physiol Behav. 2000, 71 (3-4): 315-321. 10.1016/S0031-9384(00)00335-8.
Terrien J, Zizzari P, Epelbaum J, Perret M, Aujard F: Daily rhythms of core temperature and locomotor activity indicate different adaptive strategies to cold exposure in adult and aged mouse lemurs acclimated to a summer-like photoperiod. Chronobiol Internat. 2009, 26: 1-16. 10.1080/07420520802694103.
Giroud S, Perret M, Le Maho Y, Momken I, Gilbert C, Blanc S: Gut hormones in relation to body mass and torpor pattern changes during food restriction and re-feeding in the gray mouse lemur. J Comp Physiol B. 2008, 179 (1): 99-111. 10.1007/s00360-008-0294-4.
Murphy KG, Dhillo WS, Bloom SR: Gut peptides in the regulation of food intake and energy homeostasis. Endocr Rev. 2006, 27 (7): 719-727.
Shousha S, Nakahara K, Nasu T, Sakamoto T, Murakami N: Effect of glucagon-like peptide-1 and -2 on regulation of food intake, body temperature and locomotor activity in the japanese quail. Neurosci lett. 2007, 415 (2): 102-107. 10.1016/j.neulet.2007.01.007.
Kojima S, Ueno N, Asakawa A, Sagiyama K, Naruo T, Mizuno S, Inui A: A role for pancreatic polypeptide in feeding and body weight regulation. Peptides. 2007, 28 (2): 459-463. 10.1016/j.peptides.2006.09.024.
Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P: Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res. 2009, 53: S7-S15. 10.1002/mnfr.200890054.
Nunes T, Almeida L, Rocha JF, Falcão A, Fernandes-Lopes C, Loureiro AI, Wright L, Vaz-da-Silva M, Soares-da-Silva P: Pharmacokinetics of trans-resveratrol following repeated administration in healthy elderly and young subjects. J Clin Pharmacol. 2009, 49 (12): 1477-1482. 10.1177/0091270009339191.
Juan ME, Maijó M, Planas JM: Quantification of trans-resveratrol and its metabolites in rat plasma and tissues by HPLC. J Pharmaceut Biomed. 2010, 51 (2): 391-398. 10.1016/j.jpba.2009.03.026.
Dausmann KH, Glos J, Ganzhorn JU, Heldmaier G: Hibernation in the tropics: lessons from a primate. J Comp Physiol B. 2005, 175 (3): 147-155. 10.1007/s00360-004-0470-0.
Dausmann K, Glos J, Heldmaier G: Energetics of tropical hibernation. J Comp Physiol B. 2009, 179 (3): 345-357. 10.1007/s00360-008-0318-0.
Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R: Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008, 8: 157-168. 10.1016/j.cmet.2008.06.011.
Smith JJ, Keeney RD, Gagne D, Frushour B, Ladd W, Galonek H, Israelian K, Song J, Razvadauskaite G, Lynch A, Carney D, Johnson R, Lavu S, Iffland A, Elliott P, Lambert P, Elliston K, Jirousek M, Milne J, Boss O: Small molecules activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo. BMC Syst Biol. 2009, 3: 31-10.1186/1752-0509-3-31.
Article PubMed Central PubMed Google Scholar
Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH: Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007, 450: 712-716. 10.1038/nature06261.
Field BC, Chaudhri OB, Bloom SR: Obesity treatment: novel peripheral targets. Brit J Clin Pharmaco. 2009, 68 (6): 830-843. 10.1111/j.1365-2125.2009.03522.x.
Tome D, Schwarz J, Darcel N, Fromentin G: Protein, amino acids, vagus nerve signaling, and the brain. Am J Clin Nutr. 2009, 90 (3): 838S-843S. 10.3945/ajcn.2009.27462W.
Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CMB, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JPH, Smith DM, Ghatei MA, Herbert J, Bloom SR: A role for glucagon-like peptide-1 in the central regulation of feeding. Nature. 1996, 379 (6560): 69-72. 10.1038/379069a0.
Flint A, Raben A, Rehfeld JF, Holst JJ, Astrup A: The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans. Int J obesity. 2000, 24 (3): 288-298. 10.1038/sj.ijo.0801126.
Meier JJ, Gallwitz B, Schmidt WE, Nauck MA: Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives. Eur J Pharmacol. 2002, 440 (2-3): 269-279. 10.1016/S0014-2999(02)01434-6.
Adams SH, Lei C, Jodka CM, Nikoulina SE, Hoyt JA, Gedulin B, Mack CM, Kendall ES: PYY[3-36] administration decreases the respiratory quotient and reduces adiposity in diet-induced obese mice. J Nutr. 2006, 136 (1): 195-201.
Ding KH, Qing Z, Ding X, Chen HX, Della-Fera MA, Bollag RJ, Bollag WB, Gujral R, Baolin K, Sridhar S, Baile C, Curl W, Isales CM: Effects of glucose-dependent insulinotropic peptide on behavior. Peptides. 2006, 27 (11): 2750-2755. 10.1016/j.peptides.2006.05.011.
Yip RGC, Wolfe MM: GIP biology and fat metabolism. Life Sci. 1999, 66 (2): 91-103. 10.1016/S0024-3205(99)00314-8.
Roark AM, Bjorndal KA: Metabolic rate depression is induced by caloric restriction and correlates with rate of development and lifespan in a parthenogenetic insect. Exp Gerontol. 2009, 44 (6-7): 413-419. 10.1016/j.exger.2009.03.004.
Aujard F, Perret M, Vannier G: Thermoregulatory responses to variations of photoperiod and ambient temperature in the lesser mouse lemur: a primitive or an advanced adaptive character?. J Comp Physiol B. 1998, 168: 540-548. 10.1007/s003600050175.
Blanc S, Schoeller D, Kemnitz J, Weindruch R, Colman R, Newton W, Wink K, Baum S, Ramsey J: Energy expenditure of rhesus monkeys subjected to 11 years of dietary restriction. J Clin Endocr Metab. 2003, 88 (1): 16-23. 10.1210/jc.2002-020405.
Perret M, Aujard F, Vannier G: Influence of daylength on metabolic rate and daily water loss in the male prosimian primate Microcebus murinus. Comp Biochem Phys A. 1998, 119 (4): 981-989. 10.1016/S1095-6433(98)00015-4.
Recognition is due to Dr Martine Perret for help in proofreading and improving the manuscript. Simon Miner is warmly thanked for reading the manuscript. We would like to thank Saint Antoine laboratory (IRSSA, Inserm IFR65, Paris, France) for gut hormone assays. This work was carried out with the financial support of The French National Research Agency (ANR) under the Programme National de Recherche en Alimentation et Nutrition Humaine (project ANR-06-PNRA-010-01).
Mécanismes Adaptatifs et Evolution, UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, Paris, France
Alexandre Dal-Pan & Fabienne Aujard
Institut Pluridisciplinaire Hubert Curien, UMR 7178 CNRS Université de Strasbourg, Strasbourg, France
Stéphane Blanc
Alexandre Dal-Pan
Fabienne Aujard
Correspondence to Fabienne Aujard.
AD performed the experimental protocol, analysed the data and drafted the manuscript. SB participated in the design of the study and drafted the manuscript. FA conceived the study, participated in its design and coordination, performed the statistical analyses and drafted the manuscript. All authors read and approved the final manuscript.
Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Dal-Pan, A., Blanc, S. & Aujard, F. Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiol 10, 11 (2010). https://doi.org/10.1186/1472-6793-10-11
Received: 21 December 2009
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text:
package gov.va.cpe.vpr.dao.jms;

import gov.va.cpe.test.mock.jms.ReturnsBrowserCallbackArgument;
import gov.va.cpe.vpr.sync.SyncError;
import gov.va.cpe.vpr.dao.IVprSyncErrorDao;
import gov.va.cpe.vpr.dao.IVprSyncStatusDao;
import gov.va.cpe.vpr.sync.MessageDestinations;
import gov.va.cpe.vpr.sync.SyncMessageConstants;
import gov.va.cpe.vpr.sync.SyncService;
import org.apache.activemq.broker.jmx.QueueViewMBean;
import org.junit.Before;
import org.junit.Test;
import org.springframework.core.convert.ConversionService;
import org.springframework.data.domain.Page;
import org.springframework.data.domain.PageRequest;
import org.springframework.data.domain.Sort;
import org.springframework.jms.core.BrowserCallback;
import org.springframework.jms.core.JmsOperations;

import javax.jms.JMSException;
import javax.jms.QueueBrowser;
import javax.jms.Session;
import javax.management.openmbean.OpenDataException;
import java.io.ByteArrayOutputStream;
import java.io.IOException;
import java.io.ObjectOutputStream;
import java.util.*;

import static org.hamcrest.CoreMatchers.*;
import static org.junit.Assert.assertThat;
import static org.mockito.Matchers.any;
import static org.mockito.Matchers.eq;
import static org.mockito.Mockito.*;

public class JmsSyncErrorDaoTests {

    private Session mockJmsSession;
    private QueueBrowser mockJmsQueueBrowser;
    private JmsOperations mockJmsTemplate;
    private ConversionService mockConversionService;
    private SyncService syncService;
    private QueueViewMBean mockQueueMBean;
    private IVprSyncErrorDao mockErrorDao;

    @Before
    public void setUp() throws Exception {
        mockJmsSession = mock(Session.class);
        mockJmsQueueBrowser = mock(QueueBrowser.class);
        mockJmsTemplate = mock(JmsOperations.class);
        mockConversionService = mock(ConversionService.class);
        mockQueueMBean = mock(QueueViewMBean.class);
        mockErrorDao = mock(IVprSyncErrorDao.class);

        syncService = new SyncService();
        syncService.setConversionService(mockConversionService);
        syncService.setErrorDao(mockErrorDao);
        syncService.setJmsTemplate(mockJmsTemplate);
        syncService.setVprDeadLetterQueueMBean(mockQueueMBean);

        when(mockJmsTemplate.browse(eq(MessageDestinations.DEAD_LETTER_QUEUE), any(BrowserCallback.class))).thenAnswer(new ReturnsBrowserCallbackArgument<Object>(mockJmsSession, mockJmsQueueBrowser));
    }

    @Test
    public void testCount() throws Exception {
//        when(mockQueueMBean.getQueueSize()).thenReturn(42L);
        List<SyncError> msgs = createMockErrorMsgList(42);
        when(mockErrorDao.getAllSyncErrors()).thenReturn(msgs);
        when(mockErrorDao.getSyncErrorCount()).thenReturn(42L);
        assertThat(syncService.getErrorCount(), is(42L));

    }

    @SuppressWarnings("unchecked")
	@Test
    public void testFindAllPaginated() throws JMSException {
        List messages = createMockErrorMsgList(100);
        when(mockErrorDao.getAllSyncErrors()).thenReturn(messages);

        Page<SyncError> errors = syncService.findAllErrors(new PageRequest(1, 20, Sort.Direction.DESC, "dateCreated"));
        assertThat(errors.getNumberOfElements(), is(20));
        assertThat(errors.getTotalElements(), is(100L));
    }

    @Test
    public void testFindAllPaginatedLessThanPageSize() throws JMSException {
        List messages = createMockErrorMsgList(15);
        when(mockErrorDao.getAllSyncErrors()).thenReturn(messages);

        Page<SyncError> errors = syncService.findAllErrors(new PageRequest(0, 20, Sort.Direction.DESC, "dateCreated"));
        assertThat(errors.getNumberOfElements(), is(15));
        assertThat(errors.getTotalElements(), is(15L));
    }

    @Test(expected = IllegalArgumentException.class)
    public void testFindAllPaginatedRequestedOffsetGreaterThanQueueSize() throws Exception {
        List messages = createMockErrorMsgList(15);
        when(mockErrorDao.getAllSyncErrors()).thenReturn(messages);

        Page<SyncError> errors = syncService.findAllErrors(new PageRequest(1, 20, Sort.Direction.DESC, "dateCreated"));
    }

    @Test
    public void testFindAllByPatientIdPaginated() throws JMSException {
        List messages = createMockErrorMsgList(5);
        // set them all to the same patient id
        for (Object o : messages) {
        	SyncError msg = (SyncError) o;
            when(msg.getPid()).thenReturn("23");
        }
        when(mockErrorDao.getAllSyncErrorsForPid("23")).thenReturn(messages);
        //when(mockJmsTemplate.browseSelected(eq(SyncQueues.ERROR_QUEUE), eq(SyncMessageConstants.PATIENT_ID + "='23'"), any(BrowserCallback.class))).thenAnswer(new ReturnsBrowserCallbackArgument<Object>(mockJmsSession, mockJmsQueueBrowser));
        //when(mockJmsQueueBrowser.getEnumeration()).thenReturn(Collections.enumeration(messages));

        Page<SyncError> errors = syncService.findAllErrorsByPatientId("23", new PageRequest(0, 10, Sort.Direction.DESC, "dateCreated"));
        assertThat(errors.getNumberOfElements(), is(5));
        assertThat(errors.getTotalElements(), is(5L));
    }

    @Test
    public void testDeleteAll() throws Exception {
        syncService.deleteAllErrors();

        verify(mockQueueMBean).purge();
        verify(mockErrorDao).purge();
    }

    @Test
    public void testDeleteSyncError() throws JMSException {
        SyncError e = new SyncError();
        e.setId("ID:" + 3); // not an actual JMSMessageID, but close enough
        syncService.deleteError(e);

        verify(mockJmsTemplate).receiveSelected(MessageDestinations.DEAD_LETTER_QUEUE, "JMSMessageID='ID:3'");
    }

    @Test
    public void testDeleteById() throws JMSException {
        syncService.deleteError("ID:" + 3);  // not an actual JMSMessageID, but close enough

        verify(mockJmsTemplate).receiveSelected(MessageDestinations.DEAD_LETTER_QUEUE, "JMSMessageID='ID:3'");
    }

    @Test
    public void testDeleteByPatientId() throws JMSException {
        List messages = createMockErrorMsgList(5);
        // set them all to the same patient id
        for (Object o : messages) {
        	SyncError msg = (SyncError) o;
            when(msg.getPid()).thenReturn("23");
        }
//        when(mockQueueMBean.browseMessages(eq(SyncMessageConstants.PATIENT_ID + "='23'"))).thenReturn(messages);
        when(mockJmsTemplate.browseSelected(eq(MessageDestinations.DEAD_LETTER_QUEUE), eq(SyncMessageConstants.PATIENT_ID + "='23'"), any(BrowserCallback.class))).thenAnswer(new ReturnsBrowserCallbackArgument<Object>(mockJmsSession, mockJmsQueueBrowser));
        when(mockJmsQueueBrowser.getEnumeration()).thenReturn(Collections.enumeration(messages));

        syncService.deleteErrorByPatientId("23");

        verify(mockJmsTemplate, times(5)).receiveSelected(MessageDestinations.DEAD_LETTER_QUEUE, SyncMessageConstants.PATIENT_ID + "='23'");
    }

    @Test
    public void testCountAllPatientIds() throws JMSException, OpenDataException {
        List messages = createMockErrorMsgList(13);
        for (Object o : messages) {
        	SyncError msg = (SyncError) o;
            when(msg.getPid()).thenReturn(messages.indexOf(o)+"");
        }
        when(mockErrorDao.getAllSyncErrors()).thenReturn(messages);
        when(mockErrorDao.getErrorPatientCount()).thenReturn(messages.size());
//        when(mockJmsQueueBrowser.getEnumeration()).thenReturn(Collections.enumeration(messages));

        assertThat(syncService.getNumPatientsWithErrors(), is(equalTo(13)));
    }

    @Test
    public void testFindOne() throws JMSException {
        List<SyncError> messages = createMockErrorMsgList(10);
        SyncError fauxMessage = messages.get(3);
        when(mockErrorDao.getOneByJMSMessageId(eq("ID:3"))).thenReturn(messages.get(3));
//        when(mockQueueMBean.browseMessages(eq("JMSMessageID='ID:3'"))).thenReturn(fauxMessage);
//        when(mockJmsTemplate.browseSelected(eq(SyncQueues.ERROR_QUEUE), eq("JMSMessageID='ID:3'"), any(BrowserCallback.class))).thenAnswer(new ReturnsBrowserCallbackArgument<Object>(mockJmsSession, mockJmsQueueBrowser));
//        when(mockJmsQueueBrowser.getEnumeration()).thenReturn(Collections.enumeration(Collections.singletonList(messages.get(3))));

        SyncError e = syncService.findOneError("ID:" + 3);

        assertThat(e, notNullValue());
        assertThat(e.getId(), is(equalTo("ID:" + 3)));
    }

    @Test
    public void testSyncErrorSerializable() throws IOException {
        SyncError se = new SyncError();
        new ObjectOutputStream(new ByteArrayOutputStream()).writeObject(se);
    }

    private static Map<String, SyncError> createMockErrorMsgMap(int num) throws JMSException {
        Map<String, SyncError> map = new HashMap<>();
        for(int i = 0; i<num; i++) {
            SyncError err = createMockErrorMsg(i);
            map.put(err.getId(), err);
        }
        return map;
    }

    private static List<SyncError> createMockErrorMsgList(int num) throws JMSException {
        List<SyncError> map = new ArrayList<>();
        for(int i = 0; i<num; i++) {
            SyncError err = createMockErrorMsg(i);
            map.add(err);
        }
        return map;
    }

    private static SyncError createMockErrorMsg(int index) throws JMSException {
        SyncError err = mock(SyncError.class);
        String pid = new Random(System.currentTimeMillis()).toString();
        when(err.getId()).thenReturn("ID:" + Integer.toString(index)); // sort of like a JMS message ID, but not exact
        when(err.getPid()).thenReturn(pid);
        when(err.getJson()).thenReturn("{\"foo\":\"bar\",\"baz\":" + index + "}");
        when(err.getMessage()).thenReturn("message " + index);
        when(err.getItem()).thenReturn("item " + index);
        return err;

    }

//    private static List<MapMessage> createMockErrorMsgs(int num) throws JMSException {
//        ArrayList<MapMessage> mockMessages = new ArrayList<MapMessage>(num);
//        for (int i = 0; i < num; i++) {
//            mockMessages.add(createMockErrorMsg(i));
//        }
//        return mockMessages;
//    }

//    private static MapMessage createMockErrorMsg(int index) throws JMSException {
//        MapMessage msg = mock(MapMessage.class);
//        String pid = new Random(System.currentTimeMillis()).toString();
//        when(msg.getJMSMessageID()).thenReturn("ID:" + Integer.toString(index)); // sort of like a JMS message ID, but not exact
//        when(msg.getStringProperty(SyncMessageConstants.PATIENT_ID)).thenReturn(pid);
//        when(msg.getString(SyncMessageConstants.PATIENT_ID)).thenReturn(pid);
//        when(msg.getString(SyncMessageConstants.RPC_ITEM_CONTENT)).thenReturn("{\"foo\":\"bar\",\"baz\":" + index + "}");
//        when(msg.getString(SyncMessageConstants.EXCEPTION_MESSAGE)).thenReturn("message " + index);
//        when(msg.getString("item")).thenReturn("item " + index);
////        when(msg.getString("stackTrace")).thenReturn("");
//        return msg;
//    }
}

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In a huge relief to the pontiffs of Kanchi Sankara Mutt, Jayendra Saraswathi and Vijayendra Saraswathi, a Puducherry court on Wednesday acquitted them in the sensational case of murder of a temple official in Kancheepuram in Tamil Nadu.
A total of 24 persons were made accused in the case, but one of them, Kathiravan, was killed early this year.
The judge held that the witnesses failed to support the prosecution case that the two Sankaracharyas -Jayendra (78) and Vijayendra (44)were part of a conspiracy to eliminate the temple official in September 2004.
He also said the witnesses, including Sankararaman's daughter, failed to identify the accused in the court. None of them identified any accused in the court and no incriminating evidence was made out against the accused, the judge noted.
The arrest of Jayendra Saraswathi on Diwali day in November 2004 in Andhra Pradesh and later his heir apparent, Vijayendra, came as a big jolt to the Kanchi Mutt and its followers.
During the trial, 189 witnesses were examined between 2009 and 2012, of which 83 turned hostile.
The keenly-anticipated judgement was delivered in a packed court hall for which security was beefed up in and around the area.
Sankararaman, who was murdered in his office room in the temple on September 3, 2004 using sharp-edged weapons, had levelled charges of financial misappropriation against the two Sankaracharyas and over the way they ran the Mutt.
Police from Vishnukanchi station took up investigation following a complaint and a case was registered under section 302 and 34 of Indian Penal code.
Cases were registered against the two seers under section 120-B (criminal conspiracy) and 302 (murder) of IPC in connection with the murder.
Reacting to the judgement, Sankararaman's son Anand said the verdict was "shocking and unbelievable" and wanted to know who were his father's killers.
The family will go through the judgement and decide the next course of action including whether to appeal against the verdict, he said.
The seers' counsel said the prosecution had failed to prove the conspiracy charge and the witnesses, including Sankararaman's daughter Uma Maitreyi, had failed to identify the accused.
With no material or evidence "this is not a fit case for appeal," one of their counsel, K M Subramaniam, said.
Lakshman Reddy, another of the seers' counsel, said no witness or documents were there to prove the involvement of the Sankaracharyas.
Earlier, it was alleged that the pontiff hatched a conspiracy to eliminate Sankararaman since he had allegedly made allegations against Jayendra Saraswathi.
The others acquitted in the case include the Manager of the Mutt Sundaresa Iyer, junior pontiff Vijayendra Saraswthi's brother Raghu and K G Krishnaswamy alias Appu.
M Kathiravan, one of the accused, was killed in Chennai on March 21 this year. This brought down the number of accused in the Sankararaman murder case to 23 from 24.
The Special Investigation team of Tamil Nadu police filed the charge sheet naming Jayendra Saraswathi as first accused and Vijayendra Sarawathi as the second accused in the case.
The then District Superintendent of Police in Kancheepuram K Premkumar and the Superintendent of Police S P Sakthivelu who was the Chief Investigation Officer submitted the 1873-page charge sheet before the Judicial Magistrate (I) of Kancheepuram G Uthamaraj.
Jayendra Saraswathi was arrested on Diwali day on November 11, 2004 at Mahbub Nagar in Andhra Pradesh. After two months in jail in Vellore the seer was granted bail by the Supreme Court on January 10, 2005. Vijayendra Saraswati was arrested from the mutt on January 10, 2005 and the Madras High Court granted him bail a month later.
The Sankaracharyas moved the Supreme Court and got the case transferred to Puducherry in 2005 on the ground that the atmosphere in Tamil Nadu was vitiated and there would not be free and fair trial.
Ravi Subramanian, a civil contractor of the Mutt, who was among the accused, turned approver. He, however, later turned hostile during investigation in the case in Puducherry court on January 21, 2010.
The trial in the case was shifted to Puducherry from Chengalpattu court in Tamil Nadu on an order of the Supreme Court following a writ petition filed by the senior pontiff.
The Supreme Court directed in July 2008 that the Puducherry government could appoint the Public Prosecutor to conduct the trial.
This direction was given in a petition Jayendra Saraswathi presented in the apex court where he insisted that once the trial was shifted to Puducherry, Tamil Nadu government had no authority to appoint its PP.
Subsequently, senior lawyer N Devadoss was appointed as the Special Public Prosecutor to conduct the trial.
The trial in the Puducherry Principal District and Sessions court began on April 2, 2009.
Padma, the widow of Sankararaman, his son Anand Sharma and daughter Maitreyi were among the 189 prosecution witnesses examined during the trial in Puducherry court. Of them, 81 witnesses turned hostile.
Ravi Subramanian who was approver in the case earlier, turned hostile during examination.
He retracted his earlier statements given before the court and the investigation officers in Kancheepuram.
During the four-year trial in Puducherry, four judges looked into the case. This is the first time in the legal history of Puducherry that a case from a neighbouring state had been shifted to the Union Territory which comes under the jurisdiction of the Madras High Court. No murder case has perhaps seen such number of adjournments as the present case in Puducherry.


This tour itinerary includes the main Ulaanbaatar must see sights and attractions and gives you enough time to explore and makes the most of the city in just one day, try Mongolian cuisine at a local restaurant. The colorful, tuneful, and beautiful evening performance of "Tumen Ekh", Mongolia's leading folk ensemble featuring traditional music, song, dance and contortion - the highlight of this tour.
Next, sit down for a lunch at the "Modern Nomads" restaurant, one of the fine restaurants in Ulaanbaatar, experience authentic Mongolian traditional cuisine.
You can explore Mongolia's history in this museum situated right of the Genghis Khan Square. Exhibitions cover prehistory, pre-Mongol Empire history, Mongol Empire, Mongolia during Qing rule, ethnography and traditional life, and twentieth-century history. The ethnographic collection has a unique significant displays of the traditional dress of various Mongolian ethnic groups and of snuff bottles. Most exhibits have labels in both Mongolian and English.
The State Department Store is one of the main tourist attractions in Ulaanbaatar in itself as it has all the best products from Mongolia. The sixth floor is dedicated just to tourists with wide range of souvenirs, traditional clothing and books about Mongolia tourists would want to bring home. There are cashmere, musical instruments, hats, t-shirts, models of gers and camels and horses, jewelry.
If you are once in Mongolia, this is really one of the must see tourist attractions in Ulaanbaatar. Tumen Ekh Ensemble is the best Mongolia's premier traditional performance group. Featuring folk and traditional music, song, dance and contortion. Finish tour back to your hotel, be dropped off at any preferred location in the city.


I have been fending off a cold this week which has put me off of most food, but somehow has left me craving the smooth, creamy textures and simple flavors of pudding, custard, or flan. I decided to go with the flan. I thought that I might add a little citrus for some additional vitamin C, and before you know it I was making a Key Lime Coconut Flan.
By the way, I am a total advocate of flan for breakfast. I mean eggs and milk, right! Protein and calcium, all wrapped into one delightfully creamy treat. The only concern is the sugar. I still need to work on finding a way around using sweetened condensed milk in my flan, but then again one serving of flan has about the same amount of sugar in it as most breakfast yogurts. Although that might be more reflective of the disgusting amounts of sugar going into breakfast yogurt then the fact that it is okay to eat that much sugar in your morning flan. I'll have to work on it. I have made homemade sweetened condensed milk before. I'll just have to rework it to use less sugar.
For a low fat version, use fat-free sweetened condensed and evaporated milk. It will turn out fine. I have done it before. The only concern is the other crap they put into the sweetened condensed and evaporated milk to make up for the lack of fat. Flan is one of those things that just never seems quite right when you substitute the evaporated and sweetened condensed milk out for other dairy or gelatin products. When you do, it is no longer flan, or at least not good flan.
Grease a large round baking dish or 4-5 smaller ramekins. The key to picking a good flan dish is that it should have high (~2″-3″) sides and should nestle easily in a larger (9″ x 13″) pan since you will be cooking your flan in a steam bath.
On the stove top, melt the sugar and water into a golden syrup. It can take about 10 – 15 minutes to get the sugar nicely caramelized.
Pour the caramel syrup directly into the bottom of the flan dish.
Allow the syrup to cool and solidify slightly. I usually give it about 5-10 minutes.
Meanwhile, whisk the eggs, sweetened condensed milk, evaporated milk, key lime juice, salt, and vanilla extract together.
Fill the bottom of a large pan with about 1″ of water.
Gently set the flan dish into the water bath.
Gently pour the flan custard over the caramel in the flan dish.
Carefully slid the flan into the oven.
Allow the flan to bake for about an hour – slightly less if you decide to use smaller individual ramekins. Check on the flan every once in a while to make sure that the steam bath has not dried out – it shouldn't, but best to be on the safe side.
Gently remove the flan from the oven, and lift it out of the steam bath.
Allow the flan to cool fully, and refrigerate before serving. It is best to let it refrigerate overnight, especially if you are planning to flip it out upside down for serving.
If you choose to, you should be able to lightly run a butter knife along the sides of the flan dish and flip your flan out upside-down so that the flan will stand on its own with the caramel sauce drizzling down its sides. I usually do not bother with this, and just use a spoon to scoop out the flan directly from the dish. I find it less fussy and easier to store.


Our world is determined by the limits of our five senses. We can't hear pitches that are too high or low, nor can we see ultraviolet or infrared light–even though these phenomena are not fundamentally different from the sounds and sights that our ears and eyes can detect. But what if it were possible to widen our sensory boundaries beyond the physical limitations of our anatomy? In a study published recently in Nature Communications, scientists used brain implants to teach rats to "see" infrared light, which they usually find invisible. The implications are tremendous: if the brain is so flexible it can learn to process novel sensory signals, people could one day feel touch through prosthetic limbs, see heat via infrared light or even develop a sixth sense for magnetic north.


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Govt reaffirms COVID-19 vaccines will be available this quarter
Addressing yesterday's weekly press conference about Macau's novel coronavirus situation, the Health Bureau's (SSM) Control of Communicable Diseases and Surveillance of Diseases Department Coordinator Leong Iek Hou said that Macau's first COVID-19 vaccines will be available in the current quarter and that the BioNTech vaccines purchased by the Macau government are only for those aged at least 16.
Leong also noted that the Sinopharm vaccines purchased by the local government are also only for certain age ranges.
The Macau government announced last month that it has purchased 1.2 million doses of COVID-19 vaccines developed by three vaccine developers, comprising 400,000 doses of inactivated vaccines developed by Beijing-based China National Pharmaceutical Group (also known as Sinopharm), 400,000 doses of mRNA vaccines developed by Germany's BioNTech, and 400,000 doses of adenovirus vector vaccines jointly developed by the Anglo-Swedish joint venture of AstraZeneca and Oxford University.
The Macau government said last month that it expected the first batches of the Sinopharm and BioNTech vaccines to be delivered to Macau in the first quarter of this year, while the first batch of the AstraZeneca-Oxford vaccines was expected to arrive in Macau in the second quarter of this year. The government said at that time that the first batches of the Sinopharm, BioNTech and AstraZeneca-Oxford vaccines to be delivered to Macau would each consist of at least 100,000 doses.
Leong reaffirmed yesterday that the first batches of the COVID-19 vaccines purchased by the government will be delivered to Macau in the current quarter. Leong said that the government was now formulating its COVID-19 vaccination programme, such as appointment arrangements for vaccinations, and the groups of residents who will be the first to get vaccinated, adding that it was also following up on how the vaccines will be delivered to Macau.
Leong noted that each kind of COVID-19 vaccine is only for certain age ranges. Leong said that for instance, the BioNTech vaccine is only for those aged at least 16, while the Sinopharm vaccine is also only for certain age ranges.
In the mainland, the National Health Commission (NHC) has said that all domestically developed COVID-19 vaccines are only for people aged between 18 and 59.
Leong said that the Health Bureau will assess the COVID-19 vaccine age matter based on the information provided by the respective vaccine producers, adding that when the bureau starts to roll out its COVID-19 vaccination drive, it will inform residents about the suitable age groups of the respective COVID-19 vaccines.
Leong also noted that according to the Macau government's administrative regulation on its vaccination programme, local residents' COVID-19 jabs provided by the government will be free of charge, while non-locals will have to pay. Leong said that the Macau government was currently studying whether non-resident workers will be charged for the COVID-19 shots.
"We will consider the matter based on the [respective] regulation and the latest development of the COVID-19 pandemic situation," Leong said, adding that the government hasn't decided yet whether non-resident workers will be charged for the COVID-19 shots.
Health Code address function relaunched today
Meanwhile, Alvis Lo Iek Long, a clinical director of the public Conde de São Januário Hospital Centre, announced during the press conference that the Macau government will relaunch the new function of adding one's home address to the Macau Health Code at 11 a.m. today, as the Health Bureau's technical team had meanwhile "rectified the issue" which previously affected the code system's server – which resulted in a technical glitch on Christmas Eve when the new function was initially slated to start.
The government suspended the new function of adding one's address to the Macau Health Code following the 40-minute malfunction on Christmas Eve – when residents were not able to have the health code generated on their smartphones – as the bureau's technicians could not confirm whether the glitch was due to the new function. Under the initial schedule, residents would have had to add their home address to their Macau Health Code from January 7 – after a 14-day transition period.
The Health Bureau said last week that its technical team had concluded that the malfunction which occurred on Christmas Eve was not due to the new address function, and instead it was merely due to the "abnormal" operation of the Macau Health Code system's server.
Data flow pressure tests
Lo underlined yesterday that the bureau's technical team has "repeatedly" carried out data flow pressure tests on the Macau Health Code system so as to ensure that the system can continue operating in case a large number of people use the new address function simultaneously.
"After repeated testing, the issue [which previously occurred] in the system has been rectified," Lo said, adding that the bureau's technical team has also prepared a number of contingency plans in response to the possibility of the abnormal operation of the Macau Health Code system's server again.
Lo noted that the bureau has carried out data flow pressure tests on the Macau Health Code system to ensure that the server can process up to 800,000 people using the new address function in one hour. Lo also said that if too many people use the new address function simultaneously, the Macau Health Code system will temporarily suspend the new function so as to prevent a malfunction of the system so that residents can continue getting the code generated on their smartphones, adding that the new function will be resumed once the data flow has reduced to a particular volume.
Lo said that the Health Bureau has decided to relaunch the new address function at 11 a.m. today so as to avoid the peak hours in the morning when residents cross the Macau-Zhuhai borders or enter their workplaces – the time when they are required to show their Macau Health Code.
Lo also said that those who had successfully added their address to their Macau Health Code on Christmas Eve before the suspension of the new function will not have to fill in their address again.
Lo urged residents not to rush to add their address to the Macau Health Code after today's relaunch of the new function as they will have a 14-day transition period for them to fill in the address – before the new deadline when residents must start to fill in the address.
In addition to local residents, the new address requirement will also apply to non-locals living or staying in Macau, who will need to indicate the address of the place where they usually stay, such as workplaces, casinos or hotels.
Macau has not recorded a new COVID-19 case for 192 days, while no local case has been confirmed in 281 days.
Meanwhile, Macau Government Tourism Office (MGTO) official Lau Fong Chi told the press conference that for the time being the Macau government will not launch a special programme to help locals stranded overseas return to Macau. She noted that locals could choose to return to Macau via Tokyo or the Chinese mainland.
Taiwan last week banned all transit flights from the island. Until then, Taipei was a major transit hub for Macau residents travelling during the COVID-19 pandemic.
Alvis Lo Iek Long (right), one of the three clinical directors of the public Conde de São Januário Hospital Centre, speaks during yesterday's press conference about the city's novel coronavirus (COVID-19) situation, as Health Bureau (SSM) Control of Communicable Diseases and Surveillance of Diseases Department Coordinator Leong Iek Hou looks on.
Photo: Tony Wong

redpajama_set_name: RedPajamaCommonCrawl


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Liverpool Family
New Nerf Centre set to open in Liverpool this month
Foam shoot 'em up space will be aimed at aged 5 and upwards
Dawn Collinson
Nerf Centre Liverpool is opening on Saturday May 28
How's parenting in a pandemic going for your family? Sign up for relatable tales as we share our unfiltered parenting reality with you, plus useful tips.
A new Nerf Centre, where youngsters can do battle in foam dart shoot 'em ups, is set to open in Liverpool at the end of this month.
The centre, on Vauxhall Road, is aimed at children aged five and upwards who love the worldwide hit blaster toys.
It's been created in a specially transformed industrial space by the owners of Ultimate Indoor Paintball Liverpool which is in the adjoining unit.
Andrew Connolly from Crosby, one of the co-owners, explains: "Since we opened the paintball centre about four years ago it's been doing so well we wanted to expand and do something for younger kids. With the paintball we have an age limit of eight and over, but with this it will be for five-year-olds plus.
Look inside Liverpool's first trampoline park Spring City
"We bought the unit next door and we've got a contact in California which meant we were able to get the connection with Nerf - without that you can't get an official supply of the guns and ammunition.
The new Nerf Centre Liverpool on Vauxhall Road
"She came over originally to look at the paintball and suggested the Nerf Centre so that was where the idea came from."
The new centre, which is due to open on Saturday May 28, covers a 2,500-square foot area - that's very big for five-year-olds!
Check out a kid's-eye view of Mattel Play! Liverpool
"It's taken us four weeks to transform the place, working 18-hour days," says Andrew. "We've covered it in foam matts and foam walls, so it's like a play centre and it meets all the health and safety regulations.
"We'll do hour-long sessions and two-hour birthday parties, and it will be booked out privately to groups of 10 and over, so there's no danger of really young kids being mixed in with teenagers and adults. The sessions are just for those groups to have whoever they want there."
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Andrew says they're expecting it to be the biggest hit with younger shooters, but there's no upper age limit if older ones fancy reliving their childhood.
There are 60 guns on site, two types of 30. "They're different styles and different pressures," he explains, "because eight-year-olds will have a stronger pressure than five-year-olds. It's just a little bit gentler when it hits, although there's no need for anyone to wear protective clothing because it doesn't hurt. They just need to take their shoes off and that's it, the Nerf vests are just to put the darts in."
For information about Nerf Centre Liverpool call: 0151 353 7901.


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Freedom Trail marker notes 1961 Jackson Library sit-in
by Mississippi Today August 17, 2017 August 18, 2017
A Mississippi Freedom Trail marker memorializing the 1961 Jackson Municipal Library Sit-In was dedicated Thursday in Jackson, Mississippi Development Authority officials announced in a press release.
The marker is the 25th on the trail.
"The Mississippi Freedom Trail tells an important part of our story as a people," Visit Mississippi Director Craig Ray said in the press release. "The courage shown by these college students in pursuit of their education and equal rights for all continues to inspire more than 50 years later."
The press release gave the following recap of events that day:
"Nine Tougaloo College students entered Jackson Municipal Library on March 27, 1961, to research books unavailable at the segregated Carver Library. Soon afterward, police arrested Meredith Anding, Jr., James "Sammy" Bradford, Alfred Cook, Geraldine Edwards, Janice Jackson, Joseph Jackson, Jr., Albert Lassiter, Gloria Pierce and Ethel Sawyer on charges of breach of peace."
"Support for the students spread quickly. By 7 p.m., nearly 700 people joined NAACP field secretary Medgar Evers for a prayer meeting outside the library. The next day, Jackson State University students rallied and marched toward the city jail. They were met by police resistance and force including clubs, tear gas and dogs. Although the Tougaloo students were initially convicted, fined and given 30-day suspended sentences, a judge threw out the case on appeal."
Dr. Leslie-Burl McLemore, chairman of the Mississippi Freedom Trail Task Force noted that the non-violent actions of the students "inspired young African Americans across the state to integrate public parks, swimming pools, stores and movie theaters."
"By illuminating this chapter in our history, we honor their contributions to advancing the civil rights cause," McLemore said.
McLemore unveiled the marker alongside Tougaloo College President Dr. Beverly Hogan and Rickey Jones, past chairman of the Jackson/Hinds Library System Board of Trustees
The Mississippi Freedom Trail was launched in 2011 and commemorates the people, places and events of the civil rights movement. Additional information is provided at www.visitmississippi.org.

Freedom Trail marker notes 1961 Jackson Library sit-in

by Mississippi Today, Mississippi Today
August 17, 2017

A Mississippi Freedom Trail marker memorializing the 1961 Jackson Municipal Library Sit-In was dedicated Thursday in Jackson, Mississippi Development Authority officials announced in a press release.

The marker is the 25th on the trail.

"The Mississippi Freedom Trail tells an important part of our story as a people," Visit Mississippi Director Craig Ray said in the press release. "The courage shown by these college students in pursuit of their education and equal rights for all continues to inspire more than 50 years later."

The press release gave the following recap of events that day:

"Nine Tougaloo College students entered Jackson Municipal Library on March 27, 1961, to research books unavailable at the segregated Carver Library. Soon afterward, police arrested Meredith Anding, Jr., James "Sammy" Bradford, Alfred Cook, Geraldine Edwards, Janice Jackson, Joseph Jackson, Jr., Albert Lassiter, Gloria Pierce and Ethel Sawyer on charges of breach of peace."

"Support for the students spread quickly. By 7 p.m., nearly 700 people joined NAACP field secretary Medgar Evers for a prayer meeting outside the library. The next day, Jackson State University students rallied and marched toward the city jail. They were met by police resistance and force including clubs, tear gas and dogs. Although the Tougaloo students were initially convicted, fined and given 30-day suspended sentences, a judge threw out the case on appeal."

Dr. Leslie-Burl McLemore, chairman of the Mississippi Freedom Trail Task Force noted that the non-violent actions of the students "inspired young African Americans across the state to integrate public parks, swimming pools, stores and movie theaters."

"By illuminating this chapter in our history, we honor their contributions to advancing the civil rights cause," McLemore said.

McLemore unveiled the marker alongside Tougaloo College President Dr. Beverly Hogan and Rickey Jones, past chairman of the Jackson/Hinds Library System Board of Trustees

The Mississippi Freedom Trail was launched in 2011 and commemorates the people, places and events of the civil rights movement. Additional information is provided at  www.visitmississippi.org.

This article first appeared on Mississippi Today and is republished here under a Creative Commons license.


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Considering The Cost Of Dental Implants
Jaw Bone Loss & Deterioration
3-D Imaging
Julianna Hukill, DDS
Jeffrey Link, DDS
Stephen E. Nechvatal, DMD
Shane Citron, DDS, MD
Grand Blanc Office
Lapeer Office
Learn more about Dental Implant Surgery
Learn more about Exposure of An Impacted Tooth
Dr. Stephen Nechvatal graduated from Case Western Reserve University School of Dental Medicine in 1975. He served in the U. S. Air Force from 1975 to 1979. He completed his residency in Oral and Maxillofacial Surgery in 1982 and became board certified by the ABOMS in 1994. He has practiced in Flint and Lapeer, MI since 1986. Dr. Nechvatal is on staff with Ascension/Genesys Regional Medical Center and Lapeer County Surgery Center. He has special interest in implants, bone grafting, orthognathic and temporomandibular joint surgery. Hobbies include piloting his single engine plane for which he is an air instrument rated pilot. He is also an avid fisherman, enjoys music concerts and baseball games.
5090 East Hill Road
Phone: Grand Blanc Office Phone Number (810) 445-9970
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1176 1/2 S. Lapeer Road, Suite B
Phone: Lapeer Office Phone Number (810) 667-6855


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