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In this context, it is important to emphasize that these G 1 /S molecules have short half-lives and frequently, if not most often, are regulated at the level of protein stability. This is important because changes seen at the mRNA level frequently correlate poorly with those observed at the protein level.

Thus, we know an enormous amount about cell-cycle control in the rodent β-cell and how key signaling pathways regulate these molecules.

As in the rodent β-cell, the G 1 /S molecules controlling human β-cell proliferation have also been studied, and much is now known. For example, we have a relatively complete understanding of which of the ∼30 G 1 /S molecules are present in the human islet, and they can be arranged in a working wiring diagram or road map, which looks very similar to the rodent version in Fig. 2 ( Satintrimmed Crepe Mini Dress Black Karl Lagerfeld kvIbB6oKK
). In addition, we know that adenoviral overexpression of certain cell-cycle regulatory molecules (e.g., cMyc, the cdks, or the cyclins D or E) in the human β-cell activates proliferation robustly. For example, with adenoviral overexpression of cell-cycle molecules, as many as 10–15% of adult human β-cells are able to replicate as assessed using Ki-67 immunohistochemistry or bromodeoxyuridine incorporation ( Womens Wayfly Multisport Outdoor Shoes Black 5 UK Ecco toGUcZFo5b
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Although the human β-cell G 1 /S road map is similar to that in the rodent β-cell, there are two principal differences, indicated by the black numbers in Fig. 2 . First, cdk6 is absent in rodent β-cells but abundant in human β-cells ( Fliff jeans Pink amp; Purple Isabel Marant UmaSYK
). This is relevant because genetic loss of cdk4 in mice leads to β-cell hypoplasia and diabetes, presumably because there is no cdk6 to compensate for this loss. Second, although all three D -cyclins are present in the mouse β-cell, genetic loss of cyclin D2 (but not cyclins D1 or D3) in mice leads to β-cell hypoplasia and diabetes, indicating that this is the key D -cyclin in the rodent β-cell ( Charm Bracelet Planetary C Bracelet 1 by VIDA VIDA KHOf5252o
, 76 ). In contrast, human islets contain little or no cyclin D2 ( 71 ), suggesting, paradoxically, either that cyclin D2 is irrelevant in the human β-cell or that it is absolutely essential, with its paucity being precisely the reason that human β-cells do not replicate.

Failure to signal from cell surface to cell-cycle machinery.

Most importantly in the current context, because adult human β-cells do not replicate in response to the long list of growth factors, nutrients, and maneuvers that induce rodent β-cells to replicate, but clearly can replicate when cyclins and cdks are overexpressed ( 71 73 ), it is clear that failure or inadequacy of the cell-cycle machinery in human β-cells is not the reason they do not replicate; the machinery is there and waiting to be activated. Thus, the likely missing link in adult human β-cell replication is not failure to express key cell-cycle molecules, but rather a failure to activate them in response to what would appear to be appropriate upstream signals. More specifically, the blockade(s) would appear to be somewhere among the levels of the upstream growth factors, their receptors, signaling pathways that should, but do not, alter these cell-cycle molecules.

If human β-cells possess the requisite G 1 /S molecules to drive β-cell replication, and their upregulation can drive human β-cell replication, it is then axiomatic that signaling events that should be reaching the cell-cycle machinery are not. It therefore would be particularly useful to have a human β-cell signaling road map that describes these intracellular signaling pathways, with their upstream ligands and receptors and downstream cell-cycle targets. Unfortunately, in contrast to the rich and complex road map for growth factor and nutrient induction of rodent β-cell replication, no such road map exists for the human β-cell: we remain very much in the dark regarding receptors, nutrient transporters/sensors, their downstream signaling pathways, and their putative connections to the ultimate downstream cell-cycle regulatory molecules. Simply said, the human β-cell signaling road map is almost a blank slate, a tabula rasa, as shown in the light gray lines and text in the upper portion of Fig. 4 , which should be contrasted to their counterparts in Fig. 1 . The following sections briefly summarize the little that we do know.

Hi All,

Here is a great group I found on Facebook. It is called Pernicious Anaemia Society and here is the link: Gold Plated Mona Pearl amp; Crystal Open Ended Ring Gold Shashi mBYDcW

Here is an paragraph from one of their posted: (this article has many links provided that may be of interest) 3. A research article by Scand J Haematol(l980) 25,401406 states that B12 levels are dependent on folate status. This means that a person could be folate deficient which causes the B12 level to go low. Once the person is treated with folic acid this also returns the B12 level to normal. However, if you are already deficient in B12 and getting B12 injections the artiicle may explain why it seems the injections are not working the way they should. When your folate level is low, it causes the B12 analogues (inactive B12) to increase and the cobalamin (active B12) to decrease. Inactive B12 or B12 analogues is the B12 your body cannot convert. Active B12 is the B12 your body needs and can use…Methylcobalamin and Adenosylcobalamin are the two active forms of B12 and are what your body converts cyanocobalamin and hydroxocobalamin injections to. The link to the research article is below:


3. Learn as much as you can about PA because most doctors are not forthcoming with information regarding PA/B12 Deficiency. You can read more on PA at the following links below:

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and for more information including many research articles please visit the Pernicious Anaemia Society website and click on forum:



I’m a 37 yr old mother of 3. Not over weight, no thyroid problems. i’ve been having numbness in my right thigh. I get up an immediately fall. This has become more frequent as of the past 3 weeks. the symptoms have included, tingling and cool feeling up my leg. tingling in feet and hands. Headache, nausea and dizziness and tiredness. I just had and MRI and MRA today. They also ran some tests… B12 204, MCH 34.3, MCV 100.3, RDW 12.1 and RBC, Auto 3.72. is this just what B12 deficiency does or could there be something else that the MRI/MRA will show?


meli d says

I understand that glyphosate, the active ingredient in Roundup Ready herbicide, chelates minerals in plants so that they still test as being there but are unavailable to the plant. Have we considered it’s having the same effect on humans and other animals? Valentina Pleated Floralprint Silkchiffon Maxi Dress Pink Raquel Diniz FHVud
And now we’re going to feed roundup ready alfafa to cattle across the country.


Michelle says

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The problem? None of the studies actually linked high-fat diets to heart disease. The science just wasn’t there. In fact, numerous studies have since debunked the myth. It’s been proved there is no evidence that dietary saturated fat increases a person’s risk for coronary heart disease or cardiovascular disease. ()

Additionally, a seven-year study of more than 48,000 women showed that low-fat diets don’t lead to more weight loss or less disease. () And yet another study found that, when subjects ate either a Mediterranean diet , low-fat diet or low-carb diet, those following a high-fat, low-carb meal plan not only lost the most weight, but also drastically reduced their bad cholesterol levels. ()

Mediterranean diet

It turns out our ancestors were right all along: Healthy fats can be good!

The 11 Best Healthy Fats for Your Body

Not all fats are created equal, but the ones below pack a lot of punch. From lowering bad cholesterol and helping shed excess weight to giving you shiny hair and healthy nails, your body will reap the benefits of these healthy fats.

1. Avocados

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are so numerous that they’re one of the healthiest fruits you can consume. They’re rich in monounsaturated fats, which raise levels of good cholesterol while lowering the bad — talk about a double-whammy. Avocados are also packed with the benefits of vitamin E , which help Jersey Skater Dress Bottle green Brave Soul HoxSP4WVW4
, boosts immunity and acts as an anti-aging nutrient for your skin.

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benefits of vitamin E prevent free radical damage

Plus, it’s chock-full of healthy protein; in fact, it has more than any other fruit. For pregnant women, avocado is also one of the great Light blue Corazon Puro bracelet Aliita rRIXR8lh
, as this vitamincan help reduce the risk of birth defects.

folate foods

Get more avocados in your diet and try one of these Nova Lariat Necklace in Metallic Gold Wanderlust Co sV7kVHhvZ
. Or use it to cook with by adding avocado oil into your kitchen. It has a mild taste that won’t overpower dishes the way other oils might. Its high smoke point of about 520 degrees means that it’s suitable for grilling or frying. And because it isn’t solid at room temperature, it’s a tasty choice to drizzle on salads, sandwiches or veggies.

Okay, I went and read some … I will spread out the Magnesium and start taking the B-12 and see if that helps. Can I ask what brand you’re taking on the Magnesium … the 150mg’s?


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Thank you so much!! I took one Magnesium this morning, and one 5mg B-12 …. I’ll break up taking the Magnesium through the day. I sure hope it makes a difference. HUGz!


Julee and Mark

It is possible to have too much magnesium in your system. I suggest you get your bloods taken which will indicate what your magnesium levels are on a given day. Then you can go from there with the advice of a GP. You should always get the advice of a professional regarding the use of supplements.


It is exceedingly rare to have too much magnesium in the body. The cases usually involve kidney disease, IV magnesium or massive continuous doses. A woman in labor is often given an IV of 50,000 mg to stop labor contractions. It does not hurt the woman or the unborn child.

You’ll know when you’ve had too much magnesium and will be running to the toilet to get rid of it soon enough.

Still… as the first reply states, you should have an RBC analysis to determine levels before supplementing. That includes CALCIUM supplementing… a far more dangerous mineral. Even the American Dairy Council mentions ‘toxic’ levels of calcium being anything above 3000mg. I’m sure many American women exceed this level with blind calcium supplementing and dietary intake.

Mirriam Milapo says

Hai, am 36 years old and last year December was diagnosied with vitamin B 12 deficiency. Intrisic factor antibodies were positive as well as pariental cell antibodies. Iam taking injections every month and have my enegy has improved. but am not sure whether it is penicious amemia or not because i don’t know what shows that its really penicious. i did an endoscopy and my stomach and intenstine were all okay.



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