Prepared by daughter. Not to scale. Species not yet identified. Delicious.

Together with obesity, insulin resistance is the harbringer of metabolic syndrome. Insulin resistance is when the body cannot use insulin effectively. Insulin is needed to help control the amount of sugar in the body. As a result, blood sugar and fat levels rise.  Therein lies the path to morbid obesity, diabetes, stroke, and heart problems.

So what’s the connection of metabolic disease to bacteria? Well, for one thing, we know that in obese people the bacterial population in the gut is different, and the different population of bacteria may lead to a vicious cycle contributing to obesity.

Another possible connection has to do with an  important group of molecules in our body called Toll-like receptors, or  TLRs. TLRs are a family of  membrane proteins that sense a wide variety of bacterial populations and activate our innate immune system. TLRs are like a first-defense warning station: they sense the bacterial enemy first, and, if needed, activate the proper defense mechanisms. Researchers studying TLR-2 have created knockout mice lacking TLR-2, and they discovered is that many of TLR-2 knockout mice do not develop insulin resistance when fed with a high-fat diet. Think about it: all the McCrap you can eat, yet your blood sugar level remains normal (although you still grow fat).  So why does that happen? How come these mice lacking a bacterial sensor also seem immune to insulin resistance?

To answer this, we must understand that TLR receptors (quite a few are known so far) are known to serve as a bridge (or “mediate crosstalk”) between the immune system and the body’s metabolism.  Mice without TLR-5 develop eating disorder known as hyperphagia which is characterized by an increased appetite; they also show other pre-diabetic  symptoms: hypertension, high lipids, and insulin resistance. I have posted before about how TLR-5 may control the type of gut bacteria mice have and, in turn, control their propensity for obesity.

TLR-4 deficient mice, on the other hand, seem to be protected from insulin resistance, just like TLR-2 deficient mice. So a connection between these front-line sensors of the immune system and whole body metabolism is well-known.

A group of researchers from Brazil have decided to look further into these “diabetes resistant” mice. The thing about mutant TLR deficient mice, is that they are normally grown in sterile conditions because possible infections and because the uncontrollable gut microbes add uncontrolled variables to any experiment. When scientists cannot precisely control for experimental conditions, they face two choices: One, they can deviate from the model to emulate “real world” better, but sacrifice control of one or more of the variables in an experiment. Or, maintain full control of the experiment and sacrifice a simulation whatever they are trying to model. Most scientists go with the second option: they would prefer to have a well-controlled model, even if it supposedly detracts from its supposed practicality and application to “real life”. That is because a model (in our case, mutant TLR mice), is somewhat removed from the real thing anyway: mutant TLR-deficient are basically a  an artificial construct used to investigate the effect of knocking out a TLR from the mouse, so hopefully we can draw conclusions about humans. So the second type of possible error is the one scientists generally prefer to make.

Toll-like receptors: it's complicated.

But Andrea Caricilli and colleagues have decided to look at TLR-2 knockout mice in non-sterile conditions. Rememebr: TLR-2 knockouts seem to have protection from insulin resistance. What Caricilli and her colleagues discovered was quite the opposite of what was known so far: TLR-2 knockout mice were not protected from insulin resistance. Quite the opposite: the mutant mice developed metabolic syndrome. But did  the gut bacteria do it? To check that, the researchers treated the mice with broad-spectrum antibiotics for 20 days. After that, the bacterial species that re-colonized the mice’s guts were quite different in their composition from the bacterial species that originally inhabited them. And they did not have meteabolic disease, or the symptoms were much less severe.

So here it is: changing the mice’s gut microbiota changed them from mice with insulin resistance to mice without insulin resistance. Yes, there are mutant mice, but still: insulin resistance was turned off  by changing the types of microbes in the gut.

They then transplanted the microbiota from TLR-2 mutants which had insulin resistance to regular mice. And what do you know: the regular mice then showed symptoms of insulin resistance and metabolic disease.

There is a lot more to this paper than these two experiments: they have also investigated many other parameters, trying to come up with the chain of events that bacteria trigger when causing metabolic disease. I won’t get into that, the paper is quite long with some 20(!)  figures. A lot of work went into this. But the bottom line again supports what has been shown in other studies: the bacteria that live in our gut are responsible for our metabolism, and it is the interaction between the bacteria and our immune system that not only protects us from pathogens, but also protects us (or not) from metabolic disease.

 Update: this post has been slashdotted. Exercise extreme caution.

Caricilli, A., Picardi, P., de Abreu, L., Ueno, M., Prada, P., Ropelle, E., Hirabara, S., Castoldi, A., Vieira, P., Camara, N., Curi, R., Carvalheira, J., & Saad, M. (2011). Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice PLoS Biology, 9 (12) DOI: 10.1371/journal.pbio.1001212

 

The Dead Body That Claims It Isn’t: I’m not dead.
The Dead Collector: What?
Large Man with Dead Body: Nothing. There’s your ninepence.
The Dead Body That Claims It Isn’t: I’m not dead.
The Dead Collector: ‘Ere, he says he’s not dead.
Large Man with Dead Body: Yes he is.
The Dead Body That Claims It Isn’t: I’m not.
The Dead Collector: He isn’t.
Large Man with Dead Body: Well, he will be soon, he’s very ill.
The Dead Body That Claims It Isn’t: I’m getting better.
Large Man with Dead Body: No you’re not, you’ll be stone dead in a moment.

– Monty Python and the Holy Grail

So it goes between John Cleese, Eric Idle and John Young.

But there is a sea, or rather lake, that is not dead yet either, feels happy, and is going for a walk on Thursday. The Dead Sea, located in the Judean Desert, roughly divided between Jordan and Israel, has a salinity of 33% – more than eight times that of seawater (3.5%). No animals or plants can survive these conditions, and the lake does look dead to the casual observer. But in the late 1930s Benjamin Elazari Volcani discovered that the Dead Sea does, in fact, support several types of microorganisms. A bit of history: Volcani’s research into microbial life in the Dead Sea led to him being awarded the the first doctoral degree in microbiology by the Hebrew University of Jerusalem, 1943. In 1975, Mullakhanbhai and Larsen named Halobacterium volcanii, a halophilic isolate, after B.E. Volcani. It is now know as the archaean, not bacterium, Haloferax volcanii.

At 33% salinity we all float. When you're down here with us, you'll float too.

Several other archeael isolates were found, noting that the Dead Sea is not quite dead yet. In fact, the lake sports what might be an underreported biodiversity. In addition to archaea it also has fungi, bacteria, protozoa and mermaids. OK, maybe not mermaids.

Now the Dead Sea has been found to be more alive than ever. A groups of Israeli and German divers have found freshwater springs deep in the Dead Sea. The springs are about 30m deep, and lie in of large craters 30meters in diameter. Look at the video below, taken by the divers. Between 1:54 and 2:10 you can see the freshwater mixing with the saltwater. The stark differences in salinity makes for a surreal underwater smoke effect. And, the real kicker, at 2:26 you can see a thick microbial mat, like gunk all over the rocks near the spring.

It would be very interesting to find out who, exactly, comprises this mat. As far as I know, this analysis has not been published yet. But the initial results are reported in National Geographic:

Preliminary analyses of samples collected in the craters suggest that the springs’ bacterial communities are very diverse—akin to what you’d find living on rocks in a regular saltwater sea, he added.

The top of the springs’ rocks are covered with green biofilms, which use both sunlight and sulfide—naturally occurring chemicals from the springs—to survive. Exclusively sulfide-eating bacteria coat the bottoms of the rocks in a white biofilm.

Not only have the organisms evolved in such a harsh environment, Ionescu speculates that the bacteria can somehow cope with sudden fluxes in fresh water and saltwater that naturally occur as water currents shift around the springs.

All I can say is: wow. Microbial mats in the Dead Sea, which we only find about now. The  Dead Sea thriving with whole carpets of life. Who’d've thunk?

ELAZARI-VOLCANI, B. (1943). Bacteria in the Bottom Sediments of the Dead Sea Nature, 152 (3853), 274-275 DOI: 10.1038/152274c0

Mullakhanbhai, M., & Larsen, H. (1975). Halobacterium volcanii spec. nov., a Dead Sea halobacterium with a moderate salt requirement Archives of Microbiology, 104 (1), 207-214 DOI: 10.1007/BF00447326

Buchalo, A., Nevo, E., Wasser, S., Oren, A., & Molitoris, H. (1998). Fungal life in the extremely hypersaline water of the Dead Sea: first records Proceedings of the Royal Society B: Biological Sciences, 265 (1404), 1461-1465 DOI: 10.1098/rspb.1998.0458

Press Release
2011-10-03
The Nobel Assembly at Karolinska Institutet has today decided that
The Nobel Prize in Physiology or Medicine 2011
shall be divided, with one half jointly to
Bruce A. Beutler and Jules A. Hoffmann
for their discoveries concerning the activation of innate immunity
and the other half to
Ralph M. Steinman
for his discovery of the dendritic cell and its role in adaptive immunity

(Unfortunately, Steinman died between the committee’s decision and the announcement. He still received the Prize, though.)

However, it is not news (and not good)  that we are losing the arms race against bacteria. We are overusing antibiotics in medicine and in agriculture, virtually nurturing today’s and tomorrow’s killers. A report  in Wired earlier this year paints a bleak picture:

Truly new antibiotics are critically needed because bacteria, having no experience of them, cannot immediately mount resistance to them — something that does happen with me-too compounds featuring some slight molecular change. But they’re rare. As this chart from the research group Extending the Cure shows, antibiotic development has slowed dramatically over the past 30 years, and among the few drugs being brought forth, most share the mechanisms of already-existing classes.

To understand the extent of the crisis, we have to remember that antibiotics are the foundation of a huge number of  medical procedures, from cancer treatment to dentistry. Taking away this foundation would cripple modern medicine. Together with vaccines and public hygiene, antibiotics are the reason that many of us live longer — and better — than our grandparents’ generation and before that.

So lacking drug company motivation (more on that in McKenna’s report) and facing a dwindling supply of effective antibiotics, what are we to do?

A good start is to take a second look at nature. For example, here is a Kangaroo being born:

Awww…

The interesting thing about Kangaroos and other marsupials is that their young are being exposed at a very precarious stage to the outside world. Roo is born in a fetal state: underdeveloped, blind, barely moving and has little to no body temperature regulation. All of these problems are taken care of by Kanga’s protecting Roo’s six minute trip to her pouch where things are warm and cozy, and maternal milk flows in abundance. All except one: pathogens. During his trip, Roo can acquire a whole bunch of nasty bugs from Kanga’s fur and the air. Also, the pouch is not exactly a sterile environment and there is a possibility of infection there. So how is little Roo to survive the trip to the pouch and subsequent stay?

Joey in pouch. Photograph by Geoff Shaw (Zoology, University of Melbourne, Australia). From Wikimedia Commons.

The answer is innate immunity, that collection of mechanisms which protect the host in a non-specific manner. While his adaptive immunity is quite undeveloped, Roo does produce some killer all-purpose peptides he can use against microbes. The same class of peptides are produced in Kanga’s milk. Collectively they are known as cathelicidins. Only about 30 amino acids long, these highly charged molecules kill both gram-positive and gram-negative bacteria.

Since the tammar wallaby genome has recently been sequenced,  a group of Australian scientists has decided to hunt for cathelicidins in the tammar’s genome. They also looked for cathelicidins in the genomes of the duck-billed platypus (a monotreme) in the opossum (an American marsupial), in human, mouse, cow & sheep (all placentals).  Here is what they found. Each leaf on the tree represents a cathelicidin gene. The leaf colors and shapes are for different species of origin.

From Wang J, et al. 2011 PLoS ONE 6(8): e24030. doi:10.1371/journal.pone.0024030 Reproduced under CC license.

The marsupials and monotremes have a much higher diversity of cathelicidin genes than the placental mammals. Note that there are many duplicates of the cathelicidin gene in Pig and Cow, but these duplications are very recent as we can tell by the highly similar sequences of the genes. These duplications are probably because herd animals are more susceptible to pathogens.  In any case,  pig and cow have higher copy number of cathelicidin genes, and thus perhaps a large number of proteins, but not many different ones as in marsupials and monotremes. Diverse cathelicidin genes in the genome can offer a wider protective umbrella against many different types of pathogens.

Back to the antibiotic crisis: can we use marsupial cathelicidins as an antibiotic in humans? Do cathelicidins kill human pathogens? Are they toxic to humans? The authors checked the first two. They used cathelicidins from wallaby and platypus to kill human pathogens: P. aeruginosa, K. pneumoniae and A. baumanii, including antibiotic resistant strains. Cathelicidins were much more effective than, well, antibiotics against those bacteria. Also, cathelicidins did not kill human red blood cells, which makes them a potential drug. Of course,  immune reaction against cathelicidins as a foreign  still needs to be checked, among many, many other things, but the whole idea of looking at marsupials is that, as mamals, they may be able to supply us with clues on how to synthesize a cathelicidin to be used as a drug in humans.

The really cool thing about this study is that the authors used phylogenetics to design an ancestral wallaby cathelicidin. They aligned all the wallaby cathelicidin protein sequences, which were conserved in 40 of the 46 amino-acid positions. They used PAML, GASP and Ancescon to reconstruct an ancestral wallaby sequence, estimated to be 59 million years old, marked by an asterisk (*) in the above gene tree.  They then synthesized the ancestral WAM (Wallaby Anti Microbial) peptide and used it to kill bacteria. Guess what: the ancestral WAM was even better than the existing WAMs, as even a lower concentration was needed to kill bacteria. They are still working on red blood cell toxicity (yay for PLoS-enabled comments!)

So maybe the answer to  the increase in bacterial resistance to antibiotics lies in Kanga’s pouch. After all, she was very protective of Roo.

EDIT: clarified that the part about synthesizing and testing ancestral-WAM to kill bacteria.

Wang, J., Wong, E., Whitley, J., Li, J., Stringer, J., Short, K., Renfree, M., Belov, K., & Cocks, B. (2011). Ancient Antimicrobial Peptides Kill Antibiotic-Resistant Pathogens: Australian Mammals Provide New Options PLoS ONE, 6 (8) DOI: 10.1371/journal.pone.0024030

Tonight is Shavuot. That wonderful holiday which includes midnight studies, water-bombing and dairy products. Mmmmm…. cheese. A food product heavily embedded in the science of microbiology. Cheese is the founding product of the biotech industry (along with beer and bread).

Boaz asking Ruth on a date to the cheese and wine festival.

So here’s to Lactobacilli and Lactococci which are at the center of the production of dairy products. Breaking down milk sugar (lactose) into lactic acid, which curdles the milk protein casein.   Left to its own devices, this process generally produces rotten milk, since other bacteria may join the fray. Cheesemaking starts the process by  adding some rennet first. Rennet was originally and still being produced from cows’ upper stomachs. The active ingredient in rennet is chymosin, used to curdle milk drunk by calfs.  But 90% of  cheeses produced in the US and the UK now are made using recombinant chymosin,  produced in the fungus Aspergillus niger.

Lactobacillus sp. Source: wikipedia

Cheese also needs to ripen. Propionibacterium freudenreichii ferments lactate in the cheese to produce, among other things, carbon dioxide. This produces the holes we see in Swiss cheese. But it’s a finicky bug, and needs its faithful symbiotic companion Lactobacillus helveticus (“Swiss Lactobacillus“) to provide it with essential amino acids necessary for its growth.  P. freudenreichii is named after Eduardo von Freudenreich, a 19th century microbiologist who, among other things, wrote a seminal book on dairy microbiology.

Some cheeses are somewhat riper than others, as Asterix, Obelix and Dogmatix discover.

By the way, Propionibacterium acne a relative of Propionibacterium freudenreichii is a bacteria found on our skin which at times causes… yes, acne. But don’t think about acne when you eat Swiss cheese. (Now I put some people off Swiss for quite a while).

"Acne" comes from "acme" which means point, edge or peak. Here is an acme, but not acne.

Finally, mold. Penicillinum roqufortii provides those beautiful blue streaks in the sheep-milk cheese Roquefort… and the taste. Only cheeses aged in the natural Combalou caves of Roquefort-sur-Soulzon may bear the name Roquefort. Which is why it is so damn expensive.

And I haven’t even started upon Camembert (the real one is made from unpasteurized milk) ripened by  Penicillium candidum and Penicillium camemberti. Or kefir, made from the eternal Kefir grains, a matrix of bacteria and polysaccharides  that can be reused forever…. but I’m too hungry for cheesecake to continue this.

EDIT: typos. Thanks Martin!

Not a cell wall

So, for example, when I am developing computational metagenomics analysis tools, they invariably tend to target both bacteria and archaea. However, these tools are usually not good for microbial eukaryotes, due to different rRNA size, the larger genomes with more non-coding regions, lack of operons, organelles genomes, introns, etc. So for this utilitarian purpose, “prokaryotes” would be a good verbal shortcut to the cumbersome “bacteria and archaea” when describing or documenting the software. So can we all agree on “prokaryotes” as a verbal shortcut of necessity but not as a taxonomic definition? Or am I missing something substantial here?

An illustrative example of the rational, cool-headed debate that may ensue:

Herpetology Credit: xkcd.com

Miami University has  joined the National Genomics Research Initiative (NGRI) offered by HHMI Science Education Alliance (SEA) in their Phage Genomics course. The students go directly into the lab, participating in an authentic research experience. In a full-year academic course they:

• isolate and characterize bacterial viruses from their local soil
• prepare the viral DNA for sequencing
• annotate and compare the sequenced genome

The Department of Microbiology at Miami University is offering this course in the upcoming year: four of our faculty will be teaching it. Phage isolation, electron microscopy, DNA sequencing in the first semester, annotation and comparative genomics in the second. And I get to teach the bioinformatics bit: annotation and comparative genomics. Woo-hoo! The great thing about this course, is that unlike most lab courses, the students (and faculty) will be setting up experiments intended not only to teach, but also to discover something new.  Also, the results of the research are meaningful. Genomics data generated by student participants will be used by other researchers to answer medical, ecological, and evolutionary scientific questions. Bacteriophages (viruses that infect bacteria) affect the biopsphere so profoundly, it is almost impossible to imagine. Their sheer biomass is equal to that of 75 million blue whales, and marine bacteriophages  kill about half of marine microbes every day. Bacteriophages have a huge host range, mind-boggling number of particles in the biosphere (10³⁰) and, above all, the genetic diversity is unmatched by all other life combined. Participating students will see how their data may be used by other researchers in the SEA network — truly collaborative, crowdsourced science. Here are the genomic sequences of SEA-sequenced bacteriophages already in GenBank.

If you are an incoming Miami freshman, and want to jump in and do some real science, it doesn’t get much better than this. Check out our course page, and ask about the Bacteriophage Biology course in your orientation. You may even get your name on a paper like these students from other participating universities.

Pope, W., Jacobs-Sera, D., Russell, D., Peebles, C., Al-Atrache, Z., Alcoser, T., Alexander, L., Alfano, M., Alford, S., Amy, N., Anderson, M., Anderson, A., Ang, A., Ares, M., Barber, A., Barker, L., Barrett, J., Barshop, W., Bauerle, C., Bayles, I., Belfield, K., Best, A., Borjon, A., Bowman, C., Boyer, C., Bradley, K., Bradley, V., Broadway, L., Budwal, K., Busby, K., Campbell, I., Campbell, A., Carey, A., Caruso, S., Chew, R., Cockburn, C., Cohen, L., Corajod, J., Cresawn, S., Davis, K., Deng, L., Denver, D., Dixon, B., Ekram, S., Elgin, S., Engelsen, A., English, B., Erb, M., Estrada, C., Filliger, L., Findley, A., Forbes, L., Forsyth, M., Fox, T., Fritz, M., Garcia, R., George, Z., Georges, A., Gissendanner, C., Goff, S., Goldstein, R., Gordon, K., Green, R., Guerra, S., Guiney-Olsen, K., Guiza, B., Haghighat, L., Hagopian, G., Harmon, C., Harmson, J., Hartzog, G., Harvey, S., He, S., He, K., Healy, K., Higinbotham, E., Hildebrandt, E., Ho, J., Hogan, G., Hohenstein, V., Holz, N., Huang, V., Hufford, E., Hynes, P., Jackson, A., Jansen, E., Jarvik, J., Jasinto, P., Jordan, T., Kasza, T., Katelyn, M., Kelsey, J., Kerrigan, L., Khaw, D., Kim, J., Knutter, J., Ko, C., Larkin, G., Laroche, J., Latif, A., Leuba, K., Leuba, S., Lewis, L., Loesser-Casey, K., Long, C., Lopez, A., Lowery, N., Lu, T., Mac, V., Masters, I., McCloud, J., McDonough, M., Medenbach, A., Menon, A., Miller, R., Morgan, B., Ng, P., Nguyen, E., Nguyen, K., Nguyen, E., Nicholson, K., Parnell, L., Peirce, C., Perz, A., Peterson, L., Pferdehirt, R., Philip, S., Pogliano, K., Pogliano, J., Polley, T., Puopolo, E., Rabinowitz, H., Resiss, M., Rhyan, C., Robinson, Y., Rodriguez, L., Rose, A., Rubin, J., Ruby, J., Saha, M., Sandoz, J., Savitskaya, J., Schipper, D., Schnitzler, C., Schott, A., Segal, J., Shaffer, C., Sheldon, K., Shepard, E., Shepardson, J., Shroff, M., Simmons, J., Simms, E., Simpson, B., Sinclair, K., Sjoholm, R., Slette, I., Spaulding, B., Straub, C., Stukey, J., Sughrue, T., Tang, T., Tatyana, L., Taylor, S., Taylor, B., Temple, L., Thompson, J., Tokarz, M., Trapani, S., Troum, A., Tsay, J., Tubbs, A., Walton, J., Wang, D., Wang, H., Warner, J., Weisser, E., Wendler, S., Weston-Hafer, K., Whelan, H., Williamson, K., Willis, A., Wirtshafter, H., Wong, T., Wu, P., Yang, Y., Yee, B., Zaidins, D., Zhang, B., Zúniga, M., Hendrix, R., & Hatfull, G. (2011). Expanding the Diversity of Mycobacteriophages: Insights into Genome Architecture and Evolution PLoS ONE, 6 (1) DOI: 10.1371/journal.pone.0016329

There are some interesting developments regarding the February outbreak of Legionelliosis which was traced to the Playboy mansion. Reminder: over 120 delegates of the DOMAINFest in Santa Monica, California came down with symptoms of a respiratory illness. The convention included a trip to the Playboy mansion, which later was suspected as the outbreak source. The convention was held Feb 1-4, 2011. The first inquiry to the  LA County Department of Health (LAC DPH) of a suspected legionellesis outbreak was made by the media on February 11. When tracing the outbreak, LAC DPH and CDC scientists discovered a trail of reports preceding February 11 in social media,  including Facebook and Twitter. The Wikipedia entry was updated almost at the same time when the LAC DPH inquiry was made.

Source: LA Times. From a presentation by Dr. Caitlin Reed

Note that there is quite a bit of information in this entry already!

The scientists identified several risk factors: staying at either one of the hotels, and two parties. They assessed the exposure risk based on the fraction of people who were in those venues and who became sick. To do so, they circulated questionnaires, via email and a Facebook list. They came up with this:

Source: LA Times. From a presentation by Dr. Caitlin Reed

The February 3 “Venue A” party seemed to hold the largest relative risk (RR), by far.  That was the Playboy mansion. Indeed, checking the water at the grotto where the party was held:

Source: LA Times. From a presentation by Dr. Caitlin Reed

The scientists concluded that use of social media to trace outbreaks has its pros and cons. The biggest pro was the ability to contact all conference attendees quickly, even though they are geographically dispersed. Also, the Facebook list, tweets and email encouraged a fast response to the survey. They did have some red herrings, and had to put effort into rumor control. I am not sure how much the last two were amplified by the social media effect.

The full slide presentation, and more information are at the Los Angeles Times.

A woman in Chesterfield, Ohio robbed a convenience store using her MRSA-infected arm as a weapon.  Warning: graphic picture of MRSA infected arm. Or a zombie limb. You can never know in northwestern Ohio.

Scanning Electron Microscope image of Methicillin-Resistant Staphylococcus aureus or MRSA. Credit: Janice Carr. Source: wikipedia

A US vector biologist got infected with Zika virus which is  a mosquito-borne pathogen causing joint pain and fatigue. He then passed in on to his wife during sexual intercourse. This would be the first documented case of sexual transmission of an insect-borne pathogen. Also, “Honey, Iswear, I got it from a mosquito bite” is the new excuse for two-timing spouses everywhere.

April’s fool came and went on the intertubes.  My favorite was the arsenic based sea-monkeys.

Great news for geeky kids of the 1980′s: the Commodore 64 is back!  Same nice bulky keyboard-in computer, with just a little bit more than 64K of RAM underneath:

“The upcoming Commodore 64 looks exactly like the ancient model which reshaped the home computer sector decades ago, though underneath the bonnet things have been brought well into the 21st century.

“Even though the computer refrains from relinquishing its old charm, it will come packed with modern computer hardware. The new Commodore 64 model will contain a mini-ITC motherboard, a dual core Intel 525 Atom processor, DDR3 RAM between 2GB and 4GB and Nvidia Ion2 graphics unit.

“Commodore says that the device will run on the Ubuntu 10.04 LTS OS and will come with a DVD drive, with support for Blu-Ray, a multi-format memory card reader and five USB slots. The new Commodore 64 will also come with Wi-Fi support and will come pre-loaded with 3D games and other applications including a Microsoft Office compatible productivity suite.
Read more: http://www.itproportal.com/2011/04/06/iconic-commodore-64-all-set-comeback/#ixzz1IqxQ1LXX

 

Finally, remember the name: Zhuchengtyrannus magnus (zoo-CHENG TEER-ah-nus MAG-nus) or Z. magnus. A new dinosaur discovered in Zucheng, China. Related to Tyrannosaurus rex it is 4m tall, 11m long, 6 tons of carnivorous mass. The original paper.