Bone marrow cells migrate to tumors and can slow their growth

Dr. Wafik S. El-Deiry, Professor and Chief of the hematology/Oncology Division at the Penn State Heershey Medical Center has published research that shows that bone marrow-derived cells (BMDCs) can participate in the growth and spread of tumors in the breast, brain, lung, and stomach. The researchers used a mouse model to track the migration of the BMDC cells while tumors were growing. Their results showed that the bone marrow cells retarded the tumor’s growth.

To do the experiment, the researchers divided mice into two groups: the first group expressing a fluorescence gene served as donors of the BMDC’s. The Second group of mice, whose marrow was destroyed because of radiation were injected with the first group’s fluorescent bone marrow. The BMDC’s were allowed to grow fro 8 weeks. After those 8 weeks. Colon cancer cells were injected into all the mice and tumors formed. The scientists monitored tumor growth and noticed that the tumors contained BMDCs. They also noticed that the tumors were much smaller in the mice with bone marrow transplants.

The researchers say cancer is a more complex disease than previously thought: it is increasingly clear that there are many cellular interactions occurring in the malignant tissue. El-Deiry said this new method could lead to additional treatments that can help victims overcome cancer.

Article: http://www.eurekalert.org/pub_releases/2011-10/ehs-bmc100611.php

Image: http://stemcells.nih.gov/StaticResources/info/scireport/images/figure42.jpg

AKT2 Gene Linked to Severe Hypoglycemia

On October 7th, researchers from Cambridge University published a study identifying the relationship of the gene AKT2 with a rare form of hyploglycemia. Normally, this disease causes there to be too much insulin in the blood at all times and thus blood sugar drops to dangerous lows. But in this severe case of the disease, insulin is not detectable in the bloodstream, but blood sugar still drops to dangerous lows. Up unti

l now, this disease was treated by implanting a feeding tube to allow for feeding during sleep as to inhibit blood sugar from dropping too low.
This study now discovered that the gene AKT2 plays a significant role in transmitting insulin's effect to the cells of the body. With the genetic change identified through the study AKT2 is constantly turned on. Not only is this a huge breakthrough in understanding the disease, it has already led to potential treatment ideas. Since AKT2 is related to the gene that is related to cancer AKT1, researchers think that certain drugs that are currently being developed to block the AKT1 molecule could have the same effect on the AKT2 molecule.

http://tehrantimes.com/index.php/health/3304-cause-of-severe-hypoglycemia-identified

CAMH Study Confirms Genetic Link to Suicidal Behavior

Toronto's Center for Addiction and Mental Health has found new evidence that links a specific gene to suicidal behavior. Previously, scientists had connected to the gene for brain-derived neurotrophic factor (BDNF), involved in the development of the nervous system, to suicidal behavior. CAMH scientists recently were able to confirmed that among people with psychiatric behavior, those with the methionine (met) variation of BDNF had a higher risk of suicidal characteristics then those with valine variation. Their study included data from 3,352 people, of whom 1,202 had shown signs of suicidal behavior.

Scientists admit that this is only a small clue to the larger cause of suicidal behavior, as 90 percent of people who have died by suicide already suffer from at least one mental health disorder. However, these findings could lead to the development of treatment targeting this gene, and it could help genetic testing to identify people at risk for such behavior.

Article: http://www.eurekalert.org/pub_releases/2011-10/cfaa-csc100711.php

Rapid Venom Evolution in Pit Vipers May Be Defensive

Recent research published by the Am

erican Museum of Natural History has been able to deliver some important insight into the evolution of toxins in snake venom. Although originally thought to be a feeding, or trophic, adaptation, these studies have revealed this evolution to be a critical defensive technique against predators like hedgehogs, mongooses, and opossums.

Robert Voss, curator in the Department of Mammalogy at the museum, explained how for many years herpetologists thought of the evolution of toxins merely based on interactions with prey. "But if that were true," he continues, "[one] would see equally rapid

evolution in toxin-targeted molecules of prey species, which has not yet been seen." Instead, what's been found is a curious mutation in predators of pit vipers.Snake venom is so incredibly dangerous because it contains highly toxic compounds that will attack blood proteins, or serum proteins. These are responsible for, among other things, regulation

and functioning within the immune system. When they are targeted, massive internal hemorrhaging will occur in non-resistant, warm-blooded species.

It was during research on snake-eating opossums, not the snakes themselves, that this new insight came into being. Phylogenetic study suggested incredibly rapid evolution in the gene that codes for the von Willebrand factor, an important blood-clotting protein. While sequencing several genes, this one stood alone as an unusual outlier. It was evolving much more rapidly than expected in a group of opossums discovered to be resistant to pit viper venom.

What the researchers discovered was that the rate of replacement substitutions was much higher than the rate of silent substitutions in the von Willebrand factor gene among these opossums. "The specific amino acids in vWF that interact with toxin proteins show unexpectedly high rates of replacement substitutions," explained research associate Sharon Jansa, "[they] undoubtedly affect protein function, suggesting that the vWF protein can no longer be attacked by these snake toxins."

This meant this gene was under strong positive selection, actively coevolving with the increasingly dangerous snake venom toxins. Therefore, researchers concluded it was the predator driving the snakes' rapid evolution, not the prey.

http://www.eurekalert.org/pub_releases/2011-07/amon-rve071811.php

Image link: http://farm5.static.flickr.com/4021/4350414536_fe904f8685.jpg

Genetically Engineering Autistic Mice

Discovering the causes of autism continues to be a notoriously complicated process in the scientific world, as a variety of genetic factors as well as external factors such as childhood vaccines have been implicated as possible causes. It is widely accepted that there is a substantial genetic basis for the disease, but it has been unclear exactly how and to what extent genetic mutations or deletions/duplications manifest themselves in autistic people. Recent studies in which mice have been genetically engineered may bring us closer to understanding the effect of genetic abnormalities on autism and lead us to finding preventative treatments.

Researchers at the Beth Israel Deaconess Medical Center in Boston have manipulated the UBe3a gene in mice on chromosome 15 in the 11-13 segment, a region which has been implicated in causing developmental delays in humans. (Ube3a is one of about 40 genes that fall in this segment.) Abnormalities in this region are widely accepted as being the most common genetic cause of autism, affecting about 3% of people with the disease. The researchers tripled the Ube3a gene in their test mice and then observed their behaviors. Sure enough, the manipulated mice exhibited the three most common characteristics of autistic behavior observed in humans: reduced social interaction, impaired communication, and excessive repetitive behaviors.

Researchers are continuing to research how exactly the alterations to the UBe3a are expressed in terms of neuronal defects in the brain. Further understanding of these defects could in turn lead to treatments or autism that focus on the biological causes of the disease as opposed to the symptoms it produces. It is worth noting, however, that the disease has multiple and potentially interacting causes that make the use of models tricky. Furthermore, as neuroscientist Mary Blue at the Kennedy Krieger Institute noted, clinicians may be skeptical of using mice as models for a disease which hinges so largely on the shortcomings of human communication because "mice can't talk." Nonetheless, this research resonates widely in the field of autism studies.

http://www.eurekalert.org/pub_releases/2011-10/bidm-nmm100311.php

http://health.usnews.com/health-news/family-health/brain-and-behavior/articles/2011/10/05/scientists-engineer-mice-that-have-autism

Photo: http://www.dawn.com/2011/10/04/scientists-study-autistic-mice-for-disease-clues.html

Research Article: Autism Increased Gene Dosage of Ube3a Results in Autism Traits and Decreased Glutamate Synaptic Transmission in Mice

• Stephen E. P. Smith,
• Yu-Dong Zhou,
• Guangping Zhang,
• Zhe Jin,
• David C. Stoppel,
• and Matthew P. Anderson

Sci Transl Med 5 October 2011 3:103ra97. [DOI:10.1126/scitranslmed.3002627]

Samantha Fry - "Natural Selection Leaves Fresh Footprints on a Canadian Island"

It is a commonly held belief that humans have stopped evolving. Thanks to superior technology and the developed world’s plentiful supply of food and shelter, many scientists believed natural selection to no longer have an impact of humans. A recent study by a team of researchers from University of Quebec at Montreal proves otherwise. Led by Emmanuel Milot and DenisReale, the team studied remarkably throughout data on births, marriages, and deaths collected by a catholic church in a small island town on the St. Lawrence River near Quebec. The data revealed that over 140 years, 1799-1940, the average age of women when they gave birth to their first child fell from 26years to 22years. Additionally, they had an average of 4 more children due to this earlier beginning of their reproductive life. This drastic change in such a brief time span (relative to human history) not only provides convincing evidence that humans are still evolving but it may be occurring at perhaps an increasing speed. Alternative explanations for this phenomenon, such as cultural trends or environmental influences, have been offered however they have been rejected by the research team as each would logically lead to other observable changes in the population (ex: had increased healthcare been the cause, increased infant mortality should have followed suit, which it did not). Though cultural and environmental factors may still have some influence, the majority of this change can be attributed to biological evolution. Additionally, the trait in question (age of women when giving birth to their first child) has previously been proven to be highly heritable. This, in addition to the strong homogeneity of the society, lack of drastic wealth and lifestyle disparity, and a strong pattern of inbreeding, created good conditions for a prominent change in genetics. The result- “the most recent known instance of human evolution in response to natural selection.” (Wade, NY Times)

Article: http://www.nytimes.com/2011/10/04/science/04evolve.html

http://www.wired.co.uk/news/archive/2011-10/04/recent-human-evolution

http://health.nytimes.com/health/guides/specialtopic/genetics/overview.html?inline=nyt-classifier

"Loss-of-function variants in the Filaggrin gene are a significant risk factor for peanut allergy"

One of the most common food allergies seen in the US population today is peanuts. Unlike many food allergies, a peanut allergy is not one that can be outgrown—it is lifelong. Within the past three decades, pediatricians have witnessed an increase in the number of patients born with peanut allergies. This is not solely an American phenomenon—similar trends have been noted in populations throughout the world.

Researchers have long hypothesized that there might be a genetic basis for the peanut allergy. Several facts support this hypothesis: as previously mentioned, peanut allergy is a lifelong disease. Additionally, the disease appears to be inheritable. Until this past spring, though, no known genetic link had been found between a patient’s genotype and their risk for having a peanut allergy.

That unknown link was unearthed in March of 2011, when a University of Dundee-led research team discovered a link between mutations of the Filaggrin gene and likelihood of having a peanut allergy. Published in the Journal of Allergy and Clinical Immunology, the study aimed to pinpoint a specific gene that could be linked to peanut allergies. They focused on the gene Filaggrin, that (when functioning properly) codes for a protein of the same name that makes skin an effective barrier against irritations and allergens. [See photo for structure of Filaggrin gene.] However, mutations in the gene can cause loss of function, and were previously associated with atopic diseases (when a hypersensitivity reaction occurs in a part of the body not in contact with the allergen), such as asthma and eczema. Scientists this spring wanted to see whether it might too be associated with another atopic disease, peanut allergies.

Researchers used a test pool of 71 children—all of whom were known to be allergic to peanuts—in order to try to determine whether mutations in the Filaggrin gene could be a factor in the disease. The patients were from England, Ireland, and the Netherlands. Scientists found that 1 in 5 of the patients had a mutation of the Filaggrin gene, whereas patients in a control group (who were known to be allergy-free) did not. Most importantly, the general results of this study were confirmed in a similar study in Canada, which had a much larger test pool of 390 patients with allergies, and a control group of 1000 patients.

Several implications can be drawn from the results of this study. For the first time, a genetic link was established with the peanut allergy, across multiple geographic populations. Researchers concluded that the Filaggrin mutation was in fact “strongly and significantly associated,” and “firmly linked,” with peanut allergies. While it is not the sole cause of peanut allergies, it is the “single most significant genetic risk” factor found to date. Finally, the study may even underestimate its significance as a factor, because the study only focused on the most common mutations of Filaggrin, but there may be others that play a role.

Study:

http://www.jacionline.org/article/S0091-6749(11)00120-5/fulltext

Additional articles I consulted:

http://www.dailymail.co.uk/health/article-1365255/Allergies-Gene-defect-triples-risk-peanut-allergy-children.html

http://www.physorg.com/news/2011-03-gene-linked-peanut-allergy.html