Spears. Bows and arrows. Swords. Guns. Bombs. Drones. Microbes. The evolution of weapons and forms of warfare shadows our technological advancements, from the field of metallurgy to that of microbiology.... Read more »
I’m willing to bet that most scientists were pretty destructive as kids. Not intentionally destructive, though…I bet we all liked taking things apart to see what each part of a toy did. Maybe your Teddy Ruxpin eventually sounded like a demonic doll after your experiments, or you finally pulled apart your Etch-A-Sketch to uncover the magic. Either way, it was early training for what scientists do every day to understand cells better. Today’s image is from a paper that takes this route to understand cell adhesion better.Integrins are transmembrane proteins that attach a cell to another cell or its surrounding extracellular matrix, so their role in regulating cell adhesion in normal cell function, development, and disease is of serious interest to biologists. There are several types of integrins, frequently expressed together at the same time. A recent paper describes a system to investigate how specific integrins function in cell adhesion, and found notable differences. Schiller and colleagues expressed either β1- or αv-class integrins in fibroblasts lacking all other integrins, and found that β1-class integrins are important in small peripheral adhesions, while αv-class integrins are important for large focal adhesions. In the images above, activity of the actin-based motor myosin and presence of the focal adhesion protein paxillin are shown in cells plated on micropatterned shapes. Cells with both β1- and αv-class integrins (middle row) have the highest myosin activity (pMLC) and paxillin signal, while cells with either β1- or αv-integrin alone have lower myosin activity and paxillin signal. Schiller, H., Hermann, M., Polleux, J., Vignaud, T., Zanivan, S., Friedel, C., Sun, Z., Raducanu, A., Gottschalk, K., Théry, M., Mann, M., & Fässler, R. (2013). β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments Nature Cell Biology, 15 (6), 625-636 DOI: 10.1038/ncb2747Adapted by permission from Macmillan Publishers Ltd, copyright ©2013 ... Read more »
Schiller, H., Hermann, M., Polleux, J., Vignaud, T., Zanivan, S., Friedel, C., Sun, Z., Raducanu, A., Gottschalk, K., Théry, M.... (2013) β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nature Cell Biology, 15(6), 625-636. DOI: 10.1038/ncb2747
Study is first to pinpoint how coral make their mineral skeletons; process also works in more acidic water
(further reading and links)... Read more »
Carl Blesch. (2013) Rutgers Findings May Predict the Future of Coral Reefs in a Changing World. Rutgers Today. info:/
If you are a human reader, you've probably never seen your lunch put up an invisibility shield and perform an evasive maneuver just as you reached for it. But spare a thought for the bats. If your peanut-butter sandwich were anything like a tiger moth, you'd have a hard time finding a meal.
Several kinds of insects are able to detect the echolocation calls of a bat that's approaching like an enemy submarine. Moths may fly in another direction if they hear a bat nearby, or even drop into an escape spiral. Some species of tiger moth, while making their dramatic maneuvers, also make clicking sounds that jam a bat's sonar.
"Jamming is the most effective defense against bats ever documented," says Aaron Corcoran, a postdoc who studies echolocation at the University of Maryland. The moths generate "bursts of ultrasonic clicks" like machine-gun fire—as many as 4,500 clicks a second—and those clicks mix with the echoes from the moth's body that the bat is listening for. "This distorts the echo signature, effectively blurring the acoustic image in the bat's brain," Corcoran says.
In a study published in PLOS ONE, Corcoran and his coauthors examined the timing of that jamming signal: how does a tiger moth decide when to start clicking? If it throws around its sound effects too freely, the moth risks drawing attention to itself (usually a bad idea for a prey species).
The researchers secured Bertholdia trigona tiger moths in dark chambers and played recordings of echolocating bats, observing which bat signals triggered clicking from the moths. Then they went into the woods and hung the moths on tethers from a device not unlike a giant fishing pole. (After each moth was "hoisted into the air," the paper explains, "the pole was shaken periodically by the experimenter to add motion to the tethered moth and to keep the moth flying.") Also hanging from the pole was a tiny microphone, which let the researchers record the sounds of approaching bats--as well as bats snagging nearby, non-tethered moths.
In a bat's hunt, there are three main phases: the search, when the bat scans the area with sonar; the approach, once the bat has found a target and begins sending faster, more intense sound pulses at it; and the "terminal buzz" as it homes in to make the kill.
The researchers found that tiger moths, dangling from their fishing poles, liked to start their sonar-jamming clicks early in the approach phase. "This allows the moth the maximum amount of time to jam the bat," Corcoran says. It also lets the moth make sure the bat's sonar is aimed at itself, and not at a nearby, less fortunate insect. Corcoran says, "The interesting part to me is that the moths appear very well adapted for determining precisely when they have been targeted by a bat."
Once a moth takes action, the approaching bat is in trouble, Corcoran says. A tiger moth sending out a jamming signal is about 10 times more likely to escape its pursuer than it would be otherwise. In his study, moths that sent out jamming clicks and simultaneously made an escape dive "got away every time." It's enough to make a hungry bat wish it had packed a sandwich.
Corcoran, A., Wagner, R., & Conner, W. (2013). Optimal Predator Risk Assessment by the Sonar-Jamming Arctiine Moth Bertholdia trigona PLoS ONE, 8 (5) DOI: 10.1371/journal.pone.0063609
Image: by Aaron Corcoran. You can find more photos, videos, and other tidbits at his website.
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In a North Carolina laboratory, a live moth was clamped tight in a box with a microphone and made to panic. Through the panic, its powers of prediction were probed. The moth, a species of tiger moth called Bertholdia trigona, isn’t psychic. Instead, the moths’ hearing is the key. It’s one of two weapons it [...]... Read more »
Cytosine methylation (5-mC) in DNA is very common, and is generally associated with repression of gene expression. DNA methylation was the first discovered type of epigenetic modification and remains one of the most actively investigated epigenetic processes, especially with respect to its use as a valuable biomarker for cancer and other human diseases. The presence ...The post Old Dog, New Tricks? Cytosine Methylation in Long Non-Coding RNAs appeared first on .... Read more »
Amort T, Soulière MF, Wille A, Jia XY, Fiegl H, Wörle H, Micura R, & Lusser A. (2013) Long non-coding RNAs as targets for cytosine methylation. RNA biology, 10(6). PMID: 23595112
Scientists have discovered a new enzyme that could prove an important step in the quest to turn waste (such as paper, scrap wood and straw) into liquid fuel.... Read more »
Kern, M., McGeehan, J., Streeter, S., Martin, R., Besser, K., Elias, L., Eborall, W., Malyon, G., Payne, C., Himmel, M.... (2013) Structural characterization of a unique marine animal family 7 cellobiohydrolase suggests a mechanism of cellulase salt tolerance. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1301502110
by admin in Beaker
A new study involving Sanford-Burnham's Erkki Ruoslahti, M.D., Ph.D., contributing to work by Samir Mitragotri, Ph.D., at the University of California, Santa Barbara, found that the shape of nanoparticles can enhance drug targeting. The study found that rod-shaped nanoparticles—or nanorods—as opposed to spherical nanoparticles, appear to adhere more effectively to the surface of endothelial cells that line the inside of blood vessels.... Read more »
Kolhar, P., Anselmo, A., Gupta, V., Pant, K., Prabhakarpandian, B., Ruoslahti, E., & Mitragotri, S. (2013) Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1308345110
A Sexual Laboratory of One's Own, aka A Clean Well-Lighted Place for SexPsychophysiologic studies of sexual response should be done in a comfortable, well-designed laboratory to minimize subject anxiety and discomfort (Woodard & Diamond, 2009, Fig. 5). How do scientists measure the physiological aspects of sexual arousal in women? A 2009 paper by Woodard and Diamond reviewed 45 years of research using instruments that measure female sexual function. These devices include the vaginal photoplethysmograph (right), vaginal and labial thermistors, pressure/compliance balloons, clitoral electromyography, and the electrovaginogram. For a full list, see Table 1 at the bottom of this post.The authors note that these physiological measures do not correlate very well with subjective ratings of sexual arousal. Furthermore, clinicians who treat women with sexual dysfunctions are of two minds. Some say the distinction between female desire and arousal may be artificial (see DSM-5 changes, p. 13), while others maintain that the merger of female sexual arousal disorder (FSAD) with Hypoactive Sexual Desire Disorder (HSDD) will be disastrous (Clayton et al., 2012).The previous post about Lybrido and Lybridos, the drugs in clinical trials for HSDD, talked briefly about Emotional Brain, the Dutch drug company that is developing them. Putting aside the many objections to the HSDD diagnosis for now, and the fact that the trials pathologize sexual boredom within marriage, the company has conducted some interesting studies1 to assess sexual desire. Foremost among these is the development of an at-home testing environment, or ambulatory lab, to conduct studies of sexual function (Bloemers et al., 2010).Fig. 1 (Bloemers et al., 2010). Schematic overview of the ambulatory measurement setting. (1) Generic laptop, (2) genital probe, (3) wireless sensor system, (4) handheld computer, and (5) secure central database.The participants must be so much more comfortable watching hardcore porn and measuring their own vaginal pulse amplitude and clitoral blood volume in the privacy of their homes, without the prying eyes of hoards of scientists in white lab coats (although some people might be into that).And that's what was found, for the most part (Bloemers et al., 2010):The results of this study support our hypothesis that in healthy controls, clitoral and subjective laboratory measures of sexual arousal show stronger increases to erotic stimuli in the home environment than in the environment of the institutional laboratory. This effect was apparent in response to hardcore stimuli, but not to erotic fantasy. ... To our knowledge, this is the first study that investigates ecological validity of sexual psychophysiological measures by comparing those assessed in the institutional laboratory to those assessed at home with an ambulatory laboratory. Footnote1 Albeit flawed studies, from a cognitive perspective (especially their implementation of an 'Emotional Stroop' task). I am not particularly qualified to comment on other aspects of this research.ReferencesBloemers, J., Gerritsen, J., Bults, R., Koppeschaar, H., Everaerd, W., Olivier, B., & Tuiten, A. (2010). Induction of Sexual Arousal in Women Under Conditions of Institutional and Ambulatory Laboratory Circumstances: A Comparative Study Journal of Sexual Medicine, 7 (3), 1160-1176 DOI: 10.1111/j.1743-6109.2009.01660.xWoodard, T., & Diamond, M. (2009). Physiologic measures of sexual function in women: a review Fertility and Sterility, 92 (1), 19-34 DOI: 10.1016/j.fertnstert.2008.04.041
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Bloemers, J., Gerritsen, J., Bults, R., Koppeschaar, H., Everaerd, W., Olivier, B., & Tuiten, A. (2010) Induction of Sexual Arousal in Women Under Conditions of Institutional and Ambulatory Laboratory Circumstances: A Comparative Study. Journal of Sexual Medicine, 7(3), 1160-1176. DOI: 10.1111/j.1743-6109.2009.01660.x
Woodard, T., & Diamond, M. (2009) Physiologic measures of sexual function in women: a review. Fertility and Sterility, 92(1), 19-34. DOI: 10.1016/j.fertnstert.2008.04.041
Asthma increasing the risk of ADHD? With a title like that derived from the paper by Mu-Hong Chen and colleagues* I couldn't resist posting an entry about it. Indeed the paper has one or two of the elements that I've come to love over my couple of years of blogging; in that we have two seemingly disparate conditions - one physiological, one behavioural - yet within the confines of the old 'correlation does not equal causation' quote, some possibility of a connection.Breathe @ Wikipedia ADHD - Attention Deficit Hyperactivity Disorder - has been on my blogging radar a few times in the past few months. Not only with regards to the numbers (see here) which seem to be going up all the time** but also with some rather curious associations in mind, such as solar intensity (see here). Stay with me on this one.The Chen paper is an interesting one based on a surprisingly large body of research supportive of some link between the two conditions***. Their specific take on this issue was to look at the temporal relationship between asthma and ADHD, which they did by means of a case - control study. Trawling a national database, which is something they are seemingly rather good at in Taiwan (see here) they came up with a very nice sample size of children with asthma (n=2294) and controls (n=9176) and looked at how many kids were subsequently diagnosed with ADHD.The results:"Children with asthma had a higher incidence of developing ADHD (7% vs. 4.6%, p < .001)".OK the difference in ADHD rates might not appear startling but bear in mind the numbers of cases and controls that they looked at. Indeed the overall risk - hazard ratio - after controlling for various other factors was 1.31 (95% CI: 1.07-1.59).Browsing through older posts on this blog it appears I've talked about some of Chen's work previously with an entry on allergic and autoimmune conditions being more readily diagnosed in cases of autism (see here). This tells me that this research group have some interest in the area of physiology and behaviour being linked and have the means to look at some quite big samples to test the correlations.So with correlation put to the test and potentially something found, the next questions: how and why? Given how close and cosy ADHD seems to be getting to diagnoses like autism - see the Rao & Landa study**** and accompanying press - on top of all that ESSENCE chatter (see here), one might speculate at potentially similar mechanisms being involved. Indeed, when I wrote about asthma and autism a while back (see here) a few themes emerged based on familial genetics and some overlap for immune function which may be relevant. More recent speculations on things like the hygiene hypothesis (and see here) become even more relevant when it comes to conditions like asthma. I wish I could give a more definitive answer about any connection but it's all rather complicated. One last thought to mention is that rather interesting study by Barbara Stewart (see here) on some anatomical differences found in the airways of children with autism. I'm no expert on the physiology of the lungs and asthma but wonder whether this might also be relevant (or not) to cases of ADHD too.And finally(!) another quote from the Chen study: "Further studies are required to investigate whether the prompt treatment of asthma and comorbid allergic diseases could prevent the development of ADHD or decrease ADHD symptoms". Food for thought?---------* Chen MH. et al. Asthma and attention-deficit/hyperactivity disorder: a nationwide population-based prospective cohort study. J Child Psychol Psychiatry. June 2013. ** Getahun D. et al. Recent trends in childhood attention-deficit/hyperactivity disorder. JAMA Pediatr. 2013; 167: 282-288.*** Mogensen N. et al. Association between childhood asthma and ADHD symptoms in adolescence--a prospective population-based twin study. Allergy. 2011; 66: 1224-1230.**** Rao PA. & Landa RJ. Association between severity of behavioral phenotype and comorbid attention deficit hyperactivity disorder symptoms in children with autism spectrum disorders. Autism. June 2013.----------Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, Chen TJ, & Bai YM (2013). Asthma and attention-deficit/hyperactivity disorder: a nationwide population-based prospective cohort study. Journal of child psychology and psychiatry, and allied disciplines PMID: 23730913... Read more »
Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, Chen TJ, & Bai YM. (2013) Asthma and attention-deficit/hyperactivity disorder: a nationwide population-based prospective cohort study. Journal of child psychology and psychiatry, and allied disciplines. PMID: 23730913
The evolution of living fossils is not unusual. The odd thing about them is that they have ancient origins and are, today, not very diverse groups. Sturgeon are ray-finned fishes in the family Acipenseridae, which are known from almost 200 million year old fossils. Fossils that are recognisably similar to modern sturgeons appear about 100 million years ago. There are 23 (but maybe a few more) modern species in the Acipenseridae, which is probably fairly similar to their historical diversity. A sturgeon in the genus Acipenser, possibly A. transmontanus (image Wikipedia).Other families of fish are much more diverse than the Acipenseridae. Some of the most beautiful marine fish are in the families Gobiidae (gobies) and Labridae (wrasses), with over 2,000 and 600 species respectively. And they aren't even the largest families of fish. That honour probably goes to the Cyprinidae (carps and minnows) with over 2,400 species. This pattern raises an interesting question; why are some groups highly diverse while others are not?The old glory goby, Amblygobius rainfordi (top), the Yellowtail coris wrasse, Coris gaimard, being cleaned by a cleaner wrasse, Labroides phthirophagus (middle), and the cleaning goby, Elacatinus evelynae (bottom). Notice the convergent colour evolution in the cleaner fishes (all images Wikipedia).One hypothesis is that some groups are more 'evolvable'. These groups are able to change their morphology relatively quickly and are consequently able to form more new species. For this hypothesis to be true, we should see a correlation between the amount of phenotypic change within a group and the amount of speciation. Studies that have looked at this relationship within lineages have failed to detect it.A new paper by Rabosky and others argues that a fairer test of the hypothesis is to look at the relationship among lineages. They constructed an enormous evolutionary tree containing almost 8,000 species from across the entire spectrum of diversity of ray-finned fishes. They used body size evolution as a proxy for phenotypic change and found overwhelming support for the hypothesis; families with greater diversity in body size typically contained a greater number of species.One group to buck this trend were the sturgeons. The rate of change in body size in sturgeons is amongst the fastest for all fishes. The baluga, Huso huso, is one of the largest ray-finned fishes, growing to over five and a half meters and 1,000 kilograms, while the dwarf sturgeon, Pseudoscaphirhynchus hermanni, grows to just 27 cm and 50 grams. This considerable difference in body size has arisen almost 5.4 times more rapidly than expected and only five of the 172 families in the analysis diverged faster.These results are in complete contrast to the popular conception of living fossils as slow changing evolutionary oddballs. Indeed, in this analysis sturgeon are outliers because of the speed of their evolution. Clearly some traits in sturgeon are highly conserved over large periods of time, but we should not assume that this means that all of their traits are highly conserved. Living fossils are evolving and can diverge rapidly.I've also written about living fossils here and here. ReferenceRabosky, D., Santini, F., Eastman, J., Smith, S., Sidlauskas, B., Chang, J., & Alfaro, M. (2013). Rates of speciation and morphological evolution are correlated across the largest vertebrate radiation Nature Communications, 4 DOI: 10.1038/ncomms2958... Read more »
Rabosky, D., Santini, F., Eastman, J., Smith, S., Sidlauskas, B., Chang, J., & Alfaro, M. (2013) Rates of speciation and morphological evolution are correlated across the largest vertebrate radiation. Nature Communications. DOI: 10.1038/ncomms2958
When you typically think of computer scientists working on questions in biology, you probably picture a bioinformatician. Although bionformatics makes heavy use of algorithms and machine learning, and its practitioners are often mildly familiar with computational complexity (enough to know that almost everything they study is NP-complete), it doesn’t really apply computational thinking to understand […]... Read more »
Pais, D., & Leonard, N. (2013) Adaptive network dynamics and evolution of leadership in collective migration. Physica D: Nonlinear Phenomena. DOI: 10.1016/j.physd.2013.04.014
Françoise Barré-Sinoussi, the discoverer of HIV, visits the Centre for Virus Research in Glasgow.... Read more »
Barre-Sinoussi, F., Chermann, J., Rey, F., Nugeyre, M., Chamaret, S., Gruest, J., Dauguet, C., Axler-Blin, C., Vezinet-Brun, F., Rouzioux, C.... (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science, 220(4599), 868-871. DOI: 10.1126/science.6189183
All jobs come with health risks. Some risks are obvious in the short-term, others seem very minor but with plenty of negative long-term consequences. Such as weight gain or irritable bowel syndrome. ... Read more »
Nojkov B, Rubenstein JH, Chey WD, & Hoogerwerf WA. (2010) The impact of rotating shift work on the prevalence of irritable bowel syndrome in nurses. The American journal of gastroenterology, 105(4), 842-7. PMID: 20160712
Okami, Y. (2013) Irritable bowel syndrome in Chinese nursing and medical school students—Related lifestyle and psychological factors. Open Journal of Gastroenterology, 03(01), 55-63. DOI: 10.4236/ojgas.2013.31009
When we pass through the Appalachian Mountains along its vast extent
from the humid southeast of Alabama and Georgia to the cold and barren of Nova
Scotia and Newfoundland, we cannot help but marvel of its beauty and
extensiveness. Unlike its western cousin, the Rocky Mountains, which is a mixture of forested ranges imbedded in
a matrix of lowland shrub and grass ... Read more »
Laundré JW. (2010) Behavioral response races, predator-prey shell games, ecology of fear, and patch use of pumas and their ungulate prey. Ecology, 91(10), 2995-3007. PMID: 21058559
RIPPLE, W., & BESCHTA, R. (2004) Wolves and the Ecology of Fear: Can Predation Risk Structure Ecosystems?. BioScience, 54(8), 755. DOI: 10.1641/0006-3568(2004)054[0755:WATEOF]2.0.CO;2
Hi Julie,(source: The Blue Dog)WOW! May was a seriously jam-packed month for dogs! I'm just as amazed as you are that it's already June. I think I'm in denial, although June means lots of fun things happening, like the SPARCS conference, so maybe it's actually OK that it's here.I loved your last post. So much great information - thank you for sharing! You mentioned how you avoid touching dogs if they don't want to interact and that got me thinking about a sense I haven't written about yet. We've covered views, smells, music and now, I'm going to touch on, well... touch. Not the bitey kind of touch, but the soothing, calm, stroking kind. The outside of a dog is good for our insides...It's true. Patting a dog is something we enjoy. The tactile experience of touching something soft and warm is inherently pleasing. Research has shown that human oxytocin (=happy/social/feel good/"love" hormone) levels rise when we interact with our dogs. Our blood pressure and heart rates lower when we pat dogs, as do our cortisol (=stress hormone) levels.(source)These are just some of the reasons there is so much interest in researching further benefits of human-animal interactions and animal-assisted therapies....and we can be good for a dog's insides too!(source)Interestingly, other studies have shown that dogs' heart rate, cortisol levels and blood pressure can lower when we groom and pat them. Of course, this is not universal. Dogs are individuals and their preferences will vary. Not all pats are equalResearch suggests that dogs prefer to be patted in a soothing way. Not really surprising - think of how we like to be touched and compare a back slap with a gentle stroke. I know which would be more likely to lower my heart rate and relax me!A study that examined the reinforcing value of physical contact by grooming to dogs showed that length of grooming (longer=better) was more important than location of grooming in reducing heart rate. What are you doing this week? I'm off to Sydney for a few days to meet with loads of different working dog groups to talk Action Plan. I'll be sure to tell you all about it next time. Right now, I'm going to go give my dogs a nice long pat! Mia... Read more »
McGreevy Paul D., Righetti Joanne, & Thomson Peter C. (2005) The reinforcing value of physical contact and the effect on canine heart rate of grooming in different anatomical areas. Anthrozoos: A Multidisciplinary Journal of The Interactions of People , 18(3), 236-244. DOI: 10.2752/089279305785594045
Coppola Crista L., Grandin Temple, & Enns R. Mark. (2006) Human interaction and cortisol: Can human contact reduce stress for shelter dogs?. Physiology , 87(3), 537-541. DOI: 10.1016/j.physbeh.2005.12.001
Hennessy Michael B., Voith Victoria L., Hawke Jesse L., Young Travis L., Centrone Jason, McDowell Angela L., Linden Fran, & Davenport Gary M. (2002) Effects of a program of human interaction and alterations in diet composition on activity of the hypothalamic-pituitary-adrenal axis in dogs housed in a public animal shelter. Journal of the American Veterinary Medical Association, 221(1), 65-91. DOI: 10.2460/javma.2002.221.65
Bergamasco Luciana, Osella Maria Cristina, Savarino Paolo, Larosa Giuseppe, Ozella Laura, Manassero Monica, Badino Paola, Odore Rosangela, Barbero Raffaella, & Re Giovanni. (2010) Heart rate variability and saliva cortisol assessment in shelter dog: Human–animal interaction effects. Applied Animal Behaviour Science, 125(1-2), 56-68. DOI: 10.1016/j.applanim.2010.03.002
O'Haire Marguerite. (2010) Companion animals and human health: Benefits, challenges, and the road ahead. Journal of Veterinary Behavior: Clinical Applications and Research, 5(5), 226-234. DOI: 10.1016/j.jveb.2010.02.002
I bet you don’t think about the 100 trillion microbugs thriving in your gut too much. Neither did I, until I started reading up on the Human Microbiome Project (HMP) at a conference last week. Several fun facts that came out from the project: For every human cell, there are 10-100 times of microbe living […]... Read more »
Diaz Heijtz R, Wang S, Anuar F, Qian Y, Björkholm B, Samuelsson A, Hibberd ML, Forssberg H, & Pettersson S. (2011) Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 3047-52. PMID: 21282636
Foster JA, & McVey Neufeld KA. (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends in neurosciences, 36(5), 305-12. PMID: 23384445
Your IQ at the age of eleven predicts your brain anatomy sixty years later, according to a Canadian/Scottish team of neuroscientists: Childhood cognitive ability accounts for associations between cognitive ability and brain cortical thickness in old age. The authors of the new paper, Karama et al, made use of a unique long-term study of Scottish [...]... Read more »
Karama, S., Bastin, M., Murray, C., Royle, N., Penke, L., Muñoz Maniega, S., Gow, A., Corley, J., Valdés Hernández, M., Lewis, J.... (2013) Childhood cognitive ability accounts for associations between cognitive ability and brain cortical thickness in old age. Molecular Psychiatry. DOI: 10.1038/mp.2013.64
Gene therapy is a pretty promising approach for lots of different diseases, and has already overcome a huge hurdle with the approval of the very first gene therapy product, Glybera, by the European Commission in 2012. At its core, gene … Continue reading →... Read more »
Swift, S., Rivera, G., Dussupt, V., Leadley, R., Hudson, L., MA de Ridder, C., Kraaij, R., Burns, J., Maitland, N., & Georgopoulos, L. (2013) Evaluating Baculovirus as a Vector for Human Prostate Cancer Gene Therapy. PLoS ONE, 8(6). DOI: 10.1371/journal.pone.0065557
One of the new concepts I learned when I started working on HIV was the most recent common ancestor, or MRCA. When you look at the genetic make-up of a population, you will find a certain amount of variety but also a much greater amount of overlap, i.e. stretches of DNA that are identical throughout the population. Using phylogenetics, one can look at these patterns of shared vs. mutated stretches, and reconstruct the genetic ancestor of the population. For example, you've probably heard of Mitochondrial Eve: since we all inherit our mitochndrial DNA from our mothers, scientists have been able to look at the mitochondrial DNA across all populations and determine the one ancestor (our common mother, so to speak) from which they all originated. Pretty cool, right?My line of work, for the past 6-7 years has been estimating most common recent ancestors, or MRCAs, of HIV-1 populations. A few years ago we found that in sexually transmitted infections only a handful of viruses are able to come across the genital mucosa and start the infection. Therefore, if you draw a blood sample early enough (a few weeks) after the start of the infection, from that sample we can infer the MRCA of the viral population in the patient. This is particularly relevant because in the case of a viral infection, the MRCA is likely to be the virus that initiated the infection. As the infection progresses, the viral population changes, but it is the ones that are able to break the mucosal barrier (i.e. the MRCAs) that a vaccine needs to target.Once inside the host, viral evolution is (for the most part) driven by the host's immune system as it tries to counter-attack the infection. At the same time, as the virus changes its genetic make-up to escape the immune pressure, the immune system itself changes and tries to come up with new ways to neutralize the enemy. It's an arms race that in HIV infections typically sees the immune system always one step behind: the first antibodies found in an HIV-1 infected person react with the first, unmutated virus that initiated the infection (the MRCA). As the infection progresses and the virus evolves, new antibodies are made that are able to react to the following viral generations, but typically there's always a subpolulation of viruses that's one step ahead of the antibodies and can still escape. (I hope this part is clear, I've been struggling quite a bit to find the right wording for this paragraph, so if it's not clear feel free to ask questions in the comments.)In order to design an efficient vaccine, we need to find a way to elicit broad neutralizing antibodies, where by "broad" we mean antibodies that react not only to the present or past viral generations in one host, but to a wide variety of viruses across different hosts and populations. Such antibodies are found in a minority of HIV-infected patients and, typically, by the time they arise, the infection is so spread that they cannot clear the virus. Ideally, a vaccine should boost a "short-cut" in the evolutionary path that leads to the production of broadly neutralizing antibodies much faster than our bodies are currently capable of. Unfortunately, all vaccine trials attempted so far have not been able to elicit broad neutralizing antibodies. Why? Antibodies are made by B-cells, white blood cells produced in the bone marrow. In order to produce antibodies, B cells need to be activated, which happens when they find an antigen specific to their receptor. Once activated, B cells not only start producing antibodies, but they also either become memory cells (so that if the antigen is encountered again, the immune system will know which antibodies to produce in order to clear it) or they undergo further differentiation. This process of undergoing more differentiations ensures that the "match" between receptor and antigen becomes tighter and tighter. It takes many cycles of differentiations to produce HIV-1 broadly neutralizing antibodies, and, currently, the process takes so long that most patients don't produce them ever, and the ones that do, don't get them in time to clear the infection. One reason why we believe it takes many differentiations to make HIV broadly neutralizing antibodies is that they share many similarities to self-reacting antibodies, antibodies that are normally destroyed by the body because they carry a high risk to originate auto-immune disorders (when the immune system attacks its own self instead of antigens). So, instead of eliciting the actual antibodies, could a vaccine elicit its ancestor? Remember how I said that the viral population constantly evolves and, hand in hand, so do the antibodies? Since we can estimate the viral ancestors, can we do the same for the antibodies? Can we reconstruct the differentiation pathway that leads to broadly neutralizing antibodies? In , Liao and colleagues have reconstructed the lineage of the infecting virus in one African HIV-infected patient (CH505), as well as the lineage of an antibody, found in the same patient, able to neutralize 55% of ~200 HIV-1 isolates. the researchers effectively reconstructed the coevolution of virus and antibody within the patient. The patient was followed from week 6 after the infection up until 236 weeks after the infection, and during this period no antiretroviral therapy was administered. This is important because it means that the viral evolution was driven solely by the immune pressure. Liao et al. found that the first unmutated ancestor in the B-cell lineage appears at week 14 after the infection, and it keeps mutating in ways that are reflected in the evolution of the virus. Once they retraced all the intermediate steps that led to the production of the broadly neutralizing antibody, the researchers tested all of the intermediate antibodies for reactivity against the virus, from the infecting strain to its later generations. They found that breadth and strength of reactivity increased as the antibody lineage evolved. In light of what I tried to explain above, this is a fantastic step forward in understanding how the virus evolves under the immune pressure, as it can help design a vaccine that elicits antibodies that are one step ahead (instead of behind) in the virus-host arms race. "Thus, a candidate vaccine concept could be to use the CH505 transmitted/founder Env or Env subunits (to avoid dominant Env non-neutralizing epitopes) to initially activate an appropriate naive B-cell response, followed by boosting with subsequently evolved CH505 Env variants either given in combination, to mimic the high diversity observed in vivo during affinity maturation, or in series, using vaccine immunogens specifically selected to trigger the appropriate maturation pathway by high-affinity binding to the unmutated common ancestor and antibody intermediates. [. . .] The finding that the transmitted/founder Env can be the stimulator of a potent BnAb and bind optimally to that broadly neutralizing antibody unmutated common ancestor is a crucial insight for vaccine design, and could allow the induction of broadly neutralizing antibodies by targeting unmutated common ancestors and intermediate ancestors of broadly neutralizing antibody clonal lineage trees."Of course, there's the usual caveats: will this kind of pathway be reproducible in other patients? How much of it is randomness and how much is it not only retraceable but reproducible is something we will only understand by getting more data from more patients. But it's a start, and a very promising one.  ... Read more »
Liao, H., Lynch, R., Zhou, T., Gao, F., Alam, S., Boyd, S., Fire, A., Roskin, K., Schramm, C., Zhang, Z.... (2013) Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature, 496(7446), 469-476. DOI: 10.1038/nature12053
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