Today my friend Nicholas Sansbury Smith releases Extinction Edge, the sequel to Extinction Horizon, a sci-fi thriller where humanity is driven to extinction by a lethal virus. I posted an interview with Nick for the release of his first book, but today I wanted to talk about the science behind his premise: can a virus induce epigenetic changes?In a way, Nick's premise is similar to the premise I used in Chimeras: a large part of our DNA is made of pseudogenes, which are ancient genes that are no longer coding for proteins. They are "fossils" in a way, remnants of our evolutionary history. In very layman terms: new species evolve from old ones not because old genes are replaced, rather, new gene copies arise, then mutations accumulate and differentiate the new genes from the old ones, until the old genes are silenced and the new ones take over. (There. Millions of years of evolution in one sentence.)The part that tickles a writer's imagination is the following: if we still have all these ancient genes that once made our ancestors predators and hunters, could we possibly activate them and have people regress back to those ancient states?If you've read Chimeras, you know how I made it happen in my detective Track Presius, and if you've read Extinction Horizon you know how Nick answered the question in his book. We both use a virus, though not the same one. A virus that "awakens" non-coding genes... is that completely far-fetched?Turns out, it's not. Of course, it highly depends on what genes we want to awaken.Epigenetics studies the mechanisms that turn genes "on" and "off" (i.e. expressed or not), how they are affected by the environment, and how they can be inherited from one generation to the next without being encoded in the DNA itself. One of such mechanisms that alters gene expression is DNA methylation, the addition of a methyl group to one of the A or C nucleotides in the DNA. Several studies have looked at how viruses can alter our epigenome, some in a permanent way.Viruses insert their genes inside the host cell and hijack the cell's own proteins in order to replicate. The cell, on the other hand, defends itself by trying to silence the viral genes through a series of epigenetic mechanisms. So of course viral infections and epigenetic changes go hand in hand. I'm sure that these virally induced epigenetic changes can affect us in many subtle ways, and the vast majority of these changes leave us unharmed. However, when you search the literature, you find mostly studies that have looked at viruses that are associated with tumorigenesis because clearly that's of great interest to the medical field: viruses are much easier to detect early than tumors, and if we can understand the mechanisms they use to trigger cancer, then we can also prevent them from establishing the disease.For example, the Epstein-Barr virus causes mononucleosis but it's also associated to some types of cancers, especially in immuno-suppressed individuals such as AIDS patients. As it turns out, the virus alters genome-wide gene expression in infected cells and these alterations can be pre-cancerous  (meaning the affected cells have a higher chance to accumulate tumorigenic mutations). Another virus that induces pre-cancerous epigenetic changes in liver cells is hepatitis, both the B and C kind [2, 3], which lead to liver carcinoma in about 10% of the infected individuals.Epigenetic changes have been studied in HIV infected cells, too. People infected with HIV have to take a cocktail of antiretroviral medications for life and, despite the regimen, they never completely get rid of the virus. This is because the virus inserts its genome inside cells and then some of these cells become latently infected. They do not produce virions for months, sometimes years. However, as soon as the patient stops the antiretroviral therapy, the virus suddenly "awakens" and starts spreading throughout the body. These latently infected cells form a "reservoir" and how to get rid of it has been the focus of many studies lately as it is one of the major obstacles preventing us from finding a cure for AIDS. In this review , Mbonye and Karn explain how provirions (the HIV genes inserted inside the host cell genome) become latent through epigenetic mechanisms that silence them.Studying epigenetic changes induced by viral infections is a relatively new field, but one that is very promising because contrary to genetic changes, epigenetic alterations are reversible. So, if we can find the viral triggers that lead to pathogenesis we have a potential preventive therapy by reversing those mechanisms.Extinction Edge by Nicholas Sansbury Smith: Survivors call them Variants. Irreversible epigenetic changes have transformed them into predators unlike any the human race has ever seen. And they are evolving. A bioweapon designed to save the world, a scientific discovery that will alter human history, and a new threat that will bring humanity to the edge of extinction. Chimeras by E.E. Giorgi: Haunted by the girl he couldn't save in his youth, and the murder he committed to avenge her, Detective Track Presius has a unique gift: the vision and sense of smell of a predator. When a series of apparently unrelated murders reel him into the depths of genetic research, Track feels more than a call to duty. For Track, saving the innocent becomes a quest for redemption. The only way he can come to terms with his dark past is to understand his true nature. Birdwell CE, Queen KJ, Kilgore PC, Rollyson P, Trutschl M, Cvek U, & Scott RS (2014). Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes. Journal of virology, 88 (19), 11442-58 PMID: 25056883 Tian Y, Yang W, Song J, Wu Y, & Ni B (2013). Hepatitis B virus X protein-induced aberrant epigenetic modifications contributing to human hepatocellular carcinoma pathogenesis. Molecular and cellular biology, 33 (15), 2810-6 PMID: 23716588 ... Read more »
Birdwell CE, Queen KJ, Kilgore PC, Rollyson P, Trutschl M, Cvek U, & Scott RS. (2014) Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes. Journal of virology, 88(19), 11442-58. PMID: 25056883
Tian Y, Yang W, Song J, Wu Y, & Ni B. (2013) Hepatitis B virus X protein-induced aberrant epigenetic modifications contributing to human hepatocellular carcinoma pathogenesis. Molecular and cellular biology, 33(15), 2810-6. PMID: 23716588
Rongrui L, Na H, Zongfang L, Fanpu J, & Shiwen J. (2014) Epigenetic mechanism involved in the HBV/HCV-related hepatocellular carcinoma tumorigenesis. Current pharmaceutical design, 20(11), 1715-25. PMID: 23888939
Mbonye U, & Karn J. (2011) Control of HIV latency by epigenetic and non-epigenetic mechanisms. Current HIV research, 9(8), 554-67. PMID: 22211660
The paper from Katarina Babinská and colleagues  (open-access here) presents an interesting, if preliminary take on two potentially important issues linked to at least some cases of autism: gastrointestinal (GI) issues and inflammation (see here and see here respectively).Detailing the examination of plasma levels of a compound called high mobility group box 1 protein (HMGB1), a protein which has the apparent ability to 'bend DNA' and has some pretty potent immune effects  (one paper talked about HMGB1 as being a 'nuclear weapon in the immune arsenal'), authors reported results based on the examination of 31 people on the autism spectrum compared with 16 asymptomatic controls. As well as finding as a group, that those with autism presented with significantly higher levels of plasma HMGB1, they also reported that those with some of the highest levels of HMGB1 were more likely to present with GI issues. Ergo: "Results of the study support the involvement of the systemic low-grade inflammation in the pathomechanisms of autism and its possible association with GI symptoms."Reiterating that this was a small study in terms of participant groups and that among control group participants were "10 siblings of the individuals with autism", these are interesting results. Whilst I might disagree with some of the terminology used by the authors in their paper such as the concept of 'low-functioning autism' and the term 'mental retardation' as a descriptor of the cognitive status of their participants with autism, I believe that there may be quite a bit more to do in this research area.A quick trawl through some of the other literature where autism and HMGB1 are mentioned reveals that this is not the first time that elevations in HMGB1 have been reported. The paper from Emanuele and colleagues  for example, looking at a similarly small number of participants reported that: "HMGB1 levels may be affected in autistic disorder". Further: "Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder." I'm not overly sure that based on data from 22 adults with autism one can make such statements about a single biological parameter being linked to one of the core traits that makes up a diagnosis of autism, but certainly this paper adds to the Babinská data. The paper from Russo  on epidermal growth factor (EGF) and HMGB1 with autism in mind has been previously discussed on this blog (see here). In that entry, I also linked to a piece of research correlating HMGB1 to up-regulation of something like MMP-9 (which again has been discussed here before). Follow-up work from this author  has also been published.What's more to say about HMBG1 and autism? Well, one might entertain the idea of adding HMBG1 to further research on markers of immune function in autism (see here) not forgetting the adhesion molecules too (see here). In light of the idea that there may be a link between the genetics of immune function and [some] autism (see here) one might also look at the gene producing HMBG1 and perhaps some of the other genetic/biological drivers controlling or moderating HMBG1 production.Assuming that some people on the autism spectrum are in a state of "systemic low-grade inflammation" (accepting that this description probably covers most people with and without a diagnosis at some point in their lives) and that initial correlation noted with GI issues, one might also entertain the idea of looking at what happens to HMGB1 levels as and when bowel issues are 'treated'. I say this acknowledging that bowel issues and autism can mean quite a few things (see here and see here) and that science is not quite there yet in understanding how such bowel issues come about and what one might be able to do about them. Aside that is, from the Buie papers back in 2010 (see here and see here)...Music: Dreaming of You by The Coral. You may not know their name, but you'll probably have heard the song before...---------- Babinská K. et al. Increased plasma levels of the high mobility group box 1 protein (HMGB1) are associated with a higher score of gastrointestinal dysfunction in individuals with autism. Physiol Res. 2015 Feb 10;63 Suppl 4:S613-8. Bianchi ME. & Manfredi AA. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev. 2007 Dec;220:35-46. Emanuele E. et al. Increased serum levels of high mobility group box 1 protein in patients with autistic disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):681-3. Russo AJ. Decreased Epidermal Growth Factor (EGF) Associated with HMGB1 and Increased Hyperactivity in Children with Autism. Biomark Insights. 2013 Apr 4;8:35-41. Russo AJ. Increased Epidermal Growth Factor Receptor (EGFR) Associated with Hepatocyte Growth Factor (HGF) and Symptom Severity in Children with Autism Spectrum Disorders (ASDs). J Cent Nerv Syst Dis. 2014 Sep 9;6:79-83.----------Babinská K, Bucová M, Ďurmanová V, Lakatošová S, Jánošíková D, Bakoš J, Hlavatá A, & Ostatníková D (2015). Increased plasma levels of the high mobility group box 1 protein (HMGB1) are associated with a higher score of gastrointestinal dysfunction in individuals with autism. Physiological research / Academia Scientiarum Bohemoslovaca, 63 Suppl 4 PMID: 25669692... Read more »
Babinská K, Bucová M, Ďurmanová V, Lakatošová S, Jánošíková D, Bakoš J, Hlavatá A, & Ostatníková D. (2015) Increased plasma levels of the high mobility group box 1 protein (HMGB1) are associated with a higher score of gastrointestinal dysfunction in individuals with autism. Physiological research / Academia Scientiarum Bohemoslovaca. PMID: 25669692
Multi-voxel pattern analysis (MVPA) is an increasingly popular approach for analyzing the results of fMRI scanning experiments that measure brain activity. MVPA searches for patterns of activation that correlate with a particular mental state. This is called 'decoding' neural activity.
Now a new paper in the Journal of Neuroscience from Caltech neuroscientists Julien Dubois et al. reports that MVPA is unable to decode certain kinds of information, even though single-unit recordings confirm th... Read more »
Dubois J, de Berker AO, & Tsao DY. (2015) Single-Unit Recordings in the Macaque Face Patch System Reveal Limitations of fMRI MVPA. The Journal of neuroscience : the official journal of the Society for Neuroscience, 35(6), 2791-802. PMID: 25673866
Strategies and practices to achieve supply chain resilience have been at the heart of supply chain management practice and research for almost a decade. However, such efforts have often focused on ways to make supply chains more reactive to turbulence and disruptions. In our recent article, Antecedents and Dimensions of Supply Chain Robustness, my co-authors, Christian […]... Read more »
Durach, C., Wieland, A., & Machuca, J. (2015) Antecedents and Dimensions of Supply Chain Robustness: A Systematic Literature Review. International Journal of Physical Distribution , 45(1/2), 118-137. DOI: 10.1108/IJPDLM-05-2013-0133
The Tau-A biomarker is a potential biomarker to distinguish those at risk for prolonged recovery following a concussion.... Read more »
Shahim P, Linemann T, Inekci D, Karsdal MA, Blennow K, Tegner Y, Zetterberg H, & Henriksen K. (2015) Serum tau fragments predict return to play in concussed professional ice hockey players. Journal of Neurotrauma. PMID: 25621407
Many Cambrian fossils are simply spines and sclerites unassociated with any body. Few of the exceptionally-preserved Cambrian freaks come with spines attached, and some of the most prominent of these are the chancelloriids. Originally described as sponges by Charles Doolittle Walcott back in 1920 (Walcott, 1920), modern researchers have found that the spines are very similar to those […]
The post Chancelloriids Revised appeared first on Teaching Biology.
... Read more »
Stefan Bengtson, & Desmond Collins. (2015) Chancelloriids of the Cambrian Burgess Shale. Palaeontologia Electronica. info:other/
Think of it as interval training for the dinner table. Proponents of fasting style diets will be first to tell you there are health benefits, heck we've even covered some of the science here at the labs. Well new research shows that putting people on a intermittent fasting (or IF) diet may mimic some of the benefits of actual fasting, and that (ironically enough given their popularity) adding antioxidant supplements counteracts those benefits.... Read more »
Wegman, M., Guo, M., Bennion, D., Shankar, M., Chrzanowski, S., Goldberg, L., Xu, J., Williams, T., Lu, X., Hsu, S.... (2014) Practicality of Intermittent Fasting in Humans and its Effect on Oxidative Stress and Genes Related to Aging and Metabolism. Rejuvenation Research, 2147483647. DOI: 10.1089/rej.2014.1624
Babies link the sound of a word with the image of an object in their early learning of language and this is an important ability. How do they come to have this mechanism? Are there predispositions to making links between sounds and images? Research by Asano and others (citation below) shows one type of link. […]... Read more »
Asano, M., Imai, M., Kita, S., Kitajo, K., Okada, H., & Thierry, G. (2015) Sound symbolism scaffolds language development in preverbal infants. Cortex, 196-205. DOI: 10.1016/j.cortex.2014.08.025
I want to bring the paper from Tea Skaaby and colleagues  to your attention for today's brief blog post and their observation that there may be: "a possible protective role of a higher vitamin D status on autoimmune disease". Autoimmune disease by the way, reflects a breakdown in communication and tolerance of 'self' whereby the body attacks healthy tissue.Their findings, based on an analysis of "a total of 12,555 individuals from three population-based studies with measurements of vitamin D status (25-hydroxy vitamin D)" hinted that "for a 10 nmol/l higher vitamin D" the hazard ratios for quite a few autoimmune conditions seemed to be reduced albeit with some quite wide confidence intervals (CIs). Overall however, the authors found a reduced HR "for any autoimmune disease (HR = 0.94 % CI 0.90, 0.98)" with that increasing levels of vitamin D.It's not necessarily new news that vitamin D seems to have some important biological effects when it comes to immune function  outside of the more classical physiological connections made to the stuff. Indeed, the paper by Tamblyn and colleagues  talking about an immunological role for vitamin D at the 'maternal-fetal interface' (where immune tolerance is required to "prevent fetal rejection") represents an area requiring far greater inspection particularly in light of guidance recommending vitamin D supplementation to pregnant women among other groups (see here).Without hopefully cherry-picking from the growing research literature looking at vitamin D and autoimmunity, I would also like to bring in the paper by Dong Yeob Shin and colleagues  (open-access) and the suggestion that low vitamin D status might be "associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis." Anti-thyroid peroxidase antibody (TPOAb) and autoimmune thyroiditis have been of particular interest to this blog in light of some initial data suggesting a connection with certain cases of depression (see here). That also depression has been looked at through the vitamin D lens specifically from the deficiency point of view is an interesting correlation (see here) perhaps connecting psychiatry, autoimmunity and vitamin D. I say all this acknowledging that correlation is not the same as causation and that not everyone with depression will present with autoimmune thyroiditis or other autoimmune conditions.Certainly however, I'd wager that there is perhaps more to see when it comes to how the sunshine vitamin/hormone might link up with immune function (and dysfunction) and perhaps beyond taking into account some interesting work with autism in mind too. I'd be minded to also bring in the idea that permeability of a particular membrane might also be a spot requiring a little more study in light of other research suggestions  and some preliminary tie up with vitamin D (see here) combined with more recent data . Just sayin'.Bloodbuzz Ohio by The National to close, and what a baritone...---------- Skaaby T. et al. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine. 2015 Feb 11. Antico A. et al. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012 Dec;12(2):127-36. Tamblyn JA. et al. Immunological role of vitamin D at the maternal-fetal interface. J Endocrinol. 2015 Mar;224(3):R107-R121. Shin DY. et al. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J. 2014 Mar;55(2):476-81. Fasano A. et al. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096-100. Assa A. et al. Vitamin D deficiency promotes epithelial barrier dysfunction and intestinal inflammation. J Infect Dis. 2014 Oct 15;210(8):1296-305.----------Skaaby T, Husemoen LL, Thuesen BH, & Linneberg A (2015). Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine PMID: 25666936... Read more »
Skaaby T, Husemoen LL, Thuesen BH, & Linneberg A. (2015) Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine. PMID: 25666936
In my last post I started writing about the next step a coding student can take after learning the basics. This next step is of course learning not just to code, but to code responsibly. Last time I talked about using version control to keep track of code changes as you work through a project. For this next post, I want to take the conversation further by discussing...... Read more »
Life as we know it, when we peer deep into the vastness of space we look for someone — or something — that resembles ourselves. Carbon based, needs water lifeforms, but what if we’re being narrow-minded? A new type of methane-based, oxygen-free life form that can metabolize and reproduce similar to life on Earth has been modeled by a team of researchers suggests we are being too closed minded about life.... Read more »
James Stevenson,, Jonathan Lunine,, & Paulette Clancy. (2015) Membrane alternatives in worlds without oxygen: Creation of an azotosome. Science Advances. info:/http://dx.doi.org/10.1126/sciadv.1400067
Dear Alice’s fan, this poem by Shel Silverstein is titled ‘Alice’ and now it’s your turn: are you ready to go down the rabbit hole again and be guided in our mind’s wonderland? So, let’s see what the blow up-potion and the shrinking-cake are made of.... Read more »
Kuo YT, Chiu NC, Shen EY, Ho CS, & Wu MC. (1998) Cerebral perfusion in children with Alice in Wonderland syndrome. Pediatric neurology, 19(2), 105-8. PMID: 9744628
Odumade OA, Hogquist KA, & Balfour HH Jr. (2011) Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clinical microbiology reviews, 24(1), 193-209. PMID: 21233512
MedicalResearch.com Interview with: Dr. Simonetta Genovesi MD Department of Health Science University of Milano-Bicocca, Monza Italy Nephrology Unit San Gerardo Hospital, Monza, Italy MedicalResearch: What is the background for this study? Dr. Genovesi: The prevalence of atrial fibrillation (AF) in … Continue reading →... Read more »
MedicalResearch.com Interview with:, & Dr. Simonetta Genovesi MD. (2015) Study Weighs Risks/Benefits of Oral Anticoagulation for Atrial Fibrillation in Hemodialysis Patients. MedicalResearch.com. info:/
MedicalResearch.com Interview with: William Mair, Ph.D Assistant Professor Department of Genetics and Complex Diseases Harvard T. H Chan School of Public Health Boston, MA 02115 MedicalResearch: What is the background for this study? What are the main findings? Dr. Mair: Dietary … Continue reading →... Read more »
MedicalResearch.com Interview with:, & William Mair, Ph.D. (2015) Cellular Energy Sensor Links Calorie Restriction With Healthy Aging. MedicalResearch.com. info:/
by Abel Molina in Evolutionary Games Group
There are some situations, perhaps lucky ones, where it is felt that an activity needs no external motivation or justification. For the rest, it can be helpful to think of what the task at hand can be useful for. This of course doesn’t answer the larger question of what is worth doing, since it just distributes […]... Read more »
Barton, N.H., Novak, S., & Paixão, T. (2014) Diverse forms of selection in evolution and computer science. Proceedings of the National Academy of Sciences of the United States of America, 111(29), 10398-9. PMID: 25009183
MedicalResearch.com Interview Invitation Frank Struyf MD PhD Director, Lead Clinical Development HPV vaccines at GlaxoSmithKline Biologicals GlaxoSmithKline Vaccines, Rixensart, Belgium MedicalResearch: What is the background for this study? What are the main findings? Dr. Struyf: Cervical cancer is the fourth … Continue reading →... Read more »
MedicalResearch.com Interview Invitation, & Frank Struyf MD PhD. (2015) HPV-16/18 Vaccine Provides Some Cross Protection To Other Cancer-Causing Subtypes. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Shyamasundaran Kottilil MBBS, PhD Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Medical Research: What is the … Continue reading →... Read more »
MedicalResearch.com Interview with:, & Shyamasundaran Kottilil MBBS, PhD. (2015) Oral Medication For Hepatitis C- HIV Combined Infection. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Nisha Bansal MD MAS Assistant Professor Associate Program Director for Research Kidney Research Institute Division of Nephrology University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Bansal: We … Continue reading →... Read more »
MedicalResearch.com Interview with:, & Nisha Bansal MD MAS Assistant Professor. (2015) Equation Helps Predict Mortality In Elderly Patients With Chronic Kidney Disease. MedicalResearch.com. info:/
MedicalResearch.com Interview with: Professor Daniela Jakubowicz MD Diabetes Unit. E. Wolfson Medical Center Sackler Faculty of Medicine, Tel Aviv University and Tel Aviv Medical Center Israel MedicalResearch: What is the background for this study? What are the main findings? Professor … Continue reading →... Read more »
MedicalResearch.com Interview with:, & Professor Daniela Jakubowicz MD. (2015) Bigger Breakfast, Smaller Dinner May Improve Glycemic Control. MedicalResearch.com. info:/
In an interesting short paper just published in Trends in Cognitive Science, Caltech neuroscientist Ralph Adolphs offers his thoughts on The Unsolved Problems of Neuroscience.
Here's Adolphs' list of the top 23 questions (including 3 "meta" issues), which, he says, was inspired by Hilbert's famous set of 23 mathematical problems:
Problems that are solved, or soon will be:
I. How do single neurons compute?
II. What is the connectome of a small nervous system, like that of Caenorhabi... Read more »
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