On a Tuesday, the year 1995, Graham, a 57-year-old patient on the verge of congestive heart failure, received a call that a donor has been found. This donor committed suicide via a self-inflicted gunshot wound. After the successful transplant, Graham got in touch with the donor’s family, married his wife and after a whopping 12 years later,  kills himself through the same technique. In an interview held a couple of years after his marriage, he admitted to the reporter that after seeing the donor’s ex-wife, he felt as if he had already known her for years.

Ever since heart transplant surgeries were a success in 1967, scientists were skeptical about what is now referred to as, Cellular Memory Phenomenon.  This was provoked through the close observation of recipients, who repeatedly report bizarre distant memories and new personal preferences. Exactly how much can the cells of an organ, other than the brain, mainly the heart in this case, store memories? The Discovery Channel aired a documentary titled “Transplanting memories” where various experts gave their opinion on the matter.

If such phenomenon truly exists, where are these memories located inside the cells? Could it be the DNA? But this is sheltered inside the nucleus and remains entangled except when cellular division takes place. This makes its access difficult, but after all, it cannot be THAT difficult, otherwise mutagenic agents wouldn’t have succeeded.

Possibly proteins. Dr. Candace Pert stated that, since the brain and human organs are linked through a massive network of peptides. She said “I believe that memory can be accessed anywhere in the peptide/receptor network. For instance, a memory associated with food may be linked to the pancreas or liver, and such associations can be transplanted from one person to another.”

Source:  The Medical News

Image Source: Hiveworld

Tags: cellular memory, discovery channel, Graham, heart, phenomena, suicide, transplant, transplanting memories

Not too long ago, I read about a research done at the Kennedy Institute of Rheumatology Division, which has identified a new ligand for Toll-like receptor 4. This receptor was previously known for activating the immune system through the detection of threats as lipopolysaccharide or gram-negative bacteria. The new ligand, Tenascin-C, is an extracellular glycoprotein, whose elevated expression in cases of inflammation provoked scientists to study its role in the process.

The study noted that its presence was critical to maintain the ongoing inflammation seen in cases of rheumatoid arthritis. In reference to this study, the author stated “We have uncovered one way that the immune system may be triggered to attack the joints in patients with rheumatoid arthritis. We hope our new findings can be used to develop new therapies that interfere with tenascin-C activation of the immune system and that these will reduce the painful inflammation that is a hallmark of this condition”

I was able to contact Dr Kim Midwood and obtained this brief interview:

Tags: chronic inflammation, DAMPs, endogenous, inflammation, Interview, intracellular signal, Kim Midwood, ligand, pro-inflammatory, rheumatoid arthritis, rheumatoid therapy, Tenascin, TLR4, Toll-like receptor

When you hear/ read the term “Phage Therapy“, you’ll be automatically directed to the concept of using bacteriophages, the virus-like particles that infect bacteria, to kill/ lyse the resistant bacterial strains, instead of the “useless” antibiotics that allowed bacteria to fool them & develop resistance against them. The initial target of phage therapy was to kill the bacteria using phages; because they act like any other virus; get in, multiply and lyse the cell. But, by this way, bacteria develop resistance against phages more rapidly. So, they may become useless by time. In this paper from PNAS: “Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy,” two bioengineers, Timothy K. Lua and James J. Collins, from Boston University successfully engineered the Enterobacteria filamentous phage M13 to weaken bacteria not to kill it. Sounds strange, right? By engineering M13, they gave us a variety of options:

1^st, we may make M13 overexpress a bacterial protein named lexA3 which inhibits the ability of the bacteria to repair their damaged DNA by the action of Ofloxacin –as pharmacophils, who had 2 consecutive chemotherapeutics courses, we may recall that quinolones’ MOA is generation of ROS. So, the repressor suppresses the bacterial SOS mechanism. Very promising results were observed; the adjuvant therapy increased the survival rate of mice infected with resistant E. coli. It was also observed that the adjuvant therapy reduced the rate of developing mutations/ resistance within the E. coli population.

2^nd, bacteriophage can be responsible for expression of certain proteins that can attack gene networks in bacteria which are not target for existing antibiotic classes. I will mention just one example here, expression of CsrA which is a “global regulator of glycogen synthesis and catabolism, gluconeogenesis, and glycolysis, and it also represses biofilm formation,” biofilms is thought to be related to antibiotic-resistance and OmpF porin which is used by quinolones to enter the bacterial cell, it may enhance its entrance.

Now, thanks to the engineered phages, we can use the old beloved antibiotic classes to treat bacterial infection using the engineered phages as an adjuvent therapy to potentiate the cidal action of the antibiotic on the former-resistant strains. A precaution was made to ensure that no lysogeny would take place in the human cells is that the phages were engineered to be “nonreplicative”. But we still have two problems regarding Phage Therapy in general: identifying the strain responsible for the infection & making sure that the human immune system won’t elicit an immune response against phages, they’re “foreigners” after all!

Image credits:

1- “Schematic of combination therapy with engineered phage and antibiotics. Bactericidal antibiotics induce DNA damage via hydroxyl radicals, leading to induction of the SOS response. SOS induction results in DNA repair and can lead to survival. Engineered phage carrying the lexA3 gene (lexA3) under the control of the synthetic promoter PLtetO and an RBS acts as an antibiotic adjuvant by suppressing the SOS response and increasing cell death”: http://www.pnas.org/content/106/12/4629.figures-only

2- “CsrA suppresses the biofilm state in which bacterial cells tend to be more resistant to antibiotics. OmpF is a porin used by quinolones to enter bacterial cells. Engineered phage producing both CsrA and OmpF simultaneously (csrA-ompF) enhances antibiotic penetration via OmpF and represses biofilm formation and antibiotic tolerance via CsrA to produce an improved dual-targeting adjuvant for ofloxacin”: http://www.pnas.org/content/106/12/4629.figures-only

Tags: antibiotic, bacteriophage, bioengineering, engineered bacteriophage, M13, ofloxacin, phage, phage therapy, resistant

On February 28, 1953, James Watson and Francis Crick announced to their friends that they have discovered the chemical structure of the DNA. After publishing their paper in Nature on April 2, the official announcement took place on April 25.

That is what I have read in Al-Ahram newspaper today. What a discovery! Imagine if they had not done it, we would have had no clue about genes & protein synthesis, no recombinant DNA tech- & no sequencing. We would have had no molecular biology departments in universities! Abby from NCIS & Greg from CSI would have had no job!

So, what was the real story? To what extent are the “rumors” saying that Rosalind Franklin is the real discoverer of the DNA double helix right? Is she really the “Dark Lady of DNA”?

I hope we can get the story through your comments after we read this:

1- Crick papers from the National Library of Medicine.

2- Watson’s interview with a group of top North Carolina high school students in 2003.

3- BBC celebrating the 50th anniversary of DNA structure discovery in 2003. (really interesting)

4- Rosalind Franklin: Dark Lady of DNA by NPR (National Public Radio)

Image credits:
Watson – Crick DNA model: http://www.cs.princeton.edu/
Rosalind Franklin: http://www.npr.org/

Tags: 1408f278d2a6f884de58c0c44b7a6af7, DNA, Francis Crick, James Watson, Rosalind Franklin

Hello, hello. You’re now tuned to your favorite blog: micro-writers.egybio.net. Tonight we have this very special guest, live, online. After two months of waiting, we finally got this exclusive interview with the emerged Streptococcus pyogenes strain, the most dangerous ever, M1T1. We have it here, with us, in the studio.

- Hello, M1T1. Welcome in our studio.
- Hey there.

- We knew from our resources, which are totally classified, that you got yourself in trouble recently.
- (Interrupting), I did NOT get myself in trouble. EID set me up.

- M1T1, Would you please calm down & tell us a little more about yourself?
- Well, I belong to Group A streptococci (GAS) aka Streptococcus pyogenes. M1T1 is my serotype; I’m just a clonal strain. As you know, S. pyogenes colonize human skin & throat causing either non-invasive (sore throat, tonsillitis & impetigo) or invasive (necrotizing fasciitis NF, scarlet fever & streptococcal toxic-shock syndrome STSS) infections. Actually, NF gave me my nick: Flesh-eating bacteria.

- So, you cause all people NF & STSS?
- No, kid. It depends on their genetic susceptibility, what you call “Host–pathogen interactions”. I was isolated from patients with invasive as well as non-invasive infections during 1992–2002. This is NOT entirely my fault; humans can make me extra virulent by selecting the most virulent members.

- Back to your history, when have you exactly been isolated?
- M1 & her sisters were the worst nightmare in US & UK in the 19^th century as they caused the famous pandemic of scarlet fever. “Nevertheless”, early 1980s was the golden age of my strain as well as my very close sisters M3T3 & M18. We caused STSS & NF in different parts of the world. Great times, great times!

- Only for you, I suppose! So, what made you hypervirulent? What caused you this “epidemiologic shift”?
- Two reasons Dr Ramy K. Aziz identified that improved my fitness to humans: the new genes I got from phages & “host-imposed pressure”. Both resulted in the selection & survival of me M1T1 the hypervirulent strain. Dr Aziz’s work at Dr Kotb’s lab resulted in identification of a group of genes I got from phages that changed my entire life.

- Interesting! Tell us more about that. How did phages “change your life”?
- Dr Aziz proved that I differ from my ancestral M1 when he found that I have 2 extra prophages (lysogenized phages didn’t get the chance to lyse me, so they became integrated in my genome):
1. SPhinX which carries a gene encodes the potent superantigen SpeA or pyrogenic exotoxin A (scarlet fever toxin).
2. PhiRamid which carries another gene encodes the most potent streptococcal nuclease ever, Sda1.
3. He also found that phages conversion from the lytic state to the lysogenic state resulted in exchange of toxins between our different strains (aka Horizontal Gene Transfer). Phages are very good genetic material transporters, what makes “strains belonging to the same serotype may have different virulence components carried by the same or highly similar phages & those belonging to different serotypes may have identical phage-encoded toxins.” What a quote from Rise and Persistence of Global M1T1 Clone of Streptococcus pyogenes.

- Well, It was not that interesting. So, what? What’s the significance? How that made you hypervirulent?
- You can’t get it? You’re not that smart, are you? Tell me, what made M1 hypervirulent causing scarlet fever in the 1920s and me hypervirulent causing STSS in the 1980s with a 50-years decline period?

- Superantigen?
- Exactly. You do have your moments! Superantigen encoding-gene was present in us and absent in strains isolated in the period between them. The interesting part, for me of course, that humans after 50 years of absence of hypervirulent strains had absolutely no superantigen-neutralizing antibodies. That was the real invasive party. Superantigen causes high inflammatory response because of its non-specific binding to immune system components (antibodies & complements) causing an extremely high inflammatory response. In fact, SuperAg inflammatory response is “host-controlled”.

- So, what about Sda1?
- Streptodornase (streptococcal extracellular nuclease) helps me to degrade neutrophils that entrap me in the neutrophil extracellular traps (NETs). So, I can invade humans freely & efficiently and be able to live in their neutrophils. Dr Aziz proved in his paper “Post-proteomic identification of a novel phage-encoded streptodornase, Sda1, in invasive M1T1 Streptococcus pyogenes” that it’s all about C-terminus in my Sda1; the frame-shift mutation increased my virulence while deletion decreased it.

- Now we know about your SuperAg & nuclease (DNase), what’s the “host-imposed pressure”?
- I have my own SpeB (Protease), I use it to degrade my other proteins (virulence factors), which provides me with a good camouflage & gives me access to blood. When the host immune system recognizes me, it traps me in NETs. At this time, I secret Sda1 to degrade neutrophils. Actually, SpeB protects you, humans, from my Sda1& my other toxins. When SpeB was compared in patients with severe & non-severe strep infections, it was found that SpeB wasn’t expressed in case of severe infection. Expression of SpeB may be host-controlled, as host selects the mutants with a mutation in covS, a part of my regulatory system which regulates my gene expression including SpeB gene.

- Finally, M1T1. How do you see your future?
- More new phage-encoded genes, more selection of the hypervirulent strains by the host & more regulation of expression of my virulence factors. Pretty good future! I also count on humans to not develop immunity against me like what happened in 1980, when I got new virulence factors or allelic variations in my old ones.

Thank you, M1T1. Pleasure talking to you…….M1T1? M1T1, where are you? Why do I feel this strange pain in my throat?

Image credits:
Streptococcus pyogenes: http://adoptamicrobe.blogspot.com/

Tags: covS, epidemiologic shift, flesh-eating bacteria, global M1T1 clone, group A streptococci (GAS), horizontal gene transfer, host-imposed pressure, host–pathogen interactions, impetigo, M1T1, Malak Kotb, necrotizing fasciitis, neutrophil extracellular traps (NETs), phage-encoded toxins, pyrogenic exotoxin A, Ramy K. Aziz, S. pyogenes, scarlet fever, sore throat, streptococcal nuclease Sda1, streptodornase, STSS, superantigen SpeA, tonsillitis

To yet again prove Darwin’s theory, in a new study done in the University of Wisconsin, researchers have discovered that eight hearing-related genes have evolved over a time range of 40,000 years to cope with the ever-changing complex nature of verbal communication between human beings. Some of these changes are as recent as 2000 years ago.

As sound waves enter the ear, stereocilia “shown in orange” move. This movement is converted to electrical signals headed for the brain.

Seven of those genes are concerned with the production of proteins which make up the stereocilia & membranes that surround it. The 8th gene makes up structures which transmit sound waves to the inner ear.

Since communication requires both a talking tongue on one end & an ear capable of hearing on the other, the genetic changes concerning the ear must have favored a portion of the population to become better adapted to the “hearing process”. In any defense, they could have been able to detect on a more precise level, the emotional status of the person behind the spoken words, point out unconfidence in a specific speech, or even seperate out a conversation in the midst of a crowd.

This discovery certainly challenges the idea that languages have emerged from a single mutation which in somehow allowed the tongue to correctly twist, fold up & down, curve around within the buccal cavity & create the familiar sounds we know today.

This shows that not only human evolution has been going on since humans, or even neandertals for that fact, have existed but it continues all for the sake of a more prosperous life on our mother Earth.

Source & Image Credit: Science News

Tags: ear, gene, language, stereocilia

The title stunned me as I was surfing the Yahoo News. At some evolutionary phase, birds really did have thumbs. So what happened to them? Researches at Yale University and the University of Wisconsin propose that it shifted its position after studies made on the gene expression in crocodiles, as published in PLoS ONE.

Going back now, birds have only three fingers, which until very recently where believed to be the 2nd, 3rd, and 4th respectively. The only problem this faced was that fingers in the early birds such as Archaeopteryx correspond to number 1, 2, and 3 “thumb, forefinger, and middle finger”. Fossil records clearly indicate that finger 4 and 5 “ring and pinky finger” were lost in the flying dinosaur ancestors of birds.

To end this debate, researchers began to focus on the expression of HoxD11 gene. In mice, digit 1 had no expression for this gene, which also held true for the 1st digit in birds, which suggests that in reality, it is actually a thumb. But to test this, it was compared to crocodiles, the closest living relatives to birds. The findings did in fact support what they suspected. The expression, as in mice, was absent only in finger one “the thumb”

So, birds at one time had thumbs. And the fact remains because they still do. It chose to develop at a different position in the body, that’s all.

Tags: birds, crocodile, digit, dinosaur, finger, HoxD11, thumb

Who could possibly believe that our anaerobic spore-forming Clostridia will be used as an anti-tumor therapy?! It’s called Clostridium-based tumor targeted therapy. “Give me a break,” that’s exactly what I said when I read the review of the new book Clostridia: Molecular Biology in the Post-genomic Era.

So, how does it work? There are various non-pathogenic Clostridia strains which could replicate within solid tumors upon systemic administration. The interesting part is coming right up: Why solid tumors?! It’s because of its very unique physiology; it characterized by hypoxia & necrosis which totally fits the anaerobic Clostridia. The advantage will be the selectivity & targeting of the cancer cells leading to destroying them.

It was news to me to know that Cl. perfringens causes food poisoning like any food-borne illness & causes antibiotic-associated diarrhea (When I hear the name Cl. perfringens, I orient myself toward gas gangrene right away). Its enterotoxin gene (cpe) is present on the chromosome itself (in food poisoning isolates) and on the plasmid (in the antibiotic-associated diarrhea isolates). The enterotoxin binds to claudin receptors, then there’s oligomerization or “prepore” formation & finally prepore insertion takes place to form the functional pore which kills the cells by apoptosis. So CPE/CPE derivatives could be used for cancer therapy.

Tags: anti-tumor, clostridia, Clostridium-based tumor targeted therapy, CPE/CPE, enterotoxin, solid tumors

Have you ever heard about the terrorist attacks of anthrax via mail in 2001 in US that finally ended with Bruce Ivins, the chief suspect in those attacks, committing suicide?

What about tracing microbe sources as in the Salmonella US outbreak?

This is microbial forensics.

Microbial forensics uses biological analysis such as genome sequencing, protein and carbohydrate fingerprinting to figure out the source of a biological agent. 2001 was not the year which witnessed the emergence of microbial forensics. Actually, in 1998 a doctor from Louisiana, who intentionally infected his former mistress with HIV, had a trial in court. But the anthrax attacks were really the reason for the amplification of the role of microbial forensics as it was followed by government funding and developing the sequencing techniques into more cheaper ones.

As a result, microbial forensics is extrapolated to further applications beyond biocrimes. In molecular epidemiology, it will help figuring out the source of food or water borne diseases such as in recent US Salmonella outbreak. The field also is expected to provide help in hospital-acquired infections. Many people sue hospitals every year claiming they got MRSA (methicillin-resistent Staphylococcus aureus) infection from a certain hospital. Tracing the source of the infection will prove whether those people really contracted the infection from the hospital or from any other outside source.

Image source

Reference: Ontogeny

Tags: bioterrorism, Epidemiology, forensics, MRSA, nosocomial infections, Salmonella

In a study conducted by researchers in the University of Maryland School of Medicine, physical activity has proved to counteract FTO gene “fat, mass, and obesity-associated gene” in a group of European descendants who resided in the USA, known as Old Order Amish.

FTO gene has recently been linked to obesity & increased BMI “Body Mass Index” in numerous studies. Europeans usually have one or two copies of a variation of this gene. The research has enforced this prior assumption but brought, yet, another advantage since the study was done on 704 men & women of similar descent and thus similar genetic makeup, which what makes them ideal for genetic research. This helped researchers study the effect of physical activity on the expression of this gene.

In subjects, who were physically active throughout their daily routine, having multiple copies of the FTO gene didn’t seem to affect their BMI, despite the fact that in those, who were less active, a link between their BMI and FTO gene was obvious. This suggests that the choices one has to make in everyday life can deeply impact our body’s response to its own genes.

In order to compare the different variations in this gene, subjects were asked to wear accelerometers to measure their body movement on a 24-hour basis for seven days. They were then classified accordingly in order to conduct a comparative analysis. The genetic analysis revealed that 26 SNPs in the FTO gene were linked to BMI.

In the future, this may help tailor methods to prevent obesity in genetically susceptible individuals. So, after all we can’t blame it on our genes. Our decisions might in fact make up who we are & who we will become.

Source: Medical News today

Original research paper: Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity. PMID: 18779467 (Vote for the abstract on Biowizard)

Image Source

Tags: accelerometer, Amish, BMI, fat, gene, gene variant, obesity, SNPs