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The inner life of a cell

I leave here, this excellent video of Harvard University. Not only does this very well done, but is highly updated and shows the cells as a very complex universe, full of harmony and beauty. Translation is

own, so please excuse the errors.

Hope you like it as much as me. Lionel Perez Valenzuela



PS: I recommend the article from today's newspaper La Nacion, on the discovery of a master regulatory gene, by researchers in Argentina. Excellent work of the journalist Nora Bar Here is the link:

http://www.lanacion.com.ar/EdicionImpresa/cienciasalud/nota.asp?nota_id=954587&pid=3369274&toi=5283

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Ali Baba and the 40 camels

For Lionel Perez Valenzuela

Students bored, take by assault the lab!

As fantastic as the tales of the Arabian Nights could be the stories surrounding some scientific discoveries. Who would imagine that the ship of the desert, the camel, would keep an important secret in his blood. A discovery that could revolutionize the treatment of dozens of diseases.

This story begins in the eighties when Raymond Hammers, an immunologist at that time Free University Brussels, try to solve a problem. Two of his students, undergraduates, have complained that the practical work, are boring and very predictable results. Concerned, he began searching in laboratory refrigerators, maybe I could find something exotic with to entertain students. found a pint of camel blood for research in the sleeping sickness. Decided to separate a bit for their students and suggest, to test a protocol to separate camel antibodies. Would you be able to do?

The result was surprising and left everyone confused, something new was in the blood of these strange animals.

This completely unexpected, like rubbing Aladdin's lamp, found in the blood of camels, in addition to the normal antibodies in the blood of all vertebrates, the camels had , a new type of antibody, much smaller, resistant to changes in pH and temperature.

A more detailed study of these antibodies revealed that dimers were formed by heavy chains (H) without light chains (L). In turn, the H chains lacking CH1 domain (this loss results from an altered splicing of exon encoding the CH1 domain that prevents its mRNA transcript and not a deletion in the corresponding gene) , being at much smaller than conventional H chain. This type of antibody called IgG step H

without side effects Chemotherapy

all know, the terrible effects of chemotherapy in cancer patients. Nausea, hair loss, vomiting, anemia, fatigue, among others. The main objective in the fight against cancer is to kill tumor cells, for this highly toxic compounds used, but unfortunately, also affect other body cells, especially epithelial cells and rapid cell division, such as bone marrow cells, precursors blood cells. For this reason, researchers have tried to develop more specific therapies to respect the body's normal cells.

basic science, applied science

Since the discovery by Cesar Milstein and Georges JF Köhler of monoclonal antibodies (antibodies that specifically bind to a single antigen), have designed various strategies to use as missiles, "smart" to bring into tumor cells, compounds that destroy them, such as toxins, radioisotopes or molecules capable of releasing free radicals (harmful to cells) when illuminated with a laser. Would achieve in this way selectively destroy cancer cells without affecting normal cells.

There are currently ten drugs based on antibodies. But they have some problems and can be improved. One difficulty is the large size which prevents antibodies penetrate the tumor, and exert their deleterious effect on the tumor. Another problem is that they are very complex molecules, which greatly hinders its large scale production with current methods.

camel antibodies are much smaller and its structure is simpler, because as stated above, lack light chains. Therefore are easier to produce in different systems, eg Escherichia coli or yeast. This will allow your production is much cheaper . Another great advantage is its extraordinary similarity to human sequences which makes very little antigenic (there would be no rejection problems.) Given all these advantages, many laboratories have been engaged in research and development, together with companies that have provided the necessary capital.

The smaller the better!

Ablynx The company was created specifically to develop new products from the possibilities offered camel antibodies.

One of his first targets was develop the technology to further reduce the size of antibodies, leaving only, heavy chain, the region responsible for binding to the antigen, called variable region. Thus, they were designed the nanoanticuerpos , one-tenth the size of a normal antibody. These therapeutic proteins derived from antibodies are very stable and soluble. Due to its small size can inhibit enzymes by binding to the active sites or bind to receptors.

The nanoanticuerpos would have great advantages in its practical applications based on current therapies, normal antibody whether human, murine (mouse) or humanized (mouse genetically engineered to be similar to humans and to avoid immune reactions). In these therapies, antibodies must be injected, instead, nanoanticuerpos could be administered orally, due to its solubility and resistance to low pH and proteases of the stomach. Could then be absorbed via the gut and penetrate into the bloodstream.

Initial results obtained with the nanoanticuerpos are very promising. Ablynx, and has obtained several patents and has several of its products in various stages of research

"Mr. Grocer, you have something to Alzheimer's?

"Madam, you have cancer," said the doctor, without emotion, but do not worry, cross in front and buy yourself a raspberry yogurt, that has the antibodies that you need ...

not seem incredible, but maybe we are not so far from this idea anticipatory.

At least that's what it suggests, Luis Angel Fernandez Herrero, Ph.D. Molecular Biology, a research group that studies the protein secretion and expression of antibodies in Escherichia coli, a bacterium widely used in biotechnology.

This group of researchers has focused on the secretion by the bacteria of recombinant antibodies. As antibodies are highly specific for use against various diseases. The researcher points out two alternatives, the first would be to use the antibodies alone, produce them in large quantities, purified and then administer them to patients. The second alternative, it would take a probiotic (such as yoghurt or fermented milk), which contains nonpathogenic bacteria, which produce antibodies. These bacteria produce antibodies that may act locally or reaching the bloodstream, fighting certain diseases.

This line of research has been strengthened by the discovery of camel antibodies, which as we have seen are smaller, simple and stable. All this greatly facilitates their production and secretion by the bacteria.

Camelids, survival machines that protect their young very well

Camels are animals that possess a physiology only adapted to very inhospitable climates, also have an immune system very robust and resistant to viral infections. For example, are immune to the virus disease which affects other mammals.

South American Camelids, alpaca, llama, guanaco and vicuna, also have these antibodies. Have demonstrated the presence both IgG and IgG H in blood and milk. Which opens interesting perspectives for research and application, developing new products.

is very important to note that transmission of immunoglobulins from mother to child occurs in the llama and alpaca primarily through the absorption of colostrum newborn (neonatal immunity.) The antibodies present in colostrum and milk of camels are IgG. Instead mammals IgG transferred across the placenta, have secretory IgA in milk and colostrum. This IgA has a protective effect at the gastrointestinal tract, without entering the circulation. In mammals providing colostrum IgG, these have the dual effect of protecting the gastrointestinal tract and enter the bloodstream.

A camel's milk also has other important characteristics, rich in vitamin B, vit.C rich in calcium and ten times more iron than cow's milk, is also capable of reversing boxes lactose intolerance and allergies. No beta-lactoglobulin (a milk protein) and casein has is different from the cow. This makes it less allergenic. Several countries in the Middle East and Africa, this type of milk sold to great advantage. However, there are some difficulties such as lack of a method for keep it in containers for long periods, as this milk is not compatible with ultra high temperature process (UAT).

Perhaps not too far distant is marketed worldwide camel milk rich in antibodies (which not only protect our gastrointestinal tract infections viral or bacterial, but penetrate into the bloodstream and reach all tissues) to help treat or prevent infections, allergies, arthritis remautoidea, cancer or Alzheimer's disease.

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Dr. " House or Dr. House?

By Lionel Perez Valenzuela

Questions with answers

Sometimes our students, we ask:

- Do I need to know chemistry to be a doctor or biologist?

- In what shall it profit a doctor to know the metabolic pathways?

One possible answer might be:

- Yes, absolutely, to save the lives of your patients and not to send their parents to jail, and these completely innocent.

But what kind of response is this?

Only one of the many possible.

A diagnostic error

Stalling In 1989 Patricia takes her 3 month old son, Ryan, to the emergency room at Cardinal Glennon Children's Hospital of St. Louis . The child, a very serious picture, difficulty breathing, uncontrollable vomiting and gastric problems. The doctor handler, a toxicologist, examine the child and concluded that their symptoms are the result of poisoning by ethylene glycol (antifreeze additive very common). These suspicions were confirmed by the hospital laboratory and a private laboratory, independently.

After his recovery, the child was sent to a family foster care . The parents were allowed supervised visits. In one of these visits, parents were a moment alone with the baby, and after that the child is out of kilter and died.

The parents were charged with first degree murder. The first analysis of the child's blood showed the presence of large amounts of ethylene and traces in the bottle with which the mother had fed her son during the visit.

Patricia Stalling already in prison, she realized she was pregnant. She and her husband had done a great experiment. In February 1990 his second son was born to David Stalling was taken into custody with a foster family. But the few weeks showed the same symptoms as her brother died. The diagnosis was methyl malonic acidemia. A disease that has symptoms that of ethylene glycol poisoning. Despite the prosecution rejected this new defense arguments and the mother was convicted, as it was considered proven by blood and bottle of ethylene glycol poisoning.

seemed a done deal, but ...

What is methyl malonic acidemia?

is an inborn error of metabolism. Are borne diseases to occur in a gene mutation that alters the genetic makeup of a person, disrupting its normal functions, leading to a physiological disorder that causes the following problems:

1. No synthesis of a compound essential for the organism.

2. Accumulation of toxic intermediate compounds to the CNS.

3. Accumulation of compounds that cause cell damage that occurs.

4. Stimulation of alternative routes to production unwanted substances.

In a more detailed description, methyl malonic acidemia (found methyl malonic acid in the blood) is an inherited, autosomal recessive, caused by a defect in the enzyme methyl malonyl CoA mutase (MCM). This enzyme is necessary for the metabolism of certain amino acids (isoleucine, valine, threonine and methionine), cholesterol and certain fatty acids. When proteins are degraded, these amino acids can be converted into methylmalonyl CoA, thanks to the MCM succinyl CoA can become an intermediary in the Krebs Cycle. Thus these amino acids enter the pathways that can supply energy to the cell. When the MCM is mutated, the malonyl CoA can not be converted to succinyl CoA and accumulates in blood and urine as methyl malonic acid. Causing seizures, paralysis, kidney damage and liver, impaired growth, mental retardation and ultimately death. The disease occurs in approximately one of 48,000 births, in its various forms. Since 1985 there is a treatment ( L-carnitine and metronidazole) , allowing children who survive the first attacks, cope with a relatively normal life.

Does television saves lives?

After hearing about the case of Mrs. Stalling on a television show, William Slay, head of Molecular Biology and James Shoemaker lab chief metabolic studies University of St. Louis, began investigating this case. Working alongside them Piero Rinaldo an expert in metabolic diseases of the school of medicine at Yale University.

As a first step decided to analyze the blood of Ryan. They found large amounts of methyl malonic acid and no ethylene glycol, the poison allegedly used. They also found huge concentrations of ketone bodies and methyl malonic acid in urine, something completely line with methylmalonic aciduria.

The bottle could not be tested because he disappeared mysteriously.

These results differed from those previously conducted analysis. Further investigation revealed that the hospital lab not respect their own protocols. Since the profile of blood samples from Ryan did not match the standard samples with ethylene glycol used by the hospital. Despite this the hospital laboratory said it had found ethylene glycol in the patient's blood. Moreover, the private laboratory detected an unusual molecule in the blood of Ryan, but not correctly identified, mistook the peak detection of methylmalonic acid in the HPLC (High Performance Liquid Chromatography), assuming that was ethylene glycol. also determined that although they had found nothing unusual in the samples of the bottle argued the presence of ethylene glycol.

After these findings, Patricia Stalling, was acquitted of all charges.

This is a dramatic demonstration that a proper diagnosis can save patients with rare metabolic diseases. A proper understanding of metabolic pathways and inborn errors of metabolism, is necessary for diagnosis and management, proper and immediate.

What is newborn metabolic screening?

are laboratory tests to detect inborn diseases with alterations in biochemical processes or birth.

Worldwide experience has shown that 20-30% of cases of pediatric hospital mortality, is based on a disease genetics.

should be an evaluation of the babies 2 to 8 days old. Up to 6 months of age. Keep in mind that babies with this disease usually appear completely normal and no symptoms initially. From there, the importance of conducting these studies and to further improve the early detection and treatment of metabolic diseases.

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Photosynthesis "without light?

By Lionel Perez Valenzuela

The first discovery

exploration funds abyssal sea from 200 meters to the Great Plains to 4000-6000 m depth revealed thousands of new species. At these depths, where there is no light, the pressures are enormous and water only reaches 2 ° C was thought that fauna would consist almost exclusively of scavengers and heterotrophic bacteria.

After thirty years, discovered the hydrothermal vents (also called oceanic vents). A completely new ecosystem that depended for its survival in sunlight. Around these hydrothermal vents, or fumaroles (where emerging streams of up to 400 º C, very rich in minerals), flourishing community with a variety of species (more than 300 different species have been discovered to date). This ecosystem depends bacteria and archaea, chemoautotrophic. Engage in a process called chemosynthesis, in which molecules such as hydrogen sulfide will serve as an energy source to reduce CO2 and synthesize biomolecules. These

Bacteria are the main food source of all other surrounding agencies. Some of the organisms in the ocean recesses feed on bacteria to absorb energy, but also tube worms, which feed on a less conventional. They have no gut or digestive system but are embedded in their tissues billions of live bacteria (per gram of worm contains 10 billion bacteria) that meet their metabolic needs. In turn, the worms brings to those bacterial colonies around the hydrogen sulfide they need.

However this may not be the only autotrophic type of ecosystem. Recently, it has been discovered that in addition of chemoautotrophic bacteria and archaea, are photosynthetic bacteria that use infrared radiation emanating from hydrothermal vents.

Light in the depths

Every body with a temperature above absolute zero emits electromagnetic radiation such as infrared rays, which are invisible to our eyes. As a body is heated, it begins to emit more radiation and wavelength shorter. This can be seen with a heated metal filament, that increasing the temperature is turning red, then orange and finally white, emitting visible light.

The hydrothermal springs to be warmer than the surrounding cold water, emit infrared radiation that certain bacteria and animals could detect and exploit.

During the first years following the discovery of the vents, it was found that infrared radiation has any biological function. After evidence emerged that certain shrimp and crabs blind, have pigments that do not allow images but it serves to detect extremely faint amounts of light, perhaps to avoid close or too far away from the hydrothermal springs. Only source of nutrients from the desolate sea floor.

Researchers, before this discovery was immediately asked if this light so dim, close to red, could keep some type of photosynthetic organism. It seemed a preposterous assumption: photosynthesis in the deep sea! But this assumption had its foundations since shortly before had found green sulfur bacteria living in oxygen-poor water and made photosynthesis in water deep and almost devoid of light in the Black Sea.

Bacteria champions green sulfur photosynthesis

These bacteria possess bacteriochlorophyll Black Sea and photosynthesis can make more than 100 meters deep (where the light comes highly filtered) and darkness reigns. In this situation a bacteriochlorophyll molecule captures a photon every eight hours, so bacteria must take stock of light extremely efficiently. It is also the only way we can survive because they have no alternative metabolism (other bacteria can cause fermentation and if conditions allow photosynthesis can do to accelerate their growth), but this is not the case of green sulfur bacteria, depend exclusively on photosynthesis.

therefore the best candidate to find a photosynthetic bacteria in extreme conditions without sunlight and hydrothermal vents are green sulfur bacteria and some bacteria associated with them.

Eureka!

Thus, the group led by Robert Blankenship, a photosynthesis expert at the University Arizona State, had to convince the Department of the NASA Astrobiology of photosynthetic bacteria find thousands of meters deep in the most absolute darkness. The intensities of light measures at hydrothermal vents are a hundred to one million times fainter than the measures in the Black Sea. But against all odds, the researchers discovered a new species of photosynthetic bacteria in the samples from the hydrothermal vents off the coast of Costa Rica in the Pacific Ocean.

chlorosomes What are?

How is it possible that bacteria can do photosynthesis such low light intensities, the radiation from geothermal vents?

The answer lies in the chlorosomes, oblong vesicles located beneath the plasma membrane, containing the antenna pigments of green photosynthetic bacteria. Are arranged under the cytoplasmic membrane, without being in continuity with it, although in many cases are connected through a stalk of lipid nature.

chlorosomes These trapped photons channeled into the biosynthetic machinery necessary to transform light energy into chemical energy , so we can synthesize biomolecules.

Conclusions and future work

remains even identify this new species of green sulfur bacteria, this will require improved methods of identification (eg identification of photosynthetic pigments) , cultivation and sequencing of the PCR technique of nucleic acids, found in hydrothermal water samples.

From a historical perspective we can see these works have changed the vision we had of life on earth. Now we can find ecosystems independent of sunlight, bacteria living on the ground thousands of feet deep or hot springs, salt crystals in the mines or on frozen lakes in Antarctica. The beings are remarkably resilient and adaptable, that is a lesson we have learned.

These discoveries have not only improved our understanding of life on our planet, but have expanded the habitats where there could be alien life, from the cold deserts of Mars, the surface oceans Europe (one of the moons of Jupiter) to methane clouds on Titan (a moon of Saturn ), could all be good candidates to discover that there is life beyond our planet.