Gorilla, the possible of the origin of human Malaria parasite P. falciparum

 

When the emergence of disease outbreak, first thing that in scientists or epidemiologists mind are the resources or disease reservoirs are from our phylogenetic closely related species, chimpanzees. But recently the scientists found the different story on the origin of human Malaria P.falciparum, which is from gorilla.

A research team led by virologist Beatrice Hahn of the University of Alabama, Birmingham, used the polymerase chain reaction to amplify Plasmodium DNA from a whopping 2739 fecal samples from chimpanzees,gorillas, and bonobos.

Using single-template amplification strategies and a much larger collection of ape specimens than previously analysed, the scientists show here that wild-living chimpanzees and western gorillas are naturally infected with at least nine plasmodium species. Among more than 1,100 SGA derived mitochondrial, apicoplast and nuclear gene sequences from 80 chimpanzee and 55 gorilla samples, they found a total of nine sequences that were related to P. malariae, P. ovale or P. vivax. All others grouped within one of six chimpanzee or gorilla-specific lineages representing distinct Plasmodium species,three of which had not previously been described. Significantly, all currently available human P. falciparum sequences constitute a single lineage nested within the G1 clade of gorilla parasites. This indicates that human P. falciparum is of gorilla origin, and not of chimpanzee , bonobo or ancient human origin, and that all known human strainsmay have resulted froma single cross-species transmission event.

From the finding, what is still unclear is when gorilla P. falciparum entered the human population and whether present-day ape populations represent a source for recurring human infection.(when date of the jump from gorillas to humans). Plasmodium does not mutate much, she explained, making it difficult to calibrate a so-called molecular clock that enables evolutionary biologists to back-calculate the timing of a pathogen moving from one species to another.

According to Ajit Varki, an evolutionary biologist at UC San Diego,  he believes a human gene mutation, CMAH, which arose about 2 million years ago, may provide a clue to how and when the jump occurred. The mutation changes sialic acid receptors on red blood cells, rendering them much less susceptible to P. reichenowi, and Varki suspects that the gorilla P. falciparum similarly would have great difficulty infecting human cells.

This is also support by Michael Worobey, an evolutionary biologist who has also focused on the origin of the AIDS epidemic, is similarly intrigued that gorilla P. falciparum has not repeatedly infected humans. The finding can help clarify the evolutionary history of P. falciparum.

(for more information please read the article on Natures magazines 23rd september 2010, "Origin of the human malaria parasite Plasmodium falciparum in gorillas")

Almost Indistinguishable, different in function.

If you see 2 amino acid sequence that just a 1-2% slightly different on the sequence, can we just ignore their differences and simply said the protein will be same with the same 3-D confirmation. Don’t simply make the easy conclusion like that because the slightly different can describes a lot.

One such of puzzle is related to the mammalian cytoskeletal protein β- and γ-actin, whose amino acid sequences are 98% identical.  The slightly difference of both protein make they differ in protein modification which β-actin is modified by addition of arginine (arginylation) and γ-actin is not modified, resulting the distinct role for each in the cell.

Scientists try to understand this phenomenon. This is unexpected example of the protein whose the properties are determined at the nucleotide rather than amino acid level, forcing a reassessment of what defines a synonymous change in the gene sequence.

Arginylation of certain protein occur after translation of their termini. Although discover in 40 year ago, the effect of the argynilation is fully understood than other posttranslational modifications. Proteins are arginylated during normal cell growth and in response to stress, and arginylation has been associated with protein degradation in the proteasome. One prominent group of substrates is actin group but not all actin groups are argynilated in posttranslation modification.

Selective modification of the actins is important for normal cell morphology and migration because the absence of arginylation  substantially decrease intracellular actin cellular level and changes its partial segregration.

In this case, the arginylation of β-actin on the posttranslation makes β-actin preferentially localizes at the protruding leading edge of a migrating cell, where rapid actin polymerization pushes the cell’s front forward. There, β-actin is present as a loose and branched arrangement of relatively short actin filaments. By contrast, γ-actin is found in the cell body in dense nonbranched networks and long contractile stress fibers that impart morphological stability and support cell adhesion.

Because of their slightly different of amino acid sequence they affect the rate of translation, and affect their polypeptide modification and also their stability.

What exactly the differences of their amino acid sequences that affect the translation rates.  As mentioned above to explain this is not in amino acids level but in nucleotide levels. The γ-actin contain high frequency of codon that slower the translation but the same region of codon, the alternate codon that coding same amino acid in β-actin is make the translation faster.

Fast translation allows only arginyation, thereby stabilizing the protein. In contrast slow translation allows both arginylation and ubiquitination occur that leading to fast degradation. In conclusions, the synonymous  mutation that encode same amino acid is again not exactly same in the protein comfirmation and modification.

Ada hikmah disebalik teguran PERKASA pasal isu masuk masjid Teo Nie

Politik Malaysia, isu-isu yang akan menjadi tumpuan adalah isu-isu agama dan isu perkauman. Kebelakangan ini Pribumi Perkasa Negara (PERKASA) ada menimbulkan isu tentang kebiadaban ahli parlimen Serdang, Teo Nie yang memasuki masjid tanpa menutup aurat dan ini seakan menghina Islam walaupun niat Teo Nie baik, untuk menyampaikan sumbangan kepada masjid.

Apabila isu ini dihebah-hebahkan. Jentera politik pembangkang membalasnya dengan mempersoalkan tentang kebiadaban beberapa wanita pemimpin negara yang tidak menutup aurat didalam masjid. Dengan pendedahan itu, pembangkang menggunakan modal agar pihak kerajaan tidak menggunakan isu ini untuk membedil pembangkang. Lihat photo dibawah:

Kalau dibandingkan dengan Teo Nie, ini lebih teruk. Kerana mereka dalam photo ini merupakan orang Islam, tahu buka aurat haram. Saya tak tahu la orang didalam photo ini pakai tudung ikut mazhab apa, tapi yang jelasnya sebagai penduduk di alam Melayu Nusantara, kita pengikut Mazhab Syafie, aurat perempuan harus ditutup seluruh badan kecuali muka dan tapak tangan.

Kita pergi kepada tajuk tentang hikmah disebalik teguran PERKASA. Saya ada terbaca artikel dalam selangor kini tentang cadangan Hasan Ali untuk membuat peraturan yang lebih terperinci tentang masuk masjid.http://www.selangorkini.com.my/my/berita/16660

Kita lihat dari sudut positif, teguran PERKASA membuat semua pihak membuka mata tentang peraturan dan adab untuk masuk masjid yang selama ini tidak diendahkan. Dengan adanya teguran, barulah pemimpin-pemimpin politik yang selama ini asyik bertekak dengan isu-isu politik remeh mengambil inisiatif untuk meningkatkan pengurusan sistem masjid khususnya negeri Selangor.

Akan tetapi, teguran PERKASA bagi saya agak kasar dan terburu-buru sehinggakan boleh menimbulkan salah faham tentang Islam. Orang yang bukan Islam akan melihat Islam ini tidak terbuka kerana tidak membenarkan orang bukan Islam masuk masjid jika dibandingkan dengan gereja.

Saya ingin menegaskan disini, tidak salah orang bukan Islam masuk masjid asalkan mengikut peraturan yang digaris pandu oleh Islam. Isu Teo Nie saya rasa bukan salah dia, ini disebabkan sistem pengurusan  institusi masjid. Sepatutnya mereka lebih peka tentang ini contohnya memberikan Teo Nie jubah untuk menutup aurat seperti di masjid Putrajaya.

Saya harapkan kerajaan Negeri Selangor dan negeri-negeri lain dapat menaik taraf sistem pengurusan masjid agar orang bukan Islam boleh menyertai aktiviti-aktiviti masjid agar pemahaman mereka pada Islam lebih mendalam.

"ISLAM ITU SEJAHTERA"

The power of Mother’s Love

Love is something abstract.  We can’t measure love. Love is something did not have any unit. Some people relate love with Einstein’s relativity theory. But first what are relativity theory is? According to the theory, energy and matter are relative and light is constant.

Giving an example, the 2 cars, Car A moving in 60 km/h and Car B moving 80 km/h. Doesn’t care about the direction of the both cars, 2 of them are relatively moving in 20 km/h difference.  One spotlight from a building is focusing to both cars. The light moving to both cars is constant. Thus, same with love, love is constant. We love every one that we love constantly. No more or no less. That is how they relate the love with the physics.

It’s enough to elaborate love in scientific way.  Let’s discuss about the topic, the power of mother’s love. Some people believe, when some teenager’s suicide cases because of stress, failure, and many more reasons because of they did not have enough love from parent or the parental ignorance. But how this believe support by scientific evidence. I would like to say in the genetics’ point of view.

In 2004, Szyf and Meaney published a paper in Nature Neuroscience that helped launch the behavioral epigenetics revolution. It remains one of the most cited papers that journal has ever published. The paper built on more than a decade of research in Meaney’s  lab on rodent mothering styles.

Meaney had found that the type of mothering a rat receives as a pup calibrates how its brain responds to stress throughout its life. Rats raised by less-nurturing mothers are more sensitive to stress when they grow up. When confined to a Plexiglas tube that restricts their movement, for example, they exhibit a greater surge in corticosterone, a hormone pumped out by the adrenal glands in times of stress. The likely cause is reduced numbers of a receptor for steroid hormones in the brain. This so- called glucocorticoid receptor is part of a negative feedback loop that dials down the volume on communication between the brain and adrenal glands, thereby reducing reactivity to stress.

The Nature Neuroscience paper linked this reduction in glucocorticoid receptors to DNA methylation. Rats raised by less nurturing moms tended to have more methyl groups attached to the promoter region, the “on” switch, of the glucocorticoid receptor gene. These methyl groups block access by the transcription factors that turn the gene on. As a result, fewer receptors are produced. Subsequent experiments showed that enzymes that reverse DNA methylation of the glucocorticoid receptor gene also reverse the effects of unenthusiastic mothering on the offspring’s hormonal and behavioral responses to stress.

Several of Meaney’s students have carried on with this work and extended it in new directions. Frances Champagne, a co-author of the 2004 paper, went on to show that female rats raised by nurturing mothers are more nurturing mothers themselves. She also found that pups raised by less-nurturing moms exhibit greater methylation—and reduced expression—of the gene for a particular estrogen receptor in the hypothalamus, a brain region involved with reproductive behavior. This receptor amplifies signaling by oxytocin, a hormone that promotes mother-infant bonding.

Summarize from their finding, rat raised by less nurturing mother (not enough love) likely to sensitive to stress because of reduction the glucocorticoid gene activity that reducing reactivity of stress— more DNA methylation that repress the transcription of the gene.

The scientific evidence support that the important of mother’s love. But don’t blame to their mother if have suicide cases. A lot of factors that causing stress. The important point is the finding gives us a guidance to care more about our children and never ignore them. Happy families can build a happy society that lead to the peace.

The renaissance of DNA Drugs

“Rise and rise again, until lambs become lions”. The meaning of this phrase is never give up until we achieve our goals.

Why I write this post because I would like to show my appreciation to the scientists who are optimist in developing DNA drugs after the false start. DNA Drugs is the vaccine contains plasmid that carried DNA sequence of the pathogen, so that the immune system can produce antibody as preparation to fight the infection of the disease.

Why I mean the “false start” is because the DNA Drugs has the head-to-head  competition with another potential vaccine that using adenovirus as carrier of DNA of pathogen seems not very effective with the latter vaccine. The competition is their compare the immune response of two vaccines. The DNA Drugs contains plasmids, each carrying a gene for one of five HIV proteins. Its goal was to get the recipient’s own cells to make the viral proteins in the hope they would provoke protective reactions by immune cells. The second vaccine used another virus called an adenovirus as a carrier for a single HIV gene encoding a viral protein.

The DNA recipients displayed only weak immune responses to the five HIV proteins or no response at all, whereas recipients of the adenovirus-based vaccine had robust reactions. To academic and pharmaceutical company researchers, adenoviruses clearly looked like the stronger candidates to take forward in developing HIV vaccines.

What I say they are optimistic, after the disappointing result of DNA drugs they did not just give up, they find what are the mistakes. The main reasons for those failures seemed to be that vaccine plasmids were not getting into enough cells and, where they did penetrate, the cells were not producing enough of the encoded proteins. As a result, the immune system was not being sufficiently stimulated.

The vaccines using adenovirus seems have a bigger problem. In 2007 pharmaceutical company Merck initiated a large trial of an HIV vaccine that used an adenovirus called AdHu5 to deliver HIV viral genes. In light of the potent immune responses seen in previous experiments with adenoviruses, great hope and excitement surrounded the beginning of this test, known as the STEP trial. In all, about 3,000 HIV-negative individuals received the vaccine or a placebo shot.

As the trial progressed, though, a disturbing difference between the two groups began to emerge: people who got the vaccine were no better protected than those who received the placebo, and eventually they appeared to be more vulnerable to being infected by HIV. As a result they found that 49 out of 914 men in the vaccine group became HIV-positive, whereas 33 out of 922 men in the placebo group did. With this realization, in the summer of 2009 the STEP trial was halted.

The STEP trial gives the scientists to look back on the DNA Drugs. To optimize the DNA Drugs effect, the scientist suggest the several steps as visualized on the figured below:

As conclusions, if we fail now is doesn’t means we fails forever. Keep trying and never give up.

Can we create clone of an extinct organism from a stretch of DNA?

If you hear from sci-fi (science fiction) story about when the villains get the superhero DNA sources like hair, blood and skins, so the villains clone it and make the world chaos? It seems like the very easy to clone organism, just get their DNA stretch. But in reality, is not just an easy step.

Another example,sci-fi  writers have been resurrecting Neandertals in novels for decades, imagining what it would be like to see and communicate with another species of human. So once the idea of sequencing the Neandertal genome became more than a glimmer in a paleogeneticist’s eye, some have asked, “Could we, should we, would we, bring this extinct human species back to life?” After all, biologists are trying to bring back the woolly mammoth by cloning. But for both technical and ethical reasons, experts say, bringing back a Neandertal is a pipe dream.

Could we do it? Robert Lanza laughed at the thought. Chief scientific officer for Advanced Cell Technology in Worcester, Massachusetts, he and his colleagues have cloned species from cows to goats to mice and extended their efforts to include endangered species and human embryos. But cloning Neandertals is fantasy, says Lanza. “You can’t clone from stone, and you can’t clone from DNA that has been destroyed from weather and the elements,” he points out.

From the statement above, to clone an organism is not simply get their DNA, a lot of factor must be considered.  We are specific in cloning Neandertals from their stretch of DNA.  Like Lanza says, we can’t cloned from from DNA that destroy by weather and element because of the DNA stretch that we get has a lot of missing gap in their genome.

Even we have their complete genome, it wouldn’t be enough. DNA itself doesn’t tell the whole story. Chemical modifications to the genome, the way chromosomes arrange in the nucleus, and maternal components in the egg all play a role in translating a genetic blueprint into a viable individual. “It’s not just the DNA; there’sa lot else going on,” says Lanza. None of that information is even available for Neandertals.

Then, too, cloning doesn’t typically start with a genome; it starts with two cells. One cell provides a nucleus (with DNA inside), and one is an egg cell, most often of the same species, whose DNA has been removed. The nucleus is then transferred to the egg, sometimes by fusing the two cells. “If you have just got DNA, you are asking an enormous amount of the oocyte that you are going to put the DNA into,” explains Ian Wilmut, who cloned Dolly the sheep and now works at the University of Edinburgh in the United Kingdom. “It has to reform the nucleus and reprogram [the DNA].”

That leads to the next problem: What species’ egg would play host to this DNA? The obvious candidate would be a modern human egg, but they are notoriously fickle and don’t take well to nuclear transfer, even of modern human DNA. “There’s something different about primates that we haven’t identified,” says Wilmut. “[Cloning] works very poorly.” And incompatibilities between Neandertal DNA and the human egg might further diminish the chances of a viable embryo.

Molecular geneticist George Church of Harvard University has proposed another approach: modify the DNA in a human cell line to resemble the Neandertal. “This is a daunting task,but with future technological developments and enough time and money, it may be possible,”says Adrian Briggs, who worked on the Neandertal genome sequence and is about to join Church’s lab. In theory, one could convert a human or chimp genome to a Neandertal genome—base by base—while it is still nicely nestled in a stem cell, then clone it. But there’s on the order of a million differences between the Neandertal and human genomes, and the more changes needed, the greater the risk of

introducing errors.

If, somehow, a viable embryo were produced, this developing chimera would need a surrogate mother. What species would that mother belong to? Again, the obvious choiceis a human, but no one knows whether a modern woman’s biochemistry would be compatible with that of a Neandertal fetus. And is it ethical for a human surrogate mother to birth a Neandertal baby? It’ll bring ethical issues. Once cloning works well in a variety of animals and stem cell–derived organs become commonplace, “I think the resistance to it will disappear,” he says.

I would like to share may be some other approach based on the research of J. Craig Venter, who for 15 years, J. Craig Venter has chased a dream: to build a genome from scratch and use it to make synthetic life. Now, he and his team at the J. Craig Venter Institute (JCVI) in Rockville, Maryland, and San Diego, California, say they have realized that dream.

They describe the stepwise creation of a bacterial chromosome and the successful transfer of it into a bacterium, where it replaced the native DNA. Powered by the synthetic genome, that microbial cell began replicating and making a new set of proteins. (You can read further at www.sciencemag.

org/cgi/content/abstract/science.1190719)

This is “a defining moment in the history of biology and biotechnology,” says Mark Bedau, a philosopher at Reed College in Portland, Oregon, and editor of the scientific journal Artificial Life. “It represents an important technical milestone in the new field of synthetic genomics,” says yeast biologist Jef Boeke of Johns Hopkins University School of Medicine in Baltimore, Maryland.

May be the finding can help in cloning the Neandertals but this is bring the ethical issues. “We do not—and

should not—create human beings just to satisfy our scientific curiosity,” says Pääbo, pointing out that Neandertals are a species of human.

Recombination hotspot?

Did you know what recombination hotspot is? In the meiosis the crossing over and homologous recombination produce the recombination chromosome. But not all segments in chromosome are crossing over equally in the entire genome. Is not the matter of position from centromere, but some place in chromosome are more frequent to crossing over than other segment. So the distribution of crossing over entire chromosome in the genome not equal.

So let us go to definition. Recombination hotspots are small regions in the genome of sexually reproducing organisms that exhibit highly elevated rates of meiotic recombination. What the significance of recombination hotspot?

The cause of hotspots is currently unknown, however all hotspots so far characterized share similar morphology and are approximately 1.5 to 2.0 kb in width, which suggests a common causal process. Furthermore, recent studies have used patterns in linkage disequilibrium to identify over 25,000 hotspots in the human genome, suggesting that hotspots are a ubiquitous feature of the genome.

Scientist try to compare the recombination hotspot in human and our closely relative chimpanzees, Despite 99% DNA similarity between humans and our nearest relative, chimpanzees, the locations of DNA swapping between chromosomes, known as recombination hotspots, are almost entirely different. Perhaps this is explanation about how human and chimpanzees are different eventhough their different in DNA just 1%.

Some study suggest a minimum number of required recombinations for proper meiosis; if so,what genes or pathways monitor this process? If this global monitoring system fails, aneuploidy may result? The questions can be answer by ongoing research.