As Many Exceptions As Rules: mitosis

Showing posts with label mitosis. Show all posts

Wednesday, May 1, 2013

Venomous Plants – A Hairy Situation

Biology concepts – venom, toxin, poison, nettle, urticating hairs, trichomes, defense behavior

The cobalt blue tarantula is a beautiful old world

tarantula, but not very cleverly named. They are

popular as pets, even though they are fast,

aggressive and have a potent venom. Fortunately,

they don’t have urticating hairs.

A tarantula, a jellyfish, and an ongaonga tree walk into a bar – O.K., maybe not the best start. But these three organisms do have something in common, something that has been recognized since the time of their classification and naming. Follow along.

Tarantula spiders are a popular example of venomous arthropods, arachnids to be exact. “Tarantula” is a vague term as it is used in the general population. The name comes from Taranto, Italy and came to mean any unknown, hairy, long-legged spider. In scientific taxonomy, tarantulas belong to the family Theraphodsidae, a group containing at least a dozen subfamilies and more than 900 species.

Many tarantulas have impressive fangs that deliver potent toxins to their victims. The fringed ornamental tarantula (Poecilotheria ornate) has produced a coma in a human; however, no known tarantula possesses venom that is acutely lethal to people.

But biting isn’t the only way tarantulas can defend themselves. Besides giving you the heebie-jeebies, two subfamilies of tarantula spiders have defenses called urticating hairs. These hairs are easily lost from their hairy backs or legs when the spider is touched by a predator. These small hairs can lodge in the eyes or skin of predators and cause significant physical irritation, enough to ward off a predator.

There are at least four types of urticating hairs, each differing in size and in the type of predator against which they are most effective. The old world tarantulas have type II urticating hairs that are dislodged by touch, but some tarantulas from the Americas can go one step further. They can fire their urticating hairs from a distance (types I, III or IV).

Urticating hairs often cause urticaria (hives), but

sometimes the red bumps will coelesce and form a

rash. And if you allergic, as seen here, the rash will

become big, ugly, and painful. You can see blister

development at the bottom. Explain to me why he is

affected on his belly?!

Species like the chilean rose and the mexican red-knee tarantulas have urticating hairs that can be fired by kicking their back legs against the back of their abdomen. When threatened, the tarantulas turn and rise up on their legs – ready! They point their abdomen at the threat – aim! And then they rub their legs against their abdomen and release a cloud of hairs toward the target – fire! This leaves a bald patch on their back and a very annoyed predator.

Most urticating hairs are mildly irritating to humans, unless you hold the spider up to your face. This is what happened in 2013 to a three year old boy at his birthday party. He held a rose tarantula up to his face to get a good look, and got two eyes worth of uritcating hairs! He cried for days, as they are so small as to become completely buried in the cornea and cannot be removed. He has made several subsequent trips to the hospital for care.

Other tarantulas have more damaging urticating hairs. The Goliath Birdeater has larger hairs that can cause very bad rashes, and feel like fiberglass shards embedded in the skin. Some people will become allergic to the hairs, and the rash and reaction will be even worse (see the picture above).

So what has tarantula hair got to do with jellyfish or the ongaonga tree? Urtica is the Latin word for “nettle,” and the ongaonga tree is also known as the tree nettle or Urtica ferox. And the Greek word for nettle is “cnida,” as in cnidarians – like the jellyfish and coral we talked about two weeks ago. All three of these types of organisms use stinging cells for defense or offense.

Cnidarians use nematocysts to envenomate their prey, shooting toxin filled harpoons at the target. Tarantulas (and some caterpillars) use urticating hairs, not to poison but to irritate their predators. And there are some plants, the nettles, which use urticating hairs as venom delivery systems – the best of both worlds.

The nettles (genus Urtica, approximately 80 species) have hollow uricating hairs that can deliver toxins when they are broken off and embedded in an unfortunate victim. The hairs are actually modified trichomes, epithelial structures found in many plants that are merely raised areas on the plant surface.

Trichomes evolved many variations, those termed “hairs” can be thick or thin, long or short, fuzzy or smooth. Some may be used for water absorption or evaporation, while others will physically impede the movement of insects along the plant, or act as sensors. Venus flytraps (Dionaea muscipula) have three different kinds of trichomes; two secrete digestive juices and one is the sensitive trip wire for closing the trap.

These are the trichomes (stingers) of the ongaonga

nettle. Most nettles have smaller hairs, but this makes

for a more ominous picture. Remember that it isn’t

just their sharp points, they contain venom too.

Typical toxins included in nettle tricomes are formic acid, like in many ant species, and neurotransmitters like serotonin, and histamine. The pain or itch goes away in a few hours. They raise red welts that itch, called hives. In scientific terms, all hive-producing reactions are called urticaria. Get the connection? Most nettle trichome envenomations, like those from Urtica dioica (common nettle) are irritating, but little else.

However, the ongaonga tree (Uritca ferox) is the exception. There has been at least one death associated with just brushing against it. The ongaonga has unusually large spines; the lightest touch brings pain for more than five days. Its neurotoxins also include an acetylcholine (Ach)-like chemical, yet another neurotransmitter.

The late symptoms can include breathing problems, blindness and paralysis. A 21 year old student developed a paralysis after a brush with the ongaonga. The neurotoxin caused her motor nerves to malfunction, firing too slowly and without pattern. It took weeks for her to recover.

But the news isn’t all bad. Nettle toxins may be used to in medicine, including diabetes, infection and even liver damage. A 2013 study in India treated rats with common nettle oil before performing a partial liver removal. The oils helped promote liver regeneration and decreased cell death after surgery. They also reduced the amount of oxidative damage in the surviving cells. So if you plan on destroying your liver, go run through a nettle patch first. However, I couldn’t find any studies using ongaonga oils – it is just too toxic. So be sure of your nettle patch species prior to your liver-protecting frolic.

A strange picture to see here, but follow along. You can

have part of your liver removed if it is damaged and live

just fine. A partial removal is called a hepatectomy. Some

parts can even regenerate after you have them removed.

Hepatectomy is important, as it makes it possible to have

living liver donors – you give someone part of your liver,

and you grow it back. This is where the nettle medicine

could be useful.

Our king of venomous plants comes from a different genus of the same family of plants as the nettles. You would think a plant that could kill you by touch would have a tough name, but it turns out to be just another insult added to the injury. You have tell your best buddies that you are laid up for weeks by a plant; and when asked, you have to tell them it was the “gympie gympie!” I can hear the laughter now.

The gympie gympie (Dendrocnidae moroides) lives in Australia, the land of painful deaths. The Australian Geographic website says that being envenomated by the gympie gympie is like, “being burnt with hot acid and electrocuted at the same time.” It has killed people, horses, and dogs.

Minor stings can last for hours to days with increased heart rate and sweating. The gympie’s trichomes seem to be silica based, like glass. You can heat them with a flame until they glow red, but they will still hold their shape. Add being stabbed with glass shards to the description of the gympie's sting.

Severe encounters can bring pain for months, with symptoms waning and then brought back by hot or cold air, water, or rubbing. Some people have shot themselves to relieve the pain, while others have had to be strapped to the bed.

There isn’t much you can do to treat the pain, but you might be able to shorten the length of your torture. The best first aid is to immediately apply hair removal wax and yank out the trichomes. You go for a hike and end up with silky, smooth skin and a pain that won’t stop – oh, wait, that could be just be describing the waxing.

The gympie gympie has huge leaves, like it is trying to ruin

your day. You can’t even see the hairs here, they are too

small. But you know it if you touch it. Did this guy lose a bet?

Just being this close is a very bad idea.

Usually the pain comes from rubbing against the leaves, stem, or twigs. But the gympie wants to reach out and touch you, even if you don’t reach out and touch it. It sheds its urticating hairs all the time, so if you hang around a tree long enough, you will get a nosebleed and start to sneeze painfully. And you can’t wax the inside of your nose ….. I hope.

Fortunately, few deaths have been associated with the gympie gympie. It grows in the rainforests of northeast Australia where the population is very low, about 5-10 people per 2.5 sq. mile. The aborigines live here, and they actually eat the berries of the gympie gympie. Since all its trichomes point one direction, the natives know how to move along the stems and leaves in the right direction to harvest dinner. Apparently the berries aren’t poisonous.

D. moroides toxins include those said to act as neurotransmitters Ach, serotonin, and histamine, but their chemical structures are different. They also include moroidin, a short peptide toxin that was first isolated from the leaves and stalks of the gympie.

No, this isn’t a picture of some electrical spark experiment

gone wrong. The green spines are the mitotic spindle and

the red blobs are the chromatids being pulled apart during

mitosis. More mitoses, more cell divisions. More divisions,

more cells. Too many more cells = cancer. It would be nice

to stop the spindles in that case.

Moroidin is a mitotic inhibitor; it interrupts the polymerization of tubulin during the formation of the mitotic spindle. If no spindle forms, then there is no alignment or segregation of chromatids during mitosis, so no cell division. Moroidin is supposed to be the factor that makes the sting pain last a long time, but not enough research has been done in this area. No one can even tell me specific chemicals the gympie possesses or how it causes pain! How can we make use of it in medicine if we don’t know how it works? I would think that a mitosis inhibitor might work well against cancer – let’s get to work people!

School is winding down, so why don't we start our summer posts. Each week will be a separate question in biology, from misconceptions to things that make you wonder, to weirdness galore. Next week - how good are different species at going without oxygen, and who can hold their breath the longest?

Oguz, S., Kanter, M., Erboga, M., Toydemir, T., Sayhan, M., & Onur, H. (2013). Effects of Urtica dioica on oxidative stress, proliferation and apoptosis after partial hepatectomy in rats Toxicology and Industrial Health DOI: 10.1177/0748233713480211

Hammond-Tooke, G., Taylor, P., Punchihewa, S., & Beasley, M. (2007). Urtica ferox neuropathy Muscle & Nerve, 35 (6), 804-807 DOI: 10.1002/mus.20730

For more information, see:

Tarantula urticating hairs –

http://arachnophiliac.info/burrow/urticating.htm

http://regalpet.com/content.php?1052-Tarantulas-Urticating-Hairs

http://www.animalcorner.co.uk/venanimals/ven_spidtarnw.html

http://www.arachnoboards.com/ab/showthread.php?240029-Best-way-to-treat-tarantula-urticating-hair

http://www.youtube.com/watch?v=vDkSIrbw5gA

http://arthropoda.wordpress.com/2010/01/30/tarantulas-attack-with-their-back-hair/

https://sites.google.com/site/tarantuladb/resources/urticating-hairs

http://tarantula-care.com/urticating-hairs/

http://ezinearticles.com/?The-Tarantula-Defense-Mechanism---Urticating-Hairs&id=1960205

Nettles –

http://www.richsoil.com/nettles.jsp

http://www.herbwisdom.com/herb-nettle.html

http://www.webmd.com/vitamins-supplements/ingredientmono-664-Urtica%20%28STINGING%20NETTLE%29.aspx?activeIngredientId=664&activeIngredientName=Urtica%20%28STINGING%20NETTLE%29

http://www.blueplanetbiomes.org/stinging_nettle.htm

http://www.kew.org/plants-fungi/Urtica-dioica.htm

http://www.nzpcn.org.nz/flora_details.aspx?ID=1354

http://www.youtube.com/watch?v=yGZBlhJpcT8

http://www.trimblefoundation.org.nz/urtica-ferox-onga-onga-at-rewanui/

http://www.nhm.ac.uk/nature-online/species-of-the-day/scientific-advances/disease/urtica-dioica/

http://depts.washington.edu/propplnt/Plants/Urtica%20dioica.htm

Gympie gympie –

http://www.australiangeographic.com.au/journal/gympie-gympie-once-stung-never-forgotten.htm

http://www.youtube.com/watch?v=nkTlaF1sP_A

http://therovingapothecary.blogspot.com/2012/11/a-curious-australian-plant-gympie-gympie.html

http://www.ebaumsworld.com/video/watch/81008069/

http://blog.cairnswildlife.com.au/gympie-gympie-%E2%80%93-better-known-to-us-as-the-stinging-tree/

http://wildflowerfinder.org.uk/Flowers/N/Nettle%28Stinging%29/Nettle%28Stinging%29.htm

Wednesday, January 16, 2013

When Too Much Is Just Enough

Biological concepts – endoreplication, endocycling, endomitosis, decidualization, trophoblast, megakaryocyte

Last week we learned that polyploidy plays a role in cancer development and is the number one cause of spontaneous abortions in humans. Polyploidy is just no darn good.

There’s alot to fret about once you hit the

atmosphere. But take heart, you’ve already found

a way to make a cancer-like pathway work for you.

Don’t worry about the details, you’ll get it all in

Biology class.

But what if I told you that this same evil process is crucial for the birth of every baby that has ever come kicking and screaming into this cold, cruel world? Without some very specific polyploid cells, none of us would be here. Many of the signaling pathways that contribute to cancer polyploidy also function in normal development, although they are dysregulated in the former and tightly regulated in the latter.

For example, osteoclasts (osteo = bone, and clast = to break) form from the fusion of two or more precursor cells. Since each precursor cell has its own nucleus with a 2n set of chromosomes (n=23 for humans), the fused cell may have 4n, 6n, 8n, or more chromosomes, in one or more nuclei. New evidence shows that not only can they fuse, but they can also fission to form more osteoclasts when needed. This had not even been hinted at before.

Osteoclasts eat bone; you are forever tearing down bone and replacing it with new bone. If you lift weights and build bigger muscles, you need bigger bones onto which you can attach your now stupendous guns. About every ten years or so, you have an entirely new skeleton!

Polyploid cells can be formed when diploid cells fuse, but it is more interesting when they are formed by the processes of endoreplication (endo = within). Normally, most cells just hum along, growing (G1), then replicating their DNA (S), then growing some more (G2), and finally dividing into two daughter cells by mitosis (M). The two new cells then repeat the process. This is called the cell cycle, and is abbreviated as G1, S, G2, M.

The mitosis portion of the cell cycle itself has several parts that we all learned in biology class – shout them out with me - prophase, metaphase, anaphase, and telophase! At the end of telophase, the two daughter cells finally decide they can’t be roommates any longer, and they divide up their belongings.

The phases of mitosis finish up by dividing the cytoplasm and

nucleoplasm. You can see that the cytokinesis starts first, with

the appearance of the cleavage furrow, but karyokinesis is

completed before cytokinesis is done. Therefore, you can’t have

complete cytokinesis with defective or incomplete karyokinesis.

The replicated chromosomes (each having two sister chromatids) had already separated in anaphase, so now the rest of the nuclear contents split in half and a nuclear membrane forms around each new nucleus – this is termed karyokinesis (karyo = nuclear, and kinesis = in motion). The last thing they do is divide up their cytoplasmic contents and pinch off a new membrane between the two of them, becoming two separate cells – cytokinesis.

In endoreplication, one or both of these processes is turned off, so the two daughter cells continue to share a room, but now the room has twice as much DNA (4n instead of 2n). The cell skips at least a portion of M phase, and the cell cycle becomes G1, S, G2 ----G1, S, G2, etc. It may occur just once, producing a tetraploid cell, or it may occur several times, forming huge cells with 32n or more chromosome sets.

If the cell skips mitosis all together, the process is called endocyling. In this case, the chromatids don’t separate in anaphase, and you end up with chromatids that remain stuck together at their centromeres. If they replicate again in the next S phase, you end up with an octopus-looking chromosome with several arms sticking out – called a polytene chromosome.

The left side of the cartoon shows endocycling.

Skipping mitosis altogether keeps the chromatids

connected and forms polytene chromosomes.

Endomitosis is on the right, where the cell goes

through part of mitosis, then skips the part where

the two cells separate, either by skipping

cytokinesis alone or karyokinesis and cytokinesis.

Polytene chromosomes occur naturally in some animals, like the huge (1 mm) chromosomes in the salivary glands of larval fruit flies (Drosophila melanogaster). They benefit the fruit fly larva in that the cells can produce more proteins from the many copies of the genes. This allows the fruit fly larva to make enough of the proteins that are important in forming the pupal case when it undergoes metamorphosis. All due to endocycling and polyploid formation.

On the other hand, if a cell starts through mitosis and separates its chromatids, AND THEN decides to not divide, this is called endomitosis. Cells that have undergone endomitosis have many sets of chromosomes. Endomitosis without cytokinesis results in large cells with multiple diploid nuclei because karyokinesis separated the nuclei. Endomitosis without karyokinesis and cytokinesis results in large cells with a single polyploid nucleus. You can see that polyploidy would need to be highly regulated to keep it from getting out of control.

So how is that polypoloidy is crucial for our survival? It turns out that that some specialized cells of the embryo undergo polyploidization as the embryo implants into the wall of the uterus.

The embryo has an outer layer of cells called the trophoblast; these cells become the placenta, attach the embryo to the uterine wall, and create the blood vessel connection between mama and junior. The trophoblast is the first set of cells to differentiate in the embryo and they become several different types of trophoblasts.

One type in particular, the extravillous cytotrophoblasts (ECTs), spread out from the developing placenta and burrow into the uterine wall. This creates the tight attachment between mom and embryo. The ECTs also send out hormones to rearrange the mother’s blood vessels, forming the umbilical cord and vessels. This is how the growing baby gets all its nourishment until delivery.

ECTs have been studied most in rodents; they weren’t recognized in humans until just recently. However, a late 2012 study has shown that ECTs are released from the placenta and can be studied by collecting them at the cervix. The cells were sufficient to determine the sex of the child after only 5 weeks of gestation, and were generally of 4n-8n ploidy. Interestingly, female fetuses tended to form ECTs at a rate almost 7x higher than male fetuses – you’re guess is as good as mine as to why that might be.

In panel A there is a bunch of abbreviations. VT is the villous

trophoblasts that make the connection to the decidua (DD).

In the black box which is enlarged in panel B, you can see the

extravillous cytotrophoblast (EVT here) cells invading the

decidua. Both the EVT and the decidua are polyploid.

The most amazing thing about the polyploid trophoblast cells is that they also regulate polyploidization of some of the cells of mom’s uterus. When the endometrium of the uterus prepares to accept the fertilized egg, it undergoes several changes that are together referred to as decidualization. Differentiation of stromal cells into decidual cells and other cellular differentiations make the uterus able to support embryonic growth.

The reason that cells of the decidua must be polyploid is unknown, but the fact that polyploidization begins at the point of implantation and spreads to a greater part of the uterus tells you that they are necessary. A new study points to a few possible reasons. Comparing polyploid decidua to non-polyploid decidua showed that many genes were up-regulated or down-regulated.

The up-regulated genes had to do with metabolism, especially the mitochondrial energy production. On the other hand, down-regulated genes had to do with apopotosis and immune function. These results suggest that polyploidization of the decidua is meant to increase cell functions for the benefit of the embryo, and this takes energy (so more mitochondrial function), while at the same time making sure the cells survive to support the fetus until delivery (reduced apoptosis gene function) and protection of the fetus from the mother’s immune system (the baby is a foreign body after all).

So baby has polyploid cells that mediate joining with the mother, and mom has polyploid cells that also work in the formation of the link between the two. Everyone has to bring polyploidy to the party, or ain’t nobody getting born!

However, polyploidy in fetal development is only part of the story. You don’t abandon polyploid cells altogether once you are born or give birth. All of us have polyploid cells in our bodies right now. Take megakaryocytes for instance.

When you cut yourself, or there is a leak in a blood vessel, platelets arrive to help close the hole and stop the bleeding. Platelets are of irregular shape and are sticky, so they tend to get stuck along the edges of broken blood vessels. Then other things stick to them, a few dozen enzymatic reactions take place with myriad proteins, you form a clot (called a thrombus in the medical world).

I have described how platelets are important for coagulation.

This cartoon shows a break in the cell on the bottom, and

ALL THE STUFF that has to happen to forma thrombus (clot).

Platelets are central, but they are certainly not all the story.

Platelets are not cells, they are actually just fragments of megakaryocytes that pinch off and travel around in the circulation looking for holes to plug. A healthy adult will produce 100 billion platelets each day! Megakaryocytes can afford to give away lots of cytoplasm and membrane because they are large. And they are large because they are polyploid, with lobulated nuclei due to incomplete karyokinesis and no cytokinesis.

Hepatocytes (liver cells), smooth muscle cells in blood vessels, heart muscle cells – these can all be polyploid. In hepatocytes, polyploidization occurs in cells that are done dividing and specializing (terminally differentiated) and are now just doing their job. Fetal and newborn liver cells are exclusively diploid, but 30-40% of adult hepatocytes are polyploid.

Polyploidy may be a way to increase liver metabolism and function without going through cell division. Or it may help to protect the cell from the effects of individual mutations. Since the liver is involved in breaking down toxins, it’s a good guess that some genes will mutate. Having extra copies around would prevent a mutation from inhibiting cell function. One mutated gene can be compensated for by an additional normal gene.

On the other hand, smooth muscle cells seem to undergo polyploidization as a prerequisite to senescence; they are aged and they just stop working. This interesting, since we said last week that cancer cells are more likely escape therapy induced senescence by becoming polyploid. Once again, biology can turn the ordinary on its head.

We have discussed the appearance of a polyploid mammal and crucial sets of polyploid cells in humans. These are the exceptions in higher vertebrates. But in other organisms, polyploidy is a key to evolution. Next time we’ll talk about the exceptional role of polyploidy in the development of plants.

Biron-Shental, T., Fejgin, M., Sifakis, S., Liberman, M., Antsaklis, A., & Amiel, A. (2012). Endoreduplication in cervical trophoblast cells from normal pregnancies Journal of Maternal-Fetal and Neonatal Medicine, 25 (12), 2625-2628 DOI: 10.3109/14767058.2012.717999

Ma, X., Gao, F., Rusie, A., Hemingway, J., Ostmann, A., Sroga, J., Jegga, A., & Das, S. (2011). Decidual Cell Polyploidization Necessitates Mitochondrial Activity PLoS ONE, 6 (10) DOI: 10.1371/journal.pone.0026774

Jansen, I., Vermeer, J., Bloemen, V., Stap, J., & Everts, V. (2012). Osteoclast Fusion and Fission Calcified Tissue International, 90 (6), 515-522 DOI: 10.1007/s00223-012-9600-y

For more information or classroom activities, see:

Osteoclasts and bone remodeling –

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=13&ved=0CHoQFjAM&url=http%3A%2F%2Fteachhealthk-12.uthscsa.edu%2Fcurriculum%2Fbones%2Fpa12pdf%2F1203D-all.pdf&ei=gNDPUKddqOTLAfOggYAD&usg=AFQjCNHwwn6yU3j4aoRDM1xr6CtGKsSgbQ&bvm=bv.1355534169,d.aWc

http://www.youtube.com/watch?v=78RBpWSOl08

http://www.rndsystems.com/cb_detail_objectname_FA04_OsteoclastCoStimulation.aspx

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/Bone.html

http://www.youtube.com/watch?v=0dV1Bwe2v6c

http://depts.washington.edu/bonebio/ASBMRed/growth.html

Endoreplication –

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/Endoreplication.html

http://www.news-medical.net/news/20111031/Researchers-shed-light-on-inner-workings-of-endocycle.aspx

Trophoblast and decidualization–