One of the biggest difficulties for those trying to treat and prevent Human Immunodeficiency Virus (HIV) infection is its rapid evolution, even within one person. Even though it was introduced in the mid 1990’s the drug Zidovudine is already slowing down in the fight against HIV as more strains are becoming immune to it. However, scientists are now taking a new approach to HIV treatment and may use its high variability against it.
This approach relies not on viewing HIV as a pathogen to be eliminated but as a mobile immune system gene. HIV is so deadly because, once it has infected its host, it inserts its DNA into the host genome and “blends in.” We cannot target it for removal because it uses the same mechanisms as our own body to pass along its genes. This would be fine if the virus had no effect and just stayed in the genome (in fact, some have proposed that as a mechanism of higher-organism evolution) but it does not. HIV disrupts our bodies’ normal immune system and continues to replicate and spread, cluttering our genome with DNA that has no function for us. Zidovudine and other drugs like it target HIV before it has integrated itself into the human genome, when it is still in charge of its own replication. However, once the virus has integrated itself into our DNA, these drugs are no longer effective and the virus can evolve protections against them. HIV will most likely be able to evolve quicker than we can develop drugs to act on them.
But what if we could use HIV’s evolution against itself? The fundamental problem with viruses such as HIV is that they hurt us, their host. If they harm their environment, there is less room for them. There is a constant balance for the virus to replicate itself as much as possible without killing its host before it can be transmitted. If it leans too far towards replication, it kills its host and can no longer survive. Scientists are now considering pushing HIV in the other direction: Forcing it to “play nice” with us and no longer impair its host. Theoretically, a virus that is friendlier to its host will be less of a target for immune defense. This would confer an evolutionary advantage to the “nice” HIV that may allow it to displace the current version entirely. It is now up to science to design a virus that looks and acts like HIV but has none of the harmful effects.
This particular goal is not unrealistic. Genetic modification in the lab is commonplace these days and the evolutionary potential of HIV makes it a particularly hardy specimen for this type of experimentation. If HIV could be made relatively harmless in vitro (i.e. in a Petri dish in the lab, far away from living test subjects) the new virus may be a valid treatment option for those already affected with HIV. If introduced into an HIV-positive person, the newly modified virus would compete with the other for dominance. Because it is less harmful to its host, this new virus would be more fit (reproduce better) than the original virus. Eventually the harmful HIV would be completely displaced. The person would still be HIV-positive, but would suffer none of the harmful effects of the virus as it is now. Interestingly, this treatment would continue to work with the current treatment options for HIV infection. Both strains of the virus would be suppressed, but that would only help the new, harmless virus that is not being targeted by the body for elimination.
This approach stems from the evolutionary heritage of our current immune systems, in fact. Our immune system genome currently has many non-functioning DNA sequences (last winter’s cold, for example). It is the fact that these sequences are not harmful to us that allows them to continue to exist in our bodies. These old genes may even be helpful to us if, for example, this winter’s cold is a mutation of last winters. The only difference between the immunity components our bodies develop and the lab-modified HIV would be that the virus could reproduce outside of the cell. The fact that there are some HIV-positive individuals that exhibit no symptoms of AIDS related illnesses points towards the fact that a mutual coexistence with HIV is possible.
The biggest obstacles, then, to developing this solution to HIV are social and economic in nature. Medical systems are currently built around developing pharmaceuticals to combat illnesses and infections. Using a virus against itself is, thus far, out of the realm of contemporary thinking. It would require an entirely different approach on the part of scientists and health care providers. Current HIV treatments work against its evolutionary strengths. This new approach could use the viruses own strengths against it to fight a battle we are currently losing.
The X-Ray Light Valve used in conjunction with a simple optical scanner is the next step in digital radiographic imaging as a cost-effective alternative to the Active Matrix Flat-Panel flat panel imager. It can be used to produce digital images of revolutionary quality in radiography and medical technology that parallel its counterpart, the Active Matrix Flat Panel system.
The Active Matrix Flat-Panel flat panel imager was the latest in X-ray imaging technology until researchers developed the X-ray light valve. The Active Matrix Flat-Panel Imager works in two main ways, by direct conversion and then by indirect conversion. In the process of direct conversion, incoming X-rays are converted to charge carriers with an amorphous Selenium (a-Se) layer. Then an electric field is used to move them into an embedded array of thin-film of transistors, amplifiers, and analogue-to-digital converters. The digital signal can be displayed as an image, processed and stored electronically.
The second process of indirect conversion involves the X-rays hit a phosphor layer that emits light in response. An array of photo-diodes converts the light to electrical signals that can be converted to digital signals to be displayed, processed and stored as image.The Active Matrix Flat Panel System has great advantages that make it a revolutionary asset to the field of medical imaging, technology and radiography. It produces very high resolution images with very little disturbance from electrical noise along the transistor circuitry that load the electrical signal of the image and transmit to the digital analyzer to be converted into digital format. The high speed acquisition of this data in the conversion of the image in its analogue state in form of electrical signals through the array of multiple transistors to the digital analyzer, allows real-time fluoroscopic imaging, to account the dynamics and concurrent changes in the body being imaged. However, these advantages apply specifically to the direct conversion approach. The indirect conversion method on the other hand produces images with lower resolution due to scattering of light in the phosphor layer. Overall, the main inconvenience the Active Matrix Flat Panel Imager poses is the enormous cost of producing, implementing and maintaining the equipment and system in the clinical environment. At $200,000.00, it is a very expensive method of imaging in radiography and diagnostic medicine, a cost that patients bare in paying for treatment. Very few hospitals and people in the developed countries can actually afford it and it is not even an option for hospitals and people in developing or underdeveloped countries.
The X-ray Light Valve, if perfected would be an order of magnitude less expensive at $20,000 making it much cheaper to produce and install in hospitals, and a more cost-feasible technique in medical imaging and radiography. This translates into reduced expenses in the maintenance and upkeep of such a complex system, and an affordability that makes this method of medical imaging more easily and readily available and accessible to medical institutions less capable of financing the Active Matrix Flat Panel Imager such as those in developing nations, without compromising or compensating the cutting-edge technology of high resolution fluoroscopic digital images the Active Matrix Flat Panel Image provides. The X-ray Light Valve uses a-Se to convert X-rays to charge without actually measuring the electric charge signal directly like the Active Matrix Flat Panel Imager does. It uses of a birefringent liquid crystal to receive and read the electro-optical effects caused by the interaction of the X-rays with the amorphous selenium to form electron-hole pairs.
An electric potential is generated across the amorphous selenium using a positively charged electrode at the surface of the posterior surface of birefringent liquid crystal and a negatively charged electrode on the photon receiving end of the amorphous selenium. The electrodes effectively sandwich the amorphous selenium and the birefringent crystal. The bias voltage applied across the amorphous selenium layer separates the electrons-hole pairs created from the interaction between the X-ray photons and the amorphous selenium into electrons and holes.
The electric field then causes the electrons and holes to drift apart to either electrode, with the electrons going to the interior surface of the birefringent liquid crystal in direct contact with the amorphous selenium. Since the X-rays interact with the body first, they hit the amorphous selenium at different energies that depending on how the photons interact with the part of the body being imaged. This causes different intensities or concentrations of electrons-hole pairs to be formed in the amorphous selenium depending on the varying energies at which the X-ray photons leave the body part undergoing radiography, after interacting with it. This causes variations in the charge distribution at the interior surface of the birefringent crystal that translates into the analogue form of the image. The scanner receives the double refracted light through the birefringent liquid crystal from the analogue image in the form of variations in distribution of charge, simultaneously converting it to a digital image as all optical scanners do.
On average women live 4.2 years longer than men, and the difference in age is predicted to increase to 4.8 years by 2050. Most people equate the difference in life span between the two genders to males making more unhealthy choices. However, recent research has shown that the difference in age longevity could be biological.
There is well-documented evidence that show that excess mortality rate in men is in part due to cardiovascular diseases. Males are much more prone to cardiovascular risks than women. The occurrence of coronary heart disease is three times more frequent in men than females. Moreover, mortality rates due to CHD are five times more in men than women. However, as men and women continue to age, the gender gap in cardiovascular risk goes down due to menopause in women
Estradiol plays an integral part in reducing cardiovascular diseases in women. Estradiol is a sex hormone that is present in females; nevertheless, there is very small amount of estradiol in men as well. Estradiol significantly affects the endothelial lining of blood vessels. Endothelial lining of blood vessels are important when looking at occurrences of heart disease. This is because of endothelial lining controls blood vessel constriction and dilatation, which in turn affects how the heart functions. Estradiol interacts with nictric oxide enhancing the vasodilatation in females; as result, the blood vessels are not easily clogged, which reduces the risk of heart injury.
Another reason for longevity of females is that they are not prone to as much oxidative stress than males. This oxidative stress arises from free radicals. Free radicals are reactive oxygen species that are produced in the mitochondria and result in damage of parts of the cell, which is the main reason for aging. Naturally, the defense system counteracts the free radicals by producing anti-oxidants. The balance between the free radicals and antioxidants determine amount of damage and aging during the lifetime. Mitochondria from females produce less amount of hydrogen peroxide, which causes oxidative stress. Moreover, females produce more antioxidants than males. As a result, oxidative damage is higher than females. For instance, the oxidative stress causes four-fold times higher in males’ mitochondrial DNA than females’. Estrogen levels contribute partly to the reduction of oxidative stress in females. Estrogen enhances the production of antioxidants, which reduce the production of free radicals in the mitochondria. This could explain why females have longer life span than males.
Another reason for female age longevity is that females have longer telomeres. Telomeres are non-coding DNA repeating sequences found at the ends of all chromosomes. The telomeres are responsible for protecting the ends of chromosomes from end to end fusion, recombination and degradation. During replications up to hundred base pairs from the
telomere repeats are lost. Therefore, after several replications the chromosomes are longer protected due to the shortening of the telomere. Since the chromosomes are longer protected by telomeres, the cells are longer able to go through cell division, and they eventually become apoptotic (die). Therefore, telomere shortening weakens organ regeneration. This because the cells in the organs go through apoptosis due to telomere shortening, and after a period of time, the number of dead cells increase impeding the regeneration of the organs. Since telomeres are longer in females, cells in males have shorter lifetime and their organs are impaired at younger age than in females. In addition, estrogen enhances the production of telomerase. Telomerase is responsible for inhibiting the degradation of telomeres during replication. Therefore, female telomeres shorten at much lesser rate than in males. As a result, females are able to live longer than males.
In conclusion, recent studies have revealed more biological evidence that accounts for higher life expectancy in females than males. Males are more prone to coronary heart disease, less organ regeneration, more oxidative stress. This is because of the lack of estrogen production in males. On the other hand, females produce high levels of estrogen before menopause, which accounts for their age longevity. High estrogen levels are responsible for blood vessel vasodilatation, which prevents blood vessel clogging and reduce coronary heart diseases. Moreover, estrogen is also responsible for reducing oxidative stress by producing antioxidants. This results in slower aging process in females. Additionally, estrogen enhances the production telomerase that inhibits telomere shortening. Consequently, lifetime of individual cells and organs in females is higher. There are other factors that could also increase the life expectancy of females that are not discussed here. These evidences suggest that males could be biologically prone to higher mortality rates at younger ages than females.
Tom Eskes, Clemens Haanen. “Why do Women Live Longer than Men”European Journal of Obstetrics & Gynecology and Reproductive Biology. Volume 133, Issue 2, August 2007, Pages 126-133
Do you remember biomes? The 10-12 ecological regions of the world classified by predominant vegetation and regional climates? We learned about them in middle school, probably.
Yeah, those look familiar. These biomes for years have been used by ecologists as a basic way to describe the global patterns of ecosystems and have been taught in science classrooms to generations of young students. Recently, two scientists by the names of Ellis and Ramakutty (2008) published a study suggesting we adopt a new way of looking at the earth’s ecosystems, one that “puts people in the map” by defining ecological areas of the world based on the level and type of anthropogenic, or human, influence. These interactions range from the light impacts of indigenous hunter/gatherers to the impacts of urban development and sprawl, and by mapping them the authors hoped to integrate humans into the biosphere. Posted below is the template used in their paper, and a map built using the population densities and land use data for earth’s terrestrial surface.
What Ellis and Ramakutty found, and what the map clearly shows, is that the earth’s ice-free surface is dominated by some level of human influence, approximately three quarters of it to be more precise. Nearly 90% of the earth’s net primary production (NPP) can be found in anthropogenic biomes, but half of it is located in forested or rangeland biomes that have relatively low population densities. The other half, and one third of the earth’s ice-free surface, occurs within heavily cultivated and populated biomes. Village biomes were the most extensive of the anthropogenic biomes, while urban biomes covered only 7% of earth’s surface and yet contain 60% of the human population. Overall, cropland and rangeland were the most significant anthropogenic changes to the earth in this study.
Portions of the map, such as the image to the right, are staggering. Displaying land-use in this manner is a novel and educational way of demonstrating that humans surely are an integral part of the biosphere. The map also demonstrates that the earth’s surface, specifically the area inhabited by humans, is a mosaic, a patchwork of heterogenous land use and vegetative cover. It is within this broken quilt that all of our direct interactions with the earth occur, the good and the bad, the constructive and the destructive. The authors attempt to make it clear that their map is not a threatening and leering display of doomed efforts for conservation; rather, they urge that it be used as a call to reevaluate our place on the planet, among scientists and local citizens alike.
To regress slightly from this uplifting note, it cannot be overlooked that wild lands, those untouched by humans, cover 22% of earth’s ice-free surface. Most of this area is located in the least productive parts of the planet, composed primarily of barren land and sparsely tree-covered regions. Because of this, wild lands only represent 11% of the earth’s NPP. This is disheartening news to those who love to see these wild lands on television and for those who wish to visit them, but it does not mean our earth is past the point of no return. Much of the anthropogenic biome map demonstrates humans interacting positively with the earth, in areas of low impact and high NPP.
Another important point this study raises is this: do these “anthromes” make the old-system view of natural biomes obsolete? The authors firmly state that they do not, and that their approach to understanding global ecological processes is merely conceptual, while the standing model of biomes is tested and an accurate predictor for important trends in biodiversity throughout the planet. However, this does not mean the biome method is a more accurate one. What the authors of this have shown is that humans by sheer size and range of impact, deserve to be included in the description and study of earth’s global ecosystem, as well as the management of its biodiversity.
As we progress further into the 21st century we can expect to see many changes in how we live and how the earth is altered by our living on it. Our population size alone will demand a very in-depth consideration of how natural resources should be allocated and the most sustainable ways of achieving current standards of living. Conservative living will never be an unworthwhile pursuit. But the science of conservation must evolve with the knowledge presented in Ellis and Ramakutty’s paper, enough so that it enters the conscience of the public and all those who call this planet home.
Erle C Ellis and Navin Ramankutty. 2008. “Putting people in the map: anthropogenic biomes of the world”. Frontiers in Ecology and the Environment, 6, doi: 10.1890/070062.
Landmines are and have been used in modern warfare extensively, as a way to injure or kill the enemy without having to get close to them. However, once the war is over, the landmines remain hidden in the ground, waiting to be detonated. Roughly 110 million landmines are still active in over seventy countries. Every month, 800 people are killed by landmine explosions and 1200 are seriously injured. A large majority of these people are civilians, especially children (New Internationalist Magazine). An effective and inexpensive method of removing landmines has not been found yet, until now.
Recently, scientists at the University of Edinburgh have developed a novel method for the safe and efficient removal of these mines: glowing green bacteria. Dr. Alistair Elfick engineered bacteria that glow green when it contacts chemicals from landmines. The bacteria can be dissolved in solution and sprayed from airplanes onto large areas of land. After two hours, the places where landmines can be found glow green.
The bacteria are generated through a process known as BioBricking. Synthetic biologists use this process to create new forms of organisms with a specific purpose. DNA coding for a specific function or trait are incorporated into plasmids and injected into the DNA of viable organisms, such as E. coli. Each BioBrick section of DNA can be combined with other BioBrick sections and code for more advanced functions through the action of restriction enzymes on restriction sites surrounding each DNA section. BioBrick vectors begin with a basic vector that can be transformed into what the scientist wants. Three BioBrick parts exist, which lead to the various levels of functioning for which they code. “Parts” are defined as the foundation that encode for basic functions like a specific protein or transcription factor. “Devices” are sets of parts that code for higher functions. The BioBrick vector that codes for a green luminescence when the bacteria are exposed to a certain chemical from a landmine is considered a “device.” “Systems” are compilations of “devices” that encode for the highest functions that have been generated using the BioBricking technique.
One prestigious undergraduate competition called iGEM (International Genetically Engineered Machines) deals with synthetic biology. The website describes the competition in the following terms: “Student teams are given a kit of biological parts at the beginning of the summer from the Registry of Standard Biological Parts. Working at their own schools over the summer, they use these parts and new parts of their own design to build biological systems and operate them in living cells.” Student groups from all over the world compete in various categories, with one overall winner. Some category examples are “Best Manufacturing Product” and “Best Health or Medicine Product.” In 2008, the winner of the BioBrick Trophy came from the University of Slovenia and had a project dealing with Heliobacter pylori and a designer vaccine against it. They developed two separate immunobricks, one that modified the flagellum of the bacteria so that they were recognized by the immune system and another that linked the bacteria to Toll-like receptors. In 2009, a team from Heidelberg University defined the field of synthetic mammalian biology and developed a BioBrick library comprised of mammalian cells that can be used in BioBrick research. They focused on gene regulation and synthetic gene promoters in these cells. They also performed bioinformatical studies which predict what each BioBrick promoter would do in vivo. For their product, Heidelberg was first runner up and selected as the best new standard. The number of entries for the iGEM competition has grown from about fifty in 2004 to roughly 1400 in 2009.
Clearly, the process of BioBricking can be used for several types of research. Most groups look at adding DNA sections that serve a specific medical function, as in the case of the undergraduate students from the University of Slovenia and their vaccines for H. pylori. A group of students from Heidelberg University advanced the science of synthetic biology by developing a library of mammalian cell gene promoters. However, this process can also be used for more social reasons. Researchers at the University of Edinburgh have developed E. coli bacteria that glow green when exposed to chemicals from landmines, hence saving the lives of thousands of people all over the world once this product becomes available for use.
Shetty et al. “Engineering BioBrick vectors from BioBrick parts.” Journal of Biological Engineering. 208, 2:5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373286/pdf/1754-1611-2-5.pdf
Recently a few major players in the agribusiness and food production realms released a statement announcing that they were entering a joint venture to produce a new type of soy bean. You may be thinking that soybeans aren’t very exciting as far as plants go but you likely wrong. While they may not be the most colorful or luxurious like others and grow low to the ground, these beans may hold the key to improved health for a lot of people with very little effort on the consumer’s part. Soy is a huge part of our diet and according the U.S. Census Bureau, in 2005 almost eighty percent of American fat and oil intake was from soy (Figure 1).
Monsanto and Solae released a few statements early this fall (one is linked below) highlighting the FDA approval of omega-3 fatty acid enriched soybeans. Although this is only a small step in a large battle to reform and change the nutrition profile of most Americans, it is a step in the right direction.
As recently as two hundred years ago most people across the world consumed roughly equal amounts of omega-3 and omega-6 fatty acids through their diet. In a recent study one scientist, A.P. Simopoulos, described how our diet has changed over the course of the last 4 million years. As we progressed from a hunter-gatherer society into the agricultural age and then into an industrialized society our diet shifted only slightly. In the last two hundred years; however, we have had a massive shift in diet (Figure 2)
The hypothetical change in diet shows a very drastic change in total fat intake, saturated fat intake, as well as changes in the ratio of omega-6 to omega-3 fatty acids. Monsanto and Solae are focusing directly on the issue of the omega-6 to omega-3 ratio. Currently, most Western diets (US and Europe) have an approximate omega-6 to omega-3 ratio of 15:1. This is drastically elevated compared to the historic ratio of 1:1 and might have a few significant consequences.
Polyunsaturated fatty acids, omega-6 and omega-3 fatty acids, are the precursor to a group of signaling molecules called eicosanoids. Omega-6 fatty acids are the basis for a number of inflammatory molecules, while omega-3 fatty acids are the basis for a number of anti-inflammatory molecules. The excessively high ratio of omega-6 to omega-3 fatty acids in the modern western diet may contribute to a number of inflammatory disorders commonly seen in countries with industrialized food systems. However, there is hope. The Inuits in Alaska, Japanese, and regions that consume a “Mediterranean diet” rich in omega-3 fatty acids exhibit a decrease in severity and prevalence of these disorders.
In western countries there is a high rate of many chronic inflammatory disorders. Asthma, arthritis, chronic heart disease, and some inflammatory bowel disorders have been treated with omega-3 supplementation. In a few studies which were characterized by a decrease in the omega-6 to omega-3 ratio the symptoms of these diseases wer suppressed and relieved. For those with asthma, supplementing the diet with fish oil capsules rich in omega-3 fatty acids to the effect of lowering the 6 to 3 to about 5:1 reduced episodes of bronciospasm seen in asthma. Also, lowering the ratio to roughly 2.5:1 caused second episodes of symptoms related to chronic heart disease by almost seventy percent.
To bring things full circle with our initial discussion the really cool thing about the Monsanto and Solae product is that it is just as readily absorbed into the body as naturally occurring omega-3 fatty acids. Additionally, the first step in the molecular transformation in fatty acid metabolism that forms both the inflammatory and anti-inflammatory compounds involved the same enzyme. Delta-6-desaturase, the enzyme used to convert the most commonly eaten polyunsaturated fatty acids, alpha linolenic acid (the omega-3) and linoleic acid (the omega-6) is used to change these fatty acids into the next molecule in each sequence. The only thing is that delta-6-desaturase processes the omega-6 fatty acids at a much higher rate leading to more inflammatory molecules being produced. To short circuit this problem the engineered beans produce a omega-3 fatty acid, SDA, that bypasses this problem. By skipping the first step and allowing anti-inflammatory molecules to be produced eating products made from these beans can act in the same way as reducing the omega-6 to omega-3 fatty acid ratio.
So really, our health might be as easy as a little more soy.
Simopoulos, A.P. “The importance of the ratio of omega-6/omega-3 essential fatty acids.” Biomedicine & Pharmacotherapy 56 (2002): 365-79. Print.
Soberman, Roy J., and Peter Christmas. “The organization and conseqeunces of eicosanoid signalling.” The Journal of Clinical Investigation 111.8 (2003): 1107-113.
“Health Hint: The Anti-inflammatory Diet.” Welcome to AMSA. Web. 17 Nov. 2009.