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TWiV 108 Letters

Zephyr writes:

Hello everyone, dear doctors Racaniello, Despommier, Alan Dove and Rich Condit,

I've been a devoted listener since April 2009. Like many others listeners then I quickly caught up with all previous episodes (I'll never forget that memorable one devoted to the recent West Nile Virus epidemic) and since then I haven't missed one. I really enjoy listening to your program, it combines an invaluable source of information and knowledge about Virology extending to more general subjects on science and research, with a highly entertaining and educative format, a dynamic discussion between colleagues about a specific topic, something I always felt missing during my undergraduate years.I also appreciate many of the recommendations you've given during the programs such as the podcast Meet the Scientist, that Carl Zimmer's program is another example of a podcast on science of very high quality with well made interviews, good guests and interesting topics like yours.

What moved me to write this letter is that in this week's TWiV episode No.107 Doctor Racaniello seemed to regret having overlooked for more than 2 years the news about the development of a new recombinase that can specifically recognize and excise from the host genome the HIV-1 LTR flanking sequences (actually for more than 3 years since the 1st results were published in June 2007 in Science).

That overlook must have been a quirk of fate since the topic had been already around the program in the past: In episode No. 66 another listener asked about the possibility of excising the HIV integrated virus in a letter read during the program. The question made me remind of the article published in Science I had read not so long ago. That same week I wrote a brief description of the work and bibliographic reference in the Comments section of 'TWiV 66: Reverse Transcription'. It has been the only comment I've ever written in TWiV so I couldn't forget it. After nobody else commented those results I assumed that those experiments were considered as devoid of any practical value for the treatment of HIV infections in humans.

In spite of that, since I first read that article I've firmly believed that the development of new enzymes and other proteins by means of some directed-evolution strategy will eventually become a powerful tool in research and bioengineering. Since then I've also heard from the use of a similar directed-evolution strategy in the development of new tRNA-aminoacyl-tRNA synthetase pairs that have been successfully expressed in bacterial and eukaryotic cell systems. As a result these cells can incorporate to nascent peptide chains new unnatural amino acids encoded by either a particular barely-used stop codon or one or even more tetrads, specific sequences of 4 nucleotides specifically recognized by those evolved tRNAs. This new unnatural amino acids can be used to develop enzymes capable of catalyzing new types of reactions never handled by enzymes before, to specifically label proteins in vivo, and in the study of the 3 dimensional structure of proteins as site-specific NMR landmarks.

Thanks for your program and keep up with the good work,

Zephyr

Raphael writes:

I am a student in Dr.Isern's Virology class at Florida Gulf Coast University (Can't wait for you to T.W.I.V. it up here in Fl, December 6th). Recently I watched T.W.I.V. #66, Reverse Transcription, in which you were talking about integration of HIV-1 into the host's genome. At 49 minutes and 45 seconds you mentioned that you "Do not know much about chromosomal structure," with respect to why HIV-1 generally integrates into the exposed area on a nucleosome. It would make sense that HIV-1 would integrate into "exposed area on a nucleosome" because, as I understand from genetics, the unwound/more exposed areas of DNA are being/about to be actively transcribed [euchromatin] and otherwise the DNA is too tightly bound to the core histone proteins. Secondly, I was wondering if you can do a T.W.I.V. on cancer associated viruses in general (I.e. which ones have a more definitive association with causing cancer, some mechanisms of their viral replication cycle, receptor pathways affected, what exactly do anti-viral anti-cancer drugs target, etc). Sorry if this sounds vague, yet I am purposefully wording it as such to give you leeway as to what you wish to speak about with respect to cancer causing viruses. Can't wait to see your next T.W.I.V. as well as see you live December 6th.

Sincerely,

Raphael

Career Goal:Cardiopediatric Diagnostician with specialty in infectious diseases/autoimmune disorders

James writes:

Hi Vince,

I heard you ask Dick why DNA viruses need their host cells to be replicating for them to be able to duplicate their genome and you guys concluded that the replication machinery is always off when the cells are not replicating and thus the viruses can't access it. I remember we pondered over that in my virology class last year and we concluded that when the cell is not dividing, the nuclear envelope is still intact hence the virus can't access the replication machinery which is usually inside the nucleus. On the other hand, the nuclear envelope is degraded in replicating cells and hence the virus can access the replication machinery in the nucleus. I thought that could be another reason.

James

Daytona Beach, Fl

Øystein writes:

Dear Professor Vincent Racaniello and the rest of the TWIV crew

My apologies for not having emailed you before! I am 32 year old physician currently undergoing training as a medical microbiologist in Norway. Since first discovering TWIV in the spring of 2009 I have been following every episode with enthusiasm. You're on my headphones when I'm walking, skiing, biking, driving, and especially when doing house and garden work! I listen because it's fun, and because I enjoy the spirit of discovery and discussion that your show is full of.

Almost as a side effect I have also had lots of help from TWIV in my daily job, helping , amongst other things, to inform my views during the influenza pandemic, during my work with diagnosing hepatitis B and C, and , lately , when trying to make sense of the proposed link between XMRV and chronic fatigue syndrome.

On that last note, if you haven't received it yet, I thought you might be interested in this latest article on MLV-related viruses in CFS-patients. Yes, the Harvey Alter article is finally out in the PNAS ,and I just got hold of it today:

http://www.pnas.org/content/early/2010/08/16/1006901107.full.pdf+htm

I am sure you will find an occasion to comment on it, so no pressure yet! I still retain a (hopefully!) healthy scepticism about the CFS / XMRV/MLVrV (?)-link, but have to admit the detective work and debate is intriguing.

I'll send you a separate TWIP email one day, as it deserves separate and positive, attention!

Best regards,

Øystein

Norway

Jon writes:

Heya Vincent and gang - my quick twiv contribution:

('digital finger painting' iPad using brushes app)

Raihan writes:

Greeting TWiVerrs.

I'm Raihan, a big TWiV fan in Singapore. You guys rock!!

Anyway i just wanna share with you some local news regarding the release of genetically modified mosquitoes in some states in Malaysia (Singapore's neighbour) to combat dengue.

I find this move really bold and potentailly contrevisial, but i'll leave the judgement to you guys.

http://www.channelnewsasia.com/stories/afp_asiapacific/view/1077780/1/.html

Hope this is relevant to your discussion

Keep up the amazing work,

Raihan

(Alan, ever thought of writing a joke book?)

Stephen writes:

Pertaining to your interview with Dr. Ila Singh in TWiV94, I wanted to clarify some language you and a guest used that adds to the confusion about Chronic Fatigue Syndrome. During the broadcast, you refer to CFS in shorthand as ‘chronic fatigue'. Since you are a scientist that appreciates precision, I will point out that this characterization of CFS is incorrect because the phase refers to two general, distinct descriptions of different things:

1. ‘Chronic fatigue' used by itself in a medical context refers to idiopathic chronic fatigue, fatigue that cannot be explained using any clinic definition of disease or disorder;

2. ‘Chronic fatigue' is also generally used by the patient population as a symptom of any physiological human dysfunction.

As you dive into the morass that is CFS, I can sense through your broadcasts that you are becoming aware of the historical, high-level problems related to the disease, specifically the taxonomy and clinical definition of CFS. The CDC made a mess of things by choosing such a nonsensical name as CFS, perhaps betraying an institutional culture dismissive of the disease or not. But it did serve to confuse researchers for a generation and set back the entire field up to this very day.

BTW, your shows are a great public service.

Regards,

Stephen

 

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