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Cytoplasmic Ca2+ signals are central to numerous cell physiological processes, including cellular proliferation. Historically, much of the research effort in this area has focused on the role of Ca2+ signals in cell-cycle progression. It is becoming clear, however, that the relationship between Ca2+ signaling and the cell cycle is a 'two-way street'. Specifically, Ca2+-signaling pathways are remodeled during M phase, leading to altered Ca2+ dynamics. Such remodeling probably better serves the large variety of functions that cells must perform during cell division compared with during interphase. This is clearly the case during oocyte meiosis, because remodeling of Ca2+ signals partially defines the competence of the egg to activate at fertilization. Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+-signaling pathway that is regulated during M phase. In this Commentary, we discuss the latest advances in our understanding of how SOCE is regulated during cell division.
Intracellular Ca2+ signals are central to practically all aspects of cellular physiology, including secretion, contraction, fertilization, synaptic transmission, cell division and gene expression. The fact that Ca2+ signals mediate disparate cellular responses, often in the same cell, necessitates a high level of specificity and versatility. Specificity is encoded by the spatial and temporal features of the Ca2+ signal itself, and by the sensitivity, availability and localization of downstream Ca2+-dependent effectors (Berridge et al., 2000; Clapham, 1995). In addition, the astounding temporal (microseconds to hours) and concentration (nanomolar to millimolar) ranges across which Ca2+ acts contribute to its versatility and specificity as an effective signaling module (Berridge et al., 2003; Clapham, 2007).
Ca2+ signaling is founded on cells providing a low background by maintaining cytoplasmic Ca2+ levels in the nanomolar range (~100 nM). Regulation of cytoplasmic Ca2+ in resting conditions is a homeostatic mechanism mediated by the balance of Ca2+ influx and extrusion at the cell membrane, as well as by Ca2+ uptake and release from intracellular Ca2+ stores. Similar mechanisms are involved in defining the spatial, temporal and amplitude features of Ca2+ signals. Extracellular Ca2+ concentration is typically 1-2 mM, whereas Ca2+ concentration in the endoplasmic reticulum (ER) – the primary intracellular Ca2+-storage organelle – is in the 250-600 μM range (Demaurex and Frieden, 2003). Given the existence of these Ca2+ gradients across the cell and ER membranes, Ca2+ flows down its concentration gradient into the cytoplasm whenever a Ca2+-permeable pathway is open. The active interplay between Ca2+ release from intracellular stores and influx from the extracellular space defines Ca2+-signaling dynamics and hence the ensuing cellular response. In fact, both pathways (influx and release from stores) can be functionally linked through the store-operated Ca2+ entry (SOCE) pathway, which is activated in response to Ca2+-store depletion. In addition, cells possess a myriad of Ca2+-influx pathways, including voltage-gated, ligand-gated, receptor-operated, stretch-activated and second-messenger-gated channels (Berridge et al., 2000; Clapham, 2007).
As Ca2+ is vital for all cells, tight regulation of the mechanisms involved in Ca2+ homeostasis is of paramount importance for preventing dysfunctions that lead to pathological conditions (Missiaen et al., 2000). This regulation is highly complex and varies not only with cell type but also with the developmental stage of the cell (Lipskaia and Lompre, 2004). Given the central role of Ca2+ signaling in cellular physiology, it is not surprising that Ca2+ signals have been shown to play important roles during cell-cycle progression (Whitaker, 2006). Ca2+ signals are required for nuclear-envelope breakdown, and for chromosome condensation and disjunction during mitosis (Ciapa et al., 1994; Groigno and Whitaker, 1998; Kao et al., 1990; Steinhardt and Alderton, 1988; Tombes et al., 1992; Twigg et al., 1988; Wilding et al., 1996). By contrast, Ca2+ signals are dispensable for the breakdown of the germinal vesicle during vertebrate meiosis, but are required for the completion of meiosis I (Sun et al., 2008; Sun and Machaca, 2004; Tombes et al., 1992). The idea that Ca2+ is involved in cell-cycle progression is strengthened by genetic and biochemical evidence supporting a role for calmodulin (CaM) and Ca2+-calmodulin-dependent protein kinase II (CaMKII) in mitosis and G1 (Means, 1994; Rasmussen and Means, 1989; Takuwa et al., 1993; Whitaker, 1995; Whitaker and Larman, 2001). Furthermore, the Ca2+-CaM-CaMKII module is required for centrosome duplication, which is necessary for spindle formation and chromosome segregation: when this module is defective, genomic instability results (Matsumoto and Maller, 2002). Moreover, the Ca2+-dependent phosphatase calcineurin has also been implicated in G1-S progression (Kahl and Means, 2003).
Therefore, there is significant evidence supporting a crucial role for Ca2+ signals in regulating the cell cycle. Probably the best-defined example is at fertilization, which leads to the completion of the second meiotic division (Perry and Verlhac, 2008). The fertilization-induced Ca2+ transient takes the form of a single sweeping Ca2+ wave, or multiple Ca2+ oscillations, depending on the species (Stricker, 1999). In vertebrates, the Ca2+ transient that occurs at fertilization activates CaMKII (Lorca et al., 1993), which mediates resumption of meiosis by inactivating cytostatic factor (CSF), a protein whose activity maintains metaphase II arrest (Knott et al., 2006; Lorca et al., 1993; Morin et al., 1994; Tunquist and Maller, 2003). CaMKII phosphorylates the anaphase-promoting complex (APC) inhibitor Emi2 (Hansen et al., 2006; Liu and Maller, 2005; Rauh et al., 2005), which primes it for additional phosphorylation by polo-like kinase. The dually phosphorylated Emi2 is targeted for degradation, thereby activating APC and releasing CSF-mediated arrest. This provides an elegant example of how a Ca2+ signal triggers a cascade of events that controls cell-cycle progression – in this case, completion of meiosis II.
Given the well-established role of Ca2+ signals in cell-cycle progression, an emerging area of interest is to understand how Ca2+-signaling pathways themselves are regulated during the cell cycle, particularly during the cell-division phase. It is becoming evident that Ca2+ signaling is remodeled during M phase of the cell cycle. For example, inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3]-dependent Ca2+ release is sensitized during both meiosis (Fujiwara et al., 1993; Machaca, 2004) and mitosis (Malathi et al., 2003), and this sensitization depends on the cell-cycle kinase cascade (Lee et al., 2006; Lim et al., 2003; Sun et al., 2009). In addition, during the maturation of Xenopus oocytes, the number of functional Ins(1,4,5)P3 receptors increases following their release from annulate lamellae, vesicular compartments in oocytes in which Ins(1,4,5)P3 receptor function is suppressed (Boulware and Marchant, 2005; Boulware and Marchant, 2008). Furthermore, SOCE is inhibited both during Xenopus oocyte meiosis and during mammalian cell mitosis (Machaca and Haun, 2000; Preston et al., 1991). In this Commentary, we discuss current knowledge of the mechanisms that mediate SOCE inactivation during M phase and their physiological significance.
Store-operated Ca2+ entry
The idea that Ca2+-store content regulates Ca2+ influx at the cell membrane was first formalized by Putney in 1986 in the context of the capacitative Ca2+-entry model (Putney, 1986). In the ensuing two decades, it became clear that SOCE represents a primary Ca2+-influx route in essentially all non-excitable cells in response to agonist stimulation (Parekh and Putney, 2005). SOCE signals are also operative, albeit in a secondary role, in excitable cells such as neurons (Emptage et al., 2001) and in skeletal muscle (Launikonis and Rios, 2007; Stiber et al., 2008). SOCE is an intricate physiological phenomenon whereby Ca2+ release from intracellular stores [typically induced by Ins(1,4,5)P3-coupled agonists] is followed by slow and sustained entry of extracellular Ca2+ (Putney et al., 2001). However, Ca2+ release per se is not a prerequisite for SOCE activation; rather, it is the coupling between the filling state of ER Ca2+ stores and store-operated Ca2+ channels that regulates SOCE (Parekh and Putney, 2005). In addition to store refilling, SOCE is involved in a myriad of cellular functions, including exocytosis (Fomina and Nowycky, 1999), sperm capacitation (O'Toole et al., 2000) and T-cell activation (Serafini et al., 1995). The best-characterized store-operated current is the highly Ca2+-selective Ca2+-release-activated current (ICRAC) (Hoth and Penner, 1992; Zweifach and Lewis, 1993). For example, antigen stimulation of T cells crosslinks T-cell receptors, thereby activating phospholipase Cγ (PLCγ), leading to Ins(1,4,5)P3-dependent Ca2+ release from stores, followed by Ca2+ influx through Ca2+-release-activated Ca2+ (CRAC) channels. ICRAC produces a sustained Ca2+ transient that is required for calcineurin activation. Calcineurin dephosphorylates the transcriptional regulator nuclear factor of activated T cells (NFAT), resulting in its nuclear translocation and the subsequent expression of NFAT-regulated cytokines (Lewis, 2001; Oh-hora and Rao, 2008). In addition, several non-immune cell types possess a cation non-selective, Ca2+-permeable SOCE pathway that is mediated by classical transient receptor potential channels (TRPCs) (Bailly et al., 1991).
Despite the intense interest in SOCE, both the identity of the SOCE channel and the nature of the coupling mechanism remained a matter of intense controversy for several years (Parekh and Putney, 2005). It is only in the past few years that the molecular players underlying SOCE were elucidated. The breakthrough came with the use of RNAi screens together with high-throughput functional assays to identify genes essential for SOCE. These screens initially identified stromal interaction molecule 1 (STIM1), an ER transmembrane protein with lumenal EF-hands, as the sensor of lumenal ER Ca2+ that links ER depletion to SOCE activation (Liou et al., 2005; Roos et al., 2005). This discovery was followed by the identification of Orai1 (also known as CRACM1) as the CRAC channel (Feske et al., 2006; Vig et al., 2006b; Zhang et al., 2006). The Orai1 protein spans the membrane four times and has no sequence homology to other known channels. Several lines of evidence support the conclusion that Orai1 contributes to and possibly defines the CRAC channel pore. Most importantly, mutations of key glutamates in the first and second membrane-spanning domains of Orai1 alter the ionic selectivity and permeation properties of SOCE (Prakriya et al., 2006; Vig et al., 2006a; Yeromin et al., 2006). In addition, a mutation in the Orai1 gene (R91W) abrogates Ca2+ influx in T cells and causes severe combined immunodeficiency disorder (SCID), a lethal immune disorder in humans (Feske et al., 2006). The establishment of STIM1 and Orai1 as the bona fide molecular mediators of CRAC is further strengthened by studies showing that coexpression of STIM1 and Orai1 produces large ICRAC-like currents with high Ca2+ selectivity, inward rectification and dependence on store depletion (Peinelt et al., 2006; Soboloff et al., 2006; Zhang et al., 2006). In addition, in some cell types, the ER Ca2+-sensor STIM1 also couples to and gates TRPCs to induce SOCE (Huang et al., 2006; Yuan et al., 2007; Zeng et al., 2008). Nonetheless, the identification of STIM1 and Orai1 opened the door for studies targeted at obtaining a mechanistic understanding of SOCE inactivation during cell division, as discussed below.
STIM1 and Orai1 coupling
Much has already been learned about how the elegant complexity of STIM1 and Orai1 coupling leads to SOCE (see Fig. 1, interphase). Depletion of Ca2+ stores leads to clustering of STIM1 into large puncta that are readily visible by light microscopy (Liou et al., 2007; Stathopulos et al., 2006). These puncta are stabilized in a sub-plasma-membrane cortical ER domain that localizes within 10-20 nm of the cell membrane, where they physically recruit Orai1 into coincident puncta at the cell membrane, leading to Orai1 gating and Ca2+ influx (Luik et al., 2006; Prakriya et al., 2006; Vig et al., 2006b; Wu et al., 2006; Yeromin et al., 2006) (Fig. 1, interphase). Interestingly, a recent study argued that STIM1 is directly involved in the formation of these specialized cortical ER domains: expression of a constitutively active STIM1 mutant was shown to lead to the formation of multilayered cortical ER structures that are enriched in so-called pre-cortical ER domains that have similar morphology to the cortical ER, but are distant from the plasma membrane (Orci et al., 2009).
Mammalian genomes contain two STIM homologues, STIM1 and STIM2 (Cahalan, 2009). STIM1 has been shown to be essential for SOCE, whereas STIM2 appears to be primarily involved in maintaining Ca2+ homeostasis (Brandman et al., 2007). STIM1 is a single-pass integral membrane protein that localizes mainly to the ER membrane (Liou et al., 2005; Roos et al., 2005). STIM1 has a modular construction, with lumenal EF-hands and a sterile-α-motif (SAM) (Fahrner et al., 2009), the structure of which has been elucidated (Stathopulos et al., 2008). The STIM1 cytosolic domain contains two predicted coiled-coil domains followed by a Ser/Pro-rich region and a Lys-rich region at the C-terminal end of the molecule (Fahrner et al., 2009).
The STIM1 cytosolic domain is rich in functional domains that have been identified through structure-function studies, which have provided crucial insights into the coupling function of STIM1 (Fig. 1). Several groups have identified a minimal domain within the STIM1 cytoplasmic region that is necessary and sufficient for coupling to and activating Orai1 (Kawasaki et al., 2009; Muik et al., 2009; Park et al., 2009; Yuan et al., 2009). This so-called SOAR/CAD domain is a potent activator of SOCE, binds directly to Orai1, is sufficient to induce SOCE independently of Ca2+-store depletion and is required for STIM1-Orai1 coupling. In a region that is located C terminal to the SOAR/CAD and overlaps with it (residues 400-474) is a sequence referred to as the STIM-homomerization domain (SHD), which is required for STIM1 oligomerization (Muik et al., 2009). C terminal to the SHD is a short sequence of ~12 residues that mediates the Ca2+-dependent inactivation of ICRAC (Lee et al., 2009; Mullins et al., 2009). Ca2+-dependent inactivation is a negative-feedback mechanism whereby Ca2+ that enters through the CRAC channels inactivates ICRAC (Zweifach and Lewis, 1995).
Interestingly, expression of the STIM1 cytoplasmic domain alone produces constitutively active SOCE (Huang et al., 2006). Although smaller fragments within the STIM1 cytoplasmic region, such as the SOAR/CAD domain, are more potent activators of SOCE, this result shows that the dissociation of the cytoplasmic domain from the ER membrane changes its conformation in a way that allows this fragment to gate Orai1. This is consistent with the fact that the STIM1 cytoplasmic domain localizes below the cell membrane and can interact with Orai1, as indicated by fluorescence resonance energy transfer (FRET) analysis (Muik et al., 2009). Given that STIM1 oligomerization is initiated by depletion of Ca2+ stores and the association of SAM domains in the ER lumen, these results collectively suggest a 'zippering' mechanism for STIM1 oligomerization: STIM1 oligomerization initiates in the ER lumen, leading to structural changes in the STIM1 cytoplasmic domain that allow it to form stable large oligomers that bind to and gate Orai1. This is consistent with data showing that STIM1 oligomerization that occurs independent of its ER lumenal domain is sufficient to activate SOCE (Luik et al., 2008). However, STIM1 oligomerization per se does not seem to be required for gating Orai1; rather, current data suggest that structural changes in STIM1 following oligomerization expose the SOAR/CAD domain, allowing it to gate Orai1. This is supported by the finding that STIM1 mutants within the SOAR/CAD domain do not affect the ability of STIM1 to cluster and recruit Orai1, but do abrogate its ability to gate Orai1 (Yuan et al., 2009). In addition, the expression of STIM1 from worms in mammalian cells leads to the formation of STIM1 puncta even when Ca2+ stores are full (Gao et al., 2009). Pre-clustered worm STIM1 can recruit Orai1, leading to Ca2+ influx, only after store depletion. Nonetheless, given the essential role of STIM1 in gating Orai1 channels and its role in modulating the Ca2+ dependency of SOCE (Lee et al., 2009; Mullins et al., 2009), it can be considered an integral component of the SOCE channel.
SOCE inactivates during mitosis
The cell cycle is a sophisticated and tightly controlled physiological process that involves multiple finely coordinated signaling pathways that ensure correct cell division and transmission of genetic information. The cell cycle transitions through four phases: G1 growth phase, DNA synthesis (S phase), the G2 phase and cell division (M phase) (Murray and Hunt, 1993). This cycle is unidirectional and sequential; this is crucial for ascertaining proper chromosomal duplication and equal segregation to daughter cells (Murray and Hunt, 1993). The unidirectionality of the cycle is guaranteed by several checkpoints that prevent progression to the next phase unless key events have been satisfied (Murray and Hunt, 1993). Transitions between different phases of the cell cycle are driven by cyclin-dependent kinases (CDKs) and their cyclin partners (Murray and Hunt, 1993). Deregulation of the tight control of this cycle leads to cellular transformation, with devastating pathological consequences (Vermeulen et al., 2003).
The division phase of the cycle has unique cellular requirements, as illustrated by the dramatic morphological alterations observed during M phase compared with during interphase, including nuclear-envelope breakdown, chromosome condensation, and remodeling of the cytoskeleton and intracellular organelles. These changes ensure equal segregation to daughter cells not only of genetic material but also of intracellular organelles such as the Golgi and ER. The Golgi, for example, is structured as a series of stacks in mammalian cells and these stacks fragment during mitosis to ensure equal partitioning into daughter cells (for a review, see Wei and Seemann, 2009). As discussed above, Ca2+-signaling pathways also undergo significant remodeling during M phase, which involves inhibition of SOCE.
The first suggestion that Ca2+ influx is inhibited during cell division was reported in 1988 in a study of HeLa cells (Volpi and Berlin, 1988). In this study, Volpi and Berlin showed that histamine stimulation during interphase produced an initial Ca2+ rise, owing to Ca2+ release from stores, followed by an elevated plateau, owing to Ca2+ influx from the extracellular space. By contrast, in mitotic cells, only the Ca2+-release phase was observed, arguing that Ca2+ influx is inhibited during mitosis. This observation was made around the same time that ideas regarding SOCE were being formulated. The same group later argued that SOCE inhibition during mitosis occurs through uncoupling of store depletion from SOCE, as thapsigargin (an agent that causes store depletion) activated SOCE in interphase but not mitotic cells (Preston et al., 1991). The incentive to investigate Ca2+ dynamics during mitosis was to determine whether changes in intracellular signaling might underlie the observed inhibition of vesicular trafficking during cell division (Volpi and Berlin, 1988). In an interesting twist of events, recent data indicate that vesicular trafficking is involved in inhibiting SOCE during M phase, as discussed in more detail below (Yu et al., 2009).
More recent studies confirmed that SOCE is inactivated during mitosis in HeLa, RBL-2H3, HEK293 and Cos-7 cells (Russa et al., 2008; Smyth et al., 2009; Tani et al., 2007). Investigating SOCE levels throughout the cell cycle showed that there is a slight enhancement of SOCE during the G1 and S phases, and dramatic downregulation during M phase (Tani et al., 2007). It has also been argued that SOCE inhibition during mitosis in Cos-7 cells is the result of the microtubule-network remodeling that accompanies mitosis (Russa et al., 2008).
What is the physiological significance of SOCE inactivation during mitosis? The most likely answer to this question is that tight regulation of Ca2+ signaling is required during mitosis because of its important functional role at multiple steps throughout the process. Ca2+ signals are implicated in nuclear-envelope breakdown (Baitinger et al., 1990; Wilding et al., 1996), anaphase onset (Groigno and Whitaker, 1998; Keith et al., 1985; Morin et al., 1994; Poenie et al., 1986) and cell cleavage (Poenie et al., 1985). The Ca2+ transients involved in these processes must be temporally and spatially controlled to mediate their intended cellular functions. Hence, SOCE inactivation might represent a safety mechanism that prevents sporadic Ca2+ signals from occurring during cell division that could derail its sequential progression. Erratic Ca2+ influx through SOCE might occur during mitosis due to ER remodeling that results in localized store depletion.
SOCE inactivation during oocyte maturation (meiosis)
It was almost a decade after the initial studies by Berlin and colleagues that the issue of Ca2+ influx during M phase was revisited in a different physiological context – that of gamete maturation in preparation for fertilization. Indeed, SOCE inactivates completely during Xenopus oocyte meiosis (Machaca and Haun, 2000; Machaca and Haun, 2002). This inhibition is important in the context of the overall Ca2+-signaling remodeling that endows the egg (the fully mature Xenopus oocyte arrested at metaphase of meiosis II) with the capacity to produce the specialized Ca2+ transient required at fertilization (Machaca, 2007; Ullah et al., 2007).
Before acquiring the ability to activate at fertilization, fully grown oocytes in vertebrates undergo a cellular differentiation pathway known as oocyte maturation, which consists of coordinated morphological, biochemical and physiological changes (Masui, 2001), including remodeling of Ca2+-signaling pathways (Machaca, 2007). Egg activation encompasses crucial events at fertilization that are essential for the egg-to-embryo transition, such as prevention of polyspermy and completion of meiosis. In all sexually reproducing species investigated to date, egg activation is mediated by a cytoplasmic Ca2+ rise that has specialized spatial and temporal dynamics (Stricker, 1999). The remodeling of Ca2+ signaling during oocyte maturation has been best defined for Xenopus oocyte maturation, in which it encompasses Ca2+ release, influx and extrusion. Ins(1,4,5)P3-dependent Ca2+ release is sensitized through spatial and functional remodeling during oocyte maturation (Boulware and Marchant, 2005; Machaca, 2004; Sun et al., 2009; Terasaki et al., 2001). The plasma membrane Ca2+-ATPase (PMCA) is internalized, thereby inhibiting Ca2+ extrusion in the Xenopus egg (El Jouni et al., 2005; El Jouni et al., 2008), and SOCE inactivates during oocyte maturation (Machaca and Haun, 2000; Machaca and Haun, 2002). Combined, these alterations to primary Ca2+-signaling pathways shape the fertilization-specific Ca2+ transient. Because a localized Ca2+ rise is sufficient to activate the mature egg in the absence of fertilization, SOCE inactivation might represent a safety mechanism that prevents premature sporadic egg activation in the absence of sperm.
Immature Xenopus oocytes possess a robust SOCE current that has similar biophysical properties to the CRAC current observed in mammalian cells (Hartzell, 1996; Machaca and Haun, 2000; Yao and Tsien, 1997). By contrast, in mature eggs that are arrested at metaphase II of meiosis, SOCE can no longer be activated by store depletion (Machaca and Haun, 2000). Single-oocyte analysis of the changes in SOCE current that occur following manipulation of the different kinases that drive Xenopus oocyte maturation showed that maturation-promoting factor (MPF, composed of Cdk1 and cyclin B) is necessary and sufficient for SOCE inactivation (Machaca and Haun, 2002). Therefore, the fertilization-specific Ca2+ transient in Xenopus eggs is generated without the contribution of Ca2+ influx through the SOCE pathway. Xenopus eggs respond to sperm entry with a single sweeping Ca2+ transient that lasts for several minutes (Busa and Nuccitelli, 1985; Fontanilla and Nuccitelli, 1998). This Ca2+ signal encodes all of the subsequent events associated with egg activation, including, in the following order: (1) the fast block to polyspermy due to Ca2+-activated Cl− channels that depolarize the cell membrane; (2) the slow block to polyspermy due to cortical granule fusion; and (3) completion of meiosis (for a review, see Machaca et al., 2001; Machaca, 2007). The ability of the Ca2+ signal to encode these crucial physiological responses in a sequential manner depends on its duration and spatial propagation. SOCE inactivation probably contributes to shaping the dynamics of the fertilization-specific Ca2+ signal in eggs. In contrast to immature oocytes, in which it is relatively straightforward to induce Ca2+ oscillations (Lechleiter et al., 1991), mature Xenopus eggs typically respond to Ca2+ mobilization with a single sweeping Ca2+ wave and are resistant to the generation of Ca2+ oscillations (El Jouni et al., 2005; Machaca, 2004). SOCE inhibition could contribute to this switch in the modality of Ca2+ signaling during maturation, as Ca2+ influx in the oocyte has been shown to increase the speed and frequency of Ca2+ oscillations (Girard and Clapham, 1993).
Interestingly, complete inhibition of SOCE does not appear to be a universal phenomenon during M phase, as store depletion in mammalian ooctyes that are arrested at metaphase II induces Ca2+ entry (Igusa and Miyazaki, 1983; Kline and Kline, 1992; Machaty et al., 2002; Martin-Romero et al., 2008; Mohri et al., 2001). In contrast to what has been observed in Xenopus eggs, mammalian oocytes respond at fertilization with multiple Ca2+ oscillations that last for several hours (Kline and Kline, 1992). Maintenance of these Ca2+ oscillations depends on Ca2+ influx through SOCE, presumably to refill Ca2+ stores (Igusa and Miyazaki, 1983; Kline and Kline, 1992; Mohri et al., 2001). The data from Xenopus and mammalian oocytes indicate that there is a correlation between the occurrence of SOCE and the ability of the oocyte to entrain Ca2+ oscillations at fertilization. The Ca2+ transient at fertilization takes the form of single or multiple transients in a species-specific manner (Stricker, 1999). Unfortunately, as SOCE has not been carefully analyzed in oocytes of species other than frogs and mammals, it is unclear whether the correlation between SOCE and Ca2+ oscillations is conserved across all species. Nonetheless, it is tempting to speculate that the oocytes of species that have a single Ca2+ transient at fertilization are unable to entrain Ca2+ oscillations because of the absence of SOCE, which translates to inadequate refilling of Ca2+ stores following the dramatic first Ca2+ transient. By contrast, oocytes from species that generate an oscillatory Ca2+ signal at fertilization would rely on SOCE to refill stores between Ca2+ spikes.
Although SOCE is detectable in mature mammalian oocytes, it is not clear whether SOCE is downregulated compared with that in immature oocytes. It is possible that SOCE is downregulated but not completely inactivated in mammalian oocytes during maturation, as it serves a Ca2+-replenishing function that entrains prolonged Ca2+ oscillations. This is an attractive possibility given the dependence of SOCE inactivation on MPF and the conserved nature of the kinase cascade that drives oocyte maturation in both mammals and frogs.
Mechanisms regulating SOCE inactivation during M phase
Aside from the role of MPF in SOCE inhibition, very little was known regarding the mechanistic regulation of SOCE inactivation during M phase. However, recent studies investigating the behavior of STIM1 and Orai1 during M phase have provided important insights (Smyth et al., 2009; Yu et al., 2009). During Xenopus oocyte meiosis, SOCE inactivation is mediated by removal of Orai1 from the cell membrane into an endosomal compartment and by inhibition of STIM1 clustering (Yu et al., 2009). In immature oocytes arrested in an interphase-like state with an intact germinal vesicle, Orai1 is enriched at the cell membrane, and continuously recycles between the cell membrane and an endosomal compartment (Yu et al., 2009) (Fig. 1). During meiosis resumption, however, Orai1 is removed from the cell membrane and becomes enriched intracellularly in endosomes, which contributes to SOCE inactivation. This was the first report that addressed Orai1 trafficking; hence, it is not clear whether this mechanism is involved in SOCE inactivation during mitosis. However, internalization of membrane channels, receptors and transporters has been documented during meiosis of both Xenopus and mouse oocytes (El Jouni et al., 2008; Muller et al., 1993; Schmalzing et al., 1990; Zhou et al., 2009). These internalized membrane proteins incorporate into newly formed blastomeres during early embryogenesis and, as such, contribute to the formation of the polarized epithelium during the blastocoele stage of Xenopus embryogenesis (Angres et al., 1991; Gawantka et al., 1992; Muller, 2001).
In addition to Orai1 internalization, another factor that contributes to SOCE inactivation is the inability of STIM1 to reorganize into puncta in response to store depletion in Xenopus eggs (Yu et al., 2009) (Fig. 1, M phase). Inhibition of STIM1 clustering correlates with the activation state of MPF (Yu et al., 2009), consistent with the earlier finding that MPF is required for SOCE inactivation (Machaca and Haun, 2002). Importantly, however, inhibition of STIM1 clustering does not affect the ability of STIM1 to interact with Orai1, as revealed by analysis of a constitutively active STIM1 mutant. The cytoplasmic domain of STIM1, which constitutively activates the SOCE current, co-segregates with Orai1 into the endosomal compartment during meiosis, showing that this mutant can still interact with Orai1 (Yu et al., 2009).
The inability of STIM1 to form large puncta following store depletion is associated with its hyperphosphorylation during meiosis (Yu et al., 2009) (Fig. 1). Coupled with the finding that MPF is involved in SOCE inactivation, this argued that the phosphorylation of STIM1 is responsible for inhibition of its clustering. However, this is not case, because mutations of STIM1 that affect its phosphorylation state (either alanine substitutions or phosphomimetic mutations at consensus MPF sites between residues 485 and 685) did not affect the inhibition of STIM1 clustering (Yu et al., 2009). This argues that the inability of STIM1 to cluster during meiosis is not mediated by its phosphorylation at consensus MPF sites.
As is the case during meiosis, STIM1 is also hyperphosphorylated and fails to form puncta in response to store depletion in mitotic HeLa and HEK293 cells (Smyth et al., 2009) (Fig. 1). Interestingly, a deletion mutant of STIM1 missing residues C terminal to residue 482 – a region that contains all of the consensus MPF phosphorylation sites – partially rescues both the SOCE current and puncta formation in mitotic cells (Smyth et al., 2009). In addition, alanine substitution at two residues (Ser486 and Ser668) was sufficient to partially rescue SOCE, although to a lesser extent than the 482 deletion mutant (Smyth et al., 2009). These data argue that, in contrast to what occurs during meiosis, STIM1 phosphorylation underlies the inhibition of its clustering during mitosis. However, another potential contributing factor to the discrepancy is the use of nocodazole in the study of mitotic cells. Nocodazole is a microtubule-disrupting drug that does not replicate all aspects of mitosis; this could influence the robustness of SOCE inactivation in cells arrested in M phase using this pharmacological agent. By contrast, in the meiosis studies, eggs are physiologically arrested at metaphase of meiosis II until fertilization, thereby providing a better model to study the functional behavior of SOCE during metaphase.
Another factor that might modulate the ability of STIM1 to form large puncta in response to Ca2+-store depletion during M phase is the remodeling of the ER. During both mitosis and meiosis, the ER undergoes dramatic restructuring. This has been well documented during oocyte meiosis in several species (Campanella et al., 1984; Charbonneau and Grey, 1984; Jaffe and Terasaki, 1994; Mehlmann et al., 1996; Shiraishi et al., 1995; Terasaki et al., 2001). Additional studies have described ER remodeling in a similar manner during mitosis (Lu et al., 2009; McCullough and Lucocq, 2005; Poteryaev et al., 2005). Overall, the evidence suggests that the tubular reticular structure of the ER that is typical of cells in interphase is re-structured into a more patchy cisternal organization during M phase. The function of STIM1 is tightly correlated with ER structure, as STIM1 puncta formation depends on STIM1 lateral diffusion within the ER membrane. In addition, store depletion leads not only to STIM1 clustering but also to enrichment of cortical ER, which puts STIM1 in close physical proximity to Orai1 at the cell membrane (Orci et al., 2009; Wu et al., 2006). It is possible that the physical restructuring of the ER during M phase precludes the ability of large STIM1 puncta to form or to stabilize. Therefore, SOCE inactivation during M phase appears to be mediated by both Orai1 internalization and inhibition of STIM1 clustering. Further comparative studies that address the inhibition of STIM1 clustering during mitosis and meiosis will be instrumental in defining the molecular mechanisms underlying this process.
With the discovery of STIM and Orai, much is being learned about the molecular mechanisms that control SOCE activation in response to Ca2+-store depletion, and about the functional domains in STIM1 and Orai1 that mediate their coupling. Cell division provides an interesting physiological example in which cells have devised mechanisms to reverse the coupling between Ca2+-store depletion and the activation of Ca2+ influx at the cell membrane. Such inhibition of SOCE during M phase is liable to be important for cell-cycle progression and oocyte activation at fertilization. Furthermore, understanding SOCE inhibition during M phase will undoubtedly provide important clues regarding the basic mechanisms controlling SOCE activation and regulation. More than two decades after the absence of Ca2+ influx during cell division was initially described, we are now beginning to understand the mechanisms involved. However, several fundamental questions remain unanswered. What are the mechanisms controlling Orai1 internalization during M phase? How do mammalian oocytes maintain functional SOCE during meiosis? How is STIM1 clustering inhibited during meiosis? Are homotypic STIM1-STIM1 interactions inhibited during M phase or is it the ability of STIM1 to form large puncta that is repressed? This last issue will be important to elucidate, as STIM1 is thought to form low-order oligomers (possibly dimers) in resting conditions when Ca2+ stores are full (Baba et al., 2006; Penna et al., 2008) and to reorganize into the large puncta below the cell membrane after store depletion. Therefore, the regulation of SOCE during cell division promises to be an exciting area of research, with broad physiological implications ranging from cell-cycle regulation to the activation of development at fertilization.
This work was supported by grants from the National Institutes of Health (GM61829) and the Qatar National Research Fund (NPRP08-395-3-088 and NPRP08-138-3-050). The statements made herein are solely the responsibility of the authors. Deposited in PMC for release after 12 months.
- © 2010.


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Shelly is particularly interested in working on several targeted styles/themes for her portfolio. Please take a moment to explore the type of work Shelly is looking for here:
Equinox Tattoo Collective
Travel Bookings
Other Inquiries
For inquiries about art commissions, gallery shows, conventions, guest spots, events and other happenings or opportunities- please feel free to reach out and contact Shelly. She loves to get involved in art communities at home and abroad.

subset: commoncrawl


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Losing belly fat may seem like a difficult task, but it does not have to be. All you need is patience and determination, and your efforts will surely pay off.
If you are eating out but are trying to watch your weight, then be aware of who you are dining out with. Recent research shows that both men and women eat more when in the presence of a woman, and less when in the presence of a man. Although we don't really know why this appears to be so, you can use this knowledge to your advantage the next time you go out with your girlfriends and hopefully increase your self control.
Eating a sufficient number of calories daily is necessary for belly fat loss. Starving yourself is not a successful way to diet and keep the weight off. One reason is that that failing to eat will slow the metabolism and cause fat storage. Plus, starvation diets usually result in what is called binge eating, which means you end up gaining back the weight you lost once you continue to eat normally.
Add whole grains to your diet in order to lose belly fat. Contact a doctor about your options with eating whole grains, or you can research your questions online. Avoid purchasing any food products labeled with the words "refined" or "enriched." Companies often let you know if their products contain whole grains, so keep an eye out when you are grocery shopping.
Try to stay surrounded by other active people. The more active the environment we spend time in, the more active we will be ourselves. Sitting on the couch and doing nothing can just hurt your chances to hit your goal.
Take the time to eat breakfast prior to going to work. When you're in a rush to get to your job, it's too easy to down a ready-made breakfast pastry. But, these pastries are loaded with empty calories. If instead, you eat some fruit and oatmeal at home in the morning, you will have no excuse to grab a fattening pastry.
Lose Belly Fat
Try eating broccoli to lose belly fat. A vegetable that is high in antioxidants, such as broccoli, is a healthy way to lose belly fat. Broccoli is great because it can be eaten raw or steamed, and placed in a tasty salad. Your body will definitely thank you.
Many of the new diets today totally eliminate carbohydrates from the diet to help lose belly fat. But, this is not a nutritionally sound plan. Carbs are very important for your body. The key is to consume complex carbohydrates in the form of whole grains rather than simple carbs in the form of sugar and processed foods.
Split meals with friends when eating out. Many restaurants have portions too big for just one person. Ask for two plates and split your meal with a friend or family member instead. You will eat less and save money as well.
Never rely on eating in order to feel happy. A lot of people love to cook and eat. This is acceptable. Food is one of life's great pleasures. Just be sure that you find things that you enjoy equally or more. Try finding hobbies which will also help you lose belly fat.
Make the switch to whole wheat pasta. You may want to stop eating pasta while you are losing belly fat. But, you simply need to substitute them with wheat versions. Pasta made from whole wheat is more healthy for you. You will also find that they are more filling than their alternatives.
This is key: before any event, even if it includes a meal, eat your own healthy meal at home beforehand. Being satisfied can help you make wise foods choices at the event. Wine is lower in calories than beer or cocktails making it a good low-cal alternative.
It is crucial that you consume nutritious foods even when you are watching what you eat. Diets can often cause people to turn to low calorie foods that don't contain that much nutrition. Although you may shed pounds, you are not doing anything to improve your long-term health.
Belly Fat
Now you have some tips and tricks to help you in your quest to lose belly fat. The huge lifestyle benefits of maintaining a healthy weight can make the efforts necessary to losing belly fat worth making. Try some of the things you have learned here, and research more, and soon you will have an arsenal of techniques that work for you.


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Bitcoin is an online computerized foreign currency, just like a buck or even a pound but with just a few exceptions. Introduced by Satoshi Nakamoto in 2009, Bitcoin engages in a peer-to-peer payment process whereby no intermediaries are present and merchandise might be firmly moved between any a couple on the planet. It is associated with a huge group of personal computers and the system of foreign currency for that Bitcoin system (appropriately referred to as Bitcoin) can be basically acquired by joining the large group. Bitcoin supplies a speedy inexpensive and secure financial transaction option but couple of is able to go ahead and take bounce for it. Therefore the one million money question nevertheless lingers, is Bitcoin a safe and secure expense?
Bitcoin is just a several years old, an interesting creation which has awed numerous and also for the record, has acquired a reputation in the top rated economic charts. Its acceptance has spanned and it has led a few of the top businesses like Virgin Galactic to think about it as a suitable way to obtain transaction. Bitcoin rates improve at rates as much as ten percent and then dominate since the alpha in the market and that has created a lot of enthusiastic about making an investment in it. One more special characteristic of best place to invest bitcoin is it lacks a central financial institution and neither does a central government handle it. It's an international foreign currency along with its creation and existence lies powering a complex and geeky statistical algorithm formula that allows it to shadow authority's relevant incidents.
Circumstances of political instability and govt absurdities that plunge the economy as a result of shame and guide many years of assets in a currency exchange down the drain will not happen in the crypto-currency system. This generates a safe and warm and friendly expenditure possibility with low the cost of living risks. By having an at any time-amazing upside, crypto-foreign currency also offers its downs. As I have said, it remains to be using newborn methods; and with that comes fantastic uncertainties. Bitcoin charges are unstable; currently improving sharply and might fluctuate at 30Per cent to 40Percent within four weeks. The entire world continues to be surprised at its appearance and there is present hardly any Bitcoin holders and Bitcoin. This may lead to unanswered concerns and cool anxiety amongst folks as buying a new unknown 'gold mine' can deliver devastating effects. Its newness delivers forth absence of regulations and frightens off of probable traders.


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" I decided to study dietetics because this field is very promising . Nowadays we are faced with the " obesity epidemic " and we could say that "We are what we eat". Also, this is the only study in Slovenia in the field of nutritional counselling. Studying on the beutiful Slovenian coast is just another plus. If you are interested in gaining knowledge for helping people achieving a healthier life style, than studying Nutritional counselling - Dietetics is right for you."
- Žan Virtnik, Undergraduate Nutritional counseling - dietetics student
We Add Knowledge to Life
University of Primorska, Faculty of Health Sciences, Polje 42, 6310 Izola
05 / 662 - 64 - 60 email@example.com
05 / 662 - 64 - 60 email@example.com


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OPM's Regional Leadership Development Programs
The U.S. Office of Personnel Management's Center for Leadership Development is proud to offer our highly effective state/regional leadership development programs. The Colorado Leadership Development Program (CLDP) began in 2000 and served as the foundation for state/regional leadership development programs in California, Florida, Massachusetts, Missouri, New Mexico, Oklahoma, Puerto Rico, Texas, Utah, and Washington, DC.
These programs are designed to meet the leadership development needs of selected federal professionals at the GS-12, GS-13, and GS-14 levels or equivalent, who work in federal, state or local government organizations located in those regions.
The programs are based on a "whole person" model comprised of four dimensions: intellectual, emotional, physical, and behavioral. The curriculum combines this model with bi-monthly classroom sessions and webinars taught by professional facilitators and focuses on development of the OPM Leadership Competencies or Executive Core Qualifications (ECQs). Research has shown that development of these competencies is essential to success in senior-level public sector leadership positions.
Major Components
Program Orientation
Each program features a seven month format that begins with an intense three-day orientation focused on self-awareness and understanding. During orientation, psychological and behavioral assessments (MBTI, FIRO-B, and the Leadership Practices Inventory), experiential activities, discussion groups and presentations provide participants an opportunity to explore and develop awareness of their strengths and areas for potential development.
Bi-Monthly Classroom Sessions
Throughout the remainder of the program, bi-monthly facilitated topic sessions are focused on delivery of content and activities designed to build on strengths and develop challenge areas. A number of additional assessments are conducted throughout the program to explore aspects of emotional intelligence, conflict management, and peak performance among others, to further explore self-awareness and promote opportunities for personal growth and development.
Professional Coaching
Four one-on-one individual consultations with a professional coach are conducted to guide the participant's development over the course of the program. This aspect of the program has been shown to facilitate assimilation of content, personal transformation and development, and transfer of learning.
Development Activities
Individual Development Activity
After the Orientation, participants return to their organizations and begin work on their Individual Development Activity. The selected development activity should provide the participant with an opportunity to stretch and develop their challenge areas and are to be tailored around both a personal/professional road map as well as the needs of the participant's organization. Implementation of the Individual Development Activity takes place throughout the program and a Final Report is due at the end of the program.
Team Development Activity
Over the course of the program, participants collaborate on a research-based Team Development Activity to support the development and application of effective team building and team leadership skills. On the last day of the program, teams will give a presentation on the results of their activity and the dynamics of working together as a team.
Program Benefits
- Participants in OPM's State/Regional Leadership Development Programs represent an expansive cross-section of civilian and military agencies and organizations. This interagency perspective provides participants an opportunity to network with and gain peer support from professionals of other agencies to enhance the learning process and the value of the LDP experience.
- Locally held sessions reduce travel costs and time away from the job
- Provide participants with a convenient venue for participation in premier learning and development opportunities.
- Based on feedback from past participants and their supervisors, the program significantly contributes to organizational leadership capabilities, career development and personal and professional growth. Feedback from participants demonstrates that these programs provide them with unique benefits not experienced in their prior professional development training. These include greater flexibility in leadership style; increased appreciation for the differences between individuals in the workplace; the ability to see things from different perspectives and to successfully take action; greater risk taking initiative; and unique opportunities to integrate prior training experiences.
State/Regional Leadership Program Schedules
Visit the pages below for more information about the nomination process and key dates for the State/Regional Leadership Development Programs:
Colorado Leadership Development Program (in Denver, CO)
Cohort 20: (October 21, 2019 - April 23, 2020)
Monterey Leadership Development Program (in Seaside, CA)
New England Leadership Development Program (in Bedford, MA)
Cohort 3 (August 5, 2019 - February 13, 2020)
New Mexico Leadership Development Program (in Albuquerque, NM)
North Texas Leadership Development Program (in Fort Worth, TX)
Cohort 3 (January 28 - June 17, 2020)
St. Louis Leadership Development Program (in St. Louis, MO)
Cohort 1 (July 29, 2019 -February 13, 2020)
Washington, DC Leadership Development Program (in Arlington, VA)
Cohort 5 (September 9, 2019 - March 12, 2020)
Interested in having an OPM Leadership Development Program in YOUR State or Region?
Julianne Gatewood


text: U.N. Secretary General Javier PEREZ DE CUELLAR made his first formal statement since war broke out. He said he has "witnessed with profound grief and anxiety the increasing severity of the war" and appealed to Iraq to withdraw from Kuwait. . . . U.N. Security Council President Bagbeni Adeito Nzengeya of Zaire reportedly promised to allow discussion of a NON-ALIGNED MOVEMENT peace initiative during informal consultations. But the United States, Britain and Soviet Union insist the council take no action until Iraq shows signs of relenting.


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Seprio has been negotiating purchase agreements on behalf of their customers since 2000. These agreements span all kinds of spend categories and industries. With that kind of diverse experience and analysis of the results, we find a common thread through it all… savings. Whether it be a pure cost savings to the bottom line or a cost avoidance through a negotiation, the savings are out there. Many ask, by saving these hundreds of millions year after year, what do the customers do with all of this new found cash? You might be shocked by this answer, they spend it! ALL OF IT! While it is easy to make light of this scenario, it's not one to be taken lightly if you are looking for a true contribution to your bottom line. So what is an organization to do?
After careful consideration of the savings our customers enjoy, we have created a unique concept of savings retention. When a customer sets out to reduce costs in their operating budget, the money is easily accounted for in the reduction of the OpEx at the account level. This is a very different story when the savings is achieved through that very grey area of cost avoidance. We don't see cost avoidance as a grey area at all, it's quite clear, the money was budgeted for the spend, the total cost was reduced below the budgeted amount and the result is a avoided additional cost or cost avoidance. Simple to us, but complex to the customer when we report a $10M cost savings to their organization and they can't find the money. Our response to this is simple, contain your budget variance in a separate account within finance. This number should always reconcile to the final savings number. If it doesn't, either the money was spent without visibility or the savings were never produced. In either event, it's important to quantify in order to understand the savings landscape.
Negotiating a cost savings is only part of the equation. Negotiating a supporting contract is another part. However the final piece is quantifying and CONTAINING these savings so that they can make a real contribution to the bottom line.


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In my work with international students, I have been asked many questions over the years, and one of my roles as a teacher is to help them learn how to find answers to their questions, particularly when it comes to understanding people fromso many different cultures.
First of all, I try to emphasis that people who teach them HOW to think are people worth listening to because they don't view themselves as the source of knowledge. However, people who tell or teach my students WHAT to think are probably caught up in their own wisdom and intellectual hubris, and they can't seek the flaws in their own reasoning.
The second point is learning to ask the right questions to get the right answers. Simply asking, "So, what do American families like to do at Christmas?" is the wrong question because it first starts out with an unclear definition of who Americans are.
Brazilians are Americans; Hondurans are Americans; Mexicans are Americans. (I am also concerned when people stereotype the cultures of my own students which can lead to unfortunate and harmful labeling.)
This question about "Americans" that comes from a very ethnocentric worldview makes it impossible to answer because it isn't based on a clear definition of what an American is.
So, on whatever topic or field of study you are in, learning how to think logically and rationally is one of the keys to a deeper understanding of the world around you.


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Kings and Queens offers a range of outlets for your research either online, conference, or journals. Whether that research is a working paper in development or research ready to be reviewed, published and disseminated for the research community. Here you will find details of Kings and Queens journals and conference outlets. Select your publication outlet to find out more.
Kings & Queens Conventional Conference
Kings and Queens coordinates and holds a traditional conference at the end of the academic year targeting academic researchers and tertiary educators from university, institutes of technology, and polytechnics. All are welcome to present their research findings or hear the latest research. The research presentations are held in traditional lecture theatres for others to hear.
The next Kings & Queens Conventional theatre Conference will be held on 20 September 2019, at Hamilton, New Zealand. Submit your paper NOW. Paper submission deadline is 31 July 2019.
Kings & Queens Online Conference
Avoid the need for travel time and expense with hearing conference presentations from researchers around the world. Use the blog to comment on others research. Or present your research paper to gain valuable reviewing, feedback, and constructive critique here with an online conference, then consider submitting to a journal. Upload your video presentation to gain an output. Or use the conference to network. Enquire if you need a video recorder for recording your presentation.
You can view conference papers here anytime, and you can upload papers here anytime until the close of the academic year.
Upload your video conference paper presentation NOW.
Kings & Queens Journal
Kings and Queens coordinates and edits a journal targeting academic researchers and tertiary educators from university, institutes of technology, and polytechnics. All are welcome to submit a paper to the journal or freely view previous research papers. After a traditional review process that elicits the best from your paper, your paper may be published here.


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Mark 12:24 – Jesus said to them, "Is this not the reason you are wrong, because you know neither the Scriptures nor the power of God?"
Lord Jesus, the Pharisees and the Sadducees show their ignorance. They ask their questions of Jesus, but they don't even know the Scriptures. They have fallen away from the faith because they haven't spent their time studying and knowing the Scriptures. Lord Jesus, keep me from this! I pray you, Lord Jesus, by the constant teaching of your Spirit and the constant meditating on your Word, teach my heart, guide my life, and instruct my mind. I pray, by Your Word transform my heart and mind so that all these important questions are answered not by my understanding but by the truth of your Word. Speak clearly to me in your Word and give me faith to understand, apply, and believe it. Help me stand up in faith on the truth of your Word. Amen.


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Designer's Choice - Summer Mix
From: $75.00
Availability: In-Stock
With an infusion of Rosé wine from Provence in every bite, these newest rosette-shaped gummies are the perfect treat for any Rosé lover.
Size: 2.18" x 2.18"
Fat-Free, No GMO, Gluten-Free
Water should be changed daily to help your flowers last longer
Make sure to keep your flowers away from extreme cold or heat and out of direct sunlight
Cut your stems every few days. This helps your flowers get a fresh drink!


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Joe Rooney
Service Areas: NY Metro Area
Rooney Tunes has everything you need to have an amazing time at your next event. No job is too big or too small. Being in business for over 34 years, we know what it takes to make a party amazing. We'll sit with you and listen to what your needs are, and will come up with a package that will make you happy and won't break the bank! Give us a call, I promise you won't be disappointed.


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The Toyota 86 Series commenced in 2016, with a successful 5 round championship run alongside the Virgin Australia Supercars Championship as sanctioned by the Confederation of Australian Motor Sport (CAMS).
Like similar one–make series, the Toyota 86 Racing Series demands competitors adhere to a strict set of controlled components and car setup, ensuring that driver talent, rather than team budget, is key to winning.
The Toyota 86 itself is a front engine, rear wheel drive car is ideally suited to close racing due to its superb handling, with maximum speeds down Mt Panorama's Conrod Straight of around 230km per hour.
In 2016 Toyota 86 Series saw capacity grids with minimum 32 cars competing at each round. Three of which featured a rotating roster of professional racers, including Steven Johnson, Glenn Seton, Dean Canto and Cam McConville, to allow upcoming drivers to gauge their ability.
The series receives fantastic coverage as part of Virgin Australia Supercars program, with an average TV audience of over a million across Foxtel and Channel 10 each round. While the average crowd attendance for 86 rounds in 2016 was over 100,000 per round, with marque events like the Bathurst 1000 on the program.
2017 Schedule
- Round 1: Phillip Island – April 21-23
- Round 2: Townsville 400 – July 7-9
- Round d 3: Sydney Motorsport Park – August 18-20
- Round 4: Bathurst 1000 – Mt Panorama – October 5-8
- Round 5: Newcastle500 – November 24-26


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Animal Name Tag #
Date of Sale / / If male, has he been castrated? Yes No
New Members complete the section below
Preferred Herd ID (3-5 characters as letters or numbers)
First year annual membership is free with purchase of yak from IYAK Member or an annual membership is $60.
Buyer Name(s) Buyer Ranch
Buyer Member # Buyer Herd ID
Mailing Address
City State Zip Code
Phone #
Seller Name(s) Seller Ranch
Seller Member # Seller Herd ID
If seller information has changed, fill out new information below.
Mailing Address
City State Zip Code
Phone #
Seller Signature Date / /
Cost of transfer is $15. This can be paid by check or PayPal. PayPal email is:
Mail this form, original certificate, and payment (if applicable) to:
International Yak Association
c/o Holly Modjeski
6576 N Yucca Trl
Parker, CO 80138
If original certificate is unavailable (circle here): Unavailable
Please print this form, sign and mail it the the IYAK Registrar at the address above. For questions contact the registrar at email@example.com.


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See All
Video Recipes
"Pachakam" means cooking in kerala and Pachakam.Com welcomes you to the magnificent world of easy and healthy Indian cooking with a probe into the fascinating Indian cooking recipes. Cooking is not just about making food but is an art of presenting your culinary skills to those who love food with a different flavor and Indian cooking, by no means is an exception.
Instant Coconut Balls
Category :
Published On: 05 Mar 2014
Take a cup of condensed milk.
Chop the nuts/ grate and keep it aside.
Keep the desiccated coconut ready.
In a pan, heat ghee and add the desiccated coconut and the nuts.
Add the condensed milk and boil.
Add sugar and let it boil.
Wait till it comes to thick consistency.
Make them into small balls and serve immediately.
The left over idlies from breakfast can be reused if people do not prefer eating idly in more than o...
easy n tasty dish...
Ney pathiri or deep fried rice rotti is a very common breakf...
Banana bread wheel is a simple tea time snack prepared with ...
Banana is one fruit which is cheap, nutritious and is easily...
Neyyappam is a sweet snack recipe originally from the south ...
Nizana Shammas is a hosewife who has lots of interest n cooking. She is an expert in providing various traditional recipes.
Renukadevi Kumanan is a well versed person in providing varities of South Indian recipes and also some modern recipes. She used to try varities of recipes from different cuisines.
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Batik prints, safari colours and raffia textures as Burberry's Christopher Bailey takes us to Africa
Read more about Burberry, or view recent Burberry Collections on London Fashion Review Blog.
Creative Director of Burberry, Christopher Bailey described is Spring/Summer 2012 womenswear collection as upbeat and nostalgic, and the iconic British brand certainly lived up to its promise. As will all his collections for Burberry, there was a story behind the collection – A military wife, whose husband is stationed in the Far East, say, fills her idle hours by watching and learning from local artisans. Then she applies her new knowledge to decorating her own clothes.
This story is evident in the collection with the beading running down the plackets of trench coats or lining their collars; the large geometric wooden beads that formed aztec motifs around necklines of mac jackets and t-shirts; the ornate stone buttons featuring on knitwear; and with the raffia trims featuring on the parka jackets.
The Spring/Summer 2012 collection featured full midi-length skirts in stiff silk or linen, teamed with overly embellished tees or bobbled knits underneath cropped hooded parkas; a batik print inspired by the shapes of legendary British artist Henry Moore emerged in dresses and skirts with exquisite drapery; narrow raffia pencil skirts that were paired with full skirted trench coats that were structured close to the body; and pleated crepe dresses with peek-a-boo detail in leafy green and mustard hues. The textural collection was completed with peaked, raffia pompom trimmed hats, woven leather wedges with leopard print heels and beaded anklets.
Live streaming of runway shows is rapidly becoming mainstream amongst British and international designers alike, so it was only natural for runway innovator Burberry to take things one step further. While attendees to the show waited for proceedings to commence, Burberry's twitter followers were given the change to see the Spring/Summer 2012 looks just seconds before they exited for the runway in Kensington Gardens in the first ever 'Tweet-Walk'. As an added innovation, the looks were available to purchase directly from the runway, cutting out the retailer and the usual 6 month wait. So without further ado we present all the looks from the Spring/Summer 2012 Burberry Prorsum womenswear collection…Enjoy!
Visit the official Burberry website, or check out Burberry Clothing Collections on London Fashion Review Blog
If you like the look of the Spring/Summer 2012 womenswear collection from Burberry, why not check out the seasonal collections form Vivienne Westwood Red Label, Holly Fulton and Religion.


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a pair of bronze cherubs on marble bases Read more
Georgian Antiques has 2577 antiques for sale.
click here to see them all
Circa 1880, set of 6 late Victorian oak chairs. The chairs are stamped with the makers label, 'J and T Scott, Edinburgh' who were prominent cabinet makers with shops in George Street and Princes Street. The chairs have an upholstered back and oak frame. They have a large stuffover seat and rounded backs. With their square legs which taper down with a slight kick at the back, they are very much in the Gillow's style. A simple half round beading continues around the entire chair and the back and frame of the chair is polished. At the front, the legs are ring turned and fluted with tapering beneath. Towards the bottom is a large block and from this the chair is united by an H framed stretcher with various blocks, ring and tapering. Beneath the blocks, the chair has a brass bezel and beneath this, brass and brown porcelain castors.
Scotland's largest antiques warehouse is located in a converted whiskey bond in historic Leith Edinburgh. With 50,000sq ft over five floors we offer a wide range of quality Georgian, Victorian and Edwardian furniture, as well as continental and small decorative items. Our stock is constantly changing.
Georgian Antiques has 2577 antiques for sale.
click here to see them all


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The Miami Herald reports:
Miami Gardens Congresswoman Frederica Wilson criticized Donald Trump's handling of congressionally ordered Russia sanctions Tuesday night during a boycott of his state of the union speech, suggesting the president has taken it easy on Russia because "they have something on him."
"The House and Senate voted on all kinds of sanctions against Russia. Now, the president yesterday announced he wasn't going to impose those sanctions," she said just before a press conference with the Miami media inside an Overtown church. "They have something on him. And if he imposes sanctions against Russia, they're going to tell what they have on him."
Congress over the summer passed a bipartisan law ordering up sanctions against Russia after determining that the foreign country had meddled in the 2016 U.S. elections. That law gave Trump's administration some wiggle room on timing, but pegged Monday as a date to begin implementing new penalties against companies that do significant business with Russian defense and intelligence sectors. The State Department, however, announced it would not immediately rush to levy sanctions, saying that the law was already acting as a deterrent.


text: Thank you for your interest in Diga-Talk Plus. The most reliable nationwide push-to-talk two-way digital communication system. Please fill out the information below for the free demo request. As soon as we receive the request, we will be in touch with you to further discuss the demo and send it out to you.


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"We actually aren't new to the summit area, the owner, Khalid Agour, has owned Toscana since 1999," general manager of the new joint Devrim Øzkan tells CHS. "It has always been a dream of his to have a throwback to his Moroccan roots that highlight some of the foods he grew up with."
Itto's Tapas — really, Itto's Tapas 2 — will celebrate its grand opening Tuesday at 601 Summit Ave E, the space formerly home to Toscana until it shuttered late this summer to make way for the new project. Don't worry — its closure marks only a minor setback in Hill's wave of pizza domination.
The Itto's opening comes two years to the day after the Agour brothers opened the first Itto's in West Seattle. Our friends at the West Seattle Blog helped them celebrate their first anniversary last November. Late November is also a bittersweet time for the family as it marks the anniversary of the passing of the family's matriarch and restaurant namesake, Khalid and Aziz Agour's mother Itto.
The venture has done well by her name. In West Seattle, Itto's Moroccan and Spanish tapas have developed a solid following with a menu bursting with boquerones, paella, tagines, stuffed dates, zaalook, skewers, meatballs, and dolmes along with cocktails, wine, and Moroccan beer.
The plan on Capitol Hill is to bring the neighborhood "the same cocktails and the same love of our community."
The new life for the Toscana space is neighbored by food and drink spot Single Shot, the original and only remaining Capitol Hill Sun Liquor, and Top Pot. UPDATE: And the Summit Pub!
"What we found in West Seattle was that the small neighborhood lent itself to the intimate, cozy experience we strive for. Summit has exactly that, a small space with a larger city right around the corner," Øzkan writes. "Our neighbors are amazing and we are so excited to bring a piece of our home to it."
Itto's Tapas is located at 601 Summit Ave E. Hours are Sunday through Thursday, 4 PM to "12ish," happy hour: open to 5 PM, 11 PM to 12, Fridays and Saturdays: 4 PM to "1ish," happy hour: open to 5 PM and 11PM to 12 AM. You can learn more at ittostapas.com.


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Inquiry-Based Science Curriculum Invigorates Students
According to Johnson, the students enjoyed the integrated, hands-on approach to learning science.
"They embraced the role of scientist as they observed land and water organisms in eco-towers and in an actual river and pond," Johnson said. "They were excited to use their knowledge and understanding of electricity to build working flashlights and to wire a dollhouse."
The project has had a positive impact on students' learning as indicated by data.
"After using the Einstein Kits, data showed significant growth in students' knowledge and in their attitude toward science," said Carstens. "The students loved the hands-on, inquiry-based approach to learning science and the chance to work collaboratively with their peers. The exploratory approach to learning helped them think critically and develop a deeper understanding of the concepts."
One of the students summed it up, "I like it because it makes you feel like you're a real scientist and you're doing experiments that scientists do."


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Not having time to eat breakfast impedes your ability to finish tasks throughout the day. Your focus is hazy, you feel lazy, and nothing comes as easily as when you are well fed. Not eating consistently negatively impacts your body in more ways than one.
If you care about your health, protein powders are an excellent alternative to give your body one of the most vital nutrients it needs.
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There are various protein powders to choose from, and finding the right one takes time and money. Fitness professionals all recommend BSN products for anyone who requires supplements in their diet. They're cleaner, additive free supplements that focus on quality and results over size and cost.
SYNTHA-6 is a protein powder manufactured by BSN, and it's a bestseller on the market. BSN uses exclusive technology to produce a fast dissolving yet delicious protein powder. A tasty protein powder is hard to come by.
Below is a review of BSN's SYNTHA-6 Protein Powder.
For about a decade, BSN has been a worldwide leader in regards to sports nutrition. BSN's SYNTHA-6 formula revolutionized the protein powder market. It is now the go-to product for anyone who needs extra protein in their diet.
Our Rating
SYNTHA-6 comes with a measuring spoon that helps regulate the amount of powder per scoop. You can take one scoop of SYNTHA-6 and mix it with 4 to 5 ounces of water. You don't have to limit yourself to water. In fact, you can put SYNTHA-6 in any drink you choose.
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Whey protein concentrate is responsible for the delicious taste of SYNTHA-6. This is because it contains some levels of lactose and fat. Lactose, or milk sugar, make it possible for SYNTHA-6's to have rich flavors.
Every ingredient BSN utilizes for SYNTHA-6 works to provide your daily amount of protein and fiber. Those who follow strict workout plans understand that the intake of protein and fiber in powdered form is the most efficient way of consumption.
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SYNTHA-6 comes with 22 grams of protein with a majority of it being whey protein concentrate. Whey protein concentrate comprises of about 80% protein. This is less than the protein content found in whey protein isolate.
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There are two forms of casein, and SYNTHA-6 contains the most useful form. Micellar Casein is a healthier alternative because of the lack of chemicals used in its production process.
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Milk protein isolate is cheaper to manufacture than whey protein, but it has the same beneficial qualities. SYNTHA-6 incorporates both into its formula.
Egg Albumen is a fancy way of saying egg protein powder. SYNTHA-6 uses egg albumen because of its high protein content. There are also natural vitamins found in egg albumen that transfer over to SYNTHA-6.
On top of getting your daily protein, you'll be consuming your daily dose of various vitamins.
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SYNTHA-6 incorporates glutamine peptides and not glutamine because the body absorbs the peptides at a faster rate. Glutamine peptides work with the glutamine found in your body to promote muscle repair.
Buyers all agree that SYNTHA-6 is a prime blend for muscle gains. What makes SYNTHA-6 so popular is both its taste and effective results.
SYNTHA-6 suits any dieter because it's not strictly a post-workout supplement. If you lack protein in your diet, SYNTHA-6 works to improve that. You can dissolve the powder in water as well as milk. You'll be making a protein powder shake that tastes just like a milkshake.
Based on positive buyer reviews, you can't go wrong when you order SYNTHA-6. Some buyers have been using SYNTHA-6 for years and still continue to this day.
BSN's SYNTHA-6 is available both online and through third-party retailers. Stores tend to increase the price because they are trying to make a profit.
Amazon offers discounts as well as free shipping when you order SYNTHA-6. You have the option to subscribe to monthly deliveries, which saves you money long term.
I would highly recommend buying BSN's SYNTHA-6 Protein Powder because your money won't go to waste.
Being healthy doesn't have to be a difficult feat. With SYNTHA-6, all you have to do is scoop and mix. This takes seconds and leaves you feeling energized and is the perfect recovery and pre-workout supplement. Once you start using SYNTHA-6 daily, you'll notice your body reacting in a positive way.


text: Coleman Hawkins Food And Drink By Dennis Owsley • Nov 18, 2018 Dennis C. Owsley / Copyright Dennis C. Owsley Jazz Unlimited for Sunday, November 23 will present "Food and Drink." Thanksgiving is the season of gluttony and we will present music suggestive of the season, dividing the show into breakfast, lunch, libations and dinner selections. The artists featured on this show include Bunny Berigan, Phineas Newborn, Jr., Les McCann, Art Tatum, Hank Mobley, Coleman Hawkins, Nat "King" Cole, Billie Holiday, Don Byas, Cyrus Chestnut, Louis Armstrong, Lionel Hampton, Lee Morgan, Gene Harris, Eddie Harris, Dizzy Gillespie. The Dizzy Gillespie Centennial" By Dennis Owsley • Sep 17, 2017 Dennis C. Owsley / Copyright Dennis C. Owsley Jazz Unlimited for Septemner 17, 2017 will be "The Dizzy Gillespie Centennial." Jazz needs a Dizzy Gillespie for his audience communication skills and basic humanity. We will celebrate his hundredth birthday, which will be in October, with a survey of the music in his career mainly from a time when he was playing at his best technically and imaginatively. We will hear Dizzy with his own groups and big bands, Cab Calloway, the Dirty Dozen Brass Band, Charlie Parker, Coleman Hawkins, Roy Eldridge, Bud Powell, Oscar Peterson, Jazz At the Philharmonic, Quincy Jones, Benny Carter and The Compositions Of Jerome Kern By Dennis Owsley • Nov 3, 2016 Dennis C. Owsley / Copyright Dennis C. Owsley Jazz Unlimited for Sunday, November 6, 2016 will be "The Compositions of Jerome Kern." Composer Jerome Kern was one of the first to bring jazz rhythms and harmonies to theater music. Paradoxically, he did not like jazz musicians arranging his music for their own performances. But, jazz musicians like his tunes and are still using them as a basis for improvisation up until today. We will hear music from Art Pepper, Ella Fitzgerald, St. The Norman Granz Labels-Part 2 By Dennis Owsley • Jul 22, 2015 Dennis C. Owsley / Copyright Dennis C. Owsley Jazz Unlimited for Sunday, July 26 will be "The Norman Granz Labels-Part 2." Entrepreneur-Promoter Norman Granz founded the Clef, Norgran,Verve and Pablo record labels. After Granz sold Verve, the label has become a powerhouse, recording many styles of jazz with such artists as Gerry Mulligan, Charlie Ventura, Oscar Peterson, Count Basie, Sarah Vaughan, Zoot Sims, Coleman Hawkins, Roy Eldridge, Johnny Hodges, Charlie Haden, Gil Evans, Herbie Hancock, Wayne Shorter and others. The Slide Show contains my photographs of some of the artists heard on this show. The Career Of Pee Wee Russell By Dennis Owsley • May 2, 2015 William Gottleib / Copyright William Gottleib Jazz Unlimited for May 3 is "The Career of Pee Wee Russell." Clarinetist Pee Wee Russell was born in Maplewood Missouri in 1906. All of his life, he was a contrarian who went his own way. Even though he was a very original voice, Pee Wee was very shy and people laughed at him because he looked like a clown. Whitney Balliet remarked that, "even his feet look sad." During his career, Balliet noted that he worked with the wrong musicians most of his life and during the last seven or eight years worked with musicians he should have been working with his entire life. He also became a very The Career Of Coleman Hawkins: Father Of The Tenor Saxophone By Dennis Owsley • Dec 11, 2014 Jazz Unlimited for Sunday, December 14 will be "The Career of Coleman Hawkins: the Father of the Tenor Saxophone." Coleman Hawkins was the first to recognize the beauty and utility of the tenor saxophone. Before he came along, it was a novelty instrument. Since his first recording in 1921, Hawkins has paved the way for a lot of tenor players and influenced many. He is known as the "father of the tenor saxophone." We will listen to his 47-year career that includes music with Fletcher Henderson, St. Jazz Live From The Five Spot, Village Gate And Cafe Bohemia By Dennis Owsley • Jan 12, 2014 Dennis C. Owsley / Copyright Dennis C. Owsley Jazz Unlimited for January 12, 2014 will present "Live Jazz from the Five-Spot, Village Gate and Café Bohemia." Energy reflected back to performing artists from an up close and personal audience often brings out the best performances. We will feature live performances from Donald Byrd & Pepper Adams, Les McCann, Stanley Turrentine, Mongo Santamaria, Kenny Dorham, Coleman Hawkins, Sir Roland Hanna, Kenny Burrell, Herbie Mann, Horace Silver, Charles Mingus, Miles Davis. The Career Of Bob Brookmeyer By Dennis Owsley • Oct 31, 2013 Dennis C. Owsley / Copyright Dennis C. Owsley Jazz Unlimited for Sunday, November 3 will present some of the nearly sixty year career of valve trombonist, pianist, composer, arranger and teacher Bob Brookmeyer. He has played with, arranged and composed for such people as Terry Gibbs, Clark Terry, the Birdland Dream Band, the Gerry Mulligan Quartet and Sextet, Stan Getz, the Thad Jones-Mel Lewis Orchestra, the Jimmy Giuffre Three, his own New Art Orchestra as well as his own small groups. The show will include work by such artists as pianists Roger Kellaway and Hank Jones, saxophonists Coleman Hawkins, Al Cohn, Richie Kamuca, Bill Per


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The future of food banking in Britain remains quite uncertain. Here are some thoughts on how the situation compares to the US, and some ruminations on what the future holds.
· Measurement. Unlike the US and Canada, Britain does not measure food insecurity. The End Hunger UK campaign is working with MP Emma Lewell-Buck to gain passage of legislation that would establish a national food insecurity measurement. Having this baseline of information will be useful to assess the scope of the problem. However, it will likely be a few years before a measurement is put in place and baseline data is gathered.
· Food waste. Unlike the US and Canada, Britain does not have extensive connection between food processors and retailers and food banks. There exist multiple competing entities – the Felix Project, FareShare, Real Junk Food Project, Company and Community Shops, that collect wasted food and distribute them to charities or sell them to the public through social supermarkets or pay as you feel cafes. It was quite inspiring to see advocates deliberately point out that the answers to food waste and food security were different things, as compared to the States, where they are typically conflated.
· Hunger Industrial Complex. The relationships between food banks and Big Food and Agriculture are starting to take shape. FareShare is partnering with Coke in a holiday cause marketing partnership. Interestingly, Tesco, the largest supermarket chain in the country and one that is well-known for its abusive labor practices (similar to Walmart), has partnered with these two non-profits to promote sales of turkeys, cookies and other products through contributing a small percentage of sales to Trussell Trust and FareShare.
· Stigma. Unlike the US, food banks are not normalized in the UK. Many people do not understand what they are, how they work, or what they provide. A theater troupe has even put on a play to educate the public about the trials and tribulations of people who rely on food banks. Many anti-hunger advocates, even those operating food banks, are outraged that food banks exist in as wealthy a nation as Britain. Food banks are caught between a growing demand for charitable food because of government austerity policies and a powerful aversion to the institutionalization of the emergency food system, which they fear would further encourage the shrinking of the government role in providing or the right to food.
· Economic Crisis. The economy is humming along at near full employment, but food bank usage has soared in recent years according to Garry Lemon, the Communications Director for Trussell Trust. Lemon remains concerned that a recession with a corresponding spike in unemployment would overwhelm food banks, in part because Tory policies have slashed the safety net for the unemployed (and others). Brexit looms on the horizon for early 2019, and many analysts are expecting it to lead to decreases in GDP and a recession.
· Food banks, Trump, and Brexit. In both the UK and the US, neoliberal policies that shrunk the role of the social safety net led to the explosion of food banking. In the US, it is not a stretch to say that anti-hunger advocates contributed to the election of Trump. In Rust Belt communities, they failed to address the loss of manufacturing jobs and the middle class wages that they provided. Instead, they offered two undesirable alternatives: food stamps and food banks, both of which are stigmatizing. As a result, many Rust Belt communities like my home county of Trumbull OH voted red for the first time in 44 years. In the UK, food banks are symbols of the economic dis-ease and insecurity felt as the Tory government slashes social programs. This insecurity was felt most strongly among those who supported Brexit: the less educated older and poorer voters. Perhaps not so ironically, this cohort also is an important part of Trump's base.
Putting the genie back in the bottle
Unlike Scotland, the English food advocates I met did not seem to think eliminating food banks in England was immediately feasible. The former director of the Trussell Trust was famously quoted, to much consternation, as saying that he wanted to establish a food bank in every town. The organization has backed off that vision, and is in a leadership transition right now. Garry Lemon, the newly hired communications director told me that he'd like to see food banks turned into community-based venues for people to gain skills and access services they need to leave poverty. But that's his own personal vision, not the official line for the organization.
The future of food banking in Britain is uncertain and is heavily dependent on government policy and the leadership of key NGOs.
Under an expansion scenario:
The rollout of universal credit causes more acute poverty. Brexit results in economic contraction, and a sharp rise in unemployment. Britain imports some 30% of the value of its food; Brexit also causes the price of food to increase dramatically due to a weakened pound and potential trade barriers. Food banks continue to expand and institutionalize. All of these factors place more demands on food banks, which must adapt and expand their capacity. FareShare expands its food waste collection capacity with help from the Global Food Banking Network, and it begins to distribute surplus food into Trussell Trust and some independent food banks. Trussell Trust adjusts its model, encouraging sites to acquire refrigeration units so they can distribute perishable foods from FareShare. The Tory government increases its complicity with food banks, funding infrastructure, as they see food banks to be a relatively inexpensive way to address a growing food security crisis. Food banks increasingly come to resemble a North American model, further integrated into Tory social policy.
A contraction model
The Labor Party returns to power and reverses Tory social policy. Data on food insecurity is collected and released. The British public becomes outraged at the scale of the hunger problem and demands policy changes. Scotland is successful in gaining an effective end to food banking. Wales and Northern Ireland as other devolved nations seek to repeat Scotland's successes. In England, the Trussell Trust announces its intention to downsize its food banking operations, setting a strategic goal of closing 50% of food banks within 5 years.
Moving in a different direction
In a few years, the public has donor fatigue and its support for food banks slowly diminishes. The lessons of the progressive experiments in Scotland to bend down the food banking curve begin to be implemented in England. Trussell Trust begins to shift its food banking model toward a community food center model, based on the work of Community Food Centres of Canada. Its food banks take on more food system type activities, promote healthy eating, social capital, and policy advocacy. It continues to distribute free food but within the context of a more comprehensive approach.


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May 4, 2014
What clicking the plus button in Google+ means to you
• Clicking a + button reveals who you are on Google+. That is, it shows your Google+ profile name and icon. If you're like me, and you want people to know who you are (and possibly promote your business) that's a very good thing. No, there's no guarantee that anyone will actually go look at your profile, or learn about your business, but at least you are getting out there. In the marketing world, this is known as exposure. No, it doesn't reveal anything other than who you are on Google+, so go and take another look at your profile. Are you showing your best face to the world?
Brad Hall's Google+ profile
• Clicking a + button helps attract the attention of the Google bots to the post. People like me, and my clients, are doing everything we can to get positive attention from the Google bots, which index things for a Google search. This is the main reason that the + is so different from a Facebook *like*. Facebook is not Google, and it isn't as helpful in increasing indexing for a Google search.
And those are the main reasons. Also, since I have the page +Phoenix, Arizona Historical Images , the number of plusses tells me what most people like. I've noticed that people prefer nice color photos from the 1950s and 60s less than they like maps. Although I like maps!
I hope this helps. Remember that the web is, and always has been, a public place. If you want exposure, like my clients do, to help to get your name and business in the first few pages of a Google search, then put your best face forward, and then go click those + buttons!
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Use the Poison As an Antidote
It began, as all beginnings do, with an end.
After the dust had settled, after all the pieces had fallen, after all that was left was a pain that was as bewildering as it was debilitating, I stumbled onto the words of an American Buddhist nun.
The lucidity of the teaching was so astonishing that it was enough to startle me out of my grief. Years of being raised in a Catholicism that took refuge in the ineffability of the divine had not prepared me for the possibility that religion could possess so much common sense.
It also hadn't prepared me for the possibility that I could actually—beyond my wildest religious imaginings—be fine the way I was.
I was raised, as many Filipino Catholics are, to believe that being gay was a sin.
If you happened to be Catholic and gay, you had the following options:
You could stop being Catholic.
You could stop being gay.
And if you didn't have the fortitude to do either, then you could just stop being honest.
Although I was gay and therefore a sinner, I couldn't fully betray my inclination to be honest. This led to all manner of (retrospectively) hilarious evasions when people asked me about who I was seeing.
My favorite strategy was to resort to linguistic sleight-of-hand. Filipino, unlike English, doesn't make use of gendered pronouns. So when asked about how things were with a significant other, I would answer in English if I had a boyfriend—and in Filipino if I had a girlfriend.
Other gay, Filipino Catholics would have noticed the trick immediately.
It was just one of many I had up my sleeve.
I didn't begin by being a trickster of course.
I tried hard for years to make it work.
The first few years of my adolescence passed in a fog of preoccupied androgyny. If you can't confront the truth about your sexuality, you suppress your sexuality altogether and divert the energy to all manner of non-sexual things.
(It's the best way to be happy without being gay.)
So while my peers collected romantic escapades, I stockpiled curricular achievements and extracurricular pursuits.
That strategy lasted until college—only because even Filipino Catholic universities have underground cultures of their own.
(I was still in a closet, but it was a vastly larger closet. And it was filled with all manner of fabulously glittery things.)
Those years were freer in a sense, but also the source of a soul-deep fissuring.
Because it's one thing to be gay and to not do gay things—it's another to be gay and to do gay things.
That was when the existential schizophrenia began. I alternated between the wild exhilaration of having girlfriends, the utter terror of being discovered, and the profound shame of being corrupted.
Towards the end of my college career, after completing twelve units of theology class, the shame finally won over the exhilaration (the terror wasn't too far behind).
(I remember kneeling at the feet of a Jesuit priest, sobbing in repentance, remorse and regret. Never again, Father, never again…)
I got a job after that—and a boyfriend—and it seemed that everything was fine.
Until I switched jobs and met her.
She was Filipino too. And Catholic.
But not gay.
(You can already tell how this is going to end.)
(Basically, it's going to end.)
Anyway, even sinners are granted miracles and for two years we were happy.
It was all terribly secret of course—this was when I acquired a laudable stockpile of tricks up my sleeve—but in spite of the claustrophobic confines of our closeted little world, we actually managed to imagine a future.
Now when you're young and earnest and confused, all you need is a future. It's enough to redeem the past. It's more than enough to mortgage the present.
It was a future audacious (or delusional) enough to include the standard accoutrements of a house, a dog and a cat—all closeted in by yards and yards of immaculate picket fencing.
But the shame won out in the end for her too (with the terror not too far behind) as years of catechism classes finally kicked into gear.
Don't ever tell anyone, were her parting words to me.
That was when I discovered that grief was a terrible thing.
And that the only thing worse was a grief that could not be shared.
Because the problem when you live a terribly secret life is that you have to maintain the secrecy even when it ends.
(Are you alright? My friends would ask. Smashing, I'd lie through gritted teeth as the dust swirled and as the pieces of my former life rained around me.)
And because our realities are real only insofar as they're expressed and embedded in the world (even a closet of a world with just two inhabitants still functions as a world), my grief was radically compounded by rapidly acquiring the quality of the surreal.
(If a tear falls in a forest and there's no one around to see what occasioned it, doesn't it make the grief more grievous?)
It was while I was erecting phantom memorials to my misery that I stumbled onto the words of an American Buddhist nun.
Use the poison as the antidote, she taught.
(I nearly wept with gratitude given all the venom that I'd acquired.)
Turn your vices into virtues, she implied.
(At the rate I was stockpiling vices I was bound to have virtues galore.)
All that was demanded was for me to sit.
Just sit.
It's been nearly a decade since I read those words and I can tell you that I've sat a lot.
But see, it's not the sitting that's the problem.
It's the "just"-ing.
That part I haven't gotten pat just yet.
But that's okay.
More importantly, I'm okay.
Well, truth be told, we're all okay and it's all okay.
Even when we're not and even if it's not.
That's the shocking, startling and utterly unnerving beauty of the teaching.
When I look back now on all those years and the needless suffering that was endured, I alternate between a profound sorrow, on the one hand, and an amused nonchalance, on the other.
To have been so young once and so earnest and so confused… Strange, how out of such thorny soil the seeds of irony and equanimity have borne fruit.
(Turn arrows into flowers, she said. And so I did.)
I sometimes wonder if the Buddha felt the same as he watched his countless lifetimes unfold. I wonder if he felt the same odd mix of sorrow, amusement, irony and nonchalance.
Every so often, I'll trace the scars of the wound, mark the edges of the fissure and evoke the memories of a deeply internalized shame and guilt.
And I'll marvel at feeling nothing—not even a phantom pain.
It's possible, I suppose, to measure a life by making a catalogue of what no longer hurts and what can no longer hurt.
Is the insensitivity a mark of wisdom? Or just a sign that the scarring has become too thick?
Many things still rankle of course, and I find that I need to kill the Buddha as I meet him on the road—again and again and again.
The biggest problem with being a religious convert is the enormous temptation to proselytize.
If I hadn't found refuge in the Dharma, if I didn't occasionally seek company in the Sangha, if I didn't perpetually take solace in the Buddha, I wouldn't know where I'd be.
But just because I was lost doesn't mean others need to be found.
Use the poison as the antidote.
Turn the arrows into flowers.
Transform your vices into virtues.
Learn to be happy and be gay.