Murmurings

So, I’m alive. When the dust settles, I’m still here, still kicking, and am now (apparently) a master of something.

Which brings me to the point of what to do with this blog. This was always a student’s exercise, and now that I am no longer a student, I am not sure if I will keep it going. I DO want to continue blogging, but maybe not with such a hard-science focus. So right now the toss-up is in between keeping this place, splitting my time between blogging here and elsewhere, or just starting another blog without a specific focus.

We’ll just have to see where it goes.

Mini-Review: Monkey Girl

So this is going to be brief, and not just because I am reviewing a book that is four years old.

Abstract

Monkey Girl is Edward Humes narrative coverage of the landmark Kitzmiller v. Dover Area School District. In addition to the highlights of the court proceedings, Humes delves into the events leading up to the case and often takes time to cover the background of the key players.

Discussion

I never intended to pick this one up, I really have much more important things I should be doing. But Kitzmiller v. Dover remains a fascinating legal battle and my copy was a cheap buy at a Borders that was going out of business.

I was put off by the narrative style. Apparently this is a hallmark of Humes’ reporting (he has even won a Pulitzer for it), but I never warmed up to it. Maybe it is the soulless biologist in me, but I prefer details to narrative flourishes. I felt like I was constantly being distracted from the actual matter at hand by being told how “fiery” and “soulful” people were; nor is he often satisfied with letting the chief players simply “say” things. I kind of feel like this was written with a thesaurus in one hand as though simple language would bore his readers. It had the opposite effect on me and several times I found myself scanning large passages for the kernel of actual detail. In favor of this style, it did make for a quick read.

The narrative style also lent itself to the chronological nature of the narrative and facilitated his introduction of characters in a memorable way, I am just not sure it was the only or best way to accomplish this. The text is also plagued with a great many diversions: details of peoples ancestry, local history, and similar conflicts elsewhere that feel a little like padding. Some of them seem valid, such as the tangent on the history of the Discovery Institute and excerpts from Creationism’s Trojan Horse. Which are bound to be useful if this book is your introduction to this controversy. Others, not so much. In this latter group I would count the several sentence tangent that the title comes from. A brief interlude whose only purpose seems to be to justify an eye-catching title, and does absolutely nothing to further the account. It would have been nice if this book about Dover and the Kitzmiller v. Dover court case hadn’t spent approximately a quarter to a third of its narrative elsewhere.

As far as the analysis and fact gathering go, the book does a great job. If you can stomach the style there is actually quite a bit of information within the narrative and the helpful (if a bit sparse) notes section. He seems to have a talent for succinctly and clearly presenting the arguments and motivations of the fairly large group of people involved. I also appreciate that he tracks the conflict back to its origin in the school board meetings rather than just picking up once the suit was filed. This is especially important in this particular case since the perjury committed by several board members about what had happened played a key role in the decision.

Conclusions

Overall, I enjoyed reading this book. I found it to be an informative look at the events leading up to trial and an interesting overview of the case itself. I do think that the style hurts rather than helps. Humes seems to try to walk the line between informing and entertaining, and it just didn’t work in my opinion. Humes has an excellent eye for noting and including a wealth of detail, yet he seem to have trouble differentiating between relevant and irrelevant details. It is something that probably won’t have a permanent place in my library, but it was definitely worth reading once.

Available via Amazon

Life goes on…

So as you may or may not be able to tell from the long silence, things have been kind of busy and crazy on this end. Our semester effectively ends on the 3rd of May, and well, there is a ton to get done before then. Of note, I am doing some very involved research for a literature review on HIV latency, so I might wind up posting about some of the interesting things I have been finding. HIV does some really odd things, even when the virus is supposedly ‘controlled’ by HAART.

Here Be Dragons

One of the more common misnomers flying around the pop-sci publications is this idea of “Junk DNA”. Now to be fair, this label originated with the scientific community. Even Francis Crick was dismissive of its utility, but that was thirty years ago. As it turns out, junk DNA (more accurately called non-coding DNA) contains both a variety of sequences with biological utility and large portions of our genomic history. It is the later that I wanted to bring up today.

One of the major forms of transcriptional control involves histone deacetylase. You can think of histones as essentially spools of DNA. If DNA is wrapped tightly around histones it is unavailable to be transcribed to RNA and then translated to protein. Modification of histones determines the precise manner in which the DNA interacts with them, and acetylation of histones loosens the wrapping of the DNA, making it available. So your cells employ histone deacetylase to make sure that regions of the genome stay nice and silent. Which is good, cause there is some scary stuff hiding in the sea of non-coding DNA.

Recently there has been a push to use histone deacetylace inhibitors to cause expression of genes of interest (e.g. it is suggested they could be used to flush latent virus out of memory T-Cells to destroy latent reservoirs of HIV). Now, these ideas seem really sound on the surface. If we could destroy that reservoir of latency, we could see long-term drug free remission in HIV infection. But what else might you wake up? As far as I know there is no reliable method (if there is indeed a method at all) to target histone deacetylase inhibitors to specific regions of the genome, so this would be a general approach inhibiting all of a cells histone deacetylase, which I can’t but think would lead to A) steps towards tumor transformation as cell cycle controls  were disabled, and B) the activation of unfriendly endogenous elements in the genome. Fishing out integrated HIV provirus is an excellent idea, but what else might we pull in with it?

Contextualizing Radiation

So I wrote about ionizing radiation dose a couple of weeks ago. But it wasn’t until today that I found a good, visual rendering of the equivalences between radiation doses from different activities. Randall Munroe, the delightful mind behind XKCD, has made a chart of common radiation doses, standards, and equivalences. It’s definitely worth a look.

http://xkcd.com/radiation/

Activists targetting students with violence

I tend to be wary of activists. To me, an activist is someone who has taken it upon themselves to support a particular opinion, regardless of that opinion’s status as right or wrong opinion (which is to say its truth value). This leads to a turbulent relationship with fact that may involve everything from cherry picking ideas to outright denialism, and generally makes for a very “fair-weather friend” relationship between opinion and (my personal tool of the trade) reason. Now, many activists can and do behave responsibly and rationally and they have my greatest respect (another tip of my hat to the intelligent and thoughtful feminists over at Fishnet Bluestockings, they are on my blogroll for a reason), but I find that it pays to be on my guard against those that don’t. Which is why I employ the following guidelines with activists:

• You are entitled to your opinion and the expression of that opinion in the appropriate forums and manner. To give you any less than that would be a violation of your rights and my moral code.
• Do not confuse an opinion with an argument. Don’t expect to persuade without evidence or reason, it will get you ignored.
• Attempts to persuade through lies & half-truths, the propagation of misinformation, shame or peer pressure, or any other end-run around mutual respect and properly formulated argumentation will get you ridiculed.
• Resorts to threats and violence will get you watched, reported, arrested, and (in the most regrettable cases) hurt.

I feel the need to bring this up today, since there is a group out to threaten, harass, and possibly attempt to kill me and my fellow students (as if a bisexual, transgendered person doesn’t have enough animosity directed towards her/him already). Negotiation is Over is a hate group directed at researchers in the life sciences. They call themselves animal rights activists, but they seem much more interested in attacking researchers than saving animals. And now they have specifically turned their gaze on students as they announced yesterday:

Every time a vivisector’s car or home — and, eventually, the abuser him/herself — blows up, flames of liberation light up the sky.

[…]

When we attack professors, we can only expect limited gains. They are deeply entrenched in the holocaust, have vested financial interests, and enjoy a network of support and protection. Students, however, have no round-the-clock police protection, no access to the FBI, and no access to legislators. The weakest link in the chain is the student body. Vivisectors-in-training can be shut down with relative ease.

[…]

Students also need to understand that making the wrong choice will result in a lifetime of grief. Aspiring scientists envision curing cancer at the Mayo Clinic. We need to impart a new vision: car bombs, 24/7 security cameras, embarrassing home demonstrations, threats, injuries, and fear. And, of course, these students need to realize that any personal risk they are willing to assume will also be visited upon their parents, children, and nearest & dearest loved ones. The time to reconsider is now.

It goes on like that for quite some time, with a lovely picture of a firebombed car just to make sure there can be no ambiguity about what they are advocating. As an added bonus their site has links to state by state directories of research universities they consider offenders via their “Animal Abuse Crime Database”. Guess whose uni is on their list?

But I’m not afraid of these creeps, and I urge you not to be either. Stay safe, don’t let them get to you, and promptly report any threats. These people are terrorists, and terrorists like to cause terror. So don’t give them the satisfaction. And if you have a forum for it, I hope you will speak out and let them know that their tactics are impotent. In time they will try to do something stupid and get arrested/shut down, or they will tire of their game. Either way, the wanna-be scary monsters will be stuffed back under the bed and we can get on with the business of saving lives.

Now, my opinions on the morality of animal research are complex, and I will talk about them in a later post and hopefully be able to present a rational basis for them. But my opinions on this issue are stark: this is unacceptable. Even if you personally find animal research reprehensible and feel that making transgenic mice is on par with Tuskegee, realize that this sort of behavior is not the way to go about effecting a change.

Violence remains the last refuge of the deluded and incompetent.

New Resources

This is just a heads up that a new site has been added to the ‘Resources’ links down there on the bottom right. I was trying to look up something about mitochondrial fusion proteins and kind of stumbled across a site that hosts a number of very interesting science videos. Despite the name, DNAtube appears be a multidisciplinary site hosting videos on all aspects of science and math. Probably worth checking out, I know I would be if I had time to take a study break.

HIV & HSC

They haven’t managed to kill me with exams yet; however, it’s not from lack of trying. But I found something so interesting yesterday that I just couldn’t keep myself from blogging about it. And by interesting, I mean terrifying. I tend to find life beautiful. Even if it is something most people would find gross, or disturbing, or horrible. I’m a biologist, it’s a documented weakness of our ilk. So when I say that the following engenders in me a feeling of profound wrongness and almost disgust, I want you to take my full meaning.

First, background:

• HIV comes in two flavors, CCR5 tropic and CXCR4 tropic. You might remember a post on CCR5 tropic HIV from a while back. It basically denotes which co-receptor is necessary for the virus to enter a cell (and yes, there are dual-tropic strains). We generally focus on CCR5 because, for reasons that are not entirely clear, initial infection with HIV is almost entirely CCR5 tropic with the infection shifting to CXCR4 tropic as it progresses.
• Hematopoietic stem cells (HSC) are the source of all of your blood. ALL of your blood, myeloid and lymphoid. They are a self-renewing pool of multipotent cells, which means that they can be used to make new blood as needed (this is why you can donate blood and bone marrow have it regenerate). Among the offspring of the lymphoid lineage are the T-cells that HIV usually attacks.

Got all that? Good. Sit down. Are you sitting comfortably?

In sum, we have shown that multipotent HSPCs and HSCs can be infected by HIV and that this infection is primarily accomplished by CXCR4-tropic HIVs. The infection and destruction of multipotent HSPCs may contribute to the more rapid decline in CD4 counts associated with CXCR4-tropic HIV isolate emergence. Alternatively, as infected HSCs could create an extremely long-lived reservoir of virus, preferential infection of these cells by CXCR4-tropic virus could provide a reservoir for the emergence of CXCR4-tropic isolates late in disease: as other viral reservoirs are depleted, CXCR4-tropic virus from the HSC and HSPC reservoir could begin to predominate. In addition, our demonstration that HIV can infect cells capable of stably engrafting for months in the xenograft model indicates that HIV can infect HSCs that are capable of self-renewal and, if the integrated viral genome is latent, that it can be maintained and even expanded by cell division.

The above quote comes from an article published in this month’s Cell: Host & Microbe, and I have to say that their work looks pretty solid (at least to my exam addled brain). They performed a series of experiments using viruses generated from a minimal HIV genome and expressing three variant (R5, R4, or dual) envelope proteins. With this they demonstrated that not only could CXCR4 tropic and dual tropic viruses infect hematopoeitic progenitor cells in general, but that they could specifically do so to cells capable of multilineage reconstitution in immunocomrpmised mice. Or to put it another way: XR4 and dual tropic HIV infects HSC.

Now active HIV infection appears to kill HSC cells outright, and HSC death is really bad, but if you have been following closely you’ll realize that that isn’t the biggest worry here. Latent infection of HSC could lead to a near impossible to purge, continually renewing reservoir of infection, moreover it appears that it is possible for infected HSC to differentiate and produce daughter cells that are already infected. This means that in advanced cases of HIV infection, we might need to start looking for integrated provirus in cells that HIV technically can’t infect.

This is a blow struck to the heart of our immune system. Sure, there are genetic disorders that screw with HSC, cancers even, but a pathogen? I feel like they are breaking the rule about fighting on holy ground. It is still important to see if wild-type HIV is capable of latently infecting HSC instead of killing them outright, but given the versatility of this virus, it wouldn’t surprise me, and if that is the case it is all the more reason to lock down HIV infection as early as possible. We are really close to finding a way to flush latent infection from T-cells, and it would be a serious blow if we succeed in that only to find that HIV has yet another reservoir lying in wait.

(And okay, I admit that my disgust is laced with a teensy bit of: Oh wow that is so awesome.)

Notes & Sources

1. HIV-1 Utilizes the CXCR4 Chemokine Receptor to Infect Multipotent Hematopoietic Stem and Progenitor Cells (Carter, et al. 2011)
2. Thats only the second Highlander joke in three months of science blogging. I am falling behind schedule.

Facts on Acute Radiation Syndrome (ARS)

Now that we have a basic idea of what ionizing radiation is, let’s talk about what it does to you. Today we will focus on acute radiation syndrome (also known as radiation sickness and radiation poisoning). This is the sort of thing that occurs due to short-term, high-dose exposure to ionizing radiation, such as that from nuclear weapon discharge or nuclear industrial accidents. We’ll take a look at the long term effects and generation of neoplasms in a future post.

The precise nature of radiation syndrome varies by dose, radiation type, tissue exposed, and duration of exposure. These factors are all rolled together in an SI unit called the Sievert (Sv), which is known as the dose equivalent. The measure of dose is known as the Gray (Gy), but that raw information doesn’t tell us much about biological effect. So the Gray is transformed as a function of quality factor Q which is the ratio between the effects of gamma radiation and the effects of your radiation type of interest (e.g. Q[gamma]=1, Q[alpha]=20). There is a further factor called N which relates the effects of radiation based on differences in species and tissue, for simplicity’s sake N[human]=1. The final product of this calculation is the dose equivalents in Sv, which gives us useful info on biological effect. The units of Gy and Sv are J/kg and because time is an important factor we usually see Gy and Sv expressed over seconds, hours, or days. Both the Gy and Sy deal with pretty large amounts of radiation, so it is much more likely to see quantities expressed in milli or micro versions (for instance at one point the ongoing Fukushima I accident peaked at 400 mSv/hour).

Certain types of (particle based) ionizing radiation are of greater or less concern depending on the location of their source. For instance, alpha and beta-particles have low penetrance. They can cause surface skin burns, but generally can’t penetrate far enough to cause excessive internal damage. However, an internal source of alpha or beta-particles is a more dire circumstance because just as they do not have the penetrance to enter the body, they cannot leave. This is why contamination of food, water, and dust is such a concern. High penetrance radiation, like neutron radiation or (photon based) gamma-rays is less affected by location of source.

The symptoms of radiation syndrome begin at 1 Sv and at about 8 Sv they become invariably fatal. Not all symptoms present at once, and it can take up to four weeks for the full effects of minor radiation poisoning to be seen. Usually the time between exposure and onset decreases as the Sv increase (with there being very little delay at the  8 Sv level). The immediate symptoms include: nausea and vomiting, diarrhea, headache, and fever. These occur within ten minutes to six hours after exposure. In the next one to four weeks (or sooner in the case of extremely high doses) the victim may suffer: fatigue, hair loss, bloody vomit and stools, infections, poor wound healing, low blood pressure, dizziness, and disorientation. Usually there is also some level of skin redness, peeling, ulceration, and possibly necrosis.

All of these symptoms result from a disturbance in cellular chemistry. As we discussed last time, ionizing radiation generates ions (particularly reactive ions known as free radicals). The cell is an impressive machine dedicated to controlling multiple ongoing, complex chemical reactions. So we can see why the spontaneous introduction of new reactants would be bad, and why a high concentration of them at one time would be very bad. Essentially cells will be faced with a critical failure of their functions and this will lead to massive cell death. And this is not going to be the pretty, well-controlled cell death either (no, that isn’t facetious, remind me to tell you about the pathways of cell death sometime). In most cases the immediate cause of death is opportunistic infection due to a failure of the immune system caused by the destruction of large amounts of bone marrow; however, in extreme cases the victim just basically falls apart at a cellular level.

As mentioned, these are only the acute affects of radiation exposure, even if you survive these, there are still the long-term consequences of cell damage to look forward to.

This is what is at stake in Japan. This is what a whole host of brave rescue workers are risking to try to keep everyone else safe. Show a little compassion and (if you can) a little support.

Sources & Further Reading

• CDC Radiation Emergencies Page
• WHO Ionizing Radiation Page
• Links to The Japanese Red Cross Society and Doctors Without Borders
• Yes, Stan Lee lied to us all.

A quick primer on ionizing radiation

With an eye towards discussing the effects of ionizing radiation on humans, particularly with respect to cancer, I thought it would be best to write up a quick and dirty reference post on what exactly ionizing radiation is. This is a good example of my continuing struggle to find an appropriate voice for this blog. I never really know what I can safely assume my readers know. So, let’s (hopefully) review:

Ionizing radiation consists of particles or photons capable of inducing detachment of electrons from their atoms resulting in free electrons and a corresponding positive ion. There are five broad types of ionizing radiation: alpha-particles, beta-particles, neutron radiation, gamma rays, and X-rays.

• alpha-particles: result from radioactive decay, and consist of two protons and two neutrons. They are directly ionizing.
• beta-particles: result from radioactive decay, and consist of either an electron or positron. They are directly ionizing.
• neutron radiation: results from nuclear fission, and is simply a free neutron. They are indirectly ionizing as they have no charge themselves, but can collide with and excite charged particles that then directly ionize.
• gamma rays: are high frequency photons emitted to right the energy of a decayed atomic nucleus. They are also indirectly ionizing as they are chargeless wave-packets that when absorbed can cause electron expulsion which then ionizes directly.
• X-rays: kind of overlap with gamma rays. They are high frequency photons. The only major difference is their origin.

The ionizing capability is dependent on the energy of the individual unit (particle or photon) interacting with the atom (this is why high frequency electromagnetic waves are ionizing and low frequency are not). Thus, high energy, low concentration radiation can still have an ionizing effect.

As we will discuss next time, it is generally the chemical characteristics of the resulting ions that cause damage in cell physiology and DNA.