by Jennifer Gibson, PharmD in Brain Blogger
The Internet has become a place to do almost everything — work, play, organize, and communicate. In recent years, the Internet has also become a place where people can obtain cognitive behavioral therapy for a variety of mental health conditions. According to new research, motivation is essential to engaging in effective Internet-based treatment. A recent [...]... Read more »
Andrews G, Cuijpers P, Craske MG, McEvoy P, & Titov N. (2010) Computer therapy for the anxiety and depressive disorders is effective, acceptable and practical health care: a meta-analysis. PloS one, 5(10). PMID: 20967242
Beattie A, Shaw A, Kaur S, & Kessler D. (2009) Primary-care patients' expectations and experiences of online cognitive behavioural therapy for depression: a qualitative study. Health expectations : an international journal of public participation in health care and health policy, 12(1), 45-59. PMID: 19250152
Bendelin N, Hesser H, Dahl J, Carlbring P, Nelson KZ, & Andersson G. (2011) Experiences of guided Internet-based cognitive-behavioural treatment for depression: a qualitative study. BMC psychiatry, 107. PMID: 21718523
Hedman E, Andersson E, Ljótsson B, Andersson G, Rück C, & Lindefors N. (2011) Cost-effectiveness of Internet-based cognitive behavior therapy vs. cognitive behavioral group therapy for social anxiety disorder: Results from a randomized controlled trial. Behaviour research and therapy. PMID: 21851929
Hedman E, Andersson G, Ljótsson B, Andersson E, Rück C, Mörtberg E, & Lindefors N. (2011) Internet-based cognitive behavior therapy vs. cognitive behavioral group therapy for social anxiety disorder: a randomized controlled non-inferiority trial. PloS one, 6(3). PMID: 21483704
Kessler D, Lewis G, Kaur S, Wiles N, King M, Weich S, Sharp DJ, Araya R, Hollinghurst S, & Peters TJ. (2009) Therapist-delivered Internet psychotherapy for depression in primary care: a randomised controlled trial. Lancet, 374(9690), 628-34. PMID: 19700005
Serfaty MA, Haworth D, Blanchard M, Buszewicz M, Murad S, & King M. (2009) Clinical effectiveness of individual cognitive behavioral therapy for depressed older people in primary care: a randomized controlled trial. Archives of general psychiatry, 66(12), 1332-40. PMID: 19996038
Genes code proteins. When a gene carries a defective mutation, it will either stop coding the protein or it will code a defective one. This is, unfortunately, the basis of many genetic diseases. In principle, if we could substitute the defective gene with a healthy one, the problem would be solved. That's what gene therapy boils down to. In fact, there are ways to deliver the genes to the affected cells. For example, you can take a virus that targets the cells where the defective gene is expressed, keep the virus's ability to inject its genome into the target cell, but modify its genetic content so that now it contains the healthy genes. The virus will "attack" the target cell in its usual manner and inject its genetic content inside. But now, because the virus has been artificially modified, the new genetic content won't be the usual viral genes that cause infections. Instead, they will be the new, healthy genes, which will be integrated in the cell's DNA and start coding the healthy protein.Gene therapy has been used successfully to treat various genetic diseases (see the studies listed here) and there have been very encouraging results when used to treat cancer in mouse models (see, for example, ) as well as in humans . However, there are situations where the "simple" scenario I described above will not work. We are diploid organisms, which means we carry two copies of each chromosome, and hence two copies of each gene. The two copies may or may not be identical. When they differ, we say that the individual is heterozygous at that particular locus. Now, it so happens that in some heterozygous individuals one of the two copies of the gene is dominant negative. What that means is that even if the other copy is healthy, and it codes a healthy protein, the defective protein (produced by the defective gene) interacts with it and alters its function. Basically, the mutated protein dominates over the non-mutated one and overrides its ability to function properly.When this happens, "delivering" the healthy gene will not solve the problem because the defective gene will continue to produce the defective protein, which, in turn, will override the effect of the healthy one. Does this mean we can't use gene therapy to fix the defective gene? Of course we can! We just have to use a different kind of gene therapy, namely antisense gene therapy.This is how it works.I've used the expression "genes produce proteins." Well, it's a little more complicated than that. Each strand of DNA gets first transcribed in RNA and then the RNA (which is single stranded) is translated into the protein. The idea behind antisense gene therapy is to prevent the defective RNA strand to be translated into the defective protein. How? By binding the defective RNA before it can be used by the cell to make the defective protein.DNA is made of two strands that are complementary to each other. The same principle works for RNA, even if RNA is usually found in single strands. So, if you make its complementary (the antisense strand), it will bind to it like opposite magnets do. And that's exactly what antisense gene therapy does: instead of delivering pieces of DNA, it delivers pieces of antisense RNA made to complement exactly the defective RNA.The figure below is from this website:As you can see from the figure, the defective RNA is "plugged" by its antisense complement and at that point is no longer able to make the defective protein. The healthy protein, produced by the unmutated copy of the gene, completely takes over thus eliminating the source of the disease.References  and  below show examples of antisense gene therapy used in treating brain and cervical cancers.  Suto, R., Tominaga, K., Mizuguchi, H., Sasaki, E., Higuchi, K., Kim, S., Iwao, H., & Arakawa, T. (2004). Dominant-negative mutant of c-Jun gene transfer: a novel therapeutic strategy for colorectal cancer Gene Therapy, 11 (2), 187-193 DOI: 10.1038/sj.gt.3302158  Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, & Rosenberg SA (2006). Cancer regression in patients after transfer of genetically engineered lymphocytes. Science (New York, N.Y.), 314 (5796), 126-9 PMID: 16946036 Zhang Y, Zhu C, & Pardridge WM (2002). Antisense gene therapy of brain cancer with an artificial virus gene delivery system. Molecular therapy : the journal of the American Society of Gene Therapy, 6 (1), 67-72 PMID: 12095305 Yatabe, N., Kyo, S., Kondo, S., Kanaya, T., Wang, Z., Maida, Y., Takakura, M., Nakamura, M., Tanaka, M., & Inoue, M. (2002). 2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells Cancer Gene Therapy, 9 (7), 624-630 DOI: 10.1038/sj.cgt.7700479... Read more »
Suto, R., Tominaga, K., Mizuguchi, H., Sasaki, E., Higuchi, K., Kim, S., Iwao, H., & Arakawa, T. (2004) Dominant-negative mutant of c-Jun gene transfer: a novel therapeutic strategy for colorectal cancer. Gene Therapy, 11(2), 187-193. DOI: 10.1038/sj.gt.3302158
Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP.... (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science (New York, N.Y.), 314(5796), 126-9. PMID: 16946036
Zhang Y, Zhu C, & Pardridge WM. (2002) Antisense gene therapy of brain cancer with an artificial virus gene delivery system. Molecular therapy : the journal of the American Society of Gene Therapy, 6(1), 67-72. PMID: 12095305
Yatabe, N., Kyo, S., Kondo, S., Kanaya, T., Wang, Z., Maida, Y., Takakura, M., Nakamura, M., Tanaka, M., & Inoue, M. (2002) 2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells. Cancer Gene Therapy, 9(7), 624-630. DOI: 10.1038/sj.cgt.7700479
The positively correlated associations between religiosity and low levels of promiscuity and high levels of abstinence and marriage-centricity are generally quite clear enough. We often see that religion seeks to suppress sexual promiscuity through its doctrines that promote a monogamous sexual reproductive strategy characterized by low promiscuity, exclusive heterosexuality and high premiums on marriage and fertility.Intuitively, we might guess that our sexual inclinations owe to how much exposure we have towards our adopted religion. Thus, we might, quite reasonably, suppose that someone who regularly attends Sunday school and comes from a religiously devoted family with staunch practices in the home would more likely be shaped into a long-term mating, marriage-inclined and sexually abstinent person, than someone who does not observe those traditions and customs. Indeed, it was found that treating premarital sex as sinful creates incentives to marry earlier, and condemning abortion and birth control as sin makes people have children.However, when we look at the US, which is considered the most religious nation compared to its other western counterparts, what is fascinating is that it is remarkably evenly divided - approximately 42% of adults never attend religious services, 18% attend intermittently, and 40% attend services regularly (information from the 2006 US General Social Survey).This suggests that, while a country may adopt non-secular values to predominantly guide its affairs and inform its citizens, not everyone may agree or be inclined to go along with those values. In the case of the US, this divide is exemplified by the emergence of the Religious Right and the Liberal Left.As evolutionary psychologist Kenrick (2011) colloquially and aptly states it, "the prototypical member of the Liberal Left ... may wait until at least the end of college before marrying and beginning to have children and then may delay even a few years longer to go to graduate school, law school or medical school. Because the human ability to resist sexual urges has a hard time outlasting all that postponement, these folks do not like the Religious Right's attempts to impose rules against premarital sex [or] tools of family planning. ... [The Liberal Left pose a problem for the Religious Right] because a large number of sexually loose young people playing the field threatens to disrupt the strict system that religious folks have set up to enforce and reinforce family bonds."Working on that insight, Weeden, Cohen and Kenrick (2008) proposed the reproductive religiosity model - instead of religiosity affecting our mating strategy (whether we can be promiscuous short term maters, or should be committed, abstinent long term maters), it is instead our mating strategy that makes us calculate the costs and benefits of adopting a religion, or remaining devoted to our current religion. If I am unable to bear the cost of abstinence from premarital sex and I do not want to marry early, my exit strategy is to drop my impeding religion.By analyzing data from two large sources - 21,131 respondents in the 2006 US General Social Survey and 902 undergraduate students who were probed about their family plans, sexual attitudes, religious attendance, and moral feelings about issues ranging from lying to stealing - it was found that the strongest predictors of religiosity were factors related to sexual and family values. While there were other typical variables that predicted for religiosity, such as being female, older, or a non-drinker, and being high in conscientiousness and low in sensation-seeking, statistically controlling for sexual and family value items made the links between these other typical variables with religiosity disappear. In other words, everything we might have assumed to be associated with religiosity can be boiled down to sexual and family values. The study by Weeden, Cohen and Kenrick (2008) thus provide evidence that, on average, whether we are religious or not in the first place depends on how promiscuous we want to be.If that causal link is true, could it be possible to manipulate people's mating strategy and thus alter their religiosity, in the psychology laboratory no less?A study by Li, Cohen, Weeden and Kenrick (2010) sought to test that idea. A cleverly deceptive cover story and elaborate experimental design was used, but in brief, participants were ultimately made to look at either desirable members of their own sex or desirable opposite sex members (such a priming method has been found to be effective in conjuring either a mating motivation state - when we check out attractive opposite sex persons - or a mating threat state - when we are made to look at attractive same sex persons). Participants were also made to fill out a survey on the pretext of finding out their attitudes; embedded in the survey were questions pertaining to religiosity.The results showed that when the men looked at attractive ladies and when the women looked at attractive guys, there was no discernable effect of mating motivation on religiosity. Interestingly, the laboratory setting was unable to capture any desire to give up religion when participants were made to feel more motivated to mate. However, what was more interesting was that, instead, participants who looked at attractive members of one's own sex expressed greater belief in religion. Being primed with mating insecurity leads people to become more religious.We see support here for the classic antagonism played out between the Religious Right and Liberal Left. Once again, Kenrick (2011) states it best, so he will be quoted here: "When you become aware that there are a lot of highly attractive mating competitors out there, it reduces the perceived benefits of playing a fast and loose mating strategy ... For women, a lot of attractive competitors means less attention from the attractive men who might provide good genes, and fewer fellows vying to support your offspring. For men, on the other hand, an abundance of especially handsome and available guys means that if you are playing the field, you may be playing with yourself for most of the game. Under circumstances of limited opportunities, any normal person - who does not look like a fashion model - could benefit from the religion-based supports for monogamy."This is not to say that religious practices do not reduce sexual promiscuity - all other things equal between two people who are subjected to different levels of religious piety, we would expect the one who has been told that things like premarital sex are sinful would be less inclined to do the deed. However, these studies highlight another crucial direction in the causation, that sometimes people may choose how religious they want to be based on the perceived cost of carrying out sexual "transgressions" under the religion they are affiliated to. And at the heart of the differing values the Religious Right and the Liberal Left promote, each camp is sustainable because they encourage and reinforce different mating patterns; there is antagonism only because a clash of these value systems is highly disruptive to each side's foundations for their own reproductive status quo.Weeden, J., Cohen, A., & Kenrick, D. (2008). Religious attendance as reproductive support Evolution and Human Behavior, 29 (5), 327-334 DOI: 10.1016/j.evolhumbehav.2008.03.004Li YJ, Cohen AB, Weeden J, & Kenrick DT (2010). Mating Competitors Increase Religious Beliefs. Journal of experimental social psychology, 46 (2), 428-431 PMID: 20368752... Read more »
A ketogenic diet prevents diabetes in STZ-treated rats. ... Read more »
Al-Khalifa A, Mathew TC, Al-Zaid NS, Mathew E, & Dashti H. (2011) Low carbohydrate ketogenic diet prevents the induction of diabetes using streptozotocin in rats. Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie, 63(7-8), 663-9. PMID: 21943927
Buffer This animation film was submitted by a med student to YouTube for the instructor of a course about ‘Narratives of Ageing:Exploring Creative Approaches to Dementia Care’. Students visited a locked unit at a care facility for people with Alzheimer’s disease. They used YouTube to watch streamed video made by Alzheimer’s disease advocacy groups, twitter [...]
No related posts.... Read more »
George, D., & Dellasega, C. (2011) Social media in medical education: two innovative pilot studies. Medical Education. DOI: 10.1111/j.1365-2923.2011.04124.x
Whales are highly-modified, once-hoofed mammals which are entirely aquatic. This is arguably one of the greatest of evolutionary punchlines. We just didn’t get the joke until relatively recently.
Upon viewing a whale skeleton, the fact that the animal once had terrestrial ancestors is not too difficult to detect – hints that their forerunners walked the prehistoric [...]... Read more »
Gingerich, P. (2001) Origin of Whales from Early Artiodactyls: Hands and Feet of Eocene Protocetidae from Pakistan. Science, 293(5538), 2239-2242. DOI: 10.1126/science.1063902
Thewissen, J., Sensor, J., Clementz, M., & Bajpai, S. (2011) Evolution of dental wear and diet during the origin of whales. Paleobiology, 37(4), 655-669. DOI: 10.1666/10038.1
Thewissen, J., Williams, E., Roe, L., & Hussain, S. (2001) Skeletons of terrestrial cetaceans and the relationship of whales to artiodactyls. Nature, 413(6853), 277-281. DOI: 10.1038/35095005
The submissions are now in for The Open Laboratory 2011, an anthology of the best science blogging of the year. There are 721 great science posts in the chase for 52 slots in the anthology! I’m more than flattered that four of my posts were nominated. Three of them are already here on the Scientific [...]
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Brian Bowen. (2007) Sexual Harassment By A Male Green Turtle (Chelonia mydas). Marine Turtle Newsletter, 10. info:/
It is no secret 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. Australian scientists have now found an unusual source for a new antimicrobial: the kangaroo's pouch. Kangaroos use a wide array of powerful antimicrobial proteins as part of their innate immune system. With the tammar wallaby's genome recently sequenced, scientists have found several such drug candidates, and also reconstructed an ancestral bacteria-killing protein, deemed to be 59-million years old. 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.... Read more »
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
Vegetables are healthy for you, but ever wonder if there are nutritional differences between raw and cooked vegetables? Does it matter how they are prepared? Raw vegetables are often believed to be more beneficial than cooked ones because cooking causes … Continue reading →... Read more »
Pellegrini, N., Chiavaro, E., Gardana, C., Mazzeo, T., Contino, D., Gallo, M., Riso, P., Fogliano, V., & Porrini, M. (2010) Effect of Different Cooking Methods on Color, Phytochemical Concentration, and Antioxidant Capacity of Raw and Frozen Brassica Vegetables. Journal of Agricultural and Food Chemistry, 58(7), 4310-4321. DOI: 10.1021/jf904306r
Behind every great mobile organelle is an equally awesome motor protein. The motor proteins dynein and kinesin move cargo along microtubules, and play crucial roles in countless cellular processes. A recent paper shows how these two motors cooperate. The fungus Ustilago maydis grows into long hyphal cells in laboratory culture. Their use in cell biology is powerful, as their length and motor transport is reminiscent of human neurons. These long cells grow from the cell tip and have similarly oriented microtubules at either end of the cell. In the middle of the cell, microtubules overlap with opposite polarity. The polarity of these microtubules is important – dynein motors walk to one end of microtubules (the “minus” end), while most kinesin motors walk to the other (the “plus” end). A recent paper looked at how these two motors cooperate with each other in the motility of early endosomes in U. maydis cells. Schuster and colleagues found that while dynein is important for short-range motility, kinesin is important for long-range transport through the antipolar microtubule array in the center of the cell. Top image above shows the elongated hyphal cell with the nucleus in red. Bottom image shows the growth of microtubules by showing two consecutive time-points of EB1 (red then green), which is a protein found on the tips of growing microtubules. The two different insets show the antipolar growth of microtubules at the center (left inset), compared with the growth of similarly-oriented microtubules near the cell tip (right inset). Schuster, M., Kilaru, S., Fink, G., Collemare, J., Roger, Y., & Steinberg, G. (2011). Kinesin-3 and dynein cooperate in long-range retrograde endosome motility along a nonuniform microtubule array Molecular Biology of the Cell, 22 (19), 3645-3657 DOI: 10.1091/mbc.E11-03-0217... Read more »
Schuster, M., Kilaru, S., Fink, G., Collemare, J., Roger, Y., & Steinberg, G. (2011) Kinesin-3 and dynein cooperate in long-range retrograde endosome motility along a nonuniform microtubule array. Molecular Biology of the Cell, 22(19), 3645-3657. DOI: 10.1091/mbc.E11-03-0217
Last weekend I went to the mall in search of a new pair of tennis shoes since I’ve run the life out of my current pair, and while I was there, I continued my never-ending quest to find the perfect pair of boots (just ask my husband – I’ve been on this quest for years). When I arrived at the mall, the parking lot was so full that I had to circle around before I could find a spot. The stores were equally crowded inside. Apparently none of these shoppers had read Leaf Van Boven’s
2005 review article highlighting the benefits of spending money on experiences over material goods. Juli first mentioned this finding in her post on the four ways to buy happiness, and I wanted to spend some more time on the topic since I still have a bit of trouble
accepting the findings, particularly when I’m on a quest for a material good that I’m sure will change my life (spoiler alert - I did buy a pair of boots, though I’m not sure they’re “the ones”).
surveying various cultures to determine what makes people happy, researchers
kept stumbling upon the finding that having more didn’t equate to being
happier. And people who aspire to have more are, in fact, less satisfied. For
example, the more that people endorse the statement “Buying things gives me
pleasure” the less satisfied they are with their lives. But, it seems, this is
only true if you are spending your money to buy “things” rather than
“memories.” Whether people are asked to directly compare experiential versus
material purchases or to simply write about or reflect on a specific recent purchase,
they report that the experiential purchase made them happier, contributed more
to their overall happiness, and was “money better spent.” In the moment, Recalling
their most recent vacation seems to put people in a better mood than recalling
their last shoe purchase.
Read More-... Read more »
Van Boven, L. (2005) Experientialism, Materialism, and the Pursuit of Happiness. Review of General Psychology, 9(2), 132-142. DOI: 10.1037/1089-26184.108.40.206
July Sunset Santa Fe, New MexicoI had previously reported on the use of low-dose doxepin for the treatment of insomnia. A new study on this topic has been published in the journal Sleep. Dr. Andrew Krystal from Duke University and colleagues presented results of an efficacy and safety trial of doxepin at 1 mg and 3 mg in a series of elderly subjects with chronic primary insomnia studied over a 12-week period.Long-term efficacy studies for insomnia are important because the condition is commonly chronic and long-term hypnotic treatment may be necessary.The key elements in the design of this study included:Subjects: Men and women 65 years of age and older with a DSM-IV-TR diagnosis of primary insomniaSleep study assessment: All subjects received a one-week placebo trial during which they underwent two night in a sleep laboratory. Subjects were required to greater than 10 minutes of sleep latency as well as be awake at least 60 minutes during the sleep period. In addition they were required to have a total sleep time of more than 240 minutes but less than 390 minutes during the placebo sleep study session. Subjects with evidence of sleep apnea during the sleep study were excluded.Drug randomization: 12-weeks of nightly treatment with placebo, one mg of doxepin or three mg of doxepinPrimary outcome measure: wake time after sleep onset on day one of randomization and also on day 29 and day 85 of studyDoxepin (one and three mg) reduced the time awake after sleep onset on the first night of drug treatment (night one 28 minutes and 43 minutes respectively for the one and three mg dose). This was statistically significant compared to placebo where time awake after sleep onset was reduced 11 minutes on night one. The therapeutic effect of doxepin on this key outcome measure was maintained throughout the 12-week study.Looking at components in the architecture of sleep, the three mg doxepin dose was associated with an increase in deep sleep (stage 3/4) on night one (33 minutes placebo and 42 minutes three mg doxepin). This increase was not noted by the end of the two week study. However, the time in REM sleep was increased at twelve weeks for three mg doxepin compared to placebo (67 minutes compared to 57 minutes for placebo). Subjects in the doxepin randomized group were no more likely to report problems with residual daytime sedation or alertness.The authors noted the study found no evidence of adverse events linked to doxepin at either the one or three mg dose. Cardiovascular effects are potentially important, because doxepin is a tricyclic antidepressant that can influence cardiac conduction and orthostatic blood pressure. However, no drug-related EKG or blood pressure problems were noted in this elderly cohort. Additionally, there was no evidence low dose doxepin was linked to weight gain, a problem seen at higher doses.This study confirms the efficacy and safety of low-dose doxepin in elderly individuals. Previous research showed this effect in individuals younger than 65 years. Since insomnia is common in the elderly, this study should provide clinicians and elderly insomniacs another potential treatment option.Photo of Santa Fe, New Mexico sunset from the author's collection.Krystal, A., Lankford, A., Durrence, H., Ludington, E., Jochelson, P., Rogowski, R., & Roth, T. (2011). Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia SLEEP DOI: 10.5665/sleep.1294... Read more »
Krystal, A., Lankford, A., Durrence, H., Ludington, E., Jochelson, P., Rogowski, R., & Roth, T. (2011) Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia. SLEEP. DOI: 10.5665/sleep.1294
I haven’t really touched on the early research on risks in supply chain management. One major stream is on random yields. Parlar and Wang (1993) were one of the firsts to extend the classic Newsboy and EOQ (Economic Order Quantity) models to include uncertainty.... Read more »
Parlar, M., & Wang, D. (1993) Diversification under yield randomness in inventory models. European Journal of Operational Research, 66(1), 52-64. DOI: 10.1016/0377-2217(93)90205-2
A research group at the University of Indiana has developed a program called Truthy that allows anyone to track cases of “astrotweeting”. Any search term can be entered into Truthy and the program will scan the Twitter API and build a model of how the search term originated. ... Read more »
Ratkiewicz,J. Conover,M. Meiss,M. Gonçalves,B. Patil,S. Flammini,A. Menczer, F. (2011) Truthy: Mapping the Spread of Astroturf in Microblog Streams. World Wide Web Conference Committee (IW3C2). . info:/
Vaccines are great aren't they - they offer us probably the most cost-effective means of reducing death and suffering on a worldwide scale that extends to both humans and other animals. The problem is that it's never been as easy as just dreaming up a vaccine for the latest virus to afflict us. Effective vaccines are extremely difficult to produce, even for the most well-researched pathogens and, even when you do develop one, plow billions into it's generation and testing, and get it successfully through all the necessary clinical trials it still might not work so perfectly.
This sheer deadly annoyance is known as vaccine failure - and it's a massive problem if you're interested in eradicating infectious diseases, which of course many of us are. For some info, see what's been happening with the elimination of mumps - some people, even those who have been vaccinated with the MMR twice, are getting the disease. If we can't eradicate diseases like measles and mumps - which have an amazingly good vaccine - how ever can we eliminate more difficult-to-handle viruses like HIV?
This all has encouraged a major research area has sprung up in lessening the effects of vaccine failure on immunisation campaigns through attempting to predict those that will respond well and those who won't and potentially focusing your attention on the ones who won't respond. And this research may even teach us something about immunology through highlighting those critical genes required for antiviral defence and this could be used in the de novo design of vaccines in the future.
There are all sorts of types of vaccine failure: it may be the virus differs in some crucial antigenic site when compared to your vaccine, the vaccine may work superbly initially but 10 years later the very same immunity could wane. But, one of the main types of this - and probably the most important - is the failure of a patient (someone receiving the vaccine) to mount the desired immune response: no antibodies, no T cells etc. This means that despite having been vaccinated, they will still get infected and pass the virus on. In some cases this can extend to 10% of people being immunised - even with highly successful vaccines like the MMR. Scary when you think that many of these highly infectious viruses require nearly 90% of the population to be immune before it can no longer spread.
If we rule out differences in the vaccine people get - which I don't think we can do easily as differences in strains used, storage temperatures, administration could change between patients - but you can try, you are left with differences in the people. These differences could be things like age at vaccination, previous infection history, stress levels - anything that can influence your immune system (which is a lot of things!). But, a major contributory factor you would predict to be is their genetics: the inter-personal differences in DNA sequence, which is especially true when you consider the range of proteins a vaccine requires to interact with to induce immunnity in any given person - genetic variation between the coding or non-coding squences of each of these proteins may change how well they respond a given vaccine.
A basic outline of part of the innate sensing of viruses - how may genetic variation in these components influence vaccine responses? http://www.nature.com/ng/journal/v38/n8/images/ng0806-866-F1.jpg
Much of this research is carried out by guys over at the Mayo Clinic Vaccine research group through Gregory Poland who, using standard genotypying methods,
uncover a few statistically significant associations between SNPs and the
immune response to particular vaccines: measles, rubella and smalllpox,
for example. But of course this can and should be extended to other viruses, pathogens and the like. Have a look at some of their research carried out over the last few years:
Maybe your proteins don't 'see' the vaccine as well:
Genetic polymorphisms in host antiviral genes: Associations with humoral and cellular immunity to measles vaccine.
synthetase single-nucleotide polymorphisms and haplotypes are
associated with variations in immune responses to rubella vaccine.
between SNPs in toll-like receptors and related intracellular signaling
molecules and immune responses to measles vaccine: preliminary results.
Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine.
Maybe your immune system doesn't respond like we hoped:
between single nucleotide polymorphisms and haplotypes in cytokine and
cytokine receptor genes and immunity to measles vaccination.
between cytokine/cytokine receptor single nucleotide polymorphisms and
humoral immunity to measles, mumps and rubella in a Somali population.
when using live vaccines such as the MMR, those vaccine viruses don't
replicate as efficiently as they should because of receptor changes:
Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors.
I predict that in the future they will extend their studies to bigger population sizes and to different races but once they have figured out what variations are the most important I will be interested in how this will be used in vaccination efforts across the world and how it will influence how we immunise. For example, how will the already cash-strapped vaccination efforts in sub-Saharan Africa and South-East Asia cope with using these tests? Or will it be just used in developed world clinics? Also, this work fits nicely into the systems biology efforts which also aims to understand - and predict - the human response to vaccination with the goal of generating improved vaccines (see post here).
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Haralambieva IH, Ovsyannikova IG, Umlauf BJ, Vierkant RA, Shane Pankratz V, Jacobson RM, & Poland GA. (2011) Genetic polymorphisms in host antiviral genes: Associations with humoral and cellular immunity to measles vaccine. Vaccine. PMID: 21939710
by Persuasion Strategies in Persuasive Litigator
By Dr. Ken Broda-Bahm: Rushing into the courtroom, late in returning from a break, the lawyer stood before the already seated jury, red-faced, but with a self-deprecating smile. "Ladies and gentlemen, this is what every lawyer fears, and I'm truly...mortified to have kept you waiting." And the jury responded not with irritation, but with warm smiles and chuckles. Why? Not because they enjoyed wasting their time (note: jurors don't), but because this lawyer had just humanized himself by sharing an unplanned moment of sincere embarrassment. So embarrassment is persuasive? Yes, according to a recent study (Feinberg, Willer & Keltner, 2011),...
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Feinberg M, Willer R, & Keltner D. (2011) Flustered and faithful: Embarrassment as a signal of prosociality. Journal of personality and social psychology. PMID: 21928915
Obese youth are often stigmatized by society, and this stigmatization can have drastic, and long lasting consequences ranging from decreased self esteem to increased suicidal ideation. And for those youth who remain obese into adulthood, they also face worse employment, educational opportunities and even stigmatization by healthcare professionals. Knowing that obese youth face this sort [...]... Read more »
Puhl RM, Peterson JL, & Luedicke J. (2011) Parental Perceptions of Weight Terminology That Providers Use With Youth. Pediatrics. PMID: 21949145
“I am flying home from Europe in late August with nothing but a notebook and the 2011 Goldschmidt conference Geology giveaway issue to keep me occupied. Using the old-fashioned method of reading and writing on paper, I will blog my way through the compilation of highlighted geochemistry papers as time allows. These will then be posted via time delay to keep the blog moving while preventing ... Read more »
Kharaka, Y., Cole, D., Hovorka, S., Gunter, W., Knauss, K., & Freifeld, B. (2006) Gas-water-rock interactions in Frio Formation following CO2 injection: Implications for the storage of greenhouse gases in sedimentary basins. Geology, 34(7), 577. DOI: 10.1130/G22357.1
I’ve already written a post about parasites that affect their hosts’ behaviour, but it’s such a cool subject that I don’t think anyone will mind another example of it :) Species in the braconid genus Chelonus are egg-larval parasitoids. Parasitoids are parasitic in their larval stage and free-living as adults. Egg-larval parasitoids are those that, [...]... Read more »
KAESLIN, M., PFISTERWILHELM, R., & LANZREIN, B. (2005) Influence of the parasitoid and its polydnavirus on host nutritional physiology and implications for parasitoid development. Journal of Insect Physiology, 51(12), 1330-1339. DOI: 10.1016/j.jinsphys.2005.08.003
Citizens of the Ancient World seem to have made a solid go at “going green.” Ongoing research by Harriet Foster and Caroline Jackson (2010) revealed hints of color deriving from previously blown glass in colorless glass, indicating that Romans often reused glass, adding batches of broken vessels into the raw material from which they fashioned [...]
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Foster, Harriet and Caroline Jackson. (2010) The Composition of Late Romano-British Colourless Vessel Glass: Glass Production and Consumption. Journal of Archaeological Science, 3068-3080. info:/10.1016/j.j.as.2010.07.007
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