Daffodils can fight cancer

A research describes the anti-cancer effects of a natural alkaloid extracted from Daffodils. Led by Denis Lafontaine, affiliated with the Faculty of Sciences at the ULB, the researchers have discovered that this compound triggers the activation of an anti-tumoral surveillance pathway.

 The researchers extracted a natural anti-cancer compound from Daffodils (Amaryllidaceae Narcissus). They established that this compound, an alkaloid named haemanthamine, binds to the ribosome. Ribosomes are nanomachines essential to the survival of humans cells because they synthesize all the required proteins. To sustain their unrestrained growth, cancer cells rely on increased protein synthesis: they are therefore particularly sensitive to treatments that inhibit the production and the function of ribosomes.

Haemanthamine blocks the production of protein by ribosomes, thus slowing growth of cancer cells. Haemanthamine also inhibits the production of these nanomachines in the nucleolus (the "ribosome factory"): this nucleolar stress triggers the activation of an anti-tumoral surveillance pathway leading to the stabilization of the protein p53 and to the elimination of cancer cells.

This study provides a molecular explanation to the anti-tumoral activity of Daffodils used for centuries in folk medicine. Haemanthamine belongs to a large family of therapeutic molecules of natural origin: numerous other alkaloids, used in human health, are extracted from plants, such as morphine (potent pain killer), quinine (anti-malarial agent), and ephedrine (anti-asthmatic).
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How liver responds to food

Minutes after eating, as nutrients rush into the bloodstream the body makes massive shifts in how it breaks down and stores fats and sugars. Within half an hour, the liver has made a complete switch  from burning fat for energy to storing as much glucose, or sugar, as possible. It's too short a time span for the liver's cells to activate genes and produce the RNA blueprints needed to assemble new proteins to guide metabolism.

Liver cells store up pre-RNA molecules involved in glucose and fat metabolism. ''The switch from fasting to feeding is a very quick switch and human physiology has to adapt to it in the right time frame," says Satchidananda Panda, a professor in the Salk Institute's Regulatory Biology Laboratory. It was known that a RNA-binding protein called NONO was implicated in regulating daily ("circadian") rhythms in the body.

Researchers analyzed levels of NONO in response to feeding and fasting in mice. After the animals ate, speckled clumps of NONO suddenly appeared in their liver cells, newly attached to RNA molecules. Within half an hour, the levels of corresponding proteins-those encoded by the NONO-bound RNA increased.

After mice eat, it looks as if NONO brings all these RNAs together and processes them so they can be used to make proteins. When mice lacked NONO, it took more than three hours for levels of the same proteins involved in processing glucose to increase. During that time lag, blood glucose levels shot up to unhealthy levels.

Since blood glucose levels are also heightened in diabetes, the researchers think that the mice without NONO may act as a model to study some forms of the disease. NONO has been found at high levels in the brain and muscle cells.
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Eggs can select semen

According to the latest research, female's eggs are able to select sperm with the best genes to ensure the healthiest offspring. Semen does not appear to have the same ability to detect bad genes, this shows that fertilisation is not random and specific pairings between certain eggs and sperm are more common than others. Researchers bred female mice carrying one normal and one mutant copy of a gene that increased the chance of getting testicular cancer.

 The resulting offspring followed Mendel's rules and there was a random dispersal of the mutated form among offspring. Researchers reversed the breeding- gave males the mutant copy of the cancer gene while the females had the normal version. Only 27 per cent of the offspring had the mutant variant, compared to the 75 per cent. Researchers found no evidence the mutated mice embryos were dying shortly after fertilisation, rather they were never fertilised.

The rate of metabolism folic acid - which is an important signalling molecule - is different in sperm and eggs. Research has revealed that these molecules play an important role in fertilisation. Changes in these signals may impact how much sperm and egg are attracted to one another. When sperm from multiple males arrive at an egg concurrently, eggs are able to choose the sperm whose recognition proteins are best suited for healthy fertilization. This selection process can spur the evolution of new recognition proteins, eventually resulting in reproductive isolation and, in some cases, the creation of new species altogether.
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Impacts of proteins on immune system

Different genetic make-up can impact on the activity of the immune system and our ability to fight cancer.

Proteins are made up of thousands of smaller units called amino acids, which are attached to one another in long chains.

Proteins do most of the work in cells and are required for the structure, function, and regulation of the body's tissues and organs.

 A protein called ULBP6 leads to the removal of damaged cells. There are two types of this protein found in different people.

The ULBP6 protein is found on the surface of damaged cells, including several types of cancer cells, and acts as a signal to white cells in our immune system that the damaged cell should be killed.

There are two major types of protein in the population and people who inherit a certain subtype have been shown to have a poor outcome after stem cell transplantation, a procedure used to treat leukemia, which is commonly referred to as bone marrow treatment.

The two types of ULBP6 differ only by two amino acids out of a total of around 180 and it has important influence on patient outcomes. One form of ULBP6
 forms a very strong bond indeed with its receptor NKG2D on the immune system.

This shows why transplants work less well in some people, which is an important step on the path to developing better transplant therapy for more people living with blood cancer.

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Defective HIV proviruses prevent cure

Proteins created by defective forms of HIV associate with immune systems are monitored by cytotoxic T cells.

HIV proviruses are many in HIV patients, the faulty proteins they produce can hinder measurement of viral load, exhaust immune systems and prevent suppression of the virus.

Researchers are trying to hypermutate the proviruses and destroy defective HIV proviruses and develop cure for HIV infection.

Scientists collected defective HIV proviruses from 9 HIV patients and transfected cultures of human immune cells in laboratory.

It was discovered that the transfected human immune cells were capable of making HIV protein despite mutations.

Defective proviruses contribute to viral RNA and protein production and increase the viral load of HIV patients.