Ebola

Ebola virus disease

Ebola hemorrhagic fever (Ebola HF) is a severe, often-fatal disease in humans and nonhuman primates (monkeys and chimpanzees) that has appeared sporadically since its initial recognition in 1976.

Ebola first appeared in 1976 in 2 simultaneous outbreaks, in Nzara, Sudan, and in Yambuku, Democratic Republic of Congo. The latter was in a village situated near the Ebola River, from which the disease takes its name.

Genus Ebolavirus is 1 of 3 members of the Filoviridae family (filovirus), along with genus Marburgvirus and genus Cuevavirus. 

Marburgvirus and genus Cuevavirus. Genus Ebolavirus comprises 5 distinct species:

• 1.      Bundibugyo ebolavirus (BDBV)
• 2.      Zaire ebolavirus (EBOV)
• 3.      Reston ebolavirus (RESTV)
• 4.      Sudan ebolavirus (SUDV)
• 5.      Taï Forest ebolavirus (TAFV).

BDBV, EBOV, and SUDV have been associated with large EVD outbreaks in Africa, whereas RESTV and TAFV have not. The RESTV species, found in Philippines and the People’s Republic of China, can infect humans, but no illness or death in humans from this species has been reported to date.

Transmission

Ebola is introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals. In Africa, infection has been documented through the handling of infected chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines found ill or dead or in the rainforest.

Ebola then spreads in the community through human-to-human transmission, with infection resulting from direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and indirect contact with environments contaminated with such fluids. Burial ceremonies in which mourners have direct contact with the body of the deceased person can also play a role in the transmission of Ebola. Men who have recovered from the disease can still transmit the virus through their semen for up to 7 weeks after recovery from illness.

Health-care workers have frequently been infected while treating patients with suspected or confirmed EVD. This has occurred through close contact with patients when infection control precautions are not strictly practiced.

Among workers in contact with monkeys or pigs infected with Reston ebolavirus, several infections have been documented in people who were clinically asymptomatic. Thus, RESTV appears less capable of causing disease in humans than other Ebola species.

However, the only available evidence available comes from healthy adult males. It would be premature to extrapolate the health effects of the virus to all population groups, such as immuno-compromised persons, persons with underlying medical conditions, pregnant women and children. More studies of RESTV are needed before definitive conclusions can be drawn about the pathogenicity and virulence of this virus in humans.

Signs and symptoms

EVD is a severe acute viral illness often characterized by the sudden onset of fever, intense weakness, muscle pain, headache and sore throat. This is followed by vomiting, diarrhoea, rash, impaired kidney and liver function, and in some cases, both internal and external bleeding. Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes.

People are infectious as long as their blood and secretions contain the virus. Ebola virus was isolated from semen 61 days after onset of illness in a man who was infected in a laboratory.

The incubation period, that is, the time interval from infection with the virus to onset of symptoms, is 2 to 21 days.

Diagnosis

Other diseases that should be ruled out before a diagnosis of EVD can be made include: malaria, typhoid fever, shigellosis, cholera, leptospirosis, plague, rickettsiosis, relapsing fever, meningitis, hepatitis and other viral haemorrhagic fevers.

Ebola virus infections can be diagnosed definitively in a laboratory through several types of tests:

•          antibody-capture enzyme-linked immunosorbent assay (ELISA)
•          antigen detection tests
•          serum neutralization test
•          reverse transcriptase polymerase chain reaction (RT-PCR) assay
•          electron microscopy
•       virus isolation by cell culture.

Samples from patients are an extreme biohazard risk; testing should be conducted under maximum biological containment conditions.

Vaccine and treatment

No licensed vaccine for EVD is available. Several vaccines are being tested, but none are available for clinical use.

Severely ill patients require intensive supportive care. Patients are frequently dehydrated and require oral rehydration with solutions containing electrolytes or intravenous fluids.

No specific treatment is available. New drug therapies are being evaluated.

Favipiravir looks like it may be useful in a mouse model of the disease. Estrogen receptor drugs used to treat infertility and breast cancer (clomiphene and toremifene) inhibit the progress of Ebola virus in infected mice. Ninety percent of the mice treated with clomiphene and fifty percent of those treated with toremifene survived the tests. Given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.

Prevention and control

Controlling Reston ebolavirus in domestic animals

No animal vaccine against RESTV is available. Routine cleaning and disinfection of pig or monkey farms (with sodium hypochlorite or other detergents) should be effective in inactivating the virus.

If an outbreak is suspected, the premises should be quarantined immediately. Culling of infected animals, with close supervision of burial or incineration of carcasses, may be necessary to reduce the risk of animal-to-human transmission. Restricting or banning the movement of animals from infected farms to other areas can reduce the spread of the disease.

As RESTV outbreaks in pigs and monkeys have preceded human infections, the establishment of an active animal health surveillance system to detect new cases is essential in providing early warning for veterinary and human public health authorities.

Reducing the risk of Ebola infection in people

In the absence of effective treatment and a human vaccine, raising awareness of the risk factors for Ebola infection and the protective measures individuals can take is the only way to reduce human infection and death.

In Africa, during EVD outbreaks, educational public health messages for risk reduction should focus on several factors:

·         Reducing the risk of wildlife-to-human transmission from contact with infected fruit bats or monkeys/apes and the consumption of their raw meat. Animals should be handled with gloves and other appropriate protective clothing. Animal products (blood and meat) should be thoroughly cooked before consumption.

·         Reducing the risk of human-to-human transmission in the community arising from direct or close contact with infected patients, particularly with their bodily fluids. Close physical contact with Ebola patients should be avoided. Gloves and appropriate personal protective equipment should be worn when taking care of ill patients at home. Regular hand washing is required after visiting patients in hospital, as well as after taking care of patients at home.

·         Communities affected by Ebola should inform the population about the nature of the disease and about outbreak containment measures, including burial of the dead. People who have died from Ebola should be promptly and safely buried.

Pig farms in Africa can play a role in the amplification of infection because of the presence of fruit bats on these farms. Appropriate biosecurity measures should be in place to limit transmission. For RESTV, educational public health messages should focus on reducing the risk of pig-to-human transmission as a result of unsafe animal husbandry and slaughtering practices, and unsafe consumption of fresh blood, raw milk or animal tissue. Gloves and other appropriate protective clothing should be worn when handling sick animals or their tissues and when slaughtering animals. In regions where RESTV has been reported in pigs, all animal products (blood, meat and milk) should be thoroughly cooked before eating.

Controlling infection in health-care settings

Human-to-human transmission of the Ebola virus is primarily associated with direct or indirect contact with blood and body fluids. Transmission to health-care workers has been reported when appropriate infection control measures have not been observed.

It is not always possible to identify patients with EBV early because initial symptoms may be non-specific. For this reason, it is important that health-care workers apply standard precautions consistently with all patients – regardless of their diagnosis – in all work practices at all times. These include basic hand hygiene, respiratory hygiene, the use of personal protective equipment (according to the risk of splashes or other contact with infected materials), safe injection practices and safe burial practices.

Health-care workers caring for patients with suspected or confirmed Ebola virus should apply, in addition to standard precautions, other infection control measures to avoid any exposure to the patient’s blood and body fluids and direct unprotected contact with the possibly contaminated environment. When in close contact (within 1 metre) of patients with EBV, health-care workers should wear face protection (a face shield or a medical mask and goggles), a clean, non-sterile long-sleeved gown, and gloves (sterile gloves for some procedures).

Laboratory workers are also at risk. Samples taken from suspected human and animal Ebola cases for diagnosis should be handled by trained staff and processed in suitably equipped laboratories.

Bengal gram - Reduces diabetes risk!!

The chickpea (Cicer arietinum) is a legumeof the family Fabaceae, subfamily Fabiodeae . Its seeds are high in Protein. It is one of the earliest cultivated legumes: 7,500-year-old remains have been found in the Middle East.

Other common names for the species include garbanzo bean, ceci bean, sanagalu, chana and Bengal gram.

Bengal gram reduces diabetes risk, finds study:

Consumption of Bengal gram prior to a meal could lower your risk of diabetes, according to a new study.

A team of scientists from the Indian Institute of Chemical Technology (IICT) compared the effectiveness of three commonly consumed legumes - Bengal gram, green gram and another variant of chickpea, Kabuli Channa in regulating carbohydrate digestion.

The study found that Bengal gram showed consistent results in terms of reducing sugar spikes after a starchy meal. Eating about 50 grams of sprouted raw Bengal gram before a meal will rein in blood glucose levels which usually witness a jump due to the rapid absorption of carbohydrates after a meal, the study headed by scientist A K Tiwari, concluded.

Tiwari said the study was aimed at finding the varieties of sprouts which are most beneficial for improving the health of diabetics. "The benefits of sprouts are well-known. But our study specifically shows how diabetics can prevent sugar spikes to delay the onset or in some cases, even prevent the disease," he said.

Tiwari highlighted the importance of high amount of protein and presence of digestion-resistant carbohydrate in Bengal gram.

" A protein-rich diet takes longer to be absorbed by our system. The presence of digestion-resistant carbohydrates further reduces the rate of absorption of carbohydrates into our bloodstream," he said adding that the Bengal Gram should ideally be consumed raw after germination. 

Tiwari conducted similar studies in the past.

The findings of the latest study were published in the Journal of Pharmacy and Bio-Allied Sciences.

Source: Indian Institute of Chemical Technology (IICT)

Cow urine cure gets scientific stamp!

FROM  "TIMES OF INDIA"
Study Proves Cow Urine Removes Kidney Stones 

Vijaysinh Parmar | TNN 

Rajkot: Most would cringe at the thought of drinking cow urine,even if given in a distilled form that is tasteless and odourless.However,ancient scriptures that often proclaim its disease-fighting properties have finally got scientific backing.

A recent study by Bhavnagar Medical College has proved that distilled cow urine is indeed effective in curing kidney stones.The research conducted by the colleges pharmacology department is touted to be first-ever scientific evidence suggesting beneficial properties of cow urine in treating renal disorders.

It must be noted that major part of Saurashtra,mostly coastal areas,is considered to be a renal stone belt with nearly 30% suffering from kidney stones.

Cow urine was given to albino rats after inducing renal stones in them using ethylene glycol.The results are very encouraging as we found significant reduction in urinary oxalate level and calcium oxalate crystals formation in kidney, said Dr Apexa Shukla,a student of MD (pharmacology),who led the team conducting the study.

Distilled cow urine is tasteless and free from contamination,she added.
The research paper titled Anti-Urolithiatic Effect of Cow Urine Ark on Ethylene Glycol-Induced Renal Calculi has also been accepted for publication in the International Brazil Journal of Urology,the official journal of Brazilian Society of Urology.

Cow urine is known to have diuretic and nephroprotective effect.However,there was never a scientific backing for this agesold claim, said Dr C B Tripathi,associate professor,pharmacology department.

The college is now in talks with Government Ayurvedic College to carry out trials on humans.

HIV/AIDS patients “cured” by bone marrow transplants

Could bone marrow transplants cure HIV? Two men who had procedure stop taking medication after virus 'disappears' from their blood

• Last year scientists announced that the two unnamed men no longer seemed to have the virus but they were still taking antiretroviral medication
• 
  
• The men have now come off medication - one for 15 weeks and the other for seven - and still show no signs of having HIV virus
• 
  
• Experts say it is too early to say that the men had been cured but that their progress was very encouraging
• 
  
• Warned that virus may be hiding in other organs such as the liver, spleen or brain and could return months later, he warned.

Two men with HIV have been able to stop taking their medication after receiving bone marrow transplants.

Experts say it is too early to describe them as ‘cured’ – but the Aids virus shows no signs of returning in either patient.

The men, who had HIV for about 30 years, received transplants to treat blood cancer several years ago. One stopped taking anti-HIV drugs four months ago, while the other stopped seven weeks ago.

Both men had suffered with blood cancer and had undergone bone marrow transplants (marrow being prepared pictured) to treat that disease. No one expected the procedure to have such a dramatic and beneficial side effect

Their US doctors say keeping them on the drugs after their transplants first took place prevented their new supplies of healthy blood cells from becoming infected by HIV. The patients’ old, diseased cells were then attacked by the new ones.

The International Aids Society conference in Malaysia heard that now, even though the patients have stopped taking antiretroviral drugs, the virus cannot be detected in their blood. Normally, the disease can only be kept under control with lifelong treatment.

Working out why the bone marrow transplants had such a strong effect could lead to new treatments for the 34million living with Aids. An estimated 100,000 Britons have HIV, including 20,000 who have not been formally diagnosed.

Timothy Henrich, of the Brigham and Women’s Hospital in Boston, said the men ‘are doing very well’, but warned: ‘While these results are exciting, they do not yet indicate the men have been cured. Only time will tell.’

Experts say it is too early to say that the men are cured as virus (pictured) could be hiding in organs

One possibility is that the virus is ‘hiding’ in another part of the body, such as the liver or brain, and could re-emerge in the coming weeks.

Dr Michael Brady of the Terrence Higgins Trust stressed that bone marrow transplants are ‘complex and expensive’, and could be more dangerous than daily medication.

However, he added: ‘While this is by no means a workable cure, it does give researchers another sign-post in the direction of one.’

The first person reported to be cured of HIV, American Timothy Ray Brown, underwent a stem cell transplant in 2007 to treat his leukemia. He was reported by his German doctors to have been cured of HIV two years later.

Brown's doctors used a donor who had a rare genetic mutation that provides resistance against HIV. So far, no one has observed similar results using ordinary donor cells such as those given to the two Boston patients.

Kuritzkes said the patients will be put back on the drugs if there is a viral rebound.

A rebound will show that other sites are important reservoirs of infectious virus and new approaches to measuring these reservoirs will be needed in developing a cure, Henrich said.

‘These findings clearly provide important new information that might well alter the current thinking about HIV and gene therapy,’ Kevin Robert Frost, chief executive of The Foundation of AIDS Research, said in a statement. 

'While stem cell transplantation is not a viable option for people with HIV on a broad scale because of its costs and complexity, these new cases could lead us to new approaches to treating, and ultimately even eradicating, HIV.'

Pollution-fighting algae: Algae species holds potential for dual role as pollution reducer, biofuel source

A hardy algae species is showing promise in both reducing power plant pollution and making biofuel, based on new research at the University of Delaware.

The microscopic algae Heterosigma akashiwo grows rapidly on a gas mixture that has the same carbon dioxide and nitric oxide content as emissions released from a power plant.

"The algae thrive on the gas," said Kathryn Coyne, associate professor of marine biosciences in UD's College of Earth, Ocean, and Environment. "They grow twice as fast and the cells are much larger in size compared to when growing without gas treatment."

The algae also make large amounts of carbohydrates, which can be converted into bioethanol to fuel vehicles. The findings could have industrial applications as a cost-effective way to cut greenhouse gas pollution when paired with biofuel production.

Heterosigma akashiwo is found worldwide in the natural environment. Coyne, an expert in algal blooms, discovered that the species may have a special ability to neutralize nitric oxide—a harmful gas that poses threats to environmental and human health.

That characteristic prompted Coyne and her team to investigate whether the algae could grow on carbon dioxide without getting killed off by the high nitric oxide content in power plants' flue gas, which had foiled similar attempts by other scientists using different types of algae.

A yearlong laboratory experiment shows that Heterosigma akashiwo not only tolerates flue gas, but flourishes in its presence. The algae also do not need any additional nitrogen sources beyond nitric oxide to grow, which could reduce costs for raising algae for biofuel production.
"This alone could save up to 45 percent of the required energy input to grow algae for biofuels," Coyne said.

Funded by the Delaware Sea Grant College Program, Coyne and her collaborator, Jennifer Stewart, plan to further study how changes in conditions can enhance the growth of Heterosigma akashiwo. So far, they found a large increase in carbohydrates when grown on flue gas compared to air. They also see correlations between the levels of light given to the algae and the quantity of carbohydrates and lipids present in the organisms.

The researchers are exploring opportunities for partnerships with companies to scale up the growth process and more closely examine Heterosigma akashiwo as a biofuel producer.
The prospects could support a national focus on carbon pollution reduction following President Barack Obama's major speech this week on climate change.

"Our approach to the issue is to not just produce biofuels, but to also use this species for bioremediation of industrial flue gas to reduce harmful effects even further," Coyne said.

Source: University of Delaware

New understanding of tiny RNA molecules could have far-ranging medical applications

A team led by scientists at The Scripps Research Institute (TSRI) has identified a family of tiny RNA molecules that work as powerful regulators of the immune response in mammals

Mice who lack these RNA molecules lose their normal infection-fighting ability, whereas mice that overproduce them develop a fatal autoimmune syndrome.

"This finding gives us insights into immune regulation that could be very helpful in a range of medical applications, from viral vaccines to treatments for autoimmune diseases," said Changchun Xiao, assistant professor in TSRI's Department of Immunology and Microbial Science and senior investigator for the study, which appears in the June 30, 2013 issue of Nature Immunology.

Unraveling a Crucial Process
The finding concerns a key interaction between T cells and B cells, the allied lymphocyte armies that make up most of the adaptive immune system of mammals. B cells, which produce antibodies, usually lie in wait for pathogens in special zones called follicles within lymph nodes and the spleen. But to start proliferating normally and pumping out antibodies to fight an infection, these B cells have to be assisted, in effect, by T cells known as "follicular helper" T cells (TFH cells). "The TFH cells have to migrate into the B cell follicles and physically contact the B cells in order to provide help to them," said Xiao. "However, the molecular pathways that control TFH cell differentiation and migration have not been well understood."

In 2009, other researchers proposed that this crucial process requires the suppression of the miR-17~92 family of RNA molecules. These are among the thousands of short RNA molecules (often known as micro-RNAs, miRs, or miRNAs) that are made by mammalian cells and are meant to do their jobs while in RNA form. Typically an miRNA works inside the cell as a basic regulator or "dimmer switch" for the activity of tens to hundreds of genes—it binds to transcripts of those genes and slows down their translation into proteins.

Xiao, who had been studying the miR-17~92 family since 2005, decided to examine their role in TFH differentiation. His team began by measuring the levels of these miRNAs in young, "naïve" T cells and in the TFH cells to which these T cells gave birth after exposure to foreign antigens.

Surprising Finding
To the researchers' surprise, the miR-17~92s showed the opposite pattern of expression than expected: their levels jumped as the naïve T cells began differentiating into TFH cells, but fell back by the time the process was finished. The finding suggested that, far from acting as a brake on TFH differentiation, miR-17~92s work as enablers of the process.

To confirm their suspicion, team members developed mutant mouse lines in which some or all of the miR-17~92 miRNAs were knocked out of T cells. These miR-17~92-deficient T cells turned out to be much less able to differentiate into TFH cells. As a result, the follicle-dwelling B cells that depend on TFH assistance also lost much of their ability to respond to an immune challenge. "These mutant mice showed a deficient antibody response to a standard immune-provoking protein," said Seung Goo Kang, a postdoctoral research associate in the Xiao laboratory who was the leading author of the study.

Collaborating TSRI scientists led by John Teijaro, a senior research associate in the laboratory of Michael B. A. Oldstone, professor in the Department of Immunology and Microbial Science, showed further that these transgenic mice—unlike ordinary lab mice—could not clear a chronic virus infection that is used as a standard challenge in immunological experiments.

By contrast, when the team raised transgenic mice whose T cells produced four to six times the normal amount of miR-17~92s, these T cells differentiated into TFH cells spontaneously—that is, without an immune-stimulating inoculation.

These mice developed antibody responses to their own tissues, and died young, with swollen spleen and lymph nodes. "The accumulation of autoantibodies is also seen in lupus and other autoimmune diseases in humans," said Wen-Hsien Liu, another postdoctoral research associate in the Xiao laboratory and a co-first author of the paper.

Important Targets
Liu and Kang were able to track down a key target gene of miR-17~92s, which the miRNAs suppress to enable TFH cell differentiation. The targeted gene codes for Phlpp2, a recently discovered signaling inhibitor. "Lowering Phlpp2 protein levels in our miR-17~92-knockout T cells restored much of their ability to become TFH cells," Kang said.

"Phlpp2 is one important target, but we believe there are others too, and we are now looking for those," Xiao said. He and his colleagues also plan to investigate methods for manipulating miR-17~92s and their TFH cell-related pathways, in order to boost antibody responses – to vaccines for example—or alternatively to lower autoantibody productions in people with autoimmune diseases.

Source: The Scripps Research Institute

Protein in Blood Exerts Natural Anti-Cancer Protection

The study, published June 24 online in the Proceedings of the National Academy of Sciences, suggests it may be possible to harness the power of this naturally occurring anticancer agent as a way to treat cancer, including metastases.

In several different publications it has been described the ability of decorin to affect a number of biological processes including inflammatory responses, wound healing, and angiogenesis.

In this new article, the study's senior investigator, Renato Iozzo, M.D., Ph.D., has labeled decorin a "soluble tumor repressor" -- the first to be found that specifically targets new blood vessels, which are pushed to grow by the cancer, and forces the vessel cells to "eat" their internal components. This reduces their potential to feed the cancer overall causing an inhibition of tumor progression.

"The tumor suppressors we all know are genes inside tumors that a cancer deletes or silences in order to continue growing. I call decorin a tumor repressor because its anti-tumor activity comes from the body, outside the cancer," says Dr. Iozzo, Professor of Pathology & Cell Biology, Biochemistry & Molecular Biology at Kimmel Cancer Center.

"Decorin is a soluble compound that we found has a powerful, natural protective effect against cancer -- an exciting finding that we believe will open up a new avenue for both basic research and clinical application," Dr. Iozzo says. "Acting from the outside of the cells, decorin is able to modify the behavior of the cancer cells and of the normal cells in order to slow down the progression of the tumor. For this reason, decorin acts as a guardian of the matrix, the complicated structure built around the cells in our body."

Absence of decorin promotes tumor growth

Decorin has long been known to be involved in human development. It is so named because deposits of decorin "decorate" collagen fibrils after the human body forms.

A second pool of decorin has been found circulating in blood after production by connective tissue throughout the body. This connective tissue is part of the extracellular matrix, which provides both structural support and biological regulation of tissue cells.

But no one has understood the biological function of this second pool of decorin, according to Dr. Iozzo.

The research team, including the two co-first authors, Simone Buraschi, Ph.D., and Thomas Neill, a graduate student, who work in the laboratory of Dr. Iozzo, decoded the function of soluble decorin. They found that addition of exogenous decorin to the tumor microenvironment induces autophagy, a mechanism by which cells discard unnecessary or damaged intracellular structures. "This process regulates a lot of cellular activities," says Dr. Iozzo.

The researchers specifically found that decorin evoked autophagy in both microvascular and macrovascular endothelial cells -- cells that line the interior surface of blood vessels.

"This matters because autophagy can exert a potential oncosupressive function by acting to discard critical cell components that would otherwise be involved in promotion of tumor growth through angiogenesis, the production of new blood vessels that can provide nutrition to the tumor," Dr. Iozzo says. "In contrast, absence of decorin permits tumor growth."

Therefore, the presence of decorin in the surroundings of the tumor is essential to control tumorigenesis and formation of new blood vessels, he says. Moreover, Dr. Iozzo's laboratory has characterized for the first time Peg3, a known tumor-suppressor gene, as a master player in the autophagy process induced by decorin. "This discovery is important as it opens up to the study of new unexplored genes and signaling pathways in the field of autophagy," he says.

"Circulating decorin represents a fundamental cellular process that acts to combat tumor angiogenesis," Dr. Iozzo says. "Treatment based on systemic delivery of decorin may represent a genuine advance in our ongoing war against cancer."

The study was funded by the National Institutes of Health grants R01 CA39481, R01 CA47282, and R01 CA120975.

Collaborating researchers from LifeCell Corporation, in Branchburg, New Jersey, and Goethe University in Frankfurt, Germany, also contributed to the study.

Link Between Telomeres and Obesity Discovered

New Gene Involved in Obesity

The discovery of an unexpected function for a gene that was associated to another process in the organism might be a solution in search of a problem, a clue to unsuspected connections. That is what has happened with RAP1, a gene that protects telomeres -- the ends of chromosomes -- after researchers from the Spanish National Cancer Research Centre (CNIO) surprisingly discovered its key role in obesity."We still don't know what evolutionary significance to attach to it, but it is at the very least interesting that a telomere gene is related to obesity," says Maria Blasco, CNIO director and co-author of the study published today in the journal

RAP1 forms part of the shelterin complex, a group of proteins that make up the protective hood of telomeres -- the DNA sequence at the ends of chromosomes that shortens with each cellular division and thus measures the ageing of the organism. There are six shelterins, and CNIO's Telomeres & Telomerase Group, which studies them in-depth, has discovered that RAP1, contrary to the rest, is not essential for the survival of the organism; but that does not mean RAP1 is not important. The reverse is rather the case: when comparing the genomes of different species, it can be observed that RAP1 is the most conserved shelterin of all. Despite the long history of evolutionary changes, RAP1 has not changed; it is present even in yeast. This normally implies an important role in the organism, but which one?

CNIO researchers had discovered that RAP1, in addition to being located in telomeres, is also present in the rest of the chromosome; they supposed it acts regulating the action of other genes. In order to analyse this other potential function, and its importance in the organism, CNIO researchers created a lineage of mice without RAP1 and, to their surprise, discovered a model for obesity.

MICE LACKING RAP1 GAIN MORE WEIGHT

"Mice -- especially female mice -- without RAP1 do not eat more, but do gain weight. They suffer from metabolic syndrome, accumulate abdominal fat and present high glucose and cholesterol levels, amongst other symptoms," says Paula Martínez, first-author of the study.

The reason is that RAP1 plays an important role in the regulation of genes involved in metabolism. In particular, researchers have discovered that it acts on the same signalling pathway mediated by another protein: PPAR- gamma (PPAR-γ). In fact, PPAR-γ deficient mice suffer from a type of obesity "surprisingly similar" to that seen in mice without RAP1.

The next step in the research will be to study if RAP1 also plays a role in human obesity. "This discovery adds an element to the obesity equation, and opens up a possible new link between metabolic dysfunction and ageing, via a protein present in telomeres," says Blasco.