It’s hard for me, as a patriot, to read an article in EID about Plasmodium falciparum in ancient Egypt & shut up. The first emergence of Malaria in literature was when Hippocrates described the typical undulated fever which is highly characteristic for Malaria infection. Scientists made studies to identify P. falciparum‘s DNA in remains of a Roman infant (5^th century) and another study on remains from 100-400 years ago.

They made their studies on 4000 years old mummies from Abydos, the Middle Kingdom tomb in Thebes West. Also samples from two different tombs from the New Kingdom until the Late Kingdom were taken. How did they know that those mummies had malarial infection? They simply searched for mummies had osteopathic evidence for chronic anemia. They ran PCR, a special technique called heminested PCR, using 18S rDNA primers. 2 of the 91 tested samples had chloroquine-resistance transporter (pfcrt) gene. I don’t know how, there wasn’t even chloroquine back there. They also ran immunological test which came positive for the P. falciparum histidine-rich protein-2 antigen.

Another thing came to my mind about Malaria. We must celebrate the launch of MalHaploFreq, the computer program which is designed for estimation of malaria haplotype frequencies in blood samples. Two awful facts about Malaria: There’s always drug resistance & multiple infections (the person can be infected by more than one type each one is resistant to an anti-malarial agent). All I know that they used Algorithm; this is really bad because I can’t stand math, and molecular markers to trace the spread of the drug-resistance & to predict the frequency of mutations.

Center for Disease Control and Prevention
Recently, it has been all over the news in the United States…warning americans about buying tomatoes, pepper, and different kinds of vegetables “They even suggested some pretty clever alternatives” due to a Salmonella outbreak, which made over 1,200 people sick throughout the nation.

Now “after two months of the intial discovery”, the outbreak has been linked to irrigation water contaminating a certain type of pepper at a Mexican farm, stored in a warehouse in Texas. Officials are being blamed now for putting too much spot-light over tomatoes when in fact they did not significantly contribute to the arousal of the problem in the first place. Their hope now would be to discover that the same irrigation water was also used on tomatoes and not just the pepper.

The FDA declares that it IS safe to eat tomatoes and pepper grown in the US, urging consumers to be open and ask their local grocery stores & restaurants about the source of these vegetables. 
For the time being, I would strongly avoid any Mexian salsa 🙂 

U.S. Center for Disease Control and Prevention 

A new study reveals that people infected with bilharzia, or other parasitic worms, are more likely to become infected with HIV than normal persons. This was proven through an experiment where the infectious dose of an HIV-like virus necessary to infect rhesus macaques was found to be 17 times lower in animals with acute schistosomiasis than in controls. The animals co-infected with Schistosoma mansoni also showed higher memory cell concentrations of virus casuing a more rapid progression to AIDS.

These findings prove the assumption that persons living in highly endemic areas for parasitic worms have a higher risk of acquiring HIV/AIDS.

Previous studies by other research groups have demonstrated that the presence of schistosome infections increases viral replication in animal or human hosts with established immunodeficiency virus infections.

Both findings are surely to have profound public health implications for the under-developed areas of the world where both parasitic worms and HIV virus are endemic.

Nothing made the world highly concerned about the immune system, what are its components? How does it work?, better than the emergence of HIV in the 80s. It’s a disaster, but made us know more about the immune system.

HIV’s target is CD4 receptors, which are present mostly on T-helper cells. It has glycoprotein 120 (Why do they call it 120 any way?! Is it the UV absorption again?! Or maybe it has 120 amino acids?!) It’s on its envelope. By recognition & binding to the CD4 receptors, it kills the T-helper which result in suppression of the whole cell-mediated immunity mechanism. It’s like cutting the snack’s head off. T-helper cells are responsible for giving signals (Interleukins) to other members of the IS so they can kill the viruses. By the whole suppression idea, the IS is turned off, the human body will be opened like your friend’s heart to you, to all possible invaders of m.o.

When we talked about HIV, the professor told us:” You wanna fight HIV, young docs full of enthusiasm, block its binding site, so it can’t bind to CD4 anymore.” I remembered the wise man’s words when I surveyed this article “Antibodies to the CD4-binding site of HIV-1 gp120 suppress gp120-specific CD4 T cell response while enhancing antibody response” about studying the effect of monoclonal anti-bodies against only the highly conserved part of the gp 120 (The binding site). We know that after exposure to HIV, the IS produces Ab against gp 120 to neutralize it, but the HIV tends to change the gp 120, so it can’t fit with the neutralizing Ab, moving on to more destruction. With those highly specific binders, I thought it’ll be the ultimate success.

Unfortunately, the research group made in vivo (in mice) & in vitro studies using the normal virus & another recombinant one with no CD4bs. They called it CD4bs+ Env & CD4bs- Env (Like with or without cheese). They found that the Anti-CD4bs mAb have high neutralizing activity, they raised the Ab titer (mainly IgG but not IgM). But they hinder the ability of the proteolytic enzymes/ the degrading mechanisms of phagocytes/ T-helper response to the envelope Ag/ the ability of Antigen presenting cells & MHC II to present the Ag. Let’s think about it…. They can only present the virus’s Ag, not the gp120/anti-CD4bs complexes. This is too long in writing, how about presenting? Just kidding, It’s about that the Ag is already covered, so it’s useless to be presented.

This is so awful, even the last approach to bind HIV didn’t work. What are the researchers gonna do? What’s the next move? We’ll find out soon.

Image credits:
Anatomy of AIDS virus: http://www.roshanpakistan.com/

Nature, mother nature & the famous journal, taught us that every organism has its own defense mechanisms against various predators. For example, the famous antifungal agent (cyclohexamide) is obtained from the bacteria Streptomyces, on the other hand (Penicillin), the antibiotic, comes from the fungus Penicillium.

We all know phages, the nick name of Bacteriophages, the virus-like agents that infect bacteria making it sick.. Well not sick, but only degrade it like any other virus on the planet. As a matter of fact, Bacteria have to develop defense mechanisms against these phages:

1)They can cut their genome with restriction enzymes (endonucleases)

2)They can also undergo changes in their receptors, so the phage goes blind & never find it

3)They can act on the phage itself by making DNA modifications or even repression of their gene expression.

But now we’ll talk about a different defense mechanism (they love to call it: Special Forces). To know it, you’ve to meet CRISPR sequences (clustered, regularly interspaced, short, palindromic repeats). Not crispy, it’s CRISPR. Actually when I first read it, I was totally lost. I knew the meaning of every word separated from the very next. So I checked more & got this from the amazing blog of Tim “Phage Hunter“.

As you’ve read before, they are sequences found in almost 40% of sequenced bacteria & 90% of sequenced archaea. There are already identical repeats which form RNA stem-loops. Between those repeats, researchers found DNA which is similar to that of phages. That means that the bacteria use the RNA interference mechanism (an inhibitory gene expression mechanism).
CRISPR sequences are first transcribed, and then spliced to form small interfering RNA (siRNA), which are complementary to the target mRNA (the phage’s). Once binding achieved, no translation occurs, because they simply cleave it into little pieces.

So the array of these sequences is highly useful in determining the bacterial resistance to different phages. Y. pestis (aka Black death) has three CRISPR sequences in its genome. It’s something like acquired immunity, bacteria develop it after the infection of the phage, the survivors of course.

For people On The Run: Bacteria have a complementary sequence of their phages, to capture their RNA, stop the translation process.

Image credits:
Figure shows the role of siRNA in degradation of phage nucleic acids: http://www.phagehunter.org

July 2008: Santa Cruz, University of California

A surprising type of gene regulation found in mammals under the influence of RIBOZYME

A ribozyme, as the name implies, is an RNA molecule that can catalyze a chemical reaction. Although, RNA is mostly known to play a role in the encoding of genetic info, leaving the catalysis of biological reactions up to enzymes made out of protein. Now, scientists are discovering that RNA might be taking part in both.

The hammerhead ribozyme, previously known to be associated with viroids “plant viruses”, has been found in mice, rats, horses, and other mammals, embedded within certain genes & controlling their expression. Example of such genes are those involved in the body’s immune response & metabolism of bone. In these genes, the mRNA contains sequences that form a hammerhead ribozyme.

The hammerhead ribozyme is a self-cleaving molecule that cuts itself in two. That way, the protein translation is prevented & therefore, no gene expression takes place. To turn the process back on, the self-cleaving action is stopped. Exactly what shuts off the ribozyme action is not known, but assumed to be there.

Two interesting points come up now:

1. The hammerhead ribozyme sequences first appeared in the genomes of rat & mice and then turned up in other mammals but was not found in the corresponding human genes which suggests that a different mechanism DOES exist regulating those genes in humans.

2. The genes, being regulated by a hammerhead ribozyme, are involved in the immune response & in bone metabolism. Such finding can be targeted by the pharmaceutical industry to combat certain autoimmune diseases & bone disorders, which offers potential for better & safter healthcare treatment in the future.

May 2008

Gene Therapy: Seeing the future with new eyes

For the first time, doctors have used gene therapy to restore some vision in children with a congenital vision problem called Leber Congenital Amaurosis or “LCA” caused by a faulty gene (RPE65) 

The procedure involved the injection of a solution containing the normal gene, carried on an adenovirus vector, into the back of the retina of the affected eye.

In Britain, three patients have been treated with this experimental therapy. One has significantly improved & has been video-taped prior to the treatment & then six months later, traveling through a maze. Video HERE

The other two patients, aged 17 and 23, did not report any improvement, but did not suffer any side effects either.

Similarly, a US research team experimented on three patients, one aged 19 and two aged 26, and are reported to have improved vision as measured by standard eye tests, however, one developed a hole in the retina, thought to be due to the surgery itself.

This is a very significant milestone especially because researchers have been dealing with patients in the late stages of the disease & more hope is yet to come in those with the less-advanced form.

This is only the second time gene therapy has been proved successful in humans, after trials showed it was effective in the rare inherited disorder SCID (Severe Combined Immune Deficiency)