Qnr, A candy coated pill?

Fluoroquinolones are rapidly becoming the most heavily consumed antibiotics in America. This trend started in 2001 after the anthrax attacks because ciprofloxacin was the only antibiotic approved for treating anthrax. Prior to time, beta-lactams (penicillin and other similar antibiotics) had been the most popular because of their low toxicity and activity against a broad spectrum of microbes. However, the patent life on most beta-lactams was running out so marketing of them was decreasing. The timing of the anthrax attacks and the waning hype for beta-lactams created the perfect opportunity for fluoroquinolones to move to the forefront of prescription formularies.

Fluoroquinolones kill bacteria by inhibiting the exzyme known as DNA topoisomerase. That enzyme releases supercoiling tension as the double helix is unwound during DNA replication. If that enzyme is knocked out, the DNA gets tangled up and breaks and the cells die. Bacteria have a few ways of protecting themselves from fluoroquinolones. Their cell walls can mutate so that they become less permeable to the antibiotic. They can express efflux pumps that export the antibiotic from inside them. They can also express the gene qnr. The Qnr protein, encoded by that gene binds to DNA topoisomerase and prevents fluoroquinolones from doing so. However, the topoisomerase can still perform its regular role of relaxing supercoiling tension so the cells don't die.

I have been doing some work on qnr and it turns out that there are some tricks in manipulating the DNA encoding a gene that is involved in the manipulation of DNA. I sometimes wish that genes were large enough that I could throw them on the floor and stomp on them when they start playing tricks on me the way that this one does. I sometimes also wish that I could purify enough DNA so that I could taste it. In High school, my biology teacher told us that DNA is candy-coated (referring to the deoxyribose sugars that make up its backbone). I often wonder if it is really sweet. Some days, I very much doubt it. It might be easier to have an agreeable relationship with qnr if I knew there was some positive aspect to it.

The picture below is a portrait of me working on qnr. (I'm not the hand)

A deadly illness in African children

There is a great article in Time about zinc and its effects on children suffering from diarrhea, which is one of the deadliest illnesses among African children.

Airplane Etiquette

For the first time in my life, I think I failed in citizenship.  When I was a kid, it was assumed that my school report cards would ALWAYS have satisfactory or outstanding marks in behavior.  They always did.  I am not sure if this was because I was a good kid, or simply because I was a quiet kid, but I tended to stay out of trouble with the teachers.  However, at the age of 32, I think I finally experienced what it would have been like to get a "needs improvement" or "unacceptable" in behavior on the plane I was on yesterday.  

It all started while the plane was sitting on the tarmac with the door closed and the ventilation on, but for some reason we weren't going anywhere.  I was working on my laptop on some diagrams I am drawing for a manuscript.  There had been no announcement at this point to turn off electronic devices, but when the flight attendant, (a middle aged woman with salt and pepper hair named Lilly) came down the aisle and asked me to start shutting down my computer, I promptly saved what I was doing and put my computer to sleep.  I slid it into the nifty vinyl cover I made for it and stuck it in the seat back pocket.  After several minutes, we were still sitting there and I got bored.  I decided that since electronics were not allowed, I'd paint my nails blue.  After all, I was flying into Seattle and spending the day with my sis-in-law there and blue nails seemed like a fine way of celebrating.  I pulled my computer back out and used it and it's great vinyl cover as a surface for this small project.  

I had just completed the left hand when Lilly walked by again and asked me to stow my computer, which I did.  I needed to finish painting my right hand so I pulled out a magazine and used it as the new surface for my manicure.  I had just finished the right thumb and Lilly was back telling me that actually I shouldn't paint my nails on the plane at all.  I closed up the nail polish but we still weren't moving and I got bored again so I started thinking.  

It's always a dangerous thing to think.  I started wondering why I couldn't paint my nails on the plane.  The ventilation was on, so I seriously doubted that the fumes from the polish were bothering anyone.  I couldn't smell it and I was the one closest to it.  Besides which, people wear perfume, pass gas, drink alcohol and coffee, and vomit on planes and  all of those smells are worse than nail polish (in my opinion).  Perhaps a matter of safety then.  After all, nail polish can be flammable when held over extreme heat. My thoughts went back to the point about people drinking alcohol and passing gas on airplanes and that both alcohol and methane are more flammable than nail polish.  So it clearly wasn't a safety issue.  Perhaps the flight attendant was worried that the nail polish would spill, but then I thought of all the drinks that get passed out and decided that fear of spilling things is not a concern on planes.  The only logical explanation left in my mind, was that Lilly hated me polishing my nails because the polish was blue.  I decided that the color was none of her business and since I felt as conspicuous as Michael Jackson in one sparkly glove with only six digits painted blue, I decided to paint the other four.  We had made it to the safety demo part of the flight so I figured the flight attendants wouldn't stop in the middle of that over a small matter of nail polish and so I opened the bottle up.  Before I could even get the brush out, the woman sitting next to me starts saying in a very shrill voice "You idiot! she just told you not to polish your nails on the plane!  Didn't you hear her?  Put that up now or I will call her over!  Do you want me to call her over here?!"  I put the polish away.  The woman seemed to think it was a life and death matter.  Clearly not worth it.  

When the safety demo was finished, Lilly was back.  Not over the nail polish since it was out of site this time because y bag wasn't tucked under the seat in front of me far enough.  It was under there as far as anybody else's, but I pushed it under a bit more.  I wasn't feeling particularly helpful at that point so I didn't go to heroic efforts to push it under very far.  The flight attendant was insistent that it go under farther and when I refused on the ground that the plums in the side pouch would get smashed she said she'd stick it in the overhead bin.  I pulled the bag out, and started to close it up as she was trying to yank it from my hands.  When I finally surrendered it to her after closing it up, she verified the presence of the plums in the side pouch and put it up.  Shortly after the fasten seatbelt sign went off, I retrieved my bag and observed that Lilly had place my bag precisely at an odd angle where the slamming door of the bin would smash the plums.  

Throughout the flight, I was trying to remind myself that refusing to let the woman next to me get out to use the restroom would be unnecessary and that tripping Lilly could get me charged with assault.  The woman next to me tried to demonstrate that she was nice by emphasizing her please and thank you when she asked me to let her out of her seat.  I remained silent and let her go, though I felt like telling her that once she has called a person an idiot she should give up a façade of niceness as it has become entirely useless.  At some point in the flight, she started passing a lot of gas and I turned up the airflow and noticed her sinking lower and lower in her seat throughout the remainder of the flight.  Perhaps her thoughts were also visiting the relative volatility and flammability of various chemicals.

At the end of the flight, Lilly was once again hovering over me and she glared for a full thirty seconds at my bag which was once again stowed under the seat in front of me.  I refused to acknowledge her and she finally left without speaking.

Miriam vs. Science!

Science is frustrating and consuming so it tends to attract creative people with high pain tolerance and screwed up priorities.  Scientists are the sort of people who need difficult problems to keep them occupied.  I have heard many scientists postulate that the government funds science just enough to keep us all busy and off the street, but they don't pay us well enough that we could really do any real damage.  I guess the inference is that there is a conspiracy to actually keep scientists frustrated and deeply occupied to protect society from bright, but screwed up people.

When science gets really frustrating, all scientists come up with strategies for coping.  Some people shout at their equipment.  Others shout at their students.  But many scientist get more creative than that.  My friend, Steve Salipante, made all of us come up with kill faces and assume Berserker identities.  He also had a tally sheet on the wall of us vs. science.  Each of us got a point when an experiment worked and several points if there were lots of steps leading up to the success.  Science got a point every time anything failed.  Science was always ahead....Always.  

Recently, At PARC I saw a scientist wearing a "Game Over" t-shirt, which turned out to be pretty appropriate because not even the controls for our experiments were working  that day.  I am tempted to order one for everyone in the lab, except it might be bad for morale.  

I tend to be a bit stoic about frustration in the lab.  I try to cheer everyone on and encourage them.  Then later on I go and demolish something in the name of home improvement.  Usually it works out okay in the end.  (Both the science and the demolition.) Good thing I have a 65 year old house that needs some improving.