If you have diabetes, you’ll likely need a blood glucose meter to measure and display the amount of sugar (glucose) in your blood. Exercise, food, medications, stress and other factors affect your blood glucose level. Using a blood glucose meter can help you better manage your diabetes by tracking any fluctuations in your blood glucose level.
Many types of blood glucose meters are available, from basic models to more-advanced meters with multiple features and options. The cost of blood glucose meters and test strips varies, as does insurance coverage. Study your options before deciding which model to buy.
Choosing the right meter
When selecting a blood glucose meter, it can help to know the basics of how they work. To use most blood glucose meters, you first insert a test strip into the device. Then with a special needle, you poke a clean fingertip to get a drop of blood. You carefully touch the test strip to the blood and wait for a blood glucose reading to appear on the screen.
When used and stored properly, blood glucose meters are generally accurate in how they measure glucose. They differ in the type and number of features they offer. Here are several factors to consider when choosing a blood glucose meter:
Insurance coverage. Check with your insurance provider for coverage details. Some insurance providers limit coverage to specific models or limit the total number of test strips allowed.
Cost. Meters vary in price. Be sure to factor in the cost of the test strips, as these will represent the majority of the cost in the long term.
Ease of use. Some meters are easier to use than others. Are both the meter and test strips comfortable and easy to hold? Can you easily see the numbers on the screen? How easy is it to get blood onto the strips? How much blood is required?
Special features. Ask about the features to see what meets your specific needs. Special features may include large, easy-to-handle buttons and test strips, illuminated screens, and audio, which may be useful for people with impaired vision.
Information storage and retrieval. Consider how the meter stores and retrieves information. Some can track time and date of a test, the result, and trends over time. Some meters offer the ability to share your readings in real time with your healthcare provider with a smartphone app. Or some may offer the option to download your blood glucose readings to a computer, then email the test results to your doctor.
Support. Most meter manufacturers include a toll-free number that you can call for help. Look for a meter that includes clear instructions that demonstrate the correct way to use the meter. Some manufacturers offer users manuals on their websites.
Advances in monitoring tools
Although finger pokes remain the gold standard for blood sugar monitoring, researchers have developed products designed to take the pain out of the process and continue to develop new products. Ask your healthcare provider about these alternatives.
Device
How it works
Considerations
Alternative site monitor
Allows blood samples to be taken from areas likely to be less painful than your finger, such as your arm, the palm of your hand or your thigh
Not as accurate as fingertip samples when blood sugar level is rising or falling quickly
Continuous glucose monitor
Uses a sensor placed under the skin to measure blood sugar level; transmits each reading to a smartphone, smartwatch or small recording device worn on your body; gives an alert when blood sugar levels are too low or too high
Expensive; requires sensor to be replaced every 7 to 14 days, depending on the brand; may need to check blood sugar level with a traditional monitor to confirm readings and to program the device
If you’ve looked at the costs, features and other considerations and are still unsure which blood glucose meter to buy, ask your doctor or certified diabetes care and education specialist for a recommendation.
Nearly half of adults in the U.S. and 70% of older adults ages 71+ take a vitamin; about one-third of them use a comprehensive multivitamin pill. [1] But is this truly a necessity?
There are certainly diseases caused by a lack of specific nutrients in the diet. Classic examples include scurvy (from a lack of vitamin C), beri-beri (vitamin B1), pellagra (vitamin B3), and rickets (vitamin D). But these conditions are rare in the U.S. and other developed countries where there is generally more access to a wide range of foods, some of which are fortified with vitamins. Individual vitamin supplementation may also be essential in certain cases, such as a deficiency caused by long-term poor nutrition or malabsorption caused by the body’s digestive system not functioning properly.
This page specifically discusses the use of multivitamins, which typically contain about 26 different vitamins and minerals, and often provide 100% of the Recommended Daily Allowance of these micronutrients. We will explore situations that a multivitamin may be health-promoting, as well as if there is a benefit or harm in taking extra nutrients from a pill if the diet is already adequate.
Who May be at Risk for a Nutrient Deficiency?
For those who eat a healthful diets, a multivitamin may have little or no benefit. A diet that includes plenty of fruits, vegetables, whole grains, good protein sources, and healthful fats should provide most of the nutrients needed for good health. But not everyone manages to eat a healthful diet. When it comes to specific vitamins and minerals, some Americans get less than adequate amounts, according to criteria set by the National Academy of Medicine. For example, more than 90% of Americans get less than the Estimated Average Requirement for vitamin D and vitamin E from food sources alone. [2]
Certain groups are at higher risk for a nutrient deficiency:
Older age. The elderly are at risk for poor food intake for various reasons: difficulty chewing and swallowing food, experiencing unpleasant taste changes caused by multiple medications, or isolation and loneliness that can depress appetite. They also have trouble absorbing vitamin b12 from food. The National Academy of Medicine, in fact, recommends that people over the age of 50 eat foods fortified with vitamin B12 or take vitamin B12 pills that are better absorbed than from food sources. [3]
Pregnancy. Getting enough folate, a B vitamin, is especially important for women who may become pregnant, since adequate folate can help lower the risk of having a baby with spina bifida or anencephaly. For the folate to be effective, it must be taken in the first few weeks of conception, often before a woman knows she is pregnant. Yet in the U.S., half of all pregnancies are unplanned. That’s why the Centers for Disease Control and Prevention recommend that all women of childbearing age (ages 15 to 45) consume 600 micrograms a day of folic acid. [3] This amount and other important nutrients for pregnancy—iron, calcium, vitamin-D, and DHA—are available in a prenatal multivitamin.
Malabsorption conditions. Any condition that interferes with normal digestion can increase the risk of poor absorption of one or several nutrients. Examples:
Diseases like celiac, ulcerative colitis, or cystic fibrosis.
Surgeries that remove parts of digestive organs such as having a gastric bypass for weight loss or a Whipple procedure that involves many digestive organs.
Illnesses that cause excess vomiting or diarrhea can prevent nutrients from being absorbed.
Alcoholism can prevent nutrients, including several B vitamins and vitamin C, from being absorbed.
Certain medications. Some diuretics commonly prescribed to lower blood pressure can deplete the body’s stores of magnesium, potassium, and calcium. Proton pump inhibitors prescribed for acid reflux and heartburn can prevent the absorption of vitamin B12 and possibly calcium and magnesium. Levodopa and carbidopa prescribed for Parkinson’s disease can reduce the absorption of B vitamins including folate, B6, and B12.
Which Multivitamin Should I Choose?
Multivitamins come in various forms (tablets, capsules, liquids, powders) and are packaged as a specific combination of nutrients (B-complex, calcium with vitamin D) or as a comprehensive multivitamin.
Supplements are a multibillion-dollar industry, with endless designer labels of brands from which to choose. However, an expensive brand name is not necessary as even standard generic brands will deliver results. Look for one that contains the Recommended Daily Allowance amounts and that bears the United States Pharmacopeia (USP) seal of approval on the label. This seal ensures that the ingredients and amounts of that ingredient listed on the label are contained in the pill. The USP also runs several tests that confirm the pill to be free of contaminants like heavy metals and pesticides and has been manufactured under sanitary and regulated conditions.
That said, you may wish to consider the following factors before starting a multivitamin or any supplemental vitamin.
Reasons to use a multivitamin:
I am eating a limited diet or my appetite is poor so that I am eating less than usual.
I am following a restricted diet for longer than one week. This could be prescribed such as a liquid diet after a surgical procedure, or a self-imposed diet such as on with the goal of weight loss.
I have a condition that reduces my body’s ability to absorb nutrients (celiac disease, ulcerative colitis) or have undergone surgery that interferes with the normal absorption of nutrients (gastric bypass surgery, Whipple procedure).
I temporarily have increased nutrient needs, such as being pregnant.
I’m very busy and just can’t eat a balanced diet every day.
Reasons that may not need a multivitamin:
I eat well but am feeling tired all the time (discuss first with your doctor so they can investigate other possible causes).
I eat a pretty good diet but want to improve my health as much as possible, so it couldn’t hurt to get some extra nutrition from a vitamin.
I have osteoporosis and need more calcium, or I have iron-deficiency anemia and need more iron (in both scenarios, you may only need to take those individual nutrients rather than a comprehensive multivitamin).
If you are unsure about taking a multivitamin, you may wish to consult with a registered dietitian who can evaluate your current diet to determine any missing nutrients. At that time, suggestions to improve your food intake of those nutrients will be provided, or one or more supplemental vitamins may be prescribed if that is not possible. Always inform your doctor of all supplements you are taking in case of potential interactions with medications.
Mega-doses (many times the Recommended daily allowance) of vitamins are not recommended. This can potentially interfere with the absorption of other nutrients or medications, or can even become toxic if too much is taken for a long period.
Finally, be wary of supplemental vitamin labels that bait you with promises of “supporting brain health or energy production or healthy skin and hair.” These are general statements about a vitamin that are included for marketing purposes only, but are not specific to the supplement itself. Also be wary of vitamins that contain extras, like herbs and botanicals, which are typically lacking in research about long-term effects and potential adverse effects.
Multivitamins and Health
Knowledge about the optimal intakes of vitamins and minerals to prevent chronic diseases is not set in stone. More long-term studies looking at this relationship are needed.
There is no arguing that multivitamins are important when nutritional requirements are not met through diet alone. [4] The debate is whether vitamins are needed when the diet is adequate to prevent deficiency in nutrients, as some research has shown no benefit or even harmful effects when taking supplemental vitamins and minerals.
After a review of 26 clinical and cohort studies, the U.S. Preventive Services Task Force concluded there was insufficient evidence to support any benefits of multivitamins or individual vitamins for the primary prevention of cardiovascular disease or cancer among healthy, nutrient-sufficient adults. [5]
Finding the best gambling establishment on the really-growing world of bets isn’t really easy. To make the perfect variety, in fact, and commence now keep an eye on from a new attitudes in advancement. Thousands of players shouldn’t participate in in the instance of possibly not the specific gambling house flair.
Omega-9 fatty acid is a monounsaturated fat that is also known as oleic acid. It is not considered an essential fatty acid because of our body’s ability to produce it in small amounts. However, this can only happen if the essential fatty acids (EFAs) omega-3 and omega-6 are present – if the body is low on one of these EFAs it cannot produce enough omega-9. In this instance, omega-9 transforms into an essential fatty acid because of the body’s inability to produce it.
While omega-9 is crucial to the body, it plays a much smaller role than the essential fatty acids omega-3 and omega-6. Primarily, omega-9 has a positive health affect on the lowering of cholesterol levels and promotes healthy inflammation responses within the body. Other major health benefits of omega-9 include the reduction of the arteries, reduction of insulin resistance, improvement of immune function, and provides protection against certain types of cancer.
What foods contain omega-9?
The best food source for omega-9 is olive oil. Alternative sources include:
Olives
Avocados
Almonds
Peanuts
Sesame oil
Pecans
Pistachio nuts
Cashews
Hazelnuts
Macadamia nuts
What is the suggested daily intake of omega-9?
In adults, one or two tablespoons of extra virgin oil per day provides enough oleic acid for adults.
It should be known though that consuming omega-9 gradually throughout the day (much like time-released supplements) is much more beneficial to the body than consuming the entire daily amount through a single dosage.
What are the symptoms of omega-9 deficiency?
Each EFA (3, 6, 9) share a symbiotic bond that requires each other to operate to their fullest potential and to provide the body with most positive health effects as possible. A lack of omega-9 in the body can have a detrimental effect that the benefits the other omega fatty acids provide.
Signs of omega-9 deficiency can include:
Eczema-like skin eruptions
Bumps on the back of upper arms
Cracking/peeling fingertips
Dandruff
Hair loss
Behavioral changes
Dry glands
Male sterility
Growth retardation
Dry skin
Dry Eyes
Miscarriage
Irregular heart beat
Craving of fatty foods
Stiff or painful joints
Who can benefit from using supplements containing omega-9?
Because of the expansive list of benefits of the entire omega fatty acid group provides to our bodies, every healthy adult should consume omega-9. The omega fatty acid group can help prevent and combat many common illnesses and health problems. These include countless conditions, like anorexia, ADHD, diabetes, eye disease, osteoporosis, menopausal symptoms, premenstrual syndrome, acne, eczema, alcoholism, allergies, arthritis, cancer, weight loss, high blood pressure, heart disease, tuberculosis, and ulcers.
Does omega-9 have any side effects?
While omega-3 and omega-6 have some (rare) reported side effects, omega-9 has none. However, be cautious if you are using anticoagulants or antiplatelet drugs due to an increased risk of bleeding.
Omega-6 fatty acids are essential fatty acids. They are necessary for human health, but the body cannot make them. You have to get them through food. Along with omega-3 fatty acids, omega-6 fatty acids play a crucial role in brain function, and normal growth and development. As a type of polyunsaturated fatty acid (PUFA), omega-6s help stimulate skin and hair growth, maintain bone health, regulate metabolism, and maintain the reproductive system.
A healthy diet contains a balance of omega-3 and omega-6 fatty acids. Omega-3 fatty acids help reduce inflammation, and some omega-6 fatty acids tend to promote inflammation. In fact, some studies suggest that elevated intakes of omega-6 fatty acids may play a role in complex regional pain syndrome. The typical American diet tends to contain 14 to 25 times more omega-6 fatty acids than omega-3 fatty acids.
The Mediterranean diet, on the other hand, has a healthier balance between omega-3 and omega-6 fatty acids. Studies show that people who follow a Mediterranean-style diet are less likely to develop heart disease. The Mediterranean diet does not include much meat (which is high in omega-6 fatty acids, though grass fed beef has a more favorable omega-3 to omega-6 fatty acid ratio), and emphasizes foods rich in omega-3 fatty acids, including whole grains, fresh fruits and vegetables, fish, olive oil, garlic, as well as moderate wine consumption.
There are several different types of omega-6 fatty acids, and not all promote inflammation. Most omega-6 fatty acids in the diet come from vegetable oils, such as linoleic acid (LA), not to be confused with alpha-linolenic acid (ALA), which is an omega-3 fatty acid. Linoleic acid is converted to gamma-linolenic acid (GLA) in the body. It can then break down further to arachidonic acid (AA). GLA is found in several plant-based oils, including evening primrose oil (EPO), borage oil, and black currant seed oil.
GLA may actually reduce inflammation. Much of the GLA taken as a supplement is converted to a substance called DGLA that fights inflammation. Having enough of certain nutrients in the body (including magnesium, zinc, and vitamins C, B3, and B6) helps promote the conversion of GLA to DGLA.
Uses
Omega-6 fatty acids may be useful for the following health conditions:
Diabetic neuropathy
Some studies show that taking gamma linolenic acid (GLA) for 6 months or more may reduce symptoms of nerve pain in people with diabetic neuropathy. People who have good blood sugar control may find GLA more effective than those with poor blood sugar control.
Rheumatoid arthritis (RA)
Studies are mixed as to whether evening primrose oil (EPO) helps reduce symptoms of RA. Preliminary evidence suggests EPO may reduce pain, swelling, and morning stiffness, but other studies have found no effect. When using GLA for symptoms of arthritis, it may take 1 to 3 months for benefits to appear. It is unlikely that EPO would help stop progression of the disease. So joint damage would still occur.
Allergies
Omega-6 fatty acids from food or supplements, such as GLA from EPO or other sources, have a longstanding history of folk use for allergies. Women who are prone to allergies appear to have lower levels of GLA in breast milk and blood. However, there is no good scientific evidence that taking GLA helps reduce allergy symptoms. Well-conducted research studies are needed.
Before you try GLA for allergies, work with your doctor to determine if it is safe for you. Then follow your allergy symptoms closely for any signs of improvement.
Attention deficit/hyperactivity disorder (ADHD)
Clinical studies suggest that children with ADHD have lower levels of EFAs, both omega-6s and omega-3s. EFAs are important to normal brain and behavioral function. Some studies indicate that taking fish oil (containing omega-3 fatty acids) may help reduce ADHD symptoms, though the studies have not been well designed. Most studies that used EPO have found it was no better than placebo at reducing symptoms.
Breast cancer
One study found that women with breast cancer who took GLA had a better response to tamoxifen (a drug used to treat estrogen-sensitive breast cancer) than those who took only tamoxifen. Other studies suggest that GLA inhibits tumor activity among breast cancer cell lines. There is some research suggesting that a diet rich in omega-6 fatty acids may promote breast cancer development. DO NOT add fatty acid supplements, or any supplements, to your breast cancer treatment regimen without your doctor’s approval.
Eczema
Evidence is mixed as to whether EPO can help reduce symptoms of eczema. Preliminary studies showed some benefit, but they were not well designed. Later studies that examined people who took EPO for 16 to 24 weeks found no improvement in symptoms. If you want to try EPO, talk to your doctor about whether it is safe for you.
High blood pressure (hypertension)
Preliminary evidence suggests that GLA may help reduce high blood pressure, either alone or in combination with omega-3 fatty acids found in fish oil, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In one study, men with borderline high blood pressure who took 6g of blackcurrant oil had a reduction in diastolic blood pressure compared to those who took placebo.
Another study examined people with intermittent claudication, which is pain in the legs while walking that is caused by blockages in the blood vessels. Those who took GLA combined with EPA had a reduction in systolic blood pressure compared to those who took placebo.
More research is needed to see whether GLA is truly effective for hypertension.
Menopausal symptoms
EPO has gained popularity as a way to treat hot flashes associated with menopause. But so far studies have been inconclusive. If you want to try EPO for hot flashes and night sweats, ask your doctor whether it is safe and right for you.
Breast pain (mastalgia)
Some evidence suggests that EPO may reduce breast pain and tenderness in people with cyclic mastalgia. It may also help reduce symptoms to a lesser extent in people with noncyclic mastalgia. However, it does not seem to be effective for severe breast pain.
Multiple sclerosis (MS)
EPO has been suggested as an additional treatment (along with standard therapy) for MS, although there is no scientific evidence that it works. People with MS who want to add EPO to their treatment regimens should talk with a health care provider.
Osteoporosis
Some studies suggest that people who do not get enough essential fatty acids (particularly EPA and GLA) are more likely to have bone loss than those with normal levels of these fatty acids. In a study of women over 65 with osteoporosis, those who took EPA and GLA supplements had less bone loss over 3 years than those who took placebo. Many of these women also experienced an increase in bone density.
Premenstrual syndrome (PMS)
Although most studies have found no effect, some women report relief of PMS symptoms when using GLA. The symptoms that seem to improve the most are breast tenderness and feelings of depression, as well as irritability and swelling and bloating from fluid retention.
Dietary Sources
For general health, there should be a balance between omega-6 and omega-3 fatty acids. The ratio should be in the range of 2:1 to 4:1, omega-6 to omega-3, and some health educators advocate even lower ratios. Omega-6 fatty acids can be found in sunflower, safflower, soy, sesame, and corn oils. The average diet provides plenty of omega-6 fatty acids, so supplements are usually not necessary. People with specific conditions, such as eczema, psoriasis, arthritis, diabetes, or breast tenderness (mastalgia) may want to ask their doctors about taking omega-6 supplements.
Available Forms
Omega-6 fatty acids are available in supplemental oils that contain linoleic acid (LA) and GLA, such as EPO (Oenothera biennis) and black currant (Ribes nigrum) oils. Spirulina (often called blue-green algae) also contains GLA.
How to Take It
The average diet provides sufficient omega-6 fatty acids, so supplementation is usually not necessary unless you are treating a specific condition, such as:
Eczema
Psoriasis
Arthritis
Diabetes
Breast tenderness (mastalgia)
The dose and form of omega-6 fatty acids to be supplemented depends on many factors, including:
The condition being treated
Age
Weight
Other medications and supplements being used
Speak to your doctor to determine what form and what dose of omega-6 fatty acids are most appropriate for you.
Precautions
Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.
DO NOT take omega-6 fatty acids if you have a seizure disorder because there have been reports of these supplements causing seizures. Several reports describe seizures in people taking EPO. Some of these seizures developed in people with a previous seizure disorder, or in people taking EPO in combination with anesthetics. People who plan to undergo surgery requiring anesthesia should stop taking EPO 2 weeks ahead of time.
Borage seed oil, and possibly other sources of GLA, should not be taken during pregnancy because they may harm the fetus and induce early labor.
Avoid doses of GLA greater than 3,000 mg per day. At that level, an increase in inflammation may occur.
Side effects of EPO can include occasional headache, abdominal pain, nausea, and loose stools. In animal studies, GLA is reported to decrease blood pressure. Early results in human studies do not show consistent changes in blood pressure.
Laboratory studies suggest that omega-6 fatty acids, such as the fats found in corn oil, promote the growth of prostate tumor cells. Until more research is done, health professionals recommend not taking omega-6 fatty acids, including GLA, if you are at risk of or have prostate cancer.
Possible Interactions
If you are currently being treated with any of the following medications, you should not use omega-6 supplements without talking to your health care provider first.
Blood-thinning medications: People taking blood thinners, including warfarin (Coumadin) or clopidogrel (Plavix), should not take omega-6 fatty acid supplements without a doctor’s supervision. Omega-6 and omega-3 fatty acids may increase the risk of bleeding.
Ceftazidime: GLA may increase the effectiveness of ceftazidime. Ceftazidime, an antibiotic, is used against a variety of bacterial infections.
Chemotherapy for cancer: GLA may increase the effects of anti-cancer treatments, such as doxorubicin, cisplatin, carboplatin, idarubicin, mitoxantrone, tamoxifen, vincristine, and vinblastine.
Cyclosporine: Cyclosporine is a medication used to suppress the immune system after organ transplantation. Taking omega-6 fatty acids with cyclosporine may increase the immunosuppressive effects of this medication. It may also protect against kidney damage, which is a potential side effect from cyclosporine.
Phenothiazines: People taking a class of medications called phenothiazines to treat schizophrenia should not take EPO. EPO may interact with these medications and increase the risk of seizures. The same may be true for other omega-6 supplements. These medications include:
The human body can make most of the types of fats it needs from other fats or raw materials. That isn’t the case for omega-3 fatty acids (also called omega-3 fats and n-3 fats). These are essential fats—the body can’t make them from scratch but must get them from food. Foods high in Omega-3 include fish, vegetable oils, nuts (especially walnuts), flax seeds, flaxseed oil, and leafy vegetables.
What makes omega-3 fats special? They are an integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes. They provide the starting point for making hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They also bind to receptors in cells that regulate genetic function. Likely due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.
Omega-3 fats are a key family of polyunsaturated fats. There are three main omega-3s:
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) come mainly from fish, so they are sometimes called marine omega-3s.
Alpha-linolenic acid (ALA), the most common omega-3 fatty acid in most Western diets, is found in vegetable oils and nuts (especially walnuts), flax seeds and flaxseed oil, leafy vegetables, and some animal fat, especially in grass-fed animals. The human body generally uses ALA for energy, and conversion into EPA and DHA is very limited.
The strongest evidence for a beneficial effect of omega-3 fats has to do with heart disease. These fats appear to help the heart beat at a steady clip and not veer into a dangerous or potentially fatal erratic rhythm. Such arrhythmias cause most of the 500,000-plus cardiac deaths that occur each year in the United States. Omega-3 fats also lower blood pressure and heart rate, improve blood vessel function, and, at higher doses, lower triglycerides and may ease inflammation, which plays a role in the development of atherosclerosis.
Several large trials have evaluated the effect of fish or fish oils on heart disease. In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (known as the GISSI Prevention Trial), heart attack survivors who took a 1-gram capsule of omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo. Notably, the risk of sudden cardiac death was reduced by about 50 percent. In the more recent Japan EPA Lipid Intervention Study (JELIS), participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone.
Most Americans take in far more of another essential fat—omega-6 fats—than they do omega-3 fats. Some experts have raised the hypothesis that this higher intake of omega-6 fats could pose problems, cardiovascular and otherwise, but this has not been supported by evidence in humans. In the Health Professionals Follow-up Study, for example, the ratio of omega-6 to omega-3 fats wasn’t linked with risk of heart disease because both of these were beneficial. Many other studies and trials in humans also support cardiovascular benefits of omega-6 fats. Although there is no question that many Americans could benefit from increasing their intake of omega-3 fats, there is evidence that omega-6 fats also positively influence cardiovascular risk factors and reduce heart disease.
Researchers are taking a hard look at a different sort of balance, this one between possible effects of marine and plant omega-3 fats on prostate cancer. Results from the Health Professionals Follow-up Study and others show that men whose diets are rich in EPA and DHA (mainly from fish and seafood) are less likely to develop advanced prostate cancer than those with low intake of EPA and DHA. At the same time, some-but not all-studies show an increase in prostate cancer and advanced prostate cancer among men with high intakes of ALA (mainly from supplements). However, this effect is inconsistent. In the very large Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, for example, there was no link between ALA intake and early, late, or advanced prostate cancer.
helping your body’s natural defence against illness and infection (the immune system) work properly helping vision in dim light keeping skin and the lining of some parts of the body, such as the nose, healthy Good sources of vitamin A Good sources of vitamin A (retinol) include:
cheese eggs oily fish fortified low-fat spreads milk and yoghurt liver and liver products such as liver pâté – this is a particularly rich source of vitamin A, so you may be at risk of having too much vitamin A if you have it more than once a week (if you’re pregnant you should avoid eating liver or liver products) You can also get vitamin A by including good sources of beta-carotene in your diet, as the body can convert this into retinol.
The main food sources of beta-carotene are:
yellow, red and green (leafy) vegetables, such as spinach, carrots, sweet potatoes and red peppers yellow fruit, such as mango, papaya and apricots How much vitamin A do I need? The total vitamin A content of a food is usually expressed as micrograms (µg) of retinol equivalents (RE).
The amount of vitamin A adults aged 19 to 64 need is:
700 µg a day for men 600 µg a day for women You should be able to get all the vitamin A you need from your diet.
Any vitamin A your body does not need immediately is stored for future use. This means you do not need it every day.
What happens if I take too much vitamin A? Some research suggests that having more than an average of 1.5 mg (1,500 µg) a day of vitamin A over many years may affect your bones, making them more likely to fracture when you’re older.
This is particularly important for older people, especially women, who are already at increased risk of osteoporosis, a condition that weakens bones.
If you eat liver or liver pâté more than once a week, you may be getting too much vitamin A.
Many multivitamins contain vitamin A. Other supplements, such as fish liver oil, are also high in vitamin A.
If you take supplements containing vitamin A, make sure your daily intake from food and supplements does not exceed 1.5 mg (1,500 µg).
If you eat liver every week, do not take supplements that contain vitamin A.
If you’re pregnant Having large amounts of vitamin A can harm your unborn baby. So if you’re pregnant or thinking about having a baby, do not eat liver or liver products, such as pâté, because these are very high in vitamin A.
Also avoid taking supplements that contain vitamin A. Speak to your GP or midwife if you would like more information.
What does the Department of Health and Social Care advise? You should be able to get all the vitamin A you need by eating a varied and balanced diet.
If you take a supplement that contains vitamin A, do not take too much because this could be harmful.
Liver is a very rich source of vitamin A. Do not eat liver or liver products, such as pâté, more than once a week.
You should also be aware of how much vitamin A there is in any supplements you take.
If you’re pregnant or thinking of having a baby:
avoid taking supplements containing vitamin A, including fish liver oil, unless advised to by your GP avoid liver or liver products, such as pâté, as these are very high in vitamin A Women who have been through the menopause and older men, who are more at risk of osteoporosis, should avoid having more than 1.5mg of vitamin A a day from food and supplements.
This means:
not eating liver or liver products, such as pâté, more than once a week, or having smaller portions of these taking no more than 1.5mg of vitamin A a day in supplements (including fish liver oil) if you do not eat liver or liver products not taking any supplements containing vitamin A (including fish liver oil) if you eat liver once a week Having an average of 1.5mg a day or less of vitamin A from diet and supplements combined is unlikely to cause any harm
The nervous system is made up of neurons, the specialized cells that can receive and transmit chemical or electrical signals, and glia, the cells that provide support functions for the neurons. A neuron can be compared to an electrical wire: it transmits a signal from one place to another. Glia can be compared to the workers at the electric company who make sure wires go to the right places, maintain the wires, and take down wires that are broken. Recent evidence suggests that glia may also assist in some of the signaling functions of neurons.
Neurons communicate via both electrical signals and chemical signals. The electrical signals are action potentials, which transmit the information from one of a neuron to the other; the chemical signals are neurotransmitters, which transmit the information from one neuron to the next. An action potential is a rapid, temporary change in membrane potential (electrical charge), and it is caused by sodium rushing to a neuron and potassium rushing out. Neurotransmitters are chemical messengers which are released from one neuron as a result of an action potential; they cause a rapid, temporary change in the membrane potential of the adjacent neuron to initiate an action potential in that neuron.
Parts of a Neuron
Like other cells, each neuron has a cell body (or soma) that contains a nucleus and other cellular components. Neurons also contain unique structures, dendrites and axons, for receiving and sending the electrical signals that make neuronal communication possible:
Dendrites: are tree-like structures that extend away from the cell body to receive neurotransmitters from other neurons. Some types of neurons do not have any dendrites, some types of neurons have multiple dendrites. Dendrites can have small protrusions called dendritic spines, which further increase surface area for possible connections with other neurons.
Synapses: Dendrites receive signals from other neurons at specialized junctions called synapses. There is a small gap between two synapsed neurons, where neurotransmitters are released from one neuron to pass the signal to the next neuron.
Axon hillock: Once a signal is received by the dendrite, it then travels to the cell body. The cell body contains a specialized structure, the axon hillock that “integrates” signals from multiple synapses and serves as a junction between the cell body and an axon.
Axon: An axon is a tube-like structure that propagates the integrated signal to specialized endings called axon terminals. The axon carries the action potential to the next neuron. Neurons usually have one or two axons. Some axons are covered with myelin, which acts as an insulator to minimize dissipation of the electrical signal as it travels down the axon, greatly increasing the speed on conduction. This insulation is important as the axon from a human motor neuron can be as long as a meter, from the base of the spine to the toes. The myelin sheath is not actually part of the neuron, and is produced by glial cells. Along the axon there are periodic gaps in the myelin sheath called nodes of Ranvier, which are sites where the signal is “re-charged” as it travels along the axon.
It is important to note that a single neuron does not act alone: neuronal communication depends on the connections that neurons make with one another (as well as with other cells, like muscle cells). Dendrites from a single neuron may receive synaptic contact from many other neurons. For example, dendrites from a neurons in the cerebellum of the brain are thought to receive contact from as many as 200,000 other neurons.
Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are structures within cells that contain a person’s genes.
Genes are contained in chromosomes, which are in the cell nucleus.
A chromosome contains hundreds to thousands of genes.
Every normal human cell contains 23 pairs of chromosomes, for a total of 46 chromosomes.
A trait is any gene-determined characteristic and is often determined by more than one gene.
Some traits are caused by mutated genes that are inherited or that are the result of a new gene mutation.
Proteins are probably the most important class of material in the body. Proteins are not just building blocks for muscles, connective tissues, skin, and other structures. They also are needed to make enzymes. Enzymes are complex proteins that control and carry out nearly all chemical processes and reactions within the body. The body produces thousands of different enzymes. Thus, the entire structure and function of the body is governed by the types and amounts of proteins the body synthesizes. Protein synthesis is controlled by genes, which are contained on chromosomes.
The genotype (or genome) is a person’s unique combination of genes or genetic makeup. Thus, the genotype is a complete set of instructions on how that person’s body synthesizes proteins and thus how that body is supposed to be built and function.
The phenotype is the actual structure and function of a person’s body. The phenotype is how the genotype manifests in a person—not all the instructions in the genotype may be carried out (or expressed). Whether and how a gene is expressed is determined not only by the genotype but also by the environment (including illnesses and diet) and other factors, some of which are unknown.
A karyotype is a picture of the full set of chromosomes in a person’s cells.
Genes
Humans have about 20,000 to 23,000 genes.
DNA
Genes consist of deoxyribonucleic acid (DNA). DNA contains the code, or blueprint, used to synthesize a protein. Genes vary in size, depending on the sizes of the proteins for which they code. Each DNA molecule is a long double helix that resembles a spiral staircase containing millions of steps. The steps of the staircase consist of pairs of four types of molecules called bases (nucleotides). In each step, the base adenine (A) is paired with the base thymine (T), or the base guanine (G) is paired with the base cytosine (C). Each extremely long DNA molecule is coiled up inside one of the chromosomes.
Structure of DNA
DNA (deoxyribonucleic acid) is the cell’s genetic material, contained in chromosomes within the cell nucleus and mitochondria.Except for certain cells (for example, sperm and egg cells and red blood cells), the cell nucleus contains 23 pairs of chromosomes. A chromosome contains many genes. A gene is a segment of DNA that provides the code to construct a protein.The DNA molecule is a long, coiled double helix that resembles a spiral staircase. In it, two strands, composed of sugar (deoxyribose) and phosphate molecules, are connected by pairs of four molecules called bases, which form the steps of the staircase. In the steps, adenine is paired with thymine and guanine is paired with cytosine. Each pair of bases is held together by a hydrogen bond. A gene consists of a sequence of bases. Sequences of three bases code for an amino acid (amino acids are the building blocks of proteins) or other information.
Synthesizing proteins
Proteins are composed of a long chain of amino acids linked together one after another. There are 20 different amino acids that can be used in protein synthesis—some must come from the diet (essential amino acids), and some are made by enzymes in the body. As a chain of amino acids is put together, it folds upon itself to create a complex three-dimensional structure. It is the shape of the folded structure that determines its function in the body. Because the folding is determined by the precise sequence of amino acids, each different sequence results in a different protein. Some proteins (such as hemoglobin) contain several different folded chains. Instructions for synthesizing proteins are coded within the DNA.
Coding
Information is coded within DNA by the sequence in which the bases (A, T, G, and C) are arranged. The code is written in triplets. That is, the bases are arranged in groups of three. Particular sequences of three bases in DNA code for specific instructions, such as the addition of one amino acid to a chain. For example, GCT (guanine, cytosine, thymine) codes for the addition of the amino acid alanine, and GTT (guanine, thymine, thymine) codes for the addition of the amino acid valine. Thus, the sequence of amino acids in a protein is determined by the order of triplet base pairs in the gene for that protein on the DNA molecule. The process of turning coded genetic information into a protein involves transcription and translation.
Transcription and translation
Transcription is the process in which information coded in DNA is transferred (transcribed) to ribonucleic acid (RNA). RNA is a long chain of bases just like a strand of DNA, except that the base uracil (U) replaces the base thymine (T). Thus, RNA contains triplet-coded information just like DNA.
When transcription is initiated, part of the DNA double helix opens and unwinds. One of the unwound strands of DNA acts as a template against which a complementary strand of RNA forms. The complementary strand of RNA is called messenger RNA (mRNA). The mRNA separates from the DNA, leaves the nucleus, and travels into the cell cytoplasm (the part of the cell outside the nucleus—see figure ). There, the mRNA attaches to a ribosome, which is a tiny structure in the cell where protein synthesis occurs.
With translation, the mRNA code (from the DNA) tells the ribosome the order and type of amino acids to link together. The amino acids are brought to the ribosome by a much smaller type of RNA called transfer RNA (tRNA). Each molecule of tRNA brings one amino acid to be incorporated into the growing chain of protein, which is folded into a complex three-dimensional structure under the influence of nearby molecules called chaperone molecules.
Control of gene expression
There are many types of cells in a person’s body, such as heart cells, liver cells, and muscle cells. These cells look and act differently and produce very different chemical substances. However, every cell is the descendant of a single fertilized egg cell and as such contains essentially the same DNA. Cells acquire their very different appearances and functions because different genes are expressed in different cells (and at different times in the same cell). The information about when a gene should be expressed is also coded in the DNA. Gene expression depends on the type of tissue, the age of the person, the presence of specific chemical signals, and numerous other factors and mechanisms. Knowledge of these other factors and mechanisms that control gene expression is growing rapidly, but many of these factors and mechanisms are still poorly understood.
The mechanisms by which genes control each other are very complicated. Genes have chemical markers to indicate where transcription should begin and end. Various chemical substances (such as histones) in and around the DNA block or permit transcription. Also, a strand of RNA called antisense RNA can pair with a complementary strand of mRNA and block translation.
Replication
Cells reproduce by dividing in two. Because each new cell requires a complete set of DNA molecules, the DNA molecules in the original cell must reproduce (replicate) themselves during cell division. Replication happens in a manner similar to transcription, except that the entire double-strand DNA molecule unwinds and splits in two. After splitting, bases on each strand bind to complementary bases (A with T, and G with C) floating nearby. When this process is complete, two identical double-strand DNA molecules exist.
Mutation
To prevent mistakes during replication, cells have a “proofreading” function to help ensure that bases are paired properly. There are also chemical mechanisms to repair DNA that was not copied properly. However, because of the billions of base pairs involved in, and the complexity of, the protein synthesis process, mistakes may happen. Such mistakes may occur for numerous reasons (including exposure to radiation, drugs, or viruses) or for no apparent reason. Minor variations in DNA are very common and occur in most people. Most variations do not affect subsequent copies of the gene. Mistakes that are duplicated in subsequent copies are called mutations.
Inherited mutations are those that may be passed on to offspring. Mutations can be inherited only when they affect the reproductive cells (sperm or egg). Mutations that do not affect reproductive cells affect the descendants of the mutated cell (for example, becoming a cancer) but are not passed on to offspring.
Mutations may be unique to an individual or family, and most harmful mutations are rare. Mutations that become so common that they affect more than 1% of a population are called polymorphisms (for example, the human blood types A, B, AB, and O). Most polymorphisms have little or no effect on the phenotype (the actual structure and function of a person’s body).
Mutations may involve small or large segments of DNA. Depending on its size and location, the mutation may have no apparent effect or it may alter the amino acid sequence in a protein or decrease the amount of protein produced. If the protein has a different amino acid sequence, it may function differently or not at all. An absent or nonfunctioning protein is often harmful or fatal. For example, in phenylketonuria, a mutation results in the deficiency or absence of the enzyme phenylalanine hydroxylase. This deficiency allows the amino acid phenylalanine (absorbed from the diet) to accumulate in the body, ultimately causing severe intellectual disability. In rare cases, a mutation introduces a change that is advantageous. For example, in the case of the sickle cell gene, when a person inherits two copies of the abnormal gene, the person will develop sickle cell disease. However, when a person inherits only one copy of the sickle cell gene (called a carrier), the person develops some protection against malaria (a blood infection). Although the protection against malaria can help a carrier survive, sickle cell disease (in a person who has two copies of the gene) causes symptoms and complications that may shorten life span.
Natural selection refers to the concept that mutations that impair survival in a given environment are less likely to be passed on to offspring (and thus become less common in the population), whereas mutations that improve survival progressively become more common. Thus, beneficial mutations, although initially rare, eventually become common. The slow changes that occur over time caused by mutations and natural selection in an interbreeding population collectively are called evolution.
Did You Know…
Not all gene abnormalities are harmful. For example, the gene that causes sickle cell disease also provides protection against malaria.
Chromosomes
Chromosomes
IMAGE COURTESY OF THE CENTERS FOR DISEASE CONTROL AND PREVENTION PUBLIC HEALTH IMAGE LIBRARY AND SUZANNE TRUSLER, MPH, DRPH.
A chromosome is made of a very long strand of DNA and contains many genes (hundreds to thousands). The genes on each chromosome are arranged in a particular sequence, and each gene has a particular location on the chromosome (called its locus). In addition to DNA, chromosomes contain other chemical components that influence gene function.
Pairing
Except for certain cells (for example, sperm and egg cells or red blood cells), the nucleus of every normal human cell contains 23 pairs of chromosomes, for a total of 46 chromosomes. Normally, each pair consists of one chromosome from the mother and one from the father.
There are 22 pairs of nonsex (autosomal) chromosomes and one pair of sex chromosomes. Paired nonsex chromosomes are, for practical purposes, identical in size, shape, and position and number of genes. Because each member of a pair of nonsex chromosomes contains one of each corresponding gene, there is in a sense a backup for the genes on those chromosomes.
The 23rd pair is the sex chromosomes (X and Y).
Sex chromosomes
The pair of sex chromosomes determines whether a fetus becomes male or female. Males have one X and one Y chromosome. A male’s X comes from his mother and the Y comes from his father. Females have two X chromosomes, one from the mother and one from the father. In certain ways, sex chromosomes function differently than nonsex chromosomes.
The smaller Y chromosome carries the genes that determine male sex as well as a few other genes. The X chromosome contains many more genes than the Y chromosome, many of which have functions besides determining sex and have no counterpart on the Y chromosome. In males, because there is no second X chromosome, these extra genes on the X chromosome are not paired and virtually all of them are expressed. Genes on the X chromosome are referred to as sex-linked, or X-linked, genes.
Normally, in the nonsex chromosomes, the genes on both of the pairs of chromosomes are capable of being fully expressed. However, in females, most of the genes on one of the two X chromosomes are turned off through a process called X inactivation (except in the eggs in the ovaries). X inactivation occurs early in the life of the fetus. In some cells, the X from the father becomes inactive, and in other cells, the X from the mother becomes inactive. Thus, one cell may have a gene from the person’s mother and another cell has the gene from the person’s father. Because of X inactivation, the absence of one X chromosome usually results in relatively minor abnormalities (such as Turner Syndrome). Thus, missing an X chromosome is far less harmful than missing a nonsex chromosome.
Inactive X Chromosome
COURTESY OF DRS. L. CARRELL AND H. WILLIARD, CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE.
If a female has a disorder in which she has more than two X chromosomes, the extra chromosomes tend to be inactive. Thus, having one or more extra X chromosomes causes far fewer developmental abnormalities than having one or more extra nonsex chromosomes. For example, women with three X chromosomes (triple X Syndrome) are often physically and mentally normal. Males who have more than one Y chromosome ( Home.see XYY Syndrome) may have physical and mental abnormalities.
Chromosome abnormalities
There are several types of chromosomes abnormalities. A person may have an abnormal number of chromosomes or have abnormal areas on one or more chromosomes. Many such abnormalities can be diagnosed before birth.
Abnormal numbers of nonsex chromosomes usually result in severe abnormalities. For example, receiving an extra nonsex chromosome may be fatal to a fetus or lead to abnormalities such as Down Syndrome, which commonly results from a person having three copies of chromosome 21. Absence of a nonsex chromosome is fatal to the fetus.
Large areas on a chromosome may be abnormal, usually because a whole section was left out (called a deletion) or mistakenly placed in another chromosome (called translocation). For example, chronic myelogenous leukemia is sometimes caused by translocation of part of chromosome 9 onto chromosome 22. This abnormality can be inherited or be the result of a new mutation.
Mitochondrial chromosomes
Mitochondrion are tiny structures inside cells that synthesize molecules used for energy. Unlike other structures inside cells, each mitochondrion contains its own circular chromosome. This chromosome contains DNA (mitochondrial DNA) that codes for some, but not all, of the proteins that make up that mitochondrion. Mitochondrial DNA usually comes only from the person’s mother because, in general, when an egg is fertilized, only mitochondria from the egg become part of the developing embryo. Mitochondria from the sperm usually do not become part of the developing embryo.
RNA, is another macromolecule essential for all known forms of life. Like DNA, RNA is made up of nucleotides. Once thought to play ancillary roles, RNAs are now understood to be among a cell’s key regulatory players where they catalyze biological reactions, control and modulate gene expression, sensing and communicating responses to cellular signals, etc.
The chemical structure of RNA is very similar to that of DNA: each nucleotide consists of a nucleobase a ribose sugar, and a phosphate group. There are two differences that distinguish DNA from RNA: (a) RNA contains the sugar ribose, while DNA contains the slightly different sugar deoxyribose (a type of ribose that lacks one oxygen atom), and (b) RNA has the nucleobase uracil while DNA contains thymine. Unlike DNA, most RNA molecules are single-stranded and can adopt very complex three-dimensional structures.
DNA and RNA similarities and differences
The universe of protein-coding and non-protein-coding RNAs (ncRNAs) is very diverse vis-à-vis biogenesis, composition and function, and has been expanding rapidly. Among the ncRNAs, microRNAs (miRNAs) represent the best-studied class to date and have been shown to regulate the expression of their protein-coding gene targets in a sequence-dependent manner Monocistronic versus polycistronic RNA
An RNA molecule is said to be monocistronic when it captures the genetic information for a single molecular transcriptional product, e.g. a single miRNA precursor or a single primary mRNA. Most eukaryotic mRNAs are indeed monocistronic. On the other hand, rRNAs and some miRNAs are known to be polycystronic. In the case of polycistronic mRNAs, the primary transcript comprises several back-to-back mRNAs, each of which will be eventually translated into an amino acid sequence (polypeptide). Such polypeptides usually have a related function (they often are the subunits composing a final complex protein) and their coding sequences are grouped into a single primary transcript, which in turn permits them to share a common promoter and to be regulated together.
Protein-coding RNAs / gene expression
One of the best known and best-studied classes of RNAs are messenger RNAs (mRNAs). MRNAs carry the genetic information that directs the synthesis of proteins by the ribosomes. All cellular organisms use mRNAs. The process of protein synthesis makes use of two more classes of RNAs, the transfer RNAs (tRNAs) and the ribosomal RNAs (rRNAs). The role of tRNAs is the delivery of amino acids to the ribosome where rRNAs link them together to form proteins.
mRNAs: A fully processed mRNA typically comprises multiple exons that have been assembled into a single chain following splicing of the nascent primary transcript and the removal of intervening introns. The mRNA molecule includes a 5´ cap, the so-called 5´ untranslated region (UTR), the coding region, the 3´UTR, and a variable-length poly(A) tail.
5′ cap: The 5´ cap is a modified guanine nucleotide added to the “front” (5´ end) of the pre-mRNA using a 5´-5´-triphosphate linkage. This modification is critical for recognition and proper attachment of mRNA to the ribosome, as well as protection from 5´ exonucleases.
Untranslated regions: Untranslated regions (UTRs) are nucleotide stretches that flank the coding region and are not translated into amino acids. There are two UTRs: the “five prime untranslated region” or 5´UTR, and the “three prime untranslated region” or 3´UTR. These regions are part of the primary transcript and remain after the splicing of exons into the mRNA. As such UTRs are exonic regions. Several functional roles have been attributed to the untranslated regions, including mRNA stability, mRNA localization, and translational efficiency. The ability and nature of functions performed by a UTR depends on the actual sequence of the UTR and typically differs from one mRNA to the next. The UTRs’ control of translational efficiency has been shown to span the entire spectrum, from enhancement to the complete inhibition of translation. RNA binding proteins that bind to either the 5´ or 3´UTR can influence translation by modulating the ribosome’s ability to bind to the mRNA. Additionally, miRNAs that bind to the 3´UTR may also affect translational efficiency or mRNA stability.
Coding regions: A subset of the nucleotide sequence that is spanned by the transcript’s exons is used to guide the translation into the corresponding amino acid sequence and is referred to as the coding regions. The length of a coding region is always a multiple of three, and a direct consequence of the fact that each amino acid requires three nucleic acids (the “codon”) for its definition. Since there are 43=64 nucleotide triplets but only 20 amino acids, it follows that a given amino acid can be encoded by more than one triplets. The correspondence between a triplet and an amino acid is given by the codon table which also defines the ‘genetic code.’ The codon tables of organisms are largely identical but slight variations have been discovered over the course of the last 30 years. Codons are ‘decoded’ and translated into peptide polymers by the ribosome. Coding regions begin with the start codon and end with a stop codon. In general, the start codon is an AUG triplet and the stop codon is one of UAA, UAG, or UGA.
Poly(A) tail: The variable length 3´ poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the 3´ end of the pre-mRNA. This tail promotes export from the nucleus, translation, and stability of mRNA.
The structure of an mRNA
RNA Interference
RNA interference is a process that moderates gene expression in a sequence dependent manner. The RNAi pathway is found in all higher eukaryotes and was recently found in the budding yeast as well. Viruses have also been shown to be RNAi-aware in that they use their natural host’s RNAi pathway to their benefit.
RNAi is initiated by Dicer, a double-stranded-RNA-specific endonuclease from the RNase III protein family. Dicer cleaves double-stranded RNA (dsRNA) molecules into short fragments of ~21 nucleotides, with a two-nucleotide overhang at their 3′ end, as well as a 5′ phosphate and a 3′ hydroxyl group. The RNAi pathway can be engaged by two types of small regulatory non-coding RNAs: a) small interfering RNAs (siRNAs), which are typically exogenous, and b) microRNAs (miRNAs), which are endogenous. SiRNAs are double-stranded ncRNAs that are mainly delivered to the cell experimentally by various transfection methods although they have been described to be produced form the cell itself. MiRNAs are another type of small ncRNAs that are transcribed from the organism’s DNA. After processing of the primary siRNAs and miRNAs by Dicer, typically one of the two strands is loaded onto the RNA-induced silencing complex (RISC), a complex of RNA and proteins that includes the Argonaute protein, whereas the other strand is discarded. The loaded siRNAs and miRNAs guide RISC’s binding to specific mRNAs (targets). The sequence of the siRNA/miRNA determines the identity of the target. The resulting heteroduplex of the siRNA/miRNA and its target mRNA is characterized by base-pairing that generally spans much of the siRNA/miRNA’s length. SiRNAs are typically designed to be perfectly complementary to their targets. On the other hand, miRNAs need not be fully-complementary to the mRNA that they target. This imprecise matching gives miRNAs the potential to target multiple endogenous mRNAs simultaneously. Whether induced by an siRNA or an miRNA, the downstream effect is the down-regulation of the targeted mRNA either via degradation or translational inhibition.
RNA interference in mammalian cells
Designer siRNAs are now widely used in the laboratory to down-regulate specific proteins whose function is under study. At the same time, the ability to engage the RNAi pathway in an on demand manner suggests the possibility that RNAi can be used in the clinic to reduce the production of those proteins that are over-expressed in a given disease context. Analogously, RNAi can also be used to “sponge” away excess amounts of an endogenous miRNA that would otherwise down-regulate a needed protein. The delivery method remains an important consideration for the development of RNAi-based therapies as the active molecule needs to be delivered efficiently and in a tissue-specific manner in order to maximize impact and diminish off-target effects.
Non protein coding RNAs (a.k.a non-coding RNAs or ncRNAs)
The expression of proteins is determined by genomic information, and their presence supports the function of cell life. Parts of an organism’s genome are transcribed in an orderly tissue- and developmental phase- specific manner into RNA transcripts that are destined to effect the eventual production of proteins.
Until fairly recently, it was believed that the molecules that are important for the function of a cell are those described by the “Central Dogma” of biology, namely messenger RNAs and proteins. Things began to change with the discovery of microRNAs more than 20 years ago in plants and animals. Subsequent research efforts have demonstrated that large parts of an organism’s genome will be transcribed at one time point or another into RNA, but will not be translated into an amino acid sequence. These RNA transcripts have been referred to as ncRNAs and there is increased appreciation that many of them are indeed functional and affect key cellular processes.
There are many recognizable classes of ncRNAs, each having a distinct functionality. These include: transfer RNAs (tRNAs); ribosomal RNAs (rRNAs); the above-mentioned miRNAs; small nucleolar RNAs (snoRNAs); piwi-interacting (piRNAs); transcription initiation RNAs (tiRNAs); human microRNA-offset (moRNAs); sno-derived RNAs (sdRNAs); long intergenic ncRNAs (lincRNAs); etc. The full extent of distinct classes of ncRNAs that are encoded within the human genome is currently unknown but are believed to be numerous.
Short non-coding RNAs: At least three classes of small RNAs are encoded in our genome, based on their biogenesis mechanism and the type of Ago protein that they are associated with miRNAs, endogenous siRNAs and piRNAs. It should be noted, however, that the recent discoveries of numerous non‐canonical small RNAs have somewhat blurred the boundaries between the classes.
MicroRNAs (miRNAs): MicroRNAs (miRNAs) comprise a large family of naturally occurring, endogenous, single-stranded ~22-nucleotide-long RNAs. MiRNAs function as key post-transcriptional regulators of gene expression by base-pairing with their target mRNAs. Originally believed to effect their impact exclusively through the target mRNAs 3´UTR, they have since been shown to have extensive coding region targets as well. More than one thousand miRNAs are currently known for the human genome, and each of them has the ability to down regulate the expression of possibly thousands of protein coding genes. In mammals, miRNAs are predicted to control more than ~90% of all protein-coding genes.
miRNA biogenesis: MicroRNAs (miRNAs) are either transcribed explicitly by RNA polymerase II or generated from the appropriately-long introns of protein-coding genes as a by-product of splicing.Canonical Pathway
In the canonical pathway, transcription of the primary miRNA precursor (pri-miRNA) is carried out by RNA polymerase II. The pri-miRNA is processed into a precursor miRNA (pre-miRNA) by the “microprocessor complex” which comprises Drosha, a member of the RNase III family of endonucleases, and DGCR8, a double-stranded-RNA-binding protein. Pre-miRNAs are generaly 60-70-nucleotides in length, have a two-nucleotide overhang at the 3′ end and a 5′ phosphate group, and fold into a characteristic hairpin-like structure. Exportin-5 recognizes the two-nucleotide 3´-overhang, characteristic of RNase III-mediated cleavage, and shuttles the pre-miRNA through the nuclear pore into the cytoplasm, where it is further processed by Dicer, another endonuclease. Dicer pairs with TRBP and PACT, both double-stranded-RNA-binding proteins, and cleaves the pre-miRNA to form a transient ~22-nucleotide double stranded RNA, again with two-nucleotide overhangs at the 3´end. One of the two strands, typically the one with a relatively lower stability of base-pairing at the 5´-end (“the thermodynamic asymmetry rule”) is referred to as the “guide” strand and gives rise to the “mature” miRNA that associates with the Argonaute (AGO) protein to form the core of miRNA-associated RISC (miRISC) or simply, RISC. The second strand, referred to as the “passenger” strand is typically degraded. However, there have been well-documented examples of passenger strands giving rise to mature products, known as the miRNA*, which are also involved in regulatory activities. The miRNA helps direct RISC to targets in a sequence-dependent manner thereby mediating the repression of the target’s expression.
Alternative pathways (non-canonical)
Drosha independent pathways: As mentioned above, most miRNAs either originate form their own transcription units or derive from the exons or introns of other genes and require both Drosha and Dicer for cleavage in their maturation. It was recently shown however first in Droshophila and later in mammals that short hairpin introns, called mirtrons can be alternative sources of miRNAs. Although there are several differences between mammalian and invertebrate mirtrons, both are Drosha independent. Mirtrons are short introns with hairpin potential that can be spliced and debranched into pre-miRNA mimics and then enter the canonical pathway. Post nuclear export, they can then be cleaved by Dicer and incorporated into RISC.
Dicer independent pathways: MiRNA biogenesis independent of Dicer has only been described thus far for miR-451. This miRNA is processed by Drosha but its does not require Dicer. Instead, its pre-miRNA, once loaded into Ago, is cleaved by the Ago catalytic centre to generate an intermediate 3’ end, which is further trimmed. Importantly, the Ago catalytic function for the miR-451 biogenesis was shown in Ago2 homozygous mutants that were found to have loss of miR-451 and died shortly after their birth with anemia.miRNA biogenesis
miRNA function: For miRNAs to pair with their target mRNAs, a region of the miRNA sequence near its 5′ end needs to be involved in base-pairing. The region in question spans nucleotide positions 2 through 7 inclusive and is known as the ‘seed’. Not all nucleotides of the seed region need to be paired for the heteroduplex to have a functional effect. The base-pairing in the seed region can comprise Watson-Crick bonding, although this was recently shown to neither be necessary nor sufficient.In animals, it was believed for many years that the miRNA-binding sites are exclusively in the 3′UTR of mRNAs. However, it was recently shown that animal miRNAs could target mRNA coding regions equally effectively and extensively. In plants, miRNA targeting is predominantly through coding region targets.The ways in which miRNAs cause down-regulation of their target mRNAs has been hotly debated. The possible mechanisms include: translational inhibition; removal of the poly(A) tail from mRNAs (deadenylation); disruption of cap–tail interactions; and, mRNA degradation by exonucleases, although highly complementary targets can be cleaved endonucleolytically. Other types of regulatory function of miRNAs have also been described, and include translational activation, heterochromatin formation, and DNA methylation.
miRNA nomeclature: Each miRNA is identified by a unique numerical name. The standard naming system uses abbreviated three letter prefixes to designate the species (e.g., hsa- in Homo sapiens, which is usually ignored in the literature when the organism is implied), followed by the three-letter tag mir or miR, followed by a number. The number is assigned by the miRBase Registry. The mature sequences are designated using the tag ‘miR’ (capitalized R), whereas the precursor hairpins use the tag ‘mir’. Orthologous miRNAs across organisms differ only in their species name (e.g., hsa-miR-101 in humans vs. mmu-miR-101 in mice). Nearly identical miRNAs that differ at only one or two positions are distinguished by lettered suffixes (e.g., miR-10a and miR-10b). Paralogous miRNAs, i.e. miRNAs whose precursors have multiple instances, i.e. distinct loci, in the same genome are indicated by numbered suffixes (e.g., mir-281-1 and mir-281-2); such precursors give rise to identical mature miRNAs, but not necessarily with the same time kinetics.
Ultraconserved genes or UCGs: UCGs are ncRNAs that are transcribed from ultraconserved regions (UCRs). UCRs are genomic segments that have identified to be 100% conserved between orthologous regions in the human, mouse and rat. Of these, 481 are transcribed (T-UCRs) from integenic sequences (39%), from introns (43%) while the remainder is exonic or exon overlapping.
Small nucleolar RNAs (snoRNAs): Small nucleolar RNAs (snoRNAs) are a highly evolutionarily conserved class of RNAs and have been considered on of the best-characterized classes of nc-RNAs22. They are intermediate-sized RNAs of 60-300 nucleotides in length and are predominantly found in the nucleus. Two major classes of snoRNAs have been identified which possess distinctive, evolutionary conserved sequence elements. One group contains the the box C/D motif, whereas snoRNAs in the other group carry the box H/ACA elements. SnoRNAs are components of the small nucleolar ribonucleoproteins (snoRNPs) and are involved in the post-transcriptional modification of rRNAs and some splicesomal RNAs. In particular, most C/D and H/ACA snoRNAs function in 2’-O-methylation and pseudouridylation respectively of various classes of RNAs. These modifications are important for the production of efficient ribosomes. Recently, many “orphan” snoRNAs that lack complementarities to rRNAs, tRNAs or other known stable RNAs have been identified, suggesting that they might function in cellular processes other than RNA modification.
piwi-interacting (piRNAs): PIWI-interacting RNAs (piRNAs) are 25–30 nucleotides in length and have been found in most metazoans. They are Dicer-independent and they bind to particular Argonaute proteins called PIWI proteins. These RNA-protein complexes are involved in the epigenetic and and post-transcriptional gene silencing of transposable and other repetitive elements. PiRNAs have also been recently linked to the regulation of imprinted-DNA methylation.
transcription initiation RNAs (tiRNAs): Transcription initiation RNAs (tiRNAs) are derived from sequences on the same strand as the transcription start sites (TSS) and are preferentially associated with GC rich promoters. They have been found to have a modal lenth of 18 nucleotides that map within -60 and +120 nucleotides of TSS. They are associated with highly expressed transcripts and sites of RNA polymerase II binding.
human microRNA-offset (moRNAs): MicroRNA-offset RNAs (moRNAs) are generated from sequences immediately adjacent to to mature miR and miR* loci. They have been found in the tunicate Ciona intestinalis but also in human microRNA precursors, albeit in low levels. The high level of conservation and the example of miR-219 with moRNAs conserved between humans and Ciona suggests that they might have a functional role.
sno-derived RNAs (sdRNAs): Sno-derived RNAs (sdRNAs) comprise a novel class of small RNAs in eykaryotes. The ones that derive from H/ACA snoRNAs are predominantly 20–24 nucleotides long and originate from the 3’ end, where as those derived from C/D snoRNAs are either 17–19 nt long or >27 nt long and predominantly originate from the 5’ end. 28 Through a comparison of human small RNA deep sequencing data sets it was shown that box C/D sdRNA accumulation patterns are conserved across multiple cell types, although the ratio of the abundance of different sdRNAs from a given snoRNA varied.
Long non-coding RNAs: Long non-coding RNAs are a heterogenous group of non-coding transcripts that are longer than 200 nucleotides (a rather arbitrarily condition/limit that ignores the possibility of ncRNAs with lengths between 40 and 200) that are involved in various processes. A large number of such RNAs have been identified and constitute the largest portion of the mammalian non-coding transcriptome. Such RNAs have been identified in both protein-coding loci and also within intergenic stretches. Numerous protein-coding loci give rise to non-protein-coding RNA , with notable examples being β-actin, γ-actin, RB1 etc.
Other categories: Long intergenic RNAs (lincRNAs), and others with enhancer-like functions were described only recently. Attempts to functionalize these other classes of ncRNAs are currently in their very early stages. LincRNAs arise from intergenic regions and exhibit a specific chromatin signature that consists of a short stretch of trimethylation of histone protein H3 at the lysine in position 4 (H3K4me3) – characteristic of promoter regions, followed by a longer stretch of trimethylation of histone H3 at the lysine in position 36 (H3K36me3) – characteristic of transcribed regions. This lincRNA profile is also known as “K4-K36 signature”. Transcripts from active enhancer regions with another chromatin signature, the H3 lysine 4 monomethylation (H3K4me1) modification have also been described, although it is not clear whether they represent a distinct class of lincRNAs.
The biological role of long ncRNAs as a class remains largely elusive. Several specific cases have been shown to be involved in transcriptional gene silencing, and the activation of critical regulators of development and differentiation: these exerted their regulatory roles by interfering with transcription factors or their co-activators, though direct action on DNA duplex, by regulating adjacent protein-coding gene expression, by mediating DNA epigenetic modifications, etc.
RNA splicing
is a complex process mediated by a large RNA-containing protein called a spliceosome. This consists of five types of small nuclear RNA molecules (snRNA) and more than 50 proteins (small nuclear riboprotein particles).
RNA reverse transcription
Reverse transcription is the transfer of information from RNA to DNA (the reverse of normal transcription). This is known to occur in the case of retroviruses, such as HIV, as well as in eukaryotes, in the case of retrotransposons and telomere synthesis.
RNA editing / post-transcriptional modifications
Post-transcriptional modification is a process in cell biology by which, primary transcript RNA is converted into mature RNA. A notable example is the conversion of precursor messenger RNA into mature messenger RNA (mRNA), which includes splicing and occurs prior to protein synthesis. This process is vital for the correct translation of the genomes of eukaryotes as the human primary RNA transcript that is produced as a result of transcription contains both exons, which are coding sections of the primary RNA transcript and introns, which are the non coding sections of the primary RNA transcript.
Post-trancriptional modifications that lead to a mature mRNA include the (i) addition of a methylated guanine cap to the 5′ end of mRNA and (ii) the addition of a poly-A tail to the other end. The cap and tail protect the mRNA from enzyme degradation and aid its attachment to the ribosome. In addition, (iii) introns (non-coding) sequences are spliced out of the mRNA and exons (coding) sequences are spliced together. The mature mRNA transcript will then undergo translation.
Researchers are taking a hard look at a different sort of balance, this one between possible effects of marine and plant omega-3 fats on prostate cancer. Results from the Health Professionals Follow-up Study and others show that men whose diets are rich in EPA and DHA (mainly from fish and seafood) are less likely to develop advanced prostate cancer than those with low intake of EPA and DHA. At the same time, some-but not all-studies show an increase in prostate cancer and advanced prostate cancer among men with high intakes of ALA (mainly from supplements). However, this effect is inconsistent. In the very large Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, for example, there was no link between ALA intake and early, late, or advanced prostate cancer. 
