Sunday, February 16, 2020

Understanding Why Cancer Rarely Strikes Elephants Is Vital

It is estimated that almost 10 million people die from cancer annually. Even with the widespread advancements we've made in science and technology, the complete cure for cancer has eluded humankind for long. What’s worse, it’s not just humans who are suffering from this disease. You would be surprised to know that the mortality rate in the animal kingdom due to cancer is quite similar to that of humans.

A lot of you must be aware that pet dogs and cats are often diagnosed with various forms of cancer. Wild animals get cancer, too. Tasmanian devils, sea lions, beluga whales, among others, often die as a result of being afflicted with this disease.

One animal, however, doesn’t seem to get cancer that often – the elephant. In fact, only about 5% of elephants die from cancer. This is remarkably low for an animal that is so large in size.


Can elephants provide the solution to fight cancer?
Elephants, the giants of the wild, have an average life span of 60-70 years, which is considered unusual for an animal that is so large. If we go by statistics, bigger animals have more cells, and hence, should have greater occurrences of cancer. This is simply because their cells are dividing so quickly they should just have really high rates of mutation and cancer. But that isn’t the case with elephants. This phenomenon is called “Peto’s paradox”, named after the scientist Richard Peto, who observed that cancer prevalence is not correlated with body size.


The “zombie gene” and how it helps elephants remain largely cancer-free

Now, a new study has offered clues in regard to the elephant's apparent immunity to cancer, which could lead to being a breakthrough from a medical standpoint. Apparently, elephants have, what researchers are saying, a “zombie gene”. In other words, these animals have extra copies of two cancer-fighting genes. Firstly, there is P53, which hunts for cells with miscopied DNA. The other and more significant one is Leukemia Inhibitory Factor or LIF – a gene that eliminates the mutated cells before they can form a tumor. 


Interestingly, a majority of mammals have one copy of LIF. But elephants have 7 to 11 of them. The one that is doing the job for these giant mammals appears to be Leukemia Inhibitory Factor Pseudogene or LIF6. So far, this has only been found in elephants, and this is what scientists believe is helping their bodies remain mostly cancer-free.

On checking the evolutionary record of these animals, it was later discovered that the LIF6 had actually become inactive in elephant DNA millions of years ago. Curiously, though, it then mysteriously resurrected itself. Initially, it was a broken and useless gene. However, as the elephants evolved, so did the genes, and the LIF6 managed to reawaken in them as a working “zombie gene”.


How the LIF6 gene works in elephants

To illustrate the significance of the LIF6 gene, scientists carried out lab experiments where they caused DNA damage to African elephant cells. The damage appeared to trigger P53 to turn on the LIF6 gene which then went on to destroy the impaired cells. Furthermore, when the LIF6 was prevented from functioning, the elephant-specific sensitivity to cell damage seemed to disappear.

Take a look at this video below to understand more about the "zombie gene".


Scientists also believe that the LIF6 gene is not the only one keeping cancer in check in elephants. “LIF6 is playing a small part in a broader process,” says Vincent Lynch, an evolutionary biologist at the University of Chicago. Joshua Schiffman, a pediatric oncologist at the University of Utah, agrees, and adds: “there are almost certainly going to be other findings as well.”

In 2018, a team of scientists published a study that laid emphasis on another set of genes that helps in repairing broken elephant DNA instead of killing damaged cells. Further studies are being conducted in this regard which could lead to significant breakthroughs in understanding how the elephant remains largely immune to cancer.


Importance of P53 - the tumor-suppressing gene in elephants

Meanwhile, the importance of the tumor-suppressing gene P53 in elephants cannot be undermined, too. Before the LIF6 gene was discovered, scientists believed that it was P53 that helped elephants remain mostly cancer-free. In 2015, Schiffman and his team had published a paper that found that elephants have extra copies of P53. Humans have one copy of this gene while elephants have 20.
“P53 can recognize DNA damage and then go, ‘OK what are our options?’” explains Amy Boddy, a biologist at the University of California, Santa Barbara. Cells that have normal issues can be repaired. However, the ones with severe damage become prone to cancer. This is where the P53 steps in and orders those cells to be killed in elephants. Furthermore, P53 also stops the cell from proliferating. That gives it the time to repair itself when damaged.

Thus, with these two super genes – the P53 and the LIF6 – the elephant has managed to fight off cancer for so long. 


What does this mean for humans?

Bowhead whales and blind mole rats are some of the other animals in the wild who have managed to found ways to live long lives without suffering from this dreaded disease. Perhaps, the more we understand about the basic biology of all these animals, the more it would help humans in the longer run.

Currently, scientists are working with pediatric oncologists, the zoo, and the circus to learn from elephants. The ultimate goal is to attain a complete understanding of the elephants’ defense mechanism against cancer and to use it in the cancer treatments for humans.


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Thursday, January 16, 2020

Scientists identify 'modifier gene' that determines severity of inherited kidney disease

Scientists have developed a new way to understand complex genetic diseases and have identified a gene that modifies the severity of inherited kidney disease, paving the way for personalised treatments.

Experts at Newcastle University, UK, have shown that the rate of kidney disease in people with Joubert syndrome is determined by the genetic makeup of the individual and each patient may respond differently to treatment.

Joubert syndrome is a complex disorder, affecting approximately one in 80,000 newborns, causing varying degrees of physical, mental and sometimes visual impairments. It is often associated with severe kidney disease that requires dialysis and ultimately transplantation.

The study, published online in the Proceedings of the National Academy of Sciences, is the first time that an explanation has been given for the difference of disease progression in Joubert syndrome patients.


Significant breakthrough

The Newcastle research has identified a second gene called BSND - a 'modifier gene' - which determines the severity of kidney disease in patients with CEP290 mutations of Joubert syndrome.

It has been assumed that these modifier genes exist, but they have never been found before in rare genetic conditions until now.

Professor John Sayer and Dr Colin Miles, from the Translational and Clinical Research Institute, Newcastle University, led the Medical Research Council-funded research.

Professor Sayer said: "We have shown, using mouse and human DNA samples, that BSND is a modifier gene for the severity of kidney disease in Joubert syndrome.

"This is the first time that a modifier gene for inherited kidney disease has been identified, and this information will improve diagnoses and will be used to develop therapies to reduce the severity of kidney disease in affected patients.

"Our research is a major step forwards and, in the future, we may be able to offer a therapy that switches on the protective modifier gene and reduces the development of genetic kidney disease.

"This work paves the way towards personalised therapies in patients with the inherited kidney disease."

The international study used mouse models and DNA samples from patients with Joubert syndrome to progress the research.

Scientists used mouse models of disease and genetic manipulation to see how the kidney disease responded to modifier gene manipulation, cross-referenced with DNA sequencing data from patients around the world to prove the modifier gene was relevant in humans.


Challenging disease
Professor Sayer, a Consultant Nephrologist at Newcastle Hospitals NHS Foundation Trust, said: "The treatment of genetic kidney disease is challenging, as this requires both the correction of the underlying gene defect and the delivery of the treatment.

"We have shown that the kidney disease in a mouse can be dramatically changed by switching on or off a modifier gene.

"This will mean that we can use this information to carry out treatments, including genetic therapies, to lessen the effects of inherited kidney diseases, such as Joubert syndrome.

"We are testing these treatments further in our model systems before we move into patient studies."

Within the next three years, research will start to test treatment of patients with modifier genes in the hope of developing personalised treatment plans.
Patient story

Siblings Emma, 11, and Ben Buckley, eight, have Joubert syndrome and both developed kidney failure before the age of eight.

They were diagnosed with Joubert syndrome from a few months of age and both have required dialysis and a kidney transplant.

They suffer from a range of medical issues due to Joubert syndrome, including visual impairment, communication problems and developmental delay.

The two children, of Whitley Bay, North Tyneside, have been instrumental in helping further the research over the years, allowing the Newcastle scientists to study the mutation in detail.

Parents Leanne and Michael say they welcome the findings of the Newcastle University-led study as it will help to give patients a chance of preventing kidney failure in the future.

Leanne said: "It is very important that research is done into Joubert syndrome and the linked kidney damage, as this will hopefully prevent patients in the future needing a kidney transplant.

"All throughout Ben and Emma's lives, they have lived with the effects of Joubert syndrome and scientists found they had a problem with the CEP290 gene.

"Both Ben and Emma have needed dialysis and kidney transplants because of their kidney problems and I would like to hope this research will help prevent kidney failure for other affected children.

"We were happy for Ben and Emma to provide samples for the study as anything that helps further understanding into the condition is well worth doing, so it's great to see the study's positive results."



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Wednesday, December 25, 2019

Study suggests evolutionary changes in human brain ptoentially cause anxiety

Evolutionary changes in the human brain are the potential cause of anxiety, new research has found.
Neurochemicals like dopamine and serotonin play significant roles in the emotional as well as cognitive functions of the human brain. Vesicular monoamine transporter 1 (VMAT1) is one of the many genes that are majorly responsible for regulating neuronal signalling and for transporting neurotransmitters.


The research team reconstructed ancestral VMAT1 proteins for their study which further revealed the functional changes that have taken place in the neurotransmitter uptake of VMAT1 during the course of human evolution.


The researchers previously found out that VMAT1 is one of the genes that had evolved through the human lineage.


VMAT1 contains 2 mutations or the genome changes which are human-specific.


In the study, the researchers revealed the evolutionary changes present in the uptake of neurotransmitters through the reconstruction of ancestral VMAT1 proteins.


The researchers began by applying a fluorescent substrate for visualising and quantifying the neurotransmitter uptake of every genotype.


The researchers found out that the ancestral VMAT1 protein exhibited an increased uptake of neurotransmitters as compacted to the derived genotype which is shown to be associated with depression and or anxiety in contemporary human populations.


The results of the study reveals that our ancestors may have been able to withstand higher levels of anxiety or depression, said the researchers of the study.


The researchers would next try to get a better understanding of how the variants contributes to our brain evolution.


This would be the striking evidence that links the evolution of our genome and brain, said the authors of the study.


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Saturday, September 21, 2019

Gene therapy for sickle cell disease steps closer

Researchers have found a way to repair the faulty gene that causes sickle cell disease, which they suggest is a significant step forward in the search for a viable gene therapy.

 In a study,  they report how - using the CRISPR gene-editing tool - they corrected the gene in stem cells from diseased patients and showed they could make red blood cells capable of making functioning hemoglobin. They also transplanted the stem cells into mice and found them thriving in their bone marrow months later.

Sickle cell disease is a group of inherited disorders where red blood cells form abnormal, hard and sticky, crescent, or sickle shapes instead of normal, flexible, disc-like shapes.

The sickle red blood cells stick to vessel walls and cause blockages, slowing the flow of blood and stopping oxygen reaching nearby tissues. This can cause pain and damage to tissue and organs. Also, sickle cells die faster than normal red blood cells, raising risk of anemia, which can also damage organs.

The disease is caused by a single mutation in a gene that codes for a protein chain in hemoglobin - the molecule in red blood cells that carries oxygen. The faulty hemoglobin forms stiff rods within the red cell, making it crescent-shaped.

Sickle cell disease affects millions of people around the world. The number of Americans living with it is not known, but estimates suggest it is around 100,000.

Children born with sickle cell disease in high-income countries typically survive and can go on to live full lives and enjoy most of the activities that other people do. However, in low-income countries, children born with the disease typically die before they reach their fifth birthday.


Gene therapy and the promise of CRISPR

Since its early beginnings in the 1980s, gene therapy has been a holy grail among researchers looking for ways to cure or treat genetic disorders.

CRISPR is a relatively new gene-editing tool that is said to have "triggered a revolution in genome engineering within living systems." Researchers prefer CRISPR to older methods because it is easier and faster.

The technique is a type of molecular scissors that snip out faulty strips of DNA so they can be replaced with corrected versions using other tools.


The senior author of the new study, has been trying ways to target sickle cell genes with gene-editing technology for several years.

He says with the new CRISPR technology, they can work much faster and more effectively, significantly cutting the time of experiments.

"We spent half a dozen years trying to target the beta globin gene using the old technology," he remarks, adding that within a week of trying CRISPR, they had a gene-editing tool that was much better.

For their new study, Prof. Porteus and his team took hematopoietic stem cells from the blood of patients with sickle cell disease and corrected the faulty gene using CRISPR to remove a strip of DNA and a virus to insert the correct version. Hematopoietic stem cells are stem cells that make blood cells.

They concentrated the human hematopoietic stem cells so that 90 percent carried the corrected sickle cell gene and then injected them into young mice.


Proof of concept that gene-editing can repair sickle cell

Prof. Porteus says that the hematopoietic stem cells have the ability to travel from the bloodstream into the bone marrow, where they then "set up shop and start making other blood cells."

Sixteen weeks after the transplant, the researchers found the stem cells were thriving in the mice's bone marrow.

A gene therapy for sickle cell disease would not have to replace all of a patient's sickle cells Prof.  explains. You just need a sufficient amount of normal cells. Patients whose sickle cells are below 30 percent show no symptoms of disease.

The researchers now need to take their discovery through a series of tests so they can investigate the safety aspects of the new gene editing tool.

This is going to be no mean feat - no CRISPR-edited genes have yet been tested for safety or efficacy in human clinical trials. A particular challenge is how to overcome potential so-called "off-target" effects, where the molecular scissors accidentally cut out the wrong piece of DNA.

Prof. Porteus says Stanford is building the infrastructure so they can start to take their findings out of the lab and scale them up into the types of systems that will be needed to create gene therapy for patients.

For now, he and his team can say that their gene-edited human hematopoietic stem cells appear to behave like normal, healthy human hematopoietic stem cells.

They suggest their findings are proof of concept that using gene-editing can repair sickle cell and other blood-borne genetic diseases, such as thalassemia.

    "What we've finally shown is that we can do it. It's not just on the chalkboard. We can take stem cells from a patient and correct the mutation and show that those stem cells turn into red blood cells that no longer make sickled hemoglobin."



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Wednesday, July 03, 2019

Short bouts of exercise enhance brain function

Regular exercise is not just good for your health but it can also make you smarter, a study has found. Neuroscientists, working with mice, have discovered that a short burst of exercise directly boosts the function of a gene that increases connections between neurons in the hippocampus, the region of the brain associated with learning and memory. They measured the brain's response to single bouts of exercise in otherwise sedentary mice that were placed for short periods on running wheels. The mice ran a few kilometers in two hours. 

The study found that short-term bursts of exercise -- the human equivalent of a weekly game of pickup basketball, or 4,000 steps -- promoted an increase in synapses in the hippocampus. 


The neurocientists made the key discovery by analysing genes that were increased in single neurons activated during exercise. During the research, one particular gene -- Mtss1L -- stood out. This gene had been largely ignored in prior studies in the brain. The Mtss1L gene encodes a protein that causes bending of the cell membrane.


 The researchers discovered that when this gene is activated by short bursts of exercise, it promotes small growths on neurons known as dendritic spines -- the site at which synapses form. The study showed that an acute burst of exercise is enough to prime the brain for learning.



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Friday, March 22, 2019

Excess Hair Growth In Women And When It Is a Reason For Concern

Facial and body hair in women sometimes feels like a taboo subject. We never hear or talk about it, except for hair removal advertisements, which is a shame, as it makes us believe that hair growth is a flaw that always needs to be corrected.

In the majority of cases, however, hair growth on various body parts, such as shins, thighs, lower arms and even face are not a cause for concern, but rather a peculiarity of your personal genetic makeup. That being said, in some cases, facial and body hair can start growing rapidly or suddenly become darker and thicker, which is when you should pay more attention and consider a conversation with your doctor.

Excess hair growth in women (also called hirsutism) can be a symptom of a variety of health conditions: adrenal dysfunctions, hormonal imbalance, as well as an early symptom of cancer. In this article, we will walk you through all the different causes of excess hair growth, both pathological and not.

1. Genes & Ancestry

As we have mentioned above, your genetic makeup can be the reason why you have more hair than your peers.
According to an article, for example, it was established that women of Mediterranean and Middle Eastern descent are more likely to have more facial and overall hair growth while maintaining normal hormone levels.
But ethnicity is not the only predicting factor; your personal family history can also tell you a lot as well. If women in your family have the same hair pattern you do, it is most likely not a health concern. Finally, postmenopausal females can experience hair growth due to sudden changes in hormonal levels without experiencing any other health concerns.

2. Polycystic ovary syndrome (PCOS)

One of the most common dysfunctions that causes excess hair growth in women is PCOS, which is a hormonal condition that commonly affects women of reproductive age. PCOS occurs when the ovaries fail to release an egg during the menstrual cycle and they collect in the ovaries and fallopian tubes, forming cysts in these areas.
The symptoms of PCOS include:
  • Irregular periods
  • Enlarged ovaries
  • Acne
  • A receding hairline
  • Obesity
  • Increased androgen (male hormone) levels, which cause excess hair growth according to a male pattern (see pictures to understand the difference between male and female hair growth patterns).
In fact, apart from genetic influence, all the causes of excess hair growth in women are usually linked to increased levels of androgens in the body.

3. Medications

Certain medications can increase hair growth. These include:
  • Drugs used to treat women with endometriosis, such as danazol.
  • Certain antidepressants, such as fluoxetine (Prozac).
  • A class of drugs called systemic corticosteroids, such as prednisone.

5. Adrenal Issues

Adrenal dysfunctions, such as Cushing's syndrome and congenital adrenal hyperplasia can cause hirsutism. This happens because the body is exposed to high doses of cortisol, a hormone produced by the adrenal gland, and other steroids, which causes hormonal imbalance.
Like in the case of PCOS, women with these conditions will experience hair growth typical for a male pattern, meaning growing coarse and abundant facial hair, hair on the chest, stomach and inner thighs, which shouldn't be confused with peach fuzz, also called vellus hair that is thin, practically invisible and not a reason for concern.
excess hair growth in women body
Other symptoms of these conditions are:
  • Hypertension
  • Weight gain in the upper body
  • Fluctuations in blood sugar levels
  • Muscle weakness
  • Migraines.

6. Tumors

Sudden onset hirsutism in uncommon, but if you find that only in a few months you started growing a lot more hair, it’s best to get checked by a doctor. This is because some tumors in the ovaries or adrenal glands can secrete androgens, which can bring about hirsutism.
Depending on the health concern or lack thereof, you and your doctor will help you deal with excess hair in a variety of medical treatments, changes in your current medicine or self-care hair removal treatments.
excess hair growth in women face
Please keep in mind that the information included in this article is just a general guide to excessive hair growth in women and isn’t a diagnosis. If you have any concerns, make sure talk to your doctor, who will be able to make a proper diagnosis.
 
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Saturday, February 09, 2019

Researchers Identify Gene to Treat Alcoholism

Researchers have identified a gene that could provide a new target for developing medication to prevent and treat alcoholism, according to a new study on mice.
Researchers  discovered a gene that had lower expression in the brains of non-human primates which voluntarily consumed heavy amounts of alcohol compared to those that drank less.


Furthermore, the team unraveled a link between alcohol and how it modulates the levels of activity of this particular gene.

Researchers discovered that when they increased the levels of the gene encoded protein in mice, they reduced alcohol consumption by almost 50 per cent without affecting the total amount of fluid consumed or their overall well-being.

The study modified the levels of the protein encoded by a single gene known as GPR39.

The prevalence rates of co-occurring mood and alcohol use disorders are high, with individuals with alcohol use disorder being 3.7 times more likely to have major depression than those who do not abuse alcohol.

Using a commercially available substance that mimics the activity of the GPR39 protein, the researchers found that targeting this gene dramatically reduced alcohol consumption in mice, showed the findings of the study.

"The study highlights the importance of using cross-species approaches to identify and test relevant drugs for the treatment of alcohol use disorder," noted senior author.


THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                    PS- THOSE INTERESTED IN RECIPES ARE FREE TO  VIEW MY BLOG-                                                                                           https://gseasyrecipes.blogspot.com/       
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