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Category: Research

Regeneration in humans – Finding the gene switch

Regeneration in humans is much more limited compared in other animals. Say for instance when one lost a limb, much as well say goodbye to it for the rest of one’s life. Perhaps, it would be nice if we have higher capacity to regenerate many of our indispensable body parts, like head, limbs, and many other “regeneration-incapables”. Then probably, we might not have to worry much about losing any of them knowing that they will eventually re-grow in due time.

 

 

Regeneration vs. Healing

Humans have the capacity to regenerate. However, we have a very limited capabiltiy to restoring parts of our skin, hair, nails, fingertips, and liver. At the tissue level, surely we have dedicated cells to replace lost and damaged cells. For instance, our non-injured bone eventually replenishes into a full new bone but in a span of ten years. Our skin naturally renews but give it two weeks. The story swerves differently though in the case of an injury.

 

Rather than expending energy into having it replaced with a new one, our body directs its efforts into healing it. So when our skin is deeply damaged, our body fixes it with a scar. Tissue repair mechanisms such as wound healing aren’t really a snag. They forestall pathogenic microbes from using an injured body part as an easy gateway into our body. (Besides, we do have ample microbiota naturally thriving inside of us already) The main goal is to fix it efficaciously, with relatively less effort.

 

 

 

Natural regeneration in humans

In humans, the only tissue that regenerates naturally, consistently, and completely is the endometrium.1 After it slough-offs during a woman’s menstrual period, it grows back by re-epithelialization until the next period. Humans can also regenerate an injured liver provided that the restoration involves as little as 25% of the original liver mass. The liver can grow back to its original size but may not to its original shape. Damaged tubular parts of the kidney can also re-grow. The surviving epithelial cells undergo migration, dedifferentiation, proliferation, and re-differentiation to set a new epithelial lining of the tubule.

 

 

 

Animals with higher regeneration capacities

 

axolotl regeneration
Axolotl (Ambystoma mexicanum) is one of the animals dubbed as masters of regeneration. It can grow back its limbs, even a heart, without a scar. [Photo credit: Mike Licht, Flickr]

 

Some animals have higher capacity to re-grow lost body parts. Sharks, skates, and rays can regenerate their kidneys. They can regrow an entire nephron, which humans cannot. A lizard would drop its tail as a mode of escape; its tail will be fully restored over time anyway. Sharks do not have qualms about losing teeth. They can replace any of them more than a hundred times in their lifetime. Axolotl can replace its broken heart. A starfish will once again be stellar upon the return of a lost arm. In fact, even its lost arm can fully regenerate into an entire starfish as long as the central nerve ring remains intact.2 A decapitated planarian worm needs not worry about losing its head; it can grow back, together with its brain, including the memories.2 Without a doubt, many of these animals are simply masters of their craft – regeneration.

 

 

Regeneration genes

Researchers from Harvard University published their new findings on whole-body regeneration capacity of the three-banded panther worm.3 They uncovered DNA switches that seemed to regulate genes that have a role in the regeneration process. Accordingly, they found a section of a non-coding DNA that controlled the activation of a master gene in which they called the “early growth response” (EGR) gene. When active, the EGR gene seemed like a power switch that turns on and off certain genes in the coding region during regeneration. On the contrary, when deactivated, no regeneration occurred.

 

Surprisingly, humans have EGR gene, too.  So why doesn’t it lead to greater regeneration capacities as it does in the three-banded panther worm? The researchers explained that while it works in the worm, it doesn’t work the same way in humans. The wiring may be different. The worm’s EGR gene may have germane connections that are absent in humans.

 

 

 

Switching the gene on

Regeneration in humans
Regeneration in humans is limited. If only we knew the switch that could amplify our regeneration capacity then we might not have to worry much about losing a body part. [Photo credit: Pete Johnson, Pexels]

 

Induced regeneration in humans is one of the goals of regenerative medicine. This field of medicine seeks new ways to give our regenerative capacity a boost. One of the ways is to look “molecularly”. Researchers are looking into the gene “Lin28a“. When active, this gene can reprogram somatic cells into embryonic-like stem cells. Accordingly, it has a role in tissue regeneration and recovery. However, the gene is naturally turned off in adults. Research in boosting our regenerative capacities is ongoing. Switching our organs from being regeneration-incapable to regeneration-capable may just be a matter of discovering the gene switch that could enhance regeneration capacity of humans.

 

 

— written by Maria Victoria Gonzaga

 

 

References:

1 Min, S., Wang, S. W., & Orr, W. (2006). “Graphic general pathology: 2.2 complete regeneration”Pathology. pathol.med.stu.edu.cn. Retrieved from [Link]

2  Langley, L. (2013, August 28). “Pictures: 5 Animals That Regrow Body Parts”. National Geographic News. Retrieved from [Link] ‌

 

Fasting boosts human metabolism, has anti-aging effects

In the advent of 2019, we are inspired to set new goals, pursue life-long dreams, or simply make better choices. Perhaps, one of the most common reveries we wish to realize is to be able to adopt a healthier kind of lifestyle. With this in mind, some of us look for ways to feel dutifully healthier, such as by managing our weight. So, many would turn to fad diets and caloric restrictions that promise to help. One of them is intermittent fasting. Based on studies, intermittent fasting does not only help trim weight but it seems to offer further health benefits as well.

 

 

 

Intermittent fasting – overview

 

intermittent fasting
Scientists found that fasting boosted human metabolism. This could mean that fasting may slow aging in humans. [Image credit: Zeyus Media]

 

 

In May 2018, I wrote the article: Intermittent Fasting – benefits and caution. There, I tackled briefly about intermittent fasting, its benefits, and potential risk. In essence, intermittent fasting is a cyclic pattern of a period of fasting and a subsequent period of non-fasting. The most common forms are: (1) whole-day fasting and (2) time-restricted eating. Whole-day fasting entails one-full day of “no eating”, done twice a week (thus, referred to as “5:2 plan“). In time-restricted eating, there is an interval of fasting and non-fasting on a daily basis. It could be half a day of fasting, and then the remaining half as the non-fasting period.  With intermittent fasting, it’s not so much about “what to eat…” or “how much…” Rather, it’s more about a question of when.

 

 

 

Intermittent fasting became popular because it does not only help curb weight but it also implicates other health benefits. It apparently slows aging and boosts the immune defense.[1] However, as I pointed out in that article, caution should still be taken. Intermittent fasting is not for everyone, especially those who are immunocompromised and underweight.[2]

 

 

 

Rejuvenating effects of fasting

Previously, I mentioned that studies confirming the health benefits of fasting were done on non-human subjects (e.g. rodent models). Without much scientific proofs of efficacy on humans, what would, therefore, be definite is doubt.  However, on January 29 of this year, a team of scientists from Okinawa Institute of Science and Technology Graduate University (OIST) and Kyoto University reported rejuvenating effects of fasting on human subjects. They published their findings in Scientific Reports.[3] Accordingly, they analyzed the blood samples from four fasting individuals. They also monitored the levels of metabolites involved in growth and energy metabolism. What they found was quite interesting and promising.

 

 

 

Dr. Takayuki Teruya, one of the researchers of the team, said that their results implicated the rejuvenating effects of fasting. They found that many metabolites increased significantly, about 1.5- to 60-fold, in just 58 hours of fasting. In their previous study, they identified some of these metabolites (e.g. leucine, isoleucine, and ophthalmic acid), that typically deplete with age. According to Dr. Teruya, they found that the amount of these metabolites increased again in individuals who fasted. Also, they conjectured that fasting could possibly promote muscle maintenance and antioxidant activity based on the metabolites they found. Hence, fasting may probably promote longevity as well. Dr. Teruya further said that this was not yet known until now since most studies that have said so used animal models.[4]

 

 

 

Fasting increased metabolism

During fasting, the body turns to alternate energy stores when carbohydrates are not available. Thus, the less-common metabolites from alternative metabolic pathways superseded the typical metabolites from carbohydrate metabolism. They identified butyrates, carnitines, and branched-chain amino acids as some of the metabolites that accumulated during fasting. [4] Apart from this, the researchers also found an increase in Citric acid cycle intermediates. This means that aside from prompting alternate metabolic pathways, fasting has also augmented the common metabolic activities. The metabolism of purine and pyrimidine seemed also heightened, indicating an increase in gene expression and protein synthesis. Because of this, the researchers also saw a boost in antioxidants (e.g. ergothioneine and carnosine) that protect cells from the free radicals produced by metabolism. The researchers assume to be the first to provide evidence of antioxidants as a fasting marker. [4]

 

 

 

This new-found proof infers that fasting seems to have some anti-aging effects, this time, on human subjects. Their next step is to see if they could duplicate the results in a larger-scale study. For now, let us remain cautious, look for indubitable substantiation, and weigh in the benefits and risks of all available options.

 

 

 

— written by Maria Victoria Gonzaga

 

 

References:

 

1  Cohut, M. (2018). Intermittent fasting may have ‘profound health benefits’. Retrieved from [Link]

2  Longo, V. D., & Mattson, M. P. (2014). Fasting: Molecular Mechanisms and Clinical Applications. Cell Metabolism, 19 (2), 181–192. [Link]

3 Teruya, T., Chaleckis, R., Takada, J., Yanagida, M. & Kondoh, H. (2019). Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood. ”Scientific Reports, 9”(1) DOI: 10.1038/s41598-018-36674-9.

4  ‌ Okinawa Institute of Science and Technology (OIST) Graduate University. (2019, January 31). Fasting ramps up human metabolism, study shows. ScienceDaily. Retrieved from [Link]

On Mate Selection Evolution: Are intelligent males more attractive?

A study published in Science on January 11 seems to be the first to lay empirical evidence that concur with Charles Darwin’s hypothesis: … that mate selection might have contributed to the evolution of intelligence or cognitive abilities. Scientists from China and the Netherlands collaborated in a study on budgerigars, Melopsittacus undulatus. Based on what they observed, problem-solving skills apparently increased the attractiveness of male birds. Accordingly, female birds chose to spend more time with male birds that appear to be smarter.[1]

 

 

Darwin on mate selection

In animal kingdom, mate selection is a real deal. One of the generalized traits that distinguish the animal from the plant is the former’s tendency to select a mate. Animals, including humans, have their set of preferences when it comes to choosing a mate. While plants chiefly let nature do the “selection” for them, animals tend to seek a potential mate by themselves. And when they find a suitable mate of their choice, they often make a conscientious effort to succeed at coupling. In particular, males engage first in a courtship ritual, for example, by wooing a female with a song, a dance, or by a display of beauty or prowess.

 

Sexual selection evolved as one of the means of natural selection. A male, for instance, chooses a female to mate with, and, if need be, may tenaciously compete against other males to stack the odds in his favor. Charles Darwin’s long-standing theories on sexual selection are still relevant to this day. Darwin believed that sexual selection had a key role in how humans evolved and diverged into distinct human populations.[2] In view of that, sexual selection could have contributed as to how intelligence evolved.

 

 

 

Intelligent males, more attractive

 

budgerigars on mate selection
Female budgerigars (also called parakeets or budgies) apparently prefer smarter mates, according to a study. This finding seems to support Charles Darwin theory on mate selection.

 

Many studies on birds revolved around the notion that female birds favor male birds with vibrant feathers or stylish songs. A recent study claims that intelligence is preferred over such fancy features and skills.

 

In the first experiment conducted by Chen and colleagues[3], small budgerigars (Australian parrots) were observed inside their cages to test the hypothesis that intelligence might affect mate selection. To do that, they allowed each female budgerigars to choose among a pair of similarly-looking male budgerigars to interact with. The chosen males were called preferred whereas those that were not were referred to as the less-preferred. Next, they trained the less-preferred males into learning a skill that opens closed lids or boxes. They, then, allowed the female budgerigar to observe the less-preferred male demonstrate the skill. Consequently, almost all of the females changed their preference. They chose the less-preferred males over the initially preferred males.

 

To test if this preference was social rather than sexual, they conducted a second experiment with a similar experimental design but this time a female budgerigar was exposed to two females (instead of males). The results showed that none of the female budgerigars changed their preferences. [1, 3] Based on these experiments, the researchers concluded that the demonstration of cognitive skills altered mate preference but not necessarily social preference.

 

Video of the animal model, male budgerigar that learned a problem-solving skill that seemingly increased its attractiveness to females. [Credit: Hedwig Pöllöläinen].

 

 

Conclusion

Why did mate selection evolved? The answer could be associated with the species survival or longevity. Individuals must be able to stay in the mate selection pool, if not on top of it. In general, males deemed as superior or “preferred” will gain higher chances at mating, and thereby will have better opportunities at transmitting their genes as they dominate the access to fertile females. Females, on the other hand, gain an upper hand from the mate selection by being able to choose the seemingly finest among the rest. Females must choose. That is because they have a generally limited reproductive opportunity to give life to. Moreover, the energy that a female invests in producing an offspring is so great that it has to be worth it.

 

 

— written by Maria Victoria Gonzaga

 

 

References:

 

1  Chen, J., Zou, Y., Sun, Y.-H., & ten Cate, C. (2019). Problem-solving males become more attractive to female budgerigars. Science363(6423), 166–167. https://doi.org/10.1126/science.aau8181

 

2  Jones, A. G., & Ratterman, N. L. (2009). Mate choice and sexual selection: What have we learned since Darwin? Proceedings of the National Academy of Sciences106(Supplement_1), 10001–10008. https://doi.org/10.1073/pnas.0901129106

 

3  GrrlScientist. (2019, January 11). Problem-Solving Budgies Make More Attractive Mates. Forbes. Retrieved from https://www.forbes.com/sites/grrlscientist/2019/01/10/problem-solving-budgies-make-more-attractive-mates/#515f24d66407

 

Aerobic exercise modifies fine particle exposures to young adults

Aerobic exercise contributes to the prevention and treatment of various chronic diseases as well as helps improves endothelial function. It is also beneficial in adaptation of the cardio-pulmonary system and infection resistant. Moreover, aerobic exercise attributes to the release of vasoconstrictor substances and increased nitric oxide availability. However, exposure to fine particles in ambient condition linked to some adverse health effects. This includes oxidative stress, pulmonary systemic inflammation, increased blood coagulation and vascular imbalance. Aerobic exercise in polluted environments increased inhalation of air pollutants due to increased respiratory rate and reduction of nasal resistance. Also, long-term exercise aggravates air pollutant which causes associated respiratory impairment.

 

Air pollutant exposure during aerobic exercise

There were 20 healthy non-smoking male subjects on this study and aerobic exercise frequencies have been recorded. Wherein indices measured including fractional exhaled nitric oxide, blood pressures; cytokines exhaled breath condensate and pulse-wave analysis. However, the biomarkers of eosinophilic airway inflammation were positively associated with air pollution exposure. Also, the fractional exhaled nitric oxide concentrations were greater in high exercise frequency. Thus, explain that high strength exercise might be at higher risk of particle-mediated respiratory symptoms.

 

Aerobic exercise is associated with the exposure to air pollutant which caused respiratory inflammation and arterial stiffness. In terms of cardiovascular responses the increased in aortic augmentation pressure indicate higher pulse-wave velocity. Furthermore, aerobic exercise at moderate frequency had a greater protective effect against cardiopulmonary health risk than low or excessive exercise.

 

Therefore, long-term habitual aerobic exercise in severely polluted areas may strengthen the resistance of the cardiovascular system. But increase the risk of pollutant-related airway inflammation. In addition, surrogate biomarkers of atherosclerosis, arterial wall thickness have been decreased following the long-term aerobic exercise. And also low cardiopulmonary fitness is the key indicators for cardiovascular mortality and coronary heart disease.

 

Source: Prepared by Joan Tura from BMC Environmental Health

Volume 17:88 December 13, 2018

Mitochondrial DNA not just from moms but also from dads?

If one wants to trace down lineage, that person could turn to the cell’s powerhouse, the mitochondrion. This organelle contains its own special set of DNA believed as inherited solely from mothers across generations.  Thus, looking at the mitochondrial DNA (by mtDNA genealogical DNA testing) could help track down lineage, and for this reason, help determine ancestral or familial connection. Recently though, a team of scientists reported that the mitochondrial DNA is not solely inherited from the mothers. New empirical evidence of biparental inheritance of mitochondrial DNA implicates the need to rectify the long-held notion that the inheritance of mitochondrial genome is exclusively matrilineal or female line.

 

 

Mitochondrial DNA

The mitochondrion (plural: mitochondria), reckoned as the powerhouse of the cell, generates metabolic energy, especially the form of adenosine triphosphate (ATP). And it does so through the process referred to as cellular respiration. Apart from that, the organelle is also described as semi-autonomous since it has its own genetic material distinct from that found in the nucleus. The nucleus contains more genes organized into chromosomes and in charge for almost all of the metabolic processes in the body. On the contrary, the genetic material in the mitochondrion – referred to as mitochondrial DNA – is relatively fewer in number. It carries the genetic code for the manufacturing of RNAs and proteins necessary to the various functions of the mitochondrion, such as energy production.

 

(Recent news on the evolutionary origin of mitochondria, read: Prokaryotic Ancestor of Mitochondria: on the hunt)

 

(You may also want to read: Mitochondrial DNA – hallmark of psychological stress)

 

Mitochondrial inheritance

In humans, the mitochondrial DNA is believed to be inherited solely from the mother. This notion stems from the events that happen at fertilization. The sperm contains on its neck a helix of mitochondria that power up the tail to swim toward the ovum. And when the sperm finally makes its way into the ovum, it leaves its neck and tail on the cell surface of the ovum. Mitochondria that are brought into the ovum would eventually be inactivated and disintegrated. Thus, the mitochondria in the ovum are the only ones that the zygote eventually inherits. A human ovum has an average of 200,000 mtDNA molecules.1 For this, certain traits and diseases involving mitochondrional DNA implicate maternal origin.

 

 

 

Inheritance of mitochondrial DNA– not exclusive

mitochondrial dna eve
The theory of Mitochondrial Eve is based on the exclusivity of human mitochondrial DNA inheritance to the female line, which when traced would lead to only one most recent woman, “Eve”. (Image credit: Ludela, Creative Commons Attribution-Share Alike 3.0 Unported)

 

The theory of Mitochondrial Eve holds that tracing the matrilineal lineage of all recent human beings would lead to all lines converging to one woman referred to as “Eve“. The theory is based on the exclusivity of human mitochondrial DNA inheritance to female line. Nevertheless, independent empirical findings and clinical studies challenge this precept.

 

For instance, Schwartz and Vissing2 reported the case of a 28-year-old man with mitochondrial myopathy. Accordingly, the patient had a mutation (a novel 2-bp mtDNA deletion in ND2 gene). Normally, the gene encodes for a subunit of the enzyme complex I of the mitochondrial respiratory chain. Thus, the faulty gene affected the production of such enzyme, which, in turn, led to the patient’s severe, lifelong exercise intolerance. Furhter, Schwartz and Vissing2 pointed out that the patient’s mitochondrial myopathy was paternal in origin.

 

Recently, a team of researchers observed paternal inheritance of mitochondrial DNA, but this time, on 17 people from three different families.3 They sequenced their mitochondrial DNAs and they discovered father-to-offspring transmission.

 

 

Conclusion

The mitochondrial DNA is said to be a mother’s legacy to her offspring. However, recent studies indicate that the father could also transmit it to his progeny. Somehow, paternal mitochondrial DNA gets into the ovum. Rather than disintegrated or inactivated, it gets expressed. Mitochondrial DNA from the fathers may not be as rare as once thought.  If more studies will corroborate soon, this could debunk Mitochondrial Eve theory. It might also render mtDNA genealogical DNA testing questionable. And, we may also need to start looking to the other side of our lineage to fathom hereditary diseases arising from faulty mitochondrial DNA.

 

 

— written by Maria Victoria Gonzaga

 

 

References:

 

1 Mitochondrial DNA. (2018). Biology-Online Dictionary. Retrieved from https://www.biology-online.org/dictionary/Mitochondrial_DNA

 

2 Schwartz, M. & Vissing, J. (2002). “Paternal Inheritance of Mitochondrial DNA”. New England Journal of Medicine. 347 (8): 576–580.

 

3 Luo, S.,  Valencia, C.A.,  Zhang, J., Lee, N., Slone, J., Gui, B., Wang, X.,  Li, Z.,  Dell, S., Brown, J., Chen, S.M.,  Chien, Y., Hwu, W., Fan, P.,  Wong, L.,  Atwal, P.S., & Huang, T. (2018). Biparental Inheritance of Mitochondrial DNA in Humans. Proceedings of the National Academy of Sciences 201810946. DOI:10.1073/pnas.1810946115

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

Wild dolphins learn to “tail-walk” on the water, yet it’s just a fad

Dolphins performing acrobatic tricks have, time and again, fascinated and mesmerized people. As early as 1860s, capturers took dolphins and other cetaceans (e.g. whales and porpoises) out of their aquatic habitats and held them in captivity in various parts of Europe and North America. At first, they kept them in a dolphinarium mainly as an amusement for a paying audience. Later on, they discovered that these aquatic marvels could be taught to perform tricks. Since then, people have gravitated to various dolphin shows as one of their “must-dos” off their bucket list.

 

 

 

Dolphins learning tricks

 

bottlenose dolphins
Dolphins have long fascinated people with their acrobatic tricks

 

The tricks that dolphins can do seem limitless. Apart from their fantastic leaps and bounds, they can do complex tricks like tail-walking, playing ball, synchronized swimming, and rhythmic gymnastics. How do they learn these tricks? Trainers use positive reinforcement method to teach dolphins the jaw-dropping tricks.  Accordingly, they reward them with food whenever they do a trick correctly. Watching them do these tricks, though, seems that they perform not only for the food reward but also for their own enjoyment based on their playful nature.

 

dolphins porpoising
Porpoising behavior of dolphins

 

 

Wild dolphins’ ballistic jumps

Frequently, wild dolphins leap above the water surface. They do so by swimming fast near the surface, and then execute a ballistic jump.  This behavior, called porpoising, seems a demonstration of their playful behavior. Nevertheless, another hypothetical reason surfaced.  Accordingly, this porpoising behavior points to the benefit it furnishes. The friction up in the air is less; therefore, porpoising would help save dolphin energy.1

 

Seeing dolphins doing leaps and bounds in the wild is something that is truly remarkable yet not unusual. However, a pod of playful aquatic creatures in the wild were observed doing a trick rarely seen in the wild. Furthermore, the trick was something that they learned from a formerly captive dolphin.

 

 

 

Wild dolphins’ tail-walking trick

Recently, a study2 reported what they observed in wild dolphins. They saw a pod (particularly, a group consisting of nine dolphins) off the Australian coast that learned from a previously captive dolphin how to “walk” on water using their tail.

 

Tail walking is one of the fundamental tricks taught to captive dolphins. It involves rising vertically out of the water. Then, the dolphin moves forward or backward on top of the water. This skill is rarely seen in wild dolphins.2

 

Whale and Dolphin Conservation, together with the universities of St Andrews and Exeter, conducted a thirty-year study where they revealed that dolphins in the wild were able to learn a human-coached tail-walking trick from Billie. Billie is a rescued dolphin from a creek near Adelaide’s Patawalonga River in 1988. The dolphin was in captivity temporarily. During its captivity, it learned how to tail-walk. When it was released into the wild, it taught its companions by continuing to demonstrate the skill. Soon after, its peers copied it. In 2011, nine dolphins began tail walking. However, this spectacular display of “walking” by fins turned out to be just a fad. The number of wild dolphins that tail walk declined over time. As of 2014, only two of them remained to demonstrate the skill. 2

 

Watch here:

Conservation efforts

Dolphins, just as all the other living beings, deserve an inhabitable space in order to thrive and keep surviving. The ability of the dolphins to imitate skills could be used in spreading learnt behaviours that could be beneficial to their survival.  The lengthy study that tracked the tail-walking behavior of Billie and the local dolphin community for years revealed an important insight. Accordingly, dolphins learning a behavior from each other can persist from one generation to the next. However, there is a tendency that certain learnt behaviors will fade, and, inopportunely, vanish through time.

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 Weihs, D. (2002). “Dynamics of Dolphin Porpoising Revisited”. Integrative and Comparative Biology. 42 (5): 1071–1078. doi:10.1093/icb/42.5.1071
2 Whale and Dolphin Conservation. (2018 Aug. 29). WILD DOLPHINS LEARN FROM EACH OTHER TO ‘WALK ON WATER’…BUT IT’S JUST A FAD. Retrieved from https://uk.whales.org/news/2018/08/wild-dolphins-learn-from-each-other-to-walk-on-waterbut-its-just-fad
3 Whale and Dolphin Conservation (WDC). (2014 Nov. 5). Dolphins tailwalking – Port River, Adelaide | Whale and Dolphin Conservation. Retrieved from https://www.youtube.com/watch?v=6tn5TJfR3k4