text:
In mammals, puberty onset typically occurs earlier in females than in males, but the explanation for sexual differentiation in the tempo of pubertal development is unknown. Puberty in both sexes is a brain-dependent phenomenon and involves alterations in the sensitivity of neuronal circuits to gonadal steroid feedback as well as gonadal hormone-independent changes in neuronal circuitry. Kisspeptin, encoded by the Kiss1 gene, plays an essential but ill-defined role in pubertal maturation. Neurokinin B (NKB) is coexpressed with Kiss1 in the arcuate nucleus (ARC) and is also important for puberty. We tested whether sex differences in the timing of pubertal development are attributable to sexual differentiation of gonadal hormone-independent mechanisms regulating hypothalamic Kiss1/NKB gene expression. We found that, in juvenile females, gonadotropin secretion and expression of Kiss1 and NKB in the ARC increased immediately following ovariectomy, suggesting that prepubertal females have negligible gonadal hormone-independent restraint on their reproductive axis. In contrast, in similarly aged juvenile males, no changes occurred in LH levels or Kiss1 or NKB expression following castration, suggesting that gonadal hormone-independent mechanisms restrain kisspeptin/NKB-dependent activation of the male reproductive axis before puberty. Notably, adult mice of both sexes showed comparable rapid increases in Kiss1/NKB expression and LH secretion following gonadectomy, signifying that sex differences in the regulation of ARC Kiss1/NKB neurons are manifest only during peripubertal development. Our findings demonstrate that the mechanisms controlling pubertal activation of reproduction in mice are different between the sexes and suggest that gonadal hormone-independent central restraint on pubertal timing involves Kiss1/NKB neurons in the ARC.
- kisspeptin
- Kiss1r
- G protein-coupled receptor 54
- neurokinin B
- gonadotropin-releasing hormone
- development
- reproduction
puberty comprises the physiological and behavioral changes that occur during the transition from juvenile life into sexual maturity and reproductive competence. Puberty onset is usually defined as the activation (or in some species, reactivation) of the neuroendocrine reproductive axis (11, 35, 37), which typically occurs earlier in females than in males (12, 13, 19). Although the molecular mechanisms underlying the onset of puberty remain unknown, the guiding mechanisms include an apparent reduction in the sensitivity of hypothalamic circuits to the feedback actions of gonadal steroids (estradiol or testosterone) along with gonadal hormone-independent changes in the activity of inhibitory or stimulatory neural networks within the brain (11, 22, 35, 37).
Despite the knowledge that both the gonadal hormone-dependent and -independent processes underlying puberty contain neural components, the identity of the neuronal factors and substrates involved in these mechanisms is unknown. Kisspeptin, a neuropeptide encoded by the Kiss1 gene, is a potent secretagogue for gonadotropin-releasing hormone (GnRH) in mammals (reviewed in Refs. 25 and 38) and may be a critical component of pubertal maturation based on several observations. First, humans and mice with disabling mutations or transgenic disruptions of the kisspeptin receptor gene fail to progress through puberty and remain infertile as adults (9, 14, 27, 46, 47). Second, kisspeptin administration to prepubertal rats and monkeys induces precocious gonadotropin secretion (30, 48). Finally, in rodents and primates, the hypothalamic expression of both Kiss1 and its receptor increase in association with pubertal maturation (6, 21, 29, 48). Collectively, these observations suggest that kisspeptin-induced activation of GnRH neurons serves as a gating mechanism for puberty; however, the identity of the hormonal or molecular trigger that activates Kiss1 neurons at puberty remains unknown.
In rodents, Kiss1 is expressed in the hypothalamic arcuate nucleus (ARC) and the anteroventral periventricular nucleus/periventicular nucleus continuum (AVPV/PeN) (18, 26, 42, 48, 49); in adulthood, the Kiss1 population in the AVPV/PeN, but not the ARC, is sexually dimorphic, with females having greater numbers of Kiss1 neurons in the AVPV/PeN than males (23, 26). Moreover, Kiss1 expression in the AVPV/PeN is stimulated by gonadal steroids, whereas Kiss1 neurons in the ARC are inhibited by gonadal steroids (and, conversely, stimulated by gonadectomy) (26, 50, 51). This differential steroidal regulation of Kiss1 in the AVPV/PeN and ARC may underlie the cellular mechanisms of steroid-mediated positive and negative feedback control of GnRH secretion, respectively (25, 38, 49). However, the physiological role of these two phenotypically unique populations of Kiss1 neurons in pubertal maturation is unclear.
In addition to kisspeptin, neurokinin B (NKB), a tachykinin encoded by the Tac2 gene, has recently been implicated in the control of puberty and reproduction. In rodents, sheep, and primates, NKB is expressed in the ARC, where it colocalizes with kisspeptin neurons (2, 17, 31, 40). In addition, the NKB receptor NK3 is expressed on GnRH neurons (28, 54). Moreover, like Kiss1, NKB mRNA in the ARC increases following gonadectomy (8, 10, 40, 43, 45) in conjunction with a rise in luteinizing hormone (LH) secretion, suggesting that NKB signaling is stimulatory to the reproductive axis. Indeed, humans lacking NKB/NK3 signaling have delayed puberty onset and impaired fertility (55). Despite the implication that NKB plays a role in regulating puberty and reproduction, there is little insight concerning its mechanism of action in the brain.
In the present study, we investigated the role of gonadal hormones in the regulation of Kiss1 and NKB in the ARC during the peripubertal period and examined whether sex differences in the activation of Kiss1/NKB neurons might explain sex differences in the tempo of pubertal maturation. First, we argued that if activation of Kiss1/NKB neurons in the ARC is an essential component of the pubertal process, then these neurons should be regulated by the same gonadal hormone-dependent and/or -independent factors that govern puberty onset. We postulated that if pubertal activation of reproductive circuits, including Kiss1/NKB neurons, is regulated entirely by changes in sensitivity to gonadal hormone feedback, then removal of gonadal steroids before puberty should induce a precocious activation of both Kiss1/NKB neurons and gonadotropin secretion. However, if the peripubertal reproductive axis is also regulated by gonadal hormone-independent restraint mechanisms, then removal of gonadal hormone feedback before puberty may not induce early activation of either Kiss1/NKB circuits or LH secretion (because central restraining processes are still present). Second, we hypothesized that earlier puberty onset in females compared with males reflects sex differences in the gating of Kiss1/NKB reproductive circuits. Specifically, we hypothesized that there is greater or longer-lasting inhibition (or lack of activation) of Kiss1/NKB circuitry in juvenile males compared with juvenile females. We present evidence demonstrating that 1) the mechanisms controlling pubertal activation of reproduction in mice are different between the sexes such that gonadal hormone-independent restraint on pubertal timing is more prevalent (or longer lasting) in juvenile males than in females and 2) this gonadal hormone-independent restraint mechanism acts on Kiss1/NKB neurons in the ARC, thereby delaying activation of sexual maturation in developing males compared with females.
Adult C57Bl6 male and female mice were purchased from Jackson Laboratories and allocated into breeding pairs. Beginning 19 days after pairing, litters were assessed daily, and day of birth was considered postnatal day (PND) 1. In experiments in which prepubertal mice were studied, animals between the ages of PND 14 and PND 16 were used to ensure that they were not already undergoing the pubertal transition (which is evidenced in females by vaginal opening on PND 24–28 but may actually initiate several days beforehand). All animals were housed on a 12:12-h light-dark cycle (lights off at 1800) with food and water available ad libitum. All experiments were conducted in accordance with the National Institutes of Health (NIH) Animal Care and Use Guidelines and with approval of the Animal Care and Use Committee of the University of Washington.
Gonadectomies and blood and tissue collection.
Mice were anesthetized with isoflurane and bilaterally gonadectomized (GDX) or left intact. Briefly, the animal's ventral skin was shaved and cleaned, and small incisions were made in the skin and abdominal musculature. The gonads were identified and excised, the abdominal muscle was sutured, and the skin incision was closed with surgical clips (adults) or surgical thread (juveniles). Animals that were left intact received both ventral incisions, but no tissue was removed.
Blood collections were obtained via retroorbital bleeding (∼100 μl) of animals given isoflurane anesthesia. Blood was centrifuged and the serum stored at −20°C until it was assayed for LH or testosterone (T) via radioimmunoassay. All hormone assays were performed by the University of Virginia Ligand Assay Laboratory (Charlottesville, VA), as described previously (24, 27). Brains of euthanized animals were collected and immediately frozen on dry ice and stored at −80°C. Frozen brains were sectioned on a cryostat into 5 sets, 20 microns/section, and the sections were thaw-mounted onto slides. Slides were stored at −80°C until processing via in situ hybridization. Because Kiss1 expression and hormone levels are influenced by circadian signaling (41), all blood and tissue collections were obtained within a 3-h time window between 1000 and 1300.
In situ hybridization.
In situ hybridization for Kiss1 or NKB mRNA was performed as described previously (18, 31, 50). Briefly, slide-mounted brain sections were fixed in 4% paraformaldehyde, pretreated with acetic anhydride, rinsed in 2× standard saline citrate (SSC; sodium citrate, sodium chloride), delipidated in chloroform, dehydrated in graded ethanols, and air-dried. Radiolabeled riboprobe (0.03–0.05 pmol/ml, depending on the probe) was combined with 1/20 volume yeast tRNA (Roche Biochemicals, Indianapolis, IN) in Tris-EDTA (0.1 M Tris-0.01 M EDTA, pH 8.0), and this mixture was heat denatured in boiling water for 3 min, iced for 5 min, added to hybridization buffer, and applied to each slide (100 μl/slide). Slides were coverslipped and placed in humidity chambers at 55°C for 16 h. Following hybridization, the slides were washed in 4× SSC and then placed into RNAse [37 mg/ml RNase A (Roche Biochemicals) in 0.15 M sodium chloride, 10 mM Tris, and 1 mM EDTA, pH 8.0] for 30 min at 37°C and then in RNase buffer without RNase at 37°C for 30 min. After a wash in 2× SSC at room temperature, slides were washed twice in 0.1× SSC at 62°C and then dehydrated in graded ethanols and air-dried. Slides were then dipped in Kodak NTB emulsion, air-dried, and stored at 4°C for 7–10 days (depending on the assay). Slides were then developed, dehydrated in ethanols, cleared in Citrasolv (Fisher Scientific), and coverslipped with Permaslip (Sigma).
Experiment 1: effects of gonadectomy on LH and Kiss1 expression in prepubertal males and females.
Experiment 1A assessed whether removal of gonadal hormones before the normal onset of puberty (which is typically ∼PND 24–28 and PND 32–36 for female and male mice, respectively) results in an early activation of gonadotropin secretion and a corresponding stimulation of Kiss1 neurons in the ARC. We reasoned that if pubertal activation of reproductive circuits is regulated predominantly by changes in sensitivity to gonadal hormone-dependent feedback, then early removal of hormone feedback should result in precocious stimulation of LH secretion and perhaps ARC Kiss1 expression. If, however, the peripubertal reproductive axis is regulated in part (or entirely) by gonadal hormone-independent central circuits, then early removal of gonadal hormones may not induce early activation. Juvenile (PND 14) male and female mice were GDX or left intact and then euthanized 2 or 4 days later (PND 16 and 18, respectively). Blood and brains were collected at the time of euthanization. Blood serum was assayed for LH levels as an indicator of activation (or not) of the neuroendocrine reproductive axis. Brains were processed with in situ hybridization for Kiss1 mRNA levels in the ARC; the number of Kiss1-expressing cells, as well as the relative amount of Kiss1 mRNA per cell (determined by number of silver grains), was determined for each animal. Kiss1 expression in males and females was assayed separately on the basis of experimental limitations on the maximum number of slides per assay.
Results from experiment 1A suggested a possible sex difference in the regulation of gonadotropin secretion and ARC Kiss1 neurons after prepubertal gonadectomy. In experiment 1B, an alternate set of brain sections for PND 18 males and females (GDX and intact for each sex) was analyzed together in the same in situ hybridization assay to allow for direct intersex comparisons of ARC Kiss1 expression in juvenile animals. Moreover, we have shown previously that Kiss1 gene expression in the rat AVPV/PeN is sexually dimorphic in adulthood, but this has not been examined before puberty (or in mice). Thus, for comparison of possible prepubertal sex differences in Kiss1 neurons between hypothalamic regions, experiment 1B also evaluated Kiss1 mRNA levels in the AVPV/PeN of PND 18 males and females (GDX and intact); n = 10–16 animals/group for both experiment 1A and 1B.
Experiment 2: effects of castration on serum T levels in juvenile males.
In experiment 1, we found that GDX juvenile male mice do not display increased LH or Kiss1 levels 2 or 4 days later. These findings raised the possibility that gonadectomy did not effectively reduce T levels. Therefore, we next determined whether 4 days postcastration is long enough to fully remove circulating T from the juvenile system. Juvenile PND 14 male mice (n = 7–9/group) were GDX or left intact and euthanized 4 days later on PND 18. Blood serum from these males was assayed for T levels via RIA to determine whether prepubertal gonadectomy actually removes all endogenous circulating T.
Experiment 3: effects of gonadectomy on LH and Kiss1 mRNA levels in adult males and females.
Another possible reason that males in experiment 1 did not show an effect of castration is that a 4-day duration following gonadectomy is not sufficient for the male system to display changes in LH or Kiss1 expression independent of the animal's age. In this experiment, GDX adults of both sexes were studied to determine whether the sex difference in the regulation of Kiss1 neurons observed after 4 days in GDX juvenile animals is also present (or not) in adulthood. Adult (8 wk) male and female mice were GDX or left intact and then euthanized 4 days later. To control for stage of cycle, all intact females were euthanized on the morning of diestrus (as determined with daily vaginal smears). Blood and brains were collected at the time of euthanization and assayed for LH levels and Kiss1 mRNA in the ARC, respectively; n = 6–7 animals/group.
Experiment 4: assessment of Kiss1 expression in adult males that were GDX as juveniles.
In the previous experiments, we observed a sex difference in the regulation of ARC Kiss1 neurons and gonadotropin secretion in juvenile, but not adult, mice such that GDX prepubertal males display no changes in either LH secretion or ARC Kiss1 expression 2 and 4 days later. This experiment determined whether GDX juvenile males eventually show increased LH and Kiss1 expression if allowed to age beyond the normal period of pubertal onset into adulthood or whether prepubertal GDX chronically impairs the proper development of neuroendocrine reproductive circuits (including ARC Kiss1 neurons). PND 14 male mice were GDX or left intact and then euthanized 3.5 wk later in adulthood at PND 45 (after the time of normal puberty, which is normally ∼PND 35 in males). Blood and brains were collected at the time of euthanization and assayed for LH levels and Kiss1 expression in the ARC, respectively; n = 6–8 animals/group.
Experiment 5: effects of gonadectomy on NKB expression in the ARC of juvenile males and females.
The previous experiments identified a unique developmental sex difference in the regulation of Kiss1 gene expression in the ARC of juvenile, but not adult, mice. This experiment determined whether this juvenile sex difference extends to NKB, another reproduction-related gene also expressed in the ARC. PND 14 male and female mice were GDX or left intact and then euthanized 4 days later (PND 18). Brains were collected and assayed for NKB expression in the ARC using in situ hybridization assay. For comparison with the juvenile situation, NKB expression in the ARC was also assessed in adult male and female mice that were GDX or left intact (in adulthood) and then euthanized 4 days later as well as in males that were GDX prepubertally on PND 14 and then euthanized in adulthood on PND 45 (alternate sets of tissue from experiments 3 and 4); n = 8–12 animals/group.
Data analysis and statistics.
In situ hybridization slides were analyzed with an automated image-processing system by a person blind to the treatment group of each slide. Custom grain-counting software was used to unilaterally count the number of cell clusters and the number of silver grains over each cell (a semiquantitative index of mRNA content per cell), as described previously (18, 26, 50). Cells were considered Kiss1 (or NKB)-positive when the number of silver grains in a cluster exceeded that of background by threefold. In each experiment, differences in group means of LH or mRNA levels were assessed via ANOVA, with post hoc analysis determined by Fisher's least significant difference test. Due to nonhomogeneity in the variance of AVPV Kiss1 cell numbers between groups, these data were log transformed prior to statistical analysis. For all comparisons, statistical significance was set at P < 0.05.
Experiment 1: effects of gonadectomy on LH and Kiss1 expression in prepubertal males and females.
In experiment 1A, we evaluated whether the removal of gonadal hormones on PND 14, prior to normal puberty onset, triggers early increases in gonadotropin secretion and/or Kiss1 gene expression in the ARC. In juvenile GDX females, serum LH levels were significantly elevated at 2 and 4 days postgonadectomy (PND 16 and 18, respectively) relative to LH levels of intact females (P < 0.05 for each age; Fig. 1A). In contrast, plasma LH levels were unchanged in GDX juvenile males at 2 and 4 days postgonadectomy (P > 0.05 for each age relative to intact males; Fig. 1B). Kiss1 gene expression in the ARC followed a similar sex-specific pattern. Specifically, juvenile GDX females had significantly higher numbers of Kiss1 neurons in the ARC than intact females at both postgonadectomy ages (P < 0.05 for each time; Figs. 2 and 3), whereas GDX juvenile males did not have more detectable ARC Kiss1 neurons than intact males at either postgonadectomy age (Figs. 2 and 3). Silver grains per cell, a semiquantitative measurement of Kiss1 mRNA per cell, followed a pattern similar to the number of Kiss1 cells for each sex (Fig. 3).
In experiment 1B, brain sections of PND 18 males and females were assayed together. In the ARC, the number of Kiss1 neurons was not significantly different between intact PND 18 males and females (Fig. 4A). However, in PND 18 GDX males and females (4 days after gonadectomy) there was a robust sex difference, with GDX juvenile females having significantly more Kiss1 neurons in the ARC than GDX juvenile males (P < 0.05; Fig. 4A). The number of ARC Kiss1 neurons in GDX PND 18 males was not significantly different from intact males and females (Fig. 4A). These findings indicate a sex difference in prepubertal ARC Kiss1 neurons that is observed only after removal of gonadal hormones. In the AVPV/PeN, a region with previously documented sex differences in Kiss1 expression in adult rodents (females > males), we found a significant sex difference in the number of Kiss1 neurons in PND 18 mice in both intact and GDX scenarios. PND 18 females had significantly more Kiss1 neurons (and Kiss1 mRNA/cell; data not shown) than PND 18 males, regardless of gonadal status (P < 0.05; Fig. 4B), indicating that the AVPV/PeN Kiss1 system is sexually differentiated as early as PND 18, and this sex difference is independent of the circulating hormonal milieu. Intact PND 18 males had low numbers of Kiss1 neurons in the AVPV/PeN but still significantly more than GDX PND 18 males (P < 0.05; Fig. 4B), indicating that the AVPV/PeN Kiss1 system in juvenile males responds to gonadectomy, unlike ARC Kiss1 neurons.
Experiment 2: effect of castration on serum T levels in juvenile males.
In experiment 1, we determined that both gonadotropin secretion and ARC Kiss1 gene expression are elevated 4 days after gonadectomy in juvenile females but not males. Here, we assessed whether plasma T levels were significantly different between intact and GDX juvenile mice 4 days postcastration (on PND 18). In general, serum T levels were low in intact PND 18 males given their young age. Even so, GDX PND 18 males had significantly lower, in most cases undetectable, T levels compared with intact PND 18 males (0.10 ± 0.05 vs. 0.27 ± 0.05 ng/ml, P < 0.05), confirming reduced levels of T at 4 days postcastration. Thus, the absence of elevated LH and Kiss1 expression in PND 18 GDX males is not due to the presence of residual circulating T.
Experiment 3: effects of gonadectomy on levels of LH and Kiss1 mRNA in adult males and females.
In experiment 1, both gonadotropin secretion and ARC Kiss1 gene expression were elevated in juvenile females but not juvenile males 4 days after gonadectomy. Experiment 3 determined whether 4 days postcastration is long enough to evoke changes in LH secretion or Kiss1 expression in adult males and whether the sex difference in the regulation of ARC Kiss1 neurons that was observed prepubertally is also present in adulthood. We found that, unlike the pattern observed in juvenile animals, serum LH levels were significantly elevated in adults of both sexes 4 days after gonadectomy (P < 0.05 vs. intact adults; Fig. 5A). Similarly, unlike the juvenile situation, Kiss1 expression in the ARC was significantly increased to the same degree in both adult males and females 4 days after gonadectomy (P < 0.05 relative to intact adults; Fig. 5B), indicating that the sex difference in Kiss1 regulation in the ARC is present before puberty but not in adulthood.
Experiment 4: Kiss1 expression and LH secretion in adult males that were GDX as juveniles.
The previous experiments determined that male mice do not display activation of either LH secretion or ARC Kiss1 gene expression 4 days after gonadectomy as juveniles but do so after gonadectomy as adults. Here, we tested whether the reproductive axis (including Kiss1 neurons in the ARC) of juvenile GDX males eventually becomes activated as they age into adulthood in the absence of developmental changes in gonadal hormones. If so, it would indicate that the gonadal hormone-independent restraint on male reproductive circuits is eventually overcome as males reach adulthood and that the juvenile ARC Kiss1 system can develop the adult phenotype in the absence of gonadal hormones. We found that males that were GDX as juveniles on PND 14 and euthanized 31 days later in adulthood (on PND 45) had serum LH levels that were significantly elevated above that of intact adult males (P < 0.05; Fig. 5C). Similarly, the number of Kiss1 neurons in the ARC was significantly higher in adult males that had been GDX as juveniles compared with adult males that were left intact as juveniles (P < 0.05; Fig. 5D). Likewise, Kiss1 mRNA per cell was significantly greater in adult males GDX as juveniles (P < 0.05 vs. intact adult males; data not shown).
Experiment 5: effects of gonadectomy on NKB expression in juvenile males and females.
Here, we tested whether NKB, which is coexpressed in ARC Kiss1 cells (17, 31), shows similar sex-specific changes in gene expression as Kiss1 following removal of gonadal hormones during the prepubertal period. We found that, similar to Kiss1, the number of NKB-expressing neurons in the ARC was significantly upregulated 4 days after gonadectomy in PND 18 GDX females but not PND 18 GDX males (compared with PND 18 intact animals, P < 0.05 for female comparison; Fig. 6, A and B). Similarly, PND 18 GDX females had significantly more (P < 0.05) NKB mRNA per cell compared with the other three PND 18 groups [121.2 ± 3.5 (GDX female) vs. 101.6 ± 7.0 (intact female), 99.5 ± 5.3 (GDX male), and 93.9 ± 8.2 (intact male) grains/cell]. Also like Kiss1, the sex difference in NKB regulation was no longer manifest in adulthood, since both males and females showed similar increased NKB gene expression 4 days after gonadectomy as adults (P < 0.05 for both sexes relative to intact adults; Fig. 6C). Moreover, as with Kiss1, the number of NKB-expressing neurons in the ARC was significantly higher in adult males that had previously been GDX as juveniles compared with adult males that had been left intact as juveniles (261.5 ± 15.4 vs. 140.7 ± 30.6 NKB cells, P < 0.01). NKB mRNA per cell in the ARC followed a similar pattern, being higher in adult males that had been GDX as juveniles than those left intact (P < 0.01; data not shown).
Puberty reflects the physiological processes that guide the awakening of the adult neuroendocrine reproductive axis (11, 35, 37). Despite awareness that gonadal hormone-dependent and hormone-independent mechanisms may guide the tempo of pubertal development (11, 22, 35, 37), the cellular and molecular processes that mediate this event are poorly understood, as is the enigma that females usually mature earlier than males (12, 13, 19). Recently, neuronal kisspeptin and NKB signaling have each been implicated in puberty onset, as highlighted by findings that humans lacking either a functional kisspeptin receptor or NKB receptor (or NKB itself) display salient deficits in pubertal onset and fertility (9, 14, 27, 46, 47, 55). Our present study provides further evidence that Kiss1/NKB neurons, located in the ARC, are linked to the timing of developmental activation of the reproductive axis and that the regulation of these neurons is sexually differentiated. Specifically, gonadectomy during the juvenile period stimulates Kiss1/NKB expression in the ARC and concurrently increases gonadotropin secretion in female but not male mice, suggesting that the neuronal circuits that activate the peripubertal reproductive axis are regulated in a sex-specific manner. On the basis of our findings, we infer that activation (or disinhibition) of Kiss1/NKB neurons in the ARC constitutes a critical element of the puberty-triggering mechanism. Furthermore, we deduce that during juvenile life in females, Kiss1/NKB neuronal activity in the ARC is constrained primarily by gonadal hormones, whereas in juvenile males, ARC Kiss1/NKB signaling is gated by gonadal hormone-independent factors (and, likely concurrently, by gonadal hormones as well). Thus, sex differences in the timing of puberty onset may reflect fundamentally different neuronal mechanisms (or differences in their regulation) that govern the tempo of sexual maturation in males and females.
We have shown previously that the Kiss1 population in the ARC is not sexually dimorphic in adult rodents, regardless of sex steroid milieu (26). However, our present study identifies a robust sex difference in the regulation of ARC Kiss1 neurons during the prepubertal period. We also report for the first time a prepubertal sex difference in the regulation of NKB expression in the ARC. The factor(s) regulating Kiss1/NKB neurons in the ARC of juvenile animals has not previously been identified. However, our findings suggest that, in juvenile females, at PND 16–18, ovarian hormones (presumably E2) are key regulators of ARC Kiss1/NKB neurons, because gonadectomy induces striking increases in Kiss1 and NKB expression. Thus, we infer that E2-mediated inhibition of Kiss1/NKB neurons in the ARC represents a primary mechanism for maintaining the quiescent state of the reproductive axis in intact prepubertal females. Indeed, estrogen receptors are coexpressed in virtually all Kiss1 and NKB neurons in the ARC of adult mice (10, 50), lending support to this argument. In contrast to females, juvenile GDX male mice do not display increases in Kiss1, NKB, or LH levels at PND 16–18. Thus, although gonadal hormones likely inhibit the reproductive axis in juvenile males (as in juvenile females), other regulatory inputs, apart from gonadal hormones, must either impose active restraint on or fail to activate Kiss1/NKB expression and LH secretion during prepubertal life.
NKB has recently been implicated in the control of puberty and reproduction. Humans lacking NKB or its receptor have delayed puberty onset and impaired fertility (55), suggesting a role for NKB signaling in the initiation of puberty. Although intracerebroventricular infusions of NKB agonist diminish LH secretion in adult female ovariectomized E-primed rats (44), site-specific NKB agonist infusions in discrete hypothalamic regions (rather than the ventricles) stimulate LH secretion in sheep (32), suggesting that NKB's effects are site specific. Indeed, NKB most likely acts at several places in the brain, including GnRH neurons in the medial preoptic area and Kiss1/NKB neurons in the ARC, both of which express NK3 (28, 31, 54). Our results here implicate NKB in the ARC as a critical component of the circuits underlying activation of the neuroendocrine reproductive axis.
Our results signify that the brains of juvenile male and female mice, including Kiss1/NKB neurons in the ARC, are sexually differentiated such that prepubertal females aged PND 14 can initiate activation of the reproductive axis after gonadectomy, whereas similarly aged males cannot. These findings suggest that sex differences in how and when Kiss1/NKB neurons in the ARC are regulated may be instrumental to explaining sex differences in puberty onset. Although sex differences in sexual maturation are well documented, the basis for the differential timing of puberty between males and females is unclear and may reflect either fundamentally different mechanisms operating in each sex or, alternatively, a common regulatory process that is initiated at different times in the two sexes (i.e., earlier in females than in males). Both of these possibilities could include either the presence of additional (or longer-lasting) restraining factors in PND 16–18 male vs. female brains or the absence of additional (or later induction of) activating circuits in PND 16–18 males that are already present in females at the same prepubertal age. In either case, these additional restraining/activating factors appear to be gonadal hormone independent in nature, as is their developmental onset/offset, as evidenced by that fact that LH and Kiss1/NKB in GDX males were not elevated at PND 18 but did eventually increase by PND 45 in the absence of any changes in gonadal hormone levels. The identity of the gonadal hormone-independent factor(s) that regulates prepubertal Kiss1/NKB neurons is currently unknown. Previous studies in primates and rodents have implicated several factors that may regulate pubertal circuits, including neuropeptide Y, leptin, GABA, enhanced at puberty 1, and glial factors (3, 4, 34, 35, 37). Any one or more of these nongonadal factors may provide critical input into prepubertal Kiss1/NKB neurons and perhaps even explain the sex differences in Kiss1/NKB expression in the ARC after prepubertal gonadectomy, and revealing their identity will be an important objective for future studies.
We and others have shown previously that the Kiss1 system in the AVPV/PeN of adult rodents is sexually differentiated, with adult females having many more Kiss1 neurons in the AVPV/PeN than males (6, 26). This sex difference in AVPV/PeN Kiss1 neurons may explain the ability of adult females, but not males, to display an E2-induced LH surge (23, 27). Here, we report that Kiss1 expression in the AVPV/PeN of mice is sexually dimorphic as early as PND 18. This is the first demonstration of the sex difference in AVPV/PeN Kiss1 expression in prepubertal animals of any species. [In fact, females have significantly more Kiss1 neurons in the AVPV/PeN than males as early as PND 16 (P < 0.01; Kauffman AS and Steiner RA, unpublished observations)]. Our study also presents the earliest reported age (PND 16) of Kiss1 gene expression in the AVPV/PeN, with a previous study in the mouse documenting detectable kisspeptin protein by immunohistochemistry in the female AVPV/PeN on PND 25 but not on PND 10 (6). It is noteworthy that a direct comparison between intact and GDX PND 18 males revealed a small but significant elevation in Kiss1 cell number in the AVPV/PeN of intact males. Similarly, we have found that, on PND 16, intact males have five times as many Kiss1 cells in the AVPV/PeN than GDX males at this age (P < 0.01; Kauffman AS and Steiner RA, unpublished observations), indicating that Kiss1 neurons in the AVPV/PeN of juvenile males can respond to changes in gonadal hormone status, unlike Kiss1 neurons in the ARC.
Recently, Clarkson et al. (5) suggested a role for the AVPV/PeN Kiss1 system in the initiation of puberty onset on the basis of the finding that ovariectomized prepubertal mice fail to display vaginal opening or elevated kisspeptin protein in the AVPV/PeN later in early adulthood. However, Kiss1 mRNA and kisspeptin protein levels in the AVPV/PeN are highly E2 dependent (upregulated by E2) in the adult female rodent (1, 50, 52), and thus, an important caveat when interpreting the finding of Clarkson et al. (5) is that their GDX juveniles were never replaced with E2 in adulthood. Therefore, it is possible that the low kisspeptin levels observed in the AVPV/PeN of their adult GDX animals reflect absent circulating E2 in adulthood. Moreover, in our study, Kiss1 mRNA levels in the AVPV/PeN clearly decrease in prepubertal females following GDX despite the concurrent increase in LH secretion in these same females. We interpret this to signify that Kiss1 activity in the AVPV/PeN is unlikely to be driving the elevated GnRH/LH secretion in these prepubertal animals (since the AVPV/PeN is producing significantly less kisspeptin after gonadectomy). Notwithstanding, it is certainly possible that the AVPV/PeN Kiss1 system contributes to the enhanced drive to GnRH neurons at some point during puberty; however, this would definitely not exclude an important (even central) role for other neural circuits as well, including Kiss1/NKB neurons in the ARC. Indeed, it is somewhat paradoxical that in the GDX mice lacking vaginal opening in the study conducted by Clarkson et al. (5), kisspeptin levels were also noticeably reduced in the ARC, but the possibility that the diminished ARC kisspeptin levels contributed to these animals' impaired puberty onset was not addressed.
Interestingly, although not yet assessed, there may not be a sex difference in the regulation of ARC Kiss1/NKB neurons in prepubertal rats, since GDX prepubertal rats of both sexes appear to show comparable rapid elevations in LH secretion both 2 and 4 days postsurgery, at least at the ages studied (20, 33, 39). However, adult female rats take much longer to exhibit elevated LH levels following gonadectomy than they do as juveniles (15, 16, 53), indicating that some developmental alteration in central feedback mechanisms occurs in female rats as they age through puberty. Although these earlier observations in prepubertal rats suggest that puberty in rodents is primarily gonadal hormone dependent, our findings argue that gonadal hormone-independent factors are also critical at least in mice and perhaps other rodents as well. Similarly, puberty in primates, including humans, also appears to involve both gonadal hormone-dependent and -independent processes, as evidenced by findings that GDX juvenile monkeys do not display elevated LH before the normal age of puberty (36, 37), nor do humans that lack gonadal hormone secretion before puberty (7, 19). To the extent that such divergent species can be compared (and with caution), puberty in mice may therefore share common features with other species, including humans and nonhuman primates. Therefore, our findings may have implications for the pathophysiology of puberty in humans, in which puberty is not only earlier in girls than in boys, but girls also display a much higher incidence of precocious puberty (10-fold) than boys (37). On the other hand, boys are more likely to have delayed puberty than girls (37). These sex differences in normal puberty onset and disorders in pubertal timing are widely recognized but poorly understood and may involve sex differences in the timing or regulation of Kiss1/NKB signaling in the brain.
In conclusion, we report a novel sex difference in the regulation of LH secretion and Kiss1 and NKB expression in the ARC of juvenile mice such that the developing brains of juvenile males exhibit greater (or longer-lasting) gonadal hormone-independent restraint (or less gonadal hormone-independent activation) on reproductive neuronal circuits, including ARC Kiss1/NKB neurons. This sex difference in Kiss1/NKB regulation may contribute to the differential timing of puberty onset between the sexes. Thus, although gonadal hormones most likely play a critical role in regulating puberty onset in both sexes, our findings indicate that gonadal hormone-independent processes also contribute to timing puberty in mice (as they do in primates). Additional experiments are needed to identify the central factors inhibiting/activating Kiss1/NKB neurons in the ARC and to determine the specific role of these two reproductive neuropeptides.
This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/NIH through cooperative agreements U54-HD-12629 (to the University of Washington Center for Research in Reproduction and Contraception) and U54-HD-28934 (University of Virginia Ligand Assay Core) as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. Additional funding was provided by NICHD Grants HD-056157 (to A. S. Kauffman) and HD-049651 (to R. A. Steiner) and the Fulbright Program of the US Department of State and the Ministerio Español de Ciencia e Innovación (to V. M. Navarro).
- Copyright © 2009 the American Physiological Society


text:
After everything that has gone on the last few months 2013 is a new year and this year I want to give something back.
Last year you may remember I did picnic in the park with my Made For Mum's neighbourhood and raise money for my local hospice – Keech Hospice. It (more…)

subset: commoncrawl


text:
MOVIE SYNOPSIS [ +16 years-old ] Korean production of monsters, shot in 3D, set in 1985. It follows a group of workers from an oil tanker must face a terrifying creature. Hae -jun begins working on a research ship oil as scuba charge. His father, who worked in the same location, mysteriously died years ago, and now begin to repeat the deaths, when classmates start to disappear one after another. The fault is not in any saboteur within the team, but a sea creature who infiltrated the ship, so that all danger. You can watch Chilgwanggu (Sector 7) online on TV cable or theaters with original audio in Korean at different dates. This film premiered in theaters in 2011.
Rating: 5 by 221 users./
Runtime: 101 minutes
Ha Ji-won, Oh Ji-ho, Ahn Sung-ki, Park Chul-min, Lee Han-wi, Song Sae-byuk and Cha Ye-ryun.
Fantasy, Terror, Action.
101-minute film (full movie) directed by Kim Ji-hun (AKA Kim Ji-hoon).
The original audio of Chilgwanggu (Sector 7) has dialogues in or Korean, it was produced in South Korea.
It premiered in cinemas or television in 2011.
Screenplay written by Yun Je-gyun.
Lee Doo-man.
This film was produced and / or financed by CJ Entertainment and JK Film.
Composed by Kim Sung-hyun.
Without commercial breaks, the full movie Chilgwanggu (Sector 7) has a duration of 101 minutes; the official trailer can be watched in streaming on the Internet. You can watch this full movie free in English or Korean in movie TV channels, renting the DVD or with VoD services (Video On Demand player, Hulu) and PPV (Pay Per View, Netflix).
See the page of this full movie, Chilgwanggu (Sector 7) in FULLTV Movies.


text:
sort by best latest
Because today people don't think they have a duty to stay with one partner for a lifetime. In the past there were no divorces and women were not allowed to leave the family or they would lose their children. Today people are more independent, especially women and don't believe they have to sacrifice everything to keep a relationship going.
The other thing is that nowadays we are probably not trying that hard to make the relationship survive. There is much to be done once you are with somebody and it takes a lot of hard work to be a family/couple.
You can help the HubPages community highlight top quality content by ranking this answer up or down.


text:
sort by best latest
I love America. Sort of. I love the people, for the most part, though they are part of the problem. I love the Constitution, though it was originally an imperfect document; it has stood as a shining inspiration for the planet. The government and its corruption are not on my favorites list.
The president vows to protect the Constitution and then proceeds to repeatedly trash that precious document. I'd call that treason -- multiple counts. In fact, Obama has had impeachment proceedings filed against him in Congress, in early 2012. I don't know if that showed up in the news. (I live in the Philippines)
I'm not wild about what America has become -- the new Evil Empire, attacking other countries without provocation. The Neocon manifesto has declared the world "easy pickings" for their selfish greed -- open season on planetary resources. It seems they are purposefully stirring the hornets nest so that America becomes the new social pariah. It's working. People hate America with greater fervor than ever.
It seems that the government and their Corporate Party lobbyist handlers are driving the country into financial quagmire -- over the cliff with insane money management. Piling up debt at an accelerating pace. The private Federal Reserve Bank is feeding this insane frenzy with its century-long Ponzi scheme of debt-based currency. That bubble is now about ripe for popping. When it does, the dollar will be worthless.
And the government has gone out of its way to shred the Constitution. It's now a felony to protest what the government is doing. Never in America? What an ironic laugh!
The only way to "fix" this is for everyone in America to wake up and to take responsibility. No more depending on the government for anything.
Walk away!
Boycott the Corporate Party and their propaganda media. Boycott large corporations and their products and services. Bank at local credit unions. Cut back on gasoline by riding a bike or walking. This is the only way to get the message to the horsemen of tyranny. Don't buy their fear mongering.
Be independent and happy, despite what they say or do.
You can help the HubPages community highlight top quality content by ranking this answer up or down.
I don't have the political clout to manipulate things willfully and inordinately, but that doesn't mean that I cannot do anything to improve the country. Because I am highly gifted in arts (not a hyperbole), I will offer free tuition to people who are facing fiscal difficulties. That, per se, is a great contribution to the education system.
You can help the HubPages community highlight top quality content by ranking this answer up or down.
In our own way, we can find ways to make our country better.
I always believe in giving back to society whenever possible. I am helped to recycle and slowly down the greenhouse effect. Helping those who are in need within my means and capabilities. Teaching people how to help themselves to survive.
You can help the HubPages community highlight top quality content by ranking this answer up or down.
be an honest and responsible citizen. know how to follow rules.
You can help the HubPages community highlight top quality content by ranking this answer up or down.
Follow rules? Hilarious. When the president repeatedly trashes the Constitution and Bill of Rights, effectively committing treason, then following the rules is the last thing to do. Peaceful disobedience. Ignore the tyranny
yeah hilarious. but my answer is based on my country where a lot of citizens don't know how to follow "simple rules". and yes I know what you mean.
In any country,are there rules. But following them religiously is another matter. In the Philippines we have lots of rules and laws. But the problem is implementing them.


text:
Thursday, September 7, 2017
Prof. Paul Anastas will receive a prestigious RSC Award for his seminal work in the field of green chemistry in developing innovative methods in molecular design, leading to products and processes that reduce environmental impacts.
As a part of this recognition Prof. Anastas will complete a UK tour where he will give plenary lectures looking back at the 25 years of green chemistry. The lectures will be featured at the University of York (3rd EuGSC Congress on Green and Sustainable Chemistry, September 3-6 2017), University of Oxford (September 7) and Queen's University Belfast (September 8).


text:
This shop has been compensated by Collective Bias, Inc. and its advertiser. All opinions are mine alone. #MajorBeauty #CollectiveBias
With the first day of back-to-school well on its way, I wanted to show you all how I maintain an easy, but effective skincare routine for those long, tiring nights of studying. I purchased a couple of my favourite products from Neutrogena and Clean & Clear, two of my go-to brands for skincare (and beauty too!) The products that I purchased are: Clean & Clear Oil Absorbing Sheets, Neutrogena Makeup Remover Cleansing Towelettes Refill, Neutrogena Oil-Free Acne Wash Pink Grapefruit Foaming Scrub, Clean & Clear Morning Burst Facial Cleanser Oil-Free, Clean & Clear Blackhead Eraser Scrub Oil-Free and Neutrogena Oil-Free Moisturizer Combination Skin. These products can all be found at Target for amazing prices, so you won't have to worry if you can afford them or not, because they are extremely well priced.I want to tell you a bit about each of these products and why I purchased them. The Clean & Clear Oil Absorbing Sheets are perfect for when you feel your face is getting shiny after a long day of classes but you still have a night class to get through. These come in handy because they don't smudge your makeup, and they're super small so you can easily throw them into your purse with no fuss. The Neutrogena Makeup Remover Cleansing Towelettes Refill work great for removing makeup plus they even remove waterproof mascara which we all know is quite tough to remove. Another great thing about these towelettes is the fact that they don't leave any heavy residue, so you don't even have to rinse your face after. This is my go-to product when I'm out on a Friday night at a sleepover and I don't feel like taking all my makeup off but still need to maintain a healthy skincare routine.
I also love the Neutrogena Oil-Free Acne Wash Pink Grapefruit Foaming Scrub, not only does it smell delicious but it eliminates oil and dirt from your face and rinses your face clean without drying it out. I love the Clean & Clear Morning Burst Facial Cleanser Oil-Free because the bursting beads make you feel so much more awake, they dissolve easily once lathered and revive your skin. I love the Clean & Clear Blackhead Eraser Oil-Free too because it works gently in removing your blackheads, something you're bound to get as a college student (if anything, I am at least.) Last but definitely not least, the Neutrogena Oil-Free Moisturizer Combination Skin is so nice for your finishing touch. It moisturizes your skin without drying it out and controls the shiny areas too.
Now that I have you all hooked on why I bought these particular products, I want to give you a tutorial step-by-step of my easy but effective skincare routine for back-to-college.
First off, I use the Clean & Clear Oil Absorbing Sheets to remove any excess oil from the day to stay ready for night classes. These are great because they don't smudge my makeup off and I don't have to waste time reapplying it while rushing back to classes.At night when I get back from school, I use the Neutrogena Makeup Remover Cleansing Towelettes Refill to get all my makeup off, it's very important you don't miss this step because makeup builds throughout the day and can cause breakouts if you sleep in it. (Not to mention, it's going to make a mess on your pillow and sheets too!) These towelettes are great because they're ultra-soft and you don't have to rinse your face afterwards.Next, I use the Neutrogena Oil-Free Acne Wash Pink Grapefruit Foaming Scrub to get rid of blemishes and blackheads, this scrub doesn't dry out your skin and a refreshing grapefruit scent to it too. I love lathering up with this!After that, I use the Clean & Clear Morning Burst Facial Cleanser Oil-Free, it really does wake you up because the bursting beads are full of vitamins and an invigorating citrus fragrance. It's always important to cleanse your face daily as it helps nourish your skin and remove the dirt.I also like to use the Clean & Clear Blackhead Eraser because I find when I'm stressed I tend to get many blackheads. This product is great because it was made for acne purposes and is an effective way of clearing up blackheads. I just put a bit on my nose and chin area and massage it all over, rinse and than pat dry.The last step which is very important that you don't skip is moisturizing. Moisturizing is very important because it helps to reduce dryness and irritation. (You will also thank yourself for moisturizing at a young age because it will help reduce signs of aging!)And there you have it, that's my skincare routine broken down step-by-step. If you have any questions, don't hesitate to get in touch with me, I will be more than happy to help.
Also, here's an awesome deal Target is having right now too: Buy any one participating Neutrogena facial, Neutrogena cosmetic or Clean & Clear facial product and get one 25% off from July-August 2016.
To enter to win a Neutrogena, Clean & Clear and Aveeno sweepstakes click the link below:
Neutrogena, Clean & Clear, and Aveeno #MajorBeauty Sweepstakes


text:
Exclamation Minx perfume for Women by Coty
8 out of 10 based on 1 ratings
|Design House
|Fragrance Gender
|Women's Fragrance
|Year Introduced
|Limited Edition
|Available Types
|Bottle Designer
|Scent Classification
|Floral Oriental
|Fragrance Notes
Popularity Total Hits: 14924
Voting Results
Exclamation Minx Coty - Description
Fragrance Exclamation Minx perfume for Women by Coty was introduced in 2008. Coty Exclamation Minx is classified as Floral Oriental fragrance. Scent notes of Exclamation Minx Coty include top notes of fruits, middle notes of flowers and base notes of exotic spices.
Exclamation Minx perfume for Women by Coty 8 out of 10 based on 1 ratings.
Exclamation Minx Coty - Full Story
Disclaimer: We can not guarantee that the information on this page is 100% correct. Read more.. [show/hide]
Whilst every effort has been made to ensure that the information on this site is as accurate as possible, PerfumeMaster.org cannot be held responsible for any inaccuracies or consequences arising out of the use of this site.
This page contains information, reviews, perfume notes, pictures, ads, vintage posters and videos about Exclamation Minx perfume for Women by Coty but we do not warrant accuracy of information. If you have more information about Exclamation Minx perfume for Women by Coty, you can expand it by adding a personal fragrance review.
Additionally, you may find hyperlinks to 3rd party web-sites On-line Internet stores, however PerfumeMaster.org has no access or control over those websites. We do not provide warranties neither accept responsibility for what you might find as a result of these links, or for any future consequences including but not limited to money loss. User reviews of Exclamation Minx perfume for Women by Coty represent views of individual site users only and do not represent PerfumeMaster.org views.
Exclamation Minx Coty - User Opinions and Reviews
Other Fragrances by Coty
Similar Scents to Exclamation Minx
Frargance Directory - Most Popular Brands
Copyright © 2017 PerfumeMaster.org. Powered by Perfume Master V.3.0
Privacy Policy
Privacy Policy


text:
We help you locate a Bedford recorder teacher. Recorder lessons are a brilliant way to learn a stimulating new hobby, acquire a new talent and attain confidence with recorder. Please use our service to search for Bedford recorder teachers and select which best suits your needs so you can begin your recorder tuition in Bedford today!
First Tutors: Music is the best place to contact Bedford recorder teachers in the UK, helping you discover Bedford recorder lessons in your area and Bedford tutors to help with any instrument such as piano, violin or guitar. We can help you find Bedford recorder lessons or a one-to-one Bedford recorder tutor to prepare for recorder grades and improve your recorder skills! Our search will order Bedford recorder tutors near you according to their lesson charges and proximity to you.
If you are a recorder tutor wishing to offer recorder tuition services in Bedford or throughout the UK, please register with First Tutors: Music or find out more about us here. Becoming a Bedford recorder teacher is a great way to improve your own knowledge by giving recorder lessons while assisting others, all in Bedford!


text:
AUTOMATIC is the key word here. We want to create watering systems that are easy to use, don't require a lot of monitoring and gets the job done. We do this by analyzing the site and engineering a watering system that makes sense. We take your garden's size, microclimates and needs all into account. For example: if you have a large two acre site, you might save thousands of dollars a year by having us install a satellite controlled irrigation system. Whereas a small coastal cottage property would not warrant the expense of such a system. The types of controllers we use are among the major brands of Rain Bird, Hunter and Toro. We use the Weather TRAK brand for our satellite installations.
The simple mechanics of a watering system that hold up year after year are the basis of all of our installations. For example, all of our lawn and shrub risers are installed with "swing joints" that are multi-directional swivel joints which protect the PVC pipes from breaking even when lawn mowers or children intervene. We place the remote controlled valves where they are hidden by plantings, yet easily accessed for repair and service. No valves or mainlines are located near a home's foundation. The layout and spacing of heads are designed to keep moisture away from a home's exterior.
With the water shortages and rationing, Torrey Pines Landscape has been on the leading edge of utilizing the newest irrigation technology. We replace water-wasting fixed nozzle heads with the new mini-rotating heads from Hunter Industries or Rain Bird. We are also converting some systems to underground drip systems where it makes sense to install them. We also utilize fertilizer injection with our drip systems as well.
Whether you have a large garden, or a small one, you'll have a peace of mind in knowing that we have taken the time to teach you to understand your new irrigation system. What this all means is that you can count on your new automatic watering system to apply just the right amount of water at the right time to keep your garden beautiful and healthy!


text: I paid 120 when i got it done in bangalore few months back! (might well be more than 6 months. need to check now, was somehow under the impression that its valid for an year) they told for petrol vehicles its 60 and for diesels they have to do lot of checks so its costlier.


text:
Today I have for you a super easy fruit salad, made with banana chunks, coconut & jaggery. This is more of a traditional salad made during the olden days mainly as an offering to God, I made this today for Maha Shivratri ...
You Will Need:
- 3 Bananas ( any variety ) - cut into round chunks
- 2 tbsp grated jaggery
- 2 tbsp grated coconut
- 2 tbsp almonds - chopped
- Mix in banana chunks, grated jaggery, grated coconut in a large bowl
- Garnish with chopped almonds
- Chill for 30 minutes before serving
Enjoi !!!
If you want to cut down on custard & sugar in fruit salads, then this is for you ..
This one does taste different from the regular fruit salads. The slight sweetness from jaggery & creamy coconut coats well with banana & chopped almonds add a nice cruch. I sometimes have this as an evening snack too ..
- Serve as a dessert topped with vanilla ice cream.
- Though, traditional Rasayana calls for bananas, you could add other fruits like apple, pineapple, orange, grapes etc. to this


text:
Reuters Staff
1 Min Read
April 10 (Reuters) - White Organic Agro Ltd
* White Organic Agro says signing of lease farming pacts Source text: (bit.ly/2pjsO7Q) Further company coverage:
All quotes delayed a minimum of 15 minutes. See here for a complete list of exchanges and delays.
© 2017 Reuters. All Rights Reserved.


text:
Growing up on Forge's streets has taught Kyra how to stretch a coin. And when that's not enough, her uncanny ability to scale walls and bypass guards helps her take what she needs. But when the leader of the Assassins Guild offers Kyra a lucrative job, she hesitates. She knows how to get by on her own, and she's not sure she wants to play by his rules. But he is persistent - and darkly attractive - and Kyra can't quite resist his pull. Tristam of Brancel is a young Palace knight on a mission. After his best friend is brutally murdered by the Demon Riders, a clan of vicious warriors who ride bloodthirsty wildcats, Tristam vows to take them down. But as his investigation deepens, he finds his efforts thwarted by a talented thief, one who sneaks past Palace defenses with uncanny ease.
When a fateful raid throws Kyra and Tristam together, the two enemies realize that their best chance at survival - and vengeance - might be to join forces. And as their loyalties are tested to the breaking point, they learn a startling secret about Kyra's past that threatens to reshape both their lives.
We've sent an email with your order details. Order ID #:
Listen on the Audible app or these devices.Launch Audible App
-or-Download Free Audible App
To access this title, visit your library in the app or on the desktop website.
Listen on the Audible app or these devices.Launch Audible App
-or-Download Free Audible App
Audible does not currently have the rights to sell this title in your country.
Please consider another book.Continue Browsing
Please add a payment method to continue.Add a Payment Method
Please edit your payment details or add a new card.
If the problem persists, contact customer service at (888) 283-5051Review My Payment Method
If the problem persists, contact customer service at (888) 283-5051
Please add your billing address to continue.Add My Billing Address
Please select a default credit card to continue.Select Credit Card
It looks like you've already used the specified payment method for a free trial.
Please contact customer service if you think we have made a mistake. (888) 283-5051Start Your $14.95 Membership
If the problem persists, contact customer service at (888) 283-5051
If the problem persists, contact customer service at (888) 283-5051
A strong opening, and a very trope-filled finish
- Yoshi
Good book, not great
This book was pretty good, but not a favorite. It kept my attention and moved at a good pace. I liked that the main character was a reasonably strong female. There were three male characters in her life, but only a hint at romance. I wasn't crazy about the large wildcats in the story - that seemed a bit strange. I wouldn't look for the next book in the series because in the end I didn't care enough about the characters or their relationships. I don't regret listening to this book, but I wouldn't seek out another.
- Sarah


text:
EMAN 2013 Korean version British men leather boots fashion Martin Bullock tide men's shoes at DinoDirect
Price: $96.78
Do you want to buy it for $91.94 ? Register on Extrabux and return 5% of all orders in DinoDirect and other online-shops. After registering you will earn $5 welcome bonus. The price will be even lower when using the coupon codes (on website Extrabux), cashback discount is summed up with coupons.
|Related goods


text:
LONDON, Dec 20 (IFR) - Euronext has entered into exclusive talks with the London Stock Exchange Group regarding a potential acquisition of LCH.Clearnet SA, its Paris-based clearing business.
A sale of the French clearinghouse could pave the way for a planned US$14bn acquisition of LSEG by Deutsche Boerse. Earlier this month, the European Commission laid out its objections to the proposed deal and competition regulators are focusing on derivatives clearing as part of an in-depth investigation into the planned tie-up.
While DB's Eurex is one of the most active European venues for trading and clearing listed derivatives, LSEG's London-based LCH is responsible for over 95% of cleared swaps activity - primarily through interest rate swaps clearinghouse SwapClear.
Once very distinct markets, over-the-counter and listed derivatives liquidity pools are becoming increasingly merged through portfolio margining, which enables clients to net swaps exposures with listed futures and options.
LSEG is offering to offload its French clearing business, which houses credit default swap clearinghouse CDSClear, to assuage regulators' concerns that a tie-up between the two exchange operators will create a single, dominant provider in derivatives clearing.
Around 972bn gross notional of CDS has been cleared through CDSClear since its launch in 2012 while InterContinental Exchange has cleared more than US$80trn across its US and London-based CDS clearinghouses since 2009.
While the slim volumes do little to cut LCH's dominance in cleared swaps, the business could provide Euronext with a registered swaps clearinghouse from which it can expand.
Any agreement between LSEG and Euronext would be conditional on the successful closing of the deal.
"At this stage, there can be no certainty that these discussions will lead to a transaction, or as to the terms on which a transaction, if any, might be agreed," Euronext said in a statement.
In addition to Euronext, CME Group has also been touted as a possible buyer of the Paris clearing business. The US derivatives exchange currently has registered swaps clearinghouses in the US and London. A platform in continental Europe could prove useful if European politicians force euro clearing into the European Union following the UK's departure from 28-country bloc. (Reporting by Helen Bartholomew)


text:
I am looking at buying one of these, brand new, for $375, features:
Harness the power of software applications like Adobe® Photoshop® and Corel® Painter to edit photos and create digital artwork with the Intuos3 Tablet PC from Wacom®. Enjoy cordless and battery-free performance with enhanced convenience and a natural feel with its incorporated Penabled technology. The tablet sports an ergonomic design with sloping, contoured palm rest for increased comfort and ease of use. Strategically placed programmable ExpressKeys are 'chordable' and can be used for mouse clicks, modifier keys and keyboard shortcuts. The finger-sensitive Touch Strip provides the convenience of quick scrolling, zooming, and more. The included Intuos3 Grip Pen with 1024 levels of pressure sensitivity enables you to dynamically control your software tools with minimal stress. In addition, the five-button mouse features five programmable buttons and a fingerwheel for smooth and accurate tracking. Alternating between the comfortable grip pen and the ergonomic five-button Intuos3 mouse reduces repetitive motion, so you can work easily and with minimum hassle.
Sound like a good deal? Any advice appreciated as I leap into the digital age.


text:
|Tyardley (USA)
Gas Pump Insert Cash
A gas pump that you can insert cash into (similar to a vending machine). I know theft could be a problem, but it would be similar to a ATM. This would be a convenience for people who don't use debit cards.
Reward: a hug


text:
We are delighted to have BBC Radio Suffolk on board again as our 2016 media partner along with Grapevine magazine.
We have some fantastic festival supporters for 2016:
Our fantastic patrons Our Silver Carbon Charter
We would love to hear from local and national businesses who are interested in working with FolkEast
FolkEast is an intimate, family-friendly multi-arts event encompassing music, dance, street theatre, arts and crafts, food and drink. We offer camping and day tickets at reasonable prices with the aim of attracting between 3000 and 5000 visitors over the weekend.
Sponsorship & Partnership opportunities include:
- • advertising (both online and in the programme)
- • designated areas around the site
- • marquee sponsorship
- • in-kind sponsorship
For more information please email email@example.com
We look forward to working with you.


text:
(Courtesy image)
The Women's March on Washington has handy digital resources for the event and beyond. In addition to a Facebook Messenger chatbot and a Saturday livestream, organizers have also released a Women's March App for users to connect, organize and voice solidarity even after the march has ended.
The app, built by SF dev firm doubledutch, is available for free download on the iTunes App Store and Google Play. You'll need to create a profile, which you can then link to your LinkedIn, Twitter and Facebook accounts.Download
The app has a Forum section as well as resources for educating people on the intersectionality of the movement's fight for justice. The Women's March Facebook page and Twitter feeds can also be accessed directly from the app.
Here's to a powerful spark for continued activism and organizing, because freedom never rests.


text:
Workshop of restoration and maintenance
PORSCHE 911 and PORSCHE 914
Art Restoration Garage
Tel. +33 (0) 9 81 97 19 92
To see our last restoration project
Cliquez ici
Awards :
Le Mans Classic - from 8 to 10 July - France.
The Excellence of French Know-How
Art Restoration joined in 2015 the 1,300 French firms benefiting from the EPV label !
The Entreprise du Patrimoine Vivant (Living Heritage Company, or EPV) label is a mark of recognition of the French State, put in place to reward French firms for the excellence of their traditional and industrial skills.
Official EPV website -> Cliquez ici
Seven videos to discover -> Click here
New company that performs restoration Fuchs rims as original. Located in our office, we bought our German subcontractor and thus benefit from 30 years of experience.
Website dedicated to rims restoration -> Click here
Workshop open from monday to saturday, from 8:00 to 12:00 and from 13:30 to 18:30. Call us before visiting.


text:
"From the Land of the Midnight Sun to the Land of the Rising Sun"
EZO follows Krister Kopala and his friends on an epic journey from Tromso in Northern Norway to the North Island of Japan, Hokkaido.
Krister Kopala grew up surrounded by snow, but January in Norway isn't ideal for snowboarding. 24-hour darkness, erratic weather and temperatures well below minus 20 force these guys to find snowboarding opportunities abroad.
This year they're landing in six meters of deep, fresh Hokkaido powder!
Directed, produced and shot by: Kristian Kvam Hansen. Produced for PUSH
Riders: Krister Kopala, Michael Stoerdal, Truls Berg, Roy Olsen, and friends
Additional Cinematography: Charles Lanceplaine
admin one of the founders of the internet.
Email this author | All posts by admin


text:
Glen Little gave the Shots the lead but Darren Jones saw red after he fouled Ryan Lowe in the area and though the striker missed his penalty, Mike Jones' cross found the back of the net.
The visitors made their extra-man advantage count in the second half as Jones grabbed his second and Marvin Morgan and then manager Kevin Dillon were dismissed before Nicholas Ajose wrapped up the points for the Shakers.
"I have been involved in football for 34 years and the performance from the referee was as bad as I have seen.
"I agree with the Morgan sending off but it was a second yellow rather than a red. I have to say the referee was dreadful. When we were down to nine the ref is playing advantages when he should be giving us free-kicks. What advantage do you have with nine men?"
"I feel sorry for the team and the supporters who were terrific. I am concerned about how things have gone but with nine men I thought we did well and it was a morale-boosting performance."


text:
Madurey Trailer (2004)
29 August 2004 Drama, Romance, Foreign 160 mins
Madhuravel (Vijay) in the first half is Madurai, a vegetable vendor along with his friend Pandu (Vadivelu). Madurai is a do-gooder and protector of the family of Seetha and her two daughters.
Watch the official Madurey 2004 trailer in HD below or find more Madurey videos on Vidimovie.


text:
Whether you're a girl with dangerous curves that you'd like to accent, or a slimmer beauty who wants to appear a bit more curvy, this swimsuit is for you. The combination bandeau and color block design, with a lighter panel in the middle and darker ones on the outside, give the allusion of a tinier waist. And the high cut brief will make your legs look a mile long. Perfectly priced at $48, this is a deal worth dipping your toes into.
Contrast Panel Belted Bandeau Swimsuit - Asos.com
Shop strapless swimsuits:


text:
|Page (1) of 1 - 03/22/12
|email article
|print page
RAID Inc. Announces Cluster Server Solutions Based on Latest Server Platforms(March 22, 2012)
ANDOVER, MA -- (Marketwire) -- 03/22/12 -- RAID Incorporated, an end-to-end customized solutions provider in HPC, Big Data, and virtualized environments, today announces its custom cluster offerings that are a perfect fit for HPC environments and workloads.
These custom clusters feature the latest technologies in high-performance and high-efficiency processors from Intel, AMD, and NVIDIA and boast breakthrough performance-per-watt numbers and I/O. Delivered with complete turnkey integration, these clusters also come with remote management and monitoring tools.
Architected by the RAID team after an extensive process in which a customer's unique needs are examined and their unique environment is clearly understood, these flexible and scalable cluster solutions are optimal for virtually any high-performance, database, and clustered computing environments.
"Our clusters are the product of combining premium OEM products with innovative in-house technologies to deliver best-in-class cluster solutions," said Dr. Ercan Kamber, CTO of RAID Inc. "High-performance enterprises can greatly benefit from our clusters. Based on optimized server platforms, we design all of our cluster solutions to be energy efficient and highly reliable."
To learn more on RAID's cluster computing options, please visit their website.
About RAID Incorporated
Since 1994 RAID Incorporated has provided true 100% customized solutions for the HPC marketplace. The company specializes in optimizing total system performance by enhancing computational resources, interconnects, and I/O subsystems with a concierge support model that assures the highest level of personalized service. For more information about RAID Incorporated, visit www.raidinc.com or call 800-330-7335.
Add to Digg Bookmark with del.icio.us Add to Newsvine
Media Contact for RAID Inc.
Rosa Bruno
Email Contact
Copyright @ Marketwire
Page: 1
Related Keywords: storage, SAN, HPC, High-performance computing, cluster, infiniband, server, Lustre, virtualization, Marketwire, Inc., ,


text:
Is this your business? Claim it today and take control of your Business Credit Rating.
|Company Type
|Private Limited
|Company Status
|Company Dissolved
|Company Number
|Electrical installation
|Phone Number
|0151 548 6272
CORE ELECTRO SERVICES LTD was formed on the 12th October 2010 , and are based in Unit 3,, Caddick Rd. They are currently rated G and are considered to represent an above average risk score. Their current legal status is Company Dissolved. This information was last updated on the 8th December 2015.
There are 3 major shareholders listed for CORE ELECTRO SERVICES LTD with Peter Waggott, Malcolm Wallace and Karl Wallace owning the most shares by value.


text:
B&B Italia Fifty Years Anniversary
One of the great pioneers of Italian design, Piero Ambrogio Busnelli (1927-2014) founded B&B Italia in 1973, after previously co-founding C&B Italia with Cesare Cassina. The industrial process conceived by Busnelli started in 1966 . "My idea is to replace the traditional wooden frame with an iron one, and to insert this inside a mould. Once closed, the mould is then filled with cold foam. After 30 minutes, you have a fully-fledged product ready to be extracted, Piero Ambrogio Busnelli explained. With that idea he revolutionized the furniture industry and transformed a simple furniture factory into something truly special and has remained virtually unchanged to this day, half a century later. A collaboration with the best Italian architects, the use of natural products, and the best craftsmanship mixed with innovation, technology and industrial processes created something that did not yet existed. An era of new creative potential opened up for the big names from the Cassina universe: Gianfranco Frattini, Marco Zanuso, Vico Magistretti, Mario Bellini, and Afra and Tobia Scarpa. It was the latter who developed the first project – the Coronado sofa, designed from start to finish for industrial mass production. Within five years, some of the greatest icons of Italian design were produced. These were supported by innovative advertising campaigns with names like the entrusted art director Enrico Trabacchi and amongst others his collaboration with the photographer Oliviero Toscani. After some years Busnelli acquired the company's full shareholding from the Cassinas, and changed the name from C&B to B&B. Busnelli had a great eye for talent and heired a young Renzo piano for the new B&B headquarters. The building designed in 1973 is a miniature Pompidou Centre, and the same technology system was used a few years later in Paris. Renzo Piano´s building in Italy became a manifesto of the business model Busnelli had in mind right from the start. Images and film courtesy B&B Italia.
B&B Italia Headquarter in Novedrate in the Province of Como designed by Renzo Piano 1973.
La Bambole. Design Mario Bellini 1972. Foto: Oliviero Toscani.
Diesis. Design Antonio Citterio and Paolo Nava 1979.
Charles. Design Antonio Citterio 1997.
Tufty Time. Design Patricia Urquiola 2005.
Grande Papilio. Design Naoto Fukasawa 2009.
Gio. Design Antonio Citterio 2016.
For half a century after its founding, B&B Italia is still projecting itself toward the future with its people, production places, ideas, projects and products. The documentary film "B&B Italia. Poetry in the shape. When design meets industry" by Didi Gnocchi tells the story of the personal and entrepreneurial journey of B&B Italia's founder Piero Ambrogio Busnelli, the company's current situation and its objectives for the future. 50 years of history explained in 50 minutes full of interviews, images and an exciting story narrated by Giorgio Busnelli, son of the founder. When design meets industry the result is extraordinary.


text:
- Please select a date to see the proper prices!
- Meal can be requested on the spot
Best offer
65 € / person / night, no meal
Description of the Accommodation
Rooms, services Should you be looking for a hotel in Germany, we suggest you take a look at the offers of Schlosshotel Klaffenbach Chemnitz. The hotel is offering 49 nicely furnished rooms to stay in to those seeking accommodation in Chemnitz. If you feel like having a meal not included in your chosen type of catering, you can always taste local dishes in the restaurant of the hotel. For those arriving by car parking is available nearby. An organized city tour is also available to help you discover all key highlights of the area. Nearby table tennis, bike rental, bowling, billiard and ballontrip opportunities will provide an excellent chance to spend your leisure time actively. The café and the bar have excellent atmosphere for a relaxed evening talk or a personal meeting. In the safe your valuables can be the safely secured. If you have a suitable portable device, you can connect to the Internet via a wireless network (WiFi) available at the hotel. If you wish to learn more about the exact scope of services provided by Schlosshotel Klaffenbach Chemnitz (including any available for an extra fee), you will find them on the information sheet below.
Payment Advance bank card payment or credit card guarantee may be required for the reservation, depending on the chosen date, room and price.
Arrival, opening hours The earliest check-in time to your room is 14:00, the latest check-out time from your room is 11:00. The personnel can speak English and German languages.
Schlosshotel Klaffenbach Chemnitz rooms Rooms
- Please select a date to see the proper prices!
Accommodation services
Free WiFi in shared places
Relaxation: Table-tennis, Billiard, Squash, Bowling, Bike rental at the accommodation
Organized sightseeing nearby, Hot air balloon nearby
Garden, Bar, Cafe, Elevator, Safe deposit box, Room service
Own restaurant
Hairdryer, Desk in the room, Mini-bar


text:
By The Sexperts
If you're in a long-term monogamous relationship, you may find that things just aren't as exciting as they used to be. After several months or years, sex with the same person has become a habit instead of a way to express your passion for the other. This is a problem that many couples face, but there's no reason you have to take it lying down; there are plenty of positions, and other tricks to try out that can add the spark back to your love life.
First, the Sexperts have already talked about how feeding into fetishes can change things up in the bedroom and keep both parties excited. What else is there that can add spice to a bland sex life? The answer is toys. Sex toys are a great way to experiment with your wild side, and can make any sexual encounter more fun. I'm not saying you need to breakout the strap-on and the vibrating butt plug – start with something simple like a cock ring – but by all means, if you and your partner are into the double-ended dildo, go for it!
Experiment with different positions. If you and your partner are stuck in the go-to missionary position time after time, you should expand your horizons. There are plenty of exciting positions that can make a huge difference in your sex life. Read the Kamasutra, a Cosmo magazine, the end of Sexpert articles, or watch a porn together for tips on new positions you may have never tried before.
Foreplay is extremely important! Have you ever tried starting up an old car on a cold morning? It's the same concept; you need to warm up your partner before they're ready to run the race. Foreplay before sex is a great way to change things up every time, so things never get boring. Likewise, it helps to get you and your partner in the mood, so that when the time comes the experience will be elevated. Foreplay can also help you express your passion and love for your partner. Let monogamy never be monochrome again.
Position of the Week: The Reverse Spider Monkey Flip


text:
CTV Ottawa | Morning Live | Natural Remedies for Cold & Flu
Can vitamin C prevent colds? Should you take extra vitamin D in the winter? Does Echinacea work? Find out the answers to these important questions and more by checking out my interview on CTV Morning Live. View VideoRead More
CTV Edmonton | Noon News | Cold and Flu Survival Kit
Interested in building a cold and flu survival kit? Check out my segment on CTV Noon News Edmonton to find out what you can do to prevent and manage cold and flu with healing foods and natural remedies. View videoRead More
CTV Vancouver | Morning Live | Holiday Health Tips
Holiday parties and shopping can make this the most exciting time of the year. But entertaining, late nights, and stress can bring on unwanted health issues, from colds and flu to hangovers, heartburn and sleeplessness. Check out my interview on CTV Morning Live Vancouver to find out what to have on hand to survive the health hazards…Read More
NBC West Palm Beach | Morning News | Medicine Cabinet Makeover
Looking to transform your medicine cabinet to include natural remedies? Check out my interview on NBC West Palm Beach where I share advice on remedies that can help manage muscle strains and bruising, cough and cold and sleep issues. View videoRead More
Global National | The Morning Show | Menopause Myths
There are many myths surrounding the symptoms and management of menopause. Check out my interview on The Morning Show where I debunk the myths and go through recommendations on how women can optimize their health in menopause. View videoRead More
City TV Calgary | Breakfast Television | Managing Menopause
October is World Menopause Month. But don't sweat it! Check out my interview on Breakfast Television in Calgary where I share advice on how women can take action and manage the symptoms of menopause naturally and improve quality of life. View videoRead More
CTV Ottawa | Morning Live | Natural Medicine Cabinet for Fall
Now that the kids back in school and they could be bringing home more than just their homework. Check out my interview on Ottawa's CTV Morning Live where I talk about natural remedies to manage colds, head lice, tummy aches and more. View videoRead More
CTV Kitchener | Noon news | Combatting Head Lice
September is here and that means prime head lice time. A recent study found that 97% of lice are now resistant to commonly used pesticides. Before you push the panic button, check out my interview on CTV Noon News where I dispel the myths about head lice and talk about safe strategies to eradicate these pesky bugs.…Read More
CHCH TV | Morning Live | Keeping Your Gut Healthy This Summer
Summertime BBQs, picnics and parties can be a lot of fun but not necessarily for your tummy. Eating foods high in fat, starch and sugar and low in fiber can wreak havoc on your digestive system. Find out how to beat the bloating, gas and constipation with some smart tips and healthy substitutions. View videoRead More


text:
A sweet way to end dinner.
1 cups all-purpose flour1/2 cup brown sugar1/4 tsp salt1/2 cup butter or margarine
Combine 1 cup flour, 1/2 cup brown sugar and salt in medium bowl. Cut in 1/2 cup butter until crumbly.
Pat into bottom of greased 9-inch square baking dish. Bake at 350ºF., 15 minutes.
2 bags (16 oz. each) DOLE Fresh Frozen Sliced Peaches, thawed1/2 cup granulated sugar1/4 cup cornstarch
Combine granulated sugar and cornstarch; stir in peaches. Pour into crust.
1-1/2 cups rolled oats1/2 cup packed brown sugar1/4 cup all-purpose flour5 tbsp butter or margarine
Combine oats, remaining 1/2 cup brown sugar and 1/4 cup flour in small bowl for topping. Cut in 5 tablespoons butter until crumbly. Sprinkle over filling.
Bake at 350ºF., 25 to 30 minutes or until golden and bubbly.
Explore the wide variety of career opportunities that we offer!


text:
Welcome to Made.com Unboxed
Ever wondered how other people style their MADE pieces? Have a snoop here on Unboxed, where MADE customers share photos to inspire others. Post your own snaps, and you could win a £100 voucher.
Start exploring the world of made
Cordoba Rug 170 x 240cm, Warm Beige
A real piece of art, the Cordoba Rug in warm beige by acclaimed artist Fieroza Doorsen is a striking addition to any room. In a versatile170 x 240cm size.Buy Now


text:
Closed: 13 January 2017
Group Coordinator (Newcastle)
Posted by Alzheimer's Society
Job Description
Reference Number: VAC13408
Location: Newcastle
Closing Date: 13 January 2017
Office location: Newcastle
Area role covers North Tyneside
Salary: £13,347.00 per annum (actual)
Hours: 26.00 per week
Contract type: Permanent (subject to ongoing funding)
Interview date: 27 January 2017
Alzheimer's Society is the UK's leading support and research charity for people with dementia, their families and carers. There are 850,000 people with dementia in the UK and numbers are set to rise to over 1 million by 2025.
Leading the fight against dementia takes many forms at Alzheimer's Society. In addition to funding research and raising public awareness, for example, we run some of the most effective local support services in the country. We offer regular support services in a safe and secure environment.
As the Group Coordinator you will coordinate, organise and facilitate the engaging and safe running of group services aimed to inform, educate, and support those affected by dementia. The type of service delivered in a group setting is varied and may include Dementia Café, Activity Groups and Singing for the Brain.
The sessions should be well designed and allow participants to engage fully to maximise their enjoyment and the beneficial impact; taking account of individual needs of group attendees when designing group sessions and adjusting the programme as necessary. The role will involve effective service user involvement, co-ordination of service related volunteers and liaising with relevant statutory and voluntary organisations in the area.
You will possess an NVQ Level 2 or equivalent as well as having good organisation and facilitation skills combined with excellent communication and listening skills. An understanding of the value of group activities to people living with dementia along with experience in a care or support environment will be essential. We are looking for an individual who has experience in coordinating, organising and facilitating group work, particularly focused on peer support and activity groups for people affected by dementia. It is desirable that you have experience of coordinating volunteers, and liaising with statutory and voluntary agencies.
If you have the qualities we're looking for, and are passionate about improving the quality of life for people with dementia, then we want to hear from you.
Alzheimer's Society is committed to equal opportunities.
Late applications will not be accepted.
No CV's or agencies please.


text:
The free agent market hasn't been kind to NFL veteran offensive linemen.
Because the 2013 draft was filled with talented young linemen most of the tackles had to wait months, until after the draft, to get a deal done.
Some offensive linemen are still struggling to find work, but the Miami Dolphins gave one former Pro Bowler work on Sunday, signing Tyson Clabo to a one-year deal.
"He will be a great addition to the offensive line both on the field and in the meeting room," said General Manager Jeff Ireland, who also signed Florida Atlantic linebacker David Hinds after a tryout at the team's recently rookie mini-camp.
Quarterback Clay Belton and linebacker Rob McCabe, two undrafted rookies who were signed on Friday, were waived to make room for the new additions.
According to FoxSports.com Clabo's deal is worth $3.5 million with $1.5 million of the contract being guaranteed.
Clabo is expected to compete with Nate Garner and possible Will Yeatman for the starting right tackle spot in 2103. It is also possible John Jerry, a starting guard for two of the past three seasons, could be moved over to right tackle.
"I'm a pretty tough critic on myself and I don't feel like there has been any drop in my play," said Clabo, who played in a zone blocking scheme during his practice squad stint with the Broncos, and early in his career with the Falcons. "I always want to do well. I want to feel like I did the job that I was brought here to do… My biggest driving force is success."
Clabo's addition means Jonathan Martin is expected to man the left tackle spot, with rookie Dallas Thomas, the Dolphins' third-round pick, serving as his primary backup.


text:
You are not permitted to download, save or email this image. Visit image gallery to purchase the image.
A week-long party to celebrate 150 years since the creation of the Oamaru Town Board began in earnest yesterday with a picnic at the Oamaru Public Gardens and will finish with residents rocking out with Green Party co-leader Metiria Turei.
Oamaru was officially proclaimed a town in December 1862 and to allow the public a chance to celebrate the town's birthday, local artist Donna Demente has organised a week of events.
Ms Demente said she had been inspired by the Arrowtown 150th celebrations earlier in the year.
''We really wanted to do something to celebrate it. It is our 150th after all, so we made a series of events to get people together.
''150 is quite a significant birthday and we wanted to do something specifically to acknowledge that.''
Events, including public barbecues, a screening of film footage from the 1962 centennial celebrations and an ''end of the world party'' on December 21, would conclude with a 1960s-themed music concert, which would see Green Party co-leader Metiria Turei's ukulele rock band perform its first professional gig at The Grainstore Gallery and Birdlands Winebar on Sunday.


text:
"The View" Debates: "SNL" Kellyanne Conway "Fatal Attraction" Sketch (VIDEO)
"The View" co-hosts on Monday debated a controversial "SNL" sketch spoofing Kellyanne Conway with a Fatal Attraction parody. Check out the video below.
On this weekend's "Saturday Night Live," Kate McKinnon portrayed Conway as a crazily obsessed stalker determined to get on Jake Tapper's CNN show by any means necessary. Introducing the "hot topic," Goldberg exclaimed, "God bless 'SNL.' They have devoted a lot of time to having fun with the new administration." But after showing a clip of the sketch, she noted, "Some critics say that this crossed the line."
Sunny Hostin didn't agree with the criticism. She commented, "It's satire, though. It's supposed to be pushing the bounds." She even revealed Fatal Attraction is her "favorite movie," and argued, "I thought it was really, really well-done."
Jedediah Bila also saw an upside to the bit. "If 'SNL' is picking on you, you've arrived," she said, adding, "If you can't laugh at yourself, you've got problems." Goldberg also called it a "great thing," pointing out that no president or staffer is "immune."
"The more you fight it, the more fun it's going to be to do it you," she said. And Sara Haines also noted, "'SNL' got its highest ratings in six years on Saturday. I know President Trump likes to talk about that." Watch below.


text: Human Rights Observatory Habitat Loss Seen as Rising Threat to World's Migratory Birds Habitat destruction along routes taken by the world's migratory birds poses an increasing peril to these long-distance fliers, with a vast majority crossing terrain that nations are inadequately protecting, according to scientists. The researchers said on Thursday they tracked the migratory routes, stopover locations, breeding grounds and wintering locations of 1,451 migratory species and assessed about 450,000 protected areas like national parks and other reserves. They found...Read complete article© Voice of America - Thursday, December 3rd 2015


text:
Inner Life photography
Inner Life photography
Inner Life Photography® Lead by "Junaid Butt " is a leading International Photography & Film Production Studio based in Lahore city, Pakistan, offering Creative Film Production & Photography services to clients Around the World. We specialize in delivering high quality Photo Shoots & Corporate Video Production. We also provide a Bespoke Film & Video production service to private clients and individuals.
Show more


text:
Join the 'Assisted Ventilation Therapy' group to help and get support from people like you.
Assisted Ventilation Therapy News
Study Finds Fault With ICU Treatment of Dementia Patients
Posted 10 Oct 2016 by Drugs.com
MONDAY, Oct. 10, 2016 – A new study raises red flags about the use of ventilators among dementia patients in intensive care units. Researchers analyzed data from about 635,000 hospitalizations of U.S. nursing home patients with advanced dementia. Between 2000 and 2013, ventilator use among these patients, whose average age was 84, nearly doubled at the 2,600 hospitals studied. But more than 80 percent of the patients died within a year, the study found. The results suggest ventilators are being overused, leading to unnecessary patient suffering and higher health care costs, according to the authors of the study published Oct. 10 in the journal JAMA Internal Medicine. "These findings call for new efforts to ensure that the use of mechanical ventilation is consistent with patient's goals of care and their clinical condition," said corresponding author Dr. Joan Teno. She is a professor of ... Read more
Related support groups: Dementia, Alzheimer's Disease, Mild Cognitive Impairment, Respiratory Distress Syndrome, Lewy Body Dementia, Drug-Induced Dementia, Assisted Ventilation Therapy


text:
MOVIE SYNOPSIS [ General Audiences ] Movie of Václav Marhoul. Introduced in cinemas in 2008, with production teams of Czech Republic and Slovakia. You can watch Tobruk online on TV cable or theaters with original audio in Czech at different dates. This film premiered in theaters in 2008.
Rating: 5 by 812 users./
Runtime: 102 minutes
Jan Meduna, Petr Vanek, Robert Nebrenský, Michal Novotný, Martin Nahálka, Matús Krátky, Krystof Rímský, Petr Lnenicka, Andrej Polák, Petr Stach, Radim Fiala, Matej Hádek, Karel Klinovsky, Petr Halberstadt, Petr Vrsek and Elaine Cristina Weissova.
Historic, War.
102-minute film (full movie) directed by Václav Marhoul.
The original audio of Tobruk has dialogues in or Czech, it was produced in Czech Republic, Slovakia.
It premiered in cinemas or television in 2008.
Screenplay written by Václav Marhoul and Stephen Crane.
Vladimír Smutný.
Dora Bouchoucha Fourati, Jaroslav Kucera, Ales Tybl, Iveta Malachovská and Václav Marhoul.
This film was produced and / or financed by Ceská Televize, Free - Cool - In and Silver Screen.
Composed by Richard Horowitz and Sussan Deyhim.
Ascot Elite Home Entertainment, Continental Film, Atlantic Film and Bioscop.
Without commercial breaks, the full movie Tobruk has a duration of 102 minutes; the official trailer can be watched in streaming on the Internet. You can watch this full movie free in English or Czech in movie TV channels, renting the DVD or with VoD services (Video On Demand player, Hulu) and PPV (Pay Per View, Netflix).
See the page of this full movie, Tobruk in FULLTV Movies.


text:
In this panoramic history of Islamic culture in early Europe, a Pulitzer Prizewinning historian reexamines what we once thought we knew. David Levering Lewis's narrative reveals how cosmopolitan, Muslim al-Andalus flourished-a beacon of cooperation and tolerance between Islam, Judaism, and Christianity-while proto-Europe made virtues out of hereditary aristocracy, religious intolerance, perpetual war, and slavery.
In the hundred years between the Prophet Muhammad's death in 632 and Charles the Hammer's victory over Muslim invaders at Poitiers in central France in 732, Islam conquered a huge swathe of the known world, erupting from what had been the historically irrelevant wastes of Arabia as far as central Asia in one direction and western Europe in the other.