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Seventeen vitamin K–dependent proteins have been identified to date of which several are involved in regulating soft-tissue calcification. Osteocalcin, matrix Gla protein (MGP), and possibly Gla-rich protein are all inhibitors of soft-tissue calcification and need vitamin K–dependent carboxylation for activity. A common characteristic is their low molecular weight, and it has been postulated that their small size is essential for calcification inhibition within tissues. MGP is synthesized by vascular smooth muscle cells and is the most important inhibitor of arterial mineralization currently known. Remarkably, the extrahepatic Gla proteins mentioned are only partly carboxylated in the healthy adult population, suggesting vitamin K insufficiency. Because carboxylation of the most essential Gla proteins is localized in the liver and that of the less essential Gla proteins in the extrahepatic tissues, a transport system has evolved ensuring preferential distribution of dietary vitamin K to the liver when vitamin K is limiting. This is why the first signs of vitamin K insufficiency are seen as undercarboxylation of the extrahepatic Gla proteins. New conformation-specific assays for circulating uncarboxylated MGP were developed; an assay for desphospho-uncarboxylated matrix Gla protein and another assay for total uncarboxylated matrix Gla protein. Circulating desphospho-uncarboxylated matrix Gla protein was found to be predictive of cardiovascular risk and mortality, whereas circulating total uncarboxylated matrix Gla protein was associated with the extent of prevalent arterial calcification. Vitamin K intervention studies have shown that MGP carboxylation can be increased dose dependently, but thus far only 1 study with clinical endpoints has been completed. This study showed maintenance of vascular elasticity during a 3-y supplementation period, with a parallel 12% loss of elasticity in the placebo group. More studies, both in healthy subjects and in patients at risk of vascular calcification, are required before conclusions can be drawn.
In vertebrates, all extracellular body fluids are supersaturated with respect to calcium and phosphate, resulting in a tendency for spontaneous calcium phosphate precipitation, which is often expressed as the calcium × inorganic phosphate product (1). Potent inhibitors of calcium salt precipitation and crystallization are therefore essential for survival, and consequently a broad range of low and high molecular weight inhibitors are found in the circulation. Low molecular weight inhibitors include pyrophosphate and citrate, whereas the most potent inhibitors are small and medium-sized proteins.
Fetuin-A is a 48-kD protein synthesized in the liver and secreted into the circulation; it is the most important systemic inhibitor of soft-tissue calcification. Transgenic fetuin-A–deficient mice display a severe diffuse systemic calcification phenotype with punctuate calcified lesions in most tissues (2). Besides fetuin-A, a number of small vitamin K–dependent proteins have been discovered acting as potent calcification inhibitors. Examples are osteocalcin (OC), also known as bone Gla protein, matrix Gla protein (MGP), and possibly also the newly discovered Gla-rich protein (GRP), which are all proteins between 5 and ~10 kD. In contrast to fetuin-A, these proteins are local inhibitors of calcification, i.e., they are synthesized in the tissues in which they exert their function. OC is synthesized by the osteoblasts in bone, and transgenic OC-deficient mice show increased bone mineral content (3). MGP is primarily synthesized by chondrocytes and vascular smooth muscle cells, and MGP-deficient mice show impaired growth (resulting from excessive growth plate calcification) and massive calcification of the arterial tunica media (4). An interesting question is why fetuin-A alone is unable to stop calcification of these tissues. Recently, a hypothesis was presented that provided a possible answer to this question. In their paper, Price et al. (5) demonstrate that with its molecular mass of 48 kD, fetuin-A is too large to penetrate the luminal space within collagen and elastin fibrils. But if no other inhibitors are present, these fibrils will rapidly calcify. Only calcification inhibitors that are small enough to penetrate the collagen and elastin fibrils, i.e., OC and MGP, will be able to move freely into the fibril and prevent mineral growth inside. This explains why the elastin fibrils are prone to calcification, especially during vitamin K insufficiency, and demonstrates the vital importance of vitamin K in the prevention of soft-tissue calcification. In this paper, we review the current knowledge in this field, especially with respect to the role of MGP in the regulation of soft-tissue calcification, which may have implications for the risk of cardiovascular and other diseases.
OC was the first Gla protein discovered not to be involved in blood coagulation and also the first Gla protein found to be synthesized outside the liver (6–8). Remarkably, the molecular role of OC has remained obscure for >30 y. In vitro experiments with purified OC showed that it is a strong inhibitor of calcium salt precipitation from supersaturated solutions (9). OC-deficient animals show increased bone size and high bone mineral content (3). Therefore, OC was described as a negative regulator of bone growth. Only after the hypothesis of mineralization by inhibitor exclusion was put forward did it become clear how OC may contribute to the controlled deposition of hydroxyapatite in bone (5).
In contrast to OC, the phenotype of MGP-deficient mice immediately showed the function of MGP (4). MGP−/− animals were smaller than their heterozygous littermates, resulting from calcification of the epiphysis that blocked longitudinal growth. Moreover, all large arteries rapidly calcified, resulting in death at 6–8 wk after birth. Tissue-specific expression of MGP in the vascular smooth muscle cells completely prevented arterial calcification; hepatic MGP expression did result in high circulating MGP levels, but not in the prevention of artery calcification (10). These data clearly showed that MGP is a local inhibitor of calcification and thus complementary to the systemic action of fetuin-A.
The effects of MGP deficiency could be mimicked by feeding rodents a diet containing a mixture of warfarin and phylloquinone. The warfarin + phylloquinone model is based on the preferential distribution of phylloquinone to the liver. By combining a high dose of warfarin with a relatively low dose of phylloquinone, hepatic synthesis of blood coagulation factors can be maintained at a level that prevents bleeding, and severe vitamin K deficiency will be evoked in all extrahepatic tissues. The phenotype of this model is comparable to that of the MGP-deficient mouse showing calcification of the epiphysis and severe arterial calcifications. Initially, the reported model required daily injections with phylloquinone (11, 12), but in our laboratory, a regimen was developed in which both warfarin and phylloquinone could be given in the diet (13). The calcifications (visualized in black by von Kossa staining) in a mouse on the warfarin + phylloquinone diet are shown in Figure 1. Next to arterial calcifications, severe calcifications were found in other tissues, such as the liver, kidney, and heart.
MGP deficiency in humans is known as the Keutel syndrome, a rare autosomal recessive disease that was first described in 1971 (14). Affected subjects exhibit severe cartilage calcifications, brachytelephalangism, peripheral pulmonary artery stenosis, hearing loss, and facial abnormalities (i.e., midface hypoplasia and a depressed nasal bridge). Keutel syndrome was linked to mutations in the gene coding for MGP leading to the absence or nonfunctional forms of MGP (15, 16). A striking difference with MGP-deficient animals is that effects on the vasculature are less prominent, and an explanation may be that GRP forms a backup system for MGP in humans and not in mice. GRP was discovered in the cartilage of sturgeons (17), but is also found in mammals, including humans (18). Its function has not yet been established unequivocally, but seems to be related to calcification inhibition as well (19).
Human equivalents of the warfarin + phylloquinone animals are patients using oral anticoagulants [also known as vitamin K antagonists (VKA)], including warfarin, acenocoumarol, and phenprocoumon. These drugs are widely prescribed to subjects with an increased thrombosis risk and are often taken for many years or lifelong. Obviously, their mode of action is systemic, and all vitamin K-dependent calcification inhibitors (including OC, MGP, and GRP) will remain uncarboxylated and thus inactive during VKA treatment. The first study demonstrating strongly increased calcification of the aortic valves in patients taking oral anticoagulants (20) has been confirmed by many other researchers. Koos et al. (21) demonstrated that subjects taking anticoagulants had a significantly higher degree of arterial and aortic valve calcification than control subjects. In a case report, Hristova et al. (22) described a kidney transplant recipient exhibiting massive arterial calcification after the initiation of warfarin therapy. Distal subcutaneous necrosis ultimately led to the patient's death. Rennenberg et al. (23) showed rapid calcification of the femoral artery when treating patients with oral anticoagulants, with an OR of 8.5 for calcification in patients compared with controls. Similarly, patients taking oral anticoagulants showed significantly increased levels of coronary calcification (24). From these and other data, we conclude that the use of VKA results in decreased carboxylation of MGP and probably also GRP, which may form a strong risk factor for calcification of the vasculature and heart valves.
Preferential distribution of phylloquinone to the liver is consistent with the triage theory proposed by McCann and Ames (25). Nature ensures that at suboptimal supply, vitamins and minerals are primarily used for functions required for short-term survival. Because carboxylation of the most essential Gla proteins is localized in the liver and that of the less essential Gla proteins in the extrahepatic tissues, a transport system has evolved ensuring preferential targeting to the liver to preserve coagulation when dietary vitamin K is inadequate. Only at hepatic vitamin K sufficiency, particularly the long-chain menaquinones, are transported to extrahepatic tissues. This is why the first signs of vitamin K insufficiency are seen as incomplete carboxylation of extrahepatic Gla proteins. McCann and Ames concluded that long-term micronutrient insufficiencies are a risk factor for the development of a wide variety of age-related diseases, such as osteoporosis, cardiovascular disease (CVD), and cancer.
The extrahepatic Gla proteins OC and MGP, for which conformation-specific tests have been developed, exhibit substantial undercarboxylation in subjects not taking vitamin K supplements. Recently, a conformation-specific test for uncarboxylated GRP was described, showing that this protein also partially occurs in a noncarboxylated form (M. Herfs, E. Smit, C. Viegas, S. Simes, C. Vermeer, VitaK, Maastricht University, the Netherlands, unpublished results). At this time, there is no example of an extrahepatic Gla protein demonstrated to be fully carboxylated in nonsupplemented healthy subjects. We conclude that the Western diet contains insufficient vitamin K to ascertain the requirements of extrahepatic tissues, such as bone and the vascular wall.
MGP exists as various distinct species according to its state of phosphorylation and/or carboxylation, including phosphorylated carboxylated MGP (cGMP), phosphorylated ucMGP (p-ucMGP), desphospho-carboxylated matrix Gla protein (dp-cMGP), and desphospho-uncarboxylated matrix Gla protein (dp-ucMGP). Unfortunately, there are currently no assays available to measure each individual circulating MGP species or even the total circulating MGP pool. An overview of published papers in which circulating MGP species—dp-ucMGP, dp-cMGP, total uncarboxylated matrix Gla protein (t-ucMGP)—have been used to explore their potential diagnostic utility is given in the following (see also TABLES 1 and and22).
Uncarboxylated species of MGP have been detected in the healthy population and may be a useful marker of vascular vitamin K status and disease. The most robust assay available to date is that for circulating MGP lacking both posttranslational modifications, i.e., serine phosphorylation and γ-glutamate carboxylation. This fraction of total circulating MGP is dp-ucMGP. As for uncarboxylated OC, changes in systemic vitamin K status resulting from the use of vitamin K supplementation or vitamin K antagonists are reflected in circulating levels of dp-ucMGP. Circulating dp-ucMGP levels were shown to correlate with age in healthy adults, with significantly higher levels in the elderly (65 y and older) (26). Case-control studies showed higher dp-ucMGP values among patients at risk of vascular calcification, including those with rheumatoid arthritis, aortic valve disease, aortic stenosis (AS), heart failure (HF), chronic kidney disease (CKD), and patients taking VKA (26–30). Extremely high dp-ucMGP values were measured in dialysis patients with median dp-ucMGP levels that were 3–5 times higher than in the corresponding healthy controls. It was further shown in 107 CKD patients that plasma dp-ucMGP levels increased progressively with CKD stage (31). High circulating dp-ucMGP could reflect a low dietary intake of vitamin K, resulting in lower inhibition of artery calcification.
In CKD patients, increased dp-ucMGP levels (>921 pmol/L) were associated with aortic calcification and overall mortality (31). The association with mortality was, however, lost after correction for age and other confounders, such as CKD stage, hemoglobin, and the aortic calcification score. In this patient group, patients on VKA therapy presented significantly higher levels of dp-ucMGP. A separate study in 19 VKA patients found a significant correlation between plasma dp-ucMGP levels and femoral artery calcification (30). The relationship between dp-ucMGP and vascular calcification could not be confirmed in a recently studied cohort of healthy elderly (32). Elevated levels of dp-ucMGP (>950 pmol/L) were also associated with overall mortality (adjusted HR >7) in 147 AS patients (27). Again, a positive association was found between the use of VKA and dp-ucMGP levels. In the non-VKA users in this patient group, circulating dp-ucMGP was significantly correlated with neurohormonal and hemodynamic markers of HF severity. Plasma dp-ucMGP levels were shown to increase with disease severity, as assessed by clinical, neurohormonal, and hemodynamic measurements, in a separate cohort of 179 HF patients (28). Moreover, high levels of dp-ucMGP were associated with mortality due to progression of HF (adjusted HR >5). Also in this cohort, VKA use influenced plasma dp-ucMGP levels. In conclusion, all published data show that dp-ucMGP is inversely correlated with vitamin K intake/status, and in most studies, this marker is also inversely correlated with survival and life expectancy.
Theoretically, this marker forms the mirror image of dp-ucMGP, and 2 studies have been published investigating the association with survival. Ueland et al. (27) found that AS patients with above the median levels of dp-cMGP had a higher unadjusted mortality rate, but in the multivariate model the significance of these associations were lost. Schlieper et al. (29) studied a cohort of 188 hemodialysis (HD) patients and found an inverse association between dp-cMGP and both cardiovascular (HR >2) and overall mortality (adjusted HR >2). Circulating dp-cMGP levels were 12% lower in the HD patents with more extensive calcifications (total calcification score of 7–15) compared with the HD patients with fewer calcifications (total calcification score of 0–6). When interpreting these data, it should be realized that the dp-cMGP assay became available only recently and has only been used on a limited scale; also its sensitivity is less than that of the dp-ucMGP assay.
In contrast to both assays described above, the principle of the t-ucMGP assay is not that of a sandwich ELISA, but that of a competitive, single antibody assay. The fraction recognized by this assay is the sum of p-ucMGP and dp-ucMGP. Because the observed plasma levels are >1000-fold higher than those of dp-ucMGP, we assume that the t-ucMGP mainly consists of phosphorylated ucMGP species. The phosphoserines equip the molecule with strong calcium-binding groups irrespective of the Gla content, and the data observed can best be explained by assuming that the majority of this fraction has a strong affinity for vascular calcifications. This is illustrated by the fact that low t-ucMGP levels have been found in patients prone to vascular calcification, including patients with rheumatoid arthritis, dialysis patients, and patients with CVD defined as myocardial infarction, coronary artery disease, angioplasty, AS, and calciphylaxis (26, 33). In particular, dialysis and calciphylaxis patients were characterized by extremely low values; nearly all patients had values well below the healthy adult range. In healthy adults, serum t-ucMGP levels were shown to be similar among the indicated age groups: younger than 25 y, 25–65 y, and older than 65 y (26). Nevertheless, the circulating t-ucMGP value could discriminate between healthy controls and subjects with moderate to severe hypertension (R. Rennenberg et al., Maastricht University Medical Center, Maastricht, the Netherlands, unpublished results).
In studies in which arterial calcification was quantified, low circulating t-ucMGP levels were found to parallel high calcification scores, but there are insufficient data to suggest a causal relationship, for instance, by direct binding of t-ucMGP to the sites of calcification. Lower circulating t-ucMGP levels were associated with higher calcification scores in 40 HD patients (34), 191 patients with aortic valve disease (35), and >800 patients with stable CVD (36). Among the patients with stable CVD, this inverse association was limited to patients without diabetes (n = 615). The mechanism responsible for the effect modification by diabetes state could, however, not be explained. Also, more calcification was seen in 36 hypertensive patients with the lowest values of t-ucMGP, but the trend across the t-ucMGP tertiles was not significant (study 1) (30). In another hypertensive patient group (n = 96), no significant correlation was found between circulating t-ucMGP levels and the presence of calcification, as determined during renal angiography (study 2) (R. Rennenberg et al., Maastricht University Medical Center, Maastricht, the Netherlands, unpublished results). The lack of statistical significance may be explained by the small patient population (study 1) or by the atypical method used to determine calcification (study 2). In 200 healthy postmenopausal females, the inverse relationship between t-ucMGP and calcification was only found in women with clear coronary artery calcification (CAC), i.e., CAC score >0 (G. Dalmeijer et al., Julius Center for Health Sciences and Primary Care, University medical Center Utrecht, the Netherlands, unpublished results). Circulating t-ucMGP levels were significantly lower in those with CAC (n = 75) compared with those without CAC (n = 125, CAC score <10).
Like dp-ucMGP and dp-cMGP, circulating t-ucMGP was also associated with mortality risk (36). Compared with CVD patients in the lowest t-ucMGP tertile, CVD patients in the highest tertile had ~50% lower risk of mortality in models adjusted for age, sex, and race. This association remained after adjustment for traditional CVD risk factors, kidney function, C-reactive protein, ejection fraction, peak exercise capacity, and medication use, but was limited to persons without diabetes (n = 610). The association of t-ucMGP with CVD events was in the same direction, but of lesser magnitude. When t-ucMGP was evaluated as a continuous predictor variable, each 1000-nmol/L higher t-ucMGP level was associated with a 22% lower risk of mortality and a 16% lower risk of CVD events.
Taken together, the data that have been published thus far suggest that dp-ucMGP may become a risk marker for cardiovascular disease and mortality, whereas t-ucMGP, through its calcium-binding capacity, may become a marker for vascular calcification. At present, we are developing an assay for p-cMGP, which on a theoretical basis has the highest calcium-binding capacity and would therefore be the marker of choice for monitoring vascular calcifications.
Conformation-specific anti-MGP antibodies have also been used for immunohistochemical staining of healthy and atherosclerotic vessels. In healthy arteries, there is little accumulation of either cMGP or ucMGP. In calcified atherosclerotic lesions as well as in Mönckeberg's media sclerosis, however, both forms of MGP accumulate, probably because of increased expression. It was reported that elevated levels of calcium trigger MGP expression in cultures vascular smooth muscle cells (37). As shown in , cMGP is the most predominant form in early lesions, whereas ucMGP is mainly found around atherosclerotic lesions.
Using the warfarin + phylloquinone model for arterial calcification in rodents, Spronk et al. (13) showed that menaquinone-4 and not phylloquinone inhibited warfarin-induced arterial calcification. This is explained by the different transport and tissue distribution of menaquinones, resulting in a much more prominent protective effect of menaquinones (compared with phylloquinone) on arterial calcification. Later studies, in which the long-chain menaquinone-7 (MK-7) was used to counteract warfarin-induced calcification, showed that this form of menaquinone was even more potent than menaquinone-4. This is consistent with population-based studies in which only the long-chain menaquinones had cardioprotective effects.
In a limited number of 3-mo clinical trials, it was demonstrated that vitamin K–containing supplements result in a strong and significant decrease of circulating dp-ucMGP in healthy adults (26, 38, 39). Thus far, most data have been obtained with MK-7; MK-7 was required in doses between 45 μg/d and 90 μg/d to find a statistically significant effect on MGP carboxylation. Based on its shorter half-life and different tissue-distribution pattern, it is to be expected that higher doses will be required for phylloquinone. Thus far, only one 3-y clinical trial has been published with clinical endpoints. In this 3-y study, 181 postmenopausal women received either phylloquinone (1 mg/d) or placebo against a background of cholecalciferol (8 μg/d). Although Young's elasticity modulus (a marker for vascular stiffening) decreased by 12% in the placebo group, vascular characteristics remained unchanged in the vitamin K group (40).
It is well-known that CKD patients are at high risk of vascular calcification, and each year 10% of the HD population will die of cardiovascular complications. We have found that circulating dp-ucMGP levels in these patients are higher than in any other patient group, in many cases even higher than in those taking oral anticoagulants. This is suggestive of a very poor vitamin K status of the vascular wall. Obviously, this group is an ideal target for testing whether vitamin K supplements can normalize the circulating dp-ucMGP levels and whether the change in vascular vitamin K status will result in an improved clinical outcome. Westenfeld et al. (41) demonstrated in HD patients that indeed menaquinone supplements induce a dose-dependent decrease in plasma dp-ucMGP levels.
Recently, we entered into collaborative studies with the Maastricht University Medical Center (Maastricht, the Netherlands) and the RWTH Aachen University (Aachen, Germany) in which clinical endpoints will be monitored in 2 independent trials among CVD patients. In 1 trial, the effect of menaquinones (MenaQ7, 360 μg/d) on the progression of CAC is investigated in Dutch patients with established coronary artery disease. In the second trial, the effect of phylloquinone (2 mg/d) on the progression of aortic valve calcification is monitored in German patients with preexisting valve calcification. The potential of vitamin K as a modifiable risk factor is especially exciting because of its simplicity: with the aid of food supplements or fortified foods, vitamin K consumption can be increased without major changes in the dietary pattern.
The triage theory predicts that, with limited intake, vitamins are transported to those tissues where they are important for immediate survival of the organism. For vitamin K, this implies a preferential transport to the liver, the organ where the coagulation factors are synthesized. Without doubt, bleeding caused by an impaired hemostatic system is the most life-threatening consequence of vitamin K deficiency. This mechanism explains why vitamin K insufficiency will occur sooner and be more pronounced in extrahepatic tissue than in the liver and is consistent with the relatively high levels of circulating uncarboxylated OC and dp-ucMGP observed in healthy subjects. The question is whether the undercarboxylation (10–40%) of circulating OC, MGP, or GRP, as seen in the healthy adult population, is associated with an increased risk of age-related diseases, such as soft-tissue calcification. Only long-term vitamin K intervention studies in healthy subjects may answer this question. The very high levels of dp-ucMGP found in certain patient groups warrant studies investigating a beneficial clinical outcome of vitamin K supplementation. Notably, HD patients form an excellent model for apparent vascular vitamin K insufficiency and concomitant arterial calcification. A second target group for vitamin K supplementation studies is formed by subjects taking high doses of supplemental calcium. It has been reported that the increased calcium load is a risk factor for vascular calcification. Finally, it should be mentioned that most vitamin K intervention studies have used high doses of vitamin K (both phylloquinone and menaquinones). Benefits of increased vitamin K intake at nutritionally relevant doses in healthy subjects await the outcomes of clinical trials currently in progress.
All authors have read and approved the manuscript.
1Conflicts of interest: E. Theuwissen, E. Smit, and C. Vermeer, no conflicts of interest.
2Abbreviations used: AS, aortic stenosis; CAC, coronary artery calcification; cGMP, carboxylated matrix Gla protein; CKD, chronic kidney disease; CVD, cardiovascular disease; dp-cMGP, desphospho-carboxylated matrix Gla protein; dp-ucMGP, desphospho-uncarboxylated matrix Gla protein; GRP, Gla-rich protein; HD, hemodialysis; HF, heart failure; MGP, matrix Gla protein; MK-7, menaquinone-7; OC, osteocalcin; t-ucMGP, total uncarboxylated matrix Gla protein; ucMGP, uncarboxylated matrix Gla protein; VKA, vitamin K antagonist.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Increase the personnel available to assist incoming customers. Also requiring Uhul associates to enter detail notes into each customer account for any all actions and interactions would be most helpful.
Hien V. en
I originally requested pick up & return in Redlands but on pick-up date I was asked to pick up at this location. I was upset at first because this location was out of my way but the lady on the phone told me U-Haul would credit my credit card $50 for not having the truck at the location I reserved. I saw the credit yesterday and was very impressed U-Haul kept their promise and did it in a professional manner. The young man who took care of us when we came in to pick up the rental was VERY pleasant and professional. After having received the most horrible customer service from the Lowe's in Redlands, our great experience with U-Haul saved the weekend!!!
BRIAN R. en
EXCELLENT service across the board here. Patient, competent and handy for Mr. Clueless like me. Props and hat-tips to all.
RANDALL O. en
More help Too long of time to check out For how busy it was The gentleman that helped me was very helpful did a good job
Meredith M. en
Only problem is there was a double charge to my card. Hoping to get that resolved asap.
Alex S. en
It was really good. Just had to wait a little while.
Samantha B. en
They did not have enough staff to take care of the line of customers in the store. I was probably there for a half hour in line and one guy said he would help me outside and he never came back or updated us. Also saw cockroaches crawling in the store.
RAY A. en
After hours return service could make some improvements having a highly visible return slip box an a self check out electronic system with a printed out receipt equipment to officially be checked out made easy way
Jarrell J. en
We were told that it did not matter which uhaul location we dropped our rental off at, however upon attempting to drop our rental off we found this was not the case at all.
JESUS R. en
I'd like to say I got the best service from Jesus Garcia, he was kind , helpful , and very professional. He deserves all the recocgnition and praise. I will visit and rent u haul again because of him
Harold K. en
Lewis H. en
Final cost was substantial more than advertised in rental estimate. Especially the milage cost.
Greg k. en
No fault to this location, but uhaul.com shoud be able to easily determine availability of their equipment at ALL their locations. I shouldn't have to be inconvenienced not once, but twice for a rental. Uhaul Customer service described $50 reservation guarantee as a discount, which it was not. Not happy whatsoever.
George F. en
Very helpful, professional and friendly.
ANNIE D. en
Great customer service. Manger was exceptional with assisting us! Thank you
Elizebeth M. en
Doing a great job continue.
Jose L. en
No complaints! Everyone was very professional. I highly recommend this location. Keep up the great work!
GALYN P. en
As soon as I got in the 26 foot truck oil light came on I told the worker I don't want to stop on the highway he said it's ok it just came on, being that I'm a female I really didn't want to take that chance of breaking down. The truck drove really bad the ride was scary
Stephanie W. en
Do not say that 30 miles are free then turn around a say you have to pay for mileage. If a statement is made when reservation is being done and you go to pick up, You should honor what was already arranged. Be a company of your word.
MOWELL O. en
Too long time waiting for service.
Ann R. en
Keep up the good work ! I think this U haul Center is the best. I use it often and influence froends tp use it as well. The trucls are well maintained and the service is great. Thank You ...
Dell W. en
the location was very good but we had to go back and pick-up the trailer to have in attached to the truck for insurance purposes which is fine but when loading my ford pick-up on the trail the trailer came unattached from the truck so it WAS definitely not attached proper. I feel we should not have been charged for the trailer rental. This would have made quite a mess if it came undone on the freeway so thats why I am giving the location a poor rating. Very displeased.
Stephen Y. en
Great service as always


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Common Questions: Emergencies
We understand dental emergencies can happen at the most inconvenient times. It is important to maintain your dental health with regular hygiene and exams to lessen the chance of emergencies.
What is considered a dental emergency?
- Lost tooth due to force such as a sports injury.
- Infection with rapid swelling.
- Sudden Pain, heat and/or redness.
- Bleeding
If your emergency occurs during office hours please call 250-763-3338 right away to secure your emergency appointment time. Occasionally emergencies happen when the office is closed and we will open the office to treat you. Please bring an additional $131 to cover the BC Fee Guide's After Hours Office Charge.


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Published on
No doubt you are familiar with the established benefits of virtualization: improved efficiency and resource availability at a lower overall cost. Many IT departments, however, have discovered that virtualizing applications can create new and unexpected performance problems.
As businesses drive towards the distributed IT infrastructure model, how can you be sure that your application performance and service levels will not be sacrificed following P2V migration?
Join Correlsense and Emulex for an online seminar on how your business-critical applications can survive P2V migration without a performance degradation. During this session, we will discuss:
-The growing complexity of the modern IT infrastructure and the accelerating pace of change
-The challenges of guaranteeing service levels before, during and after a P2V migration
-The importance of end-to-end visibility in monitoring application and storage performance
We will conclude with a discussion of the Correlsense and Emulex solutions plus Q&A.


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"British author J.K. Rowling's first adult novel "The Casual Vacancy" will be adapted for the small screen, the BBC announced on Monday, unlike her Harry Potter adventures which went on to become one of the biggest film franchises of all time.
Public broadcaster BBC One and BBC Drama have commissioned the exclusive adaptation from The Blair Partnership literary agency which represents the author. The series is expected to air in 2014.
Rowling will collaborate "closely" on the project, with the number and length of episodes to be decided once the adaptation has formally begun.
"I always felt that, if it were to be adapted, this novel was best suited to television and I think the BBC is the perfect home," Rowling said in a statement.
Danny Cohen, controller of BBC One, said the project "highlights the ambition and scale of BBC One Drama, as well as the ability of modern television to attract the world's biggest talent and most exciting creative ideas."
The Casual Vacancy, which examines the clash of ideals, classes and generations in the seemingly sleepy English town of Pagford, has topped the bestseller lists in several countries, although it did not match the success of the Potter phenomenon."
Read more: http://www.nydailynews.com/entertainment/tv-movies/rowling-adult-adapted-bbc-article-1.1212455#ixzz2E3CZJKLk
I cannot wait!
Have you read The Casual Vacancy??
By why so long a wait ?!! ---
"No story lives on unless someone wants to listen. The stories we love best do live in us forever. So whether you come back by page or by the big screen. Hogwarts will always be there to welcome you home." -- J.K. Rowling
Monday, December 3, 2012
J.K. Rowlings THE CASUAL VACANCY Becoming TV Series?!?!
Brought To You By: Valen Steel @ 12/03/2012 07:37:00 PM
Labels: BBC, Book 8, Catching Fire Trailer, Harry Potter New Books, J.K. Rowling., The Casual Vacancy, TV Adapation
4 comments:
- AnonymousDecember 16, 2012 at 5:27 PM
eee! Hope its by the same ppl who make Downton Abbey. Love that show!!!!!ReplyDeleteReplies
Fantastic idea!! I love that show.Delete
- AnonymousDecember 17, 2012 at 2:08 PM
yes &&&& I think it should come out sooner as well. 2014? psh.ReplyDeleteReplies
Yeah. 2014 is very far away.Delete
Subscribe to: Post Comments (Atom)


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Round O is a community in Colleton County, South Carolina, United States. The population of its zip code was 1,815 at the 2000 census.
Truck Accident Litigation Lawyers In Round O South Carolina
What is truck accident litigation?
A trucking accident occurs when big rigs or semi trucks collide with other vehicles or pedestrians. Due to the large size of trucks, an accident can greatly endanger the lives of other smaller vehicles. Common causes of truck accidents include driver fatigue, speeding, disobeying safety procedures, repair and maintenance failure among others. People who are injured in truck accidents may be compensated for their injury, lost income, and pain and suffering.


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By clicking on one of the links below, you will be able to provide feedback to improve the navigation and comprehensiveness of the site. The more detailed you can be in comments the easier it will be to take your suggestion into consideration. This survey is 18 questions and will take approximately 15 minutes to complete. Thank you for your time!
Encuesta a los usuarios del AZCourtHelp


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South Central Cartel
... read moreAs one of the original early-'90s West Coast gangsta collectives to follow NWA's lead, South Central Cartel first appeared with their debut album South Central Madness in early 1992 before releasing a succession of albums throughout the remainder of the decade. After their follow-up, 1994's N Gatz...
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Photos: America in Color from 1939-1943. Posted Jul 26, 2010. Share This Gallery. It's worth noting that the "red/blue" divide is significantly geographical in basis. First, it's strongly an urban (and suburban) / rural divide.


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Creepy Photo Display
Time to Complete:00:30
Skill Level:
What you'll need:
- Halloween photos
- Glass jars
- Food coloring
- Water
- Plastic eye balls
How to Make It
- Print photos on the KODAK PIcture Kiosk or the My KODAK MOMENTS App.
- Fill jar with water leaving room for other elements.
- Add yellow and red food coloring until you reach desired shade.
- Insert photo in jar.
- Insert plastic eyeballs.
- Attach lid.


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Siena street view, Italy. Those little alleys are fascinating in this medieval town. Love the textures on wall, ceiling, ground…everywhere.
About One Photo a Day: As we publish one fresh photo to a handful of social media platforms daily for promotion, we keep it in the blog section at bestcityscape.com. The photo is chosen from Songquan Deng's latest travel project. Please feel free to share with your friends. Comments are welcome!


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Compact mini refrigerator of 3.3 cu ft capacity has adjustable glass shelves with chiller compartment beverage can dispenser holds up to eight 12 oz cans.
Avanti® Compact refrigerator in white color measures 32 3/4" x 17 3/4" x 18 1/2" and features beverage dispenser that holds up to eight 12 oz cans. Refrigerator has temperature control, compartments for storage and has capacity to hold 3.3 cu.ft.
Color FamilyWhite
Capacity in Cubic Feet or Number of Bottles3.1-4
Refrigerator TypeRefrigerators
Refrigerator FeaturesOutdoor Use
Height in Inches32.75
Width in Inches18.5
Depth in Inches17.75
Weight (lbs.)45
True ColorWhite
Number of Doors Drawers Taps1 Door
The product was not found. Please verify the sku and try again.


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A Woman is set to marry the crush who stood her up in 1982 after Facebook search
This story has really got us thinking about what it takes to find and keep true love. Mandy Ashforth (48) has spent more than 30 years searching for her true love Barrie Moat (50) who she met whilst on holiday in Bridlington, Yorkshire. The pair enjoyed a happy holiday romance... Read More →


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Featured AdPromote Your Ad
ADVERTISE HERE [Click to Learn More]
A Featured Ad is a unique, long-term ad upgrade option that allows you to purchase the top ad placement on the first page of a specific category for either one, three or six months.View Details »
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$15 · Wanted: any work or cash work!
Hi there, - I am a young physically fit man who has just moved here from Vancouver Island. Looking to fill some time as well as ...
Ad Id: 29470017
Posted: May 28, 2017
Details: New, Wanted


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Micanopy Junction (GNIS FID: 295446) is a populated place located in Alachua County at latitude 29.522 and longitude -82.23.
The elevation of Micanopy Junction is 72 feet. Micanopy Junction appears on the Rochelle U.S. Geological Survey Map. Alachua County is in the Eastern Time Zone (UTC -5 hours).
Alachua County: Cities & Towns | ZIP Codes | Features (airports, churches, hospitals, etc.)
BIG Map |
Driving Directions |
Data Source - USGS GNIS FID: 295446
BOUNDARY MAPS: Micanopy CCD | Alachua County
Micanopy, FL
(3.4 miles WSW)
McIntosh, FL (5.1 miles S)
Hawthorne, FL (9.9 miles ENE)
Gainesville, FL
(10.6 miles NNW)
Reddick, FL (10.9 miles S)
East Williston CDP, FL (14.5 miles SW)
Evinston, FL
(2.4 miles S)
Boardman, FL (3.9 miles SSE)
Cross Creek, FL (4.7 miles ESE)
Rochelle, FL
(5.1 miles N)
Tacoma, FL (5.3 miles W)
Phifer, FL (5.5 miles NNE)


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Q: What is the difference between an authorized brand and an unauthorized brand?
A: The product may be from the same factory as a well-known brand, and at times there is more stock than orders, so the leftover stock is purchased by companies like ours, however, it can't be sold under the well-known brand name. Also, a factory may make a model with the same quality as a well-known brand, but not exactly the same in every detail, these can be purchased to sell on. Either way, there is usually only a few hundred of these items available to wholesalers to sell.
Q: What is "UA" ? What is "Reps" ? What is the difference between "UA" and "Reps" ?
A: "UA" means Unauthorized and, "Reps" means Replica. UA Version the shoes are almost exact the same as the authentic one. Same material and most of the details. Reps version normally looks the same as the authentic ones with cheaper material.
A:We have upgraded every details that our youtuber have talked about. The details which makes the difference between our original UA and Authentic Ones.UA II is the upgraded version. Looks and feels exact the same as Authentic one. Every details are perfect. No one can tell if they are authentic or not anymore.
Q: What is your return policy?
A: 7 Days money back guarantee. If the shoe is still in 'as new condition'. The shoes can be returned to our US warehouse.
Q:Where do you ship? What shipping method do you use? How long will it take for me to receive my package?
A: We ship worldwide.We use DHL Express Shipping. It usually takes about 5-7 days to arrive.
Q:Why are the prices are so cheap?
A: We get the products directly from the factory. The shoes are not authentic and they are unauthorized for sale by the big brands Our prices reflect the actual cost shoes cost to make before the big brands add on their huge profit margins.
Q:Are the photos of the shoes are real ?
A: Yes they are. We have personally taken those photos. If you are still a bit worried and want to make yourself feel better you can even Facetime with us and we will show you the shoes. Or if you would like a closer look at the shoes you can email us and request more photos from different angles.
Customer Reviews
- Really comfortable ! Review by Amanda Boatright
Price Value Quality
- Pretty decent shoe Review by Jack Northe
Quality Price Value
- These are really nice shoes. True to size Review by A. Harter
Price Value Quality
I received this item for a discount in exchange for my honest and unbiased review. As an online shopper, I rely heavily on the review of products before purchasing, even those that I receive at a discount, so I take a lot of pride in the reviews I write in order to inform others that are looking to purchase an item online. Please be assured that my opinions are my own and I am in no way affiliated with the seller. (Posted on 12/8/2016)
- Netter Schuh für diesen Preis Review by Moorhexe64
Quality Price Value
Hatten ihn eine Nummer größer bestellt und passt grad mal so.
Für den Preis ansonsten absolut ok. (Posted on 12/7/2016)
- Großartig ! Review by Ms. Shabby
Price Value Quality
- Gute Schuhe zu einem Witzpreis Review by Kapp
Price Value Quality
Die Größe fällt normal aus. Eine gute Alternative für die, die nicht paar hundert Euro für die "Echten" ausgeben wollen :) (Posted on 12/7/2016)
- Love! + fast shipping Review by Kyler
Price Value Quality
- love love love these shoes Review by Connie
Quality Price Value
- love love love these shoes Review by Connie
Quality Price Value
- Everyone loves them Review by Ross
Price Value Quality
- comfortable Review by mitch
Quality Price Value
- happy Review by Oscar
Price Value Quality


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Efficiency is the name of the game at Agents of Efficiency (obviously) so we're making it even more efficient for you to improve your business. Every week, we sort through all the boring stuff to bring you only the best tips from the wide world of the web. For this week's #2tips4tues, we examine the best ways to manage unhappy customers.
In Entrepreneur.com Tim Murphy advises on how best to handle customers who need to vent after a negative experience. "Often, customers leave negative reviews when they feel ignored. In fact, how customers feel they're being treated determines whether they'll buy from a company 70 percent of the time, according to a McKinsey study. People now use public channels as their first form of communication after a poor customer service experience. Many view it as their only avenue of recourse. For this reason, it's important to stay in constant communication until a customer issue is resolved."
Gregory Ciotti of Help Scout provides excellent advice in a recent Inc.com piece on resolving those issues for maximum satisfaction. He breaks down how tone and language greatly affect customer perception. "Customers don't care about what you can't do; they want to hear what's going to be done. In addition to the usual suspects (can't, won't, didn't), phrases that resign a customer to their fate are usually interpreted as negative (you have to, you need to) … Focus on the fix over the problem, and avoid words that cause defensive, knee-jerk reactions."


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Daily Message December 28 2012
"Donate is whatever thing about the full moon in winter,her light cast diagonally the delicate white blizzard,informative everything she touches,that is straight hygienic magick to me."
- Jasmeine Moonsong
Merry Precise and Moderate Origin :))) Blessings to you and yours for a magickal day today. Today is Friday, December 28, 2012.
Fridays are ruled by Venus, a den whose properties make the addition of, love, beauty, management and approach. It's a impressive day to purpose on relationships, love, romance sexual matters, friendships and partnerships. It's a high-level day for new opportunities to come about. If you are working with stones today be after to wear natural or cat's eye for protection. Use rubies in amulets.
Tonight's Moon is the Want Nights Swollen Moon in Malignancy. The Swollen Moon is the time of limit power and the magical night for magick and ritual as it's a night anywhere energy is in prosperity. The Swollen Moon represents the Holy being in her Father aspect. She is dripping and verdant rapid knowledge. The moon in Malignancy stimulates uncontrolled association involving people. It pinpoints thirst, supports add to and nurturance. It tends to domestic concerns. The magickal color of the day is Promising, and the incense of the day is Cypress. Hug an resplendently magickal day!
Hospitality and Blessings,
Jasmeine Moonsong
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To Let - from 32,841 sq. ft. to 182,500 sq. ft. of two office block to let in The Seamark Buiding in Elmpark Green. The Seamark Building is the iconic gateway to Elmpark Green which is Ireland's first sustainable, mixed-use campus.
The Seamark Building is the iconic gateway to Elmpark Green which is Ireland's first sustainable, mixed-use campus.
The Seamark Building has been designed with full flexibility in mind. Both blocks work independently of each other or can be seamlessly combined. Each block has its own dedicated double height glazed reception allowing natural light to flood in.
Close by you will also find the Aviva Stadium and the RDS. Meanwhile, local shopping centres, The Merrion and Blackrock provide a whole array of boutiques, shops and supermarkets to choose from.
Right on your doorstep are some of Dublin's best coastline stretches, with spectacular views across the bay to Howth. Also, just a stone's throw from the campus, Sandymount Beach offers superb opportunities to get into the great outdoors with its long promenade and cycle track.
Situated close to the DART railway and N11, the Seamark Building's location in Dublin 4 is one of its major attractions. Positioned on Merrion Road with ease of access to the Port Tunnel, the property is situated 15km from Dublin Airport. The location also provides easy access to Belfast and Northern Ireland. The N11 dual carriageway also offers direct access to and from the city centre. It features a Quality Bus Corridor (QBC) that provides public transport links to the City, the North, South and other surrounding areas.
Also on your doorstep is the Aircoach which takes passengers to Dublin Airport via the Port Tunnel. With such easy access it's clear why Elmpark Green is a highly desirable office address.
- Location: The building scores excellently as a sustainable site with access to amenities, services and housing within walking distance, reducing long distance commutes and transport pollution.
- Transport: The Seamark Building offers multiple transport links including bus and rail services. Cyclists can benefit from a local cycle network, storage and changing facilities provided in the building.
- Vegetation: Generous open space has been provided with native and adaptive planting prioritized, reducing the need for additional watering, increasing site biodiversity and providing visual interest for occupants.
- Water Efficiency: Water efficient sanitary fixtures have been specified, reducing overall building water consumption.
- Energy Efficiency: Energy supplied to the Seamark Building from a centralised campus energy centre.
- Views: The Seamark Building offers an abundance of daylight and views with significant glazing along all sides of the external façade. Direct access to daylight and a connection to the external environment is proven to enhance mental wellbeing and productivity.
- Waste Recycling: The Seamark Building provides excellent waste collection facilities that enable tenants to streamline waste recycling and achieve noteworthy landfill diversion rates.
- Healthy Indoor Environment: During construction low VOC paints, coatings, adhesives, and sealants were specified preventing the introduction of air pollutants which may cause irritation to occupants.
- Building Materials: During construction products and systems produced regionally, with high levels of recycled content and those with sustainable certification were prioritised thereby reducing the building's ecological footprint.
Located on Merrion Road in the heart of Dublin's prestigious Dublin 4, the Seamark Building has a whole host of amenities within easy reach. Ballsbridge, one of Dublin's most charming suburbs, is a short stroll away. It's bustling village atmosphere as well as its many restaurants, cafés and pubs make it an attractive place to visit.
Each block is fully independent and has it's own dedicated entrance and facilities.
Double height reception, revolving entrance doors, stone flooring and reception desk.
Stone tile to walls on ground floor, plasterboard and paint at basement and upper floors.
Total 32 showers and 6 toilets allocated between block 1 and 2. Ceramic floor tiles, plasterboard and painted ceilings, proprietary cubicle system and high quality lockers and benches.
Provided on an occupancy ratio of 1 person : 10 sq m net internal floor area (assuming 60% each gender). Wheelchair accessible toilet and cleaners
store provided at each floor level. Plasterboard and painted walls, ceramic floor tiles, plasterboard and painted ceilings, selected proprietary cubicle system, stone vanity top.
Raised access floors, internal walls plastered and painted, perforated metal ceiling tiles, 4 pipe fan coil air conditioning, LED lighting with daylight control sensors and capped plumbing points for future tea stations (by others).
Based on an occupation ratio of 1 person : 8 sq m net internal floor area.
Fully air-conditioned throughout tenant areas by means of a four pipe fan coil system.
Life safety generator to backup Fire Systems/Fire Fighting Lifts and smoke extract systems.
Fully addressable fire alarm system to Category L1 in accordance with IS 3218 2013 and the Fire Safety Certificate.
Intruder alarm system provided on the ground and basement levels.
Programmable card access system for the ground floor and basement level external access doors.
CCTV system provided to the basement and ground floor main entry points.
Nine high speed passenger lifts (13 person) with full destination control and two goods
lifts (1,000kg). One lift in each block designated as a fire fighting lift.
The Seamark Building has a target BER rating of A3 to B1 and a target LEED rating of Platinum (LEED Core and Shell 2009 - V3). Factors which
contribute to LEED Platinum rating include:
-- Excellent location with access to amenities, services and housing, multiple transport links including bus and rail services and a local cycle network.
--Generous open space and landscaping.
--Water efficient sanitary fixtures.
-- Energy efficiency achieved through use of the centralized energy center.
-- An abundance of daylight and views with significant glazing along all sides of the
external façade.
-- Excellent waste collection facilities.
-- Low VOC paints, coatings, adhesives, and sealants specified.
-- Specification of products and systems produced regionally with high levels of recycled content.


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Foldable Scooter Color: Red
List Price: $1,987.95
Discount: $0.00
Sale Price: $1,987.95
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One of the many games that will be played on Saturday, February 4th is the 8:00PM game between the San Jose Sharks and the Phoenix Coyotes. This is not the only 8:00PM Eastern game scheduled that day either. There are three in total, although this is the only one that features a division leader. The other ones include the St Louis Blues going head to head with the Nashville Predators, and the Minnesota Wild playing the Dallas Stars. Earlier in the day, Pittsburgh and Boston face off in the first scheduled game of the day.
San Jose are the division leaders in the Pacific Division after winning 29 of the 49 games that they have played. Out of the remaining 20, they were able to take six games to overtime, which gives them 64 points. Phoenix is fourth in the Pacific with 52 points. They have won 22 games and have eight that ended in a loss in overtime. Sign up now and you can watch live hockey online. All you need is a subscription and an internet connection to be able to watch high quality NHL matches right on your computer or mobile device.
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A person who is convicted of a crime in West Virginia has the right to appeal the conviction. Appeals usually challenge either the sufficiency of the evidence against the defendant or the various evidentiary and procedural rulings that take place during the course of a trial. As a recent case out of the West Virginia Supreme Court makes clear, a person appealing a conviction has a tough road to hoe.
Mr. Imoh was convicted on three counts of second-degree robbery and two counts of conspiracy and sentenced to 10 to 36 years in prison. At trial, three witnesses testified that Imoh and another man – Mr. Robbins – used the threat of force to rob them of their cell phones. In one instance, Robbins swiped the phone from the victim. Imoh allegedly told that victim that he would have to fight both Imoh and Robbins in order to get the phone back. In another instance, Imoh and Robbins asked two men to borrow their phones, saying that it was an emergency. Imoh then allegedly told the men that their phones "got copped" and said he would "beat their asses" if the men continued to follow him and Robbins.
Imoh later appealed the decision, arguing that he should have been acquitted of the charges against him. An acquittal means that the prosecution has failed to meet its burden of proving the defendant's guilt beyond a reasonable doubt. It doesn't necessarily mean that the person is innocent. The Supreme Court affirmed the conviction, finding that there was sufficient evidence of Imoh's guilt. It explained that "a criminal defendant challenging the sufficiency of the evidence to support a conviction takes on a heavy burden." That's because the appeals court is required to view the evidence in the light most favorable to the prosecution and draw any inferences from that evidence – or credibility determinations regarding witnesses – in favor of the state. "[A] jury verdict should be set aside only when the record contains no evidence, regardless of how it is weighed, from which the jury could find guilt beyond a reasonable doubt," the Court said.
In this case, the Court said there was enough evidence to show that Imoh threatened the victims with bodily harm when he and Robbins took their phones. It focused in particular on the victims' trial testimony. "During trial, all three of the victims at issue testified that petitioner placed them in fear of bodily injury in order to take possession of their belongings," the Court observed.
The long odds that a convicted person faces on appeal are all the more reason to fight criminal charges head on and from the outset. Despite the result in this case, it's important to note that some appeals are successful. If you're facing criminal charges, you should seek the counsel of an experienced criminal defense attorney. The West Virginia criminal defense lawyers at the Wolfe Law Firm have been serving clients throughout the state for more than 25 years. Call us at 1-877-637-5756 or contact us online for a free consultation.
Related blog posts:
Are You Eligible for Bail? Pretrial Detention in West Virginia Criminal Cases – U.S. v. Lezine
When Can the Cops Stop and Search You on the Street? U.S. v. Richardson
West Virginia Plea Deals: Hard to Withdraw – State v. Frank D.


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