Biology Online is a Biology blog and dictionary site that provides up to date articles on the latest developments in biological science. The Biology Online Dictionary is a completely free and open dictionary with over 60,000 biology terms. It uses the wiki concept, so that anyone can make a contribution.
Category: Health and Medicine

Pathobiology of allergy and its most severe form, anaphylaxis

When allergy season looms, some people with serious hypersensitivity to allergens tend to be apprehensive of what may come. Some would rather stay indoors than risking the odds of sucking up triggers that could instigate severe allergic reactions. Apart from triggers from the environment, other common factors for allergy include food, medication, certain toxins, venom from insect stings or bites, stress, and heredity. How does an allergy manifest? Which cells are involved in forming an allergic reaction?

 

 

 

The immune system

allergy
How does an allergy occur? The pathobiological mechanism involves several white blood cells that play a role in mounting an allergic reaction.

 

The immune system protects the body from foreign substances (generally referred to as antigens) that could pose a threat to our well-being.  It prevents harmful bacteria, viruses, parasites, etc. from invading and causing harm. The white blood cells (also called leukocytes) constantly scout for antigens in order to destroy or disable them. The white blood cells include lymphocytes, neutrophils, basophils, eosinophils, monocytes, macrophages, mast cells, and dendritic cells.

 

 

 

Allergy – overview

 

allergy pathway
The allergy pathway.
Image (by Sari Sabban) distributed under the CC 3.0 Unported license.

 

An allergy is a state of hypersensitivity of the immune system in response to an allergen (i.e. a substance capable of inciting an allergic reaction). In this regard, several white blood cells play a role in mounting an allergic reaction.

In summary, the entry of an allergen into the body triggers an antigen-presenting cell, such as a dendritic cell. The dendritic cell takes up the allergen, process it, and then present its epitopes through its MHC II receptor on its cell surface. It, then, migrates to a nearby lymph node, waiting for a T lymphocyte to recognize it.

Upon recognition, the T lymphocyte may differentiate into a Th2 cell (type 2 helper T cells), which is capable of activating B lymphocyte. B lymphocyte, when activated, matures into a plasma cell that could synthesize and release IgE antibody in the bloodstream. Some of the circulating IgE may bind to mast cell and basophil. Thus, re-entry of such allergen could incite the IgE on mast cells and basophils to recognize its epitope. In effect, this activates the mast cell or basophil to release inflammatory substances (e.g. histamine, cytokines, proteases, chemotactic factors) into the bloodstream.

 

 

 

Anaphylaxis – a dreadful allergic reaction

The allergic reaction mounted by the immune system is supposed to protect the body. However, the allergens perceived by the body as a threat are generally harmless. The body tends to overly react to the allergens, and so leads to symptoms. Histamine, for instance, brings about the common symptoms of allergy: pain, heat, swelling, erythema, and itchiness.

 

Anaphylaxis is the most severe form of allergic reaction. It can occur rapidly and it affects more than one body system, such as respiratory, cardiovascular, cutaneous, and gastrointestinal systems. It occurs as a result of the release of inflammatory substances from mast cells and basophils upon exposure to an allergen. Within minutes to an hour, symptoms could manifest as a red rash, swelling, wheezing, lowered blood pressure, and in severe cases, anaphylactic shock.

 

In the presence of breathing difficulties, racing heart, weak pulse, and/or a change in voice, the situation is precarious. It calls for an immediate medical attention.

 

Why does anaphylaxis occur? IgE-mediated anaphylaxis is the common form of anaphylaxis. Initial exposure to an allergen leads to the release of IgE so that re-exposure to the allergen leads to its identification and the eventual activation of mast cells and basophils.  Apart from immunologic factors, though, other causes of anaphylaxis are non-immunologic. For example, temperature (hot or cold), exercise, and vibration may cause anaphylaxis. In this case, IgE is not involved. Rather, these agents directly cause the mast cells and the basophils to degranulate.

 

 

 

Novel mechanism identified

Recently, a team of researchers1,2 found a novel mechanism that could explicate the hasty allergic reaction during anaphylaxis. They were first to uncover a mechanism involving the dendritic cells. Accordingly, a set of dendritic cells seem to “fish” allergens from the blood vessel using their dendrites. The dendritic cell near the blood vessel takes up the blood-borne allergen. Rather than initially processing it, and then presenting the epitope on its surface, it hands over the allergen inside a micro-vesicle to the adjacent mast cells.

 

Mast cells, unlike basophils that are in the bloodstream, are located in tissues, such as connective tissue. Thus, the question as to how the mast cells detect blood-borne allergen could be answered by the recent findings.

 

Rather than being internalized by the dendritic cells for processing, the allergen was merely taken into a micro-vesicle that budded off from the surface of dendritic cells. This, thus, saves time. It cuts the process, leading to a much rapid allergic reaction.

 

However, these findings were observed in mouse models. Therefore, the researchers have yet to observe if this novel mechanism also holds true on humans. If so, this could lead to possible therapeutic regulation of allergies, especially the most dreadful form, anaphylaxis.

 

 

— written by Maria Victoria Gonzaga

 

 

References:

1 Choi, H.W., Suwanpradid, J. Il, Kim, H., Staats, H. F., Haniffa, M., MacLeod, A.S., & Abraham, S. N.. (2018). Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesiclesScience 362 (6415): eaao0666 DOI: 1126/science.aao0666
2 Duke University Medical Center. (2018, November 8). Using mice, researchers identify how allergic shock occurs so quickly: A newly identified immune cell mines the blood for allergens to directly trigger inflammation. ScienceDaily. Retrieved November 22, 2018 from www.sciencedaily.com/releases/2018/11/181108142440.htm

 

First time! Human blood cell turned into a young sex cell

In essence, our body consists of two major types of cells – one group involved directly in reproducing sexually (called sex cells) and another group that are not (called somatic cells). In particular, the female sex cell is referred to as the ovum (also called egg cell) whereas the male sex cell, the sperm cell. The somatic cells, in turn, are the cells in the body that have varying functions, such as nourishing the sex cells as well as keeping the body thriving and functional.

 

 

 

Origin of sex cells

Our body produces sex cells through the process called gametogenesis. The process is essentially a step-by-step process of meiosis. Oogenesis (i.e. gametogenesis in females) takes place in the ovaries to produce ova or egg cells. In brevity, the oogonium (the female primordial germ cell) undergoes meiosis to produce four haploid egg cells. Conversely, spermatogenesis (i.e. gametogenesis in males) occurs in the testes to yield sperm cells. Quintessentially, the spermatogonium (the male primordial germ cell) will go through meiosis to give rise to four haploid sperm cells.

 

 

 

Sex cells vs somatic cells

In humans, a sex cell may be identified from a somatic cell in being a haploid cell. That means a sex cell would have half the number of chromosomes as that of a somatic cell. Hence, an egg cell or a sperm cell would have 23 chromosomes whereas a somatic cell would have 46. Haploidy in sex cells is important in order to maintain the chromosomal integrity in humans across generations.

 

At fertilization, the sperm cell and the egg cell unite to form a diploid cell (called zygote). The zygote, then, divides mitotically, giving rise to pluripotent stem cells. A pluripotent stem cell is a cell capable of giving rise to various precursors that eventually will acquire specific identity and physiological function via a process called differentiation. A differentiated cell means that the cell has matured and acquired a more specific role, for instance as a skin cell, a blood cell, a liver cell, etc.

 

 

 

Somatic cell converted to sex cell

sex cell
Soon, a somatic cell could be converted into human sex cells.
[Image credit: Karl-Ludwig Poggemann, Flicker.com, CC by 2.0]

 

Intrinsically, a human somatic cell that has “differentiated” could never become a sex cell just as a sex cell could neither become nor give rise to a somatic cell. However, this may no longer hold true in the years to come.

 

Japanese researchers have, for the first time, successfully converted a somatic cell into a sex cell precursor.1 In particular, they had successfully created an oogonium from a human blood cell. They turned blood cells into “induced pluripotent stem cells” (iPS).2 Essentially, the blood cells – turned iPS – appeared to have undergone “molecular amnesia”. It means they forget their initial identity. As a result, they could become any type of cell, even as a sex cell.

 

The researchers transformed human blood cells into oogonia (plural of oogonium). They did so by incubating them for four months in artificial ovaries derived from embryonic mouse cells. They retrieved promising results. Admittedly though, they acknowledged they are still in the early steps of a rather long journey of research. The oogonia, indeed precursors to egg cells, are, at this point, still young, and thereby, unfit for fertilization. The researchers have yet to induce them to become mature, fully differentiated egg cells. Nevertheless, they remain optimistic in having reached this point, and, undeniably, pioneered an important milestone.

 

 

 

 

Ethical issues

If, in the future, research on the conversion of a somatic cell into a sex cell pushes through to completion, it could lead to significant resolves to infertility issues. However, ethical concerns shall, likely, surface as well. For instance, a possibility could occur in time. A mere hair cell or a skin cell from an unsuspecting person could be turned into an egg or a sperm cell. And from there, an offspring could come into existence.

 

 

 

— written by Maria Victoria Gonzaga

 

 

References:

 

1 Yamashiro, C., Sasaki, K., Yabuta, Y., Kojima, Y., Nakamura, T., Okamoto, I., Yokobayashi, S., Murase, Y., Ishikura, Y., Shirane, K., Sasaki, H., Yamamoto, T., & Saitou, M. (2018 Oct 19).Generation of human oogonia from induced pluripotent stem cells in vitro. Science, 362(6412):356-360. doi: 10.1126/science.aat1674.

 

2 Solly, M. (2018 Sept. 24). Scientists create immature Human Eggs Out of Blood Cells For the First Time. Retrieved from [link]

 

“Mutualism factor” could explain why body does not attack normal flora

When sadness reeks in and you feel as if you are all by yourself, think again. That is because you are never alone. As a matter of fact, millions of microorganisms reside in our body day in and out. They are the normal flora. Our body is a world of microscopic living entities that inhabit our body without essentially causing a disease. Rather, they live in us in harmonious mutualism. Thus, our body is not ours alone. Hence, we can say we are not absolutely sterile from the moment we are born.

 

 

 

Normal flora

Typically, the body has about 1013 cells and harbors about 1014 bacteria.1 The multifarious yet specific genera of bacteria that predominate the body is referred to as the normal flora. In essence, the normal flora thrives in a host in a mutualistic lifestyle. The microbes take advantage from living stably in the body. In return, they confer benefits to the human host. For instance, their presence helps prevent other more harmful microbes from colonizing the host. Some of them biosynthesize products that the human body can use. Nevertheless, an immunocompromised host could suffer in cases when these bacteria became overwhelming in number, and thereby cause detectable harm, like infections or diseases.

 

 

 

Normal flora in the gut

normal flora in the gut
Escherichia coli, one of the many bacterial species of the normal flora in the human gut

 

Microbes that normally thrive in the gut are greater in density and diversity compared with those in other body parts. Nevertheless, they vary in density depending on the location in the gastrointestinal tract. For instance, the stomach harbors about 103 to 106/g of contents whereas the large bowel of the large intestine has about 109 to 1011/g of contents. The normal flora in the stomach has fewer normal microbial inhabitants due to its acidity. The ileum of the small intestine contains a moderate microbial number, i.e. 106 to 108/g of contents.1

 

Some of the various bacterial species of the normal gut flora includes the anaerobes, Enterococcus sp., Escherichia coli, Klebsiella sp., Lactobacillus sp., Candida sp., Streptococcus anginosus and other Streptococcus sp.. Some of these bacteria aid in the production of bile acid, vitamin K, and ammonia since they possess the necessary enzymes.

 

 

 

Coexistence

Certain normal gut bacteria can become pathogenic. They could cause a disease when opportunity presents such as when changes in their microbiota favor their growth. Be that as it may, a healthy individual would not be usually harmed by their presence. Thus, question arises — why our immune armies do not, by and large, act against the normal flora as aggressively as they would in the presence of more harmful pathogens.

 

Karen Guillemin, a professor of biology and one of the authors of a paper that appeared in a special edition of the journal eLife, was quoted3: “One of the major questions about how we coexist with our microbial inhabitants is why we don’t have a massive inflammatory response to the trillions of the bacteria inhabiting our guts.

 

 

 

“Mutualism factor”

Guillemin and her team of scientists reported that they uncovered a novel anti-inflammatory bacterial protein they referred to as Aeromonas immune modulator (AimA).  Accordingly, AimA is a protein produced by a common gut bacterium, Aeromonas sp., in the animal model, zebrafish.  The researchers found that AimA alleviated intestinal inflammation and extended the lifespan of the zebrafish from septic shock.2 Furthermore, they described it as an immune modulator that confers benefits to both bacteria and the zebrafish host.

 

The newly-discovered protein seems to be the first of its kind. Nevertheless, it is structurally similar to lipocalins, a class of proteins that, in humans, modulate inflammation. Based on their findings, the removal of this protein caused more intestinal inflammation in the host and the destruction of the normal Aeromonas gut bacterium. The reintroduction of AimA reverted to “normal”, i.e. the host, relieved from inflammation and Aeromonas’ typical density, restored. AimA appears to represent a new set of bacterial effector proteins. And, Guillemin referred to them as mutualism factors.3

 

Guillemin and her team postulate that many more of these mutualism factors exist even in humans, and yet to be found. These mutualism factors may have therapeutic potential for use in modulating inflammation especially in medical conditions such as sepsis and certain metabolic syndromes.

 

 

 

— written by Maria Victoria Gonzaga

 

 

References:

 

1 Davis, C. P. (1996). Normal Flora. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston. Retrieved from [link]

2 Rolig, A. S., Sweeney, E. G., Kaye, L.E., DeSantis, M. D., Perkins, A., Banse, A. V., Hamilton, M.K., & Guillemin, K. (2018). A bacterial immunomodulatory protein with lipocalin-like domains facilitates host–bacteria mutualism in larval zebrafish. eLife. [link]

3 University of Oregon. (2018, November 6). Novel anti-inflammatory bacterial protein discovered: Newly discovered protein alleviates intestinal inflammation and septic shock in an animal model. ScienceDaily. Retrieved from [link]

Mosquitoes wiped out by CRISPR–Cas9 gene drive

Up to what extremes are we willing to take in order to ensure the survival of our species? Mosquitoes may be tiny and insignificant. But, they are one of the deadliest ectoparasites that ever lived. They do not just feed on our blood. They could even leave us with a gift – like a “Pandora’s box” of dreadful diseases. Thus, we took a long stride. We armed ourselves with various weapons against these obnoxious flying “bloodsuckers“. And recently, researchers from Imperial College London came up with a novel strategy aimed at destroying them at their molecular level — by hacking their DNA with CRISPR technology.

 

 

 

Little flies

mosquitoes
Mosquitoes belong to the Order Diptera of Class Insecta

 

Mosquitoes are winged insects that belong to the Order Diptera. Their name means “little fly“. They have slender bodies, a pair of wings, three pairs of legs, a proboscis, and a pair of feathery antennae. Their life stages include egg, larva, pupa, and adult. Gravid female lays eggs on the water surface. Larvae hatch from the eggs and grow into pupae. Pupae, also called wrigglers, develop further and then emerge from the water as adults.  Adult males feed on nectar whereas adult females feed on blood. The females have specialized proboscis that they use to puncture the skin of their host and to suck blood.

 

 

 

Pandora’s box

Female mosquitoes feed on the blood because they need nutrients from the blood when they produce eggs. Blood does not coagulate in their proboscis because of the presence of anticoagulants in their saliva. They inject saliva into the skin of the host. Inopportunely, the saliva also serves as the main route by which mosquitoes introduce pathogens into the host’s bloodstream. Some of the mosquito-borne diseases include yellow fever, dengue fever, chikungunya, malaria, lymphatic filariasis, tularemia, and Zika disease.

 

 

 

CRISPR, the game changer

CRISPR-Cas9 – a customizable tool that cuts and inserts small pieces of DNA at specific areas along a DNA strand. (Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH)

 

Scientists from Imperial College London had a breakthrough when they used CRISPR technology for a gene drive to completely wipe out a population of mosquitoes grown inside the lab.1

 

Short for clustered regularly interspaced short palindromic repeats, CRISPR is a gene-editing tool that scientists use to splice specific DNA targets and then replace them with a DNA that would yield the desired outcome.2

 

The researchers used CRISPR–Cas9 gene drive to suppress the population of caged Anopheles gambiae mosquitoes (human malarial vector). They modified the gene responsible for determining sex in male mosquitoes and turned the male gene dominant. Then, they added these “hacked’ mosquitoes to a caged population of unaltered male and female mosquitoes. The next generations of females could no longer lay eggs and could not bite. And by the eight generation, the population had no longer had females.3

 

 

Wiping out mosquitoes

Not all species of mosquitoes act as our straight foes. Thousands of mosquito species do not serve as vectors of diseases. Only a few hundreds (about 200) of them transmit human pathogens (e.g. Aedes aegypti, Anopheles spp.). Unfortunately, these few hundreds carry viruses, bacteria, protozoans, and helminthes that can cause serious, even fatal, diseases. Furthermore, current methods to eradicate them, e.g. spraying or fogging using insecticides, proved less ineffective since they developed resistance to such insecticides. Thus, the CRISPR technology could prove useful in this regard. However, the question remains: What will happen when these mosquitoes are completely eradicated from the face of the earth?

 

Obviously, humans reap directly the benefit of eradicating mosquito-borne diseases. However, it might also lead to an irrevocable ecological impact we could regret. Particularly in the food chain, loss of certain mosquito species could lead to the insufficiency of food for insectivores, such as birds and fish.  And over time, humans might eventually suffer as well from this jarring food-chain disturbance.

 

Mosquitoes have lived for so many million years. Do we have the right intent and purpose to deny them the right to live side by side with us? Could it be that we are in the verge of desperation? Definitely, we possess a powerful tool in our hands by the advent of CRISPR technology. However, what good of a purpose would it be if we use it solely for our own good?

 

 

— written by Maria Victoria Gonzaga

 

 

References:

1 Kyrou, K., Hammond, A. M., Galizi, R., Kranjc, N., Burt, A., Beaghton, A.K., Nolan, T. & Crisanti, A. (2018). A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nature Biotechnology. Retrieved from https://www.nature.com/articles/nbt.4245
2 Gonzaga, M. V. (2018). CRISPR caused gene damage? Rise and pitfall of the gene-editor. Biology-Online.org. Retrieved from

CRISPR caused gene damage? Rise and pitfall of the gene-editor


3 Houser, K. (2018 Sept. 25). SCIENTISTS WIPED OUT A MOSQUITO POPULATION BY HACKING THEIR DNA WITH CRISPR. Futurism.com. Retrieved from https://futurism.com/the-byte/gene-drive-mosquitos-crispr?fbclid=IwAR13KtvXDAeOnL7tjTIOL0-E4Q59HHquKev73tiBfirxypfcNkxeZUNEi7A

Reproductive Success of Medicago sativa: Pollen and Resource limitation

Medicago sativa is a perennial flowering plants that belongs to a legume family.  This plant is known in forage crop, grazing, silage, green manure and cover crop.  Medicago sativa develops potential for medicinal uses and thrive mostly in an arid climate. The aim of this particular research is to determine the floral traits and pollinators visitation activities that affect pollen limitations. It also identifies possible effects of resource allocation on pollen supplementation and the impacts of pollen on flower opening.

 

Medicago sativa floral traits and pollinators

Plant reproduction is limited due to pollen resources, floral traits and pollinator activities. Medicago sativa was observed at about 120 hours by collecting pollens and nectars. The pollinator type was then noted. It was then recorded the visitation frequency and behavior of flowers based on insects as effective pollinators or occasional pollinators. The pollinators then, captured using insect nets to find out the presence of pollen grains.

 

The result shows a positive relationship between pollinators visitation frequency and the number of open flowers. It also found out that, it is more efficient for pollinators to visits opening flowers. Since, filaments of Medicago sativa will dry easily particularly in an arid regions. Moreover, flowers of Medicago sativa was completely open and the pollen released between 09:00 to 14:00 hours. Additionally, some insects identified as effective pollinators because it can collect more pollen and visit more often. However, a reduction of pollinators will decline the amount of pollens and reduced the probability of cross pollen transfer.

 

Overall, this research found out that pollen resources is the limiting factor for the reproductive success of Medicago sativa. It also shows that resource reallocation can increase pollen limitation and plants might reallocate among flowers. However, insufficient pollen deposition is typically caused by pollinators assemblage, visitation and abundance.  In which flowers is the main effects of resource limitations and pollinators plays an important role in outcrossing.

 

Source: Prepared by Joan Tura from BMC Ecology

Volume 18:28 August 29, 2018

 

 

 

 

 

 

 

 

 

 

Biomolecule β-Hydroxybutyrate – key to vascular youth?

One of the hallmarks of old age is vascular aging. Researchers found that a biomolecule, β-Hydroxybutyrate (BHB), can serve as a key to turning the time around. Apparently, BHB has anti-aging effects on the vascular system.

 

 

 

β-Hydroxybutyrate – a biomolecule

 

Beta-hydroxybutyrate biomolecule
Molecular structure of the biomolecule, β-Hydroxybutyrate

 

β-Hydroxybutyrate is a biomolecule with a chemical formula, C4H803. Many regard it as a ketone; however, under a strict definition, it would not technically fit as a ketone. That is because its carbonyl carbon binds to only one instead of two other carbon atoms. Nonetheless, BHB appears to be physiologically related to other ketone bodies (such as acetate and acetoacetate) based on the metabolic aspect. For instance, the tissue level of BHB rises during calorie restrictions, fasting, prolonged intense workout, and when following a ketogenic diet.1 Accordingly, BHB level occurs the highest among the three circulating ketones in the body.

 

 

 

β-Hydroxybutyrate – biological sources

The body naturally produces BHB through the process of ketogenesis. Low-carb diet and fasting lead to the rise of BHB level. Firstly, the body breaks down fatty acids to produce acetyl CoA. This precursor goes through a series of reactions leading to acetoacetate synthesis. In turn, the acetoacetate circulates via the bloodstream, and subsequently reaches the liver. The BHB-dehydrogenase enzyme in the liver reduces the acetoacetate to BHB. 1

 

Another biochemical pathway that leads to the synthesis of this biomolecule uses butyrate. The body metabolizes butyrate and produce D-β-hydroxybutyrate through the aid of the enzyme, hydroxybutyrate-dimer hydrolase.

 

 

 

β-Hydroxybutyrate –  biological action

In humans, D-β-hydroxybutyric acid is one of the major endogenous agonist of hydroxycarboxylic acid receptor 2 (HCA2), a receptor protein encoded by the HCAR2 gene. It binds to and activates HCA2. Upon activation, HCA2 can inhibit the breakdown of fats and mediates niacin-induced flushing. Moreover, it induces the dilation of blood vessels.

 

Based on recent research, BHB might serve as a biomolecule that could help turn time around for the vascular system. Old age faces an increased risk to cancer and cardiovascular diseases since the vasculature ages as well. Dr. Ming-Hui Zou, director at Georgia State University, explains. “When people become older, the vessels that supply different organs are the most sensitive and more subject to aging damage….”2

 

 

β-Hydroxybutyrate –  vascular study

biomolecule for vascular youth
The biomolecule, β-Hydroxybutyrate, apparently has anti-aging effects, particularly keeping the vascular system young

 

Zou et al. 2, 3 conducted a study on vascular aging, exploring the link between calorie restrictions and delayed vascular aging. Accordingly, calorie restrictions averted vascular aging.

 

They found that BHB, the biomolecule naturally produced from the liver, has anti-aging effects, particularly on endothelial cells. The endothelial cells line the interior surface of the vascular system. Based on the results, BHB promoted mitosis of endothelial cells, thus, pre-empting vascular aging.3 Furthermore, they saw that BHB binds to a certain protein, which stimulates a series of reactions that consequently rejuvenate, thus, keep the blood vessels young.2

 

 

 

BHB could eventually become a biomolecular tool that promotes mitosis of endothelial cells. In being able to do so, it could help prevent endothelial cell senescence. Hence, this potential rejuvenating effect on the vascular system may soon become valuable not just in keeping the blood vessels young but also in preventing cardiovascular diseases related to old age.

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 Martins, N. (2018 Sept. 26). Beta-hydroxybutyrate or BHB –All You Need to Know. Retrieved from https://hvmn.com/blog/exogenous-ketones/beta-hydroxybutyrate-or-bhb-all-you-need-to-know
2 Georgia State University. (2018 Sept. 10). Researchers Identify Molecule With Anti-Aging Effects On Vascular System. Retrieved from https://www.technologynetworks.com/neuroscience/news/fasting-molecule-delays-vascular-aging-309380
3 Han, Y. M., Bedarida, T., Ding, Y., Somba, B. K., Lu, Q., Wang, Q., Song, P., & Zou, M.H. (2018). β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4. Molecular Cell, 71(6):1064-1078.e5. https://doi.org/10.1016/j.molcel.2018.07.036

Mitochondrial DNA – hallmark of psychological stress

We often hear that stress can be unsettling as it could make us ill when it becomes chronic and overwhelming. However, is there really a biological ratification behind it? Is it scientifically founded? Apparently, independent studies hinted a biological connection indicating how stress can cause biological damage, and eventually lead to certain ailments. And, the mitochondrial DNA — the genome in the mitochondrion appears to play a role.

 

 

 

Biological features of mitochondria

mitochondrial process
Mitochondrial processes that lead to the generation of ATP.
Credit: Boumphreyfr, under the Creative Commons Attribution-Share Alike 3.0 Unported license

 

The mitochondrion (plural: mitochondria) is an organelle that supplies molecular energy for various biological activities. In essence, this rod-shaped structure found within the cell accounts for the generation of ATP, the cell’s major energy source. Thus, the mitochondrion is known to be the “powerhouse of the cell“.

 

Through the process of cellular respiration, glucose (a monosaccharide) is “churned” to extract energy, primarily, in the form of ATP. Firstly, a series of reactions leads to the conversion of glucose to pyruvate. Then, it uses pyruvate, converting it into acetyl coenzyme A for oxidation via enzyme-driven cyclic reaction called Krebs cycle. Finally, a cascade of reactions (redox reactions) involving the electron transport chain leads to the production of ATPs (via chemiosmosis).

 

The mitochondria have their own genetic material, called mitochondrial DNA. Because of this, the mitochondrion is regarded as semi-autonomous and self-reproducing organelle. It means it can manufacture its own RNAs and proteins.  Generally, we inherit the mitochondrial genome maternally, as opposed to the nuclear genome that we inherit from both parents.

mitochondrial DNA
Mitochondrial DNA.
Credit: National Institutes of Health

 

 

 

Mitochondrial fate during stress

mitochondrial DNA and stress
Psychological stress can cause biological damage, such as the release of mitochondrial DNA from damaged and worn-out mitochondria.

 

When confronted with a stressful situation, our body responds intrinsically. We tend to breathe fast. The heartbeat goes wild. Our muscles tense up. And, we sweat profusely. All these responses (so-called “fight-or-flight“) can be an arduous task as they abruptly demand energy. When triggered for so long, eventually, we feel exhausted.  Sooner or later, stress sets in and it takes its toll on our health.

 

The mitochondria work for an extended time just to meet up the spike of demand for energy. In effect, they become vulnerable to damage from too much work.  Inopportunely, the mitochondria have limited repair mechanisms unlike the nucleus.1 And in the end, it results in the disruption of the organelle, thereby, releasing the mitochondrial DNA into the cytoplasm. Eventually, the genetic material reaches the bloodstream where they become genetic cast-offs.

 

 

 

Mitochondrial DNA cast-offs

The ejected mitochondrial DNA, apparently, becomes genetic wastes and stress might have something to do with this outcome. This theory came about based on a series of studies. Firstly, Gong et al. found that chronic mild stress resulted in mitochondrial damage in hippocampus, hypothalamus, and cortex in mouse brains.2

 

Secondly, another team of researchers (Lindqvist et al.) reported that individuals who had recent suicide attempt had higher plasma level of freely circulating mitochondrial DNA in blood than those of healthy individuals.3

 

Thirdly, Martin Picard (a psychobiologist at Columbia University), together with his team, observed similar findings in their participants exposed to a stressful situation. Accordingly, their participants – healthy men and women – were asked to defend themselves against a false accusation. Their blood samples were taken before and after the interview. The researchers found that the mitochondrial DNA in the serum of the participants increased twice 30 minutes after the test. 1 Picard explained that the mitochondrial DNA might have acted like a hormone. Furthermore, he theorized that the ejection of these genetic cast-offs might have mimicked the adrenal gland cells releasing cortisol in response to stress. 1

 

 

 

Mitochondrial DNA as an inflammatory factor

Zhang et al. observed that circulating mitochondrial DNA triggered inflammatory responses. Accordingly, the genetic cast-offs can bind to TLR9 (a receptor) on the immune cell. This binding might have incited the immune cell to respond the same way as they do when reacting with antigens. It might have stimulated the cell to release cytokines that call for other immune cells to the site. 1

 

 

 

So far, these conjectures from independent studies disclose the possible direct biological damage due to stress. There could be a biological insinuation that stress could play a part in the manifestation of ill-health conditions. And, the upsurge of circulating mitochondrial DNA cast-offs is one of them. More information and studies on mitochondrial DNA are delineated on a report on mental health published in Scientific American.

 

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 Sheikh, K. (2018 Sept 13). Brain’s Dumped DNA May Lead to Stress, Depression. Scientific American. Retrieved from https://www.scientificamerican.com/article/brain-rsquo-s-dumped-dna-may-lead-to-stress-depression/
2 Gong, Y. Chai, Y., Ding, J. H., Sun, X. L., & Hu, G. (2011).Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain. Neuroscience Letters, 488 (1): 76-80. https://doi.org/10.1016/j.neulet.2010.11.006
3 Lindqvist, D., Fernström, J., Grudet, C., Ljunggren, L., Träskman-Bendz, L., Ohlsson, L., & Westrin, Å. (2016). Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity. Translational Psychiatry, 6 (12), e971–. http://doi.org/10.1038/tp.2016.236

Porphyromonas gingivalis: Periodontitis bacterium induces memory impairment and neuroinflammation

Porphyromonas gingivalis is a bacterium commonly associated in periodontitis a chronic inflammatory disease in the oral cavity.  Periodontium is composed of periodontal ligament, cementum, alveolar bone and gingiva. Porphyromonas gingivalis is a gram-negative bacterium that contains toxic components. It is characterized by the presence of edema and destruction of tissue supporting the teeth. In which periodontal bacteria enters into circulation that leads to bacteremia and system dissemination of bacterial products. Moreover, Porphyromonas gingivalis can promotes systemic effects through expression of inflammatory mediators like pro-inflammatory cytokines. As a consequence it is confirmed to be associated with systemic diseases such as diabetes, respiratory disease and cardiovascular disease.

Potential effects of Porphyromonas gingivalis

Neurodegenerative diseases have been recognized as the major cause of cognitive and behavioral damage. It is known that peripheral infections could activate microglial cells within the nervous system enhancing development of neurodegeneration. Thus, the inflammatory molecules in the brain could be enhanced by periodontitis that increase inflammatory levels promoting the development of Alzheimer’s disease. In this particular research Porphyromonas gingivalis infection may impair cognition by elevating expression of pro-inflammatory cytokines. It is also shown that the infected mice displayed impaired memory and learning abilities. Elevated levels of pro-inflammatory mediators in the blood can lead to direct or indirect transport to the brain.

 

Periodontal infection caused by Porphyromonas gingivalis promotes neuro-inflammatory response via releasing pro-inflammatory cytokines. In which inflammation induces alterations in neurovascular functions causing increased in blood brain barrier permeability and aggregation of toxins. In brain trauma, infection and presence of endogenic abnormal protein aggregates can activate secretions of TNF-α. That plays a pivotal role in the development and functions of central nervous system. Moreover, aging is also associated to chronic inflammation which exerts additional stress to the brain nerve cells. Additionally, during systemic inflammation the functions of the blood-cerebrospinal fluid barrier were also significantly affected.

 

Therefore, Porphyromonas gingivalis periodontal infection may induce age-dependent brain inflammation. Also periodontitis can cause memory impairment which has a similar effect on the development of Alzheimer’s disease. Furthermore, aging is the major risk factor of Alzheimer’s disease and is correlated with elevated glial responsiveness. And in due course might increase the brain’s susceptibility to injury and disease.

 

Source: Prepared by Joan Tura from BMC Immunity and Aging

Volume 15:6, January 30, 2018

 

Nutrients and bioactive potentials of green and red seaweeds

Seaweeds are macroscopic multicellular algae that have been used as food since ancient time. It was originated in Japan and then China particularly to the people who lived near the coastal areas. In addition to its nutritional value, seaweeds are rich source of structurally diverse bioactive compounds including polysaccharides, phlorotannins and pigments. Because of this, the demand  increases in the global trade wherein Korea is the major producers. In traditional Korean cuisines seaweeds used as soup, snack, pickle, vegetable and salad. Hence, this present research focuses on the edible green and red seaweeds found in Korea.

 

Green and Red Seaweeds Bioactive Compounds

Green seaweeds used to treat stomach disorders and hangovers because it contains 55% polysaccharides, 30% proteins, 13% ash and 1% lipids. It also have micro mineral such as calcium, manganese, iron, selenium, sodium, phosphate and potassium. Additionally, green seaweeds also used to treat wastewater and have significant medicinal value for rheumatism, high blood pressure and diabetes. In recent findings it has potentials bioactive properties to treat cancers and diabetes mellitus. Also it contains essentials oil to inhibit foodborne pathogens, anti-inflammatory, antioxidant and blood lipid reduction. Moreover, it has been used in traditional medicine for sunstroke, urinary diseases and hyperlipidemia. It is also useful to reduce eutrophication in mariculture waters that helps the survival rate productivity of shrimps and prawns.

 

Red seaweeds are the main source of hydrocolloids and contain vitamins A, B and C. It is also a rich source of carbohydrates particularly galactose and glucose. These red seaweeds are popularly known in agar production. And used as a raw material in bio-ethanol industry due to its high level of ethanol extraction efficiency. Likewise, both red and green seaweeds contain antioxidants properties due to its hydroxyl radical scavenging activity. That is responsible for neuro-protection against oxidative stress. In all, seaweeds have potential properties for anticancer, anti-diabetic, anti-obesity, anti-inflammatory, antimicrobial and anti-coagulant.

 

Therefore, seaweeds are vital source of food and medicine on different applications. The presences of secondary metabolites are potential to develop as functional materials due to its promising bioactive properties. Korea is one of the biggest consumers and producers wherein people mostly incorporate seaweeds on daily diets. This research suggests that increase consumption offers healthy benefits as well as utilization of seaweed materials as functional ingredients.

 

Source: Prepared by Joan Tura from  BMC Fisheries and Aquatic Sciences

Volume 21:19, 6 April 2018

 

Turning blood into universal “friendlier” type

One of the crucial needs that arise during or after a devastating natural disaster is the availability of the “universal” blood type O. The increased demand for blood surges following the aftermath of a catastrophy. Storms, hurricanes, and earthquake calamities are major causes for an abrupt call for blood donations. Researchers from the University of British Columbia headed by Stephen Withers knew so well the gravity of this need that they are adamant in finding a way to somehow curb the limitations hampering the availability of a universal, friendlier blood type. Withers and his team recently identified a potential enzyme candidate that appears to be efficient and at the same time cost-effective in converting blood types into type O.

 

 

 

Blood group systems overview

Blood type
Image credit: Amy Claxton, Flickr.com

 

The blood is the circulating fluid in our body that performs multifarious functions. Its major functions are for transporting nutrients, delivering oxygen, moves metabolic byproducts for excretion, providing immune defense, and homeostasis. It is comprised mainly of plasma (55%) and cellular elements (45%) (e.g. red blood cells and white blood cells). The red blood cells (RBCs) are the major cellular component of the blood and are essential for their role in delivering oxygen throughout the body. The white blood cells (WBCs), in turn, are involved in the detection of non-self particles (antigens) and the subsequent immune action against them.

 

Blood type (or blood group) is a classification system used to identify which type the blood belongs to. The blood type is determined based on the presence (or absence) and types of antigens present on the cell surface of the RBCs.  Various blood classification systems are used to classify types; however, the ABO and the Rh systems are the most important ones. The ABO system is used to classify blood into types A, B, AB, and O. The Rh  system, in turn, is used to denote blood as either positive (+) or negative (-) based on the presence and absence of the Rh factor, respectively.

 

 

Why type O blood?

Type O blood is considered as the universal blood because it has neither A nor B antigens on the surface of the RBCs. Type AB blood, in contrast, has both A and B antigens. If A antigens are present on the cell surface of the RBCs, the blood is typified as type A whereas type B has B antigens. Determining blood type is important because blood administered into the body that does not match with the innate blood type can trigger an immune response. Transfusion involving a blood type different from one’s own can instigate the WBCs of the body to attack the transfused blood cells, and this could lead to serious effects. Thus, an individual with type A (Rh-), for instance, can receive transfusions of type A (Rh-) and type O (Rh-). Based on this precept, type O (especially Rh-) can be administered to any blood type.

 

 

 

Metagenomics for creating a universal type of blood

Blood banks constantly need type O. Withers and his team focused their research works in searching for enzymes that can convert types A and B to type O by applying metagenomics. Accordingly, they found enzymes from the human gut that apparently can turn type A and B into O as much as thirty times more efficiently than previously identified enzymes.1 Withers said, “We have been particularly interested in enzymes that allow us to remove the A or B antigens from red blood cells. If you can remove those antigens, which are just simple sugars, then you can convert A or B to O blood.”

 

In reaching their goal, they focused on mucins, which are glycoproteins secreted by the mucous membranes in the gut wall. These mucins in the gut wall display a number of sugars, including antigen A and antigen B. They found that the gut microbiome can cleave these sugars from the gut wall and use them as food source. Using metagenomics, they identify genes from these gut microbial species that code for proteins that cleave target antigens on the cell surfaces of RBCs. Thus, type A blood, for instance, can be converted into type O blood through the enzymes that remove antigen A from the RBCs. The goal is to identify the most economical, most efficient, and safest enzyme that can be used to turn donated blood into a particular type as needed.

 

 

 

Disastrous events take so much of human properties and lives. Apart from the apparent destruction of homes and livestock as an aftermath of natural calamities, blood donations become crucial to save lives of the people needing blood transfusions. Suddenly, life takes a stance on the edge between survival and death. Blood transfusions have to be extensive, safe, and economical. Although research on how to turn blood types into a more universal type has still a long way to go before it can be approved for medical use, this is a significant development.

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 American Chemical Society. (2018, August 21). Gut bacteria provide key to making universal blood (video). American Chemical Society.. Retrieved from https://www.acs.org/content/acs/en/pressroom/newsreleases/2018/august/gut-bacteria-provide-key-to-making-universal-blood-video.html?_ga=2.17288057.1746138702.1535160738-1328130083.153516073