Kinesin-dependent movement on microtubules precedes actin-based motility vaccinia virus

Viruses are biological particles which are causative agents of various diseases and examples of which are the herpes simplex virus, adenovirus, and vaccinia virus. Infections are caused by viruses only under specific conditions wherein they are situated inside a living host cell, an event which accounts for its intracellular nature of existence and infection. In addition to this, viruses tend to maximize the usage of the cell components of the host organism in order for them to attain a high copy number inside the hosts body system. To accomplish such kind of activity, viruses need to multiply by replication and move the replicated viral particles into the different sites of the hosts body and this activity requires the utilization of the intracellular energy and components of the host such as the microtubules and dynein-dynactin complex. The aforementioned viruses, herpes simplex, adenovirus, and vaccinia virus, all utilize the microtubules and dynein-dynactin complex of the host to initiate replication and continue with the infection cycle. Furthermore, cell-to-cell spread of viruses from infected cells to non-infected cells is facilitated by the usage of diffusion and cytoskeleton movements within the host cell where the latter accounts for the transfer of relatively small viruses and the latter explains for the relocation of the viral particles through the help of actin-based motility as initiated by the hosts cytoskeleton. In order to further explore the topic of actin-based motility of viral particles, the goal of this paper is to focus on the discussion of the mechanism by which vaccinia viruses are able to elicit cell-to-cell spread. The discussion is aimed to center its attention on the exploration of the tyrosine phosphorylation of the intracellular mature virus (IMV) as explained by the activity on A36R membrane protein, WASP-interacting protein (WIP) and N-WASP, and event which results to the production of long, virus-tipped projections at the plasma membrane of the host cell which facilitates cell-to-cell movement of vaccinia viruses. The significance of this study is evident on the fact that the vaccinia virus constitutes the best-characterized model of cytoskeleton-driven viral motility and a demonstration of the additional features of these microscopic activities is important in the enhancement of present knowledge on the nature and dynamics of viral particle behavior and activity so as to prevent and control the proliferation of detrimental to lethal viral disease like the smallpox, a disease that is caused by the family of vaccinia virus.  

The experimental process employed to accomplish the goal of this research paper is composed of seven steps and these are the generation of stable GFP--actin cell lines, pEL vector constructs, preparation of the antibodies, infection, pEL-driven expression and immunoflorescence on fixed preparations, live cell imaging, analysis of the images produced, and, the construction of recombinant AR36-YdF vaccinia virus. The first step, explains the amplification via polymerase chain reaction methods of the chicken cell lines and human sarcoma cells that served as the host cells of the viruses while the second step characterized the amplification of the F13L and A36R open reading frames of vaccinia virus which were used as the vector of infection. The third step, preparation of antibodies, was accomplished by using rat monoclonal antibodies, an event which is essential in the visualization of the actin, through the usage of the anti--actin antibody AC-74, and microtubules, through the usage of pactin-mb5tubulin-EGFP. The fourth step, on the other hand, is comprised of the vaccinia infection on the host cell lines and subsequent performance of immunofloresence procedures to view the infected cells and viral particles. Live cell imaging is accomplished by utilizing a specialized camera that was able to detect the volume imaging and cell plane viewing and this step was followed by deconvolution and image reconstruction to better scrutinize the features of the images and manifest virus movements via microtubule assistance. The last step, construction of recombinant A36R-YdF vaccinia virus, was accomplished by harvesting the freeze-thawed recombinant vaccinia particles and confirming the fidelity of the recombinant through PCR methods, a step which marked the verification of the observed experimentally observed importance of actin-based viral movement for vaccinia particles.

Results show that actin tails have originated from the plasma membrane through the help of the cell-associated envelope virus (CEV) and this is in contrary to the previous observation that intracellular enveloped particles (IEVs) have nucleated actin tails. This observation is supported by the fact that electron microscopy was able to produce images that explains the distinction of IEVs from CEV at the tip of actin projections, and event which caused the confusion of the nature of actin sources. Despite the fact that researchers cannot rule out the possibility that the formation of actin filaments helping vaccinia virus during cell-to-cell spread is participated by IEVs, the notion that the mechanism by which actin-based movement of vaccinia virus is more obviously allotted to CEV is an important finding in this paper. This paper has disproven the previous assumption that actin polymerization is initiated at the periphery of plasma membrane and often with associated CEVs at the tip of the projections because it was confirmed by imaging that actin filaments only form close to the periphery of the plasma membrane. It was also clarified in this paper that actin polymerization is induced on the inner cytoplasmic surface of the plasma membrane through the help of the A36R, an integral membrane protein. Moreover, imaging analysis revealed that high quantity of virus release is achieved by vaccinia particles while maintaining low CEV retention at the plasma membrane. In general, this paper confirmed the idea that vaccinia virus makes use of microtubules and cytoskeleton to enhance its infection process.

Global Change and Loss of Biological Diversity

Any changes that alter the self perpetuating nature of the world are termed as a global change. The global changes interfere with the global fluid envelopes that include land, the oceans and the atmosphere. Global changes are experienced all over the world. These global changes include changes in the atmospheric composition of gasses, the decreasing ozone concentration, the climate change and their consequences. The climate changes and other global changes have resulted into unpredictable weather conditions and widespread famines, changes in the land use, invasion of biologically sensitive resources and changes, increased ultraviolet radiations from the space and general changes in the atmospheric compositions. All these changes are a threat to the global biodiversity.

Global change and Biodiversity
The global warming among other global changes that have been experienced over the last few decades has raised major concerns on the future of the global environment. The ability of the earth to support and sustain the biodiversity is at stake due to the global changes that have been experienced over the last century. The changes are a threat to the human race as well as general biological diversity of the world. Scientist argues that with the current trend, the earth will not be able to sustain the human civilization in the next few centuries. This is evident from the increasing concentration of carbon and other greenhouse gases in the atmosphere, the increased temperatures as a result of global warming, melting of the ice sheets and submerging of the sea line. The rate at which animal and plant species are getting extinct is also worrying.
There is no doubt that many of the global changes that are being experienced today are man driven, either directly or indirectly. The global changes may either be biophysical which affect the physical world as well as the biological diversity or they may be social and economical changes that affect the lives of human beings and their interaction with the physical and biological world. These changes includes the general alteration of the global biological fabric, flows and distribution of chemical elements such as carbon, sulphur, nitrogen and the metals and the global energy balances. These changes are direct impacts of changes in the land use, changing the land cover, industrialization and globalization, increased population, increased use of fossils oils and encroachment of natural resources among others.

Antropocene also has been used to explain the global changes that have been experienced throughout the history of the earth. This approach looks at the Holocene and the impacts of human society development on the environment. Holocene is the periods in the history of the world that came after the glacial geological period. During this period, there have been changes in the activities of the human kind that have had a big impact on the earth and as consequently led to global changes. Important advancements in this period includes the invention of fire, development of agriculture, invention of fossil fuel energy and machines, industrialization and the explosive increase in the world population in the 19th and 20th century. During the Holocene era, human activities have become the driving force on the morphological and geological changes in the earth. Mans activities have modified the physical and biological aspects of the earth.

Mans effect on the earth system cannot be quantified. The power of man on earth has been compared to the power of earth itself. It is true that man has either inhabited or visited all parts of the world. Man has even extended his influence beyond the earth releasing communication gadgets to the space and landing in the moon. Biologists and geologists identified the great influence of human kind on the global environment in the early 20th century in the rise of industrialization. Over the years, these human influences on the environment have attracted a lot of attention among biologists and environmentalists. The changing human activities in the world are directly responsible for the loss of biological diversity. Unless measures to reduce the influence of human activities on the physical and biological fabric are controlled, the globe may be unable to support the biological diversity in the near future.

Since the industrial revolution, the increased carbon gases concentration in the atmosphere has been the greatest threat to the biological diversity. The increased carbon dioxide and other greenhouse gases concentration in the atmosphere over the last century are well documented. The increased dependency on fossil fuels as a result of massive industrialization in the 20th century is the basic cause of the increased carbon dioxide concentration in the atmosphere. Another factor that has also played a major role is the encroachment of natural forests. The rapid increase in population has created the need for more land for food production through agriculture as well as for human settlement. This increased clearing of forest has disrupted the self perpetuating carbon cycle.

Scientific analysis that have been carried in the second half of the 20th century indicated that the concentration of carbon dioxide increased from about 315 ppm in the mid twentieth century to about 350 ppm towards the end of the century. The analysis also indicated that the rate of increase in the concentration increased over the interval. The increase in the carbon dioxide concentration being experienced in the modern time is estimated to be equal only to the increase experienced in the glacial interglacial era which resulted into global changes and affected the global biological diversity significantly. However, the historical changes in the concentrations of gases in the atmosphere were as a result of natural causes while the current changes are as a result of human causes.

Recent research indicates that the increases dependence of the world economy on fossil fuel is the primary cause of the increased carbon in the atmosphere. The encroachment of natural forests for agriculture, settlement and industry and infrastructure development and changes in land use has been rated as the secondary causes of the carbon increase. The increased carbon dioxide from burning fossil fuels has altered the natural balance between the isotopes of carbon in the atmospheric carbon dioxide. Carbon dioxide from fossil fuel is carbon -13 depleted and has thus diluted its concentration in the atmosphere. The result has been increased concentration of carbon-12 and carbon-13 which has adverse effects on the food chain. Any alteration that affects the food chain is a threat to the global biological diversity. The increased carbon dioxide has had negative impacts on the ozone layer and general reduction in air quality especially in industrial areas and busy cities.

There are other gases that have been associated with global changes that threaten the ecosystem of the world and the biodiversity. Chemicals such as the deadly chlorofluorocarbons in the ecosystem have increased significantly. The concentration of methane gas in the atmosphere has increased tremendously over the years and scientists have estimated that its concentration has doubled over the last two and half centuries. This has been as a direct consequence of the increased agricultural and industrial activities over the same period of time. Nitrogen imbalance as a result of increased use of nitrogenous fertilizers in agriculture has also been reported with an increase in the concentration of oxides of nitrogen in the atmosphere.

The immediate effects of the increased concentration of greenhouse gases in the atmosphere are the climate change the world is experiencing today. It is one of the global changes that have impacted negatively on the ecosystem leading to loss of diversity. More solar radiations are reaching the earths surface as a result of the depletion of the ozone layer which acts it as a filter. Some of the impacts of climate changes are the increased global temperatures, unpredictable weather, increased floods and drought. For over three decades, the impacts of greenhouse gases on the ozone layer have been known to the scientists. The gases have been known to catalyze the break down or react irreversibly with the ozone layer leading to its depletion. The increased radiations from the space have adversely affected plants, animals, human beings and the world ecosystem in general.

Scientists have also reported an increase in carbon in the soil which affects the ecosystems in the soil and the atmosphere as a result of increased decomposition. There are numerous species of microorganisms that have been found in the soil. These microorganisms play an important role in maintaining the quality of soil. The terrestrial ecosystems have also responded negatively to the increased concentration of carbon gases in the atmosphere and the resultant climate change. This has resulted into permafrost thawing and the associated decomposition of frozen materials. This occurs as a result refreezing of organics materials which have resulted into increased carbon into the ecosystem as more frozen carbon undergoes microbial decomposition.

The increased temperatures are continuously and catastrophically exposing the frozen carbon to microbial activities which is estimated by scientists to be up to twice the atmospheric carbon. The thawing of the permafrost combined with other impacts of the climatic change is slowly turning life on earth to extinct. The changes in the plants growth rate as a result of increased carbon, and the energy changes have not shown any sign of compensating the increase in carbon concentration as a result of microbial decomposition of thawing permafrost. Though the process is slow, in the long run, the increased carbon will be catastrophic and will affect the ability of the earth to support the diverse biological ecosystem.

The rate at which different mans activities which have led to various global changes is causing animal and plant species to become extinct is alarming. Scientific research indicates that all biological species in the world are ephemeral under natural conditions where episodes of mass extinction occur rarely and after thousands or millions of years. It is estimated that a species exists in the ecosystem for an average of ten million years before becoming extinct naturally. Human activities have however affected the biodiversity of the world where the rate of extinction has been raised several folds above the natural background rate. This increased rate is directly as a result of changes in the land use and encroachment of natural ecosystems, biological invasions and the increased environmental degradation.

Scientists estimates that if the current trend at which species are becoming extinct is maintained, most of the plants and animal specials will disappear from the ecosystem in the next one or two centuries and the biological diversity enjoyed in the world will be lost. The world will experience mass extinction that has never been experienced in the earths history since the Cretaceous Tertiary Boundary. Man has intentionally or inadvertently invaded the biodiversity for many years. He has eliminated some species in the ecosystem while at the same time introducing others altering the natural balance. The wave of globalization has increased the mobility of humans. As the human becomes mobile, the plant and animal spaces have also become more mobile leading to biological invasion. The long term effect of this mobility is the loss of biological diversity as the biota of the whole planet become homogeneous.

The realities of global changes are becoming more evident in the world. It could have been difficult to explain the impacts of high concentration of greenhouse gases half a century ago, but today, the impacts are almost obvious. There are many global changes that have happened as a direct impact of the human activities in the globe. Moreover, many of the global changes are intertwined. For this reason, biological diversity has been threatened by the global changes that are influenced by mans activity. The biodiversity is being lost at an alarming rate.

Florida Superfund Site

There are lot of zones in the country which can be attributed as the most polluted. The Norwest 58th Street land fill was one of them in this paper you will observe the hazards it created and how authorities over a period of time brought their plan into action and cleaned up the superfund site.

Superfund program
Since the dawn of civilization, man has been gnawing the earths resources with great acceleration. With each step of development, we have meticulously depleted earths resources and have contaminated it to the most horrible levels.  Today in the United States of America, we have superfund sites, which are notably the most contaminated sites in the country.
To understand the complete meaning of a superfund site we must understand the primary consequence of the site. This is the place where families see their homes getting destroyed and we can also see small business getting lost without any fault of theirs. The Superfund program is in factual terms the Comprehensive Environmental Response, Compensation and Liability act, which comprehends waste sites as well as those sites which get doomed due to accidental spills or releases of high decree pollutants into the milieu.
The superfund program is a partnership between the state and federal departments of the country. Their core objective is to eradicate and control these polluted sites. The initial financing for these operations is done mainly by the federal blocks, but the state has to bear a certain percentage for these cleanups. However the basic function of the program is to remedy the adversity as early as possible. Once the site is cleared of its prime concern, the cost of the maintenance of the particular site is the sole responsibility of the state. The fact that there is an absence to send these programs for a review in the federal department makes the state take more interesting steps for the cleanup.

The following will exhume the characters of a superfund program
There are procedures for emergency response actions and more concern is laid on the permanent remedy for the problem
There are active provisions for a cleanup fund and for recommendation analysis.
The authorities make the parties responsible for the concern to pay for the studies and site recommendations
There is staff hired to manage state funded remedy and implement remedy
Encouragement for public participation becomes crucial for decision making (Environment law Institute. Page 13. 2001)

Norwest 58th Street Landfill
 Florida State has its own share of superfund sites. These locations are marked by the states as the most hazardous and polluted locations of Florida. The Norwest 58th Street Landfill is one such site that has had decades of contamination. This site is a belt of 660 acres located in Hialeah. For three decades from 1952 to 1982, it was a marked municipal landfill site. On intricate analysis, it was found that 65 of the waste had its origins from industrial and domestic fronts. The remaining 35 of the waste were mainly sourced from liquid wastes, appliances and automobiles. The site was also given more waste from Miami Dade water and sewer authority water treatment facilities. These departments filled the site with calcium carbonate sludge and squashed rocks. The site has received one of the worst quantity wastes in its zone. The site started off accepting waste at 60,000 tons but by the end of the 3rd decade it was reaching up to one million ton every year.
Since this site was a landfill, not many thought were given on the load of waste it would be give. From industrial to domestic, everything and anything was dumped with no concerns of its possible future effects. Its worse effect came into play when it started polluting the only water reserve, because it was located below the landfill. The land got highly contaminated with arsenic, chromium, zinc and even benzene. The pollution went so high that vinly chloride was analyzed from the ground water below the site.

Norwest 58th Street Landfill cleanup plan
After 1982, the landfill was only accumulating construction debris, and major contaminating wastes were not dropped at the site. The plan was to effectuate all the remedy for the people living nearby. The plan firstly closed the land fill and provided water to inhabitants living close to the landfill. Complete monitoring of the ground water was chalked out along with legitimate plans to control odor. The plan also consisted of cover inspections and maintenance of the site at an absolute level.

Norwest 58th Street Landfill cleanup effect
The Florida state painstaking brought the remedy to the site. After fulfilling promises of provision of municipal water to residents, the process of covering up the landfill begin in 1991. It took nearly four more years just o complete close the entire landfill. A multiple set of five year plans were brought into existence to maintain the remedy and to oversee the complete entire maintenance operation. Today the area has seen the return of a majority of endangered animals and the state is planning to create a fifteen field soccer complex in a portion of the landfill.

Antibiotic resistance of pathogenic bacteria

Preel (2009) states that, antibiotic resistance is spreading not only in Europe, but all over the world. One of the major factors that have resulted to this is the excessive use of these drugs. Ambile-Cuevas (2007) states that, antibiotic resistance has brought with it adverse financial as well as medical effects to human being. Hyper-resistant bacteria have emerged greatly endangering the pillars of global health. Some of these bacteria have become resistance to all forms of modern treatment forcing physicians to prescribe older medications that are toxic. Doctors have also decided to use medications they only read about on paper. This situation is particularly grave in southern Europe where consumption of antibiotics is greater than other places. Research, according to Preel (2009), has revealed that more than half of the doctors in this region had treated at least one patient infected with an almost or completely antibiotic resistant bacterium.

Antibiotic resistance as a problem
Overuse of antibiotics has resulted in the emergence of bacteria immune to a wide range of drugs of 20th century (Anon, n.d.).  If the current situation continues it will be completely impossible to carry out some of the most important medical operations. Lack of effective antibiotics is a very serious problem when it comes to operations such as intensive care and transplants. Various health services including premature children, cancer departments, as well as reanimation services that heavily rely on antibiotics will be among the most affected. This will lead to breakdown of the pillars of health system that depend on antibiotics. Antibiotic resistance results in the death of very many patients. Inappropriate administration of antibiotics is particularly a great health danger when it leads to the death of people who have never been to hospital in their life. People are regularly dying as a result of complications of common antibiotics resistant strains such as E.coli, golden staph, and Mycobacterium tuberculous. Resistant antibiotics also bring about financial breakdown of not only individuals, but also hospitals and the nation. The scourge if left unchecked will spread to other parts of the world leading to development of a global tragedy. DIANE Publishing Company (2004), states that poor counties will be the worst hit by this disaster, because in these countries antibiotics circulate more freely and are available even without prescription. Antibiotic resistance leads to increased bacterial infection. E.coli in particular is the most common antibiotic resistant bacteria.

Emergence of resistant bacteria, as a result of irresponsible antibiotic administration, is the greatest medical fraternity nightmare. Resistant strains of bacteria such as staphylococcus aureus spread in the community very fast and are very dangerous they cause diseases that are more severe as compared to other type of bacteria found on hospital wards. Resistant strains have the capacity of affecting both young and old healthy people.

Getting rid of human antibiotics is not the ultimate solution to this problem, because they are extensively used in livestock, dairy, and poultry farming for animal husbandry and fattening purposes. Traces of antibiotics are then excreted in urine and dung and deposited on the ground.

How people have contributed to emergence of resistant bacteria.
Uncontrolled use of antibiotics allover the world has caused this problem. In developing nations people can obtain last-line antibiotics over the counter. Excessive use of antibiotics, leading to emergence of antibiotic resistant strains, is bringing to an end an era where illnesses, caused by bacteria that lead to death, were easily cured. Irresponsible administration of antibiotics is particularly the major factors that have led to emergence of resistant strains. These drugs are mostly thrown at any from of illness, starting from the slightest cough to the most serious infection. Antibiotics have also been extensively used in agriculture by farmers in order to rear healthy animals. A study by the University of Pittsburgh School of medicine, as indicated by Hansen (2008), revealed that bacteria obtained from most of the chickens brought in to different supermarkets carried the enzyme that made them resistant to antibiotics.

To support the fact that what goes in comes out, a study was carried out in Queensland and it was discovered that a significant amount of antibiotics was present downstream (Fisher, 2008). Traces of antibiotics were coming from sewage released into the Brisbane River. These antibiotics, it was concluded, contributed to development of resistant bacterial strains of bacterial that were initially ecologically beneficial. Natural bacterial flora was adversely affected by these antibiotics. Toxicologists, according to Warren (1998), have issued a warning saying that such excesses will result in reservoirs of bacteria that are resistant overwhelming the environment

Doctors argue that visit to developing nations is one of the possible factors for rapid emergence of antibiotic resistant E.coli amongst people who have previously not had any contact with hospital system. Excessive use of antibiotics in hospitals has also resulted in the emergence of antibiotic resistant strains (Sciandra, 2005). Infections resulting from these strains have plagued patients for years. Failure to properly wash and cook food, according to (Hansen, 2008) is the other factor that has led to multiplication of resistant strains. These foods act as a source of contamination
Mechanism through which bacteria acquire resistance to antibiotics

Bacteria just like other organisms have got defense and attack mechanisms. Some bacteria, according to Knobler (2003), produce toxins and kill other bacteria. To respond to this other bacteria produce enzymes that neutralizes these toxins. The same mechanism is being used to develop antibiotic resistance. Bacterial species develop mechanisms that are aimed at defying drugs that cure dangerous diseases. Antibiotic-resistant genes have the ability of being carried on mobile pieces of DNA (Fisher, 2008). This allows them to be carried on from one bacterium to the other.

Bacteria that are a real problem clinically
Infections, such as multi-drug resistant tuberculosis, resulting from these strains have lead to the death of very many people. Multi-drug resistant tuberculosis is a difficult illness to treat. It requires costly oral as well as intravenous treatment with last line drugs. It finally reaches a stage where this disease cannot be treated. The community version of resistant golden staph, which emerged in the late 1990s, is the other killer (Hansen, 2008). It is also referred to as Methicillin-resistant Staphylococcus aureus. Infection with this strain, according to Hansen (2008), results in the death of about 2,000 compromised patients annually. This community version has a flesh-eating toxin and is more dangerous than the hospital version. The current well known germ to cause infection in human beings, which have become resistant to antibiotics outside health facilities, is the gram negative E.coli. This germ can defy almost all forms of antibiotics. E.coli, as asserted by Knobler (2003), produces the enzyme beta lactamase which physically destroys antibiotics.

Measures and research are being done to overcome antibiotic resistance
Development of penicillin as well as other antibiotics is one of the major advancement in medicine in the 20th century (Anon, n.d.). These drugs acted as a medical miracle preventing the death of very many people. Overuse of antibiotics is however, bringing the advantages associated with that development to an abrupt end. Excessive use of penicillin according to Fisher (2008) leads to development of multi-drug resistant bacterial strains. Infections resulting from resistant bacterial strains have very devastating psychological effects. People suffering from these infections are often withdrawn, because others think they are going to be contaminated. Infection can also be easily passed on from one person to another.

One big problem in this issue is that there is no major investment in future antibiotics. Pharmaceutical industries are doing very little if any to invest in the development of effective antibiotics. Pharmaceutical companies which are mostly profit oriented fail to invest in antibiotics because these drugs cure. Research reveals that only two promising antibiotic drugs are currently being developed. Companies invest in drugs that alleviate adverse symptoms brought about by other diseases such as diabetes and AIDS, because patients are bound to take these drugs or life (Hansen 2008).

Studies, as stated by Hansen (2008) have found out that certain antibiotics can have harmful ecological effects in low doses and also in conjunction with others. One of the straight forward measures that can be used to reduce cases of infection of animals with antibiotic resistant bacterial strains is preventing them from drinking from dams contaminated with dung. Proper maintenance of daily access tracks is the other measure that can be used to minimize infection with resistant strains. White et al (2005), states that developing better sewage retention ponds can also help reduce chance of infection with antibiotic resistant strains. Proper washing as well as cooking of foods is another measure that can be used to reduce chances of infection with resistant strains.

These articles are accurate and not just aimed at creating panic and hysteria. Emergence of antibiotic resistant strains of bacteria is a human tragedy. These strains bring about infections that put the pillars of global health in danger. Resistant strains emerge due to excessive use of antibiotics. This overuse has resulted in the emergence of bacteria immune to a wide range of drugs of 20th century, referred to as the multi-drug resistant strains. The major problem resulting from antibiotic resistant strains is death due to various medical complications. These complications lead to financial depletion of both families and the nation. Overuse of antibiotics is not only harmful to human beings, but also to the environment.

Biology of Obesity and Energy Homeostasis

The incidence of obesity has become a major health issue that is barely unrecognized in every medical journal. Despite widely researched works on the pathogenesis of obesity, it is rather unfortunate that it remains a life-threatening health risk in susceptible individuals. The onset of obesity is gradual in form and arises from daily accumulation of fat in adipose tissues in excess of body anabolic needs (building up process). One can trace fat storage in humans to the adaptive need for energy conservation until when needed. Fat is stored in order to serve as source of energy for later breakdown in scarce resources. This is a body physiological response toward maintaining a perfect homeostatic environment. Homeostasis allows body to remain energized even in the absence of immediate food for ingestion within bearable length of time. However, due to inherent physiologic conditions, mutations in regulatory systems of peptideshormones and bad eating habit, some are more vulnerable to excessive fat accumulation thus leading to obesity. Scientifically, obesity occurs when the Body Mass Index (BMI) for an individual exceeds the limit of standard in relation to persons height and body weight. A body mass index exceeding or equals 30kgm2 gives rise to objective assessment of the condition known as obesity in an individual. BMI below this limit is overweight i.e. 25 kgm2 to 29 kgm2. The normal level of body mass index ranges between 19 kgm2 and 24 kgm2.

There are cellular regulators of fat storage in the body. The regulators signal when fat storage is in excess and stop further process of accumulation. Obese individuals have weak feedback signals wherein a loss of minimum weight already signals extreme hunger that makes these subjects respond by eating immeasurably more than body needs. The etiology of obesity and imbalance control of energy homeostasis is traceable to both hereditary and environmental factors. The central signal that allows for body regulation of fat lies within the first part of the Central Nervous System called the brain. Being that glucose supplies the ATP requirements for brain function, brain in turn acts in response to feedback sensation of hypoglycemia (reduced blood glucose) and hyperglycemia (excessive blood glucose) in order to normalize the concentration of glucose in body circulation. It is important to note that an increase in glucose level promotes prompt release of insulin by the pancreas to convert excess glucose into storable glycogen and complex chains of triglycerides. The liver starts to decrease release of glucose in this situation. Conversely, when there is insufficient glucose and the body drives towards exhaustion of energy, fat cells release triglycerides into the bloodstream for compensation.

Certain hormones in body mechanisms regulate fat production, usage and storage. Leptin is one hormone that signals excessive amount of fat in the body thereby promoting decrease in appetite (Flier  Maratos-Flier, Sep2007). In this case, increases in weight problems are due to the mechanisms of our body malfunction and switch away from this stabilization system. This could be due to mutation in the production of leptin or mutation of the leptin receptors thereby causing abnormal response or no response.

Energy homeostasis is the process involving series of molecular signals, wherein body environment constantly balances between food intakes with energy need. Despite unguided consumption that is not proportionate to energy requirements in our body, the center of appetite regulation in the brain adjusts gastrointestinal systems of body metabolism accordingly to ensure homeostasis. Certain system malfunctions and overwhelming of existing homeostatic system tend the body towards obesity. This paper will explore the role of gastrointestinal system we shall equally take into consideration the different chemicals and hormones involved in the maintenance of body weight. With the discovery of these mechanisms, diseases that threaten life such as diabetes and obesity might further receive expert understanding for possible way out of obesity scourge.

The Digestive System
The digestive system of the body is responsible for the break-down of the food we take eat, making it absorbable for different organs of body system to function properly. The product of digestion is molecular and soluble in such a way that it is deliverable through micro and macro vasculatures of the body. Digestive organs include the mouth, Pharynx, Esophagus, Stomach, Large Intestine, Small Intestine, Rectum and Anus. These organs together with accessory organs contain cellular and molecular system of controls that regulate nutrition and energy consumption. Digestive system accessory organs include Salivary glands, Liver, Gall bladder and Liver.

Meanwhile, mouth is the first part of digestive system where functions include enzyme digestion and mastication. In mastication, there is mechanical grinding of food particles in order to pass through the esophagus without obstruction. The food then passes thereafter to the pharynx, from the pharynx to the esophagus and into the stomach. The stomach mixes the food with stomach juices and regulates the entry into the small intestine. Movement takes place into the small intestine after which the food proceeds to the large intestine for further digestion and eventual exit through the anus. Several enzymes break down the food depending on its composition and location along the gastrointestinal tract. The primary digestive enzymes for respective food nutrient include amylase for carbohydrates, lipase for fats and proteases for proteins.

Regulation of Food Intake
Satiation is the term used to describe the regulation of food consumption. The feeling of fullness during complete satisfaction explains the concept of this process. Signals sent by the brain to achieve stoppage of food intake further explain this concept. The process serves as food consumption control and helps prevent consequences related to overeating one consequence is dyspepsia. How does this work The hindbrain is responsible for the reception of satiation signals arising from the areas in the gastrointestinal system especially the stomach.

Gastrointestinal peptides that regulate food intake but not produced in the brain are leptin, insulin, glucagons and amylin. CCK, APO AIV, GLP1, oxyntomodulin, PYY, enterostatin, ghrelin, GRP, neuromedin-B and PP. These molecules present in abundant in the digestive tract are peptides regulating digestion and controlling food appetite through molecular networks of mediating factors. The liver and the gall bladder also make vital contribution in the absorption water insoluble vitamins and fats.  Excessive secretion of peptides and other factors lead to over absorption of digested food from the small intestine and large intestine (primary site of absorption) thus precipitating obesity.

Satiation Signals by the Gastric gland
 The stomach structure contains a number of rugae that expands during eating. However, it only expands to certain limit. Experiments had shown that control of pyloric sphincter at the exit of the stomach is chemical-mediated by gastric gland in that through signal response, it contracts and relaxes, thus, opens to allow food passage to small and large intestines. Through this rhythmic action, pyloric sphincter has its role in satiation process. The closure of the pylorus terminates ingestion in of food. In addition, the depletion of energy will promote ingestion, and food will move downward for the nutrients to be absorbed in the small intestines. For the pyloric sphincter to close, a certain amount of ingested food is required. However, 40 of ingested food emptied into the intestine is required, before the pylorus can close. This proves that the pre-gastric, gastric and intestinal signals function all together to regulate food intake.

In relation to the ingestion of food, glutamate, acetylcholine, nitric oxide, calcitonin-gene-related peptide, substance P, galanin, and cocaine-and-amphetamine-related transcript are the neurotransmitters that send signals to the brain. With the framework of mechanoreceptors present in the stomach endothelium, appropriate responses signal to control satiation and stomach fullness. Examples of signals-related mechanoreceptors are sensors of tension, stretch and volume.

Another example of peptides found in the stomach is the bombesin-related peptides, gastrin-releasing peptide, and neuromedin B. The gastric myenteric neurons produce these substances, and scientific studies found out that they could reduce food consumption when there is satiation in order to achieve energy balance or homeostasis.

Satiation by the Intestines
Unlike gastric satiation that depends on volume for its satiation, intestines satiate in physiologic response to nutrient absorption. It stops absorption when they have absorbed sufficient nutrition required by the body system. Studies also found out that Cholecystokinin is the primary peptide responsible for intestinal satiation. The effect of intestinal satiation is again on the prevention of excessive food intake. Through this system, there is achievement of energy homeostasis and prevention of obesity.

Cholecystokinin from I-cells is located in the duodenal mucosa, jejuna mucosa of the upper intestines, brain and the enteric complex of nerve cells. In response to ingestion of excess amounts of proteins and lipids, body releases Cholecystokinin to hinder further food intake and ensure energy balancehomeostasis. This type of satiation specifically the carboxy-terminal octapeptide group of the CCK does not affect water intake that can cause dehydration, it is only specific for the regulation of nutrient intake and absorption.

Complementary to the upper intestinal satiation is the lower intestinal satiation that involves the secretion of GLP1 by L-cells located in the distal small intestine and colon. Satiation through GLP 1 occurs by preventing food motility in the gastrointestinal tract as well as gastric emptying as a mechanism to regulate food consumption. Many doctors already use GLP1 to treat patient with diabetes. This has shown to be effective as patients lost considerable weight following ingestion of drug containing GLP1 chemical.

Furthermore, oxymontomodulin and PYY are another peptides involved in satiation specifically in the lower intestine. Studies also found out that Oxyntomodulin decreases food intake, especially in rodents. In humans, it decreases the feeling of hunger and controls obesity without leaving out the maintenance of energy homeostasis.  Satiation peptides specific for fats
 Enterostatin and apolipoprotein A-IV are peptides specifically involved in fat satiation. For enterostatin, the mechanism behind control of satiation is due to F1-ATPase  subunit that serves as blocking receptor, thus controlling absorption. Through expert studies, enterostatin showed no effect on human regarding food intake restriction through appetite reduction. However, same study discovered that APO A-IV decreases food consumption.

We have seen how chemicals-mediated satiation process controls excessive weight gain by preventing food overload and maintains energy homeostasis. Specific satiation peptides involve in the regulation of food consumption especially fatty and carbohydrate substances that mostly lead to obesity due to ability of the body to conserve them for future need. It is a strongly believe that further research works in the subject of regulatory satiation process will open more scientific understanding on the subject and the consequential outcome of the research will solve the struggle on obesity and energy homeostasis in the field of internal medicine. The future is brighter

Theory of evolution

The contemporary theory of evolution, according to Nardo (2009), was developed by a proletarian English naturalist known as Charles Darwin, in the 19th century. Darwin proposed that all living things evolved slowly from a common ancestor through natural selection over billions of years. The principle behind this theory, as illustrated by Scotney (2009), was that individuals passed on their best adapted character traits to their offspring. This theory proposed that random mutations on the gene occur over time within the organisms genetic code leading to development of beneficial character traits that are retained since they support survival. Over time, as asserted by All About Science (2010), these beneficial character traits accumulate and transform individuals into a species completely different from their ancestors. Darwins theory presumes that life developed from non-living things and stress that organisms evolve naturally from simple ancestors over time. Ancient Greek philosophers hypothesized the development of life from non-living things as well as the evolutionary descent of man and other living organisms from a certain ancestor. Darwin contributed to this philosophy by bringing in a plausible mechanism known as natural selection. Natural selection according to Darwin acts to accumulate and retain minor beneficial genetic mutations. Darwin claims that if a member of a certain species develops a certain character trait that helps it to survive, that trait will be inherited by its offspring and passed on to their offspring. According to natural selection members of a particular species that do not have the advantageous character traits would eventually die out, leaving on the members of the species that have the advantageous traits. Natural selection allows for the preservation of beneficial character traits thus allowing species to struggle better in the wild. This can better be explained by looking at the work breeders have done over the centuries. By selecting the good looking animals, breeders are able to eliminate undesirable traits over time while retaining the desirable ones.

Evolution evidence can also be obtained from categorizing the similarities between organisms living on distant locations. Biogeography was one of the central themes of Darwins reason when he summed up his findings of evidence collected around the globe. Darwin realized that, though diverse, plant and animal species from the same continent had structures as well as character traits that were very similar. Species from different continents were however different (Buehler, 2009). Geographic diversity was also realized when species from islands were compared to those from the mainland. Darwin finches were the principal exhibit in devising the theory of evolution. According to Buehler (2009), Darwin stated that changes in different species over time occur in different direction if they are isolated and live away from each other over a long period of time. Times in evolution are very long and are measured in geological time for example, billions of years. The theory of plate tectonics, fossil records, and continental drifts support the principle of speciation as an outcome of long periods of geographic separation.

Comparative anatomy and comparative embryology also provide evidence for diversity and similarity. Analogous anatomical features that are used for the different purposes are often found in different living organisms. A good example is the human hand used for holding. The hand has got a skeletal anatomy identical to the fore limb of a cat used for walking. This skeletal anatomy is also similar to that of a whales flipper used for swimming as well as the wing of a bat used for flying. The skeletal structure of the four limbs of these animals suggests that they are all descendants of common ancestral animal. The process of evolution of modern animals, as stated by Buehler (2009), occurred independently of all other animals leading to development of a limb structure that fits the diverse usage. Modern animals have, however, not changed totally and as a result their structures are referred to as homologous structures. The principle of homology directs a structural likeness of body parts that are used to perform different activities. Based on the same fact organisms that are not related in any way have evolved similar body parts to carry out the same task. This likeness of structures for the sake of the same task is the outcome of convergent evolution. Structures such as these are referred to as analogous, indicating that their similarity is not an outcome of descent with modifications.

Contemporary molecular biology also provides some of the most convincing evidence of evolution. Modern molecular biology demonstrates that similarities at the molecular level can be used to verify evolutionary relationship. Molecular evidence supports the theory of evolution in a unique way. Based on the power of molecular analysis it can be concluded that the modifications Darwin referred to are the outcome of unsystematic alteration of genes. The instructions of making proteins in the body are stored in the genes. Physical traits, which are developed by proteins, are the ones that are modified through natural selection. This modification determines the ability of an organism to live in a particular environment and have as many offspring as possible. It is the number of fertile offspring, but not the survival for the fittest, that is used to measure Darwins fitness. Many organisms are very sensitive to climatic changes and if they do not adapt to climatic changes they become extinct.