Cell division

This mesmerising time-lapse of cell division is real, and it’s spectacular.

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This is life.

 If you’ve ever wondered what cell division actually looks like, this incredible time-lapse by francischeefilms on YouTube gives you the best view we’ve ever seen, showing a real-life tadpole egg dividing from four cells into several million in the space of just 20 seconds.
 Of course, that’s lightening speed compared to how long it actually takes – according to Adam Clark Estes at Gizmodo, the time-lapse has sped up 33 hours of painstaking division into mere seconds for our viewing pleasure.

The species you see developing here is Rana temporaria, the common frog, which lays 1,000 to 2,000 eggs at a time in shallow, fresh water ponds.

According to the team behind the footage, they had to build their own equipment to film it like this, and had to devise a way to get the lighting and microscope set-up just right.

“The whole microscope sits on anti-vibration table. [I]t doesn’t matter too much what microscope people use to perform this,” francischeefilms describe on their YouTube page.

“There are countless other variables involved in performing this tricky shot, such as: the ambient temperature during shooting; the time at which the eggs were collected; the handling skills of the operator; the type of water used; lenses; quality of camera etc.”

Check out the footage. URL:https://youtu.be/Wz4igVjNGq4

Source:http://www.sciencealert.com

Study finds protein ‘cement’ that stabilizes the crossroad of chromosomes

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Cell division is the basis of life and requires that each daughter cell receive the proper complement of chromosomes. In most organisms, this process is mediated at the familiar constricted intersection of X-shaped chromosomes. This area, called the centromere, is where special proteins gather and attach to pull daughter cells apart during cell division. The structure and biology of the centromere is of considerable scientific interest because problems with it can lead to abnormalities in the chromosomes of daughter cells, which are the basis of such disorders as Down syndrome.
Penn team finds protein 'cement' that stabilizes the crossroad of chromosomes

A new study by researchers at the Perelman School of Medicine at the University of Pennsylvania published in Science this week describes how the centromere is stabilized during replication. DNA in the nucleus is packaged into protein/DNA complexes called nucleosomes. As it turns out, the centromere is distinguished not only by its DNA sequence but also by a special type of nucleosome, which includes a protein called CENP-A.

Senior author Ben E. Black PhD, associate professor of Biochemistry and Biophysics, and his Penn team described the structure of CENP-A almost five years ago. The question the investigators asked now was, how does the cell ensure that CENP-A-containing nucleosomes remain at, and thus continue to mark, the centromere during the massive changes a cell undergoes when it divides?

Simply put, it involves an accessory protein called CENP-C. “Overall, my lab is interested in better understanding the molecular basis of inheritance and the role of the centromere, as a ‘control locus,’ for maintaining heredity,” says Black.

His team applied a battery of biophysical techniques to study the structure and stability of CENP-A-containing nucleosomes in a test tube. Their data indicate that CENP-A-bearing nucleosomes have an unexpectedly flexible structure, adopting a relaxed conformation in the absence of CENP-C, and a more compact shape in its presence. This CENP-C-induced shape shift correlates with changes in how DNA wraps around the centromere’s nucleosomes, making the structure similar to that found in living cells.

Their findings also address the question of the stability of CENP-A molecules at centromeres. Under normal conditions CENP-A binds centromeres and effectively never lets go. Indeed, when the authors tracked where proteins “reside” in live cells, they found that, unlike traditional nucleosomes that package the DNA throughout the rest of the chromosome, CENP-A-containing nucleosomes apparently never dissociate after newly generated CENP-A protein is first delivered to the centromere during a short time window following . “The CENP-A is basically cemented at the centromere of origin,” Black explains. But in cells lacking CENP-C, CENP-A dissociates readily, suggesting that CENP-C binding to CENP-A is what imparts that stability.

Investigators have known for the past 20 years that part of chromosome inheritance is controlled by epigenetics, implicating the protein spools around which DNA is wound as the driving force, rather than what is encoded in the DNA sequence itself. Those spools are built of histone proteins, and chemical changes to these spool proteins can either loosen or tighten their interaction with DNA. This, in turn, alters a gene’s expression up or down. In the case of the centromere, it marks the site where spindle fibers attach independently of the underlying DNA sequence.

Earlier, Black and other chromosome researchers established that CENP-A is the key epigenetic protein at the centromere and replaces the regular histone protein H3. CENP-A attracts other proteins, and in cell division builds a massive structure called the kinetochore, for pulling duplicated chromosomes apart during cell division.

Black notes that these data suggest a model of epigenetic biology distinct from the traditional view of nucleosomes as static scaffolds on which key functional molecules assemble. Instead, the team’s data suggest that histone variants and post-translational modifications, which change the biological properties of nucleosomes through changes in shape (by adding or removing enzyme docking sites) make nucleosomes active participants in cell division and gene expression.

“This is conceptually very similar to thinking about how enzymes can be regulated—their activity can be turned on and off,” he explains. “In this case, we’re not talking about how enzymes affect a chemical reaction; we’re talking about how the nucleosome and this entire part of the chromosome is stabilized. If stability is lost, then the chromosome and all the genes carried on it would not be delivered faithfully to each cell upon division. This is the sort of genetic catastrophe that is a hallmark of cancer cells. Or if it happens in the sperm or egg cell lines, it leads to spontaneous abortions or children with disorders such as Down syndrome.”

This mode of nucleosome regulation and stabilization may well be common to other epigenetic processes, Black adds. Indeed, he says the results suggest that other histone variants and histone post-translational modifications may serve a similar function as the example at the centromere with CENP-A and CENP-C, for instance in the regulation of gene expression.

“I don’t know how widely this occurs,” he says, “but I’d be very surprised if this was the only place in nature that had evolved to take advantage of the fact that the shape of nucleosomes can be regulated by protein-binding events.”

Black says CENP-A-mediated stability could explain how oocytes retain the epigenetic information that preserves the fidelity of chromosome inheritance over so many years of fertility, and he is preparing to test that hypothesis now.

‘BAD LUCK’ OF RANDOM MUTATIONS PLAYS PREDOMINANT ROLE IN CANCER, STUDY SHOWS

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Scientists from the Johns Hopkins Kimmel Cancer Center have created a statistical model that measures the proportion of cancer incidence, across many tissue types, caused mainly by random mutations that occur when stem cells divide. By their measure, two-thirds of adult cancer incidence across tissues can be explained primarily by “bad luck,” when these random mutations occur in genes that can drive cancer growth, while the remaining third are due to environmental factors and inherited genes.
“All cancers are caused by a combination of bad luck, the environment and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development,” says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

“Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their ‘good genes,’ but the truth is that most of them simply had good luck,” adds Vogelstein, who cautions that poor lifestyles can add to the bad luck factor in the development of cancer.
The implications of their model range from altering public perception about cancer risk factors to the funding of cancer research, they say. “If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others,” says biomathematician Cristian Tomasetti, Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. “We should focus more resources on finding ways to detect such cancers at early, curable stages,” he adds.
In a report on the statistical findings, published Jan. 2 in Science, Tomasetti and Vogelstein say they came to their conclusions by searching the scientific literature for information on the cumulative total number of divisions of stem cells among 31 tissue types during an average individual’s lifetime. Stem cells “self-renew,” thus repopulating cells that die off in a specific organ.
It was well-known, Vogelstein notes, that cancer arises when tissue-specific stem cells make random mistakes, or mutations, when one chemical letter in DNA is incorrectly swapped for another during the replication process in cell division. The more these mutations accumulate, the higher the risk that cells will grow unchecked, a hallmark of cancer. The actual contribution of these random mistakes to cancer incidence, in comparison to the contribution of hereditary or environmental factors, was not previously known, says Vogelstein.
To sort out the role of such random mutations in cancer risk, the Johns Hopkins scientists charted the number of stem cell divisions in 31 tissues and compared these rates with the lifetime risks of cancer in the same tissues among Americans. From this so-called data scatterplot, Tomasetti and Vogelstein determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated.
“Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue,” says Vogelstein. One example, he says, is in colon tissue, which undergoes four times more stem cell divisions than small intestine tissue in humans. Likewise, colon cancer is much more prevalent than small intestinal cancer.
“You could argue that the colon is exposed to more environmental factors than the small intestine, which increases the potential rate of acquired mutations,” says Tomasetti. However, the scientists saw the opposite finding in mouse colons, which had a lower number of stem cell divisions than in their small intestines, and, in mice, cancer incidence is lower in the colon than in the small intestine. They say this supports the key role of the total number of stem cell divisions in the development of cancer.
Using statistical theory, the pair calculated how much of the variation in cancer risk can be explained by the number of stem cell divisions, which is 0.804 squared, or, in percentage form, approximately 65 percent.
Finally, the research duo classified the types of cancers they studied into two groups. They statistically calculated which cancer types had an incidence predicted by the number of stem cell divisions and which had higher incidence. They found that 22 cancer types could be largely explained by the “bad luck” factor of random DNA mutations during cell division. The other nine cancer types had incidences higher than predicted by “bad luck” and were presumably due to a combination of bad luck plus environmental or inherited factors.
“We found that the types of cancer that had higher risk than predicted by the number of stem cell divisions were precisely the ones you’d expect, including lung cancer, which is linked to smoking; skin cancer, linked to sun exposure; and forms of cancers associated with hereditary syndromes,” says Vogelstein.
“This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors. However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors. The best way to eradicate these cancers will be through early detection, when they are still curable by surgery,” adds Vogelstein.
The scientists note that some cancers, such as breast and prostate cancer, were not included in the report because of their inability to find reliable stem cell division rates in the scientific literature. They hope that other scientists will help refine their statistical model by finding more precise stem cell division rates.

What Most Doctors Won’t Tell You About Colds and Flus.

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The next time you experience a cold or the flu, remember this: rather than take conventional drugs to suppress uncomfortable symptoms, it’s better for your health to allow the cold or flu to run its course while you get plenty of physical and emotional rest.

Conventional medicine and the pharmaceutical industry would have you believe that there is no “cure” for the common cold, that you should protect yourself against the flu with a vaccine that is laden with toxic chemicals, and that during the midst of a cold or flu, it is favorable to ease your discomfort with a variety of medications that can suppress your symptoms.

Unfortunately, all three of these positions indicate a lack of understanding of what colds and flus really are, and what they do for your body.

Colds and flus are caused by viruses. So to understand what colds and flus do at a cellular level, you have to understand what viruses do at a cellular level.

Do you remember learning about cellular division in grade seven science class? Each of your cells are called parent cells, and through processes of genetic duplication (mitosis) and cellular division (cytokinesis), each of your parent cells divides into two daughter cells. Each daughter cell is then considered a parent cell that will divide into two more daughter cells, and so on.

Viruses are different from your cells in that they cannot duplicate themselves through mitosis and cytokinesis. Viruses are nothing but microscopic particles of genetic material, each coated by a thin layer of protein.

Due to their design, viruses are not able to reproduce on their own. The only way that viruses can flourish in your body is by using the machinery and metabolism of your cells to produce multiple copies of themselves.

Once a virus has gained access into one of your cells, depending on the type of virus involved, one of two things can happen:
The virus uses your cell’s resources to replicate itself many times over and then breaks open (lyses) the cell so that the newly replicated viruses can leave in search of new cells to infect. Lysis effectively kills your cell.

The virus incorporates itself into the DNA of your cell, which allows the virus to be passed on to each daughter cell that stems from this cell. Later on, the virus in each daughter cell can begin replicating itself as described above. Once multiple copies of the virus have been produced, the cell is lysed.

Both possibilities lead to the same result: eventually, the infected cell can die due to lysis.

Here is the key to understanding why colds and flus, when allowed to run their course while you rest, can be good for you:

By and large, the viruses that cause the common cold and the flu infect mainly your weakest cells; cells that are already burdened with excessive waste products and toxins are most likely to allow viruses to infect them. These are cells that you want to get rid of anyway, to be replaced by new, healthy cells.

So in the big scheme of things, a cold or flu is a natural event that can allow your body to purge itself of old and damaged cells that, in the absence of viral infection, would normally take much longer to identify, destroy, and eliminate.

Have you ever been amazed by how much “stuff” you could blow out of your nose while you had a cold or the flu? Embedded within all of that mucous are countless dead cells that your body is saying good bye to, largely due to the lytic effect of viruses.

So you see, there never needs to be a cure for the common cold, since the common cold is nature’s way of keeping you healthy over the long term. And so long as you get plenty of rest and strive to stay hydrated and properly nourished during a cold or flu, there is no need to get vaccinated or to take medications that suppress congested sinuses, a fever, or coughing. All of these uncomfortable symptoms are actually ways in which your body works to eliminate waste products and/or help your body get through a cold or flu. It’s fine to use over-the-counter pain medication like acetaminophen if your discomfort becomes intolerable or if such meds can help you get a good night’s rest. But it’s best to avoid medications that aim to suppress helpful processes such as fever, coughing, and a runny nose.

It’s important to note that just because colds and flus can be helpful to your body doesn’t mean that you need to experience them to be at your best. If you take good care of your health and immune system by getting plenty of rest and consistently making health-promoting dietary and lifestyle choices, your cells may stay strong enough to avoid getting infected by viruses that come knocking on their membranes. In this scenario, you won’t have enough weak and extraneous cells to require a cold or the flu to work its way through your body to identify and lyse them.

Curious about how to differentiate the common cold and the flu? Here is an excellent summary of the differences from cbc.ca:
A cold usually comes on gradually — over the course of a day or two. Generally, it leaves you feeling tired, sneezing, coughing and plagued by a running nose. You often don’t have a fever, but when you do, it’s only slightly higher than normal. Colds usually last three to four days, but can hang around for 10 days to two weeks.

Flu, on the other hand, comes on suddenly and hits hard. You will feel weak and tired and you could run a fever as high as 40 C. Your muscles and joints will probably ache, you will feel chilled and could have a severe headache and sore throat. Getting off the couch or out of bed will be a chore. The fever may last three to five days, but you could feel weak and tired for two to three weeks.

One final note on this topic: because the common cold and the flu are both caused by viruses, antibiotics are not necessary. People who take antibiotics while suffering with a cold or flu often feel slightly better because antibiotics have a mild anti-inflammatory effect. But this benefit is far outweighed by the negative impact that antibiotics have on friendly bacteria that live throughout your digestive tract. In this light, if you really need help with pain management during a cold or flu, it is usually better to take a small dose of acetaminophen than it is to take antibiotics.

Sources: drbenkim.com & realfarmacy.com