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Int J Biol Sci 2022; 18(2):800-808. doi:10.7150/ijbs.65457 This issue Cite
1. Department of Clinical Laboratory, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
2. Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
*These authors contributed equally to this work.
The RHO GTPase family has been suggested to play critical roles in cell growth, migration, and polarization. Regulators and effectors of RHO GTPases have been extensively explored in recent years. However, little attention has been given to RHO family interacting cell polarization regulators (RIPORs), a recently discovered protein family of RHO regulators. RIPOR proteins, namely, RIPOR1-3, bind directly to RHO proteins (A, B and C) via a RHO-binding motif and exert suppressive effects on RHO activity, thereby negatively influencing RHO-regulated cellular functions. In addition, RIPORs are phosphorylated by upstream protein kinases under chemokine stimulation, and this phosphorylation affects not only their subcellular localization but also their interaction with RHO proteins, altering the activation of RHO downstream targets and ultimately impacting cell polarity and migration. In this review, we provide an overview of recent studies on the function of RIPOR proteins in regulating RHO-dependent directional movement in immune responses and other pathophysiological functions.
Keywords: RIPOR1, RIPOR2, RIPOR3, RHO GTPase, RHOA, RHOC, 14-3-3 protein, polarization, migration
Cell migration plays a fundamental role in both normal physiological processes such as immune responses and abnormal pathologies such as tumor metastasis [1]. Establishing and maintaining front-rear polarity is integral to the movement of cells in specific directions. Cell polarization necessitates dynamic reorganization of the actin cytoskeleton, temporal changes in gene transcription, spatial localization of specific proteins, and reorientation of secretory trafficking [2].
The mechanisms underlying cell polarization and migration involve cooperation among multiple proteins, such as the small GTP-binding proteins RHO GTPases [3]. In mammals, 20 members of the RHO GTPase family have been identified and classified into eight subfamilies: RHO, RHOBTB, RHODF, RND, RHOUV, RHOH, CDC42 and RAC [3,4]. A better understanding of RHO GTPase function and how their activities are regulated is needed to elucidate the mechanisms of cell polarization and migration.
RHO GTPases act as molecular switches to control multiple cellular events by switching between an inactive GDP-bound state and an active GTP-bound state [5-7]. This cycling activity is strictly regulated by three groups of factors: guanine nucleotide exchange factors (GEFs), which promote GDP/GTP exchange; GTPase-activating proteins (GAPs), which facilitate the hydrolysis of GTP to GDP; and guanine nucleotide dissociation inhibitors (GDIs), which prevent nucleotide exchange and regulate relocalization of RHO GTPases, thereby inhibiting their access to downstream effectors.
One of the most well-characterized subfamilies of RHO GTPases is the RHO subfamily, which contains three highly homologous proteins: RHOA, RHOB, and RHOC. In addition to other classic RHO regulators, recent studies have linked RHO family interacting cell polarization regulators (RIPORs) as novel partners of RHO subfamily members [8-11]. The RIPOR family is composed of RIPOR1 (also called FAM65A), RIPOR2 (also called FAM65B, C6orf32, KIAA0386, or PL48), and RIPOR3 (also called FAM65C).
In this review, we summarize recent research on the functions of RIPOR1 and RIPOR2 in the RHO signaling pathway, with a focus on advances in deciphering the mechanisms of RIPOR proteins in RHO-dependent directional movement in immune responses, tumor cell metastasis and other pathophysiological functions.
In 1997, RIPOR2 was first cloned from differentiating cytotrophoblasts and reported as a novel gene with markedly elevated mRNA expression during the differentiation of DMSO-induced HL-60 cells [12]. RIPOR2 was then found to induce the formation of neurite-like protrusions in the murine myoblast cell line C2C12 in 2007 and in quail myoblast QM-RSV cells in 2008 [13,14]; however, little is known about how RIPOR2 modulates cell morphogenesis. Later studies by Rougerie et al. and our research group demonstrated that RIPOR2 directly bound to RHOA in neutrophils [10]. RIPOR2 led to a reduction in active RHOA and RHOA-mediated transcriptional activation, suggesting that RIPOR2 is a RHOA inhibitor. Moreover, inhibition of RHOA activity, as well as overexpression of RIPOR2, suppressed T cell migration, further confirming the involvement of RIPOR2-RHOA in cell polarization [8]. Collectively, these findings demonstrated that RIPOR2 is involved in regulating T cell and neutrophil migration through RHOA signaling. Since these findings, an increasing number of studies have been carried out to decipher the important roles of RIPORs in cell migration and polarization. In 2016, Mardakheh et al. revealed that RIPOR1 directly interacted with active RHOA, RHOB and RHOC [11]. In contrast, the functions of RIPOR3 have not yet been elucidated.
RIPOR1, RIPOR2 and RIPOR3 share an identical RHO-binding motif in the N-terminal region (Figure 1), which shows moderate similarity to the RHOA-binding homology regions (HRs) in several known RHOA effectors, such as protein kinase N-1, -2, and -3 (PKN1, PKN2, PKN3), Rhotekin (RTKN1), and Rhophilin (RHPN1). The invariant glycine (Gly155 in RIPOR2) and alanine (Ala156 in RIPOR2) are highly conserved among these RHOA effectors. Except for these two amino acids, the amino acids within the RHO-binding motif (RBM, aa 138-210) in RIPORs are also highly homologous, especially Arg151 and Leu152. Mutation of Arg151 and Leu152 to Ala or of Gly155 and Ala156 to Arg in RIPOR2 abolish the interaction between RIPOR2 and RHOA [10]. The N-terminal parts of RIPORs are evolutionarily conserved, and more than 70% identity is observed among the RIPORs. In addition, a RIPOR1 mutant lacking the N-terminus failed to interact with RHOA and was unable to inhibit RHOA activity [10]. These observations highlighted the importance of the N-terminal segment of RIPOR proteins. RIPOR3 shows high homology with RIPOR1/2 in the RBM, implying that RIPOR3 is a potential interacting protein of RHOA. Indeed, we confirmed this interaction between RIPOR3-RHO proteins through the RBM by coimmunoprecipitation assays (data not published). Finally, a brief phylogenetic analysis of RIPORs suggested that RIPORs are encoded only in vertebrate genomes and the RBM is highly conserved in all RIPORs irrespective of species (data not shown).
Analysis of the protein sequences of RIPORs also revealed some unique structures among RIPORs. For example, RIPOR1 contains a HEAT repeat domain in its C-terminal region, although the function of this domain has not been elucidated (Figure 1).
Based on PhosphoSitePlus data, the three RIPORs are potentially phosphorylated. Upon chemoattractant stimulation, RIPOR2 showed a motility shift and was stabilized in neutrophils. This phenomenon was phenocopied in cells treated with the phosphatase inhibitor okadaic acid [10]. However, deletion of phospholipase C (PLC) β2/β3 and phosphatidylinositol-3-kinase (PI3K)γ impaired the motility shift of RIPOR2 [10]. Therefore, chemokines induce RIPOR2 phosphorylation in part through PKC and AKT [9-10,15]. Treatment with the proteasome inhibitor MG132 stabilized RIPOR2, implying that its turnover is controlled by the proteasomal pathway [9-10]. These findings shed light on the underlying mechanisms by which RIPOR2 phosphorylation might impede its degradation by the proteasome. Moreover, in cardiomyocytes, RIPOR2 can be phosphorylated by phosphatase and tensin homolog-induced putative kinase 1 (PINK1) to participate in autophagy [15].
The domain architecture of RIPOR family and sequence alignment of amino acids of the RBM in RIPORs (RIPOR1: NP_078795.2,RIPOR2: NP_055537.2,RIPOR3: NP_543019.2) with PKN1 (NP_998725.1), PKN2 (NP_006247.1), PKN3 (NP_037487.2) and the HR of RTKN (NP_149035.1) and RHPN1 (NP_443156.2).
Notably, stimulation with the chemokine CCL19 was found to disrupt the RIPOR2-RHOA interaction, an effect that was abrogated by phosphatase inhibitor treatment [9], implying that chemokine-induced RIPOR2 phosphorylation decreases the interaction between RIPOR2 and RHOA.
RIPOR2 phosphorylation also alters its subcellular localization during cell migration. Stimulation with the chemokine fMLP induced the accumulation of RIPOR2 at the leading edge of neutrophils. However, the distribution of the nonphosphorylated RIPOR2 S5A mutant (incapable of phosphorylation by PKC/AKT) was not affected by chemokine stimulation [10]. Interestingly, phosphorylation was found to result in relocalization of RIPOR2 from the plasma membrane to the cytosol, thereby disrupting the interaction of RIPOR2 with RHOA [9]. In summary, phosphorylation of RIPOR2 not only disrupts the RIPOR2-RHOA interaction but also impacts the subcellular localization of RIPOR2.
Data from the PhosphoSitePlus database indicate that the RIPOR1 and RIPOR3 proteins contain several phosphorylation sites [16]. For this reason, we speculate that both RIPOR1 and RIPOR3 may be phosphorylated, although additional experiments are warranted.
Other PTMs, including ubiquitination of RIPOR1/2, acetylation of RIPOR2/3 and arginine methylation of RIPOR3, have also been deduced from high-throughput mass spectrometry data [16]. However, the precise cellular consequence of these PTMs on RIPORs remains elusive.
14-3-3 family proteins (also called tyrosine 3- monooxygenase/tryptophan 5-monooxygenase activation proteins (YWHAs)) are highly conserved proteins that are widely expressed in eukaryotic cells [17,18]. 14-3-3 family members were recently identified as novel interacting proteins of RIPOR1/2 [10,11]. These proteins bind to Ser/Thr-phosphorylated proteins as hetero- or homodimers by recognizing three types of conserved motifs: RSXpSXP, RXY/FXpSXP, and pSX1-2-COOH [17,19]. Protein sequence analysis showed that RIPORs have many potential 14-3-3 binding sites (Figure 2). The 14-3-3 consensus sequences in RIPORs also match the substrate motifs for many protein kinases. Our work showed that RIPOR2 can be phosphorylated by PKC and AKT at serine residues 21, 37, 341, 523, and 535 in regions that match the 14-3-3 consensus sequences. Not surprisingly, the RIPOR2 S5A mutant showed a much lower affinity for 14-3-3 proteins [10]. As regulatory molecules, 14-3-3 proteins modulate the conformation, activity, and subcellular localization of their interacting partners [20]. Indeed, overexpression of 14-3-3 proteins led to higher levels of RIPOR2, implying that 14-3-3 proteins promote RIPOR2 stabilization [10]. In addition, several 14-3-3 proteins interacted with RIPOR1 in a RHO-dependent manner [11], although the effects of 14-3-3 proteins on RIPOR1 have not been examined.
The potential 14-3-3 binding motifs in RIPORs.
The biological significance of the role of RHO in T cell development, activation, and migration is well documented [21-23]. RIPOR2 functions in the adhesion, polarization, and migration of T cells in a RHOA-dependent manner. Depletion of RIPOR2 by small interfering RNAs increased the percentage of cells exhibiting arrest in vitro. A similar effect was further verified in lymphocyte arrest on blood vessel endothelial cells [8]. Inhibition of RHOA activity, as well as overexpression of RIPOR2, was found to impede T cell migration. In contrast, the RIPOR2 Δ113 mutant, which was unable to bind RHOA, did not exert this effect [8]. RIPOR2 was found to inhibit GTP loading on RHOA and preferentially bind active RHOA proteins to block RHOA activity in neutrophils [10]. These observations suggest that the function of RIPOR2 in cell migration is mediated mainly through RHOA inhibition.
In addition to its role in T cell migration, RIPOR2 is reported to act as a negative regulator of cell proliferation in a RHOA-independent manner. The RIPOR2 S5A mutant but not RIPOR2 RL151-152AA lost its antiproliferative effect [25]. Previous studies showed that 14-3-3s are binding partners of HDAC6, a cytoplasmic deacetylase that promotes cancer cell proliferation in a deacetylase activity-dependent manner. HDAC6 regulated 14-3-3 interactions in a deacetylation activity-dependent manner [26]. Furthermore, RIPOR2 inhibited the deacetylase activity of HDAC6. Consequently, phosphorylated RIPOR2 interacted with 14-3-3 and HDAC6 to form a tripartite complex [24-25], and this complex suppressed HDAC6 activity, resulting in disruption of the mitotic spindle formation and mitotic failure in resting T cells [25].
The active forkhead box O1 (FOXO1) transcription factor is required for maintaining the quiescence of T cells by promoting RIPOR2 transcription and expression [8,25]. In T cells, T cell receptor (TCR) stimulation led to cytoplasmic localization of FOXO1 in a PI3K-AKT pathway-dependent manner [27]. Notably, under TCR stimulation, RIPOR2 expression was reduced upon TCR activation [25]. Thus, an increased cytoplasmic localization of FOXO1 upon TCR stimulation can be hypothesized to negatively regulate the expression of RIPOR2, which is essential for T cell proliferation.
In summary, these results indicate that RIPOR2 plays roles in the migration and proliferation of T cells by modulating the functions of RHOA and HDAC6, respectively.
Autophagy is a highly conserved process in all eukaryotes in which intracellular components are transported to lysosomes for degradation and recycling [28,29]. Distinct from microautophagy and chaperone-mediated autophagy, macroautophagy is well established and involves the formation of autophagosomes [29]. Autophagosomes carry and deliver cargo to lysosomes and then fuse with lysosomes to form autolysosomes, in which the contents are subsequently degraded [28-29]. Autophagy functions as a major cytoprotective process by maintaining cellular homeostasis and recycling cytoplasmic contents, and dysfunction of autophagy has been associated with multiple human diseases [30-31].
Zhou et al. reported that RIPOR2 is involved in autophagy. A circRNA termed autophagy-related circular RNA (ACR) activates PINK1 expression by directly binding to DNMT3B and blocking DNMT3B-mediated promoter methylation of PINK1. RIPOR2 is a downstream target of PINK1. PINK1 phosphorylates RIPOR2 at serine 46, and phosphorylated RIPOR2 inhibits autophagy and cell death in cardiomyocytes [15]. However, it remains unclear whether phosphorylated RIPOR2 governs autophagy in a RHOA-dependent manner.
During the development of skeletal muscle, myoblasts from myotubes recognize other myoblasts, adhere, and fuse to form multinucleated myotubes; this process is critical in cellular differentiation and fusion [14,32]. Multiple proteins, such as myogenic transcription factor (MRF4), neural cell adhesion molecule (N-CAM), and M-cadherin, are involved in these tightly regulated processes [13,33-34]. Accumulating evidence suggests that RIPOR2 also functions as one of the fundamental regulators of myogenic differentiation [14,35].
In 2007, RIPOR2 was first characterized in human fetal muscle cell differentiation [14]. RIPOR2 silencing reduced the protein level of myogenin, a marker of early myogenic differentiation, and abrogated primary human fetal muscle cell differentiation and fusion [14]. RIPOR2 was also implicated in the formation of filopodia, which has been reported to be critical in key morphogenesis events at certain stages of muscle development [14,36]. RIPOR2 binds to HDAC6 and dysferlin, the protein mutated in limb girdle muscular dystrophy 2B. The RIPOR2-HDAC6-dysferlin trimeric complex is transient, and RIPOR2 expression is necessary for the complex to form. Treatment of myogenic cells with pan-HDAC or HDAC6-specific inhibitors alters RIPOR2 expression. Inhibition of RIPOR2 expression in developing zebrafish results in abnormal muscle with low birefringence and myoseptal tears and in increased embryonic lethality [35].
RHOA has also been implicated in myoblast fusion [32]. Active RHOA was found to induce lysosomal degradation of M-cadherin, one of the cell adhesion molecules involved in the fusion of myoblasts [33,37], and abrogated the interaction between M-cadherin and its partner p120-catenin, leading to inhibition of myoblast fusion [32]. Given that RIPOR2 expression increases during muscle cell differentiation and that the amount of active RHOA decreases during myoblast fusion, it is possible that the effects of RIPOR2 on myoblast fusion events in membrane protuberances depend on RHOA inhibition. Therefore, RIPOR2 is likely to act as an inducible repressor of RHOA activity to promote cell-cell fusion during muscle or placenta formation.
N-CAM, another RIPOR2 binding partner, is also related to myoblast fusion [13,37-38]. However, the functional impact of the N-CAM-RIPOR2 interaction on myoblast fusion is still unknown.
Cochlear hair cells are crucial for hearing due to their role in converting sound-induced vibration into electrical signals. This function relies on the specialized bundle of stereocilia at the apical surface of the hair cell [39]. Stereocilia are tapered at their base near their site of insertion into the apical hair cell and are formed into a unique stairstep shape [40]. Accumulating evidence suggests that the structure and dynamic properties of the actin core are essential for the functions of stereocilia [40].
Several studies have indicated that a loss-of-function mutation in RIPOR2 is correlated with hearing [41-44]. Diaz-Horta et al. identified a splice site mutation (c.102-1G>A) in the RIPOR2 gene (MIM611410) that completely cosegregated with the phenotype in a large consanguineous Turkish family with recessive nonsyndromic, prelingual, profound hearing loss [41]. The enrichment of RIPOR2 in the stereocilia of both inner and outer hair cells may suggest that a lack of functional RIPOR2 can hinder the development of the mechanotransduction apparatus. Moreover, knockdown of RIPOR2 causes hearing loss in zebrafish. A later report showed that RIPOR2 was localized in the basal taper of the mechanically sensitive stereocilia of hair cells, where oligomeric RIPOR2 interacted with RHOC to form the circumferential ring, an essential component of the taper region [42]. RIPOR2 negatively regulates the structure and orientation of the hair cell stereociliary bundle via a mechanism based partially on the RIPOR2-nonmuscle myosin heavy chain 9 (MYH9) interaction to stabilize MYH9 [43]. MYH9-mediated coupling between microtubules and actomyosin is involved in the formation of nonmuscle myosin II (NMII) [45]. Given that RIPOR2 inhibits HDAC6 activity and that HDCA6 destabilizes microtubule structures by promoting α-tubulin deacetylation, it might be possible that RIPOR2 contributes to microtubule flexibility rather than lengthening kinocilia in inner and outer hair cells [43,46].
However, it might be possible that RIPOR2 functions in maintaining normal hearing through mechanisms other than affecting the MYH9 abundance or inhibiting HDAC6 activity [44]. An in-frame deletion (c.1696_1707del) mutation in RIPOR2 has been linked with hearing loss [44]. Strikingly, this mutation did not alter RIPOR2's function in filopodia formation, suggesting that a RHO-independent mechanism may exist. Further studies are needed to clarify the RHO-dependent and RHO-independent mechanisms of RIPOR2 in mediating hair cell function.
According to data from The Cancer Genome Atlas [47], the expression of RIPOR2 is downregulated compared to that in normal tissues in the majority of cancer types, especially in uterine corpus endometrial carcinoma and diffuse large B-cell lymphoma. However, the precise roles of RIPOR2 in tumorigenesis and progression are still poorly understood.
Zhang K et al. reported that RIPOR2 was upregulated in PC3 holoclones with cancer stem cell characteristics. PC3 cells, a line of androgen-independent human prostate cancer cells, were divided into three morphologically distinct colonies: holoclones, meroclones, and paraclones. Compared with meroclones and paraclones, holoclones exhibited increased self-renewal activity and proliferation capability. In addition, gene expression patterns differed among the three colony types. The expression of RIPOR2 was significantly upregulated in PC3 holoclones. Furthermore, PC3 prostate tumor-initiating cells with the molecular profile RIPOR2high/melanotransferrin (MFI2)low/LEF1low increased tumor angiogenesis [48]. Despite these findings, the molecular mechanisms underlying RIPOR2-related angiogenesis are still unknown.
Among the RIPOR family members, RIPOR2 is the best studied. As described above, RIPOR2 is involved in a plethora of physiological and pathological processes, such as immune cell polarization, migration, and autophagy (Figure 3). Despite their structural similarities, RIPOR1 and RIPOR3 show potentially distinct functional features relative to RIPOR2.
To better understand the potential functions of the RIPOR proteins, we examined the mRNA expression patterns of RIPORs in 79 human tissues [49] (Figure 4). RIPORs are differentially expressed in human tissues. RIPOR2 is predominantly expressed in immune cells, including T cells, B cells, NK cells, monocytes and myeloid cells. Our previous study showed that the RIPOR2 mRNA level is much higher in bone marrow neutrophils than in other cell types [10]. In contrast, RIPOR1 and RIPOR3 are ubiquitously expressed in the majority of tissues. The distinct expression patterns of RIPORs suggest the different biological functions performed by these proteins. RIPOR1 regulates Golgi apparatus reorientation during HeLa cell migration. It functions as a scaffold protein that links RHO proteins to Golgi-localizing proteins (Cerebral Cavernous Malformation-3 (CCM3) and mammalian STE20-like protein kinase 3 (MST3), and MST4), resulting in relocalization of Golgi-localized proteins from the Golgi apparatus toward the leading edge of cells during directional cell migration. In response to wounding, the Golgi apparatus was found to be reoriented in HeLa cells at the edge of the wound. Depletion of RIPOR1 impeded Golgi apparatus reorientation and directional migration of HeLa cells following wounding. This effect was consistent with that of RHOA activity inhibition [11]. Therefore, the divergent interacting proteins of RIPORs may account for their distinct functions (Table 1).
Interactors of RIPOR Family
Protein | Interactors | Process/Pathway Affected | Cells | Reference |
RIPOR1 | RHOA | linking active RHO subfamily and Golgi-localizing proteins to regulate Golgi reorientation | HeLa cells | [11] |
RIPOR2 | RHOA | Inhibiting RHOA activity to negatively regulate immune cell migration | T lymphocytes Primary neutrophils | [8-10] |
HDAC6, 14-3-3 | Interacting with HDAC6 deacetylase and 14-3-3 to inhibit T-cells proliferation | T lymphocytes | [25] | |
HDAC6, Dysferlin | Interacting with HDAC6 and dysferlin to promote myogenic differentiation | Primary muscle cells | [35] | |
HDAC6 | Inhibiting HDAC6 activity to maintain the structure and function of the auditory hair cell bundle | Hair cells | [43] | |
MYH9 | Stabilizing non-muscular myosin heavy chain 9(MYH9) to maintain the structure and function of the auditory hair cell bundle | Hair cells | [43] | |
RHOC | Interacting with RHOC to form a RIPOR2 ring-like structure critical for mechanosensory hair cell function | Hair cells | [42] | |
N-CAM | Interacting with NCAM | - | [13] | |
RIPOR3 | unknown | - | - | - |
The pathophysiological functions of RIPOR2. (A) In primary neutrophils, the front localization of phosphorylated RIPOR2 stabilized by 14-3-3 leads to unequal distribution of active RHOA. (B) In resting T cells, RIPOR2 combines with RHOA and exerts suppressive effects on its activity at the plasma membrane to maintain immune cells in a quiescent state. Upon chemokine stimulation, 14-3-3 interacts with phosphorylated RIPOR2 by protein kinases, breaking the RIPOR2-RHOA interaction and relieving RHOA inhibition. (C) In resting T cells, FOXO1 upregulates RIPOR2 protein level, and then phosphorylated RIPOR2 binds to 14-3-3 and HDAC6 to form tricomplex, inhibiting deacetylation of α-tubulin and thereby discouraging mitotic spindle assembly. (D) By interacting with DNMT3B, ACR suppresses DNA methylation of PINK1 to upregulate the expression of PINK1, increasing RIPOR2 phosphorylation, which contributes to autophagy inhibition and cell death in cardiomyocytes. (E) Tricomplex formed by HDAC6, RIPOR2, and dysferlin inhibits the deacetylation activity of HDAC6, resulting in the accumulation of acetylated α-tubulin, which is believed to promote muscle cell differentiation. (F) RIPOR2 is located in the basal taper of mechanically sensitive stereocilia of hair cells, where it interacts with RhoC to form a circumferential ring--RIPOR2 oligomerization, a structure necessary for the taper region. As well as stabilizing MYH9 in hair cells, RIPOR2 inhibits HDAC6 activity in order to regulate stereociliary bundle structure.
High-density oligonucleotide arrays are used to examine patterns of gene expression in a panel of 79 human tissues. The data is from BioGPS.
Analysis of RNA-seq data in The Cancer Genome Atlas showed that RIPOR1 is upregulated in gastrointestinal tumors such as cholangiocarcinoma, colon adenocarcinoma, esophageal carcinoma, and liver hepatocellular carcinoma. Intriguingly, the expression level of RHOA in these gastrointestinal tumors is also increased [47]. Given that RHOA is generally considered an oncogene [50], we hypothesize that RIPOR1 may act as an oncogene or tumor suppressor in a context-dependent manner, although further investigations are warranted in the future.
Likewise, little is known about the biological functions of RIPOR3 in cells. As no studies have yet examined RIPOR3, we can only speculate from its mRNA expression profile that the functions of RIPOR3 may differ from those of RIPOR1 and RIPOR2. Further investigations are needed to decipher the biological functions of RIPOR3 and determine whether these functions are altered in pathological conditions.
These findings illustrate the unity and versatility of the RIPOR family in health and disease. As a first insight, the RIPORs share many similarities in amino acid sequences, protein interaction partners, and biological functions. Moreover, the differences in their roughly homologous amino acid sequences might account for their varying functions through interactions with proteins in addition to RHO (A, B, and C).
Here, we highlight the roles of RIPORs in physiological and pathological contexts - especially roles linked with the actin cytoskeleton, including cell polarization, migration, adhesion, and organelle trafficking - based on studies conducted in this decade. Currently, it is clear that the regulation of RHO GTPase functions is shared by three members, but their other molecular functions are still poorly understood. Given their sequence divergence and tissue-specific expression, RIPORs are expected to function in diverse biological processes. More research is needed to clearly clarify the roles of RIPORs in homeostasis and disease.
RIPOR: the RHO family interacting cell polarization regulators; GEFs: guanine nucleotide exchange factors; GAPs: GTPase activating proteins; GDIs: guanine nucleotide dissociation inhibitors; MST4: mammalian STE20-like protein kinases 4; PKN1: protein kinase N-1; RTKN1: Rhotekin; RHPN1: Rhophilin; PLC: Phospholipase C; PI3K: phosphatidyl-inositol-3-kinase; PINK1: phosphatase and tensin homolog-induced putative kinase 1; HDAC6: histone deacetylase 6; FOXO1: forkhead box O1; TCR: T cell receptor; DNMT3B: DNA methyltransferase 3 beta; MRF4: myogenic transcription factor; N-CAM: neural cell adhesion molecule; MYH9: non-muscular myosin heavy chain 9; NMII: non-muscle myosin II; MFI2: melanotransferrin; CCM3: Cerebral Cav-ernous Malformation-3 protein; MST3: Mammalian STE20-like protein kinases 3.
All authors contributed to manuscript conceptualization and preparation. All authors have read and agreed to the published version of the manuscript.
This work was in part supported by the National Natural Science Foundation of China (No. 91954106, 81872109 to K.G.), the Natural Science Foundation of Shanghai (No. 18ZR1430100 to K.G.) and the Open Research Fund of State Key Laboratory of Genetic Engineering, Fudan University (No. SKLGE-2111).
The datasets generated and analyzed during the current study are available from the corresponding authors on reasonable request.
The authors have declared that no competing interest exists.
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32. Charrasse S, Comunale F, Grumbach Y, Poulat F, Blangy A, Gauthier-Rouviere C. RHOA GTPase regulates M-cadherin activity and myoblast fusion. Mol Biol Cell. 2006;17:749-59
33. Kaufmann U, Martin B, Link D, Witt K, Zeitler R, Reinhard S. et al. M-cadherin and its sisters in development of striated muscle. Cell Tissue Res. 1999;296:191-8
34. Krauss RS. Regulation of Skeletal Myoblast Differentiation by Drebrin. Adv Exp Med Biol. 2017;1006:361-73
35. Balasubramanian A, Kawahara G, Gupta VA, Rozkalne A, Beauvais A, Kunkel LM. et al. Fam65b is important for formation of the HDAC6-dysferlin protein complex during myogenic cell differentiation. FASEB J. 2014;28:2955-69
36. Segal D, Dhanyasi N, Schejter ED, Shilo BZ. Adhesion and Fusion of Muscle Cells Are Promoted by Filopodia. Dev Cell. 2016;38:291-304
37. Ishido M, Uda M, Masuhara M, Kami K. Alterations of M-cadherin, neural cell adhesion molecule and beta-catenin expression in satellite cells during overload-induced skeletal muscle hypertrophy. Acta Physiol (Oxf). 2006;187:407-18
38. Charlton CA, Mohler WA, Blau HM. Neural cell adhesion molecule (NCAM) and myoblast fusion. Dev Biol. 2000;221:112-9
39. Goutman JD, Elgoyhen AB, Gomez-Casati ME. Cochlear hair cells: The sound-sensing machines. FEBS Lett. 2015;589:3354-61
40. Manor U, Kachar B. Dynamic length regulation of sensory stereocilia. Semin Cell Dev Biol. 2008;19:502-10
41. Diaz-Horta O, Subasioglu-Uzak A, Grati M, DeSmidt A, Foster J 2nd, Cao L. et al. FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing. Proc Natl Acad Sci U S A. 2014;111:9864-8
42. Zhao B, Wu Z, Muller U. Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function. Elife. 2016 5
43. Diaz-Horta O, Abad C, Cengiz FB, Bademci G, Blackwelder P, Walz K. et al. Ripor2 is involved in auditory hair cell stereociliary bundle structure and orientation. J Mol Med (Berl). 2018;96:1227-38
44. de Bruijn SE, Smits JJ, Liu C, Lanting CP, Beynon AJ, Blankevoort J. et al. A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss. J Med Genet. 2020
45. Asensio-Juarez G, Llorente-Gonzalez C, Vicente-Manzanares M. Linking the Landscape of MYH9-Related Diseases to the Molecular Mechanisms that Control Non-Muscle Myosin II-A Function in Cells. Cells. 2020 9
46. Janke C, Montagnac G. Causes and Consequences of Microtubule Acetylation. Curr Biol. 2017;27:R1287-R92
47. Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B. et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017;19:649-58
48. Zhang K, Waxman DJ. PC3 prostate tumor-initiating cells with molecular profile FAM65Bhigh/MFI2low/LEF1low increase tumor angiogenesis. Mol Cancer. 2010;9:319
49. Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S. et al. BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol. 2009;10:R130
50. Jansen S, Gosens R, Wieland T, Schmidt M. Paving the Rho in cancer metastasis: Rho GTPases and beyond. Pharmacol Ther. 2018;183:1-21
Corresponding authors: E-mail: kungaoedu.cn (K.G.); E-mail: 2000672edu.cn (S.W.).
Received 2021-7-28
Accepted 2021-11-27
Published 2022-1-1


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Tyson Fury is rightly wary but Dillian Whyte's win would be a seismic shock
Portugal, "and when one big heavyweight catches the other guy clean all plans and predictions go out the window.
I know Tyson is the best heavyweight out there but I have been through so much to get this fight. I also know I can hurt him.
Tyson Fury weighs-in at 18st 12lb 13oz for his WBC heavyweight title fight with Dillian Whyte at Wembley.
A couple of days later, in the shadow of the huge arena where Fury will defend his WBC title against his British challenger, the world champion and undoubted favourite was just as blunt and respectful.
"Dillian's definitely a fearless guy. I've sparred him a lot in the past and he didn't show any weaknesses.
So I'm anticipating a good fight, a real tough fight, because Dillian is a strong heavyweight who is in the top five in the world.
He poses a real challenge, as do all these heavyweights. It only takes one punch to knock a man out as we've seen many times.
Unhappy Leclerc rues run choices in Imola F1 qualifying
Unhappy Leclerc rues run choices in Imola F1 qualifying
Learn more

subset: commoncrawl


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Meet The Dirt Company, a visionary business on a mission to revolutionize household cleaning products with sustainability and health in mind. Their focus lies in:
- Creating clean, eco-friendly laundry products that respect the planet and your health
- Utilizing plant-based, organic, and 99% natural ingredients
- Prioritizing reusable, refillable, and recyclable packaging
- Minimizing waste and carbon footprint
The Dirt Company has designed sleek glass bottles, which are not only safe and durable but also recyclable. They have replaced single-use plastic containers, reducing the environmental impact significantly. Their refill packs are made from about 40% post-industrial waste and can be returned, sanitized, and reused multiple times through their innovative Refill, Return program.
All their formulas are ultra-concentrated, which means you only need a small amount for each wash, minimizing packaging and carbon footprint. To top it off, The Dirt Company donates 50% of its profits to cleaning up the ocean, proving their dedication to making a positive impact on the environment.
Their products are designed for maximum efficiency and minimum waste. When a refill pack reaches the end of its life, The Dirt Company recycles it into a 100% recycled scoop for your machine wash, ensuring nothing goes to waste. So, say goodbye to single-use jugs and hello to a cleaner, greener, and healthier laundry experience.


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A recent notice of proposed rulemaking by the U.S. Department of the Treasury's Financial Crimes Enforcement Network (FinCEN) demonstrates how the agency intends to balance protecting individual privacy and access to law enforcement, McGuireWoods New York partner Jeff Chapman and Pittsburgh partner Alex Madrid and associate Chelsey Klein wrote in Law360.
In the March 22, 2023, article, "Banks and Beneficial Ownership: Striking the Right Balance," the authors explained that FinCEN requires certain companies registered to do business in the United States to report beneficial ownership information (BOI) regarding the individuals or entities that own or substantially control the company. This highly sensitive information is crucial for regulators and law enforcement, but also is of interest to creditors, the media and financial institutions.
The notice proposes creation of a nonpublic database with multitiered secured access to different categories of authorized users. It also restricts which types of financial institutions may access the database, and how. Financial institutions seeking to query the database must obtain the consent of the company that reported the BOI to FinCEN.
The authors said requiring such consent will place a substantial burden on the financial institutions seeking information and arguably undermines one of the important reasons BOI is collected, since the request for consent may alert wrongdoers that they are under investigation. Other important questions about the proposed rule, which would take effect Jan. 1, 2024, remain unanswered.
It is "unclear whether regulators will expect or require financial institutions to use the BOI database as part of their 'know your customer' due diligence or whether institutions may continue to utilize their preexisting due diligence processes," the authors wrote. "While the notice demonstrates FinCEN's attempt to strike the right balance between competing interests, financial institutions will be watching carefully for further guidance before next year."


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Recently, a bitcoin whale with an untouched wallet for 12 years moved 400 BTC, worth approximately $11 million, to multiple addresses. This is not the only instance of long-term HODLers awakening after years of inactivity – a different dormant BTC whale transferred over 2,000 BTC for the first time in nine years last week.
- The Satoshi-era BTC whale sent 360 BTC (worth around $9.8 million) to one address and transferred the remaining 40 BTC ($1.1 million) to various others.
- This HODLer had not moved their stash since 2011, only two years after the primary cryptocurrency's first block was mined by Satoshi Nakamoto, known as Genesis Day.
- Another dormant BTC wallet recently sent out 2,071.5 BTC (worth over $60 million at the time) to an address starting with "bc1q."
- The whale's full stash before the transaction was 6,071.5 BTC, equivalent to around $4 million on December 19th, 2013.
- In addition, a wallet that participated in Ethereum's initial coin offering in 2016 transferred one ETH to a new address this week.
- There is no clear explanation for these sudden transactions, but some speculate that it could be a protection measure taken by crypto investors with substantial holdings.
- Others joke that the whales may have finally located their private keys, allowing them to conduct these transactions.
- Bitcoin's price has recently been on a decline, losing over 8% of its value in the past week and currently trading at approximately $27,300.


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Seeking Talents for "The Flesh Lusts for Power" - Shorts
Giselle, an off-course college student, discovers the perfect love of Jesus Christ, but when she wants more from him, she seeks to get closer to a priest who she sees as the liaison between herself and the divine. The Flesh Lusts for Power follows Giselle's rollercoaster of a conversion, which she keeps secret from her family, and serves simultaneously as a defense and critique of Catholicism, presenting it as a beautiful yet volatile element.
5 roles
Giselle has always been a chameleon, changing to become what she thinks others want her to be. She is always discerning who she needs to be in any given situation. She is quick, observant, and an absolute slave to the praise of others. Who she was never mattered, but the trophies, medals, and certificates of achievement did; but after 21 years of striving after wind, she is tired. However, when, from a charismatic new priest named Paul she hears that there is a love that is completely
Paul is the new priest at The Church of St. Theresa. He is quietly charismatic, eloquent, and humble. Every movement he makes denotes that he knows he is serving a higher power, and when people speak to him, they see a reflection of Christ. When he meets Giselle, he sees someone in need of his help. He also sees opportunity. Paul needs not only to be loved but adored, so his motives for helping Giselle are not as pure as they initially seem. He needs her to adore him as she does Jesus.
Bernice is Giselle's suffocating mother. In her eyes, the world responds to image alone. Because of this, she mercilessly pushes Giselle toward success in all areas of life, no matter the cost. Bernice, however, also has her own turmoil to trudge through. Early life experiences with the Church and Elizabeth, her Hard Core Catholic mother, alienated her completely from the faith. She has never looked back, learning instead how to rely solely on herself, instead of looking to the divine for help.
Elizabeth is Giselle's grandmother and Bernice's mother. The Catholic faith has always been at the center of her life. She tried her best to raise Bernice to be Catholic, but failed to do so. She considers this her personal failure and tries to correct it every time they see each other, using methods others would call abrasive, but Elizabeth believes are heartfelt. Following the recent death of her beloved husband, Andy, her motivation to get her family to church has become stronger than ever.
Scott is Giselle's father. Once an affectionate soul, he has been completely worn out by years of being subjected to Bernice's racetrack pace of life. Unlike Giselle, he is almost oblivious to his own dissatisfaction. Nowadays, all he seeks is peace. Whenever we see him, he is blocking out the conflicts of the house. Though he may not subscribe to it, he sees Bernice's ideology concerning image and achievement as a harsh truth of life and believes she is doing her best to help Giselle.


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Bitcoin experienced a volatile ride yesterday after the US CPI data for April was announced, following days of little movement. Altcoins also saw similar fluctuations, with most currently trading slightly lower than the previous day.
Bitcoin's Price Fluctuations
Bitcoin failed to surpass $30,000 on Saturday and remained steady without any significant changes until Monday and Tuesday, when it fell to $28,000. Expecting volatility after the US CPI announcement, which was slightly lower than expected, bitcoin's price rose immediately from $27,500 to over $28,300. However, just minutes later, the cryptocurrency experienced a sharp drop of over $1,500, reaching a six-week low of under $27,000. The volatile trend continued for the next few hours before reversing again.
Currently, bitcoin is trading at around $27,500 with a market cap just over $530 billion and an increasing market share of almost 47%.
ATOM's Price Increase
The altcoins experienced similar price fluctuations yesterday, but most are trading at slight losses. Although Ethereum rose to nearly $1,900 during the bitcoin pump phase before dropping below $1,800, it is currently trading slightly above the latter. Binance Coin, Ripple, Dogecoin, Polygon, Tron, and Shiba Inu are also slightly in the red on a daily scale. On the other hand, Cardano, Solana, Polkadot, and Litecoin have insignificant gains. ATOM is the exception, experiencing a notable gain of approximately 6% in the past 24 hours and trading above $10.
The total market cap is over $1.130 trillion, but has lost approximately $70 billion during the previous week.


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Duct Cleaning review in
Chris and Cory were very professional, friendly, and expedient in their work. They communicated clearly with their customer, and did an overall great job! Well done!
- Approximate cost of services:
- $647.00
Was this review helpful?
- Company Response
Thank you so much for your kind words! We truly appreciate your feedback and are delighted to hear that Chris and Cory provided a professional, friendly, and expedient service. Clear communication with our customers is a top priority for us, and we're glad to know that it was evident during your experience. We'll make sure to pass along your compliments to Chris and Cory for their great job. If there's anything else we can assist you with in the future, please don't hesitate to reach out. Thank you again for your support!


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, Canadian - April 09, 2015
My friend Amber and I recently completed the Inca Trail to Machu Picchu with Inca Trail Reservations . We had a really great time on our 4 day, 3 night hike... despite all the rain ! I can't decide which aspect of the trek was better... the unbelievable sights or the amazing meals provided by the Inca Trail Reservations chef and porters !
Every day of the hike had its own highlights, not just the final day. There are many interesting Incan sites to explore along the way and reaching the historical site of Machu Picchu was incredibly rewarding and breathtaking ! Thanks for the experience, Inca Trail Reservations !
Review of : Inca Trail 4 days / 3 nights


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Submitted to: Meeting Abstract
Publication Type: Abstract Only Publication Acceptance Date: 4/8/2016 Publication Date: N/A Citation: N/A Interpretive Summary: Technical Abstract: Damage to maize crops by insect herbivores such as beet and fall army worm causes significant impact in the Southern United States in terms of both yield loss and insecticide use. Enhanced understanding of how maize can defend itself against such attacks at a molecular level will enable development of maize varieties with enhanced insect resistance through transgenic manipulation and molecular breeding programs. An important first step in this task is the characterization of the molecular and biochemical responses of fully sequenced maize inbred lines to insect herbivory. To this end we performed comparative physiological, molecular and biochemical analyses of the inbred maize lines B73 and W22 to caterpillar herbivory and elicitor treatment. Differences that were observed between the two lines in regards to chemical defenses and caterpillar feeding provide insight into maize defenses against insect herbivory. |


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By making modernizations and updates to your elevator machinery, you can not only extend the life of your units and parts, but you can also save money on replacement and energy costs. Check out a few updates you can make to your lifts, stair chairs and elevators that can save you cash in the long run.
Replacing the Motor Drive
In the past, motor generator technologies were able to convert AC power to DC power in an effort to supply a DC hoist motor. That was a time when DC motors had better torque control than AC motors. But today's modern AC digital drives don't require the need to convert from AC to DC power, bringing with them many advantages, such as:
- You get a lot more energy savings, as power is only being consumed while the elevator is in use.
- Regenerative drives can contribute power back to the building.
- Less heat is generated, translating to less work from your building's cooling systems.
Old DC drive systems suck up more than 40,000 kWh of electricity every year! By modernizing your inefficient elevator, you can save 72 percent in energy costs.
Replacing the DC Motor
At the same time that you replace the drive, you should undertake conversion of the DC motor. By doing this, you get even more cost savings:
- Lower your electricity bills with better power factor correction.
- When you have a higher efficiency system, you use less energy.
- Heat reduction reduces the amount of cooling needed in your building.
Smart Controllers
Modern digital controllers use statistics and advanced algorithms that can result in much higher performance with much better energy efficiency. That's because smart controllers continually scan all activity and reassign calls as needed to cut down on wait time and energy consumption. By implementing modern controllers and new hoist motors, you can reduce your electrical usage by 60 percent.
Elevator Upgrades
If your existing elevators are old, you may want to consider updating them. Modernized lifts provide a better customer experience, to be sure, but all that new technology can also help your units last longer, run more smoothly, and detect issues before they become serious. Upgrading now can save you unnecessary downtime and hurried replacements, which saves you money in the long run.
It's easier to prevent future issues when you keep a detailed operational log of your elevators. You can track how often each cab is used and called, which helps you predict which ones will need repairs or maintenance first. Nipping the problem in the bud on a timeline that works for you keeps you from an emergency situation that leads to hasty, expensive actions.
Contact Mowrey Elevator
If it's time for a repair or update on your elevator, stair lift or chair lift, come to us for all the latest energy efficient parts and components. Contact us today or browse our website to learn more.


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Attract Good Luck with 9 Gemstones of Navratri
- Posted by: Admin
Navratri, the significant and auspicious Hindu festival celebrated across India, fills the devotees of Maa Durga with joy, love, and faith. This auspicious Hindu festival is observed for nine days.
Each day of the Navratri festival denotes a different form of Goddess Durga, and every facet of Goddesses holds a unique significance. As per the Vedas, the commencement of the New Year and the change of seasons invoke various forms of Devis, and believers across India worship these avatars to seek blessings and strength to overcome hardships.
This year, the Navratri festival starts on 15th October 2023 and will continue till 24th October 2023. The Ghatasthapana or Kalashsthapana mahurat is from 11:44 AM – 12:30 PM on 15th October. The festival is also known as, "Shardiya Navratri". The populace across the country will be honoring Maa Durga by meditating, keeping fasts, praying, seeking blessings, and decking themselves up in the best attire and accessories.
Some females will opt for new expensive rings, and some will adorn precious gemstones to beautify their persona and drift away from their adversaries. It's ultimately a celebration of goodness's victory over evil.
Table of contents
In this blog, we have put together a list of Navratna gemstones for Navratri, explaining their meaning, association, and significance regarding Navratri and the nine forms of Devi Durga.
So, scroll down to read the surprising facts and benefits of wearing a particular navratna gemstone on each day of Navratri, and have a blessed year ahead!
Why Navratna Gemstones for Navratri?
According to ancient texts, the cosmic energies of the gemstones get activated during these auspicious nine nights. Using the relationship between the Navratna gemstones for Navratri and the occasion, one can amplify its spiritual benefits, blessings, and energies.
Let's look at different gemstones to wear on each day of Navratri and why.
DAY 1 - Ruby or Manikya
The first form or avatar of Goddess Durga is Maa Shailputri. This avatar symbolizes peace, purity, innocence, and calmness. She is a provider of prosperity, fortune, and spiritual awakening. Like Ruby stone or Manikya, the orangish-red color is dedicated to Maa Shailputri, representing vitality and warmth.
As per Vedic astrology, wearing a Ruby or Manikya on the 1st day of Navratri brings incredibly good luck, positive energy, fame, success, wealth, stability, and a life full of happiness. It can also help cure multiple physical diseases such as ulcers and tuberculosis.
A Lucky Navratras Tip – Recite the mantra "Om Hrim Sum Suryay Namah" after wearing Manik stone for 108 times.
Read More : Top 5 Amazing Benefits of Ruby Stones
DAY 2 - Yellow Sapphire or Pukhraj
The second form of Maa worshipped on the 2nd day is Maa Brahmacharini. She is the Goddess of Meditation, also known as Devi Tapasvini or Devi Yogini. It is one of the simplest, calmest, and most magnificent forms that eliminate anger and instill peace.
As per Vedic Astrology, wearing Yellow Sapphire or Pukhraj on the 2nd day of Navratri can help maximize these benefits and avail characteristics of Maa Durga in this form. It provides the wearer prosperity, good luck, knowledge, intellect, financial stability, spirituality, wisdom, and creativity.
A Lucky Navratras Tip – Recite the mantra "Om Brim Brihaspataye Namaha" after wearing Yellow Sapphire stone for 108 times.
Read More:- The Transforming Yellow Sapphire: Its Benefits and Significance
DAY 3 - Garnets or Raktamani
The third avatar of Devi Durga is Maa Chandra Ghanta. She is shown holding weapons, symbolizing a win over evil. She bestows her devotees with courage, strength, and bravery to keep negative energy away and fight challenges in life, just like Garnets or Raktamani.
According to expert astrologists, wearing red-colored Garnets or Raktamani on the 3rd day of Navratri protects the wearer from negative energies and dangers. Moreover, it fosters fearlessness, grace, vitality, and bravery in the wearer to help them overcome any hurdle in life.
A Lucky Navratras Tip – Recite the mantra "Om Suryay Namaha" for 108 times.
Read More : The Top 5 Benefits of Almandine Garnet Stone
DAY 4 - White Sapphire or Diamond
The fourth form of Devi worshipped on the 4th day is Maa Kushmanda. "Ku" means little, "Ushma" means warmth, and "Anda" means egg; together, it means "Creator of the Universe". The cosmic energy emitted by Maa Kushmanda can be attained using White Sapphire or Safed Pukhraj.
Wearing a White Sapphire or Safed Pukhraj on the 4th night of Navratri can bless the wearer of the gemstones with a blissful marriage, healthy pregnancy, and childbirth. It can also eliminate insecurities and lack of confidence, boost creativity, induce new ideas, and improve a luxurious lifestyle.
A Lucky Navratras Tip – Recite the auspicious manta "Om Shun Shukraye Namah" after wearing Safed Pukhraj.
DAY 5 - Red Coral or Moonga
Maa Skandmata is the fifth form of Devi Durga. She gave birth to Kartikeya or Sakand, after which she was named "Skandmata". She bestows her devotees with love, attachment, affection, and stability in relationships. All these properties can be energized with Red Coral or Moonga.
Wearing Red Coral or Moonga on the 5th night of Navratri can benefit people suffering from the malefic effects of Mars in their birth chart. Maa Skandmata blesses her devotees and the wearer of Red Coral or Moonga with power, prosperity, wisdom, wealth, and intellect.
A Lucky Navratras Tip – Recite the mantra "Om Bho Bhomay Namaha" for 108 times after wearing Moonga.
DAY 6 - Emerald or Panna
The sixth avatar of Goddess Durga is Maa Katyayani. The angry form of the Goddess in which she slays the demon named Mahisasur and takes the form of "Shakti". She can present authoritative powers to her devotees, and an Emerald stone or Panna can help imbibe this blessing.
According to Vedic astrology, wearing an Emerald or Panna on the 6th night of Navratri can help manifest the characteristics of Maa Katyayani. The 6th-day avatar and Emerald are both associated with Mercury. Thus, it can help balance the malefic effects and offer energy, intellect, and wealth.
A Lucky Navratras Tip – Recite the mantra "Om Budhaye Namha" after wearing the Panna stone for 108 times.
Read More:- Emerald: The Benefits of the Prosperity Stone
DAY 7 - Blue Sapphire or Neelam
The 7th day of Navratri is devoted to Maa Kaalratri. She is considered the destroyer of all evil spirits, negative energies, demons, and ghosts. The color of the 7th day is also royal blue, just like a Blue Sapphire or Neelam.
Wearing a Blue Sapphire or Neelam helps attain the same characteristics as Maa Kaalratri making one fearless and shield from all negativities that prevent you from achieving goals. The 7th-day avatar and Blue Sapphire or Neelam share the same features and bring health, wealth, and prosperity.
A Lucky Navratras Tip – Recite the mantra "Om Sham Shanicharaya Namah" for 108 times after wearing Neelam.
Read More:- Blue Sapphire: Receive Instant Positive Life-changing Results!
DAY 8 - Pearl or Moti
The eighth form of Devi Durga is Maa Mahagauri. On this day of Navratri, devotees worship Maa Mahagauri wholeheartedly with pure intentions, and all their past, present, and future wrongdoings are nullified. Wearing a Pearl stone or Moti can help amplify these benefits.
According to astrology, wearing a Pearl or Moti on the 8th day of Navratri can help imbibe the blessings of Maa Mahagauri. It helps bring peace, calmness, and clarity of thought, improve senses, relax the mind, resolve conflicts, and improve financial stability.
A Lucky Navratras Tip – Recite the mantra "Om Son Sonmay Namaha" for 108 times to gain abundant blessings.
DAY 9 - Cat's Eye or Lahsuniya
The 9th day is dedicated to Maa Siddhidatri. The name "Siddhidatri" means the supernatural giver, signifying that this form of Devi Durga is the metaphysical origin that can satisfy a believer's desires. Wearing a Cat's Eye or Lahsuniya can help boost these blessings.
Wearing a Cat's Eye or Lahsuniya on this day can help overcome hurdles and miseries in life and make every dream come true. It makes the wearer courageous and reduces the malefic effects of Ketu. It will improve financial status, prosperity, and luxurious life.
A Lucky Navratras Tip – Recite the gemstone mantra "Om Shram Shreem Shroum Sah Ketave Namah" for 108 times after wearing Cat's Eye stone.
The nine divine forms of Goddess Durga transmit their mystical energies to the gemstones. You too can gain good health, wealth, fame, prosperity, intellect, love, a luxurious lifestyle, and more this Navratri.
All you need to do is consult an expert astrologer at GemsRoot! Our astrologers at GemsRoot can help you attain the benefits of these auspicious nine days by recommending the most fruitful gems according to your zodiac sign and birth chart. They are available 24x7 for customer support and respond to any queries you may have.
Therefore, bless and empower yourself by adorning lucky Navratna gemstones from GemsRoot.


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Canadian Spa Basket Cover Lifter. This Basket Cover Lifter is the ideal choice to complement your Hot Tub, making cover removal and replacement a quick, one-handed operation and reducing wear and tear. Our patent pending design also has two rollers to make moving the cover in and out of the basket a snap. Gas shocks to assist in raising and lowering cover. Mounts directly behind spa too remove cover. Fits up to 96(2.4m) Spas and requires clearance of 32 (80cm). Has rollers to assist larger covers for easy on and off. Basket Cover Lifter Installation. The item "Basket Hot Tub Cover Lifter Basket Holder Easy One Hand Gas Assist" is in sale since Tuesday, April 7, 2020. This item is in the category "Garden & Patio\Swimming Pools, Saunas & Hot Tubs\Hot Tub Covers". The seller is "mr_spa" and is located in Redhill, Surrey. This item can be shipped to United Kingdom.
- Country/Region of Manufacture: Canada
- Type: Cover Lifter
- Brand: Canadian Spa Company


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Risk for death 3.49 times higher for those receiving no cancer treatment versus standard treatment or treatment with minor deviations.
Fewer than one in 20 patients diagnosed with colorectal cancer (CRC) in Sub-Saharan Africa (SSA) receive guideline-concordant treatment, according to a study published in the September issue of the Journal of the National Comprehensive Cancer Network.
Lucia Hämmerl, M.D., from Martin Luther University Halle-Wittenberg in Germany, and colleagues assessed concordance of CRC treatment with National Comprehensive Cancer Network Harmonized Guidelines for SSA. A random sample of 653 patients with CRC diagnosed from 2011 to 2015 from 11 population-based cancer registries in SSA was obtained. For 54 percent of the patients (traced cohort), information on clinical characteristics, treatment, and/or vital status was collected from medical records in treating hospitals.
The researchers found that 52.8 percent of the traced patients were from countries with a low human development index (HDI). Overall, 55.1 and 73.6 percent of patients had colon cancer and nonmetastatic (M0) disease, respectively. Only 3.1 percent of those with M0 disease received guideline-concordant treatment, while 20.6, 31.7, and 35.1 percent received treatment with minor deviations, treatment with major deviations, or no treatment, respectively. In patients who received no cancer-directed therapy, the risk for death was 3.49 times higher than in patients who received standard treatment or treatment with minor deviations. The risk for death was 1.67 times higher for patients from countries with a low versus a medium HDI. Overall survival was 70.9 and 45.3 percent at one and three years, respectively.
"For policymakers and institutions in SSA, we hope our study results can be an important basis for targeted and meaningful investments and measures to improve the outcomes and survival of patients with CRC in the region," senior author Ahmedin Jemal, Ph.D., from the American Cancer Society in Atlanta, said in a statement.


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H2I File
What are H2I files and how to open them
Are you having problems opening a H2I file or are you simply curious about its contents? We're here to explain the properties of these files and provide you with software that can open or handle your H2I files.
What is a H2I file?
A .H2I file is a H2cdimage Sectors Status file.
We have not yet analyzed in detail what these files contain and what they are used for. We're working on it.
How to open H2I files
Important: Different programs may use files with the H2I file extension for different purposes, so unless you are sure which format your H2I file is, you may need to try a few different programs.
We have not yet verified any programs for Windows that work with this specific file format. If you know one, please use the 'Suggest a program' link below. Thanks!
Last updated: October 8, 2012
Help us help others
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Feeling old and stiff? Just do this!
While it's easy to blame daily stiffness on age, your lived experience alone won't tell the whole story. For whatever reason, many individuals who struggle with body aches settle for suffering with them, either because they're 'getting up there in age' or 'it's just how life is'. Well, this viewpoint is absolute baloney. Whether you're 25 or 85, there are strategies you can implement today to get you feeling younger, spryer, and more functional with everyday tasks.
One of the most important lessons to learn in fitness is that age isn't all that important if your mindset and exercise routine is on point. Sure, there is a natural degradation of joints and tissues, and your overall fitness capacity will drop over the years, but that's no reason to fight back for what control you still have. Hint — exercise is medicine and it's one of your best friends when it comes to navigating soreness, chronic pain, and old age.
It's time to introduce a comprehensive movement program to get you moving more and fighting back body stiffness. You may just surprise yourself with how much you can control the destiny of your aging!
3 strategies to heal your body soreness.
First off, if you have any known injury histories or chronic conditions, please check in with your provider before adhering to the advice below. While integrating more movement will naturally benefit your life, it's key to work with someone who knows what volume and modalities are right for you. Without further ado, let's dive into the program!
1) Make sitting your enemy.
It's simple, we were made to move. Unfortunately, in our modern world, sitting is commonplace. While small bouts are completely fine, sitting on your ass for hours on end will bring many complications. This includes but is not limited to back pain, hip discomfort, a decreased range of motion, and decreased endurance with physical tasks. It's no mistake that the seniors who get off the couch are the ones who stay functional for longer.
There is significant evidence to prove that excessive sedentary behavior will also spike the risk of colon, lung, and uterine cancer. It can even reduce one's mental health, concentration, and productivity. These economic and health effects cause the global cost of physical inactivity to be estimated at 68$ billion.
If you want to maintain your health & fitness as you age, one of the biggest factors is how often you move throughout your day. To get started, try following these 5 strategies!
- Stand up every 30 minutes — even for 30 seconds. This is one of the most valuable pieces of health advice out there.
- Set timers on your phone for sedentary leisure activities. If this doesn't fly, consider being active in front of your screen! Who says you can't do chair squats while watching TV?
- Avoid technology use in awkward positions. If you're going to use your phone, ensure you're seated up with the elbow not supported. Endless scrolling in bed will only add to your soreness and pain.
- Plan your social life around physical activity. If you find friends who can inspire you to move, you'll be much more inclined to do more physical activity throughout your week.
- View chores as an opportunity to move and feel better! Do your best to spread these tasks throughout the day to keep you active.
2) Mobility work before and after bed.
Typically, we feel most sore and creaky waking up from a night's sleep, and after the day is through. To give your tissues an extra boost, try 5 minutes of mobility before and after bed. Even though this time commitment is minimal, it has the power to alter the trajectory of your musculoskeletal health. Yes, this is a big claim…but it's also true. Daily mobility work is one of the most overlooked health strategies, and if done correctly, can change the game for all ages and populations.
To get you started, here are 3 simple movements that will be accessible to nearly all populations. As you go through them, ensure that you take your time, access deep breaths, and only move within your pain-free range of motion.
Lumbar Rocks
Cues: 10–15 reps / side. Start by lying on your back with the knees bent to approximately 90 degrees. Next, raise your hands behind your head and slowly rock your knees from side to side. Begin with a smaller range of motion, gradually increase the length of each rep as you warm up. This is a great active way to get movement through the low back and pelvis.
Cat Cows
Cues: 10–15 reps. On inhale, elevate mid-spine while lowering the neck. On exhale, depress mid-spine and raise the neck. Strive for as much pelvic and shoulder blade movement as possible! If you want a great secondary option, try 'thread the needles' to add more spinal rotation into the mix.
Thoracic Extension Stretch
Cues: 20–30 second hold x 2, or 5 reps with 5–10 second hold each. Move to behind your chair and grab onto the backrest. Step away with your feet until you can hinge with your hips without bending at the elbows. Next, focus on lowering the chest towards the floor while keeping the arms straight. This will significantly improve your overhead mobility while giving you a moment to decompress the spine. Feel free to hold this position or do a rep-based approach where you hinge and hold for 5–10 seconds before resetting and doing it again.
This is one of the most powerful mobility exercises out there because it challenges the spine, overhead mobility, shoulders, hamstrings, and more. If you need a quick reset after a few hours of work, or you're just feeling sore and stiff, this movement can help tremendously! Please note, this exercise can also be completed by using a wall.
3) Walk, hiking, and other activities that get your heart pumping.
Walking is a simple act that can make a huge difference for your musculoskeletal and mental health. If you're really struggling, try 5–10 minute bouts and gradually work your way up. The more frequent the better so spread out a few 'workouts' per day rather than trying to walk 3 or 4 miles at a time. For those who have severe chronic pain, even getting across the room will likely be worthwhile. Here are just a few pros to walking:
- mobilizing the low back and lower body
- increasing heart rate and blood flow
- supporting your independence
- decreasing anxiety and worry
- getting outdoors (so, so valuable for all facets of health)
Whether you can walk 2 miles or just a few steps, commit to continuous movement! This simple act will remind you that there's always something you can be doing to fight back on your pain and work towards recovery.
A huge factor around increased sedentary behavior and stiffness is osteoporosis. To delay the demineralizing of your bones, the maintenance of weight-bearing activities is absolutely key. This is why older folks should keep on walking, hiking, or even running! While modifications to volume or intensity may be in order, it's completely possible to keep on moving if you doing it wisely.
Make time for physical activity when you're young, so you don't have to waste it being immobile later on.
In closing,
While there are certain elements of aging we can't avoid, there are still plenty of things we can do to prevent stiffness in the later years. If you're serious about maintaining activity well into your 70s and 80s, take this program very seriously. While these habits are incredibly simple, consistently applying them to your daily life can change the game.
You're only as old as you think you are! Use exercise as medicine and enjoy reaping all the benefits it has to offer. You got this.
This is original content from NewsBreak's Creator Program. Join today to publish and share your own content.


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BWF Indoor FunDay
Join us for a spectacular day of laughter and excitement at our ultimate Family Funday! 🎉 Get ready to bounce, play, and create unforgettable memories with your little ones aged 0-12 years old. 🌈
Important update: gate tickets unavailable.
Purchase them here until they sell out or until the night before Fun Day.
🅿 Limited parking: Bear in mind that our venue has restricted parking.
🚗 Carpool: We encourage you to lift share or arrange drop-offs to make the most of our limited parking and to be eco-conscious. Please ensure that any children dropped off are accompanied by an adult at all times.
BWF FunDay
Get ready to embark on a spectacular adventure at our ultimate Family Funday! 🎉 We're thrilled to invite you and your little ones, aged 0-12 years old, to join us for a day filled with boundless joy, laughter, and unforgettable memories. 🌈
Our goal is to create a magical experience for your family, and we've pulled out all the stops to make it happen. As you step into our enchanting world of bouncy castles, you'll witness your children's imaginations taking flight, their smiles radiating pure happiness, and their laughter filling the air. 🏰🎈
But that's just the beginning! Our bouncy castles are only the tip of the excitement iceberg. Prepare to be amazed as your little adventurers explore a wonderland of thrilling activities. They'll navigate exhilarating slides that set hearts racing, tackle inflatable obstacle courses designed to test their bravery and agility, and let their imaginations run wild in a playground of endless possibilities. 🤸♀🌟
This isn't just an event; it's a celebration of family, fun, and togetherness. Bring your loved ones, your friends, and your boundless enthusiasm as we come together to create cherished memories. Mark your calendars because this day promises to be a highlight of your year, a day of unforgettable laughter, an abundance of bouncy castles, and endless entertainment. 🎪✨
Don't let this magical experience slip through your fingers – join us for an epic day of epic fun during the school holidays and make memories that will last a lifetime! See you there!


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What is Responsive Email Design?
Email marketing is one of the most effective forms of digital marketing, allowing businesses to reach their target audience directly in their inbox. However, as technology continues to evolve and change, so do the ways in which people access their email. To remain effective, it is important that email marketers adopt a design that is optimized for multiple devices and screen sizes. This is where responsive email design comes in.
Defining responsive email design
Responsive email design is a method of designing emails that automatically adjusts its layout and content to the screen size and device it is being viewed on. This allows for a consistent and optimized viewing experience for the recipient, regardless of the device they are using to view the email. Responsive email design aims to create a seamless user experience for the recipient, providing them with the information they need in an easy-to-read format without having to zoom in or scroll sideways.
Benefits of Responsive Email
Responsive email design offers several key benefits for businesses and marketers. Firstly, it allows for a consistent and professional appearance, regardless of the device used to view the email. This can help build trust and credibility with the recipient, improving their chances of engaging with the email and taking action. Additionally, responsive email design can help improve emails' deliverability, reducing the chances of them being marked as spam or sent to the recipient's junk folder.
Creating a Responsive Email Design
When creating a responsive email design, several key factors must be considered. Firstly, keeping the layout simple and easy to read is important, using clear, concise text and a clean, uncluttered design. This will help to ensure that the email is optimized for smaller screens and will not become cluttered or difficult to read. Additionally, it is important to use responsive HTML and CSS, to ensure that the email adjusts to the screen size and device it is being viewed on.
Testing and Optimizing Responsive Email
Once a responsive email design has been created, it is important to test it thoroughly to ensure that it is working correctly and providing the desired user experience. This can be done by sending test emails to a variety of different devices and checking the layout and content of each one. Any issues or problems can then be corrected, and the email optimized to provide the best possible experience for the recipient.
Responsive email design is an essential aspect of email marketing in today's digital landscape, allowing businesses to reach their target audience with an optimized and consistent viewing experience, regardless of their device. By keeping the layout simple, using responsive HTML and CSS, and thoroughly testing and optimizing the design, businesses can ensure that their email marketing efforts remain effective and relevant, helping to drive engagement and results.


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This is a story with a slight twist. The characters are real people being myself, my best friend and his older sister. This is something that I really wish had actually happened. I have given us all fictional names so I am Tony, my best friend is Phil and his sister is Susan.
I had met my best friend Phil whils... » Read more


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Camiseta Real Madrid As the title of the holiday suggests, Thanksgiving is about giving thanks for all the things in your life. but giving thanks—or, in other words, expressing gratitude—is more than just a nice holiday ritual. The practice can have a seriously positive impact on your health, happiness, and overall well-being.
Let's take a look at why practicing gratitude is a must if you want to be your happiest, healthiest self, as well as some fun gratitude practices to incorporate into your Thanksgiving Day celebrations this year.
How does gratitude impact health and happiness?
First things first. before we jump into specific gratitude practices you can use to make yourself happier and healthier this Thanksgiving (and all year round!), let's quickly cover how, exactly, gratitude influences health and happiness.
Gratitude can make you a happier, healthier person in a variety of ways, including:
Gratitude increases happiness and combats depression. One study found that people who practiced gratitude exercises experienced increased happiness and decreased rates of depression—and according to data from UC Davis, practicing two gratitude activities (writing letters expressing gratitude and counting their blessings) reduced the risk of depression in at-risk patients by 41 percent over a six-month period.
Gratitude strengthens relationships. research has shown that gratitude makes you more likely to provide help to others, which can go a long way in forging strong relationships—which play a important role in both health and happiness.
Gratitude lowers stress. According to the data from UC Davis, people who practice gratitude have 23 percent lower levels of cortisol—also known as the "stress hormone."
Gratitude lowers blood pressure. The data from UC Davis also shows that people who practice gratitude have 16 percent lower diastolic blood pressure and 10 percent lower systolic blood pressure than their less grateful counterparts.
Gratitude improves self-esteem. In a 2013 study, researchers found that athletes who expressed gratitude (both to their coaches and teammates) reported higher levels of self-esteem than their fellow athletes who didn't show the same gratitude.
Gratitude has also been shown to strengthen the immune system, improve sleep quality, lower inflammation…the benefits go on and on.
Clearly, if you're looking to increase your health and happiness, gratitude is a solid way to do it. but how, exactly, do you practice gratitude—especially on Thanksgiving, gratitude's unofficial holiday?
Kick off your Thanksgiving meal with a round of gratitude
For most people, the highlight of Thanksgiving is the big Thanksgiving meal. but before you dig into that turkey, mashed potatoes, and pumpkin pie, why not take a minute to incorporate a bit of gratitude into your holiday dinner?
Before you start eating, take a moment to express one thing you're grateful for this Thanksgiving—for example, the opportunity to share the holiday with family and friends. Then, encourage everyone else at the table to do the same.
Kicking off your meal with a round of gratitude is a terrific way to honor the "thanks" element of Thanksgiving—so make sure to carve out a moment for that thanks before you start carving your turkey.
Use Thanksgiving as a jumping off point for a gratitude practice
Expressing gratitude before your Thanksgiving meal is great. but gratitude is like any other practice; the more you do it, the more benefits you'll experience as a result. Or, in other words, if you really Camiseta Vissel Kobe want to reap the benefits? It needs to extend past Thanksgiving—and work its way into your regular routine.
If you don't have a regular gratitude practice, Thanksgiving is a terrific opportunity to start. use the holiday as a jumping off point for establishing a more regular gratitude practice. For example, you might start your Thanksgiving by jotting down three things you're grateful for—and then make a commitment to do the same thing each morning through the new Year (or beyond!).
The longer and more consistently you practice gratitude, the happier and healthier you'll be—so this Thanksgiving, make a commitment to yourself to make gratitude a regular part of your routine.
Start a gratitude chain
Practicing gratitude yourself can have a major impact on your health and happiness. but why stop there? Why not encourage your friends, family, and loved ones to practice gratitude—and reap all the health and happiness-boosting benefits in the process?
This Thanksgiving, consider starting a "gratitude chain"—and spreading the benefits of a gratitude practice throughout your network. For example, you might text pals or family members one thing you're grateful for this Thanksgiving, and encourage them to keep the chain going by texting something they're grateful for to their pals or family members. Or, if you want to keep things going past Thanksgiving, you might starta text chain with a few loved ones, and have a check-in each week where you each share something you're feeling particularly grateful for.
The point is, a gratitude practice will make you a happier and healthier person—but it will make you and your loved ones happier and healthier when you share that practice.
This information is for educational purposes only and is not intended as a substitute for medical diagnosis or treatment. You should not use this information to diagnose or treat a health problem or condition. always check with your doctor before changing your diet, altering your sleep habits, taking supplements, or starting a new fitness routine.
Deanna deBara
Deanna deBara is a freelance writer based in Portland, OR. She covers a wide range of wellness topics, including fitness, nutrition, relationships, and mental health. Her work has appeared on Greatist, Men's Health, Ravishly, The Fix, What's good by The Camiseta Selección de fútbol de Portugal Vitamin Shoppe, and more.


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With offices based in Connecticut, Illinois, and Massachusetts, we are able to support families locally, across the country and around the world. Please call us at 847-440-6707 to schedule an office or telephone.
Phone Number: 847-440-6707
Fax: 866-707-3814
135 Chestnut St #3104
New Britain, CT 06050
PO Box 3160 151 Rantoul St.
Beverly, MA. 01915


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Quizzes & Activities
Market Structures (Revision Quizlet Activity)
- Level:
- A-Level, IB
- Board:
- AQA, Edexcel, OCR, IB, Eduqas, WJEC
Last updated 1 Jan 2022
Here are twenty key terms relating to market structures. We have produced a key term glossary and some quizlet revision activities to go with them.
Key terms to revise
Barriers to Exit: Costs associated with a decision to leave a market / industry, for example, lost goodwill with customers
Bi-lateral monopoly: Situation where there is a single (or few) buyer(s) and seller(s) of a given product
Cartel: Formal agreement among firms. members may agree to fix prices, share total industry output and so on
Collusion: When rival companies cooperate for their mutual benefit, common in an oligopoly
Concentration ratio: Measures the proportion of an industry's output accounted for by the largest firms.
Contestable market: An industry with no entry barriers where the threat of competition impacts on the behaviour of existing firms
De-regulation: Opening up of markets to competition by reducing one or more barriers to entry
Duopoly: Any market that is dominated by two suppliers
Duopsony: Two major buyers in a market each of whom has significant buying power with suppliers
Entry barriers: Ways to prevent the profitable entry of new suppliers in the long run
Franchise monopoly: When the government grants a business the sole right to sell or manufacture a product or service in a particular area
Legal Entry Barriers: Barriers including patent protection, legal franchises, trademarks and copyright
Local monopoly: A monopoly limited to a specific geographical area
Market Power: Selling power arising from a firm having a large enough share of the industry to be able to set prices
Market structure: Described the number of firms, the nature of costs, the extent of barriers to entry and the bargaining power of consumers on the demand-side of a market
Monopolistic competition: Market structure with many buyers and sellers of slightly different products and easy entry to, and exit from, the industry
Monopsony: When a single buyer controls the market for a particular good or service
Nationalisation: The transfer of ownership of a firm from the private to public sector.
Oligopoly: A market dominated by a few producers, each of which has control over the market
Privatisation: Sale of state-owned companies to the private sector, normally through a stock market listing.
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Jialing Cai, a 25-year-old marine biologist and amateur photographer has been awarded Ocean Photographer of the Year 2023. Her top-prize-winning capture of a paper nautilus gracefully gliding on a piece of ocean debris was taken during a blackwater dive following a volcanic eruption in the Philippines. Cai has been awarded a £1,500 cash prize, the opportunity to join an Ocean Census expedition, an Instagram takeover at SeaLegacy plus more.
Cai's journey into the realm of blackwater photography was ignited by her fascination with diel vertical migration, where zooplankton ascends from the deep ocean to the surface under the cover of night. She recalls her moment of revelation, saying, "That hit me like lightning. My professor was telling me the deep sea was within my reach, that it would come to me. That realization was mind-blowing. It's why I've become so obsessed with blackwater photography."
• Check out the best underwater housing - perfect for taking high-res photos beneath the waves
The top three entries stood out against thousands of submissions showcasing the undeniable beauty and fragility of marine life. Andrei Savin secured second place with his astonishing image of a crab nestled amidst the vibrant tentacles of a sea anemone while third place was awarded to Alvaro Herrero Lopez-Beltran for his poignant image of an entangled whale, a stark reminder of the perils our oceans face.
In the fine art category, Jade Hoksbergen came out on top impressive the judges with her image of a whale shark and its entourage of remoras titled The Maldives. Todd Glaser's aerial shot of a group of surfers beneath a rainbow at the famous Benzai Pipeline landed him first place in the adventure category while Gergo Rugli placed second with another surf shot and Franco Banfi followed behind in third with a capture of a scuba diver in East Greenland.
Sylvie Ayer was awarded winner of the conservation: hope category for her photo of a manatee enjoying the crystal clear waters of the Homosassa River while Florian Ledoux was crowned the winner of conservation: impact for his image of a polar bear cub on fragile ice. In the young photographer's category. In the Young Photographer's category, Jarvis Small came first with his capture of a bodyboarder paddling out to sea.
In total, prizes worth more than £500,000 have been awarded to the overall and category winners which include a range of cash prizes, experiences, inclusion in Oceanographic Magazine, and an exhibition taking place in Sydney.
The OPOTYA is more important now than ever, as it not only does highlights the relationship humans have with the ocean, it also highlights the difficulties it faces often due to human impact.
Each year the OPOTYA donates 20% of its profits to its partner charities working on crucial conservation projects all over the world. To view the full gallery of winning images head to the Oceanographic website.
Check out the best cameras for wildlife photography so you can capture beautiful shots from a distance


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Nota bene: If you buy through the links in this article, we may earn a small share of the profits.
The jacket never really goes away, does it? Sure, the temperate weather means packing up your puffers and down jackets in favor of a spring wardrobe, but a lightweight jacket (or two…or three, or four) that you can trust for breezy evenings and scorching dates remains a must-have. Yes, it would be nice to jump directly to tees and sandals or shorts and swolos, but the seasonal shift is wrought with unpredictable weather and sudden chills. Thus, a jacket you can trust is essential.
25 Spring Style Essentials Every Guy Should Own
The season is full of surprises. Here's what you'll need to survive.The good news here is that are all kinds of lightweight jackets — layers from brands like Todd Snyder, Everlane, Nike and more — that work just fine in higher temps, from easy-wear shackets and pullovers to the more elegant chore coat and Harrington styles. Below, we've put together a guide to all lightweight jacket styles you should absolutely know, and we've highlighted a few styles of each.
The Denim Jacket
Ask just about anyone what kind of coat they most associate with the phrase "lightweight," and chances are you'll hear "denim jacket." Sturdy and full of character, a hearty denim jacket is as classic a jacket style as they come. True to its centuries-old heritage, the Levi's Type 1 Trucker is particularly solid for the season ahead, with a vintage-inspired look and cinch back for an adjustable fit.
Three Foolproof Ways to Wear a Denim Jacket This Spring
Classic though it may be, it's a surprisingly difficult item to styleThe Shacket
The lowly shirt-jacket may seem like a lightweight afterthought, but when the suns blessed rays break through on an otherwise cold day, you'll be glad you have an easy-on layer to enjoy them in. Versatile, lightweight and industrious — that's the shacket way.
The Best Shirt Jackets for Men Never Go Out of Style
Behind every great man, there's an even greater shacketThe Leather Jacket
There's never a bad time to bust out old faithful — that is, your go-to leather jacket. In the event you don't have one, now is the time to invest. Sure, it's a real investment, but the payoff is looking like a badass rockstar for the rest of your life.
The 10 Best Men's Leather Jackets
You'll look cool. Like, really cool.The Track Jacket
So you want to look like a tennis star/mob boss/very Irish? Look no further than the classic track jacket. A stalwart layer for decades, the knit zip style provides just enough breathable warmth and comfort for cool days, along with an abundance of in-your-face style. Our recommendation? Go bold and snag the matching bottoms, too.
The Work Jacket
Rugged, rip-proof and reliable — the work jacket is an uncontested behemoth in the realm of lightweight jackets. Of course, there's the revered Flint and Tinder Waxed Trucker Jacket (great for surviving the apocalypse), which we'll never stop recommending, but there are tons of other styles from heritage brands like Dickies and Carhartt for you to get your blue-collar stolen valor on, too.
Which Flint and Tinder Waxed Jacket Is Right for You?
There's no one right answerThe Trench Coat
Trench coats and their ilk are decidedly dressier option than many of the styles on this list, making them ideal for the worker bee and corner office creature (or, that dude who likes to keep it sharp). The best feature a water-resistant coating — it's the reason Percival's suave Sherlock Jacket is one of our favorite looks of the season — that'll protect your Sunday best from springtime conditions without looking like a total bum.
Elevate Your Rainy Day 'Fits With the Best Trench Coats for Men
The style has a storied lineage — it's time for you to add to its historyThe Harrington Jacket
Even looked at an old photo of Steve McQueen or Paul Newman? There's a strong chance it featured a Harrington jacket. Sporting flap pockets and retro high-button collar situation, it's a devilishly unique way to signal that, yes, you might indeed own a boat. Or at least know how to sail one.
The Bomber Jacket
The bomber jacket might have uptight military origins (the style was originally commissioned for the U.S. Army by Dobbs Industries, and subsequently their offshoot, famed Alpha Industries), but in 2023, the style couldn't be more casual. Denoted by a cropped, banded cut and utilitarian finish, it's an easy-to-wear style that'll pair nicely with your sickest kicks and crispy denim.
The Chore Coat
If we had to pick just one style for the now, it would almost undoubtedly be the chore coat. Well-pocketed, lightweight and crafted with multi-function in mind, the style works with nearly everything in your closet, regardless of whether your skew workwear or black tie. Look out for funky materials or an interesting pattern — with so many options to choose from, you should have no problem selecting one that perfectly suits your style.
All Hail the Chore Coat, Workwear Warrior of Fall Outerwear
The official layer for getting shit doneThe Coach's Jacket
The coach's jacket earned its name on the backs of athlete-adjacent folk, and the sportiness shines through in a causal, button cut that'd look right at home courtside or at the club. Due to its lightweight nature, you'll want to opt for a tough base — nylon or a poly blend should do the trick — to get the most from the style.
The Lightweight Blazer
TDLR: Haven't you heard? A blazer and jeans combo is cool again. Try to add some sort of edge to your sport coat for an especially well-dressed spring — windowpaining, an unusual material, perhaps even a pop of color.
The Best Lightweight Spring Blazers for 2023
Airy enough for comfort but substantial enough for seasonal surprises, a good spring blazer is a total game changerThe Rain Jacket
TDLR: Perhaps the most essential item on this list, the rain jacket should be kept close at hand, ready to slip on at the first sign of clouds. The style doesn't need to be heavy like a proper winter jacket — in all but the wettest parts of the country, a technical shell will do just fine.
Spring Showers Be Damned: The Best Rain Jackets for 2023
Stay dry through every sun shower and torrential downpourWe've put in the work researching, reviewing and rounding up all the shirts, jackets, shoes and accessories you'll need this season, whether it's for yourself or for gifting purposes. Sign up here for weekly style inspo direct to your inbox.


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The Village of Warwick's Annual Apple Eve event will take place on Sunday, December 31, 2023, on Railroad Green beginning at 11:30 p.m., in time for the dropping of the Apple at midnight. Everyone is invited to welcome in the New Year, so bring your noisemakers and join the fun!
The apple was created by John Redman and made its debut in 2017 to welcome in the Village's Sesquicentennial year. Apple Eve has since become a beloved tradition – we hope to see you there!