Wednesday, May 18, 2022

The Impact of Sunscreen Products Upon the Viability of Coral

It has been reported that the compound oxybenzone (shown below) that is the active ingredient in sunscreen preparations exhibits a toxicity to corals. The mechanism of this toxicity has not been fully understood.


Oxybenzone

William Mitch and his colleagues at Civil and Engineering at Stanford University, California have successfully delineated the mechanisms involved in regard to this toxicity. They have established that oxybenzone caused increased mortality of a sea anemone under conditions that simulated the natural (UV) radiation (290 to 370 nanometers). Furthermore they found that both the anemone and a mushroom coral formed oxybenzone–glucoside conjugates (see image below) that were powerful auto-oxidants. Corals are composed of layers, of calcium carbonate secreted by soft bodied animals called coral polyps. These polyps live in a symbiotic relationship with a host zooxanthellae such as algae that gives the coral its color. Corals devoid of algae are bleached as a consequence of climate change.




Algal symbionts took up these conjugates, and their mortality correlated well with the corresponding concentration of oxybenzone glucosides within the animal cells. Since many commercial sunscreens preparations contain compounds structurally analogous to oxybenzone, an understanding of the mechanism of this toxicity should enable the synthesis of more eco-friendly sunscreen products.

According to the authors of a paper published in a recent article in the prestigious journal, Science, “Research in the US Virgin Islands found no substantial settlement of coral larvae, survival of juvenile corals, or regeneration of adult tissue in induced lesions over a 5-year period in Trunk Bay, where high levels of recreational swimming resulted in up to 1.4 mg of oxybenzone per liter of seawater. Meanwhile, a thriving coral community was found at neighboring Caneel Bay, with lower recreational use but presumably the same impacts from global stressors. Exacerbation of coral declines by sunscreens washed off tourists would be ironic and particularly pernicious, given the promotion of ecotourism in the interest of protecting coral reefs.”

Finally, the authors go on to say that, “With recent moves by regulatory authorities in Hawaii and elsewhere to ban oxybenzone, understanding the mechanism(s) of its phototoxicity is important to ensure that the sunscreen components that are selected as alternatives are truly safer for corals.”

The ecological factors that promote and sustain the delicate balance in the natural world can easily be disrupted by human encroachment. It is vitally important to support the kind of scientific investigations that uncover these human factors and find ways to mitigate their impact.




Sunday, May 15, 2022

The Filovirus

One of the suspected and postulated origins of COVID-19 virus in human populations is the transfer of the virus across the species barrier i.e. from bats. This capacity to “jump” across species is of added concern given the severity of illness originating from human infection by a family of viruses referred to as filoviruses. A filovirus is a filamentous RNA virus (see image below).



 

Infection by this virus is the causative agent of so-called “hemorrhagic fevers” in humans and primates, that includes the Ebola and Marburg viruses. These viruses can result in multiple organ system involvement. The Marburg virus, for example, can produce nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea may appear. Symptoms become increasingly severe and can include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhaging, and multi-organ dysfunction. These diseases are most prevalent in sub-Saharan Africa.



 

In 2002, the Lloviu filovirus was found in Schreiber bats (Miniopterus schreibersii) in northern Spain. This infection resulted in a massive die-off of these animals. Gabor Kemenesi and his colleagues from the National Laboratory of Virology at Szentagothai Research Center at the University of Pecs, Hungary successfully isolated and sequenced the Lloviu filovirus from Schreiber bats in Hungary. During a active surveillance of these bats, they found the Lloviu virus resident in these dead and living cave-dwelling bats.

Furthermore, antibody testing detected nine seropositive bats out of 74 live bats and four positives among 351 live bats sampled. The Lloviu virus is known to infect human cells in culture, but unlike the Ebola virus appears to be nonpathogenic to humans, at least for the time being.


Sunday, January 23, 2022

Epstein Barr Virus Infection May be Associated with the Onset of Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic and debilitating disease that is a result of the destruction of the myelin sheath that serves as insulation for the peripheral nerves within the central nervous system (CNS).  The loss of myelin has serious implications for the patient suffering from this syndrome – it results in a gradual deterioration of motor function. 

To date the etiology of this disease has been unclear.  It has long been suggested that Infection with the Epstein-Barr virus (EBV) may be responsible for triggering the onset of MS.  In a recent issue of the prestigious publication Science (January, 2022), Kjetil Bjornevik, from the Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, has provided compelling statistical evidence that EBV infection triggers the onset of MS.  According to the author, “analyzed EBV antibodies in serum from 801 individuals who developed MS among a cohort of >10 million people active in the US military over a 20-year period (1993–2013). Thirty-five of the 801 MS cases were initially EBV seronegative, and 34 became infected with EBV before the onset of MS. EBV seropositivity was nearly ubiquitous at the time of MS development, with only one of 801 MS cases being EBV seronegative at the time of MS onset. These findings provide compelling data that implicate EBV as the trigger for the development of MS.” 

EBV (see diagram below) preferentially attacks B cells; B cells are the part of the immune system repertoire responsible for the production of antibodies.   In MS the myelin sheath is degraded through an inflammatory response.  It has been shown that in MS the B cells responsible for this inflammatory are derived from plasmablasts that are generated in the marrow and take residence inside the brain and its internal lining.  These plasmablasts divide and produce clusters of daughter cells that produce immunoglobulins.  These immunoglobulins contain specific antibodies that target myelin-producing glial cells within the central nervous system (CNS).

EBV Virus


One of the accepted therapies that attempt to take advantage of this etiology is the use of monoclonal antibodies that target CD20 - a protein preferentially found on the surface of B cells.  However, it has significant drawbacks in so far as these monoclonals do not readily pass through the blood brain barrier (BBB) and they are unable to bind to plasmablasts.

What remains unclear, however, is the mechanism through which EBV triggers this sequence of events in MS patients.  One possibility involves what is referred to as molecular mimicry in which some EBV proteins may be similar enough in structure to myelin that the immune system is induced to produce antibodies against the infected individual’s myelin and CNS antigens – this would represent an autoimmune response.  In addition, EBV encodes an interleukin-10–like protein, which activates B cells.  The author of this study, reports that recent evidence seems to suggest that molecular mimicry may be the actual mechanism underlying the association between EBV infection and MS.

The results of these kind intensive studies of the etiology of MS are extremely important in that the product of this work may finally produce effective therapies for MS patients.

Thursday, October 28, 2021

What drives Cancer?

In a recent article in the Science, a prestigious scientific journal published by the American Association for the Advancement of Science (AAAS), Dr. Arianna Baggiolini and her colleagues, from the Memorial Sloan Kettering Cancer Center In New York, NY, proposed a model to explain why some melanocytes preferentially transform into the cancerous state while other melanocytes do not.

Melanoma is a cancer that preferentially arises from cells of the melanocyte lineage.  Melanocytes (see image below) are responsible for   skin pigmentation through the production of melanin so that skin cells, especially keratinocytes, are protected from UV-induced DNA damage.  Melanoma typically resides in the skin.  It has been well established that a so-called “founder mutation” is required to initiate uncontrolled proliferation of cells – a phenomenon that is characteristic of all cancers.  Interestingly, these mutations, also referred to as driver mutations (oncogenes), are also found in healthy skin.  The question arises – why is it that oncogenesis preferentially arises in in some melanocytes and not others.


Dr. Baggliolini and her group of investigators conducted an experimental study in an attempt to explain this behavior.  The animal they chose for their studies was genetically modified zebra fish deficient for the tumor suppressor p53 to drive expression of the BRAFV600E oncoprotein in each stage of melanocyte differentiation.  The evidence they obtained led to a concept they refer to as oncogenic competence – an additional variable is present that renders the melanocytes more susceptible to transformation to tumor cells.

In regard to Melanoma, to give rise to cancer, melanocytes require a driver mutation. For melanoma, such mutations frequently occur in proteins of the mitogen-activated protein kinase (MAPK) pathway, with the BRAFV600E mutation (in which Val600 is replaced with Glu) being most prevalent.  Furthermore in normal human skin, individual melanoblasts and neural crest cells also possess this driver mutation.

Human skin contains many individual melanocytes harboring potentially oncogenic driver mutations. However, what determines which of those cells can evolve to produce melanoma has not been unambiguously determined. Baggiolini and her experimental team found that both neural crest cells and melanoblasts were capable of giving rise to melanomas but, surprisingly, that melanocytes were somewhat resistant. These findings from zebrafish were confirmed in a parallel study using human pluripotent stem cells (hPSCs) rendered deficient for the tumor suppressors retinoblastoma (RB), p53, and p16 and in which the precursor cell line was induced at various stages of melanocytic differentiation.  The results show that melanocytes, but not neural crest cells or melanoblasts, were largely incapable of forming tumors when subcutaneously transplanted into immunodeficient mice.

The result of these experimental studies has clearly shown that the additional factor required to explain why some melanocytes do go on to produce cancer while other melanocytes with the driver mutation do not, is the enzyme ATAD2.  This enzyme is responsible for chromatin reorganization.  In those melanocytes in which this enzyme is expressed at lower levels, the likelihood of transformation of melanocytes into the cancerous state is increased.

This is a very interesting finding for it establishes a link between tumorigenesis and chromatin organization.

Friday, June 11, 2021

Biology of a Virus


 

It has been over a year since the world population has been dealing with the COVID-19 pandemic.  As a result of intense scientific investigation and study, effective vaccines have been developed and are being distributed worldwide.  

Given this reality, it would be of value to more fully understand what viruses are and how they function.

The following document may be of some help in this regard.

Sunday, February 7, 2021

The Basis of Antiviral Immunity

     Models of COVID-19 and the Spike Protein

The human immune system is a highly sophisticated and powerful system that the body utilizes on an ongoing basis in order to ensure the continued survival of the individual in a hostile environment. It is comprised of a heterogeneous population of cells, factors and organs that function together to maintain the general health of the individual. The immune system is, in fact, a product of millions of years of evolution. Rudimentary immune systems and processes can be found in many more primitive forms of life including single-celled organisms.

Immunologists have delineated two arms of the human immune system – innate and adaptive. The innate branch of the immune system possesses pattern recognition mechanisms designed to recognize any non-self antigen – an antigen is any substance, usually protein, that can elicit an immune response. When an antigen is recognized as foreign, the innate immune system is designed to mobilize quickly to neutralize the foreign organism that carries this antigen.

The other part of the immune system is referred to as the adaptive immune system. As the name infers, the adaptive immune system can adapt to new foreign invasive bacteria and viruses that find their way into the host. It is precisely this arm of the human immune system that responds to SARS-COV-2 (COVID-19). It is this system that neutralizes virally-infected cells and can induce the production of so-called, “memory cells.” It is this capability that is exploited and enhanced by vaccination strategies.

Both T-cells and B cells represent the primary cellular arsenal for the adaptive immune system essential for the eradication of invading viruses. The progenitors of the cellular components of the human immune system originate in the bone marrow. The COVID-19 pandemic has revealed the wide variability of the immune response to the COVID-19 virus ranging from an asymptomatic response to an acute and sometimes life threatening severe acute respiratory syndrome. This apparent variability has raised questions regarding the mechanisms through which antiviral responses are employed and the nature of the longevity of immunological memory.

As we are well aware, viral infections often lead to disease states within the impacted host. Viruses occupy a special place in regard to life on planet earth. They are essentially inert when outside a living cell showing no properties that are ordinarily assigned to living things. However, once they gain entry into a host cell, they subvert the cellular machinery, effectively diverting ordinary cell processes to a singular goal – the production of viral particles. This usually leads to the death of the host cell facilitating the release of new viral particles that go ahead and infect neighboring cells within the target tissue – in the case of COVID-19 its target tissue is found in the lungs.

The dynamics of the human body’s response to an invasion by a virus is intricate, immediate, and multi-faceted. The current understanding of this process is that it involves the integration of the two arms of the immune system we have previously referred to i.e. the innate and the adaptive. The first and rapid response is that of the innate system. The innate immune responses result in the production of factors that lead to inflammation at the site of entry – this is the so-called “inflammatory response.” This response leads to the activation of the adaptive immune system.

Viral particles are essentially composed of an inner core of either DNA or RNA and an outer shell of protein. It is the proteins on the viral surface that are potential antigens. Viral proteins and particles are subsequently taken up by specialized cells in the immune repertoire that are called dendritic cells (DCs) These cells transport the ingested antigen(s) to the lymphoid organs (lymph nodes and spleen for example), where they are specifically recognized by T and B cells. The T cells constitute the cellular branch of the adaptive system and the B cells represent the humoral branch responsible for the production of specific antibodies against the viral intruder. It is the cellular (T cell) and humoral (B cell) branches of adaptive immunity that collaborate to enable highly specific defenses against diverse viruses.

According to Dr. Linda Bradley from the Tumor and Microenvironment and Cancer Immunology Program at Sanford Burnham Prebys Medical Discovery Institute at La Jolla in a recent report in the prestigious journal, Science, “The magnitudes of the T and B cell responses are determined by such factors as the pathogenicity of the virus, the extent of inflammation, the frequencies of virus-specific T and B cells, and the kinetics of viral replication. CD8+ T cells differentiate into effector cells that limit viral replication through production of cytokines and direct killing of infected cells."

Furthermore, in regard to immune responses to COVID-19, this report goes on to state that, “Viral recognition elicits cytokine-producing effector cells, such as T helper 1 (TH1) cells, which inhibit viral replication and support CD8+ T cell as well as B cell differentiation. Effector T cells can enter the circulation and relocate to tissue sites of infection, where they mediate local antiviral responses. CD4+ T cells also differentiate into T follicular helper (TFH) cells that are crucial for the development of antibody-producing B cells (plasma cells) in lymphoid tissues and support memory B cell development. Antibodies can neutralize viruses by preventing host cell entry or promoting the lysis of infected cells. As a result of the coordinated interplay of innate and adaptive responses, the peak T and B cell responses lead to decreasing viral load and subsiding inflammation, often within 1 week of infection."

It is an understanding of the mode of action of a particular virus and the immune system’s responses to it, as outlined above, that plays a critical role in developing a vaccine that can effectively augment the natural immunity. For a virus to successfully infect a host it must gain entry to the host, successfully evade the immune response, gain entry into the host cell, and successfully commandeer the host cells machinery to make more viral particle and spread the infection. Any vaccine that successfully interdicts any of these mechanisms will necessarily prove efficacious.

 

Wednesday, December 23, 2020

Holiday Message for the Coming Year - 2021

The year 2020 has been in many ways disturbing and unsettling.  What, of course, comes to mind almost immediately is the COVID 19 pandemic that has claimed so many lives and has been so economically devastating to many facets of the national economy, and especially for those who have lost their livelihoods and businesses.  Added to this national burden are the deep fractures that have been exposed in regard to a national sense of unity, shared-mission and purpose.

Along with this overwhelming sense of loss, however, is the untold bravery, courage and unwavering energy displayed by so many who have risked their own lives and safety to come to the aid of all of us for the unselfish commitment to the greater good.  These individuals have come from many diverse positions - as doctors, nurses, emergency response teams, members of the police and fire departments and first responders of all kinds.  To this list, we should include all those responsible for providing food; for delivering the mail; for the taxi and bus drivers, train operators and pilots; for the teachers; for all those who care for the elderly and for all those who provide the essential services that we all too often take for granted.

My wish for the New Year (2021) is that we grow wiser from the events that have befallen us and see the future as a time for healing and learning from our collective missteps.  My hope is that the new year will be a time of new beginnings.  My dream is that we will finally come to recognize that regardless of our national origin, religious affiliation, skin color or sexual orientation we are all members of the same species with the same physical bodies, the same architecture of the brain, the same genetic makeup, the same constellation of feelings, of hopes and of dreams.  Each of us is worthy of the same opportunities to grow and develop as sentient beings on this most remarkable planet that also needs our kindness, care, and attention.  Earth is, after all, our only home.

Best Wishes to All