Climate Change - New Concerns

There is a growing concern among climatologists that the earth may be entering an era of accelerated climate change.  This reevaluation has at its core evidence of so-called feedback loops.  Some examples of the feedback process are the following:

·         As sea ice melts it reduces the albedo effect (reflection of the sun's heat from the surface) and, therefore, leads to an increase in ocean temperature that results in a further melting of the sea ice

·         As areas of permafrost – found in Siberia - melt due to increased average temperature in the atmosphere, this releases carbon dioxide (CO₂) and the more potent greenhouse gas, methane from vast stores of biomass that exist below the permafrost.  It is estimated that the total store of this organic material represent twice the amount of carbon (CO₂) already in the atmosphere.  The release of these greenhouse gases further increases the average global temperature resulting in further melting of the permafrost.  This kind of feedback involving the permafrost has also been implicated in the warming crisis that has been reported to occur at the end of the Permian Period (~ 250 million years ago) by A. Hallam and P.B. Wignall in their book entitled, Extinctions and Their Aftermath

·         The disruption of the thermohaline circulation (THC) as discussed in detail in a previous article (Climate Change Revisited).  It is important to understand that the THC influences global climate by transporting heat and freshwater between the oceans globally.

 

The prospect of these feedback mechanisms accelerating climate change has so concerned James E Hansen, Director of the NASA Goddard Institute for Space Studies that he has warned that, "Unless the world slashes CO₂ levels back to 350 ppm (the current level is 391), we will have started a process that is out of humanity's control."  He cited the possibility of a sea level rise of five meters during this century - if this should become reality it would be catastrophic.  Other scientists in his field believe the rise will not be that extreme but do envision a sea level rise as high as two meters.  This projection is also very troubling.

 

These data indicate that not only are we currently feeling the impact of climate change but also that these changes may very well be accelerating.  This is a global crisis that necessitates a global solution. 

Climate Change Revisited

The recent weather catastrophe that struck an area of the United States where some fifty million individuals reside brings to the forefront once again the issue of climate change.  The storm surge precipitated by the hurricane referred to as, "Sandy," was unprecedented in its severity for this region of the country.  The damage that it wrought in both its physical manifestations and its emotional impact on the lives of those directly affected together with the mounting cumulative evidence including extreme hot weather, droughts, the frequency and severity of forest fires, etc. are representative of the expected consequences of the ever-increasing concentration of greenhouse gases in the atmosphere as predicted by sophisticated computer-modeling developed by climate scientists.   

 

I have eluded to some of these factors in previous reports, that show a connection between increased surface temperature of the oceans and the expected increased severity and possible frequency of hurricanes and typhoons that derive their energy from ocean temperature. I would like to take this opportunity, however, to address a very particular aspect of climate change that may directly relate to extreme weather conditions more likely to impact global weather patterns in the more distant future..

 

Since the upper layers of the ocean have direct interaction with the atmosphere, changes in this upper level have a direct bearing on climate over shorter periods of time (decades).  However, deep ocean circulation has a direct influence over future climate conditions.  For water to sink from the ocean's surface to the deeper ocean, it must be more dense – the two criteria that meet this requirement are temperature and salt content i.e. the water must be cold and salty.  The water in the Atlantic Ocean and the Greenland Sea – between Greenland and the Scandinavian countries –  and the ocean around Antarctica are large bodies of water that meet these requirements.  This deep dense water contributes to the deep water circulation that is global in extent.  This process is knows at the thermohaline circulation (THC).  It is important to understand that the THC influences global climate by transporting heat and freshwater between the oceans globally.

 

As ice melts as a direct consequence of the level of greenhouse gases in the atmosphere, the water in its immediate vicinity becomes less dense as a result of simple dilution.  As a consequence, such water will be less likely to sink to the deep ocean.  Consequently, this weakening of the THC, lessens the heat flow from the tropics to the North Atlantic.  It is anticipated that if the level of greenhouse gases is allowed to increase unabated over the long term, the THC would be expected to breakdown entirely.  If this should happen, the winters in the North Atlantic and Western Europe could be become extremely severe.

 

This kind of scientific analysis demonstrates that if humanity fails to address the problem of greenhouse gas emission in a meaningful way, both the near term and long term effects could prove disastrous to life as we know it. 

So-called Junk DNA – Not Really Junk

In the year 2000 as a result of a momentous effort to define the human genome, the first complete sequence of human DNA was delineated.  From this work, it was determined that only about 3% of the entire DNA structure was relegated to the genes – containing the information for the structure of those proteins that help defines us as human.  It was assumed that the remaining 97% of the DNA played no important biological role and was determined to be "junk."

 

To some it seemed inconceivable that so much DNA real estate would serve no biological purpose.  As a consequence, a number of laboratories from around the world became involved in an ambitious joint project designed to determine the role, if any, of the non-gene parts of the entire human genome.  This work required a meticulous examination of extended sequences of DNA.  This endeavor was referred to as the Encyclopedia of DNA Elements (ENCODE).  The goal of this project was to find those portions of the non-gene DNA that had an identifiable purpose.

 

In 2007, ENCODE came out with its first preliminary report clearly showing that this part of the DNA contained many varieties of functional elements.  As a consequence of this work, a series of papers has been published in the September (2012) issue of the prestigious scientific journal, Nature detailing ENCODE's findings.

 

These extensive and exhaustive studies clearly demonstrate that large non-gene areas of the human genome contain information of functional significance.  ENCODE has catalogued an impressive inventory of hidden switches for the expression or suppression of encoded genes, signals –transcription factors - and signposts integrated throughout the length of the human genome.  In essence, it now appears that much of the DNA landscape is relegated to regulatory processes.  To place this in perspective, roughly 1.2% of the genome is involved in protein coding, while some 8 – 9% is involved in regulatory processes.  Furthermore, it seems that these regulatory elements are more susceptible to change – mutation - than the genes that they regulate; this fact has profound evolutionary implications.  Finally, it now appears that around 80% of the entire genome is actively transcribed into RNA; this is a remarkable finding that requires further elucidation.

 

In conclusion, it appears that the concept of "junk" DNA can now be effectively put to rest.  These results open up whole new vistas for further investigation.  

Our Internal Clock

Life on the planet has developed in the setting of the rhythmic cycles of day and night – light and dark.  As a result mammals have evolved an internal biological clock referred to as the so-called, "circadian clock."  This clock represents a physiological mechanism that establishes the internal rhythms of many diverse processes such as sleeping and waking patterns, body temperature, hormonal activity and the overall general metabolism.  As one might expect, aberrations in this system can have profound impacts on general health and well-being.

This clock is in effect an inherent mechanism that is driven by regulatory networks of clock genes that control gene expression through transcription factors.  It has been well established that the primary transcription factors are CLOCK and BMAL1 - responsible for the expression of the Period (PER) and Cryptochrome (CRY) genes.  The periodicity of the clock mechanism is established by a feedback loop in which PER and CRY proteins inhibit CLOCK-BMALI.  This feedback mechanism results in rhythmic gene expression.  In fact, it has been clearly shown that essential liver function and processes, for example, are under the control of the circadian clock.

These internal rhythms are so essential to good health that when they are disturbed by genetic mutation or environmental influences, ill-health is often the consequence.  To cite a number of examples of environmental disturbances, jet lag and shift work have been implicated in sleep disorders, and both cardiovascular and metabolic disease.

Through the work of Dr. Tsuyoshi Hirota and colleagues from the Division of Biological Sciences and Center for Chronobiology at the University of California at San Diego and La Jolla, a small molecule that functions as a modulator of the circadian clock has been identified.  This compound referred to as KL001 acts specifically on the protein products of the CRY gene that regulates a particularly critical metabolic pathway in the liver that is responsible for the synthesis of glucose – gluconeogenesis.  This was no meager accomplishment since over 60,000 compounds were analyzed using human cell lines in the laboratory.  Since KL001 is involved in regulating a pathway associated with glucose synthesis, it may prove to have some therapeutic potential in regards to the treatment of type 2 diabetes.

Our Ancestors – A New Addition to the Family

 It has been estimated that approximately six million years ago, the ancestral lineage that would ultimately lead to human beings diverged from that which lead to our nearest relations – chimpanzees and apes.  The fossil evidence demonstrates that between two and three million years ago, our ancestors showed indications of human attributes.  These ancestors, Lucy being an excellent example, walked upright but possessed small brains and hands that were obviously designed for the climbing of trees.  Members of this group are collectively referred to as our australopithecine predecessors.

The discovery of the complete lineage to modern humans remains unfulfilled.  However, Doctor Lee Berger, a paleoanthropologist at the University of Witwatersrand in Johannesburg, South Africa, has recently made a discovery that may provide a significant piece in this puzzle.

Fossil fragments that have been dated to be some two million years old have been found in an old miner's pit at the so-called "Malapa site" northwest of Johannesburg.  These fragments include pelvis and leg bones, ribs and vertebrae, arm bones, clavicle and skull.  From these various pieces, the partial skeletons of an adult female and young male have been assembled. 

From these cumulative findings, it became apparent to Berger and his colleagues that an entirely new hominid species had been discovered.  It was called Homo sediba.  Although the fossil evidence demonstrates a relatively small brain – a skull enclosing a volume of 420 cubic centimeters that is about one-third of the size of the brain of modern humans, its pelvis is bowl shaped.  This was an unexpected discovery, since it was previously believed that this shaped pelvis evolved to accommodate a large brain.  In addition, the shape of the skull shows an expanded frontal region indicating the further development of the frontal lobes – an area of the brain associated with higher order intelligence.  Although sediba's arms were long, the fingers were short and straight probably adapted to the fashioning of tools.

This finding sheds new light upon the evolutionary progression to modern humans – Homo sapiens.  It may also suggest that Homo habilis and Australopithecus afarensis might be, in fact, side branches and not in the direct lineage.  As a result, yet another piece of the intriguing evolutionary process has been elucidated.

Ocean Acidification and Climate Change – A Case In Point

It has long been understood that the uptake by the oceans of the increasing levels of carbon dioxide (CO₂) in the atmosphere,  produced as a result of human activity, leads to the reduction in the pH – increased acidity – of the water.  This increased acidity has the effect of disturbing the carbonate (CO₃) balance in the oceans.  What has not been clearly defined is the extent of these changes.

The index for assessing the degree of this imbalance is the so-called "carbonate saturation state."   The aquatic organisms that are especially susceptible to changes in the carbonate saturation state are those that create part of their structure from available calcium carbonate (CaCO₃).

Doctor Nicolas Gruber and his colleagues at the Department of Environmental Physics at the Institute of Biochemistry and Pollutant Dynamics , ETH Zurich, Switzerland and at the Atmospheric and Oceanic Sciences Program at Princeton University, Princeton, NJ have studied the California Current System (California CS) in attempt to quantify these changes.  The California CS is of particular importance in that it represents an essential marine ecosystem.

As a result of their findings, they have projected that by the year 2050 the carbonate saturation state will drop to levels that represent under-saturation of carbonates critical to the marine environment.  They have come to this conclusion using two different scenarios – one projecting high emissions of CO₂ and the other low emissions.  According to the authors, "Habitats along the sea floor will become exposed to year-round under-saturation within the next 20 to 30 years.  These projected events have potentially major implications for the rich and diverse ecosystem that characterizes the California CS."

These findings represent yet another example of the perils the global human community faces as a direct consequence of the anthropogenic buildup of greenhouse gases in the atmosphere.  It remains to be seen whether or not the plethora of known global environmental disruptions will provide sufficient motivation for the human community to implement meaningful solutions to this enormous problem.  

A Possible New Approach to the Treatment of Osteoarthritis

Osteoarthritis (OA) is a degenerative condition that involves the breakdown of joint cartilage that affects over 70 percent of individuals between the ages of 55 and 70 in the United States.  If untreated, it can eventually lead to severe disability.  Currently, the available options for individuals suffering from OA are medication to relieve pain and eventual surgical invention often involving joint replacement.

The disease process is complex and multi-faceted.  It involves:

• degradation of the integrity of the extracellular matrix
•   lack of sufficient replacement and repair of this matrix
•   abnormal cell death
•   accelerated differentiation of cartilage cells.

Dr. Kristen Johnson and colleagues from the Genomics Institute of the Novartis Research Foundation in San Diego California are developing an approach to the treatment of OA using mesenchymal stem cells (MSCs).  Stem cells are cells found in the body that are so-called pluripotent cells in that they have the capacity, under the appropriate conditions, to differentiate into a variety of tissue cells.  MSCs are normally found in the bone marrow and are capable of differentiating into a variety of cell types including chondrocytes – the cells responsible for making new cartilage.

In their research, Johnson's group discovered a small molecule called kartogenin that they have shown can stimulate the differentiation of MSCs into chondrocytes and therefore lead to the enhanced production and repair of cartilage – a process known as chondrogenesis.

These results are significant in that they suggest a non-invasive stem cell- based procedure as a therapy for OA in place of the current surgical option.