HIV vaccine production

Research on HIV over the past decade has led to many promising ideas for vaccines to prevent infection by the AIDS virus, but very few candidate vaccines have been tested in clinical trials. One reason for this is the technical difficulty of manufacturing vaccines based on the envelope proteins of the virus, according to Phil Berman, who led development of a major component of the only vaccine to have shown any efficacy against HIV in a clinical trial.

Berman, the Baskin Professor of Biomolecular Engineering at UC Santa Cruz, has now developed new methods for the production of HIV vaccines. His approach solves major technical problems which have bedeviled the field. Berman described the new methods, and the candidate vaccines his lab has produced.

Researcher was able to use robotics to shorten the time required to produce stable cell lines, needed to make the proteins for a vaccine, while at the same time greatly increasing how much of the protein the cell lines can produce. The improved yield makes it possible to reduce the size of the bioreactor needed to make vaccine for large clinical trials—from 200- to 10,000-liter vessels to 50- or 100-liter vessels—resulting in tremendous savings in the equipment required and cost of materials.

They were  able to create cell lines that make HIV envelope proteins with the right kind of carbohydrate components (called glycans) needed for an effective immune response. The carbohydrates attached to the protein are really important, something no one realized until recently. The conventional way of making these envelope protein vaccines incorporated the wrong kind of carbohydrates.

Cell lines derived from Chinese hamster ovary (CHO) cells are the industry standard used to produce complex recombinant proteins for therapeutic use. These cells are also useful for the production of HIV vaccines. The gene for the desired protein is transferred into CHO cells in a process called transfection, and tens of thousands of transfected cells are screened to find the few rare cells that produce large amounts of the protein. The best cell lines are grown in large batches, in a process similar to yeast fermentation for making beer, and the proteins are then isolated and purified.

Berman's lab developed a new robotic method to isolate high-producing cell lines making HIV envelope proteins. This shortened the time required to produce stable cell lines from 18 to 24 months to just 2 or 3 months, while increasing yields by a factor of 100 to 200. Those improvements are in comparison with Berman's previous experience creating the AIDSVAX vaccine, first at Genentech and then at VaxGen.

Fluorescent antibodies were used to label the HIV gp120 protein and identify high-producing cell lines. Credit: Phil Berman, UCSC. AIDSVAX was one component of an experimental vaccine regimen used in a large-scale clinical trial known as RV144, which showed 31 percent efficacy in preventing new HIV infections. The RV144 results showed that protection was correlated with antibodies to a certain segment of an HIV envelope protein called gp120.

 The original AIDSVAX vaccine had the completely wrong type of carbohydrate, and that we might improve the level of protection if we could find a way to make it with the proper type of carbohydrate. They set out to create a cell line that can produce the unusual glycans found on HIV envelope proteins rather than the complex glycans CHO cells normally produce. This was made possible by the powerful new gene editing technology known as CRISPR/Cas9.

 They used CRISPR to create a new cell line they called MGAT CHO, which produces proteins lacking complex glycans containing sialic acid and enriched for the simple "high mannose" type found on HIV envelope proteins. An unexpected benefit of this new cell line was that it enabled a simpler, less expensive process for recovering and purifying the proteins.

Carbohydrates may not be immunogenic, but HIV turns out that the most important antibodies are directed to carbohydrate. It leads to an improved version of the vaccine used in the RV144 trial. Berman's lab currently has two cell lines he said are ready to start producing vaccines on a large scale. He is now looking for partners and funding to bring them into clinical trials. Researchers have continued to use the AIDSVAX vaccine in clinical studies because it has been so hard to make new HIV vaccines.
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How food influenced how fat is stored

Scan images reveal for the first time how weight is stored in the body. Compared to a low-fat diet, eating Mediterranean foods with a minimal-carbohydrates intake for lunch just three times a week significantly reduces fat storage around the heart and liver. Adopting a diet rich in vegetables, fruit and nuts also significantly reduces waist circumference.

 Moderate exercise combined with a Mediterranean/low carbohydrates diet may reduce the amount of some fat deposits. Moderate, but persistent, weight loss may have dramatic beneficial effects on fat deposits related to diabetes and cardiovascular diseases. Storing excess fat around the organs increases the risk of heart disease, type 2 diabetes and stroke.

The researchers analysed sedentary adults with abdominal obesity or abnormally high levels of lipids in their blood.The study's participants were given either a low-fat or Mediterranean-diet lunch at least three times a week for months. Both lunches contained the same number of calories. All of the participants also received a daily 28g snack of walnuts. Some of the participants were given free gym membership to complete moderate physical activity.

Whole-body MRI scans were taken at six and 18 months. Mediterranean diets reduce waist circumference and internal fat. Results reveal exercise combined with a Mediterranean diet significantly reduces fat storage around the heart and liver more than eating low-fat food.

Such a diet also decreases waist circumference. Weight loss is similar between people eating either diets. These findings suggest that moderate exercise combined with a Mediterranean/low carb diet may help reduce the amount of some fat deposits even if you don't lose significant weight as part of the effort.
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Effects of DNA on dieting

Research in animal models with different genetics shows that one diet really doesn't fit all, and what works for some may not be best for others. The researchers used four different groups of animal models to look at how five diets affect health over a six-month period. The genetic differences within each group were almost non-existent, while the genetics between any two of the groups would translate to roughly the same as those of two unrelated people.

The researchers chose the test diets to mirror those eaten by humans-an American-style diet (higher in fat and refined carbohydrates, especially corn) and three that have gotten publicity as being 'healthier': Mediterranean (with wheat and red wine extract), Japanese (with rice and green tea extract) and ketogenic, or Atkins-like (high in fat and protein with very few carbs).

The fifth diet was the control group who ate standard commercial chow.
Although some so-called healthy diets did work well for most individuals, one of the four genetic types did very poorly when eating the Japanese-like diet, for example. The fourth strain, which performed just fine on all of the other diets, did terrible on this diet, with increased fat in the liver and markings of liver damage.

They measured physical signs, especially evidence of metabolic syndrome, which is a collection of signs of obesity-related problems, including high blood pressure and cholesterol, fatty liver and levels of blood sugar. They also studied any behavioral differences, from how much they moved around to how much they ate.

Perhaps as could be expected, both in earlier research and in anecdotal evidence in humans, the animal models tended not to do great on the American-style diet. A couple of the strains became very obese and had signs of metabolic syndrome. Other strains showed fewer negative effects, with one showing few changes except for having somewhat more fat in the liver.

With the Mediterranean diet, there was a mix of effects. Some groups were healthy, while others experienced weight gain, although it was less severe than in the American diet. The results demonstrated that a diet that makes one individual lean and healthy might have the complete opposite effect on another. It depends very much on the genetics of the individual and there isn't one diet that is best for everyone.
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Causes of abdominal fat

Excess abdominal fat may be the result of excess consumption of sugar and simple white carbohydrates. However,
sleep deprivation, stress or wrong exercise can leads to abnormal fat.

Having abdominal fat increases the risk of type 2 diabetes and heart problems.
Cortisol, the stress hormone, plays a part in laying down central adipose tissue. You can avoid stress by engaging in yoga practice and mindfulness to your daily routine.

High-sugar diet can increase abdominal fat, cut down on sugar, saturated fats and white refined foods such as white bread, pasta, rice and potatoes, as they metabolise quickly, resulting in elevated blood sugar levels that promotes fat storage.

Eat more of lean meats, vegetables, fruits, monounsaturated and polyunsaturated fats, such as those found in nuts and avocados. Avoid eating fruit after a meal, as fruit can cause food to ferment in your stomach, leading to bloating and lots of gas.

Fat can play a vital role in weight loss, by slowing the release of nutrients into the bloodstream, add little fat to your meal. Hormonal disruption can affect fat distribution, seek medical help.
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Vitamin B increases the risk of lungs cancer

According to a new study, high-dose and long-term use of vitamins B12, B6 and smoking increase the risk of lung cancer. Using high dose of vitamin B6 and B12 may leads to development of lungs cancer.

Researchers analyzed data from some patients and evaluate vitamin and other mineral supplements in relation to cancer risk. They discovered that men who take high-dose of vitamin B6 and B12 supplements for a decade had higher risks for developing lung cancer.

Human body needs vitamins B6 and B12 to ensure red blood cells are healthy and to process proteins, fat and carbohydrate. Foods rich in vitamin B are: meat, fish, cheese, eggs and milk, and fortified cereals.

 Some vitamin B supplements contained doses which were higher than the daily recommended amount, eating foods rich in vitamin B is enough for vitamins required. The discovery shows that taking high doses of B6 and B12 for a long period of time could increase the risk of developing lung cancer.
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Bacteria may boost athletic performance

Bacteria in the digestive tract can boost performance of athletes. The bugs in our gut affect our energy metabolism, making it easier to break down carbohydrates, protein and fiber. They are also involved in inflammation and neurological function.

The microbiome could be relevant for applications in endurance, recovery and mental toughness. Researchers collected fecal samples on a daily basis from athletes training for marathon, a week before and after the race. The researchers sequenced the genomes of the sampled bacteria, using computational metagenomic methods to figure out how many and what types of microbes inhabited the fecal samples.

 When they compared the pre-race and post-race samples, the researchers found a sudden spike in the population of one particular type of bacteria after the marathon. This bug's natural function is to break down lactic acid. During intense exercise, the body produces more lactic acid than usual, which can lead to muscle fatigue and soreness.

Researchers discovered that the bug is very good at breaking down lactic acid in a test tube and remains viable after it passes through the digestive system of mice. The researchers are now feeding the bacteria to mice to measure its effects on lactic acid levels and fatigue.
This leads to discovery of a bacteria in ultramarathoners that can break carbohydrates and fiber which is useful during a 100-mile.
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Healthy foods for type 2 diabetes

Type 2 diabetes is when a pancreas does not produce enough insulin or when their is resistant to insulin.
Blood glucose levels can be manage with healthy foods and active lifestyle.

What you eat regularly is essential for weight control and reducing blood glucose levels when you have type 2 diabetes. Balance is the key for eating healthy diet, you don't have to fast, avoid carbohydrates or any class of food.

Choosing healthy foods from different classes of foods can lower blood sugar. Foods with low-glycemic levels slowly digest to avoid spikes in blood sugar levels.

 Eat foods like apples, pears, peaches, bananas, mangoes, papayas, almonds, walnuts, whole grains, fish, nuts, seeds, avocados, coconut, organic meat, eggs and wild caught fish.
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Low carbohydrates diets can imitate effect of ecstasy on your brain

 Low-carb diet changes your metabolic  from burning more carbohydrates to burning of more fat than carbohydrates, this is a process known as ketosis.

When human body uses up carbohydrates glucose reserves, the body stimulates the breakdown of stored fat into fatty acids and releases them into the blood.

When fatty acids reach the liver they are changed into acetoacetate, a metabolic fuel that belongs to a family of ketones.

Acetoacetate decomposes to carbon dioxide and acetone, low-carbohydrates dieters and people who are fasting usually have sweet smelling breath.

A healthy liver minimises the acetone lost through the lungs by converting most of the acetoacetate it produces to beta-hydroxybutyrate BHB. This can cause euphoric feelings.

During ketosis, BHB can reach high levels in the brain, where it can bind to the same anxiety-reducing receptors as recreational drugs with similar effects.
 Side effects of ketosis are loss of calcium from bones, kidney stones and growth retardation.

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How sugar spreads cancer

Researchers have discovered how sugar modification in cells enhances the spread of skin cancer.

The study reveals that FUT8, an enzyme that transfers the sugar fucose onto proteins, is the major cause of melanoma metastasis.

Scientists thought that the process in which carbohydrates attach to cell called glycosylation plays an important role in melanoma progression.

Researchers examined more than 30 samples of cancer tissue in patients, focusing on a particular type of glycosylation fucosylation, or the addition of sugars to a molecule by FUT8 and other enzymes.

Using laboratory mice, the researchers were able to reveal the role of FUT8 in metastasis, they subsequently focused on the factors behind the spread of melanoma.

Addiction of fucose to a particular molecule, L1CAM, by FUT8 spurred melanoma metastasis. When the
enzyme was removed, the onset of the cancer were hindered from spreading.

Dangers of eating late

Eating late increases the risk of weight gain, diabetes and heart disease.  Researchers discovered that eating late raises glucose and insulin levels.
Late-night meals also raise cholesterol and triglycerides, increase risk of heart disease.

Researchers instructed nine adults of healthy weights to spend eight weeks to eat during the daytime, which involved consuming three meals and two snacks between 8am and 7pm.

Then the group followed a delayed eating routine, having three meals and two snacks eating from noon to 11 pm for eight weeks.

 The researchers measured changes in weight, metabolism and energy used, they discovered that when participants ate later, compared to when they ate during the daytime, their weight increased.

They found late-night meals caused people to gain weight by reducing their body's fat metabolism. Test showed
that eating later led the participants to metabolize fewer fats and store carbohydrates which can raise blood sugar levels.

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Ketogenic diets can cure diabetes

Diabetes is a group of metabolic diseases of high blood glucose (blood sugar), either because insulin production is inadequate, or because the body's cells do not respond properly to insulin, or both.

Ketogenic diet involves eating five per cent carbohydrates, 20 per cent protein and 75 per cent fats per day. Foods high  in fat are nuts, cheese, fish, meat and avocado.

It was created in 1924 to reduce seizures in children with epilepsy, but has become a popular weight loss tool. Instead of using glucose from carbohydrate for fuel, the body is forced into ketosis, when the body metabolises fat as fuel.

Reducing carbohydrates in food reduce  blood sugar levels and insulin levels. It
can also lower blood pressure and improve cholesterol levels

Ketogenic diet can cause hypoglycemia, or low blood sugar, mental fogginess,
fatigue and headaches, kidney stones and bone fractures.









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Too much protein can reduce your lifespan

Latest research states that high protein diet at 50 years could reduce your lifespan, changes in metabolism dictates changes in diet.

According to Steve Simpson, a professor of life sciences at the University of Sydney,  the standard balanced diet suggested by National Health Service is five different fruits and vegetables a day, carbohydrates and few portions of protein.

The different classes of food are useful for proper development, but we must change them as we grow.

Eating diet high in protein from age 50 reduces lifespan, the Okinawa islanders of Japan eat less of animal protein and more of plant based diet, they have more of people who lived beyond 100 years.