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  • October 15, 2014
  • 12:43 PM

Marburg Virus and Keap1: induction of antioxidant response whilst inhibiting selective autophagy ?

by thelonevirologist in Virology Tidbits

Under normal conditions, Keap1 interacts with Nrf2 via the Nrf2-ECH homology domain 2 (Neh2) located within the N-terminal end of Nrf2 and ubiquitinates Nrf2 in a Cullin-3 dependent manner., leading to the proteasomal degradation of Nrf2 via the 26S proteasome independent of autophagy. Inactivation of Keap1 by binding p62/SQSTM1 via the C-terminal KELCH domain of Keap1 and the Keap1 interacting domain (KIR) of p62/SQSTM1 induces the degradation of Keap1 via selective autophagy, thus releasing Nrf2. In the case of oxidant independent activation of Nrf2, this translocation is preceded by phosphorylation of p62/SQSTM1 at Ser-351 of the KIR domain of p62/SQSTM1 whereas in the case of reactive oxygen species, nitric oxide, or electrophiles cysteine residues (Cys-151, Cys-273, and Cys-288 being the critical residues) of Keap1 are modified whereas Cadmium or Arsenic binds Keap1 at these residues while at the same time prevents Keap1 from interacting with p62/SQSTM1 and thus stabilising Keap1. MARV VP24 binds to Keap1 and releases Nrf2, followed by nuclear translocation of Nrf2 and subsequent induction of gene expression.... Read more »

Fan W, Tang Z, Chen D, Moughon D, Ding X, Chen S, Zhu M, & Zhong Q. (2010) Keap1 facilitates p62-mediated ubiquitin aggregate clearance via autophagy. Autophagy, 6(5), 614-21. PMID: 20495340  

Baird L, & Dinkova-Kostova AT. (2011) The cytoprotective role of the Keap1-Nrf2 pathway. Archives of toxicology, 85(4), 241-72. PMID: 21365312  

Wu KC, Liu JJ, & Klaassen CD. (2012) Nrf2 activation prevents cadmium-induced acute liver injury. Toxicology and applied pharmacology, 263(1), 14-20. PMID: 22677785  

Ma, Q. (2013) Role of Nrf2 in Oxidative Stress and Toxicity. Annual Review of Pharmacology and Toxicology, 53(1), 401-426. DOI: 10.1146/annurev-pharmtox-011112-140320  

Mateo M, Carbonnelle C, Martinez MJ, Reynard O, Page A, Volchkova VA, & Volchkov VE. (2011) Knockdown of Ebola virus VP24 impairs viral nucleocapsid assembly and prevents virus replication. The Journal of infectious diseases. PMID: 21987766  

Noda, T., Ebihara, H., Muramoto, Y., Fujii, K., Takada, A., Sagara, H., Kim, J., Kida, H., Feldmann, H., & Kawaoka, Y. (2006) Assembly and Budding of Ebolavirus. PLoS Pathogens, 2(9). DOI: 10.1371/journal.ppat.0020099  

Edwards MR, Johnson B, Mire CE, Xu W, Shabman RS, Speller LN, Leung DW, Geisbert TW, Amarasinghe GK, & Basler CF. (2014) The Marburg virus VP24 protein interacts with Keap1 to activate the cytoprotective antioxidant response pathway. Cell reports, 6(6), 1017-25. PMID: 24630991  

Bamberg S, Kolesnikova L, Möller P, Klenk HD, & Becker S. (2005) VP24 of Marburg virus influences formation of infectious particles. Journal of virology, 79(21), 13421-33. PMID: 16227263  

Kosmider B, Messier EM, Janssen WJ, Nahreini P, Wang J, Hartshorn KL, & Mason RJ. (2012) Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus. Respiratory research, 43. PMID: 22672594  

  • October 15, 2014
  • 09:46 AM

Video Tip of the Week: MedGen, GTR, and ClinVar

by Mary in OpenHelix

The terrific folks at NCBI have been increasing their outreach with a series of webinars recently. I talked about one of them not too long ago, and I mentioned that when I found the whole webinar I’d highlight that. This recording is now available, and if you are interested in using these medical genetics resources, […]... Read more »

Acland A., R. Agarwala, T. Barrett, J. Beck, D. A. Benson, C. Bollin, E. Bolton, S. H. Bryant, K. Canese, D. M. Church.... (2013) Database resources of the National Center for Biotechnology Information. Nucleic Acids Research, 42(D1). DOI:  

  • October 15, 2014
  • 08:34 AM

Biochemical 'Memory' Can Help Bacteria to Grow

by This Science is Crazy! in This Science Is Crazy!

A new study explores ‘memory’ in E. coli to see how it impacts on their ability to grow in environments with fluctuating food sources. Recent exposure to a food source can reduce and even practically eliminate the 'lag' phase of growth when the food is reintroduced.... Read more »

  • October 15, 2014
  • 08:00 AM

Frankenstein Meets Genetic Modification

by Mark Lasbury in As Many Exceptions As Rules

Halloween conjures up monsters, like Mary Shelly’s Frankenstein. Her story is just as applicable for us today – the story of science being responsible for what it creates. The so-called Frankenfoods are called dangerous – but why? Studies that label them dangerous have been retracted or are merely correlative. New studies have shown that genetically modified crops are safe for livestock and humans. However, there are valid concerns, so every GMO must be tested rigorously.... Read more »

Snell C, Bernheim A, Bergé JB, Kuntz M, Pascal G, Paris A, & Ricroch AE. (2012) Assessment of the health impact of GM plant diets in long-term and multigenerational animal feeding trials: a literature review. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 50(3-4), 1134-48. PMID: 22155268  

McCall WV, Andrade C, & Sienaert P. (2014) Searching for the mechanism(s) of ECT's therapeutic effect. The journal of ECT, 30(2), 87-9. PMID: 24755719  

  • October 15, 2014
  • 05:16 AM

Hookworm infection and microchallenge for coeliac disease?

by Paul Whiteley in Questioning Answers

I'm getting rather baffled by some of the literature appearing with the autoimmune condition coeliac (celiac) disease in mind. The paper by Kalliokoski and colleagues [1] started the bafflement ball rolling with their suggestion that: "administration of IgA-deficient celiac disease patient serum or total IgG induces both deterioration of the intestinal mucosa and clinical features of celiac disease in mice". Then came the paper from Namatovu and colleagues [2] who concluded that: "Neighborhood composition influences CD [coeliac disease] risk". Such discussions were based on a condition which science seemed to be getting a handle on in terms of the genetic and biological processes involved... or maybe not."Klaatu Barada N... Necktie... Neckturn... Nickel"Enter also the findings reported by John Croese and colleages [3] observing that: "Necator americanus and gluten microchallenge promoted tolerance and stabilized or improved all tested indices of gluten toxicity in CeD [coeliac disease] subjects" and the bafflement ball starts to roll away yet faster and further.A few points from the Croese paper are worth noting:This was a year long study looking at a small number of adults with "diet-managed" CD (N=12). In case you might not know, the diet in question is a gluten-free diet.Said participants were "inoculated" with 20 hookworm larvae (see here for a picture if you really wish) and subsequently fed increasing doses of gluten - consumed as pasta - ranging from micrograms to grams over the course of some weeks. "Symptomatic, serologic, and histological outcomes evaluated gluten toxicity. Regulatory and inflammatory T cell populations in blood and mucosa were examined".Results: Not all the participants went the distance with the gluten challenge; two of which were labelled 'gluten intolerant' (which is a little odd because intolerance of gluten is I presume a hallmark of all CD). That being said, there were some interesting findings observed such as: "the mean IgA-tissue transglutaminase titers declined". I'm not an expert on CD but elevated IgA-tissue transglutaminase is closely associated with CD and I believe levels should fall when a person adopts a gluten-free diet [4]. The fact that levels declined when a gluten challenge (ingesting gluten) was in place was, in the words of the authors, "contrary to the predicted rise".Researchers also described how: "Intestinal T cells expressing IFNγ were reduced following hookworm infection". Again with my non-expert hat on, these are some interesting results. The interferons have been previously discussed on this blog with autism in mind (see here) but with CD in focus, are thought to be part of the destructive immune system processes which describe the condition (see here). The suggestion that hookworm infection might be somehow placating such immune processes is intriguing.Obviously, there is a lot more to do in this area before anyone decides that hookworm infection is a panacea for CD. I've already mentioned the small participant number and attrition rate but given also that CD is usually described as a lifelong condition, one year of experimental study is not nearly enough to discuss any long-term effects. That other studies from the authors have reported less eventful results [5] is also worth mentioning.But, I'm also minded to discuss another paper from this research group [6] which was covered on a sister blog (see here). On that occasion, authors talked about how hookworm infection seemed to influence production of the TH-17 cytokine, IL-17A too: "Hookworm infection suppressed basal production of the inflammatory cytokines IFN-γ and IL-17A". I've become quite interested in IL-17 over the years, again with the autism research connection in mind (see here) and a possible link with autoimmunity. The fact that IL-17 might also represent one way of distinguishing subgroups with CD [7] is likewise intriguing and offer something in the way of a variable on response to such helminthic therapy...Music to close. How about some bluegrass... The Grascals and Bugle Call Rag?And since, I have your attention, here's a link to my latest paper [8] on the potential use of gluten and casein-free diets for autism (shameless self-publicity I know).----------[1] Kalliokoski S. et al. Injection of celiac disease patient sera or immunoglobulins to mice reproduces a condition mimicking early developing celiac disease. J Mol Med (Berl). 2014 Sep 12.[2] Namatovu F. et al. Neighborhood conditions and celiac disease risk among children in Sweden. Scand J Public Health. 2014 Sep 23. pii: 1403494814550173.[3] Croese J. et al. Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J Allergy Clin Immunol. 2014 Aug 29. pii: S0091-6749(14)01010-0.[4] Dahele AV. et al. Serum IgA tissue transglutaminase antibodies in coeliac disease and other gastrointestinal diseases. QJM. 2001 Apr;94(4):195-205.[5] Daveson AJ. et al. Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial. PLoS One. 2011 Mar 8;6(3):e17366.[6] McSorley HJ. et al. Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. PLoS One. 2011;6(9):e24092.[7] Sapone A. et al. Differential mucosal IL-17 expression in two gliadin-induced disorders: gluten sensitivity and the autoimmune enteropathy celiac disease. Int Arch Allergy Immunol. 2010;152(1):75-80.[8] Whiteley P. Nutritional management of (some) autism: a case for gluten- and casein-free diets? Proc Nutr Soc. 2014 Oct 14:1-6.----------... Read more »

Croese J, Giacomin P, Navarro S, Clouston A, McCann L, Dougall A, Ferreira I, Susianto A, O'Rourke P, Howlett M.... (2014) Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. The Journal of allergy and clinical immunology. PMID: 25248819  

  • October 14, 2014
  • 09:30 PM

What is the habenula?

by neurosci in Neuroscientifically Challenged

Despite the fact that it is present in almost all vertebrate species, very little was known about the habenula until fairly recently. In the past several years, however, the habenula has received a significant amount of attention for its potential role in both cognition (e.g. reward processing) and disorders like depression. Still, the habenula remains a little-known structure whose functions are yet to be fully elucidated.Where is the habenula?The habenula is part of the diencephalon and, together with the pineal gland, makes up a structure called the epithalamus. The pineal gland is found on the posterior side of the thalamus and is attached to the diencephalon by a stalk. At the base of that stalk there are two small swellings (one on each side); these are the habenulae. The habenula is traditionally divided into a lateral and medial section.What is the habenula and what does it do?The habenula receives information from the limbic system and basal ganglia through a fiber bundle called the stria medullaris. It sends information to areas of the midbrain that are involved in dopamine release, such as the substantia nigra and ventral tegmental area. The habenula also has neurons that project to areas like the raphe nuclei, which are involved in serotonin release. Thus, the habenula is one of the few known structures in the brain that can exert an influence over large populations of both serotonergic and dopaminergic neurons.The habenula and reward processingDopamine and dopamine-rich areas of the brain like the substantia nigra and ventral tegmental area are thought to be important to processing information related to rewards. When we receive a reward--which could be anything from a slice of cheesecake to a line of cocaine--there is corresponding dopamine activity that seems to be associated with how satisfying we expect the reward to be. If the reward is larger than we expected (e.g. a big slice of cheesecake, topped with syrup and with a side of ice cream), our dopamine neurons get excited with activity that seems to help us remember the details of how we obtained the reward. In this way, our dopamine system helps us to recall how to get the reward again. When this encoding of the details associated with a reward becomes hyperactive, it can result in the obsessive reward-seeking we see in addiction.But when the reward is smaller than we expected (e.g. a few crumbs of cheesecake on an otherwise empty plate), dopamine activity in the substantia nigra and ventral tegmental area is inhibited. Smaller-than-expected rewards, however, cause increased activity in the habenula, while larger rewards lead to an inhibition of activity there.Thus, it has been hypothesized that the habenula is involved in encoding information about disappointing (or missing) rewards. The habenula has also been found to be activated in response to punishment (e.g. electric shocks) and stimuli that we have previously associated with negative experiences. Based on all of this information, it is thought the habenula plays an important role in learning from aversive experiences and in making decisions so as to avoid such unpleasant experiences in the future.The habenula and depressionThe habenula has been found to be activated in response to stress, and so it may not be surprising--given the strong relationship between chronic stress and depression--that the habenula is suspected to be involved in the pathophysiology of depression. Habenular neurons are hyperactive in depression; some have suggested this activity may correspond with an increased propensity toward pessimism. Structural abnormalities of the habenula have been found in the brains of patients who suffered from major depressive disorder, and in one case a patient who was not responsive to typical treatments for depression did respond to deep-brain stimulation of her lateral habenula. Regardless, although there are some indications of habenular involvement in depression, the association between the habenula and depression is still unclear. More research will be needed to determine if there is a causative link, and if so what the nature of that link is.The habenula and sleepThe habenula also seems to play a role in sleep. It has mutual connections with the pineal gland, which secretes melatonin--a hormone important for regulating circadian rhythms and promoting sleep. There is also some evidence that the habenula itself produces melatonin. Lesioning the habenula in experimental animals results in a disruption of rapid eye movement (REM) sleep, and thus the habenula may have role in both promoting sleep and sleep quality. Some have suggested the role of the habenula in sleep may also be related to its role in depression, as depressed individuals often suffer from sleep disorders.The functions of the habenula are just beginning to be understood. Until fairly recently, our neuroimaging techniques were not even powerful enough to visualize the habenula with adequate resolution. Now that this has changed, the tiny structure is becoming recognized as an important part of the brain. The next decade is likely to reveal some interesting new data about just how important this once-obscure brain region really is.Hikosaka O (2010). The habenula: from stress evasion to value-based decision-making. Nature reviews. Neuroscience, 11 (7), 503-13 PMID: 20559337... Read more »

  • October 14, 2014
  • 02:15 PM

Melanoma Cells: A Fatal Attraction to LPA

by Ines Alvarez-Garcia in PLOS Biologue

A hot day, blue sky and an even bluer sea. A perfect day to spend on the beach. But while our skin is sizzling, very few of us are aware of what some of our cells might be up to. … Continue reading »The post Melanoma Cells: A Fatal Attraction to LPA appeared first on PLOS Biologue.... Read more »

Muinonen-Martin, A., Susanto, O., Zhang, Q., Smethurst, E., Faller, W., Veltman, D., Kalna, G., Lindsay, C., Bennett, D., Sansom, O.... (2014) Melanoma Cells Break Down LPA to Establish Local Gradients That Drive Chemotactic Dispersal. PLoS Biology, 12(10). DOI: 10.1371/journal.pbio.1001966  

  • October 14, 2014
  • 01:34 PM

These Tiny Animals Live Only on Driftwood

by Elizabeth Preston in Inkfish

Maybe you gave your last realtor a long series of must-haves: a washing machine in unit, proximity to the train, a gas stovetop. But there’s no way you’re as picky as the driftwood hopper. This minute crustacean will only live in rotting chunks of driftwood. David Wildish, a marine zoologist at Fisheries and Oceans Canada, […]The post These Tiny Animals Live Only on Driftwood appeared first on Inkfish.... Read more »

  • October 14, 2014
  • 10:22 AM

Treating school uniforms to reduce dengue: the Finances

by Yao-Hua Law in TORCH

 [A shorter version of this article first appeared on SciDev.Net] Scientists working to reduce dengue among school children in Thailand are testing something new: insecticide-treated school uniforms. A recent model published in PLoS One suggests that this intervention can be economically attractive in the context of Thailand. Using data from dengue studies in Thailand, the […]... Read more »

  • October 14, 2014
  • 09:34 AM

What do we share with other primates in terms of cognition?

by Henkjan Honing in Music Matters

Below a beautiful summary of the recent literature on the neurobiology of action imitation/understanding, language, and rhythmic processing/auditory timing (Mendoza & Merchant, in press). The neural circuitry that is thought to be involved in all three higher cognitive functions is shown here for three closely related primates: the macaque monkey, chimpanzee and human brain.... Read more »

Merchant, H., & Honing, H. (2013) Are non-human primates capable of rhythmic entrainment? Evidence for the gradual audiomotor evolution hypothesis. Frontiers in Neuroscience, 7(274). info:/

  • October 14, 2014
  • 09:30 AM

Zombies And The Loss of Free Will

by Mark E. Lasbury in The 'Scope

Nature is rife with examples of how one organism can rob another of its free will, turning them into zombies so to say. Who would have guessed that Alfred Hitchcock's The Birds was really a zombie movie.... Read more »

  • October 14, 2014
  • 07:10 AM

Prenatal genetic testing and autism: a delicate subject

by Paul Whiteley in Questioning Answers

I realise that the paper by Lei-Shih Chen and colleagues [1] covers a most sensitive topic when it comes to the autism spectrum, exploring: "the attitudes toward PGT [prenatal genetic testing] and termination decisions of 42 parents of children with ASD [autism spectrum disorder]". Indeed, this is not the first time that this research group has looked at this area of autism research [2] and it seems like they will be talking about it further too (see here).I chose to discuss the most recent paper on this blog because (a) the Chen paper is peer-reviewed science, (b) the likelihood of PGT being 'applied to autism' at some point in the future is growing (if not here in some parts of the world?), and (c) similar to the screening tests available for conditions like Down's syndrome (see here), there are going to be conversations to be had about the decisions and choices potentially offered to parents on the basis of any screening results. Charities here in the UK such as Antenatal Results and Choices (ARC) are probably going to figure in those conversations which, in some quarters, have already begun to happen (see here). I write this blog from a cold, scientific perspective so please don't get offended by some of the discussions.The Chen paper describes the results of a qualitative study where parents of children with ASD were given "a hypothetical scenario" regarding PGT and asked their hypothetical response to using PGT and their hypothetical response to a positive test response. "Of the 31 parents who were either willing or unsure about undergoing the PGT, approximately three-fourths would continue their hypothetical affected pregnancies". A few things struck me about the Chen paper. First is a line introducing the abstract which reads: "In the United States, prenatal genetic testing (PGT) for Autism Spectrum Disorders (ASD) is currently available via clinical genetic services". I was quite taken aback by this sentence. As far as I was aware science was still feeling around as to the underlying genetics of autism (that is, if you consider autism to be a unitary concept rather than a more plural condition and to be solely driven by structural genetics over and above environmental factors or epigenetic changes). If someone is suggesting otherwise, please do point me towards the peer-reviewed science for that prenatal genetic test outside of something like just screening for Fragile X syndrome [3] or the preliminary results reported by Wapner and colleagues [4] mentioned with autism in mind...The next thing that caught my eye was the high number of parents who, if faced with the hypothetical PGT situation, said they would continue with their pregnancy. I'm not so surprised at this, given that researchers were asking parents who already had a child with autism and so perhaps knew a little bit about both the good and not-so-good times which go with raising a child with a developmental disability. I also emphasise the word 'child' there before their condition/label. If the questions were put to parents with no personal experience of autism, one wonders whether similar outcomes would have been reported. Likewise if parents were for example, offered differing scenarios under such experimental conditions with other conditions outside of autism, such as Down's syndrome, the question remains about what results might have shown also bearing in mind the literature in this area [5].Finally, and I again tread very carefully with this, was the observation that: "Parents who reported they would terminate the affected pregnancy in this hypothetical situation were primarily Asians". I go to great lengths on this blog not to over-generalise autism research such that not every finding has to apply to every single person with autism. In this instance I'd also point out that the sample size for the Chen results was very small and outside of cultural differences and representations [6], one similarly cannot assume that every person/parent of Asian origin is going to report like this. Neither however should judgement be passed on those parents who did choose this hypothetical option and the road(s) which might have led them to this hypothetical decision. This might however suggest that as per other examples, autism is looked at in very different ways according to factors such geography and culture.As I mentioned at the top of this post, prenatal testing (genetic or otherwise) is always going to be a sensitive subject when applied to autism and will inevitably stir up considerable emotions for many people, not least those who are themselves on the autism spectrum. I'm going to leave you with some more discussion about this area from Prof. Andrew Whitehouse - he of the 'Is autism one or multiple disorders?' paper - and a very sensible post he wrote (see here) which covers most of the important issues well.----------[1] Chen LS. et al. Autism Spectrum Disorders: A Qualitative Study of Attitudes toward Prenatal Genetic Testing and Termination Decisions of Affected Pregnancies. Clin Genet. 2014 Sep 24.[2] Chen LS. et al. Autism genetic testing: a qualitative study of awareness, attitudes, and experiences among parents of children with autism spectrum disorders. Genet Med. 2013 Apr;15(4):274-81.[3] Gutiérrez JF. et al. Prenatal screening for fragile x: carriers, controversies, and counseling. Rev Obstet Gynecol. 2013;6(1):e1-7.[4] Wapner RJ. et al. Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis. NEJM. 2012; 367: 2175-2184.[5] Scott CJ. et al. Prenatal diagnosis and termination of pregnancy: perspectives of South African parents of children with Down syndrome. J Community Genet. 2013 Jan;4(1):87-97.[6] Bie B. & Tang L. Representation of Autism in Leading Newspapers in China: A Content Analysis. Health Commun. 2014 Jul 29:1-10.----------Chen LS, Xu L, Dhar SU, Li M, Talwar D, & Jung E (2014). Autism Spectrum Disorders: A Qualitative Study of Attitudes toward Prenatal Genetic Testing and Termination Decisions of Affected Pregnancies. Clinical genetics PMID: 25251361... Read more »

  • October 13, 2014
  • 05:30 PM

Yes folks... broccoli chemical impacts on autism presentation

by Paul Whiteley in Questioning Answers

Please do not adjust your set. Broccoli, or least a chemical found in broccoli called sulforaphane has, under placebo-controlled, double-blind experimental conditions, been reported to impact on the presentation of autism according to the paper by Kanwaljit Singh and colleagues [1] (open-access).Eat your greens @ Fir0002/FlagstaffotosI had to do a bit of a double-take myself when I first read about these results (see here). Indeed, even the authors themselves seemed to be a little taken aback by their own findings if other media on this study is to be believed (see here). Still peer-reviewed science is peer-reviewed science and that goes just as much for this study as any other.The paper is open-access but a few details might be useful:The study was previously registered in the US database (see here). It involved comparing "capsules of sulforaphane-rich broccoli sprout extracts" with "indistinguishable placebo capsules" containing microcrystalline cellulose (wood pulp) in a small group of young men (aged 13-27 years) diagnosed with an autism spectrum disorder (ASD) administered daily over 18 weeks. As I mentioned, the study was also double-blind.Various measures - behavioural and physiological - were recorded at baseline (prior to study start) and at choice points during the 18 week study period. The results of the behavioural measures including the Aberrant Behaviour Checklist (ABC) and Social Responsiveness Scale (SRS) completed by parents/caregivers and the Clinical Global Impression Severity (CGI-S) and the Clinical Global Impression Improvement (CGI-I) scales completed by "study physicians" are included in the main paper results and conclusions.Results: well, first and foremost there were a few adverse events reported during the trial. The authors note that: "Sulforaphane treatment effectively improved core aberrant behaviors of ASD, and was safe and well-tolerated". But... "the sulforaphane group gained significantly more weight over the 18-wk period, compared with placebo" and there was mention of "single unprovoked seizures" occurring in two participants taking the active treatment. These seizures may well be unconnected to the sulforaphane capsules but one cannot rule out the possibility that they were connected.Forty participants completed the trial, or at least "part of the outcome measure evaluations" boiling down to "14 placebo and 26 sulforaphane". The statistical evaluation undertaken involved looking at "the differences between scores of individuals at 4, 10, 18, and 22 wk from their respective average pretreatment values". But the authors also undertook a separate intention-to-treat analysis that "included all 44 participants".The headlines: "many of the participants who were treated with sulforaphane in this study had statistically significant and clinically meaningful improvements during treatment with sulforaphane". With all due respect to parent/caregiver reports, I was particularly drawn to the fact that study physicians although blinded to who was on active treatment and who was taking a placebo were able to rate "13 of the 40 participants" as showing noticeable improvements in behaviour and sociability and "all were receiving sulforaphane". That's quite a feat by any study's standard.The authors conclude: "The substantial improvements of individual ASD patients’ trajectories were conspicuous and suggest that further investigation of sulforaphane in ASD is promising".These are interesting results crying out for further independent [longer term] replication. The fact also that this was a trial of adolescents and adults with autism also fills a gap in the autism research market alluded to in previous posts on this blog (see here). Mechanism of effect? Well, there does seem to be quite a bit more to do in this area. The authors note that sulforaphane "was selected because it upregulates genes that protect aerobic cells against oxidative stress, inflammation, and DNA-damage, all of which are prominent and possibly mechanistic characteristics of ASD". Oxidative stress does indeed appear on the research radar when it comes to autism, at least some autism (see here) and sulforaphane fits the bill in terms of its potential 'protective' effects [2]. I've also talked about such mechanisms with another source of sulforaphane in mind (see here). That all being said, I don't doubt that there may be other biological processes at work.So, in conclusion 'eat your greens' might very well be an important phrase for some on the autism spectrum. Whether eating the source material carries the same effect or will be equally well received as taking a daily pill is another matter...----------[1] Singh K. et al. Sulforaphane treatment of autism spectrum disorder (ASD). PNAS. 2014. October 13.[2] Guerrero-Beltrán CE. et al. Protective effect of sulforaphane against oxidative stress: recent advances. Exp Toxicol Pathol. 2012 Jul;64(5):503-8.-----------Kanwaljit Singh, Susan L. Connors, Eric A. Macklin, Kirby D. Smith, Jed W. Fahey, Paul Talalay, & Andrew W. Zimmerman (2014). Sulforaphane treatment of autism spectrum disorder (ASD) PNAS : 10.1073/pnas.1416940111... Read more »

Kanwaljit Singh, Susan L. Connors, Eric A. Macklin, Kirby D. Smith, Jed W. Fahey, Paul Talalay, & Andrew W. Zimmerman. (2014) Sulforaphane treatment of autism spectrum disorder (ASD). PNAS. info:/10.1073/pnas.1416940111

  • October 13, 2014
  • 05:27 PM

Free Radicals and Wound Healing

by Gabriel in Lunatic Laboratories

Free radicals, said in the right crowd and you might hear someone scream for their life. Of course, to be perfectly transparent antioxidants have already shown to be bad in plenty of cases, so maybe it’s just bad PR. Still they were long assumed to be destructive to tissues and cells causing a host of age related problems with them. Well new research is showing that “free radicals” generated by the cell’s mitochondria—the energy producing “powerhouse” structures in the cell—are actually beneficial to healing wounds.... Read more »

Suhong Xu,, & Andrew D. Chisholm. (2014) C. elegans Epidermal Wounding Induces a Mitochondrial ROS Burst that Promotes Wound Repair . Developmental Cell. info:/

  • October 13, 2014
  • 10:18 AM

Guiding light to boost algae biofuel production

by This Science is Crazy! in This Science Is Crazy!

New study uses waveguides dotted with SU-8 pillars to scatter light in a tank of algae. By varying the spacing of the pillars, light intensity across the tank was approximately uniform and increased algae growth by 'at least 40%' compared to scheme with uniformly-distributed pillars... Read more »

  • October 13, 2014
  • 04:46 AM

Cognitive-Behavioural Therapy (CBT) for anxiety in autism

by Paul Whiteley in Questioning Answers

I'll readily admit that despite having a tinge of psychology running through my research career, I'm not overly enthused about the impact of the discipline on the autism spectrum down the years. I'm not necessarily just talking about the Freudian effect which set autism research back decades and shamefully added needless worry and stigma to those on the spectrum and their loved ones, but also the grand over-arching psychological theories which seemed, for example, to completely miss the 'heterogeneity' aspect to the condition(s) nor seemingly took into account the importance of comorbidity. Thankfully psychology is trying to make amends for its past sins when it comes to autism as per the article by Happé and colleagues [1] which also featured in a recent special edition of The Psychologist (see here). That being said, old habits still seemingly die hard [2] and 'unifying' generalisations still abound..."Farewell and adieu to you, fair Spanish ladies"With all this in mind, I've always been a little hesitant when it comes to the application of psychological therapies to autism. I'm not necessarily talking about the various behavioural/educational interventions [rightly or wrongly] put forward with autism in mind, but more the 'talking therapies' and in particular, the idea that cognitive-behavioural therapy (CBT) might be something to consider for at least some of those on the autism spectrum.The paper by Danielle Ung and colleagues [3] has kinda restored my faith in how psychology might yet be useful to helping some aspects of daily living for some on the spectrum; specifically with a focus on abating the often crippling effects of comorbidity such as anxiety. Based on their review and meta-analysis, the authors concluded that: "CBT demonstrates robust efficacy in reducing anxiety symptoms in youth with high-functioning ASD [autism spectrum disorder]".I've talked before on this blog about anxiety and how, for some on the autism spectrum, the effects of anxiety seem to take precedent over and above the effects of autism in a persons day-to-day life. I can't overstate the impact that anxiety can have on a person with autism and how, alongside physiological consequences, there may well be some new triads to look at when it comes to such issues (see here). With all this in mind, anything that can be done to alleviate excessive anxiety from the lives of people with autism should be looked into outside the roads which some might have already travelled. CBT already has some practical use with certain types of anxiety outside of anything directly linked to autism so pairing CBT with anxiety in autism seems like a logical step to take.The Ung paper is not the first however to report on how CBT might be useful for anxiety comorbid to autism:Sukhodolsky and colleagues [4] similarly meta-analysed the peer-reviewed literature up to 2012 (see here) and found some pretty good effect sizes based on their re-analysis of the cumulative data.Storch and colleagues [5] actually carried out a trial of CBT (versus treatment as usual) with children with autism and "clinically significant anxiety" and suggested that: "CBT adapted for anxious youth with high-functioning ASD demonstrates large effects in reducing anxiety symptoms".Reaven and colleagues [6] concluded similar things based on their group CBT intervention "specifically developed for children with ASD".That being said, the result from Sung and colleagues [7] are also worth mentioning because of their comparison of CBT with a "Social Recreational (SR) program". They reported: "lower levels of generalized anxiety and total anxiety symptoms at 6-month" for both CBT and SR programs and concluded that: "factors such as regular sessions in a structured setting, consistent therapists, social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD". The indication there is that the specific effects of CBT on anxiety in autism may very well turn out not be the whole story as per other activities potentially indicated for some on the autism spectrum (see here).Psychology still needs to tread carefully when it comes to autism and perhaps hold back from trying to over-psychologise(?) any effect noted from CBT for certain people on the autism spectrum. As per those Sung results, the idea of comparing CBT to interventions outside of just 'treatment as usual' is an area where more investigation needs to be focused so as not to imply that CBT is the be-all-and-end-all for anxiety when present in cases of autism. Further inquiry perhaps also needs to be undertaken into various types of CBT available and whether specific programs [8] might show greater benefits for specific people or groups of people on the spectrum. Also how more physiological measures linked to anxiety, might need to be included in those further investigations to represent something of a more objective measure of effectiveness. All this to make sure that CBT for anxiety in autism does not go the same way as CBT for schizophrenia [9] for example.Oh, and just before I go, I'm gonna be blogging soon about some of the work on intolerance of uncertainty linked to anxiety in autism as something of a potentially new dimension for looking at the presentation of anxiety in relation to at least some autism.And now for some (hopefully relaxing) music ... Passenger and Let Her Go.----------[1] Happé F. et al. Time to give up on a single explanation for autism. Nat Neurosci. 2006 Oct;9(10):1218-20.[2] Fletcher-Watson S. et al. Interventions based on the Theory of Mind cognitive model for autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2014 Mar 21;3:CD008785.[3] Ung D. et al. A Systematic Review and Meta-Analysis of Cognitive-Behavioral Therapy for Anxiety in Youth with High-Functioning Autism Spectrum Disorders. Child Psychiatry Hum Dev. 2014 Sep 23.[4] Sukhodolsky DG. et al. Cognitive-behavioral therapy for anxiety in children with high-functioning autism: a meta-analysis. Pediatrics. 2013 Nov;132(5):e1341-50.[5] Storch EA. et al. The effect of cognitive-behavior... Read more »

  • October 12, 2014
  • 02:57 PM

Nothing Sticks to a new Bioinspired coating for medical devices

by Gabriel in Lunatic Laboratories

Putting things in the body can be tricky, I mean we need things from joint replacements to cardiac implants and dialysis machines, these medical devices are needed to enhance or save lives on a daily basis. However, any device implanted in the body or in contact with flowing blood faces two critical challenges that can threaten the life of the patient the device is meant to help: blood clotting and bacterial infection. Problems that sound easier to fix than they actually are.... Read more »

Don Ingber et. al. (2014) A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling. Nature Biotechnology. info:/10.1038/nbt.3020

  • October 12, 2014
  • 11:30 AM

Your Artificial Sweeteners, Your Bacteria, and Your Health

by Geoffrey Hannigan in Prophage

It seems like one cannot help hearing about this paper throughout the microbiome and related fields. The paper "Artificial Sweeteners Induce Glucose Intolerance by Altering the Gut Microbiota" was recently published in Nature, and it has had a lot of press...... Read more »

Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C., Maza, O., Israeli, D., Zmora, N., Gilad, S., Weinberger, A.... (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. DOI: 10.1038/nature13793  

  • October 12, 2014
  • 10:55 AM

Is EV-D68 causing mysterious polio-like symptoms in children?

by EE Giorgi in CHIMERAS

Bubble fun at the Santa Fe Renaissance Fair © EEG One of the twists in my latest book, Gene Cards, is an unknown pathogen threatening the fictional city of Liasis. I confess that when I came up with the idea I was a little nervous. My story is set in the future, and with all the state-of-the-art technology we already have, is it feasible to think that we will still deal with diseases without a known causative agent? The thing is, new viruses and new pathogens arise all the time. Take the flu, for example. Every time it jumps from one species to another, it has the potential to recombine in new strains and create a new virus. Influenza viruses are usually recognizable from their surface proteins, hemagglutinin and neuraminidase. But the point is that for as long as there are pathogen that thrive in animal reservoirs and then suddenly jump to humans, these pathogens could potentially lead to unknown organisms. And it's hard to test for something you don't know. Another issue with viruses is that they can "hide" in cells (like neurons) that are not accessible through standard test, making them harder to detect unless one resolves to invasive techniques.One thing is to theorize that it's possible, and one thing is to find it's happening, as you can read in this post from TWiV: "In February 2014 I wrote about children in California who developed a poliomyelitis-like paralysis, also called acute flaccid paralysis or AFP. However, the cause of this paralysis was not known. The CDC has released its study of these cases and concludes 'The etiology of AFP with anterior myelitis in the cases described in this report remains undetermined'."The CDC report is available online, and perhaps the most striking quote is the following:"Additional laboratory testing for infectious diseases conducted at the CDPH Viral and Rickettsial Disease Laboratory did not identify a causative agent to explain the observed clinical syndrome reported among the patients."So, what is the story, here?Acute flaccid paralysis happens when muscles become weak or limp and can no longer contract. In order to be diagnosed as AFP, the symptoms must arise spontaneously and not be caused by a trauma. A number of viruses can cause this condition, including polio. When caused by polio, the paralysis is associated with inflammation of the spinal cord, and the whole condition takes the name of "acute flaccid paralysis associated with anterior myelitis." A total of 23 cases of acute flaccid paralysis associated with anterior myelitis have been reported in California between June 2012 and May 2014."Affected patients resided in diverse geographic areas throughout California with no indication of clustering. During the 30-month inquiry, no indication of seasonality or temporal trends in disease onset was established."Twelve patients had been vaccinated against polio, two hadn't, and for the rest no information was available. Nineteen of the 23 patients had been tested for the "usual suspects" (polio, enteroviruses, West Nile virus, rabies, etc.), but only two tested positive for Enterovirus EV-D68, which in most cases actually manifests as a respiratory disease. The CDC report excludes polio as a cause of the 23 cases in the study and concludes that no common etiology could be found.[. . .] whether these cases represent an actual increase from baseline incidence of AFP with anterior myelitis in this population is unclear. A study examining AFP in children aged 15 years in California during 1992-1998 reported an incidence of 1.4 AFP cases per 100,000 children per year, with the most common diagnoses being Guillain-Barre syndrome (23%), unspecified AFP (21%), and botulism (12%). None of the 245 reviewed cases had recognized anterior myelitis, which is characteristic of paralytic poliomyelitis.If you do a quick search on PubMed, you'll see that the most common etiology for AFP is polio, and in those cases it's usually associated with anterior myelitis. A Korean study carried over the span of 10 years (from 2001 to 2010) found a total of 285 AFP cases, for which Guillain-Barre syndrome was the major leading causes [1]. Usually triggered by an infection, Guillain-Barre syndrome is a disorder that affects the peripheral nervous system. With prompt treatment, it is 100% curable, though if not treated promptly, it can cause life-threatening complications.What about the two patients who tested positive for Enterovirus D68? EV-D68 was first isolated in 1962. Since then, there have been rare reports of clustered cases, particularly in summer. However, this summer, there has been an unusual increase in reported cases of severe respiratory diseases, and most of these cases tested positive for EV-D68. Here are the latest numbers from the CDC:"From mid-August to October 8, 2014, CDC or state public health laboratories have confirmed a total of 664 people in 45 states and the District of Columbia with respiratory illness caused by EV-D68."What makes this virus worrisome is that it affects young children (usually under the age of 10) and that currently there is no vaccine or treatment against it. And while it normally manifests as a respiratory disease, in some rare instances, the virus can affect the nervous system. In the two California AFP cases that tested positive for EV-D68, the virus was found through nasal swabs. There is a possibility that in the other cases the virus was not found because it was elsewhere, namely in the nervous system (where it would be found only through invasive procedures).In a different report, the CDC describes "a cluster of nine children evaluated at Children's Hospital Colorado with acute neurologic illness characterized by extremity weakness, cranial nerve dysfunction (e.g., diplopia, facial droop, dysphagia, or dysarthria), or both. Neurologic illness onsets occurred during August 8‚ September 15, 2014."Four of eight Colorado children tested were positive for EV-D68. And even though these symptoms are not quite equivalent to AFP, they still fall within the spectrum of acute neurologic illnesses. Bottom line: we can't quite hold EV-D68 as responsible of the mysterious AFP cases, but we can't exclude it either. Viruses tend to target specific cells in the body, and sometimes they can spread beyond their usual "hunting grounds." When a pathogen is symptomatic (or manifests certain symptoms) only in one particular subset of the population, the reported cases appear to be unrelated, making it very hard to reconstruct the etiology of the outbreak.[1] Kim H, Kang B, Hwang S, Lee SW, Cheon DS, Kim K, Jeong YS, & Hyeon JY (2014). Clinical and enterovirus findings associated with acute flaccid paralysis in the Republic of Korea during the recent decade. Journal of medical virology, 86 (9), 1584-9 PMID: 24114945[2] ... Read more »

Zangwill KM, Yeh SH, Wong EJ, Marcy SM, Eriksen E, Huff KR, Lee M, Lewis EM, Black SB, & Ward JI. (2010) Paralytic syndromes in children: epidemiology and relationship to vaccination. Pediatric neurology, 42(3), 206-12. PMID: 20159431  

  • October 11, 2014
  • 04:14 PM

Poop Pills, Yeah they are a Thing Now

by Gabriel in Lunatic Laboratories

When someone is lying it isn't too abnormal to hear someone say, "you're full of sh..." well you get the idea. Our poop defines us, the microbes that live in our digestive tract make it possible for us to digest food, absorb nutrients, and stay healthy. Heck they may even cause your cravings! Unfortunately sometimes --whether due to abuse of antibiotics or some medical condition like C. diff infection-- gut bacteria can work against us, leading to all sorts of problems. As of now, the only real way to fix it is a poop transplant, which can be invasive and the most effective poop transplants are not done anally, but orally.... Read more »

Ilan Youngster, MD,, George H. Russell, MD,, Christina Pindar, Tomer Ziv-Baran, PhD, Jenny Sauk, MD, & Elizabeth L. Hohmann, MD. (2014) Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection. Journal of the American Medical Association . info:/10.1001/jama.2014.13875

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