Bacillus Anthracis Issues

The CDC is investigating an unintentional release of anthrax  from the Department of Defense (DOD) to multiple labs in multiple states.  An article from Voice of America indicates 24 labs in 11 states and 2 countries (South Korea and Australia) have received "suspect samples" of concern.

Anthrax has quite a history, both in its naturally occuring state and as a biological weapon, as documented by the Center for Disease Control (CDC).  There have been a number of anthrax "releases" over time,  Recently, in 2014 there was a release at CDC's Roybal Campus .  The year 2001 saw a wave of anthrax attacks.  A CDC review discusses the 2001 attacks in some detail as well as discussing epidemiological findings. and provides a history of anthrax., both in a naturally occurring state and as a biological weapon.

One interesting development has been the appearance of bacillus anthracis in heroin used by European drug users.  The strain involved originated in Turkey, raising a question as to how bacillus anthracis would get into the heroin supply.

The CDC provides basic information on Bacillus Anthracis.  The bacteria Bacillus Anthracis exists in a dormant, sporulated state in nature, can enter the body by a variety of routes (e.g. cutaneous or inhalation pathways), become activated, spread throughout the body, multiply and produce toxins.

These incidents all represent an interesting pattern in the release of bacillus anthracis into the biosphere, taking into consideration emerging environmental issues regarding climate change.  The question is to what extent the environment adapts or reacts to environmental challenges thrown its way.

As this CDC case investigation indicates, it is difficult to investigate individual cases of anthrax when they occur.  Human cases of anthrax are rare, despite the fact that Bacillus Anthracis can be found naturally in the soil and commonly infects domestic and wild animals throughout the world.  There may be a number of reasons for this apparent paradox, which is under investigation.

My blog article "Panspermia and Evolution" discusses Bacillus Anthracis and the distribution of life in the context of extreme environments.  These are the types of situations involving low probability, high impact events.

Bacillus Anthracis is mentioned in a few of my blog articles, "Evolution of Adaptive Immunity" and in an article on "Ebola".

Bacillus Anthracis needs oxygen in order to sporulate.. This is a very interesting characteristic that may provide clues to it's activity, especially in the human body. Iron is a key element in the human body, intimately associated with a number of metabolic processes, including its role in hemoglobin and the delivery of oxygen throughout the body.

Indeed, Bacillus Anthracis uptakes iron when exposed to superoxide stress.   Bacillus anthracis experiences rapid sporulation in a high iron, glucose free environment.  Apparently, Bacillus Anthracis may operate as a signaling mechanism triggering iron accumulation when exposed to environmental stresses, impacting the iron catalyst of the  Fenton reaction.

Transferrin blocks growth of Bacillus Anthracis via iron deprivation, an effect that is differentially expressed in cutaneous anthrax vs inhalational anthrax. This difference, in the latter case, is due to phagocytosis by macrophages, a process which occurs upon inhalation, allowing the inhaled spores to germinate intracellularly, multiply and cause infection.

It is apparent that Bacillus Anthracis forms the heart of a mystery, a challenge, as we seek to better understand the manner in which it expresses, affecting a number of medical processes in the human body. At the same time, we examine other issues impacting society on a global level, issues of climate change, global warming and their interactions with the changing environment in which we live.  These issues will be discussed in further blog articles.

Center for Disease Control (CDC):
  CDC Investigating unintentional DoD shipment of anthrax
  Anthrax
  A History of Anthrax
  CDC Director Releases After-Action Report on Recent Anthrax Incident
  CDC Responds to Anthrax - 2001
  Review of Fall 2001 Anthrax Bioattacks
  Injectional Anthrax in Heroin Users - 2000 -2012
  Anthrax - Basics
  Investigation of Inhalational Anthrax Case - United States

Voice of America -"Carter Vows to Find Those Responsible for Anthrax Shipment"

American Veterinary Medical Association (AVMA) - Anthrax FAQ

marilyndunstan.blogspot.com
   Panspermia and Evolution
   Evolution of Adaptive Immunity
   Ebola

Medical Microbiology - Bacillus
Journal of Bacteriology - Cellular Iron Distribution in Bacillus Anthracis
Journal of Microbiological Methods - Rapid Sporulation of Bacillus Anthracis in a high iron-glucose free media
Journal Biological Chemistry - Human Transferrin Confers Serum Resistance Against Bacillus anthracis

IUPAC - Gold Book - Fenton Reaction

Wikipedia:
  Oxidative Stress
  Phagocytosis
  Macrophage

Seattle-Tacoma International Airport - Medical Issues

Seattle-Tacoma International Airport, Third Runway,Sea Tac, Washington

Examination of the impact of the Seattle-Tacoma International Airport on the region poses a number of analytic challenges.  In a previous blog article, Seattle-Tacoma International Airport - Pollution, I discussed pollution issues.  Links to my other blog issues on the airport may be found listed below.

The focus of this blog article is on health related issues which may be related to airport operations, keeping in mind that there are other sources of pollution that may contribute to health conditions, and that there are factors other than environmental conditions which may contribute to health conditions.

Other sources of pollution may include vehicular traffic, such as cars, trucks, vans, buses and rail systems, as well as industry and commerce as well as other human activity such as wood burning. Many factors, in addition to pollutants, contribute to health.  Economic and sociological factors such as poverty, education and disenfranchisement all are factors which influence health.

There is considerable information available from the King County Health Department on the geographical distribution of various medical conditions.  These are listed below. Incidences of cancer, respiratory disease, cardiac and pulmonary heart conditions vary throughout the county.

MEDICAL ISSUES

Known

• A number of medical conditions may be impacted by environmental factors, including cancer, respiratory/pulmonary,sleep disorders,  blood/vascular disorders, immune system disorders, cardiac disorders and neurological/psychiatric/psychological issues that can emerge as a result of increased environmental exposure. The impact of air pollution on the generation of reactive species such as oxygen and other radicals may also adversely impact sleep states.
• Environmental pollutants often increase generation of reactive species or oxygen radicals, increasing oxidative stress, impacting a number of medical conditions, and may create new ones.
• Electromagnetic fields (microwaves) - Potential effects vary according to the distance from the source with general public exposure lessened.  Health effects studied include cancer, physiological and thermoregulatory responses, reproductive issues, cataracts, and impacts on calcium ion mobility.  Effects have not been sufficiently established to be able to determine regulatory standards.
• Studies have been made by the Washington State Department of Health on glioblastoma multiforme and other conditions.
• A February 25, 1999 report from the State Health Department and King County Health Department indicates: "While the state health department found that the occurrence of all SeaTac Concerned Citizen cancers in the area within 5 miles of the airport was less than expected in comparison to King County, the Seattle-King County health assessment found an increase in cancer deaths around SeaTac Airport."  This study examines health issues in the neighboring communities around the airport.
• There are extensive studies from the King County Department of Public Health available regarding a variety of health and socioeconomic factors for the communities in King County. These reports indicate increased incidence of cancer and pulmonary disease, but decreased risk of heart attack, stroke and Alzheimers relative to other areas.  There is also a higher degree of cigarette smoking in the region, complicating analysis.  There is a range of socioeconomic indicators showing lower socioeconomic indicators in the region.

Past Legacy

• One of the cardinal features of evolution is the incorporation of biologicals and minerals into a system in order to advance features that have evolutionary advantage.  This is called biomineralization.  It is not inconceivable that out of the many molecules emitted through airport operations (and other sources throughout the region), that one in the witches brew of combinations might find a home within the human body, evolving the system, or throwing a monkey wrench into it. Calcite enabled the creation of the eye in trilobytes  in the pre-Cambrian.  However a serious problem in this process is the issue of interoperability between systems in such processes.
• To what extent does the ground on which we sit impact health?  The area holds the legacy of the ASARCO Tacoma Smelter Plume  formed in 1899, and the emissions since that period.  This legacy impacts rock, soil, water and air.  The Seattle-Tacoma International airport sits on a considerable amount of fill, which is in addition any deposition that may have fell on the underlying soil.  Other parts of the region may also have been impacted by sand, rock and gravel transported from sites more heavily impacted by the ASARCO Smelter's operations.
• The airport sits on Fraser Glaciation,  Vashon Stade.  To what extent do the rocks around the airport and the water affect health? It is possible that the area of the airport could hold some clue to past evolution.  A sloth was discovered in a swampy area north of the airport in 1961, and a mammoth tusk was discovered in the South Lake Union area of Seattle. Both sit at the Burke Museum.  DNA analysis from an archaeological find could perhaps provide scientists with clues to help solve emerging problems germane to our evolution and our ancestors.

Emerging or Unknown

• The emergence of new and novel health risks may occur in the witch's brew of chemical soup surrounding the airport and other areas subject to environmental risk. Illnesses that normally occur in other areas of the world may emerge in this arena, given the geological milieu in which the airport sits, the meteorological conditions, and the increased levels of pollutants, including carbon dioxide.  Carbon dioxide is a sensitive indicator of global warming and climate change and may also impact the respiratory system in a similar fashion in the immediate neighborhood of the airport.
• Seasonal flu and emerging viruses, could recombine in the environment surrounding the airport, mixing human and bird migration patterns with environmental factors impacting local populations.  Thus viruses could serve as a vector for the incorporation of novel or emerging features resulting from the witches brew of chemicals.
• Chemicals emitted in the witches brew of chemical emitted from airport operations could be impacted by solar radiation, a source of energy, especially during periods of geomagnetic storms.  Potentially subatomic collisions could evoke a transitional state in molecules, and be incorporated into the body.  Any impact from the creation of transitional molecules would be in addition to any direct effect from any solar storms.
• The witches brew of chemicals emitted by air transport, given the power, acceleration, deceleration and forces put on aircraft engines, abrasion, means that more exotic chemicals may be created.  However, it is possible that similar types of reactions may also be occurring in different parts of the region, perhaps to a different extent.

Establishing Correlations between Pollutants and Medical Conditions

• While some pollutants in particular are points of focus, the extensive lists provided make it difficult to correlate exposures to any one or any combination of health outcomes.  This is an issue of multiple correlation analysis in the face of numerous variables and outcomes, many of which may interact with each other to alter individual correlation between any two variables. 
• Analysis of risk focuses on cancer metrics.  While the emergence of the cancer risk is important (and critical), identification of other outcomes is also important. Early indicators of future outcomes may serve as helpful markers of environmental distress before its impact becomes too severe.
• Environmental markers might include blood coagulation measurements, markers for the impact of oxidative stress, markes for nuclear DNA and mtDNA damage, and markers for the preference of glycolysis in cells (Warburg Hypothesis), among other things.
• Categorization of medical systems, or medical coding, puts medical conditions in "boxes" which may make analysis difficult when causes and/or outcomes cross boundaries, medical conditions are inappropriately categorized or new information informs medicine.
• The division of conditions into physiological versus psychological causes presents such difficulties, especially when these conditions are subject to such a wide disparity of treatment throughout the existing sociological framework. The bifurcation of conditions into physiological versus behavioral outcomes tends to create categories that diminish or ignore the health and sociological impact of pollution exposure and/or cross category lines.
• Some indices that represent psychological stress may combine various psychological indicators in a weighting formula that may impede the ability to do correlation analysis on any one factor. One is left with memories of Upton Sinclair's "The Jungle", a book about meat packing plants, wondering how the whole was constructed from the parts.   Thus, the question remains in indices and tests as to whether the manner in which the indices are constructed drive a certain result or whether indices keep pace with changes in their individual components.
• Occupational and environmental health outcomes are not appropriately measured in a manner that can express the full continuum of types of work that exists in the sociological sphere.  This reflects the existing dysfunctional definitions of work and disability, and impacts correlation analysis between occupational and environmental health.
• Medical fields studying intersecting fields of study, such as neurology, psychiatry and psychology can come into conflict at times, making it more difficult to study health outcomes emerging from environmental factors. 
• Definitions based on subjective issues such as behavior and, belief systems, emerge to complicate the analysis of the impacts of environmental pollutants.
• The drive to cut medical costs conflicts with testing the impacts of increased environmental load on the public, leaving the impacts uncertain and placing the burden on those impacted. 
• Increased population and economic activity has impacted Western Washington so that environmental risk exists in many places throughout the region, to varying degree.
• The medical system currently does not provide sufficient support to provide both testing and treatment of medical conditions which may arise from the increased exposure to environmental pathogens. There are barriers to entry into the medical system which impede the ability to measure outcomes and protect human test subjects in the evolutionary process.
• Assessment of different contributors to morbidity and mortality may confound research into the underlying environmental issues.  An example of this is assessing the contribution of smoking to morbidity and mortality versus the environmental effects caused by airport operations.
• Different statistical measures may be used by reports, confusing the reader or making it difficult to interpret data shown in different forms;  Data may be presented with an incidence rate (occurrence of a condition in a population over a period of time), a prevalence rate (percentage of a population having a condition at a specific period of time) or mortality rate (percentage of deaths in a population over a period of time).  The US Government publishes data on morbidity and mortality .

The challenge is to put together to what extent the environmental factors drive the medical and  socioeconomic factors and are in turn influenced by them, in a positive feedback loop.

Sources:
Puget Sound Clean Air Agency - Final Report - Puget Sound Air Toxics Evaluation - October 2003
Department of Ecology - Toxic Cleanup Program (ASARCO Smelter Plume)
World Health Organization - Electromagnetic Fields
Port of Seattle - Part 150 Study
Port of Seattle - Groundwater Monitoring
Port of Seattle - Stormwater Pollution Prevention Plan
Scandanavian Journal of Health - Glioblastoma Multiforme
Tacoma Smelter Plume Information - Washington Department of Ecology
King County Community Health Indicators - King County (Top 10 Leading Causes of Death)
King County Public Health -School District Health Profiles
King County Health Profile
King County Public Health - Data and Reports

Blog Articles:
Externalities and Risk - The Seattle-Tacoma International Airport
Seattle-Tacoma International Airport - Environmental Issues
Seattle-Tacoma International Airport - Pollution

Ebola

Raudfjorden Beach, Svalbard, Norway

The Ebola outbreak has proven to a challenge for worldwide heatlh leaders.  The CDC has information about Ebola on its website, as does the World Health Organization (WHO).  The CDC information is delineated into a number of topical areas of interest to subject audiences.  I'm interested in the etiology of Ebola, its transmission, and issues surrounding its current outbreak.

My interest in Ebola began during my actuarial career, reading the "Hot Zone" , a 1994 non-fiction book about incidents involving viral hemorrhagic fevers, including ebolaviruses and marbug viruses. The memory of the book stayed with me since I was reading it while sailing down the west coast of Vancouver Island in 15 foot swells in a sailing vessel.  I can recall eating copious amounts of ginger cookies to ward off seasickness as I read of hemorrhagic fevers killing off people very quickly, in a very bloody and gory fashion, as all the while I was lurching back and forth in the sea and swell on the Pacific Ocean.  The ginger cookies did their job and the memory is etched in my experience, gone but not forgotten, as Ebola emerges again, this time, expressed  in the news of an outbreak.

These hemorrhagic diseases killed off people before they had a chance to spread extensively, and, were confined to certain areas in Africa and mostly away from major population centers.

According to the CDC, the virus can be spread through direct contact with blood and body fluids of a person infected with Ebola, with objects such as syringes infected with Ebola and infected fruit bats or primates.  The question remains as to factors impacting the geographical distribution of Ebola, how it independently arises, factors of etiology and its potential spread elsewhere.

The recent upswing in the Ebola virus prompted me to question its etiology, transmission and other issues.  For example, because of the increase in number of cases, I wondered if the virus had recombined with another virus to increase its transmission and decrease its mortality, or if there were other factors.   In this blog article I consider a number of issues, and raise some questions relating to the virus.


Etiology

• Does Ebola predate the AIDs/SIV/HIV viruses and does it provide some idea of the origin of these viruses? The CDC expresses that it does not know the origin of the original host of the Ebola Virus;  It is interesting to study the context of the Ebola virus regarding its emergence out of the Kinshasha Highway  across the Congo into Uganda as discussed in "The Hot Zone".  Did the virus have origins in bat habitats such as caves, rock, lava tubes, environments exposed to varying bacteria and archaea?
• The Ebola virus is a negative sense RNA virus. The production of proteins from a negative sense RNA virus require first the production of Messenger RNA (mRNA) and then proteins from mRNA. Ebola does not have reverse transcriptase, which would ordinarily be needed to enable insertion of its genetic contents into the DNA.   Is its 'purpose' then to directly produce mRNA (messenger RNA), and why? Research has shown that the filoviruses behind Ebola are very old and that there is direct insertion of genetic content with indications of evolutionary divergence a long time ago.  - The Lin Edwards article, "Ebola and Marburg viruses may be much older than thought" discusses this subject.
• Does the Ebola virus relate to issues concerning New World Monkeys and Old World Monkeys and the divergence of the two species?  If so, would this tend to indicate the same type of environmental conditions that may have existed at the time of that divergence?
• What is the distribution of the virus?  Does the virus act with regards to specific populations, affecting certain populations in a negative or positive way, and leaving others untouched.  What factors in these populations would account for the outbreak?  Are other populations at risk?

Transmission

• Did the Ebola virus recombine with another virus (for example the Corona Mers Virus  , Seasonal Flu Virus or enteroviruses) to allow it to decrease its mortality rate and increase its transmission?  Is it continuing to do so and would further recombination with the current seasonal flu change it further along these lines? 
• A subject of interest to is transmission of Ebola from the natural host to a target population.  Is Ebola being expressed, sustained within the target population or being sequestered?  Does this imply sequestration in a host for transmission or expression later under circumstances that may enable it to be used as a regulatory operator or a mediator of group identity or expression of  immunity systems?  Is it developing a symbiotic relationship with the host or another virus in a toxin/anti-toxin sort of manner (discussed by my blog article on Dr Luis Villarreal and his work on group identity systems)? How does this concept explain the existence of this virus in a reservoir species?
• What is the risk for the spread of Ebola?  To what extent is the risk environmental and to what extent can it be transmitted from person to person? 
• Is Ebola being transmitted in a less than lethal form under our eyes without our knowledge?
• Can Ebola be spread by more species of animals than listed under the CDC website?  
• How might Ebola change to become more transmissible to a greater variety of populations impacted by different environmental factors?  How would this risk change if the Ebola virus were to combine with the seasonal flu in a variety of different ways?

Geological Factors

• What factors in Africa are most significant in the etiology of Ebola?  Heat, humidity, coeexistence with and diversity of animal species, alkaline environments, carbon dioxide sequestration and outgassing (e.g. Lake Nyos), the Archaean basement substrate of the West African bedrock, granite, uranium, endospores such as bacillus anthracis, and  natural nuclear fission reactors from underground uranium (Gabon)? 
• What is the impact of the African mining fields?  Iron, gold, lead, silver, arsenic, mercury , uranium and nickel are among products of mining.  Nickel has a positive feedback impact on inflammatory markers. 
• How do endospores such as bacillus anthracis  fit into the story of Ebola, set in the mining context of West Africa, with its iron, gold, silver, arsenic, uranium, nickel and mercury, and the expression of inflammatory markers and feedback indicators?
• Are these various environmental issues constrained to Africa or are they present in other environments, and where do other similar environmental conditions exist?  Do these conditions have to exist in the same place or can an individual experience them by exposure to a variety of locations? For example, Archaean basement layers of rock exist in the Arctic, in Svalbard, which I visited in 2005. How would exposure to Archaea and other factors present in West Africa differ from the situation in Svalbard where it is much colder! Where else can we find archaea and chiral substances?
• How do increases in solar radiation  and changes in the Earth's magnetic field impact the expression of Ebola in Africa? To what extent would these factors affect the expression of Ebola in other areas of the planet?

Environment and Physiology

•  Does the emergence of a disease that promotes bleeding have significance as it relates to climate change or other planetary or environmental factors?    Is some environmental change occurring that would result in blood clotting more easily, something that would need to be countered by less viscous blood and changes in the coagulation cascade?
• How might the environmental factors in Africa affect blood coagulation?  Through mitochondrial regulation as it is impacted by environment, haplogroups and uncoupling in oxidative phosphorylation?  Through the impacts of oxygen reactive species?  Through solar radiation, geomagnetic storms and cycles?  Through the Warburg effect  (which replaces aerobic respiration with glycolysis)? Through arsenic mining?  Through positive feedback mechanisms involving hypoxemia  and inflammatory responses?  
• Is it possible that the Archaean basement layer of rock in West Africa impacts the blood coagulation cascade  and the blood vasculature through chirality?  Would concepts of fractal dimension  and tortuosity explain concepts of blood coagulation and vascular inflammation and other disorders, including stroke and cancers, including those of the blood and lymphatic systems?  
• What impact does the water people drink (and breathe through water vapor) impact people, including the impact on group identity systems and physiological parameters?
• Does the outgassing  of carbon dioxide  as a result of global warming, the release of iron from iron sequestered in the rock, and the release of endospores from sequestration, explain any of the natural events happening today, as regards vascular and coagulation issues?
• Is it possible that Ebola, as a disorder that promotes bleeding, developed as a feedback mechanism to counter the impact of increased blood coagulation due to the environmental impacts raised above? 
•  Bleeding may increase as blood coagulation factors are used up; does Ebola act to promote such bleeding to counter increases in clotting factors secondary to these environmental issues?  Is it possible that Ebola thus impacts the regulatory mechanisms of the coagulation cascade?

Detection

• Could an easy detection test be done for Ebola using, for example, saliva? This might prove less expensive and easier to measure for initial testing prior to full blood workups if it was sufficiently sensitive and specific.
• Could the d-dimer test and PPT tests be used as early indicators of Ebola.
• Can a series of early indicators, including markers of respiratory and coagulation system function and exposure to certain environmental factors, be developed to ascertain risk patterns for specific populations?  
• Where might the solution to Ebola be found?  Only time will tell.  Are lamprey VLR's a potential solution for isolating, detecting, and finding a cure for Ebola, considering their ability to detect bacillus anthracis and their affinity for carbohydrate glycoproteins?  Considering the age of the filoviruses and the characteristics of Ebola itself, is this a potential area to investigate?

Summary

Does the emergence of Ebola reflect the re-emergence of ancient historical patterns?  Have these patterns been carried by reservoir species from the depths of time to the particular victims of Ebola? Will Ebola adapt and spread elsewhere or re-emerge in other parts of the planet, independently?

Are the issues happening in West Africa an early indicator ('Canary in a Coal Mine')  of planetary changes?  These changes include changes in Earth's magnetic field, climate change, global warming and solar radiation, and downstream effects including release of sequestered minerals and gases such as carbon dioxide and methane from rock and oceans.  These are all areas of concern.  Historical examples of changes in Earth's magnetic field are shown over longer periods of time and more recent geologic time periods in this Wikipedia article on the Earth's Magnetic Field.

Finally, I am reminded of the childhood game, "Animal, vegetable or mineral" and associations with the "Tree of Life" (and probably, by extension, "The Tree of Good and Evil").  Ebola is a disease with a past, reflecting deep phylogeny and the rivers of time as embedded in the history of our rocks.

Sources:

marilyndunstan.blogspot.com
Evolution of Adaptive Immunity

Wikipedia:
Ebola virus disease
"The Hot Zone"
Kinshasha Highway
Archaea
Sense (molecular biology)
Messenger RNA
Reverse Transcriptase
Filoviridae
New World Monkey
Lake Nyos
Endospore
Bacillus Anthracis
Natural nuclear fission reactor
Nickel
Chirality
Sunlight
Earth's Magnetic Field
Oxidative Phosphorylation
Reactive Oxygen Species
Geomagnetic Storm
Warburg Effect
Glycolysis
Coagulation Cascade
Fractal Dimension
Tortuosity
Outgassing
Carbon Sequestion
Animal Sentinel
Earth's Magnetic Field-Geomagnetic Polarity
Earth's Magnetic Field-Brunhes Geomagnetism
Earth's Magnetic Field

World Health Organization:
Ebola Virus Disease

CDC:
CDC
Ebola (Ebola Virus Disease
2014 Ebola Outbreak in West Africa (Outbreak Distribution Map)

Phys Org: 
Ebola and Marburg Viruses May be Much Older Than Thought

JoVE Visualize: Anthrax lethal toxin inhibits translation of hypoxia inducible factor 1? and causes decreased tolerance to hypoxic stress

Geology and Mineral Resources of West Africa - The Archaean Basement

National Academy of Sciences: High-affinity lamprey VLRA and VLRB monoclonal antibodies

Berkeley Lab: Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor

NASA Science News - Earth's Inconsistent Magnetic Field

Evolution of Adaptive Immunity

Two Trees (creative digital image)

I attended a "Weiser Endowed Lecture in Immunology" featuring Dr Max Cooper of the Emory University School of Medicine, speaking on "Evolution of adaptive immunity" at the University of Washington in 2012.  Dr Cooper's work is foundational in this subject area.

It is interesting that immunity systems follow a phylogenetic pathway much as the phylogeny of species themselves do. The evolutionary pathway of jawless vertebrates (of whom hagfish and lampreys are surviving members), possess differences in comparison to the common evolutionary pathway followed by other vertebrates.

Lampreys and hagfish do not possess a thymus , nor do they possess a spleen.    Lampreys and hagfish do not possess Major Histocompatibility Complex (MHC) 1 or 2, T-cell receptors or recombination activating genes (RAG 1 and 2) which play an active role in the recombination of T-cell and immunoglobulin  receptors. Lampreys and hagfish posses hematopoietic tissue, the former in the intestine and the latter in the portal vein.  With these changes, the lampreys and hagfish diverged off the common immune system evolutionary pathway prior to the development of certain MHC class immunity in other species.  This is an important benchmark due to the major role that the MHC class plays in vertebrates.  It is a vital aspect which makes the concept of a separate phylogenetic pathway earmarked for the immune system so interesting.  If lampreys do not possess a thymus, then what substitutes in its place?

Lampreys and hagfish utilize a system of leucine-rich repeats )(LRR's) to mediate immune system responses using Variable Lymphocyte Receptor (VLRs), (VLRA's, VLRB's and VLRC's).  The interesting aspect of the jawless vertebrate immune system function is comparing its action in structure and function to the immune systems we are familiar with.  VLRB's have structures similar to toll like receptors (proteins that play a key role in the innate immune system), while their functions are similar to those of antibodies,  and they possess humoral characteristics (using macromolecules in extracellular fluids in immunity systems). They act using discrete populations of lymphocytes (types of white blood cells) .

VLRBs act as an adaptive immune system and can differentiate foreign from self in recognizing lymphocytes.

Lampreys posses a diverse variety of leucine-rich repeats which code for germline and mature genes. They possess a specificity for carbohydrate and protein receptors on bacterial and mammalian cells. They bind antigens with high avidity and affinity, describing the binding capacity of multiple versus single interactions of antibodies with antigenic epitopes.

 In "Evolutionary implications of a third lymphocyte lineage in lamprey", the authors find a thymoid source for VLRA and VLRC assembly in the lamprey gill tips, while VLRB assembly occurs in hematopoietic typhosole and kidney tissues.  VLRC appeared more numerous than VLRA, and predominated in the skin.  They conclude that a similar body plan of two T-cell type lymphocytes in a thymoid type structure and one B-cell type lymphocyte in the blood and kidneys shows some similarity in basic structure to the immune system for jawed vertebrate, while achieving adaptive immunity through different means.

Monclonal VLRB antibodies  from immunized lamprey larvae can recognize plasma cells from myeloma patients.  VLR4, a monoclonal VLRB specific for BclA, the bacillus collagen-like protein, has shown to be specific for B. Anthracis spores.  Information on B. Anthracis can be obtained from the US Centers for Disease Control (CDC) CDC - Anthrax and the World Health Organization (WHO) WHO - Anthrax.

Research indicates a number of applications where VLR's can recognize certain immumogens  An immunogen is any antigen that is capable of inducing humoral and/or cell-mediated immune response rather than immunological tolerance.  These applications include diagnosis, research and bioterrorism investigations.

Leptin

Butter

I attended a lecture in 2008 about leptin signaling given at Harborview Medical Center through their research programs on diabetes, metabolism and obesity.  The lecture, although highly technical, was  interesting and it gave me plenty to think and read about.

Leptin is what is called a signal transducer.  A signal transducer is an extracellular  signaling molecule that activates a receptor inside or on the cell surface, initiating a series of events, biochemical reactions.    Leptin signaling is involved in a number of areas relating to the management of energy throughout the body, regulating or giving permission for the use of energy for a variety of vital functions.  As I read more about leptin, it led me into a labyrinth of other, associated issues.

Leptin is involved in signaling relating to mesolimbic (dopaminergic) reward centers, food, satisfaction, glycemic control, saiety and reproduction.  Leptin deals with long term energy storage, provision of energy to the brain and gives permission for the use of energy falling within its defined duties.  Intuitively, one wonders what happens if energy demands are requested for things that aren't associated with its associated duties.

Leptin acts to communicate to the Central Nervous System the availability of energy stores.  It acts to restrain food intake and induce energy expenditure, when necessary.   Leptin acts with other systems, such as the Sympathetic Nervous System,  and with factors such as thyroid hormone  and insulin,  in regulating energy use throughout the body and in insuring the thermodynamic  efficiency of skeletal muscle, for example.  Leptin is also involved involved in the cardiovascular system, for example in cardiac hypertrophy.

Leptin is increased, or up-regulated, in obese people.  It increases appetite, generates a low metabolic rate, decreases thyroid function and is impacted by sleep apnea  issues.  Dysregulation of leptin adversely impacts fertility.  Leptin acts on lipid and glucose metabolism.  Leptin also regulates bone metabolism.  This may serve to improve structure with increasing weight by regulating the allocation of higher density bone development.    Leptin resistance occurs during obesity when increasing leptin levels do not have an impact.

Leptin acts in the brain in a neuroprotective  fashion that may also impact memory.  Leptin may be necessary to protect the cell against cell death (apoptosis).

Leptin plays a key role in thermoregulation, working through diverse systems such as the brain's preoptic area and hypothalamus.  Studies in the brown adipose tissue (BAT)  of mice injected by virus indicated involvement of leptin in regulating BAT circuits.  Severely obese mice that lack leptin or its receptor show decreased BAT thermogenesis, and are thus challenged to maintain their body temperature and adapt to cold temperatures.

Leptin may be a key component in considering survival issues under a variety of scenarios or projections associated with climate change modeling.  It may react to a variety of seasonal (zeitgeber) cues, as well as sexual cues regarding melatonin , odor and reproduction.  It will react to hedonistic feelings regarding food, appetite and to the allocation of resources regarding shorter term versus longer term energy needs.

Leptin plays its role along with a host of other players in this complicated web of life.