Neuroscience and epigenetics

Chris has a new site up at http://uncrediblehallq.net. If you read his site, redirect your links there.

The quality and frequency of my posting has been rather shitty these days, mostly because I have a lot to deal with.

Anyway, here's a real post.

Epigenetics is the ancillary system of your genes which causes them to be expressed in different locations by different stimuli. For example, it is why you are not a blob of uniform cells, but rather a person made of different types of cells which have the exact same genetic information.

There are a few terms in epigenetics you should be familiar with if you want to know anything about it:

- DNA methylation: DNA methylation is the addition of a methyl group to the carbon-5 position of cytosine residues ('residue', in this context, is a fancy word for an individual nucleic acid) that are followed by a guanine (at least, in 99% of cases of methylation ). A methylated cytosine followed by a guanine is called a CpG dinucleotide. The human genome doesn't have a lot, which is due to the deamination of these methyl-cytosine complexes, which are called 5-methylcytosine. This is important in cancer.

- DNA histone: DNA histone is the stuff that makes DNA curl into chromatin - if you didn't have histones, you would almost certainly not be alive, because without histones, DNA is a 1.8-meter long tangled mess of crap. With histones, DNA condenses into 90-millimeter bits of chromatin that are tightly packed in the nucleus, which is more condensed into 90-micrometer chromosomes during mitosis. Different folding of histones would change the folding of DNA.

- Transcription factors: Transcription factors enable the replication and transcribing of DNA into RNA, which is translated into proteins.

- Prions: Prions are proteins gone nuts. They can infect cells and catalytically convert other native state versions of the same protein to the infectious state.

Why is epigenetics so important in neuroscience? Epigenetic abnormalities cause a number of neurological issues, and has been implicated in a number of seemingly non-developmentally-related conditions such as schizophrenia (which is sort of our favorite illness to speculate about the causes of, as it is very poorly understood and very devastating and very interesting in its symptoms.) It is indeed also a factor in neural stem cell developmental issues, and is also implicated in differences in things such as intelligence.

Much research has been devoted to the role of epigenetics in psychiatric disorders. It's going to become much more important in the next few years; I suspect those of my fellow neuroscience people who investigate the psychiatric will do more gene-based research surrounding these things.

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The stupidity of dignity

Via EvolutionBlog, an article on the stupidity of dignity, which is a much-needed topic to discuss.

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Neuroimmunology

I had been mystified by this subfield until now, and it is profoundly relevant to research of neurological disease, both somatic and psychological:

The brain is extremely immune-protected, since there is a blood-brain barrier made by the glia surrounding our neurons (astrocytes). Very few substances get through the blood-brain barrier, and the molecules that get through produce some interesting effects, but viruses and bacteria which enter the nervous system are acted on by molecules which also affect the nervous system - in a sense, these molecules possess a double duty , particularly cytokines and chemokines.

Psychoneuroimmunology, in particular, is very interesting. It focuses on the 'mind-body connection', which is largely a lot of stuff about placebos and nocebos and how attitude affects your immune system and things of such ilk. What I'd like to see psychoneuroimmunologists address is microbes and mental illness.

As stated before, viruses and bacteria can cause mental illness - schizophrenia might be caused by a virus. I know little of how the blood-brain barrier is formed, but presumably, for example, if a pregnant woman has a virus, it might be easier for it to cross the BBB and wreak all sorts of shit.

I am not sure about how encephalitis and other brain-affecting disorders affect the neuroimmune system, but there seems to be a major role filled by cytokine RNA in detecting it. Cytokines, for those of you who don't know what they are, are proteins that are used in cellular signaling. Activation of them can affect sleep and disposition, and their actions are controlled to an extent by psychological triggers. Presumably, this is probably the biological basis of 'laughter is the best medicine' and other sorts of adages which are the same in meaning.

The entire immunological makeup of a person, however, will affect the brain. Human Genome Sciences, for example, is developing a treatment called belimumab, a human monoclonal antibody, for the treatment of lupus. Lupus has neurological symptoms, among them seizures, psychosis, and abnormalities of the CSF. Given the fact that lupus is triggered by environmental factors, belimumab should be effective in minimizing the development of lymphocytes which act against the body; specifically, it inhibits the b-lymphocyte stimulator. Given the interaction of lupus with the nervous system, one can make a few inferences about how this drug might act: the drug will keep B cells from interacting with the cytokines and chemokines in the nervous system, since it will reduce the B cell count, and reduces the amount of harmful B cells in the cerebrospinal fluid (since the CSF acts as immunological protection).

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Florida sucks, and the evolutionary significance of amusing gastric phenomena .

Florida should not be a state.

Luckily, however, we have one more piece of evidence to add to the already-quite-massive amount of evidence for evolution: hernias, farts, and hiccups prove we evolved.

Farts: our surprising ally in the quest for a more reasonable America.

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Auditory processing.

Via Pure Pedantry, an article on the double dissociation of 'what' and 'where' in the auditory cortices of cats.

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We are just another species

I haven't driven this point enough: humans are just animals. I hate using the word 'people', because it implies we're elevated above every other species.

Elevating ourselves above another organism may be our way of emotionally reconciling the fact that we have to eat another organism to survive - vegetarians, for example, won't eat meat, because they are causing the death of a living, possibly sentient organism, and it has been ground into us from birth that murder is wrong. I, for example, am not vegetarian, but will not eat animals that have been demonstrated to have intelligence equivalent to a human's at any age - I will not eat ham, beef, or octopus - or that have not lived their full life - I will not eat veal or lamb. (I have no problem eating chicken, turkey, and fish - they're fairly stupid animals, and I am perfectly happy to help eliminate the world's population of stupid.)

We have to consume organisms, though, because we can't eat rocks - we require certain molecules to survive, and these molecules are only found in organisms.

So there is a quandary about whether specific morality that we apply towards humans ought to be morality that we apply towards other organisms. I see the problem that if we acknowledge that species we share the planet with are our equals, we will effectively have less resources to draw from because we will have to allocate enough resources to them to survive - pets and animals in zoos would be tantamount to slaves (I have no problem with getting rid of zoos and replacing them with educational centers on the premises of an animal rehabilitation center, but I have a problem with the whole pet thing on a personal level - my folks have a dog and it's pretty much a member of the family, and they're domesticated so they can't very well survive in the wild unless they're more genetically identical to wild canine animals.), and civilization will go to shit because it would not exist unless we had agriculture, which involves essentially enslaving entire populations of species (except non-conscious organisms who don't have a fully-developed nervous system or who don't have one at all; I don't give a shit about the ones no other organism needs to consume to survive nor do I give much of a shit about embryonic organisms, they're effectively non-living).

Spreading across the galaxy would be little help, since it would just create the opportunity for more humans and more planets full of 6.8 billion idiots, so we need a better solution to conducting ourselves sanely, maintaining human rights, and respecting the other species that we share the universe with.

1) Higher intelligence. I have devoted my life to researching the neurogenetics of intelligence, and together with those who prefer researching mechanical ways of improving intelligence, we can make people more able of accurately processing the information we receive.

2) Better perception. We need better eyes, better noses, better ears, better tongues, better senses of touch, better senses of balance, better senses of temperature, and better senses of what's going on in our bodies.

3) Less people. Make birth control more economical, make elective sterilization free and legal on demand for all ages, make abortion free and legal on demand everywhere that it isn't, and counsel people on how much money it actually takes to raise a well-educated, competent person - and institute a licensure system for people who want to reproduce, because frankly, nobody has the right to raise a neglected, undereducated kid, and put MASSIVE pressures on groups who are idiotic enough to be reticent about making sure people have reproductive freedom. (This has the added advantage of mostly getting rid of the poverty and abuse problem - more resources and better-adjusted people.) Populations are already declining in some countries, but they're declining in the wrong countries among the wrong people.

4) Better education. To paraphrase Bush-o-lini, the nation's children is not learning.

5) More money for research. We need to halve the defense budget and divide the money which the government saves evenly among the Department of Education, the Department of Energy, the Department of Health and Human Services, the Department of the Interior , and the NSF. Science is the backbone of civilization.

6) Better healthcare. There is an entire continent where 99% of its population receives substandard healthcare. This is stupid. (Let's take away asshole Mugabe's fortune for a day and make him live like the poorest people in his country - see how he likes it. Kim Jong Il, the Burmese junta, and the janjaweed blow just as much.)

7) No religion. I think, if you read my blog, you can see why I subscribe to antitheism and why I'm an atheist. We do not need mass superstition or cults.

8) A very inculcated respect for everything we share the world with (the Native Americans got this right). This will be difficult, but this is vital to the success of our species in the long run.

Some of these are obvious; I wish these were more obvious.

Right now, the universe is a bad joke that keeps telling itself; we need to make the universe a more amusing place.

I find it funny how the topic of humans being another species leads, quite simply, to a very general solution for lots of other problems.

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Beating down the fundamentalist jihad

I have no more tolerance for the creationists - especially the way they behave toward me and my fellow atheists.

I say we start protesting.

They want to wage wars? Let's wage our own war of reason.

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Depression and drugs

Apparently, the gub'mint has released a statement that depression and marijuana are not to be mixed, particularly in people between the ages of 12 and 17. Is it based on sound science, though?

While drug use in anyone under the age of 18 is completely idiotic, the report is poorly cited and makes poor logical conclusions:

Millions of American teens* report experiencing weeks of hopelessness and loss of
interest in normal daily activities, and many of these depressed teens are making
the problem worse by using marijuana and other drugs. Some teens use marijuana
to relieve the symptoms of depression (“self-medicate”), wrongly believing it may
alleviate these depressed feelings. In surveys, teens often report using marijuana
and other drugs not only to relieve symptoms of depression, but also to “feel good,”
or “feel better,” to relieve stress, and help them cope.
However, recent studies show that marijuana and depression are a dangerous
combination. In fact, using marijuana can worsen depression and lead to more
serious mental health disorders, such as schizophrenia, anxiety, and even suicide.
Weekly or more frequent use of marijuana doubles a teen’s risk of depression and
anxiety. Depressed teens are more than twice as likely as their peers to abuse or
become dependent on marijuana.
Alarmingly, the majority of teens who report feeling depressed aren’t getting
professional help. They have not seen or spoken to a medical doctor or other
professional about their feelings. For parents, this means they need to pay closer
attention to their teen’s behavior and mood swings, and recognize that marijuana
and other drugs could be playing a dangerous role in their child’s life.

Nowhere in the paper are the citations even mentioned, and to my knowledge, a lot of people use drugs because they're depressed - biochemically, however, THC binds a cannabinoid receptor - CB1 - neuropharmacologists are currently debating the causality of the correlation of psychotic symptoms and THC (for the record, since neuropharmacology is an entirely different field of neuroscience than the field of neuroscience which I am studying, I can only give my personal experience - I have known a few stoners, and to my knowledge, they are not psychotic). The most common hypothesis is the self-medication hypothesis, which attributes the use of marijuana among depressed individuals to substance abuse by many who are mentally ill and who do not have access to the proper treatment. More disturbing is the list of statements made by the DEA without assessment of information:

Executive Summary
Two million teens report feelings of depression and loss of interest in
daily activities during the past year.
Depressed teens are twice as likely as non-depressed teens to use
marijuana and other illicit drugs.
Depressed teens are more than twice as likely as their peers to abuse
or become dependent on marijuana.
Using marijuana can cause depression and other mental illnesses.
Marijuana use can worsen depression and lead to more serious
mental illnesses such as schizophrenia, anxiety, and even suicide.
Teens who smoke marijuana at least once a month are three times
more likely to have suicidal thoughts than non-users.
The percentage of depressed teens is equal to the percentage
of depressed adults, but depressed teens are more likely than
depressed adults to use marijuana and other drugs.
Teen girls who use marijuana daily are more likely than girls who do
not use marijuana to develop depression.

There the feds go again with their causality. I wonder if NIMH and NINDS have started any sort of stink about this - SAMHSA is independent of the NIH, though, which is highly suspect, and their citations don't say anything about causal implication.

Here's the report - though I do not condone or support marijuana use by anyone who is not legally an adult, I think it is fallacious and idiotic to make unsupported statements about a drug .

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PZ Myers is coming to Madison

PZ Myers, proprietor of Pharyngula and the most awesome evolutionary biology professor in the United States (tied with Sean Carroll), is coming to Madison in September, provided I can set stuff up properly.

Maybe we can get in touch with his younger son and see if there's anything else we might need to know.

Also - pimping his daughter Skatje's blog, Lacrimae Rerum - it's some good shit. The Myerses may just be my favorite atheist family.

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Neuroscience jobs for the pre-doctoral student (graduate and undergraduate)

So, as I have said before, I am an undergraduate at the University of Wisconsin - Madison. I have been trying to find a lab job, even one as small as dishwashing that has the chance to turn into a research project.

It's pretty hard to find one - couple that with the fact that due to financial constraints I have to visit my folks this summer in their hole in Northern Virginia, which makes me more hard up for a lab job due to the fact that it is much easier to get a lab job at my university than it is to get a summer internship for the NIH or a biotech company which most likely demands at least a bachelor's degree or a freaking 4.0 GPA, and I'm trying to get at least two years of research experience before grad school because it is competitive. (Mom, I know you read this because your IP shows up on my sitemeter; try to understand my plight before you bring down the NO-YOU-MUST-VISIT-ME-THIS-SUMMER hammer.)

This is not nearly as difficult as the situation of a friend of mine who has even stricter financial constraints than I do. I honestly feel bad for her and have been trying to help her when I can by searching for resources.

I am fishing for comments on this post; please comment if you have tips or possible job postings or anything that might help a financially strapped student (even scathing but constructive criticism is welcome, I won't fault you if it's genuinely constructive and will usually learn from it!). Or, if you know my email, email me.

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Epidemics

The vast majority of people don't know this, but neurology has been known to have its own pandemics to deal with . While the world is on the subject of H5N1, I'll post about some neurological diseases that have developed into epidemics.

-Encephalitis and encephalomyelitis
-Kuru
-Meningitis
-Polio
-Trypanosomiasis

Encephalitis - this is a nasty disease and is an inflammation of the brain. There are two main encephalitides that have developed into epidemics: Japanese encephalitis and La Crosse (yes, Wisconsin has its very own encephalitis!) encephalitis. The main symptoms of encephalitides are sudden fever, headache, vomiting, stiff neck and back, impaired judgment, drowsiness, weak muscles, a clumsy and unsteady gait, and irritability (from NINDS Fact Sheet on meningitis and encephalitis). Epidemics occur in East and Southeast Asia, where 30,000-50,000 cases occur annually. Case fatality is anywhere from 0.3-60%, depending on the population and age.

Kuru - also known as the zombie disease, due to the fact that it mostly occurred among cannibalistic tribes of Papua New Guinea via eating a dead person's brain. This is a prion disease, and is similar to CJD in that it produces spongiform encephalopathy. Luckily, this disease was wiped out by 1980.

Meningitis - Also a nasty disease and is the inflammation of the meninges, which are the membranes surrounding the brain (arachnoid, dura mater and pia mater; this is one of the two diseases here which every college student is or ought to be vaccinated for. It occurs sometimes in college dormitories, and has many of the same symptoms as encephalitis. Case fatality is low, but it occasionally kills in as little as 48 hours!

Polio - The FDR disease. Most people in the United States are vaccinated against this. Polio, oddly enough, was endemic to Europe for thousands of years until it hopped across the pond, and it preferentially infects motor neurons - which means that when you get it, you may stop breathing and be quite paralyzed. Iron lungs were used quite frequently for this; nowadays, biphasic cuirass ventilation replaces the iron lung in situations where patients cannot breathe (see also Ondine's curse for another interesting and sad condition where people cannot breathe, albeit not autonomically.)

Trypanosomiasis - What we call trypanosomiasis is called by laymen sleeping sickness and Chagas's disease. This disease makes people sleepy and is caused by a small parasite in the saliva of tsetse flies, in the case of sleeping sickness, and mosquitoes, in the case of Chagas's disease. Its symptoms are fever, headaches, and joint pains; in addition, Chagas's disease causes conjunctivitis.

Enjoy wondering how it might be to get one of these little suckers.

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A rant on funding, again

We need a science White House. At this point, I am almost past caring whether it is Democratic (though I would prefer a Democratic White House) or Republican (OH SWEET REASON NO), I just want them to give more money to the NIH and NSF. The Department of Defense doesn't need all the crap it gets. No military in the world is nearly as technologically advanced as ours.

The reason I say this is because there is good research that is getting tossed by the wayside because it doesn't have enough money or there are laboratories that cannot afford to hire an adequate number of researchers.

For example, John McCain showed his ignorance of all but the most obvious research when he made a snide comment about a bear DNA investigation that was part of investigating ecological dynamics in a key species. McCain is a man who has no understanding of science, although we can't fault him more than a reasonable amount because he's not science-educated.

There are plenty of PhDs who are unemployed because of the shortage of fundings. GrrlScientist is an ornithologist who has been unemployed for the past while, for example, and she delivers an interesting and rather exquisite rant on her own unemployment.

This is research not getting done because of governmental ignorance. How much development would we have had if Bush was not in office? Let's think of research topics that might be done if the government gave us more money:

- topics concerning keystone species which are vital to their environment
- research into rare diseases
- more investigation of the neural bases of intelligence
- MORE STEM CELL RESEARCH

There is also a lamentable lack of science education. We American-born scientists (in this number are also counted mathematicians, computer scientists, and engineers in addition to biology, chemistry, physics, and medicine) are a small bunch; apparently, we have to import the rest of our colleagues from Asia and Europe because the vast majority of the rest of you can't be arsed to have as motivation for your job anything other than money. I don't give a flying crap how much I earn as long as I'm doing neuroscience; I would live in a space similar to my friend Bill's crusty old attic if I had to (although with sufficient weatherproofing and maybe a space heater).

We would have more American-born scientists if the vast majority of the aforementioned rest of you stopped being greedy and had some discipline and actually knew something about science. (Interestingly, this reminds me of a discussion I had at Atheists, Humanists, and Agnostics at UW-Madison, the atheist group that I am a member in, when we were talking about the theists' so-called 'miracles'. None of the theists who were arguing this point - I say this because the only theist who usually sides with us, my friend Rachel the Spinozan panentheist, is as far as I know majoring in science and wasn't really participating in the conversation, and the theists I personally know who are scientists are comparably sane to my fellow scientist atheists - were majors in science, and Chris, Nick, Travis and I, who are all science majors and all atheists - well, Chris is also a philosophy major - were using probably the most substantive arguments which arise mainly from science to argue that the rather fundamentalist theists were full of shit, and our arguments apparently went over their heads - they apparently went over the heads of the other atheists, too.)

And no, we're not going to resort to framing and marketing it like some sort of product. Is the American public really this stupid?

Seriously, if it gets much worse, I WILL bail on the United States after I get my PhD, as one more scientist who takes their talent to where it will be acknowledged. You can say hello to me in Amsterdam.

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